The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Assessment of dementia risk scores in predicting mild cognitive impairment: A comparison of CogDrisk, CAIDE, LIBRA, and ANU-ADRI.","authors":"Md Hamidul Huque, Kaarin J Anstey","doi":"10.1016/j.tjpad.2025.100324","DOIUrl":"10.1016/j.tjpad.2025.100324","url":null,"abstract":"<p><strong>Background: </strong>Given the lack of widely accessible dementia treatments, identifying individuals at high risk of dementia is vital for prevention. No prior study has compared multiple validated dementia risk tools for predicting mild cognitive impairment (MCI) across multiple datasets. We assess the performance of the CogDrisk, ANU-ADRI, CAIDE, and LIBRA in predicting MCI.</p><p><strong>Method: </strong>Data were obtained from the ARIC, Whitehall II, and PATH Through Life cohorts. Participants without dementia or MCI at baseline were included. Risk scores were computed using available risk factors and analysed using logistic regression, with Area Under the Curve (AUC) estimates. Multiple imputation was used to evaluate the impact of missing data.</p><p><strong>Results: </strong>The ARIC (n = 5778), Whitehall II (n = 6387), and PATH (n = 2115) cohorts had mean baseline ages of 51.9, 55.8, and 62.5 years, with follow-ups of 28.2, 15.7, and 11.2 years, respectively. AUCs for MCI prediction were generally similar across tools and datasets. Dementia prevalence following MCI was highest in ARIC (23.6%), followed by Whitehall II (14.1%) and PATH (7.0%). In ARIC, CogDrisk showed slightly better AUCs for predicting MCI cases that progressed to dementia. Whitehall II and PATH showed mixed results, with wider confidence intervals for progressing MCI cases, and higher AUCs for non-progressing MCI cases using CogDrisk and ANU-ADRI. All tools performed consistently when predicting dementia without prior MCI.</p><p><strong>Discussion: </strong>Dementia risk scores demonstrated comparable performance of MCI prediction and are more sensitive for identifying cases that progress to dementia, supporting their greater utility for informing risk reduction strategies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100324"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144837786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reevaluating the neuroprotective promise of dietary nitrate: Commentary on Rajendra et al. (2025).","authors":"Parth Aphale, Himanshu Shekhar, Shashank Dokania","doi":"10.1016/j.tjpad.2025.100339","DOIUrl":"10.1016/j.tjpad.2025.100339","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100339"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of the burden of young-onset and late-onset dementia in China from 1990 to 2021: A study based on GBD 2021 data.","authors":"Ke-Qiang Lu, Ke-Jia Lu, Zheng-Jun Ji","doi":"10.1016/j.tjpad.2025.100307","DOIUrl":"10.1016/j.tjpad.2025.100307","url":null,"abstract":"<p><strong>Background: </strong>Most epidemiological studies on dementia in China have focused on the elderly population, with a lack of systematic comparisons between the burden of young-onset dementia (YOD) and late-onset dementia (LOD).</p><p><strong>Methods: </strong>Based on data from the Global Burden of Disease (GBD) study, this research systematically evaluated changes in the burden of YOD and LOD in China over different time periods. The analysis employed average annual percentage change (AAPC), Bayesian age-period-cohort (BAPC) modeling, decomposition analysis, risk factor attribution analysis, health inequality analysis, and frontier analysis.</p><p><strong>Results: </strong>AAPC analysis showed that the growth rate of YOD has significantly outpaced that of LOD since 2012. Forecasting results indicated that the age-standardized rates for both YOD and LOD are expected to continue rising in the future. Decomposition analysis revealed that between 1990 and 2021, the main drivers of the increasing YOD burden shifted from population growth to epidemiological changes and population aging, whereas population growth remained the dominant driver for LOD. Risk factor analysis indicated that the impact of high BMI on both YOD and LOD has become increasingly pronounced. Health inequality and frontier analyses suggested that, although disparities in YOD and LOD burden across different SDI regions were not significant, there remains substantial room for improvement in managing both conditions in China.</p><p><strong>Conclusion: </strong>In recent years, YOD has exhibited a more rapid increase compared to LOD, with its driving forces gradually shifting from population-related factors to epidemiological transitions. This highlights the need to strengthen identification and intervention strategies targeting younger and middle-aged populations. Tobacco use, high fasting plasma glucose, and high BMI are key modifiable risk factors shared by both YOD and LOD, with particular attention needed on the sustained impact of high BMI. Although international disparities in health inequality are not pronounced, China still holds considerable potential for improvement in the prevention and control of both YOD and LOD. Future interventions should be more forward-looking, systematic, and tailored to specific population groups.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100307"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disclosure of Alzheimer's disease blood-based biomarker results in a primary care setting: Opportunities and challenges.","authors":"Corey J Bolton, Ayda Rostamzadeh, Nathaniel Chin, Nicole R Fowler, Judith Heidebrink, Annalise Rahman-Fillipiak, Raymond R Romano, Lindsay R Clark","doi":"10.1016/j.tjpad.2025.100310","DOIUrl":"10.1016/j.tjpad.2025.100310","url":null,"abstract":"<p><p>Blood-based biomarkers (BBMs) for Alzheimer's disease (AD) have advanced rapidly and may be a critical tool for broad community-based screening for AD and detection of AD pathology in individuals with cognitive impairment. To meet the impending demand for AD diagnosis, BBMs could be implemented in a primary care setting to maximize accessibility and efficiency. However, this primary care implementation would be associated with numerous challenges, including issues related to disclosure of test results to patients. In this perspective article, we highlight the need for and potential challenges of AD BBM results disclosure in a primary care setting. Drawing from existing studies of AD risk disclosure, we highlight key areas of consideration to maximize patient safety and comprehension of results. Resources are suggested to aid health systems in implementing BBM testing in primary care settings. Finally, we emphasize the need for further research on the accuracy of BBMs and the practice of disclosure in primary care settings.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100310"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systematic review and meta-analysis of rural-urban disparities in Alzheimer's disease dementia prevalence.","authors":"Abe Mollalo, Mackenzie Kramer, Maxwell Cutty, Benyamin Hoseini","doi":"10.1016/j.tjpad.2025.100305","DOIUrl":"10.1016/j.tjpad.2025.100305","url":null,"abstract":"<p><strong>Background: </strong>The prevalence of Alzheimer's disease (AD) dementia varies between rural and urban areas worldwide, with studies reporting mixed patterns. In this study, we conducted a systematic review and meta-analysis to pool the odds ratio (OR) of rural-to-urban prevalence and explored contributing regional and socioeconomic factors.</p><p><strong>Methods: </strong>We performed comprehensive searches in PubMed, MEDLINE, CINAHL, Web of Science, and Scopus (January 2000-August 2024) for peer-reviewed studies reporting individual-level AD dementia prevalence comparisons between rural and urban settings. A random-effects model was used to calculate pooled OR at a 95 % confidence interval (CI). Prespecified subgroup analyses examined variations by WHO-defined regions, healthcare expenditure, income level, and educational attainment.</p><p><strong>Results: </strong>The meta-analysis incorporated 19 studies (22 datasets, N = 584,863) and found significantly higher AD dementia prevalence in rural areas (pooled OR = 1.247, 95 % CI: 1.059-1.468), with considerable between-study heterogeneity (I²=95.5 %). Regional subgroup analyses revealed marked disparities in the Western Pacific (OR = 1.416, 95 % CI: 1.083-1.851) and Southeast Asia (OR = 1.382, 95 % CI: 1.058-1.805), contrasting with nonsignificant findings in the Americas (OR = 0.989, 95 % CI: 0.785-1.247). Socioeconomic stratification showed pronounced rural disadvantages in: (1) lower healthcare expenditure regions (≤7.5 % GDP: OR = 1.268, 95 % CI: 1.043-1.542) and (2) among lower-middle to upper-middle income countries (OR = 1.260, 95 % CI: 1.030-1.542). This disparity attenuated in high-income settings (OR = 1.206, 95 % CI: 0.979-1.486) and in regions with healthcare expenditure >7.5 % GDP (OR = 1.16, 95 % CI: 0.87-1.53). Educational stratification revealed significant rural-urban disparities in regions with lower educational attainment (≤8.1 mean schooling years: OR=1.43, 95 % CI: 1.15-1.79). In contrast, regions with higher educational attainment (>8.1 years) showed no significant difference (OR=1.05, 95 % CI: 0.89-1.25).</p><p><strong>Conclusion: </strong>This review provides useful evidence that AD dementia prevalence is higher in rural areas than in urban areas, particularly in resource-limited settings. Our findings call for targeted rural interventions in vulnerable regions and further research into how healthcare infrastructure and education jointly influence AD dementia disparities.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100305"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel early imaging biomarker for glymphatic function: Cerebral cortical arterial pulsatility index from 2-Minute phase-contrast MRI.","authors":"Sung-Hye You, Byungjun Kim, Moonjung Hwang, Kyung-Sook Yang, Hye-Won Park, InSeong Kim, SuGil Kim, Kyung Min Kim, Bo Kyu Kim, Jae Ho Shin","doi":"10.1016/j.tjpad.2025.100323","DOIUrl":"10.1016/j.tjpad.2025.100323","url":null,"abstract":"<p><strong>Background: </strong>Arterial pulsatility is one of the driving forces of glymphatic flow.</p><p><strong>Objectives: </strong>To evaluate the feasibility of the pulsatility index (PI) of cortical arteries in the centrum semiovale (PI_CSO) as a novel non-invasive imaging biomarker for Alzheimer's disease (AD) in the context of glymphatic function.</p><p><strong>Design: </strong>Retrospective cross-sectional study.</p><p><strong>Setting: </strong>Single tertiary academic center equipped with both 3.0 T MRI systems.</p><p><strong>Participants: </strong>A total of 160 individuals were enrolled: 50 healthy volunteers, 46 cognitively normal controls, and 64 AD patients who underwent diffusion tensor imaging (DTI) and 2D phase-contrast MRI.</p><p><strong>Measurements: </strong>Diffusion Tensor Imaging Analysis along the Perivascular Space (DTI-ALPS) index and PI_CSO were assessed using 2D phase-contrast MRI. Correlations with age, DTI-ALPS index, and Mini-Mental State Examination (MMSE) scores were analyzed.</p><p><strong>Results: </strong>PI_CSO was significantly higher in the AD group than those in healthy volunteers (P<0.001) and cognitively normal aging (P=0.001) groups. PI_CSO correlated positively with age (rho=0.613, P<0.001) and negatively with both the DTI-ALPS index (rho=-0.439, P<0.001) and MMSE scores (rho=-0.486, P<0.001) in total group.</p><p><strong>Conclusion: </strong>PI_CSO derived from 2D phase-contrast 3.0T MRI may serve as a novel imaging biomarker for Alzheimer's disease in relation to glymphatic function.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100323"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and co-occurrence of dementia risk factors in Denmark: A nationwide study.","authors":"Janet Janbek, Thomas Munk Laursen, Kasper Jørgensen, Martin Mejlby Jensen, Marie Holm Eliasen, Anne Illemann Christensen, Sebastian Walsh, Andrew Sommerlad, Carol Brayne, Gunhild Waldemar","doi":"10.1016/j.tjpad.2025.100365","DOIUrl":"10.1016/j.tjpad.2025.100365","url":null,"abstract":"<p><strong>Background: </strong>The clustering of dementia risk factors is common and has implications for policies targeting risk reduction.</p><p><strong>Objectives: </strong>To estimate the prevalence of 16 dementia risk factors and their co-occurrence.</p><p><strong>Design: </strong>Cross-sectional based on a closed cohort on 1 January 2022 with nationwide data on risk factors from 1969/1977.</p><p><strong>Setting: </strong>Denmark PARTICIPANTS: Whole population; closed cohort of individuals ≥65 years on 1 January 2022, and a subpopulation of responders in the 2010/2013 Danish National Health Survey.</p><p><strong>Intervention (exposures): </strong>Sixteen dementia risk factors: hypertension, cardiovascular disease, diabetes, hypercholesterolemia, obesity, smoking, alcohol, physical inactivity, depression, hearing loss, vision impairment, traumatic brain injury, sleep disorders, hospital-diagnosed infections, social isolation, and low education.</p><p><strong>Measurements: </strong>Period and point prevalence proportions of the dementia risk factors and of all possible combinations of factors (those occurring in ≥10 % of individuals). The prevalence estimates reflect a population-level view of persons who have experienced, were diagnosed, or were treated for the risk factors assessed.</p><p><strong>Results: </strong>In the whole population (N = 1,214,286) and the subpopulation (N = 88,565), 5 % had no risk factors, 12 % had only one, and 82 % had multiple. Hypertension was the most prevalent (57 %), and vision impairment the least (2 %). Men, individuals ≥85 years, and those with low education had the highest prevalence of risk factors (with exceptions).</p><p><strong>Conclusions: </strong>Clustering of risk factors is very common, and findings emphasize the need to focus on multidomain interventions for dementia risk reduction that account for the clustering of risk.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100365"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144970033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of sugar intake with incident dementia in the UK Biobank: a prospective cohort study.","authors":"Yue Che, Wenming Wei, Tingting Mao, Lina Qin, Hanchi Wang, Yijia Li, Weixuan Da, Jin Feng, Li Liu, Bolun Cheng, Huan Liu, Yan Wen, Yumeng Jia, Feng Zhang","doi":"10.1016/j.tjpad.2025.100311","DOIUrl":"10.1016/j.tjpad.2025.100311","url":null,"abstract":"<p><strong>Background: </strong>Excessive sugar intake has been implicated in increased dementia risk; however, existing studies are constrained by small sample sizes and a primary focus on total sugar, with limited investigation into specific sugar subtypes. This study explores the relationship between sugar intake, its subtypes, and the incidence of dementia.</p><p><strong>Methods: </strong>We analyzed 172,516 participants from the UK Biobank who completed at least one 24-hour dietary recall (Oxford WebQ). Cox proportional hazards models estimated the hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) for total sugar and its subtypes (free sugar, fructose, glucose, sucrose, maltose, lactose, and other sugars) about the risk of dementia. Sex-stratified analyses were also performed.</p><p><strong>Results: </strong>Higher intakes of total sugar (HR = 1.292, 95 % CI = 1.148--1.453) and free sugar intake (HR = 1.254, 95 % CI = 1.117--1.408) were significantly associated with increased dementia risk. Positive associations were also observed for non-milk extrinsic sugars (HR = 1.321, 95 % CI = 1.175--1.486) and sucrose (HR = 1.291, 95 % CI = 1.147--1.452). These associations were evident in women, with higher intakes of total sugars, free sugars, glucose, sucrose, and non-milk extrinsic sugars independently linked to increased dementia risk, whereas no significant associations were found in men.</p><p><strong>Conclusion: </strong>Higher consumption of total sugars, free sugars, sucrose, and non-milk extrinsic sugars confers increased dementia risk, particularly among women.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100311"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Psychiatry meets neurodegeneration - A collaborative approach to dementia prevention.","authors":"Carolin Kurz, Martin Haupt, Stefanie Auer, Nicola Lautenschlager, Alexander Kurz","doi":"10.1016/j.tjpad.2025.100317","DOIUrl":"10.1016/j.tjpad.2025.100317","url":null,"abstract":"<p><p>The advent of amyloid-targeting therapies and biomarker-based risk stratification has transformed the understanding of Alzheimer's disease and related disorders. These conditions are now recognized as chronic, detectable and modifiable, often presenting decades before clinical symptoms appear. While this paradigm shift enables earlier intervention, it also raises ethical and psychological challenges that necessitate a redefined role for psychiatry. Instead of merely supporting late-stage care, psychiatry is well-placed to facilitate risk communication, promote resilience, and encourage adaptive behavior in individuals navigating preclinical or prodromal neurodegeneration. This article outlines an ethical, stepwise communication framework, clarifies the distinction between diagnosis and probabilistic risk, and explores psychiatric contributions-from motivational models to lifestyle-based prevention-that bridge the gap between biological insight and subjective experience. By reinterpreting risk as a chance for intervention rather than resignation, psychiatry broadens the therapeutic scope and helps safeguard independence, dignity and quality of life-making it a pivotal participant in dementia prevention and individualized, person-centered care.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100317"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medical risk factors, ApoE haplotype, and Alzheimer's disease: a large-scale analysis.","authors":"Uri Elias, Lidor Gazit, Roei Zucker, Amos Stern, Michal Linial, Gilles Allali, Tamir Ben-Hur, Gad A Marshall, Shahar Arzy","doi":"10.1016/j.tjpad.2025.100301","DOIUrl":"10.1016/j.tjpad.2025.100301","url":null,"abstract":"<p><strong>Background: </strong>The multifactorial nature of Alzheimer's disease (AD) has become increasingly evident. In addition to well-established features like neurodegeneration, amyloid-beta and tau deposition, or glial changes, other processes-such as metabolic, circulatory, and inflammatory factors-may also play a key role in driving or accelerating AD-related pathology and cognitive decline. These factors represent important targets for slowing disease progression.</p><p><strong>Objectives: </strong>Although many studies have examined individual risk factors and meta-analyses have been performed, a large-scale, comprehensive comparison using formal medical data from a single, unified cohort is needed.</p><p><strong>Design: </strong>A retrospective case-control study leveraging comprehensive health database.</p><p><strong>Setting: </strong>Data were obtained from the UK-Biobank, a large (∼500 K people) population-based biomedical database in the United Kingdom.</p><p><strong>Participants: </strong>The study included participants aged 40-69 at enrollment between 2006 and 2010, comprising 3,843 individuals who were clinically diagnosed with AD by August 2022 and 387,275 individuals without dementia or cognitive-impairment diagnoses.</p><p><strong>Measurements: </strong>ICD-10-coded diagnoses, recorded at least 10 years prior to AD diagnosis, were analyzed. Logistic regression was used to estimate the impact and significance of various medical conditions and their interactions with genetic risk factors, while accounting for demographic determinants.</p><p><strong>Results: </strong>The analysis identified 45 medical factors (96 ICD-10 entities) across multiple systems-particularly metabolic, circulatory, gastrointestinal, and sensorimotor-that significantly differentiated individuals with clinical AD from cognitively unimpaired individuals. Interaction analyses revealed that circulatory and metabolic factors had a weaker influence on AD risk in Apolipoprotein E ε4 carriers, suggesting a gene-environment interaction in disease susceptibility.</p><p><strong>Conclusions: </strong>These findings enhance the understanding of system-level risk factors for clinical AD, highlight the relevance of less frequently reported factors in the AD prevention literature-such as gastrointestinal and sensorimotor disorders-and underscore the complex interplay between genetic susceptibility and vascular risk factors.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100301"},"PeriodicalIF":7.8,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144795552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}