公共卫生研究摘要 (2025-12-24)

共收录 64 篇研究文章

1. The Effectiveness of Social Support-Based Interventions for Dietary and Physical Activity in Adults Living With Overweight and Obesity: Protocol for a Systematic Review.

期刊: JMIR research protocols 发表日期: 2025-Dec-23 链接: PubMed

摘要

Obesity is a global public health concern, affecting roughly 1 in 3 individuals. Social support has been identified as a key factor in promoting healthy behaviors, including dietary improvements and increased physical activity. While previous reviews have focused primarily on weight loss outcomes, there is limited evidence on how social support-based interventions specifically influence diet and physical activity behaviors. This study aims to evaluate (1) the effectiveness of social support-based interventions in improving dietary and physical activity behaviors among adults living with overweight and obesity (plus weight changes and psychosocial factors as secondary outcomes) and (2) identify which types of social support are most effective in facilitating positive behavioral changes. A comprehensive search will be conducted across 7 databases and registers (MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, Cochrane Library, and ClinicalTrials.gov) and gray literature sources (Google Scholar, ProQuest, and PsyArXiv), in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent reviewers will screen randomized controlled trials and quasi-experimental studies involving adults living with overweight or obesity who have participated in social support-based interventions targeting diet and physical activity. The revised Joanna Briggs Institute critical appraisal tools will be used to assess the risk of bias. Findings will be reported qualitatively, and where appropriate, meta-analyses will be performed to generate pooled effect estimates for the primary outcomes. Secondary outcomes will also be reported qualitatively. A pilot database search was conducted on November 29, 2024, to refine the search syntax. The screening, data extraction, quality assessment, and analysis will be conducted, with completion expected by March 2026. This review will synthesize current evidence on the effectiveness of social support-based interventions for improving diet and physical activity among adults living with overweight and obesity. The findings will help inform the development of future interventions and contribute to public health strategies.

2. Acceptance of Electronic Medical Records and Associated Factors Among Health Care Workers in Northwest Ethiopia: Cross-Sectional Study.

期刊: JMIR medical informatics 发表日期: 2025-Dec-23 链接: PubMed

摘要

Although electronic medical records (EMRs) play a vital role in strengthening the health care system by improving efficiency, data management, and patient care, their development in Ethiopia is still in its early stages. Hence, most public health care facilities manage their patient information using paper-based recording, which results in errors, delays, and reduced service quality. This study aims to determine the level of acceptance of the EMR system and describe contributing factors. A cross-sectional study was conducted at health care facilities in Bahir City, Northwestern Ethiopia. A total of 322 health workers participated in the study, drawn from 5 health facilities that have implemented the EMR system. Descriptive statistics and bivariate and multivariate binary logistic regression were done to determine factors associated with EMR acceptance computed from mediating factors (perceived ease of use and perceived usefulness), and which is more appropriate in early-stage implementation. Out of the total 322 respondents, 256 (73%) respondents with 95% CI 67.4-78.2 had a good acceptance of using EMRs. In regression analysis, significant predictors including work experience over 10 years (odds ratio [OR] 14.32, 95% CI 4.60-44.58), income dissatisfaction (OR 0.28, 95% CI 0.10-0.82), owning a personal computer (OR 11.08, 95% CI 4.03-30.24), EMR-specific training (OR 4.71, 95% CI 1.52-14.54), basic electronic health management information system/district health information system 2 training (OR 3.06, 95% CI 1.02-9.17), and system usability (OR 38.24, 95% CI 12.26-119.27) were identified. The study demonstrated a moderate level of EMR acceptance among health care workers, with system usability identified as the strongest predictor. Significant factors influencing EMR acceptance included longer work experience, ownership of a personal computer, and prior EMR or electronic health management information system/district health information system 2 training. Context-specific strategies are needed to enhance system usability, provide targeted digital health training, and improve access to technological resources in order to support broader EMR adoption in health care settings.

3. Assessing the Readiness of Local Vaccine Manufacturing in African Countries: Protocol for a Scoping Review.

期刊: JMIR research protocols 发表日期: 2025-Dec-23 链接: PubMed

摘要

Although Africa experiences the highest burden of infectious diseases, the continent currently produces less than 1% of its vaccine needs. In 2021, the African Union set a target to locally produce at least 60% of the continent’s vaccine needs by 2040. However, at the time of developing this scoping review protocol, there is no consolidated, evidence-based framework for assessing national or regional “readiness” to establish or scale vaccine production. This protocol aims to describe a methodological approach that will be used to review existing literature to identify, map, and synthesize the existing evidence on all relevant frameworks, indicator sets, and policy documents (global or national) developed pre- and post-COVID-19 pandemic (January 1, 2010, to December 31, 2025) that addresses readiness for local human vaccine manufacturing with focus on African countries. This scoping review will be conducted and reported in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines, following the 9-step framework outlined in the Arksey and O’Malley methodology and further informed by guidance from the Joanna Briggs Institute. We will search MEDLINE (PubMed), Scopus, Web of Science, Africa-focused databases (eg, Africa-Wide Information, African Index Medicus, and African Journals Online), and gray literature. Eligibility criteria will follow Population, Concept, and Context guidelines (Population: 55 African Union member states; Concept: readiness frameworks, indices, indicators, and policies for human vaccine manufacturing; Context: African national or regional initiatives or global frameworks applied to Africa). Materials in English, French, Portuguese, or Arabic will be included. Publication types will be limited to frameworks, policies, guidance, and reports. Two reviewers will perform calibrated dual screening (Cohen κ) and standardized data charting. We will create an evidence map and inductive thematic synthesis using a vaccine-specific Political, Economic, Social, Technological, Legal, Environmental, plus Market taxonomy. Consistent with the guidance by the Joanna Briggs Institute, critical appraisal will not be performed. An optional expert consultation will help identify missed sources and validate domains. Ethics approval for the expert consultation component was obtained from the University of Geneva Research Ethics Committee (application submitted May 21, 2025; approval September 9, 2025). The initial search strategy has been finalized, and pilot searches were completed (May-August 2025). The screening calibration is planned; dual-review title and abstract screening begins in December 2025, with full-text screening and data charting scheduled for January-March 2026. Thematic synthesis and expert consultation are planned from April to May 2026. We anticipate submitting the completed scoping review paper by June or July 2026. This review will generate Africa’s first continent-focused evidence map of vaccine-manufacturing readiness, compiling indicators by domain, comparing frameworks, identifying gaps, and informing a multidomain Country Readiness Assessment Index for policy and investment decisions. Open Science Framework 10.17605/OSF.IO/UVSWX; https://osf.io/uvswx. DERR1-10.2196/81231.

4. Effectiveness of Financial Incentives for Health Behavior Change: A Narrative Review and Analysis.

期刊: Annual review of public health 发表日期: 2025-Dec-23 链接: PubMed

摘要

Financial incentives have been widely studied and implemented as instruments to encourage healthy behavior. This narrative expert review synthesizes evidence from 39 systematic, meta-analytic, narrative, and scoping reviews examining incentive-based interventions for four health behaviors: physical activity, smoking cessation, vaccination, and medication adherence. The reviewed studies encompass a wide range of populations and contexts, though the evidence is primarily in high-income settings, with less representation from low- and middle-income countries. Across domains, financial incentives tend to produce modest, often short-lived improvements; greater effectiveness is observed when incentives are substantial, promptly delivered, and contextually tailored and when behavioral outcomes are tracked using objective measures. Targeted incentives may reduce disparities in health behavior, though their ethical and social acceptability merit careful consideration. Gaps in the literature include short follow-up windows and limited cost-effectiveness data. Future research should probe long-term outcomes, explore heterogeneity of response to better understand mechanisms of sustained change, and study the effects of nonfinancial or social incentives.

5. Response to letter to the editor regarding: Can handgrip strength reflect muscle dysfunction in individuals in intensive care units? A prospective observational study.

期刊: Australian critical care : official journal of the Confederation of Australian Critical Care Nurses 发表日期: 2025-Dec-22 链接: PubMed

摘要

6. Time-limited ICU trials: A method for value-based rapid response team decision-making.

期刊: Intensive & critical care nursing 发表日期: 2025-Dec-22 链接: PubMed

摘要

7. Trimodal aptamer-regulated nanozyme biosensor with cross-validation for trace aldosterone detection toward integrated depression diagnosis and treatment evaluation.

期刊: Talanta 发表日期: 2025-Dec-22 链接: PubMed

摘要

Depression is a complex psychiatric disorder characterized by persistent affective dysregulation and somatic symptoms. As a major global public health concern, its diagnosis still largely relies on subjective questionnaire-based assessments. Aldosterone (ALD), a mineralocorticoid hormone associated with chronic stress, has emerged as a promising objective biomarker for depression. However, its clinical application is impeded by both its exceedingly low concentration in physiological fluids and the shortcomings of conventional detection methods. Herein, we reported a multifunctional aptamer-regulated nanozyme biosensor that integrated colorimetric, fluorescent, and electrochemical modes for precise, sensitive, and trace-level ALD detection. The biosensor employed NH2-Fe3O4 nanoparticles as a nanozyme scaffold, exploiting their oligonucleotide-tunable peroxidase-like catalytic activity, intrinsic fluorescence quenching capability, and excellent electrical conductivity. Upon ALD introduction, competitive desorption of 6-FAM-labeled aptamer from the nanozyme surface induced simultaneous signal changes across all three modalities. The biosensor exhibited a wide detection range (3 pg mL-1 to 20 ng mL-1) and an ultra-low limit of detection (LOD) of 1.016 pg mL-1. It not only enabled accurate quantification of serum ALD levels in depressive rats across different treatment groups for drug efficacy evaluation, but also performed reliable analysis of ALD concentrations in clinical human serum samples for depression diagnosis. Notably, the biosensor also supported non-invasive detection of ALD in saliva and urine, demonstrating strong potential for point-of-care testing (POCT) owing to its simplicity and rapidity. This multimodal strategy offers a powerful and practical platform for the objective diagnosis and therapeutic monitoring of depression.

8. Rethinking nursing: The re-classifying of a professional lifeline.

期刊: Nursing outlook 发表日期: 2025-Dec-22 链接: PubMed

摘要

9. Breastfeeding history is associated with women's health: Evidence and implications for practice and policy.

期刊: Nursing outlook 发表日期: 2025-Dec-22 链接: PubMed

摘要

The relationship between breastfeeding extent and duration with short- and long-term women’s health is a national concern. Our team of women’s health and breastfeeding experts provides recommendations and reviews the relationship between breastfeeding extent and duration with short- and long-term health in women. We provide policy-based recommendations at multiple level focused on promoting breastfeeding in all postpartum women to ultimately achieve better women’s health. The short-term relationships of lactation to women’s health are generally well known. The long-term relationships, while somewhat controversial, may be an important influence in several health conditions, including cancers, heart disease, metabolic disease and hypertension. The significance of effects or lactational history on women’s health deserves attention and actions to promote breastfeeding. While the infant benefits are undisputed, both short- and long-term effects of not breastfeeding on women’s health could be a cause for high morbidity and mortality and health care costs.

10. Pedagogical practices to support student workload management: A collaborative study with nursing educators.

期刊: Nurse education in practice 发表日期: 2025-Dec-19 链接: PubMed

摘要

This study aims to explore nursing educators’ definition of an adequate student workload in a first-semester undergraduate nursing curriculum and to identify pedagogical strategies that contribute to maintaining a balanced workload. Undergraduate nursing students often perceive their workload as excessive, which can lead to stress and negatively impact academic performance. Ensuring a well-balanced workload is crucial for student well-being and academic success, a responsibility where nursing educators play a key role. A collaborative qualitative research study was conducted. Eight nursing educators participated in five sessions to share their perspectives on student workload balance and effective pedagogical practices. A thematic analysis was performed to identify key pedagogical practices. Nursing educators define an adequate student workload as one that is well-balanced and enables students to develop the necessary competencies for clinical placements in the first semester. Sixteen pedagogical practices were identified and categorized based on their application before, during and after the course. Nursing educators play a critical role in managing the workload of first-semester students. Implementing structured pedagogical practices can help create a balanced workload, promoting student success and well-being.

11. Ischemic stroke nanomedicine.

期刊: Biomaterials 发表日期: 2025-Dec-19 链接: PubMed

摘要

With the changes in lifestyle and the intensification of population aging, the incidence of stroke has been increasing annually, making it a global public health concern. Early diagnosis and precise treatment remain critical factors in improving patient outcomes. Despite advances in clinical management, current diagnostic and therapeutic approaches still face significant limitations. Nanomedicine, leveraging the unique physicochemical properties of nanomaterials, has emerged as a transformative strategy to overcome these challenges. Translating nanotechnology-based innovations into clinical practice for stroke management hinges on a clear understanding of recent advances, persistent challenges, and future research priorities. This review elucidates the pivotal role of nanomedicine in advancing the early diagnosis and treatment of ischemic stroke, focusing on its major pathogenic factors, the diverse compositional features of nanomaterials, and surface design strategies. The discussion encompasses nanoplatforms serving as contrast agents for various imaging modalities, nanocarriers for drug delivery, and multifunctional nanosystems for therapeutic applications. Furthermore, the review explores the current challenges and considerations in the clinical translation of nanomedicine for ischemic stroke management, while proposing future research directions to highlight the advantages of nanotechnology in stroke theranostics and facilitate its clinical adoption.

12. Rethinking diabetic foot ulcer care: Integrating exercise and physical activity.

期刊: Journal of diabetes and its complications 发表日期: 2025-Dec-18 链接: PubMed

摘要

Because repetitive trauma and pressure contributes to diabetic foot ulcer (DFU) development and progression, offloading is one of the main therapies used in treatment. The term offloading has become conflated with a reduction in movement altogether, increasing sedentary time and, with it, the risk of associated adverse health outcomes. The aim of this narrative review is to evaluate the literature on movement-based interventions (reducing sedentary time, increasing physical activity (PA), or increasing exercise) in DFU patients. We found 16 articles that looked at the effect of exercise in individuals with a DFU. While many studies demonstrate the therapeutic potential of exercise, methodological inconsistencies between them prevent firm conclusions from being drawn regarding the efficacy of movement in promoting ulcer healing. The collected evidence underscores the need to address factors such as patient adherence, weight-bearing progression, and specifics surrounding movement programs (frequency, intensity, etc.) in future studies. Addressing these gaps, as well as determining barriers and facilitators to engaging in movement unique to those with a DFU, will advance research rigor and, with it, our understanding of how movement can be effectively leveraged to improve DFU care.

13. Hindlimb unloading results in accelerated bone loss compared to aging in select bone compartments of female murine femurs.

期刊: Journal of biomechanics 发表日期: 2025-Dec-16 链接: PubMed

摘要

Disuse- and age-induced bone loss both increase skeletal fragility and therefore are important to public health. There is a strong research foundation in each type of bone loss individually, but no study has directly compared the two in a controlled setting in female mice. In this study, we compare skeletally mature 6-month-old female mice subjected to hindlimb unloading for three weeks (HLU), to aged 22-month-old female mice to identify similarities and differences. Bone microarchitecture results indicated that there are compartmental differences that change in response to HLU and aging, but HLU demonstrates an intermediate phenotype between control groups of age-matched controls and aged mice. Similar results were observed biomechanically after three-point bending, with HLU demonstrating an intermediate phenotype in bone strength compared to aging. On histological examination, there was a significantly higher level of bone marrow adiposity after HLU greater than aging. There was a higher amount of DNA damage markers such as yH2Ax when comparing aged to young samples, but this was not seen with HLU. These findings indicate that disuse- and aging in bone show some phenotypic similarities but proceed along different timelines.

14. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Alzheimer’s disease (AD) is characterized by abnormal blood levels of specific proteins associated with amyloid plaques, tau pathology, and neurodegeneration, which are considered biomarkers of AD. To better understand the genetic architecture of AD in South Asians, we assessed the association between single nucleotide polymorphisms (SNPs) previously associated with AD and AD biomarkers with blood-level measures of seven AD biomarkers in 2,547 South Asians from the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD). We performed SNP-based association analysis between 152 AD- and 9 AD biomarker-associated SNPs with 7 AD biomarkers, including amyloid beta 40 (Ab40), amyloid beta 42 (Ab42), Ab42/Ab40 ratio, total tau (tTau), tau phosphorylated at threonine 181 (pTau181), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL). The model adjusted for age, sex, the first 10 genetic principal components (PCs), and incorporated the genetic relationship matrix and plate as random effects. Significance was declared at Benjamini-Hochberg FDR q<0.1. Identified loci were followed up with haplotype analysis to understand the potential driving factors. Among 152 AD-associated SNPs, rs199515_C (WNT3/MAPT) was associated with tTau in the expected direction (beta=0.21, p = 0.00052), whereas rs2718058_A (NME8) was associated with pTau181 in the unexpected direction (beta=0.13, p = 0.00057). Among the 9 biomarker-associated SNPs, rs242557_A (MAPT) was associated with tTau (beta=-0.139, p = 2.3e-08) and pTau181 (beta=0.099, p = 1.4e-04), and rs429358_C (APOE-e4) was associated with Ab42/Ab40 ratio (beta=-0.141, p = 0.0012). Follow-up analysis in MAPT, the gene that encodes the tau protein, identified a significant association between H1/H2 haplotype and tTau (global-p=0.00205). Specifically, H1j (p = 0.0015), H2 (p = 0.027), H1r (p = 0.031), and H1b (p = 0.041) were associated with lower levels of tTau, whereas H1c (p = 0.04) and H1o (p = 0.012) were associated with higher levels. Moreover, APOE-e4 stratified analysis detected significant H1j-tTau (score=-3.61, p = 0.00031) and H1c-pTau181 (score=2.55, p = 0.01) associations in e4 carriers only. The analysis highlights a critical role of MAPT in tau pathology in South Asians. The observed association does not seem to be fully driven by known risk haplotypes. It also provides evidence to suggest modification by APOE-e4. Further investigation of MAPT haplotype structure in this population is warranted.

15. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Mitochondrial dysfunction has been implicated in various age-related health issues and neurodegenerative disorders, but the role of mtDNA mutations is underexplored, especially in younger and more diverse populations. One key aspect of mtDNA is heteroplasmy, the presence of more than one allele in mtDNA, which may contribute to mitochondrial dysfunction. Additionally, mitochondrial haplogroups are maternally inherited groups of mtDNA variations that reflect ancestral lineages and may influence disease risk. Here, we evaluated the effects of mitochondrial heteroplasmy (mtHz) burden and mitochondrial haplogroup (mtHg) on cognition at mid-life. We studied 2308 participants from the Coronary Artery Risk Development in Young Adults study (mean age 45.25 ± 3.55 years, 58.2% female, 45.5% Black, and 55.5% White at baseline). Heteroplasmy burden 5 years from baseline was measured by the sum of Mitochondrial Local Constraint Score, which takes each variant’s observed-to-expected ratio adjusted by its homoplasmy count in population to calculate the constraint effect of the variant. Haplogroups were determined with reference to PhyloTree Build 17. We conducted multivariate linear regression to investigate associations of mtHg and mtHz to cognitive outcomes assessed 10 years from baseline, adjusting for baseline age, sex, race, and years of education. Race-stratified analysis was conducted to determine mtHg effects within race, with common haplogroups H and L3 as reference for White and Black participants respectively. There was no association between heteroplasmy burden and cognitive function. Haplogroups in macro-haplogroup L was significantly associated with worse cognitive outcome across all participants, particularly in processing speed and global cognition. mtHg N was associated with improved processing speed among White participants, and with better executive function, verbal memory, and global cognition among Black participants. mtHg K was associated with worse executive function among White participants. However, none of the race-specific associations were significant after adjusting for multiple comparisons. Our findings suggest potential associations between mtHg and cognitive performance, pointing to mtDNA variation as a possible factor of mid-life cognitive health. Race-stratified results underscore the need to account for different haplogroup distributions within racial groups and warrants further investigation to clarify the underlying genetic, environmental, and social contributors.

16. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

NIAGADS is a national genomics data repository that facilitates access of genotypic and sequencing data to qualified investigators for the study of the genetics of Alzheimer’s disease (AD) and related neurological diseases. Collaborations with large consortia and centers such as the Alzheimer’s Disease Genetics Consortium (ADGC), Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium, the Alzheimer’s Disease Sequencing Project (ADSP), and the Genome Center for Alzheimer’s Disease (GCAD) allow NIAGADS to lead the effort in managing large AD datasets that can be easily accessed and fully utilized by the research community. NIAGADS is supported by National Institute on Aging (NIA) under a cooperative agreement. All data derived from NIA funded AD genetics studies are expected to be deposited in NIAGADS or another NIA approved site. NIAGADS manages a Data Sharing Service (DSS) that facilitates the deposition and sharing of genomic data and association results with approved users in the neurodegenerative disease research community. In addition, researchers are able to freely use the NIAGADS Alzheimer’s Genomics Database (www.niagads.org/genomics/) to search annotation resources that link published AD studies to AD-relevant sequence features and genome-wide annotations. As of January 2025, NIAGADS houses 130 datasets comprised of >237,000 samples including array data, sequencing, gene expression, annotations, deep phenotypes, summary statistics, among others. Qualified investigators can retrieve ADSP sequencing data with ease and flexibility through the NIAGADS DSS. To date, the ADSP and other contributing studies have completed whole exome sequencing (WES) of 20,499 samples and whole genome sequencing (WGS) of 58,507 samples. Raw WES and WGS files, quality controlled VCF files, and phenotype data files are available via qualified access. The next round of sequencing currently underway will generate around 15,000 additional genomes to be released in 2026. NIAGADS is a rich resource for AD researchers, with the goal of facilitating advances in Alzheimer’s genetics research. By housing datasets from many projects and institutions, NIAGADS enables AD researchers to meet their research goals more efficiently. Datasets, guidelines, and features are available on our website at https://www.niagads.org.

17. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Alzheimer disease (AD) is the considered the most common cause of dementia second to vascular dementia (VaD) worldwide. AD and VaD are multifactorial conditions also influenced by genetic and environmental factors that accelerate the global burden of cognitive impairment and dementia in an ever-increasing ageing population even in the LMICs. Despite the best efforts to create the clinical biological construct of AD, post-mortem findings in >80% of probable AD cases show variable degrees of vascular pathology. Frequencies of brain white matter changes explained by a vascular cause rise exponentially from as high as 20% in 60-year-olds with almost doubling every decade thereafter in western populations. While these frequencies from imaging studies are not known among LMIC populations, it is expected the burden is high. For example, estimates in the burden of small vessel disease markers in the data from the INTERSTROKE studies suggest incidence of ischaemic or lacunar strokes was 4.7-fold greater in LMICs than in HICs. This translates to a high burden of vascular related cognitive impairment in Africa. Hypertension and diabetes mellitus are the main modifiable risk factors for the vascular disease. It is not clear in what ways other risks contribute to the vascular burden, but the harmful effects of hypertension are mediated by sustained structural changes in smaller arteries leading to arteriolosclerosis and fluctuations in cerebral perfusion. Cerebrovascular changes particularly arteriolosclerosis rather than infarction(s) appear early and amyloid plaque accretion occurs primarily before the onset of cognitive deficits, whereas neurofibrillary tangles, neuron loss, and particularly synaptic loss, parallel the progression of cognitive decline. The combination of vascular pathology and neurodegenerative changes are additive at each level of pathology lowering the threshold for development of AD dementia. Considering recent large sample studies, could AD therefore result from two different lobar processes such that vascular factors or disease affects the frontal lobe whereas neurodegenerative pathologies largely propagate from the temporal lobe even in African populations? Vascular disease remains a major contributor to morbidity and mortality, the whole burden of dementia can be reduced by vigorously tackling vascular risk factors at the individual, community and population level in Africa.

18. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Previous studies have related associations of carotenoids with cognitive function and Alzheimer’s disease. However, evidence regarding the associations of carotenoids with cognitive impairment (CI) is scarce. This study aimed to investigate the relation of dietary intakes of total carotenoids, provitamin A and non-provitamin A carotenoids to CI among middle-aged and elderly people. We conducted a prospective study among US adults aged 50 years and older based on the Health and Retirement Study from 2014 to 2020. Average daily intakes of dietary total carotenoids, provitamin A carotenoids (α-carotene, β-carotene and β-cryptoxanthin) and non-provitamin A carotenoids (lutein-zeaxanthin and lycopene) were assessed by a 163-item semi-quantitative food frequency questionnaire (FFQ). CI was evaluated using the Langa-Weir classification. Cox proportional hazards model examined the association between energy-adjusted carotenoids intake and CI. Among 5259 participants (mean age of 67.3±9.6 years), the median daily intake of total carotenoids, provitamin A carotenoids and non-prvitamin A carotenoids were 9.6 mg/d (IQR, 6.8-13.9), 3.2 mg/d (IQR, 2.0-5.2) and 6.0 mg/d (IQR, 4.3-8.6), respectively. After adjustment of sociodemographic characteristics, lifestyle variables, and other dietary factors, the consumption of total carotenoids was found to significantly reduce the risk of CI, with a hazard ratio of 0.81 (95% CI 0.67-0.97). Furthermore, both provitamin A carotenoids and non-prvitamin A carotenoids were independently linked to a 19% and 23% lower the risk of incident CI, respectively. Our findings support a beneficial role of carotenoid consumption on CI in middle-aged and elderly people, and guiding further investigations into the mechanisms and further validating the cognitive health benefits of a carotenoid-rich diet.

19. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Identification of mechanisms that link midlife cognitive function with parental history of AD among people racialized as Black, White, and Latinx may reveal potential interventions to reduce disparities in cognitive aging and dementia. Direct measurement of parental cognition is critical, because underdiagnosis of ADRD in minoritized populations may introduce bias in family studies. We evaluated the effect of parental AD/MCI history on middle age cognitive function, and determined whether genetic, biomarker, cardiovascular, or socioeconomic factors account for parental risk. Parents (n = 1124) were participants in the Washington Heights Columbia Aging Project (WHICAP), where diagnosis (48% normal cognition, 26% AD, 26% MCI) was established via consensus conference at baseline and follow-up waves that occur approximately every 2 years. Cognitive outcomes for their adult offspring (n = 1799, mean age = 56.1, SD = 11.0; range = 27 - 91; 66% Latinx, 19% Black, 14% White) for executive function, language, speed/attention, and memory domains were developed using a confirmatory factor analysis and scores from an extensive neuropsychological battery. Regression analyses controlling for offspring age, sibling relatedness, and remote/in-person assessment determined the association of parent status (AD/MCI vs normal) with offspring cognition. Subsequent analyses considered whether characteristics of parents (sex/gender, educational attainment, income, occupational prestige, APOE4 status, and cardiovascular burden) and offspring (cardiovascular burden and plasma levels of amyloid beta 42:40 ratio, pTau-181, NfL, and GFAP) accounted for the relationship between parental cognitive impairment and offspring cognition. Offspring of parents with AD/MCI had worse speed/attention, language, and memory than offspring of parents without AD/MCI. The effect of parent AD/MCI on offspring language scores was similar across race, ethnicity, and gender, but varied by group for attention, executive functioning, and memory. Accounting for parent education or income attenuated the effect of parent AD/MCI on offspring cognition by about 50%. None of the other genetic, biomarker, or cardiovascular variables in parents or offspring explained the effect of parent status on offspring cognition. In a community representative cohort, parent socioeconomic position was a significant driver of the effect of parent AD/MCI on poorer cognition.

20. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Untreated vision loss has been identified as a late life modifiable risk factor of dementia. The association of vision impairment (VI) and cognitive deficit in ageing is yet to be fully understood. In this case-control analysis, the vision comorbidities of two dementia cohorts (UK Biobank n = 11721, All of US n = 2350) were analysed using electronic health records in ‘International Classification of Disease-10’ (ICD-10) format. Mann Whitney-U analysis compared how dementia patients differed to controls with regards of pre-defined blocks of VI conditions. VI diagnostic block counts and age of first diagnosis of VI were used to understand prevalence, pattern occurrences and severity of impairments. ‘Visual disturbances and blindness’ counts showed a small but notable increase in the dementia group compared to controls in UKB (r = 0.034, p <0.0001) and AoUS (r = 0.15, p <0.0001). Earlier diagnoses of ‘muscles, movement, accommodation and refraction’ (r = -0.16, p <0.001) and ‘disorders of the lens’ (r = -0.11, p <0.001) VIs were also more associated with dementia patients. Time between first VI diagnosis and dementia onset was shorter in Alzheimer’s disease compared to Vascular dementia (p <0.001), but no other within-group differences were seen. Our findings demonstrated a significant association between diagnosis of selected VI groups and dementia and support early management of VI conditions for its prevention.

21. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The use of antidepressants in elderly patients with major depressive disorder (MDD) was associated with elevated risk of dementia, but the results published are conflicting. Using the Taiwan Nationwide Health Insurance Research Database, 30,390 patients with MDD and 24,312 well-matched controls were enrolled between 2002 and 2004. MDD patients were stratified into 6,078 patients with antidepressant-resistant depression and 24,312 patients with antidepressant-responsive depression, and all participants were followed up until the end of 2013. Those who developed any dementia, Alzheimer’s disease (AD), vascular dementia (VaD), and unspecified dementia were identified. Patients with antidepressant-resistant depression and antidepressant-responsive depression were more likely to develop any dementia, AD, VaD, and unspecified dementia than controls. Patients with antidepressant-resistant depression group exhibited significantly higher risk of developing any dementia (hazard ratio [HR], 13.02 vs. HR, 7.70) and unspecified dementia (HR, 12.81 vs. HR, 7.33) than patients with antidepressant-responsive depression, which was also higher than controls. Subsequent analysis demonstrated that patients with antidepressant-resistant depression who were resistant to SSRIs only (HR, 12.01) or both SSRIs and non-SSRIs (HR, 13.87) consistently showed higher risks of developing any dementia than patients with antidepressant-responsive depression (HR, 7.70), which is also higher than controls. With antidepressant-responsive depression group as reference group, patients with antidepressant-resistant depression who were only resistant to SSRIs (HR, 1.56) and those with both resistant to SSRIs and non-SSRIs (HR, 1.80) have higher risk of developing any dementia, but there was no significant difference between the two groups. The use of antidepressants in elderly patients with MDD was associated with elevated risk of dementia.

22. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Kidney function has been shown to predict cognitive impairment in previous studies. However, limited longitudinal studies have investigated the association between kidney function and cognitive impairment. This study aimed to explore this association in a non-demented elderly population. This prospective cohort study (2011-2019) is based on the Taiwan Initiative for Geriatric Epidemiological Research (TIGER). After exclusion, 515 non-demented older adults were included at baseline (2011-2013). Kidney function was evaluated by calculating the estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Kidney dysfunction was defined as participants with an eGFR <60 mL/min/1.73 m2 or the existence of proteinuria. Cognitive assessment includes global and domain-specific cognition (memory, executive function, verbal fluency, and attention), using the Taiwanese version of the Montreal Cognitive Assessment and a battery of neuropsychological tests, respectively. The generalized linear mixed model was utilized to explore associations of kidney function with cognitive impairment over time adjusting for important covariates [e.g., age, sex, years of education, apolipoprotein E ε4 status, depressive symptoms, body mass index (BMI), cigarette smoking, alcohol consumption, comorbidities, and serum levels of biomarkers, including interleukin-6 (IL-6) and C-reactive protein (CRP)]. The baseline mean age of this population was 72.7. The presence of kidney dysfunction at baseline was associated with poor performance in some cognitive domains as below. Baseline kidney dysfunction was significantly associated with poor performance of memory over time (immediate theme recall: β = -0.07, immediate free recall: β = -0.06, delayed theme recall: β = -0.06, delayed free recall: β = -0.05). Similar findings were found for executive function (Trail Making Test part B: β = -0.07). These associations became more evident in women or participants with higher years of education (β = -0.05 to -0.12). However, no significant association was observed for global cognition, attention, and verbal fluency. Baseline kidney dysfunction was associated with worse cognitive performance over time in older adults. Early screening for kidney dysfunction and cognitive impairment is essential for implementing preventive interventions to slow the progression of dementia. Further research is needed to elucidate the underlying mechanism between kidney dysfunction and cognitive impairment.

23. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The increasing prevalence of dementia among the elderly population poses a significant public health challenge, particularly in urban areas like Baguio City, Philippines. With a growing number of individuals living with dementia, there is an urgent need to foster dementia- friendly communities (DFCs) that can enhance the quality of life for those affected. This study aims to assess the current status of dementia-friendliness in Baguio City, the barriers and facilitators, and community recommendations. Ultimately, the main goal is to create an action framework dedicated to promote a dementia-friendly Baguio City. A qualitative approach was employed, utilizing in-depth interviews with 16 stakeholders, including healthcare providers, family members, caregivers, and community leaders. Participants were selected through purposive sampling to ensure diverse perspectives, and data were analyzed thematically to identify key concepts. The study revealed that Baguio City currently lacks a dedicated dementia ordinance and formal support programs specifically for individuals living with dementia. Awareness level among the public was low, with prevalent misconceptions equating dementia with normal aging. While a newly established daycare program for persons living with dementia was noted as a positive initiative, challenges such as late detection, out-of-pocket healthcare costs, and inadequate infrastructure for individuals with dementia were prevalent. The community’s attitude towards people living with dementia is generally supportive. With regards to nursing homes, some families recognize the need, but some express mistrust toward them. Recommendations include developing dedicated dementia policies, enhancing community awareness strategies, and improving local healthcare and support services. By implementing the action framework derived from this study, stakeholders can collaboratively work towards establishing a dementia-friendly community that prioritizes early detection, comprehensive care, and support while also promoting dementia prevention initiatives. Creating such an environment is critical for improving the well-being and quality of life for the growing elderly population in Baguio City, ultimately ensuring that individuals living with dementia are recognized, respected, and supported within their communities. Through collective effort and commitment, Baguio City can serve as a model for other areas striving to foster inclusivity and compassion for those affected by dementia.

24. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Many women experience declines in physical function across and beyond menopause. While there is an established bidirectional association between gait speed and cognition, longitudinal studies are needed to quantify the magnitude of these relationships. Additionally, prospective studies, particularly among older adults, are prone to selection bias due to differential loss-to-follow-up. We leveraged data from the Study of Women’s Health Across the Nation (SWAN) to quantify the associations between gait speed and cognitive function, accounting for loss-to-follow-up. SWAN is a multi-ethnic, community-based cohort of women followed through menopause into older adulthood. At study visits in 2012-13 (V13) and 2015-16 (V15), participants completed a timed four-meter walk to assess gait speed and tests of working memory, processing speed, and verbal memory. A summary measure of cognition, the cognitive z-score, averaged z-scores across cognitive tests. Linear regressions were employed to predict V15 cognitive z-score from V13 gait speed and vice versa, adjusting for demographic and socioeconomic characteristics. Inverse probability weights for missingness due to death, stroke, poor physical function, and other reasons adjusted for differential loss-to-follow-up from baseline. The sample included 1,258 women who completed gait speed and cognitive tests at visits 13 and 15, with a mean age of 65.5 years (SD=2.7) at V15. Half the sample was White, 23.5% Black, 12.2% Chinese, 10.8% Japanese, and 3.5% Hispanic. Adjusting for race, education, age, and financial strain, faster gait speeds at V13 were associated with higher global cognitive z-scores at V15 (β=0.20, 95%CI:0.05,0.35) but higher global cognitive z-scores at V13 were not significantly associated with faster gait speeds at V15 (β=0.017, 95%CI:-0.002,0.036). Adjusting for covariates and loss-to-follow-up, weighted models indicated gait speeds at V13 were positively associated with global cognitive z-score (β=0.22, 95%CI:0.06,0.37) and global cognitive z-scores at V13 were positively associated with gait speeds at V15 (β=0.022, 95%CI: 0.000,0.044). This SWAN sample exhibited a bidirectional relationship between gait speed and cognitive performance across time. Weighted estimates exceeded unweighted estimates, suggesting that models not accounting for selection bias underestimate associations. Future research will examine the longitudinal associations between specific domains of cognition and other measures of physical functioning among SWAN women.

25. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

In African countries, most people with dementia are cared for at home, but limited knowledge about dementia, lack of diagnosis and misdiagnosis and no formal supports leaves families with sole caring responsibilities. Limited knowledge leads to stigma and potential marginalization of those affected. This qualitative study examines the support needs of people with dementia and those who care for them at home in rural Kenya. The study was part of a wider study, ENGAGE, and used semi-structured interviews to gather data. We interviewed 17 people including people living with dementia, carers, health care workers and community members in Meru County. Participants were aged between 42 and 88 years and included 12 females and 5 males. Data were analysed using thematic analysis and findings were structured based on 4 of the Alzheimer Scotland 8 Pillar Model of Community Support namely; personalised support, support for carers, general healthcare and treatment and community connections. There is a huge knowledge gap and burden associated with caring for people living with dementia in rural Kenya. The lack/limited knowledge about dementia among family members, carers and health care workers was highlighted. Educating these individuals about dementia and equipping them with caregiver skills was considered vital to ease burden and address misconceptions about dementia. The role of the national and county government in developing training for carers and health workers was emphasised and so was the need for governments to build care homes for those at advanced stages of dementia and those with no family support. Participants called on the government to provide personalised support (finances and health insurance cover) to families affected. Religious institutions, such as the church were seen as having a moral responsibility to ensure that people with dementia and their families are not excluded from the community. With the number of people living with dementia projected to increase in Kenya, addressing the support needs of those affected is urgent. This study comes at an opportune time when the Ministry of Health in Kenya is developing a dementia policy, and findings from this study can inform the development of this policy.

26. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Dementia is associated with substantial economic burden for individuals, their care partners and family, communities, and society. There are myriad types of costs including those associated with medical care, long term care, supportive services, quality of life as well as others such as vulnerability to exploitation. There is a gap in annual, nationally representative, comprehensive cost estimates and variability across types of costs and persons. Tracking these costs over time as prevention, treatment and policy evolve will support efforts to reduce the economic impact of dementia. We used nationally representative data from the Health and Retirement Study (HRS) of U.S. adults over age 50 and other nationally representative data sources. We employed the U.S. Cost of Dementia Model (USCDM) - a dynamic microsimulation model and estimated medical and long term care costs, costs of time and earnings loss associated with unpaid family caregiving and quality of life of persons living with dementia and their care partners. In 2025, an estimated 5.6 million people are living with dementia in the United States. The medical and long-term care costs for dementia total $232 billion. Families and friends provide 6.8 billion hours of care, which is worth $233 billion. Many care partners also reduce their work hours or leave their jobs entirely, leading to a loss of $8.2 billion in annual earnings among care partners of parents with dementia. In addition to financial costs, people with dementia and their care partners experience a significant loss in quality of life, valued at $302 billion for those living with dementia and $5.9 billion among caregivers of parents or spouses with dementia. The USCDM, a comprehensive, well-validated dynamic microsimulation model, provides national, comprehensive estimates of total costs of dementia and by type of costs and who bears them. It is part of a larger effort to build capacity for researchers and policymakers to reduce the future impact of dementia.

27. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The Gateway to Global Aging Data (Gateway) is an open research platform supporting the Health and Retirement Study International Network of Studies (HRS-INS), a global network comprising longitudinal and multidisciplinary surveys of older populations across 46 countries. The Gateway integrates survey metadata, harmonized data files, and advanced tools to facilitate comparative studies on aging, brain health, and risk factors. Three initiatives-the Data Enclave, the Policy Explorer, and the Environmental Exposome -further enhance the platform’s capacity to study complex research questions. The Gateway delivers harmonized datasets and comprehensive survey metadata to enable cross-national and longitudinal analyses of critical domains such as health, economic status, and social networks. The Data Enclave provides a secure, remote-access computing environment for analyzing survey data while maintaining robust privacy protections and compliance with data-sharing policies. In parallel, the Policy Explorer links individual-level survey data to historical and current policy variables, empowering researchers to explore how macro-level policy environments influence aging outcomes, and the Environmental Exposome integrates data on physical, natural, and chemical environments. The Gateway have facilitated significant advancements in aging research. Harmonized data have revealed cross-national differences in aging experiences. The Data Enclave has enabled secure analyses of survey data, including cognitive health trends, while the Policy Explorer has supported research into the effects of retirement policies and social support systems on individual outcomes. The Environmental Exposome stimulate research on the effects of environmental factors on health and wellbeing. The Gateway to Global Aging Data serves as a critical resource for advancing cross-national research on aging. Through the integration of harmonized data and innovative tools, the Gateway empowers researchers to uncover policy-relevant insights, addressing global aging challenges and informing strategies to promote healthy and equitable aging worldwide.

28. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Social determinants of health (SDOH) contribute to cognitive resilience, ranging from healthy populations to aging individuals with cognitive impairment, including those with Alzheimer’s disease (AD) and related dementias. Plasma phosphorylated tau 217 (p-tau217) has been proven to be a specific biomarker reflecting AD pathology and severity (Jack et al., 2024). We aim to assess factors contributing to cognitive resilience among the Thai population. We prospectively enrolled participants into the INDE cohort in King Chulalongkorn Memorial Hospital, Bangkok, Thailand (NCT06375213), collecting exhaustive clinical information, neuropsychological tests, and plasma p-tau217. A regression model was fitted with Montreal Cognitive Assessment (MoCA) scores and plasma p-tau217 levels to calculate residuals, representing cognitive resilience. Positive residuals indicate high resilience, whereas negative residuals indicate low resilience. A second regression model examined factors associated with cognitive resilience, focusing on each SDOH, with adjustments for age and sex. Among 297 participants (73.4% female and median age 66 years [IQR: 61, 71]), 166 (55.9%) had high resilience (Table 1). A linear regression model showed an inverse relationship between MoCA and log-transformed plasma p-tau217 levels (β = -3.96, p < 0.01), and a box-and-whisker plot illustrated MoCA distribution across resilience groups (Figure 1). Multivariable linear regression analysis demonstrated that property ownership exceeding 10-million-baht, higher educational attainment, and meeting American Heart Association (AHA) physical activity recommendations were significantly associated with greater cognitive resilience. Higher education level correlated with increased resilience in a progressive manner. In contrast, greater distance from the city, current smoking, longer sleep duration, and increased daily sitting time were significantly linked to lower resilience (Table 2). SDOH notably impacted cognitive resilience, determined by the residuals of p-tau217 and cognitive score. Public policy and clinical intervention regarding factors associated with cognitive resilience are warranted, even in low- and middle-income countries (LMICs).

29. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Global health challenges like aging and dementia are shaped by socioeconomic disparities, environmental factors, and social determinants of health. We developed a behavioral age gap (BAG), measuring the difference between expected behavioral age and chronological age METHOD: We utilized a cross-sectional sample (n = 161,981) comprising countries from Latin America, Europe, Asia, and Africa. Behavioral age was estimated using a Gradient Boosting Regressor with 10-fold cross-validation, incorporating multiple risk factors (hypertension, diabetes, heart disease, female sex, visual impairment and hearing impairment) and protective factors (cognition, functional ability, education) associated with healthy aging. BAG was calculated as the difference between predicted and chronological age, and adjusted gaps were derived from the residuals of regressing BAG on chronological age. Chronological age was accurately estimated using biobehavioral predictors. Key protective predictors were functional ability, education, and cognition, while main risks were hearing impairment, heart disease, and hypertension. Participants were categorized into delayed or accelerated aging groups to explore biobehavioral factors in aging. Both models demonstrated high predictive accuracy, especially for accelerated aging. BAGs varied significantly across regions and income levels, increasing from Europe to Asia, LA, and Africa. Participants from LIC displayed accelerated aging compared to HIC. Adverse exposomes were linked to accelerated aging with large effect sizes. This work positions BAGs as markers of aging disparities, emphasizing the influence of inequalities and exposomes, while providing measures for targeted interventions and research.

30. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

It is vital to incorporate thoughtful, rigorous and intentional approaches to the engagement of Indigenous people living with dementia and their families in research and policy. Engaging people living with dementia can be different when working in partnership with Indigenous communities. Authentic engagement requires engagement at multiple levels to preserve self-determination across the entire research process. The Indigenous research landscape in Canada is framed by both federal research requirements and community-driven Indigenous ethical principles. The federal research requirements, articulated in the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, outline when and how community engagement should be undertaken with First Nations, Métis and Inuit individuals and communities. This includes when research will be done in partnership with Indigenous communities, or when research will be done with or analyses conducted with broader populations that may include and impact Indigenous people. These requirements provide a fail safe for academic Institutional Research Ethics Boards with which to hold researchers accountable to in a western model of research. It is perhaps more important, however, to consider community-led Indigenous ethical principles when engaging Indigenous people living with dementia and their families in research. Concepts such as respect, reciprocity, relevance and responsibility guide all our work but there are also distinctions-based approaches to ethical research relationships. Research with First Nations communities needs to consider the OCAP (Ownership, Control, Access, and Possession) research principles; research with Métis communities can refer to the Métis principles of research, and research with Inuit communities should implement Inuit research principles. In this session, we present examples of our commitment to upholding and asserting Indigenous self-determination while engaging Indigenous people with lived experience of dementia in research with the communities we each work with. Genuine relationships are the foundation and these relationships must be embedded and include people living with dementia in all stages of research, from initial research design, data collection, analysis and knowledge mobilization. We do this through sharing in ceremony, including traditional Knowledge Keepers and protocols and ensuring research and knowledge is co-produced and owned by the communities leading the research.

31. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Globally, the size and proportion of older adults are growing at an unprecedented rate. Given the rising incidence of health complications among older adults, it is critical to understand opportunities for improving the delivery of health care. Artificial intelligence (AI) is a promising technology that many argue has the potential to improve patient care, particularly by supporting and assisting older adults in diagnosing, managing, and treating health conditions. Although there have been significant studies on AI innovations in health care, there is an overall lack of literature on patient perceptions of the implementation of AI, specifically in older adult populations. This study addresses this gap in research by engaging older adults and focusing on AI and healthy aging. Utilizing an appreciative inquiry framework, the data collection consists of interviews with older adults to develop an understanding of how older adults perceive the use and consideration of AI in Northern Ontario, Canada. We analyze the findings using Braun and Clark’s (2022) thematic analysis six-step approach. The findings from this study highlight how AI technologies can better support older adults in Northern Ontario. The study highlights identifying older adults’ perceptions toward AI in healthcare settings, as well as the perceived barriers and facilitators to AI utilization in Adult Day Centers/Older Adults Centers and Retirement Homes. The study contributes to the development of specialized educational materials or training programs designed to raise awareness and practice, encourage advocacy, improve comfort levels with AI technologies, and ultimately enhance older adult patient care. The findings will be informed to policymakers and stakeholders for adjusting policy reform and analysis. This study shed light on how older adults feel toward AI, how they envision improvements, and what improvements could be made for future health practices using AI technologies. Overall, this research could help identify factors contributing to better AI-enabled care of older adults, and it could shed light on how AI technologies could evolve to better meet the needs of older adults.

32. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Adulthood socioeconomic status (SES) is associated with better late-life brain health but links with lifecourse SES are unclear. Among Kaiser Healthy Aging Diverse Life Experiences (KHANDLE) participants who completed a brain MRI (n = 444), we defined high financial capital in childhood if family finances were “pretty well off” or “about average” and in adulthood if household income was 3$75,000; high cultural capital in childhood if at least one parent had a high school diploma, and in adulthood if the participant had a bachelor’s degree; high social capital in childhood if the participant had an adult they could trust most/all of the time, and in adulthood if the participant had someone in whom they could confide. SES trajectories were defined as consistently high, high childhood/low adult, low childhood/high adult, and consistently low. Linear regression models estimated associations of childhood and adulthood capital with mean cortical thickness (CT) overall and in AD signature regions. Childhood models adjusted for age at MRI, sex, race/ethnicity and MRI scanner model. Adulthood models additionally adjusted for childhood capital. SES trajectories were examined overall and stratified by sex. Participants’ mean age was 75.1 (SD=6.0); 56% were female (Table 1). There were no significant differences in CT by financial capital in adulthood or childhood (Table 2). Participants with high (vs. low=reference) childhood cultural capital had greater left hemisphere CT (mean b=0.04 [95%CI=0.01, 0.08]), while those with high (vs. low=reference) adulthood cultural capital had smaller left hemisphere CT (mean b=-0.04 [95%CI=-0.07, -0.01]). Those with high (vs. low=reference) childhood social capital had smaller left entorhinal CT (b=-0.08 [95%CI=-0.01, 0.16), while those with high (vs. low=reference) adulthood social capital had greater CT, especially in the entorhinal cortex (Left b=0.11 [95%CI=0.02, 0.19]; Right b=0.09 [95%CI=0.01, 0.18]). Examination of SES trajectories from childhood to late life revealed a pattern whereby men, but not women, with high financial capital at any point in the lifecourse (ref.=consistently low) trended toward greater left CT (Figure 1). High childhood cultural capital is an important protective factor for late-life brain health. Sex-specific patterns of SES trajectories may provide insights for targeted brain health promotion.

33. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Black Americans are disproportionally affected by dementia and are underrepresented in Alzheimer’s disease research. Furthermore, Black men have the shortest life-expectancy of any race/sex population subgroup in the U.S. and cardiometabolic disease is their leading cause of death. Therefore, there is a pressing need for culturally-informed interventions to address modifiable risk factors for dementia within this population subgroup. Black Impact is a 24-week wellness program designed in partnership with academic, community, and government organizations in Central Ohio to promote cardiometabolic health in Black Men. Black men are screened for cardiometabolic disorders at various community engagement events and enrolled in the program based on their Life’s Essential 8 score, a composite measure of blood sugar, hypertension, hyperlipidemia, body mass index, nutrition, smoking, physical activity, and sleep quality. Participants complete 45 minutes of group exercise and 45 minutes of health coaching weekly for 24 weeks. Arterial stiffness is assessed using pulse wave velocity at baseline, week 12, and week 24. Cognitive assessments are performed at baseline and week 24 using selected measures the NIH Toolbox, including receptive vocabulary (Picture Vocabulary), processing speed (Pattern Comparison), cognitive flexibility (Dimensional Change Card Sort), nonverbal reasoning (Visual Reasoning), and memory (RAVLT Immediate and Delayed Recall). Neighborhood disadvantage was assessed using the Area Deprivation Index. Hierarchical linear regression and serial mediation analyses were conducted to examine associations among neighborhood disadvantage, cardiometabolic health, and cognitive performance at baseline. Participants include 88 Black men (mean = 55.1 years old, 15.4 years of education). Higher neighborhood disadvantage was associated with lower Life’s Essential 8 scores and lower receptive vocabulary. Higher arterial stiffness was associated with lower Life’s essential 8 scores and poorer cognitive flexibility. Serial mediation analyses showed a significant direct effect of neighborhood disadvantage and receptive vocabulary; the indirect effect via Life’s Essential 8 and arterial stiffness was not significant. Hierarchical regression analyses indicated that neighborhood disadvantage predicted receptive vocabulary above and beyond the influence of age, education, Life’s essential 8, and arterial stiffness. Neighborhood disadvantage may provide unique value towards understanding within-group social determinants of cardiometabolic and cognitive health among Black men.

34. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Dementia poses serious challenges for individuals and communities. We first piloted a 12-month multidomain program-encompassing exercise, nutrition, cognitive training, social engagement, and vascular risk management-in O City to assess feasibility. Building on these results, we then revised the intervention into a 6-month basic course plus a 6-month continuation class for H Town, aligning with municipal needs and the common practice of transitioning participants to self-directed groups. We also trained local instructors and assessed a structured process for participant enrollment and follow-up. In 2023, we conducted a one-arm trial in O City with 80 community-dwelling older adults (aged 65-86). We defined feasibility as attendance at ≥60% of sessions over 12 months, and measured acceptability on a five-point scale. Cognitive function was monitored via the Japanese version of the Montreal Cognitive Assessment (MoCA-J; range 0-30), and food diversity was evaluated using a standardized questionnaire. In 2024, we implemented a revised format in H Town featuring a 6-month basic program followed by a 6-month continuation class. We employed a structured enrollment protocol comprising (1) identifying older adults with hypertension or hyperglycemia, (2) mailing invitations (n = 801), and (3) conducting an informational session. Three local instructors were trained, and we recorded participant enrollment and willingness to continue. In O City, 75% of participants met the 12-month attendance criterion, and the mean acceptability score was 4.4 out of 5. Mean MoCA-J scores remained stable (22.8 ± 3.1 to 23.1 ± 3.5), while food diversity improved significantly (7.5 ± 2.8 to 8.4 ± 2.5; p = 0.008). In H Town, 33 older adults (4.1%) attended the informational session, and 19 enrolled. More than 70% indicated willingness to continue at personal cost after completing the revised program. Feasibility and acceptance of this multidomain dementia-prevention program were demonstrated in two municipalities through distinct implementation models. Findings from O City informed the 6-month structure in H Town, which aligns with local practices for transitioning participants to self-directed groups. Future controlled studies should further clarify cognitive and health outcomes and refine recruitment and follow-up strategies for broader community impact.

35. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

In South Korea, the annual incidence rate of dementia is 18.8 cases per 1,000 elderly individuals, rising with age from 12.5 cases per 1,000 (65-74 years) to 87.2 per 1,000 (≥85 years). In 2021, 22.7% of individuals aged 65 and older had mild cognitive impairment, indicating that one in five elderly individuals is affected. Dementia significantly contributes to functional limitation and dependency, underscoring the need for effective prevention and management strategies. The purpose of this study is to identify population-specific and modifiable cognitive reserve markers using Korean Longitudinal Study of Aging data collected prospectively from 2006 to 2020 in South Korea. Additionally, it aims to determine the magnitude of these markers as protective factors against the occurrence of mild cognitive impairment and dementia. The study utilizes data from 10,254 individuals aged 45 and older who completed relevant questionnaires on cognitive reserve markers and mild cognitive impairment or dementia diagnoses in waves 7-9 (2018-2022), excluding those with prior diagnoses of mild cognitive impairment and dementia. Cognitive reserve indicators include education level, economic activity, type of occupation, leisure activities, physical activity, and financial management ability. Dementia incidence was self-reported, with additional data on timing. Covariates include sociodemographic factors (age, sex, marital status, income) and modifiable risk factors (e.g., hypertension, depression). Descriptive analyses will assess the incidence of dementia and mild cognitive impairment by cognitive reserve markers. Cox proportional hazards regression will estimate associations between cognitive reserve markers and the risk of dementia or mild cognitive impairment. This prospective cohort study will identify modifiable cognitive reserve markers and evaluate their protective effects, contributing to Korean-specific brain health initiatives for dementia prevention and cognitive health promotion.

36. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The aim of the LEAD 2.0 Trial is to understand whether a 6-month online exercise and diet intervention is feasible among older adults at risk for dementia. Here we describe preliminary data on recruitment feasibility and baseline characteristics of LEAD 2.0 participants. The LEAD 2.0 Trial is a 6-month factorial, randomized controlled trial among older adults with subjective cognitive decline (SCD). Feasibility will be evaluated based on recruitment (target: 9 participants/month), adherence (target: 75% of sessions attended), and retention (target: 80% of participants complete 6-month assessment). The exercise intervention included two virtual, group sessions and one independent, pre-recorded video session each week. The diet intervention included one weekly session of healthy diet counselling with goal setting. Stretch and brain education served as time/frequency/social matched controls for exercise and diet counselling interventions respectively. Assessments at baseline, 6 months, and 12 months were also conducted virtually. A total of 574 participants were screened from July 2023 to November 2024, with the greatest proportion responding through targeted e-blasts through ZoomerMedia Limited (46.9%), research participant databases (12.2%), and participant referrals (8.4%). Of those sources, the highest portion of eligible individuals came from research participant databases (45.7%), promotion through local/provincial/national organizations (37.5%), and participant referrals (31.3%). Of 574 individuals screened, 236 passed lifestyle screening, 167 passed cognitive screening, and 146 were randomized (9.1 recruited per month). Eligibility was expanded from executive SCD to all SCD after one month of recruitment. Average age of participants was 72.5 ± 5.2 years, 80.8% were female, 85.6% were White, 88.4% had a college/university degree or greater, 61.6% were married, and 79.5% were retired. Recruitment to the LEAD 2.0 Trial occurred at target rates using a broad range of recruitment avenues. Targeted e-blasts produced the largest number of participants screened, while research participant databases produced the greatest recruitment yield. Men, people of minority ethno-cultural groups, and people with low education remain under-represented.

37. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Cognitive frailty (CF), a condition characterised by the co-occurrence of physical frailty and cognitive impairment, has been linked to dysregulated gut microbiota (i.e., dysbiosis) and increased intestinal permeability. Emerging evidence suggests that the gut microbiome plays a crucial role in maintenance of gut-brain barrier integrity, suppression of neuroinflammation, regulation of neurotransmitter production, and ultimately promotion of psychological health. This study aimed at examining the effects of a 6-month multidomain intervention (i.e., physical exercise, cognitive training, psychosocial training and nutritional guidance) on gut microbiota composition. A total of 27 CF participants (12 control; 15 intervention) were recruited and stool samples were collected for 16S rRNA sequencing. The stool samples were homogenised, and DNA was extracted, followed by PCR amplification, DNA library preparation, and sequencing. Statistical analysis was performed using GraphPad Prism. Normality was assessed using the Shapiro-Wilk Test, and differences between groups were analysed using the Ordinary One-way ANOVA Test. Correlations between genus abundance and psychosocial parameters were evaluated using Pearson’s correlation analysis. Microbiota profiling revealed a significant increase of the Blautia genus in the intervention group (IV6, intervention after 6 months) when compared to the control group (C6, control after 6 months) (p = 0.0132), suggesting a positive shift in gut microbial balance following lifestyle modifications. The Blautia genus abundance was negatively correlated with depression (r = -0.4120, p = 0.0022) and loneliness scores (r = -0.3328, p = 0.0184), indicating its potential protective role against psychosocial factors. On the contrary, the Prevotella genera exhibited a positive correlation with depression scores (r = 0.2820, p = 0.04), reinforcing its association with neuroinflammation which disrupts neurotransmitter balance. The present results highlight the positive impact of lifestyle interventions on gut microbial composition and their possible implications for psychosocial health in older adults with CF. The Blautia genus enrichment may serve as a biomarker or therapeutic target for improving psychosocial well-being in CF individuals. This warrants further investigation of the mechanistic pathways linking gut microbiota modifications with psychosocial outcomes. This study is part of the Transforming Cognitive Frailty to Later-Life Self-sufficiency (AGELESS) project funded by the Ministry of Higher Education, Malaysia under the Long-Term Research Grant Scheme (LRGS/1/2019/UM/01/1/3).

38. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Previous evidence suggests that urban design features, like neighbourhood walkability, are associated with cognitive outcomes and mental well-being in older adults. Here, we examined associations between walkability and cerebrospinal fluid (CSF) markers of amyloid, neurodegeneration, and neuroinflammation, as well as depressive symptoms, considering neighbourhood deprivation and cognitive status. We analysed cross-sectional data from 255 participants (both cognitively impaired and unimpaired) from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort. The predictors included walkability assessed within 300m radius around participants’ residences. Outcomes included CSF biomarkers of AD pathology (Aβ42), neurodegeneration (T-tau), and neuroinflammation (YKL-40), as well as depressive symptoms (Geriatric Depression Scale; GDS-30). Participants also had data on neighbourhood deprivation levels measured with the Area Deprivation Index (ADI). We performed multiple linear regression models to examine associations between walkability and the outcomes, with stratification by neighbourhood deprivation level (low, medium, high) and cognitive status (CU, MCI and Dementia). All models were adjusted for age, sex, education, APOE ε4 status, and MMSE scores. Participants’ age ranged from 45 to 87, 53% were women, and 26% were diagnosed with dementia (39% AD, 18% Lewy Body and 17% Frontotemporal Dementia; Table 1). In the whole sample, higher walkability was only associated with lower T-tau levels, with no associations observed for other outcomes (Table 2). Stratified analyses by area deprivation, showed that higher walkability was associated with lower T-tau and YKL-40 levels among individuals living in areas with higher ADI. Additionally, higher walkability was marginally associated with lower GDS-30 scores among individuals in medium-deprivation areas. Stratified analyses by cognitive status, showed that higher walkability was associated with lower Aβ burden only among individuals with dementia (Figure 1). Our findings link neighbourhood walkability to neurodegeneration, as well as neuroinflammation and depressive symptoms in highly and moderately deprived areas and to lower Aβ in individuals with a dementia diagnosis. Future research should explore the mediating mechanisms linking walkability to brain and mental health, including physical activity and mental health promotion. Urban planning strategies may consider both walkability and neighbourhood socioeconomic context to optimize cognitive and mental health outcomes in aging populations.

39. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The quality of culturally appropriate brain health promotion materials Indigenous people in Canada is lacking. Canada’s National Dementia Strategy calls for additional work to improve brain health promotion and dementia prevention for Indigenous people as a priority. Health promotion and healthy brain aging for Indigenous communities also needs to be understood in a distinctions-based and culturally specific way. Providing brain health promotion materials that are strengths-based, while also being grounded in Indigenous knowledge systems and experiences is an urgent priority in Canadian health systems and plays an important part in enhancing patient safety and closing gaps in health inequities. The primary outcome of this project was to develop understanding regarding how the Brain Health Pro can be adapted to a Métis context in the province of Alberta, Canada. Our overarching ethical approach embeds integrated knowledge translation into the development and implementation of brain health promotion material so that the research outcomes are directly applicable and useful to communities. Interviews were completed using the Métis visiting methodology (Keeoukaywin) to allow for the emergence of new themes. Data was co-analysed using Indigenous approaches to thematic qualitative analysis. Twenty Métis people in Alberta participated in a total of 63 interviews between July and November 2024. Participants felt that the current content and mode of delivery of Brain Health Pro was not appropriate for Métis people living in Alberta. Themes included a western dominance of brain health (including a lack of Indigenous people in the video content, no Métis Ways of Knowing; a lack of non-virtual options (for those who may not have reliable internet access); and a need for holistic approaches to risk reduction (e.g. berry picking could provide physical activity, social interaction and healthy traditional food options and be an avenue for intergenerational knowledge mobilization). The work will be developed to facilitate spread, scale and adaption to other local Indigenous contexts. Additionally, the principles and methodology may be applied internationally to develop locally driven and culturally specific dementia care intervention for Indigenous populations or other underrepresented populations.

40. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Virtua Health, the largest health system in southern New Jersey, serves >140,000 Medicare patients, including 70,000 primary care patients aged ≥65 years, across 38 primary care practices. Fewer than 25% of these patients are screened annually for cognitive impairment, with only 2.5% having a confirmed diagnosis of Alzheimer’s or related dementias, far below the national average of 10.9%. To address this gap, Virtua Health, through the Davos Alzheimer’s Collaborative Healthcare System Preparedness (DAC-SP) U.S. Early Detection Fellowship program, is implementing an early detection program for cognitive impairment in primary care, building on the foundational elements of its participation in the DHHS-HRSA funded Geriatric Workforce Enhancement Program (GWEP), the CMS GUIDE model, and creating a geriatric service line. The DAC-SP Early Detection Blueprint will accelerate early detection of cognitive impairment in primary care by developing workflows and standing order sets in 5 pilot practices with plans for future expansion. Rapid Cycle Quality Improvement will address barriers, incorporate stakeholder feedback, and guide structure and process adjustments for early detection of cognitive impairment. Digitized iPad-based cognitive screening will be integrated into Annual Wellness Visits. Positive cognitive screens will trigger clinical pathways and standing orders to assist providers in diagnosing and managing cognitive impairment. Scheduling accommodations will support providers in the early detection and diagnostic process. Virtua Health hopes to increase screening of eligible patients for cognitive impairment by 30-50% across 5 pilot practices and exceed the 10.9% national average dementia diagnosis rate. Project participation will create new care pathways and improve patient access to team-based comprehensive dementia evaluation, advanced diagnostic modalities, care navigators, brain health programs, and disease-modifying therapies. The DAC-SP U.S. Early Detection Fellowship is a catalyst for system-wide change, creating a sustainable model to enhance dementia care, reduce disease burden, and improve quality of life for older individuals, their families, and caregivers. Standardized care pathways, AI tools, clinician training, and stakeholder collaboration enable Virtua Health and its primary care providers to play a pivotal role in early detection of dementia, leading to improved access to disease-modifying therapies, promotion of brain health, and better management of cognitive impairment.

41. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Although about 45% of the risk of dementia could be modifiable, nearly 80% of the population still believe dementia is a normal part of aging. Dementia prevention awareness campaigns could be low-cost feasible strategies to promote dementia risk reduction. Nonetheless, what are their real impacts and what strategies may work better have not been analyzed. Thus, this was the aim of our study. A systematic review of literature published up to July 2024, with no language or publication time restrictions was conducted. Studies in any population, using any research design, and assessing the effect of a dementia prevention awareness strategy were included. The literature search was conducted through five databases (PubMed, Scopus, Google Scholar, Lilax, Scielo). Duplicate documents were removed using EndNote, and relevant studies were selected through blinded screening by two independent reviewers and using an AI (ASReview). Results were analyzed using a narrative synthesis and studies’ risk of bias. From 3,898 articles retrieved, 16 studies comprising a total of 34,441 participants fulfill inclusion criteria and were included. Campaigns were tested mostly in Europe (43.8%), Australia (31.3%), and United States (17.6%), and included people from all ages (<24y: 50.0%, 24-59y: 87.5%, >60y: 81.3%). Most of the studies were quantitative (cross-sectional:3; pre-posttest:9; RCT:2). The most used awareness strategies were web pages (50.0%), community talks (43.8%), and printed material (37.5%). In the group of studies using cohort designs (pre-posttest and RCTs: 11), most of the studies found an increase in population’ knowledge about risk factors or protective behaviors (n:7/8), intention to change behavior (n:2/2), and knowledge about dementia (n:1/1). However, no consistent results were observed in dementia risk-reduction awareness (n:3/6) and no studies assessed health behavior change. Positive results are seen most often at short-term and using instructive strategies (MOOC, talks). One study assessed people at risk of dementia, with no significative differences. Overall, studies’ risk of bias was high. Dementia prevention awareness campaigns could increase knowledge about dementia risk factors across the lifespan. Nevertheless, the effect on dementia risk-reduction awareness and behavioral change is uncertain, and more high-quality studies targeting populations at risk of dementia are needed.

42. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Compared to individuals carrying two copies of the E4 allele of Apolipoprotein E (APOE), E2 homozygotes have a ∼99% reduction in late-onset Alzheimer’s disease (AD) risk. Given its strong risk profile and multitude of biological effects, APOE presents as a clear candidate for gene therapy. In principle, a full ‘correction’ of E4 to the highly neuroprotective E2 allele could delay or prevent AD for millions of individuals. Here, we aimed to determine the therapeutic potential of cell-type and pool-specific (CNS vs periphery) APOE allele replacement and explore potential mechanisms therein. We assessed the physiological and neuropathological changes associated with an in vivo APOE4 to APOE2 transition selectively in hepatocytes, astrocytes or microglia using a novel transgenic APOE “switch mouse” (APOE4s2) model. These mice express a floxed human APOE4 coding region followed by the human APOE2 coding region. mRNA and proteomic analyses were employed to validate an efficient E4 to E2 transition in target cell-types. Behavioral measures and a suite of neuropathological analyses were applied to assess the effects of an late-stage allelic switch on amyloid, cognition, and plaque-associated glial reactivity. RNA and protein analyses confirm that APOE4s2 mice synthesize APOE4 pre-switch, and that tamoxifen induces efficient recombination and expression of human APOE2 in target tissues. Single-cell transcriptomics reveals that glia-selective replacement of APOE4 with APOE2 results in distinct cell-autonomous and non-autonomous alterations to the transcriptome. Neuropathological analyses show that while both an astrocyte- and microglia-specific E4 to E2 ‘switch’ significantly decrease total amyloid burden, the effects of a hepatocyte-specfic APOE replacement are much more subtle. Further, there are unique (and sometimes disparate) cell-type driven responses in gliosis and cognitive outcomes. Together, these data suggest that while either an astrocyte- or microglia-specific E4 to E2 replacement is sufficient to mitiage amyloid pathology, the cellular response to AD pathology differs substantially depending on the cell type targeted. Overall, this proof of concept data provides insight that will be valuable for guiding development of future APOE directed therapies.

43. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Sex differences have been demonstrated in AD. The exact mechanism of sex biases in brain diseases remains unclear but likely involves an interplay between the endocrine and the nervous systems. Estrogen and progesterone, the primary ovarian hormones dominant at different cycle stages, can exert opposing effects to the brain. Randomized clinical trials and observational studies also revealed that the peri-menopausal phase of the life cycle of aging women is particularly associated with declines in memory function, increased risks of mild cognitive impairment and dementia. Despite so, the potential connection between hormone replacement therapy use and the risk of dementia remains a subject of ongoing debate for years, and that the intrinsic cellular changes underlying the enhanced disease vulnerability observed in postmenopausal women remain elusive. Mining of brain transcriptomic and metabolomic datasets from the ROSMAP cohort was performed. In vivo behavioral analyses, brain transcriptomic, metabolomic and electrophysiological analyses were conducted in an accelerated ovarian failure mouse model, ERRα knockout, and the Lafala-AD transgenic mouse models. Elevated estradiol to progesterone ratio (i.e., estrogen dominance) during the onset of perimenopause is correlated with elevated risk to cognitive and memory decline. Human brain transcriptomic and metabolomic changes pointed to the impaired function of ERRα (estrogen-related receptor alpha). Progesterone-guided estrogen receptor signaling stimulates ERRα activity indirectly by its actions on neuronal cholesterol homeostasis. Consequently, this prevents truncation of the TCA cycle at succinate dehydrogenase, which would otherwise cause a net catabolic shift of N-acetyl-aspartyl-glutamate (NAAG) driven by an adaptive aspartate-dependent response that attempts to reconstruct a “mini-cycle”. The free glutamate released alongside the net catabolism of NAAG is stochastically released pre-synaptically, thereby increasing spontaneous neuronal activities. Coupled with the bioenergetic incompetency that occurs during estrogen dominance, this slowly depletes cellular ATP and increases susceptibility to energy crises triggered by additional excitatory insults, such as age-related intraneuronal accumulation of APP or Aß. Collectively, our work reveals an unforeseen interaction cholesterol balance and mitochondrial energy production in neurons. The findings also shed light on the potential impact of estrogen dominance during the perimenopausal transition, contributing to increased susceptibility to AD/ADRD among aging women.

44. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Therapeutic strategies aimed at clearing or preventing the accumulation of Aβ have dominated disease-modifying Alzheimer’s disease (AD) drug development for decades, with monoclonal antibody (mAb) immunotherapies at the forefront of this effort. Anti-Aβ immunotherapies are now showing some promise in the clinic, leading to modest reductions in cognitive decline in AD patients. The only modest reduction in cognitive decline elicited by anti-Aβ mAbs underscores the need for improved antibodies that lead to a greater reduction in cognitive decline in AD. mAbs that target disease-related conformations and assemblies of Aβ offer the promise of improved efficacy. This talk presents the creation and study of monoclonal antibodies designed to target disease-related conformations adopted by Aβ. These antibodies were raised against peptide antigens that mimic β-hairpins of Aβ and oligomers formed by the β-hairpins. X-ray crystallography reveals the high-resolution structures of the antigen binding domains from several mAbs bound to their Aβ targets. These structures reveal atomic-level details about the Aβ epitopes recognized by the mAbs. Several of the mAbs recognize unique Aβ pathology in AD brain tissue and in 5xFAD mouse brains. The X-ray crystallographic studies in combination with these immunostaining studies offer clues about the structures and conformations that Aβ adopts in the brain. Immunotherapeutic studies in AD mice will reveal if targeting these epitopes offers therapeutic potential to possibly reduce brain amyloid and lead to cognitive and behavioral improvements. Monoclonal antibodies generated against conformationally constrained Aβ β-hairpins and oligomers are new tools for probing the structural landscape of Aβ in the brain. These antibodies offer the promise of new diagnostics and new avenues for AD therapies.

45. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The cross-species translation of cognitive testing is a critical approach for advancing our understanding of Alzheimer’s disease (AD). Mouse models of AD enable causal mechanistic insights into how genetic and biological factors influence cognitive decline. Recent developments in touchscreen-based cognitive tasks allow for consistent testing paradigms in both humans and mice, bridging the gap between preclinical and clinical research. Through an ongoing collaboration between Western and McGill Universities, we are leveraging homologous touchscreen tests of cognition in parallel studies of next-generation mouse models of AD and humans at risk for AD. Mouse models with humanized knock-in genes (amyloid, tau, ApoE ε3 or ε4) are being used at Western University to explore how genetic factors interact with age and sex to influence executive function. These experiments use the Continuous Performance Task (CPT), a sensitive touchscreen-based probe of selective attention. Since 2021, we have been integrating the CPT into the longitudinal PREVENT-AD study led by McGill University and the Douglas Research Centre. Over 425 individuals (aged 60-80 years) with intact cognition at baseline and family history of AD are enrolled in PREVENT-AD. Since 2011, this cohort has contributed a comprehensive dataset that includes multimodal neuroimaging, cerebrospinal fluid biomarkers, neurosensory measures, and standard cognitive assessments. We have acquired CPT in >220 individuals, with longitudinal data collected from approximately 80 of these participants and counting. This talk will explore the integration of touchscreen-based cognitive testing into both human and mouse studies and its role in elucidating the mechanisms of AD risk. I will discuss how PREVENT-AD human and mouse touchscreen CPT data can shed light on the interaction of ApoE genotype, age, and sex in early cognitive dysfunction. Additionally, I will explore whether touchscreen tests of cognition differ from standard neuropsychological tests in their sensitivity to early AD-related decline. Finally, I will outline plans to expand the use of touchscreen tests within PREVENT-AD and other large-scale consortia. By linking genetic risk, cognitive performance, and neurobiological markers, this cross-species approach will advance our understanding of AD’s earliest manifestations and support the development of targeted interventions.

46. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Alzheimer’s disease is characterized by the accumulation of Aβ plaques in the brain, but the pathways leading from early Aβ deposits to eventual neurodegeneration are not fully understood. The specific role of microglia in AD is controversial, with microglial activation to be protective or detrimental depending on disease progression. We developed a 3D human iPSC-derived neurosphere model to better characterize how microglia respond to Aβ pathology. Neurospheres were grown from iPSC-derived neuronal progenitor cells and cultured for 60 days. iPSC-derived microglia were added separately to assess their functional impact. Continuous synthetic oligomeric Aβ treatment was used to model amyloidosis. Genetically encoded sensors roGFP1 and GCaMP6f allowed to monitor neuronal oxidative stress and calcium activity, respectively. Single nuclei RNA sequencing (snRNA-seq) was performed to examine transcriptomic differences induced by Aβ and microglia. Neurospheres grew to consist of a complex network of healthy mature neurons and astrocytes. The added microglia readily infiltrate the 3D tissue. Chronic Aβ treatment resulted in the formation of plaque-like aggregates and subsequently led to severe oxidative stress and loss of neuronal activity. Microglia were able to prevent these neurotoxic effects in neurospheres that received mild 3 weeks Aβ treatment, but failed to do so after severe 5 weeks treatment. snRNA-seq revealed that, after 3 weeks treatment, microglia induced upregulation of genes linked to oxidative regulation in astrocytes. After 5 week treatment, microglia more noticeably drove the expression of many AD-associated genes, such as APOE, CLU, and FTL, in astrocytes and neurons. Microglia also appear to have enhanced ability for Aβ clearance after treatment with anti-Aβ antibodies. We developed a human 3D neurosphere model to study microglial responses to Aβ pathology. In this model, microglia acquire a neuroprotective phenotype which may be enhanced by anti-Aβ antibodies. Microglia are essential for driving the transcriptomic profile linked to AD after severe Aβ treatment. By mimicking critical AD pathological features, this model offers a platform to identify therapeutic targets with translational relevance.

47. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The locus coeruleus (LC) is one of the first epicentres of tau pathology in Alzheimer’s disease, displaying pathology decades before clinical symptom onset. We investigated whether LC integrity was associated with cortical deposition of amyloid and tau in vivo in asymptomatic, at-risk older adults. 208 healthy older adults with first-degree familial history of Alzheimer’s disease were included from the PREVENT-AD cohort (mean age 68.4 ± 5.14y, 69% female). 155 subjects were also examined longitudinally over 38.8 ± 14.0 months. Subjects underwent longitudinal 3T MRI: 1mm3 T1w MPRAGE and Neuromelanin-sensitive brainstem imaging (0.7x0.7x1.8mm). Cortical amyloid and tau were quantified using PET imaging (single timepoint), with 18F-NAV4694 and 18F-flortaucipir tracers, respectively. Regional specific uptake value ratios (SUVR) were calculated for each, relative to cerebellar grey matter. LC was automatically delineated on individual neuromelanin-sensitive brainstem scans by identifying 10 brightest connected voxels within an approximate region of interest and calculating contrast-to-noise relative to a pontine control region (LCCNR). We tested associations between LCCNR and regional amyloid and tau SUVR using robust linear mixed effects models for each region with random intercepts across subjects. Longitudinal change was tested as an interaction term between the PET measure and time. We also tested the dependence of the Tau-LC association on global amyloid pathology at baseline using linear regression. All analyses were corrected for baseline age, sex and education and p-values were FDR-adjusted. We observed negative associations between LC integrity and amyloid SUVR across almost all cortical regions (Figure 1). Associations between LC integrity and cortical tau were restricted to temporal lobes, including parahippocampal gyrus, and inferior parietal regions (Figure 1). Associations with both amyloid and tau were particularly strong in the left hemisphere. These associations were observed only at baseline, with no longitudinal effects observed. The relationship between baseline LC integrity and cortical tau was modulated by global amyloid in lateral temporal cortices, particularly along in the left lateral temporal cortex (Figure 2). LC degeneration was associated with greater expression of key hallmarks of AD pathology in asymptomatic older adults. We support the model that LC is central to the earliest pathophysiological changes of AD.

48. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

ApoE4 is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD). Compared to ApoE4 noncarriers (ApoE4-), ApoE4 carriers (ApoE4+) exhibit earlier onset and more rapid progression of memory impairment. However, separate lines of work have suggested the opposite pattern in other cognitive domains: ApoE4+ individuals exhibit superior executive function compared to ApoE4-, but this advantage decreases with age. The antagonistic pleiotropy hypothesis proposes that ApoE4 may confer advantages to brain function at earlier ages, but these advantages become detrimental later in life. To investigate this hypothesis, we took a cross-species translational approach focusing on cognitively unimpaired human adult ApoE4+ and ApoE4-, ages 60-80 years, in combination with knock-in mouse models that express humanized wild-type App, MAPT, and ApoE3/4 genes. To quantify executive function, we utilized the cross-species touchscreen-based Continuous Performance Task (CPT) to evaluate selective attention. Human participants were drawn from the PREVENT-AD program at the Douglas Research Centre, with testing conducted on MS SurfacePros. Mice performed the same task using an operant chamber platform. Behavioural results suggest that ApoE4 facilitates attentional processes in both older adult and mouse ApoE4 carriers, as indexed by discrimination performance on the CPT. Further strengthening this translational pattern, we found that the facilitative effect of ApoE4 on CPT was more pronounced in female ApoE4+ of both species. In mice, we examined the ApoE-dependent effects on attention longitudinally (spanning 12 months), finding that the positive effect of ApoE4 was sustained across this interval in females, though it became less robust with age. In contrast, ApoE4 was beneficial in males only during early life. Notably, these effects were observed in the absence of detectable brain pathology CONCLUSION: These results support the antagonistic pleiotropy hypothesis, whereby ApoE4 carriership confers greater attentional performance early in life and in the absence of classical AD pathology. This effect is detectable in both sexes but is stronger and more sustained across age in females. All these patterns are conserved across humans and mice, suggesting that this cross-species translational platform is well suited to explore the mechanistic basis of ApoE4 antagonistic pleiotropy as it relates to domain-specific cognitive function.

49. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Traumatic brain injury (TBI) accelerates risk for multiple Alzheimer’s Disease and Related Dementias (ADRDs) featuring Tau protein hyperphosphorylation and tauopathy. Mild TBI (mTBI) causes a temporary disruption of brain function typically caused by blast, blow, or jolt to the head. While many individuals recover fully within a few weeks or months, some may experience long-term cognitive deficits, but how TBI progresses to ADRDs including tauopathies remains complex and elusive. The present study identified the combinations of risk genes and timing of mTBI induced by open-field blasts (OFB) that alter candidate fluid and imaging biomarkers involved, so that making early intervention possible to prevent or delay the progression of ADRD. human wild-type Tau/CamKII bitransgenic (rT1) and Non-carrier/non-carrier mice were assigned randomly into two groups: OFB-induced repetitive mTBI and sham control and evaluated for transgene and TBI-dependent behavioral deficits at 3 months post-injury. The brain tissues were collected for proteomics studies using high-resolution label-free global and phospho-proteomics by liquid chromatography coupled with tandem mass spectrometry, followed by A.I. informed phenomic analysis integrating behavioral-related proteomic datasets with human databases. Immunoblotting validated selected phenomics findings. We identified co-expression subnetworks that were strongly correlated with PTSD-like behavioral endophenotypes in humans including psychomotor agitation, fear response, and physical activity in rT1 mice following OFB-induced repetitive mTBI. Biologically-informed neural networks (BINN)-enhanced eXplainable Artificial Intelligence (XAI) analysis of the differential expression (DE) profiles in human ADRD cohorts that differentiate symptomatic CTE and AD from asymptomatic AD and age-matched human controls, identified overlapping networks in both mouse and human studies. Key proteins that regulate synaptic vesicle cycling, synaptic plasticity, and energy metabolism displayed DE in rT1 mice as a function of tau transgene and TBI interactions and drivers to accelerate their trajectory towards ADRD. Several of the TBI-triggered DE proteins (YWHAG or 14-3-3 γ, HNRNPA2B1, and hexokinase), overlapped reported phosphoTau and Tau oligomer interactomes with proposed causal roles in metabolic deficits and neurodegeneration. This study unveiled ADRD predictable converging molecular signatures that appear to drive the Tau-TBI interaction conferring both chronic neuropsychiatric impairments and neurodegenerative disease progression, shedding light on the complex etiology of ADRD.

50. Basic Science and Pathogenesis.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Alzheimer’s disease (AD) and related dementias are a growing health and economic burden in India, the most populous country in the world. Blood levels of amyloid beta (Aß), tau, and other proteins marking neuronal injury are biomarkers of AD risk. Understanding genetic associations with blood biomarkers of AD in South Asians may help lead to improved prevention and treatment in this understudied population. We performed gene-based analyses on 1) missense/loss-of-function single-nucleotide variants (SNVs) and 2) promoter/brain-specific enhancer SNVs across 84 genes previously associated with AD and 22 genes previously associated with AD biomarkers in the Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study in India (LASI-DAD; N = 2,545) with the variant-Set Test for Association using Annotation infoRmation (STAAR) across 7 AD biomarkers measured in blood: Aß40, Aß42, Aß42/Aß40, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), tau phosphorylated at threonine 181 (pTau), and total tau (tTau). We adjusted for age, sex, and 10 genetic ancestry principal components, with random intercepts for genetic relatedness and biomarker plate. Analyses incorporated weighted annotation scores (e.g., deleteriousness). Significant results (FDR q<0.1) were followed up with single variant analysis to determine the SNVs driving the associations. We found that 5 genes previously associated with AD (ICA1L, SCIMP, APOE, TSPOAP1, CLU) and 1 gene previously associated with AD biomarkers (APOE) were associated with pTau, Aß42/Aß40, and tTau in missense/LoF analysis in LASI-DAD (FDR q<0.1). The top SNVs of ICA1L, SCIMP, and TSPOAP1 (rs201355940, 17:5223434:C:T, rs144482724) were rare in LASI-DAD (MAFs<0.005) and had high CADD Phred scores (11.2-36.0) indicative of deleteriousness. In promoter/enhancer analysis, 1 AD-associated gene (CCDC6) and 3 AD biomarker-associated genes (CCK, APOC1, SLIT3) were associated with Aß40, Aß42/Aß40, and/or tTau. The top SNV in CCDC6 (rs1171833) had a CADD Phred score of 19.6 and was common in LASI-DAD (MAF=0.27). Several associated variants appeared to have an ancestral origin unique to India. Rare and common variants in AD- and AD biomarker-associated genes may impact blood levels of AD biomarkers in South Asians. Gene-based analysis may aid in identifying rare deleterious variants not seen in other populations.

51. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The Impact of Intensive Treatment of Systolic Blood Pressure on Brain Perfusion, Amyloid, and Tau in Older Adults (IPAT Study, R01AG076660) is a randomized, controlled, clinical trial being conducted to determine the effects of intensive blood pressure treatment on brain amyloid and tau measured with positron emission tomography (PET) in older adults with hypertension. IPAT plans to enroll 180 participants with hypertension (SBP > 130 mmHg), age 60-85, and randomize these participants into Usual Care (UC) or Intensive Blood Pressure Treatment (IT) group (NCT05331144). Our objective is to evaluate IPAT study recruitment strategies to understand the most effective approaches for study enrollment and the primary exclusion reasons for individuals interested in the study. The main recruitment strategies employed in the IPAT are: 1) affiliated hospital system databases (MyChart), 2) hospital employee and consumer marketing e-mails, and 3) community outreach events such as educational talks and senior health fairs. The study enrollment yields from various recruitment strategies are presented in Figure 1. In the first 2 years of the IPAT Study, from October of 2022 to November of 2024, 1735 individuals were phone screened and 140 were consented. The primary reasons for phone screening exclusion were: 1) SBP was <130 mmHg (n = 390), and 2) lack of interest from participants after opting to be contacted (n = 254). The primary reasons for participation halting post-consent were: 1) SBP < 130 mmHg (n = 13), and 2) were unable to undergo an MRI or PET/CT scan (n = 7). Participant’s demographics are presented in Table 1. Of note, among the consented, 80% are Non-Hispanic White and 88% have a higher education level (≥ 13 years). Recruitment from hospital databases yielded the largest randomization rate of 31%. The primary reason for phone screening and post-consent exclusion is SBP <130 mmHg, which suggests that the current recruitment strategies likely have reached to a population with normal or well-controlled blood pressure. Thus, IPAT enrollment should consider recruiting from underserved populations who have limited access to blood pressure management such as from the socioeconomically disadvantaged minority groups or from rural communities.

52. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Neighborhood disadvantage captures the socioeconomic context of an individual’s environment and is associated with poorer cognition and increased vulnerability to MCI and AD independently of individual-level socioeconomic status (SES). Studies of neighborhood disadvantage and cognition in older adults are often constrained to populations from a single state or city, but are rarely conducted across the national level with a representative distribution of neighborhood disadvantage. Moreover, little is known about potential moderators of the relationship between neighborhood disadvantage and cognitive function. In particular, whether individual differences in prior level of cognitive reserve may attenuate the negative association between neighborhood disadvantage and different cognitive domains in older adulthood remains unexplored. In 1149 community-dwelling dementia-free men (mean age: 67.56; range: 61.37-73.25) living across the US, we quantified each individual’s neighborhood level of socioeconomic disadvantage using the area deprivation index (ADI), a validated index based on American Community Survey data. We assessed associations between ADI and five cognitive domains (executive function, episodic memory, processing speed, verbal fluency, visual-spatial ability), while controlling for individual differences in young adult cognitive reserve (i.e., general cognitive ability [GCA] assessed on average at the age of 20) and household SES. We then investigated the moderating effect of cognitive reserve on the ADI-cognition associations. As a comparison, we also examined years of education as a moderator of the ADI-cognition associations. Greater neighborhood disadvantage was associated with poorer executive function (β=-0.09, p < .05) and processing speed (β=-0.12, p < .05), but not episodic memory, visual-spatial ability or verbal fluency. Moreover, the negative impact of neighborhood disadvantage on executive function was weaker among individuals with greater young adulthood cognitive reserve (ADI x GCA: β=0.07, p < .05) but not more years of education. Higher young adulthood cognitive reserve confers greater cognitive resilience against neighborhood disadvantage in older adulthood. Education did not show the same effect. Fostering early life cognitive development to enhance cognitive reserve-perhaps through improved nutrition and education quality-may buffer against environmental threats to executive function, which is among the earliest cognitive functions affected in later life. That, in turn, may decrease individual vulnerability to MCI and AD.

53. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Lead exposure has adverse impacts on cognition and dementia risk factors such as hypertension. A major historical source of lead exposure was via atmospheric pollution due to leaded gasoline. We mapped historical atmospheric lead levels (HALL) in the contiguous US using measurements obtained by the US EPA from 1960 to 1974, a period of high leaded gasoline combustion. We extrapolated HALL by kriging and calculated mean HALL for each public use microdata area (PUMA). Our analyses include only PUMAs which contained at least one lead measurement in 1960-74. We obtained individual-level data of self-reported memory problems, from the American Community Survey (ACS) in two time periods, 2012-2017 (n = 368,208) and 2018-2021 (n = 276,476). The samples were restricted to respondents aged 65 and older living in their natal state. We calculated odds ratios using HALL as the exposure variable and self-reported memory problems as the outcome, controlling for respondents’ age, sex, race/ethnicity, and education. We used individuals in PUMAs with the lowest HALL (< 0.4 µg/m3) as reference in comparison to those in PUMAs with moderate (0.4-.79 µg/m3), high (0.8-1.19 µg/m3) and extremely high HALL (>=1.2 µg/m3). In the 2012-2017 ACS, in comparison to older adults living in PUMAs with the lowest HALL, the odds of reported memory impairment were higher in those in PUMAs with moderate (Odds ratio (OR)=1.21; 95% CI=1.17-1.25), high (OR=1.21; 95% CI=1.17-1.25) and extremely high HALL levels (OR=1.19; 95% CI=1.13-1.25). We replicated the study using 2018-2021 ACS data and found comparable outcomes for older adults living in PUMAs with moderate (OR = 1.17; 95% CI=1.12-1.21), high (OR=1.20; 95% CI=1.16-1.25) and very high HALL (OR=1.22; 95% CI=1.15-1.29). We observed in two very large (n >250,000) independent representative samples that older adults had approximately 20% higher odds of reporting memory problems if they lived in PUMAs that had HALL > 0.4 µg/m3compared to <0.4 µg/m3. This adds to the evidence implicating lasting health outcomes, including cognition, due to earlier life lead exposure from air pollution. The precipitous decline in atmospheric lead exposure in the last quarter of the 20th century may help to explain the declining incidence of dementia in the US.

54. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Residential segregation in the U.S. is a fundamental cause of health disparities contributing to socioeconomic, environmental, and structural differences between neighborhoods. Its role in risk for and resilience to dementia is not well known. KHANDLE and STAR are harmonized cohorts of 40% Black, 20% White, 17% Asian, and 14% Latinx older adults. Participant self-reported residence geolocations were linked to interpolated decennial (1970-2017) census tract population data by race/ethnicity. City-level residential racial segregation was assessed using the dissimilarity index, linked to participant’s mid- (age 30) and late-life (age 65) timepoint. The city-level dissimilarity index sums, across a city’s census tracts, the differences in the ratio of racial/ethnic group’s population at the census tract-level compared to the city-level for each racial minority groups versus White populations. This number is then divided by 2 and reflects the distribution within a city of a minority group (Asian, Black, or Hispanics) compared to White group on a scale of 0 (complete integration) to 1 (complete segregation). Executive function (EF), verbal episodic memory (VEM), and semantic memory (SM) were collected at study baseline (year 2017-2018) using the Spanish English Neuropsychological Assessment Scale battery. Linear regression models examined the association of city-level dissimilarity at separate residence age and domain-specific cognition, adjusting for age and sex/gender, for the whole sample regardless of race/ethnicity. Among 2476 participants (average age 72.7; SD = 6.9) years, 62% were female, and 47% had a college education. Higher city-level dissimilarity (more segregation) at age 30 was associated with lower SM for all groups (Asian-White: β[95% CI]=-0.641[-1.164, -0.118], Black-White: β[95% CI]=-0.69[-1.219, -0.162], Hispanic-White: β[95% CI]=-1.191[-1.775, -0.607]). Higher city-level Black-White dissimilarity at midlife was additionally associated with lower VEM (β[95% CI]=-0.681[-1.19, -0.172]) and Hispanic-White dissimilarity was associated with lower EF (β[95% CI]=-0.548[-1.02, -0.076]). At age 65, only higher Black-White dissimilarity was associated with lower SM (β[95% CI]=-0.535[-1.051, -0.019]). Midlife residential segregation measured by the city-level dissimilarity index is associated with lower late-life semantic memory, which support evidence in other studies that found higher segregation was associated with lower cognition. Early adulthood may be a sensitive period where residential segregation is especially impactful on late-life cognition.

55. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

A vast amount of data has been collected on the genetic, lifestyle, and environmental risk factors contributing to Alzheimer’s Disease and Related Dementias (ADRD); however, no consensus exists on how to integrate these findings for prediction of an individual’s ADRD risk. Each study uses different inclusion/exclusion criteria, and variations in baseline age and follow-up can significantly affect the results. For example, exercise is often cited as a key preventative measure for ADRD, yet its impact varies widely-showing strong effects in some studies (Larson, 2006), and no effect in others (Knutosor, 2021). Similar challenges exist for other risk factors, including diabetes, Vitamin D, and even the presence of amyloid plaques in cognitively normal individuals. We have solved this challenge by analyzing ADRD risk and resilience data within the framework of a causal model, enabling us to reconcile seemingly disparate data and make individualized predictions using digital twins. We developed a mechanistic model of brain health and neurodegeneration based on engineering principles of mass balance and closed-loop feedback. The model was calibrated using in vitro, in vivo, clinical, and post-mortem data. Biologically relevant variability was identified by examining mechanisms linked to hazard ratios. Using this model, we generated a digital population that replicates hazard ratio and Kaplan-Meier data (Figure 1). This digital population reconciles conflicting data and provides a consistent framework to compare the effect size of risk factors. We can stratify the population into subgroups based on which biological processes fail to compensate, leading to disease progression. Additionally, we can create an individual’s digital twin by using the digital population as a Bayesian prior then applying individual health data using Bayesian inference. The resulting digital twin can be used to predict the individual’s risk of ADRD and guide personalized treatment and prevention strategies. Computational tools are needed to synthesize decades of ADRD research into causal hypotheses that accurately model the range of possible disease etiology. Mechanistic models, enhanced by artificial intelligence, offer an ideal framework for integrating diverse datasets and prior knowledge. Our scalable, high-throughput platform enables the creation of digital twins, improving healthcare and optimizing treatment strategies.

56. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Older adults living in “rural” regions have an increased risk for developing impaired cognition (both cognitive impairment and dementia) based on risk factors such as reduced medical care access, transportation burden, lower socioeconomic position, higher rates of chronic conditions, etc. While “rural” classification is a recognized indicator of under-represented group (URG) status by NIH definitions, there is no standard definition of rurality designated for use in research which complicates this knowledge. A comparison of known risk factors for cognitive decline/dementia and existing classification systems was done to analyze under-represented groups and disadvantaged status in “rural” persons. 790 active University of Kentucky Alzheimer’s Disease Research Center Cohort participants in 2024 were identified for this cross-sectional, descriptive analysis. Health Resources and Services Administration (HRSA), Medically Underserved Areas/Health Professional Shortage Areas (MUA/HPSA), Area Deprivation Index (ADI) State Decile (cutoff set at ≥ 7th decile), ADI National Percentile scores (cutoff set at ≥70%), and Rural-Urban Continuum Code (RUCC; cutoff set at ≥4) classifications were used to describe participants based on demographic information provided. These classifications were then analyzed with participant demographics including ApoE4 status and 15 medical conditions relative to cognitive impairment to evaluate relative risk against prevalence of cognitive impairment within the cohort. Diagnostic classifications, mean age, and education did not differ significantly across classifications. Risks for tobacco use, alcohol use, traumatic brain injury, cardiovascular risks, stroke or transient ischemic attack, diabetes, hypertension, hyperlipidemia, vitamin B12 deficiency, hypothyroidism, sleep disturbances, depression, anxiety, cancer and chronic kidney disease were variably distributed across classifications. HRSA Rural and MUA/HPSA, as well as ADI National percentiles were associated with higher mean relative risk (∼1.2) and additive relative risk (2.3 to 3.6) profiles, whereas ADI State deciles and RUCC scores were not predictive of increased medical risks for cognitive impairment and dementia (RR<1.0). These data demonstrate that different classification systems designed to identify disadvantaged populations have different risk profiles for cognitive impairment and dementia. Understanding “rurality” and disadvantaged classification systems is complex but remains very important for research designed to identify high risk URG populations for cognitive decline & dementia.

57. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Despite increased dementia incidence in women and the gendered nature of many known cognitive reserve (CR) factors, few studies have examined sex differences in CR on late-life cognition. How gendered CR factors, such as occupation and child rearing, differentially affect cognition in older adults remains unclear. We examined sex differences in the contribution of gendered CR factors on late-life cognitive decline. Participants were 4375 older adults (57% women, M(SD) age = 74.82(6.75) years) of the Cache County Memory Study, followed for a maximum of 11.39 years. The Modified Mini-Mental State (3MS) assessed cognition across four triennial waves. Demographics, number of offspring (women only), and occupational history were obtained. Occupational attainment was classified as: 1) Professional-Technical-Managerial, 2) Clerical-Sales, 3) Service, 4) Agriculture-Natural Resources, 5) Processing-Machine trades-Bench-Structural work-Miscellaneous, and 6) Never Employed. For women, categories 4 and 5 were combined due to sparseness. The associations between number of offspring, occupational attainment and baseline marital status with cognitive decline were examined using linear mixed effects models, controlling for age and education. All men reported a history of employment; 14.6% of women reported never being employed. Those in professional-technical-managerial occupations obtained the highest 3MS scores in both sexes. Among men, service workers scored lower on the 3MS (mean differences 1.8 - 3.2 points) than all other occupations, with the exception of agriculture-natural resources (p’s < .007) whereas among women, service workers scored lower than those in professional-technical-managerial, clerical-sales positions, and those who never worked (mean differences 1.3 - 1.8 points; p’s < .001). Notably, women who never worked did not score significantly lower than women with an employment history. Cognitive scores did not differ for women with or without offspring (p’s > .20), whereas widowed women experienced more rapid decline than their married counterparts (b = -.44, p < .001). Marital status was not associated with late-life cognition in men. Our analyses suggest that late-life cognition in men and women is differentially affected by gendered lifespan CR factors. In future work, we will explore sex differences in CR factors accumulated across the lifespan to elucidate interactive effects of early vs. late-life experiences on cognition.

58. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Cognitive decline and depression significantly affect the aging population, posing challenges for geriatric healthcare. Cognitive reserve (CR) is hypothesized to moderate these impacts by preserving cognitive function despite neuropathological changes. To examine the association between depression and cognitive decline and the moderating effects of cognitive reserve proxies (education, occupational complexity, and cognitive activities) over four years. Utilizing data from 32,325 participants aged 50+ from the Survey of Health, Aging, and Retirement in Europe (SHARE), cognitive performance was assessed using memory, numeracy, and verbal fluency tests in baseline and follow up of 4 years. Depressive symptoms were measured with the EURO-D scale, and CR was evaluated through educational attainment, occupational complexity, and engagement in cognitive activities. The moderation effects of CR on the relationship between depressive symptoms and cognitive performance were tested using bootstrapping with resampling strategies. Lower and average levels of CR were associated with a stronger negative correlation between depressive symptoms and cognitive performance, while higher levels of CR showed no adverse effects. Education and engagement in cognitive activities significantly reduced the negative impacts of depression on cognitive functions, unlike occupational complexity, which showed no significant effect. Cognitive reserve plays a critical role in moderating the longitudinal effect of depression on cognitive performance among older adults. Enhancing CR through education and cognitive activities could mitigate the adverse effects of depression on cognitive health, highlighting the need for public health policies to incorporate CR-enhancing strategies in later life.

59. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline (LatAm-FINGERS) is the first multicenter, non-pharmacological randomized clinical trial in the field of dementia developed in Latin America. The study aims to investigate the influence of a multidomain intervention on cognitive impairment in older adults with associated risk factors, including cognitive training, physical activity, clinical monitoring and changes in eating habits. Participants underwent dietary habit change interventions conducted by a nutrition team. Monthly, group discussions focused on topics presented in the “Food Guide for the Brazilian Population”. After 12 months of intervention, individualized consultations with a nutrition team were conducted to assess food intake using a 24-hour recall method, obtaining data on the consumption of macronutrients, fiber, calcium, vitamins D and B12, and body composition based on weight and height measurements, as well as anthropometric measurements. The data were tabulated, and the results were presented as mean and standard deviation or relative frequency. Twenty-two participants from the systematic group were evaluated, with a mean age of 69.4 ± 4.9 years, predominantly composed of women (54.5%). Regarding the assessment of food consumption, the average water intake was 1430 ± 529 ml, the average caloric intake was 1568.3 ± 501.3 calories, carbohydrate intake was 176.2 ± 64.8 grams, protein intake was 77.3 ± 37.9 grams, lipid intake was 60.9 ± 24.6 grams, and fiber intake was 18.0 ± 9.0 grams. In terms of micronutrients, the average calcium intake was 575.9 ± 267.7 mg, Vitamin D was 1.6 ± 2.1 μg, and Vitamin B12 was 1.9 ± 3.0 μg. For anthropometric markers, the mean weight of the participants was 71.4 ± 17.4 kg, body mass index (BMI) was 27.3 ± 5.4 kg/m2, neck circumference was 36.9 ± 4.0 cm, waist circumference was 90.7 ± 14.7 cm, arm circumference was 30.2 ± 4.3 cm, calf circumference was 37.3 ± 4.2 cm, waist-to-hip ratio was 0.9 ± 0.1, and waist-to-height ratio was 0.6 ± 0.1. The results highlight the need for personalized nutritional interventions for older adults to improve the intake of critical micronutrients and macronutrients to reduce metabolic risks.

60. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

A worldwide increase in dementia cases is expected due to demographic changes and the growing elderly population. However, recent studies suggest a declining incidence. This analysis aimed to examine the trends in the incidence and prevalence of diagnosed dementia in recent years based on data from all individuals covered by statutory health insurance in Germany. This study was based on claim data of primary and specialist care practices (German population coverage: 88%) from 2015 to 2022. Individuals aged ≥65 years with a confirmed dementia diagnosis in at least two out of four consecutive quarters were included. The incidence and prevalence of dementia were age- and sex-standardized calculated. The incidence decreased by 26%, from 2,020 per 100,000 insured individuals in 2015 to 1,500 per 100,000 insured individuals in 2022. The prevalence decreased by 18% during the same period, from 10,380 to 8,470 per 100,000 insured individuals. These trends were more pronounced in younger age groups and among women. The number of diagnosed dementia cases declined from 1.56 million in 2015 to 1.43 million in 2022, representing an 8.4% reduction. Despite ongoing demographic changes, German primary and specialist care practices show a significant decline in the incidence and prevalence of diagnosed dementia cases, contrary to expected projections. It remains an open research question whether a healthier lifestyle, better education, and improved management of risk factors by individuals or a reduced focus on dementia diagnoses due to limited therapeutic options by physicians have contributed to these trends. Further analyses of long-term cohort studies are needed to validate these findings.

61. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

The LIfestyle for BRAin Health (LIBRA) index is a well-validated tool for assessing modifiable dementia risk in midlife and older adults. Less is known about LIBRA in younger adults. Thus, we investigated the occurrence of LIBRA factors and associations between the LIBRA index and cognitive functioning across adulthood, spanning ages 20 to 75. We considered variations by age decade, sex, and socioeconomic status (SES). The data source was the population-based mega-cohort “German National Cohort” (NAKO). Proportions and Cochran-Armitage trend tests were calculated for 10 out of 12 LIBRA factors (coronary heart disease, diabetes, hypercholesterolaemia, hypertension, depression, obesity, smoking, physical inactivity, chronic kidney disease, and low-to-moderate alcohol consumption; no information available on healthy diet and high cognitive activity). Cluster-adjusted (for study sites) linear regression analysis was used to assess associations of LIBRA scores and cognitive functioning (composite neuropsychological test score), adjusted for age, age2, sex, education, SES, employment status, marital status, household size, migration status, and German language proficiency, for the total and stratified samples. The analytical sample of 149,948 participants had a mean age of 50.1 (13.6) years; 50.4% were women, and education levels were high (56.2% had tertiary education). Behavioural risk factors (smoking, physical inactivity, depression) occurred more frequently in younger adults, while risk factors related to vascular health conditions (hypertension, diabetes, coronary heart disease) were more common in older adults (Figure 1). Higher LIBRA scores were consistently associated with lower cognitive functioning across adulthood. An SES gradient in LIBRA scores was observed across age decades and sexes (Figure 2). Men had lower LIBRA scores, but associations with cognitive functioning were more pronounced in women. Our findings provide novel evidence suggesting that LIBRA is a useful tool in younger adulthood (20-39 years), a group still neglected in dementia risk research. Modifiable risk factors were already frequent in this age range and associated with lower cognitive functioning. The observed sex/gender and socioeconomic disparities indicate compounded disadvantages faced by lower SES groups and women, emphasising the need for tailored, ideally early interventions possibly targeting behavioural risk factors. Longitudinal studies could help to disentangle life-course dynamics of LIBRA factors and cognitive functioning.

62. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Education and occupational complexity have been individually associated with better cognitive performance and lower odds of cognitive impairment, mostly in high-income countries. Thus, it is important to investigate this association in the context of low- and middle-income countries where there is greater variability in educational attainment and occupational complexity. We use nationally representative data from Brazil and Mexico to assess the associations of education and occupational complexity combinations with cognitive performance and to investigate if occupational complexity mediated the association between education and cognitive performance. The sample included adults 50 years or older from the 2018-2019 waves of the Brazilian Longitudinal Study of Aging (ELSI, n = 9,914) and the Mexican Health and Aging Study (MHAS, n = 16,172). Participants were classified as cognitively impaired or not impaired using a regression-based approach compared to a normative sample. Educational attainment was categorized into low (≤8 years of education) and high (>8 years of education). Occupational complexity was defined using the International Standard of Classification of Occupations 2008 and categorized into never worked, skill levels 1/2, and skill levels 3/4. Linear regression models investigated the combined association of education and occupation with cognitive function. The mediation analysis used the counterfactual framework. Participants of the ELSI had a mean age of 64.0±9.6 years, median (interquartile range) years of education of 4 (2-10) years, 50.0% were women, 15.8% had never worked, and 6% were cognitively impaired (Table 1). Participants of the MHAS had a mean age of 62.8±10.3 years, median years of education of 6 (3-9) years, 56.0% were women, 20.0% had never worked, and 7% were cognitively impaired (Table 1). Within the levels of education, there was a dose-response with increasing occupational complexity in the association with cognitive function (p for trend: ELSI < 0.001; MHAS < 0.001) (Figure 1). Occupational complexity explained 57.8% of the relationship between education and cognitive function in the ELSI, but was not a mediator in the MHAS (Figure 2). Our results highlight the cumulative benefits of education and occupation on cognition, with occupational complexity’s mediating role in the education-cognition association differing between Brazil and Mexico.

63. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Occupational exposure to inhalable airborne toxicants has been associated with later life dementia but the findings are inconsistent, and research is limited. The mechanism has been uncertain, with genetic and environmental influences are difficult to disentangle. This study examines the relationship between occupational exposures and dementia risk in a twin sample facilitating assessment of familial confounding. Data were obtained from 316 participants (50.32% women) in the Swedish Adoption/Twin Study on Aging (SATSA), a longitudinal twin cohort. Inhalable occupational exposures (dust, soot, and/or gases; smoke; odours; damp air; solvents; insufficient ventilation; and dirt) were self-reported in the first questionnaire during1984 (mean age=51.57 years). Principal component analysis was applied to occupational exposures to derive the first principal component (PC1), representing a multipollutant occupational exposure. All-cause dementia diagnoses (N = 48) were based on cognitive testing, clinically evaluation, and healthcare register linkage until 2016. Cox proportional hazards models were used to examine the association between PC1 and individual occupational risk factors with all-cause dementia. Additional within-twin pair analyses were conducted using stratified Cox models, to account for genetic and other familial influences. Models were adjusted by age, sex, education, and smoking. Occupational exposure (PC1) was not associated with risk of dementia in the total sample (HR 1.05, 95% CI 0.87-1.26). Exposure to dust, soot, and/or gases was associated with higher risk of dementia in the total sample (HR 1.99, 95% CI 1.06-3.74), with a comparable estimate in within-twin pair analyses (HR 2.30, 95% CI 0.31-17.29). Associations between other occupational exposures and dementia were not statistically significant: smoke (HR,1.23, 95% CI 0.62-2.44), smell (HR, 0.86, 95% CI 0.44-1.68), damp air (HR, 0.87, 95% CI 0.38-2.00), solvents (HR, 0.62, 95% CI 0.26-1.47), insufficient ventilation (HR, 0.96, 95% CI 0.50-1.82), and dirt (HR, 1.60, 95% CI 0.83-3.10). Exposure to dust, soot, and gases may be associated with higher risk of dementia, with comparable effect estimates within twin pairs indicating that the association is not explained by familial confounding. No statistically significant associations were between other inhalable occupational exposures and dementia risk. Future research should involve larger cohorts with more detailed occupational exposure measurements.

64. Public Health.

期刊: Alzheimer’s & dementia : the journal of the Alzheimer’s Association 发表日期: 2025-Dec 链接: PubMed

摘要

Lewy body dementia (LBD) risk differs by sex, with males at higher risk than females. Environmental and occupational exposures throughout life also vary by sex and may contribute to this difference. Despite the identification of various environmental and occupational risk factors in Alzheimer’s and Parkinson’s diseases, research on LBD remains limited. We included data from 130 individuals with LBD (51 females, 79 males) and 124 controls of similar age (64 females, 60 males) from LBD-TOROS, a remote cross-sectional survey study. Environmental and occupational factors during childhood and adulthood, including residential history, beverage consumption (e.g. caffeinated drinks), toxicant exposure, physical activity, smoking, and alcohol use, were compared between groups using Chi square and Mann-Whitney U tests. Associations between significantly differing variables and LBD risk were assessed with logistic regression. Analyses were conducted for the overall cohort and sex-stratified cohorts. The majority of the cohort identified as cisgender and straight (94.1%), and non-Hispanic and White (75.2%). Individuals with LBD had lower years of education, lower income, and lower subjective social status than controls (Table 1). Compared to controls, individuals with LBD had a higher prevalence of exposure to metal dust/dust fumes in childhood and in adulthood, glue/adhesive at work, welding/brazing/flame cutting metal, soldering, and smoking (Table 2). In the overall cohort, smoking, not living in a suburb, exposure to glue/adhesive at work, welding/brazing/flame cutting metal, soldering, and metal dust/dust fumes in adulthood were significantly associated with LBD risk. For females, decaffeinated coffee, caffeine-free soda during childhood, not living in a suburb, and exposure to pesticides at work in adulthood were associated with LBD risk. For males, not living in a large city, private well water, caffeinated green tea, welding/brazing/flame cutting metal, soldering, metal dust/dust fumes in adulthood, and smoking were associated with LBD risk. Environmental and occupational factors in both childhood and adulthood can increase LBD risk. Identifying sex-specific risk factors can provide insights into disease pathogenesis and guide effective prevention and management strategies. However, current LBD literature stems mostly from male participants, and more research is needed on LBD in females.