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

{"title":"Opposite causal effects of type 2 diabetes and metformin on Alzheimer's disease.","authors":"Dongming Liu, Hongbao Cao, Ancha Baranova, Chenxin Xu, Fuquan Zhang","doi":"10.1016/j.tjpad.2025.100129","DOIUrl":"10.1016/j.tjpad.2025.100129","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) is commonly co-morbid with Alzheimer's disease (AD). However, it remains unclear whether T2D itself or the antidiabetic drug metformin contributes to the progression of AD.</p><p><strong>Objective: </strong>This study aimed to investigate the overall and independent effects of T2D and metformin use on the risk of AD.</p><p><strong>Methods: </strong>Summary genome-wide association study datasets were utilized for the Mendelian randomization (MR) and multivariable MR (MVMR) analyses, including ones for T2D (N = 455,017), metformin (N = 456,276), and AD (N = 453,733). Additionally, using the proportional imbalance method, we analyzed AD-related adverse drug events in the FDA Adverse Event Reporting System (FAERS) database (covering Q1 2004 to Q2 2024).</p><p><strong>Results: </strong>Our two-sample MR analysis indicated that T2D is not associated with the risk of AD (OR: 1.03, CI: 0.99-1.08, P = 0.128). However, while not statistically significant, genetic signature for metformin exposure demonstrated a trend toward an increased risk of AD (OR: 1.05, CI: 1.00-1.09, P = 0.053). Interestingly, in MVMR analysis, which evaluates independent effects of T2D and metformin exposure on T2D, we found a robust association of T2D with a decrease in the risk of AD (OR: 0.82, CI: 0.68-0.98, P = 0.031), while the use of metformin was associated with a higher risk of AD (OR: 1.26, CI: 1.06-1.50, P = 9.45E-3). In the FAERS database, a total of 228,283 metformin-related adverse event reports from 67,742 cases were found. For metformin as the target drug and AD as the target adverse event, signal analysis reported 29 cases of AD (ROR: 0.83, 95 % CI: 0.58-1.19, P = 0.3126).</p><p><strong>Conclusions: </strong>Our study reveals the opposite independent causal effects of T2D and metformin exposure on AD. These findings highlight the importance of assessing AD risk when prescribing metformin to patients with T2D.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100129"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient management pathways in dementia - Resource utilisation, diagnosis and drug treatment in the Stockholm region, Sweden.","authors":"Emil Aho, Dorota Religa, Mozhu Ding, Bengt Winblad, Linus Jönsson, Karin Modig","doi":"10.1016/j.tjpad.2025.100132","DOIUrl":"10.1016/j.tjpad.2025.100132","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;New diagnostic and therapeutic options for Alzheimer's disease are beginning to be introduced and expected igto become more widely available in the coming years. Improved understanding of current pathways in diagnosis and initial care of patients with dementia can help inform choices around how best to integrate new technologies in existing care structures.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The aim of this study is to describe the care management pathways defined by the involvement of specialist and primary care for individuals with newly diagnosed dementia. It also seeks to characterise individuals in different management pathways based on resource use prior to diagnosis, the type of dementia diagnosis received, and the proportion who receive symptomatic anti-dementia drug treatment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Observational cohort study SETTING: Stockholm region, Sweden.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;All newly diagnosed dementia cases between 1st January 2018 to 30th June 2020 (n = 9,781). Dementia diagnoses in primary care were based on Regional Stockholm health care database and diagnoses in specialist care were based on the National Patient Register in Sweden.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;Care management pathways were categorized into three groups: primary care only (diagnosed and followed up in primary care), specialist, no follow-up (diagnosed in specialist care but not followed up in specialist care), and specialist with follow-up (diagnosed and followed up in specialist care). These classifications were based on patients' care episodes from the date of diagnosis and the subsequent 18 months. age at diagnosis, resource utilisation one-year prior diagnosis and diagnosis given and symptomatic anti-dementia treatment 18 months after initial diagnosis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 9,781 newly diagnosed dementia cases were identified. In the 18 months following diagnosis, 63 % of patients were diagnosed either partly or fully in specialist care, while 37 % were diagnosed solely in primary care. Patients diagnosed and managed only in primary care were older, spent more days in hospital, and received more social care in the year preceding their diagnosis. Their total care costs were also the highest. Alzheimer's disease was the most common diagnosis (48 %), while 27 % had an unspecified dementia diagnosis, varying by care setting (61 % for patients managed in primary care only and 6 % for patients diagnosed and followed up in specialist care). Overall, 47 % of patients received symptomatic anti-dementia treatment, with the highest share for patients diagnosed and followed up in specialist care (73 %) and the lowest in primary care only (19 %). Diagnosis varied by age and care setting Alzheimer's was most common in settings involving specialist care, whereas unspecified dementia was more common in primary care only regardless of age.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;The findings t","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100132"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658664","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronotype as a potential risk factor for cognitive decline: The mediating role of sleep quality and health behaviours in a 10-year follow-up study.","authors":"A N Wenzler, A C Liefbroer, R C Oude Voshaar, N Smidt","doi":"10.1016/j.tjpad.2025.100168","DOIUrl":"10.1016/j.tjpad.2025.100168","url":null,"abstract":"<p><strong>Background: </strong>- With rising life expectancies and ageing populations worldwide, preserving cognitive health is an urgent global priority. Chronotype could be a potential risk factor for cognitive decline, potentially through mediators sleep quality, alcohol intake, physical activity, and smoking.</p><p><strong>Methods: </strong>- This study used data from participants aged 40 years and older from the Lifelines cohort study (n = 23,798). Chronotype, assessed with the Munich ChronoType Questionnaire, was included as a continuous score of mid-point sleep corrected for sleep debt on workdays. Multiple linear regression examined the association between chronotype and cognitive decline, including moderation by age, educational attainment, and sex. The KHB-method was applied to test mediation by sleep quality, alcohol intake, physical activity, and smoking.</p><p><strong>Outcomes: </strong>- Cognition was assessed with the Ruff Figural Fluency Test (RFFT), measuring non-verbal fluency and executive functioning. Cognitive decline was calculated by subtracting the RFFT sum score at baseline from the 10-year follow-up score.</p><p><strong>Results: </strong>- Chronotype was associated with cognitive decline. Educational attainment, but not age or sex, moderated the relationship. No significant associations were observed in the low- (0.07, 95 % CI: -0.44, 0.57) or middle- (-0.41, 95 % CI: -0.88, 0.06) educational groups. In the high-educational group each one-hour increase in chronotype corresponded to a 0.80-point decline in cognition per decade (95 % CI: -1.34, -0.26). In this group, sleep quality and current smoking mediated 13.52 % and 18.64 % of the association, respectively.</p><p><strong>Interpretation: </strong>- Chronotype was associated with greater decline in non-verbal fluency and executive functioning among higher educated participants, highlighting the importance of targeted prevention strategies.</p><p><strong>Funding: </strong>- This work is part of the BIRD-NL consortium funded by the Dutch Medical Research Council, ZonMw (Dementia research program) project number:10,510,032,120,005.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100168"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143982909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations between the EAT-Lancet planetary health diet and incident dementia.","authors":"Jessica Samuelsson, Isabelle Glans, Anna Stubbendorff, Ulrika Ericson, Sebastian Palmqvist, Oskar Hansson, Emily Sonestedt","doi":"10.1016/j.tjpad.2025.100166","DOIUrl":"10.1016/j.tjpad.2025.100166","url":null,"abstract":"<p><strong>Background: </strong>The impact of the environmentally sustainable EAT-Lancet diet on dementia risk remains poorly understood. The aim was to investigate associations between the EAT-Lancet diet and incident dementia.</p><p><strong>Methods: </strong>Associations of the EAT-Lancet diet with all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were investigated among 25,898 participants from the Malmö Diet and Cancer study, Sweden. Participants aged 45-73 years were recruited for the baseline examination between 1991 and 1996, and the mean follow-up time was 18 years. To assess robustness of estimations, we used seven previously constructed EAT-Lancet diet scores. Multi-adjusted Cox proportional hazard analyses were performed, with results presented per 10 % in increment scores. Additionally, we explored the potentially modifying effect of APOE ε4 status in this context.</p><p><strong>Results: </strong>With one of the scores, higher adherence to the EAT-Lancet diet was associated with a reduced risk of AD and all-cause dementia. Moreover, the results suggest an interplay between the EAT-Lancet diet and APOE ε4 status. A risk-reducing effect was observed among APOE ε4 non-carriers with three of the scores in relation to AD, and with five of the scores in relation to all-cause dementia. No associations were observed among APOE ε4 carriers, or in relation to VaD.</p><p><strong>Conclusion: </strong>The results indicate a risk reducing effect of adhering to the EAT-Lancet diet among APOE ε4 non-carriers, and no negative effects on dementia risk were detected. Future studies should consider the potentially modifying effect of APOE ε4 status, and the implications of methodological differences in measuring adherence to the EAT-Lancet diet.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100166"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Herpes zoster as risk factor for dementia: a matched cohort study over 20 years in a 10-million population in Italy.","authors":"Lorenzo Blandi, Paola Bertuccio, Carlo Signorelli, Helmut Brand, Timo Clemens, Cristina Renzi, Anna Odone","doi":"10.1016/j.tjpad.2025.100167","DOIUrl":"10.1016/j.tjpad.2025.100167","url":null,"abstract":"<p><strong>Background: </strong>Herpes Zoster is caused by the reactivation of the Varicella-Zoster Virus. Zoster may influence the occurrence of dementia, but contradictory results about this association emerged from recent studies. These findings did not consider the severity of Zoster and observed individuals for limited follow-up time. Our study used a region-wide Italian registry to investigate the association between severe Zoster infection and dementia occurrence over a 23-year period.</p><p><strong>Methods: </strong>We included people aged ≥ 50 and hospitalised with Zoster, and two comparison cohorts from both the general population and the hospitalised population without Zoster. By random sampling, the matching 1:5 was based on sex, birth year, and entry date in the cohort. Dementia and Zoster were identified through validated algorithms. A Fine-Gray sub-distribution hazard model was used, accounting for competing risk of death.</p><p><strong>Results: </strong>We identified 132,968 individuals, of whom 12,088 with severe Zoster, 60,440 matched controls among the general population, and 60,440 matched controls among the hospitalised population. In severe cases of Herpes Zoster, the overall adjusted sub-distributed hazard ratio of dementia was 1.13 (95 % CI 1.07-1.19) compared to the general population, and 1.08 (95 % CI 1.03-1.14) compared to hospitalised population. Hazard ratios were still significant in different strata group, including by sex, age group (including in 50-65 younger adults) and at different follow-up period.</p><p><strong>Conclusions: </strong>Our population-based study found an increased risk of developing dementia among severe Zoster cases. Those results support the importance of improving Zoster prevention and extending the vaccination recommendations to younger age groups.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100167"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144039539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the editor in response to Shih-Wei et al.","authors":"Lorenzo Blandi, Paola Bertuccio, Carlo Signorelli, Helmut Brand, Timo Clemens, Cristina Renzi, Anna Odone","doi":"10.1016/j.tjpad.2025.100197","DOIUrl":"10.1016/j.tjpad.2025.100197","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100197"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to \"INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease\" [J Prev Alzheimers Dis 2025;12(1): 100005.].","authors":"Eric Siemers, Todd Feaster, Gopalan Sethuraman, Karen Sundell, Vladimir Skljarevski, Erika N Cline, Hao Zhang, Jasna Jerecic, Lawrence S Honig, Stephen Salloway, Reisa Sperling, Mirjam N Trame, Michael G Dodds, Kimball Johnson","doi":"10.1016/j.tjpad.2025.100213","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100213","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100213"},"PeriodicalIF":4.3,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebrovascular disease in Alzheimer's disease: Brain structure as a critical mediator of cognitive decline.","authors":"Chao Tang, Yaqi Ding, Jiaxin Yang, Dian He","doi":"10.1016/j.tjpad.2025.100209","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100209","url":null,"abstract":"<p><strong>Background: </strong>The co-occurrence of Alzheimer's disease and cerebrovascular disease is increasingly prevalent in aging populations, yet the mechanisms of their interaction remain incompletely understood. This study aims to investigate the associations between CVD and AD and their composite effects on cognitive function, identifying key mediating pathways in these relationships.</p><p><strong>Methods: </strong>Participants underwent standardized clinical evaluations, detailed neuropsychological testing, and comprehensive neuropathological examinations. Structural equation modeling with multiple mediation analyses was employed to disentangle direct and indirect effects of vascular pathology on cognition and identify key mediating pathways. Relationships between specific cognitive domain assessments and whole brain and hippocampal volumes were analyzed, while interactions between traditional AD biomarkers (amyloid, tau) and vascular factors were examined.</p><p><strong>Results: </strong>CVD substantially increased AD risk. Structural equation modeling revealed that vascular factors influence cognitive performance primarily through hippocampal atrophy, APOE genotype, and cerebral atrophy. Participants with concomitant AD +CVD pathology displayed a distinctive hybrid pattern of brain-cognition relationships, with stronger correlations between hippocampal atrophy and cognitive performance compared to pure AD or CVD cases. Pathway-specific analysis demonstrated that hippocampal atrophy served as the strongest mediator of vascular effects on cognition, followed by cerebral atrophy and APOE genotype.</p><p><strong>Conclusion: </strong>Our findings demonstrate that cerebrovascular disease significantly increases the risk of Alzheimer's disease and substantially influences its clinical expression through multiple pathways, with structural brain changes serving as critical mediators of vascular effects on cognition. These results highlight the importance of addressing vascular health as an integral component of strategies to prevent and treat Alzheimer's disease and related cognitive disorders.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100209"},"PeriodicalIF":4.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative efficacy of cognitive training modalities in cognitive impairment: A systematic review and network meta-analysis.","authors":"Li-Bing Liang, Shan Wang, Kun-Peng Li, Cai-Qin Wu","doi":"10.1016/j.tjpad.2025.100207","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100207","url":null,"abstract":"<p><strong>Background: </strong>Cognitive training is a widely utilized non-pharmacological intervention to enhance cognitive performance in individuals with cognitive impairment. Despite its potential, significant ambiguity remains regarding its definition, optimal modalities, and design parameters. It remains unclear which types of cognitive training are relatively optimal for different levels of cognitive impairment or how intervention designs can maximize therapeutic benefits.</p><p><strong>Objectives: </strong>This systematic review and network meta-analysis aimed to compare the effects of various cognitive training modalities on cognitive, psychological, and quality-of-life outcomes in individuals with cognitive impairment. Additionally, it sought to identify optimal intervention approaches, clarify key design parameters, and examine critical factors influencing treatment efficacy.</p><p><strong>Methods: </strong>A comprehensive search was conducted across 12 databases from the establishment of the database until October 24, 2024, to identify eligible randomized controlled trials (RCTs) evaluating cognitive training interventions. Data were analyzed using pairwise meta-analysis and network meta-analysis in Review Manager 5.4 and Stata 18.</p><p><strong>Results: </strong>Totally 43 RCTs were included. Pairwise meta-analysis revealed that cognitive strategy training demonstrated superior to active control (AC) or passive control (PC) in improving language function, immediate memory, depressive symptoms and quality of life. However, no significant effects were detected regarding cognitive impairment severity, delivery format, interventionist expertise level, training duration, or control type. Network meta-analysis further identified reminiscence therapy as the most pronounced effective intervention for improving global cognition across all stages of cognitive impairment.</p><p><strong>Conclusions: </strong>Reminiscence therapy has been demonstrated as a relatively optimal cognitive training modality for enhancing cognitive function in individuals with varying levels of cognitive impairment. Future studies should prioritize longitudinal investigations to validate the durability of therapeutic benefits and incorporate neuroimaging and biomarker analyses to elucidate underlying mechanisms. High-quality RCTs remain imperative to strengthen the evidence base and evaluate the consistency of effects across diverse cognitive training interventions.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100207"},"PeriodicalIF":4.3,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of multimorbidity and disease clusters with neuroimaging and cognitive outcomes in UK Biobank.","authors":"Shehab Uddin Al Abid, Catherine M Calvin, Danial Qureshi, Michele Veldsman, Elżbieta Kuźma, Thomas J Littlejohns","doi":"10.1016/j.tjpad.2025.100208","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100208","url":null,"abstract":"<p><strong>Background: </strong>The relationship between multimorbidity, particularly disease clusters, with neuroimaging and cognitive outcomes that typically manifest prior to clinical diagnosis of dementia, remains understudied. This study investigated whether multimorbidity is associated with dementia-related neuroimaging and cognitive outcomes in the UK Biobank cohort.</p><p><strong>Methods: </strong>This cross-sectional study used data from UK Biobank participants who attended imaging assessments between 2014-2023, and were free from neurological conditions, including dementia. Multimorbidity was defined as the coexistence of two or more long-term conditions, selected from a standardised criteria of 39 conditions. Latent class analyses were used to identify disease clusters. Neuroimaging outcomes were measured using magnetic resonance imaging, and cognition was assessed by seven tests measuring different cognitive domains. Multivariable linear regression was used to assess the association between multimorbidity and disease clusters with neuroimaging and cognitive outcomes.</p><p><strong>Results: </strong>A total of 43,160 participants were included (mean [standard deviation] age, 64.2 [7.7] years, 53.1 % female). Multimorbidity was present among 14,339 (33.2 %) participants, and was associated with reduced grey matter volume, total brain volume, left hippocampal volume, increased cerebrovascular pathology as well as reduced domain-specific cognitive function. A strong dose-response relationship was observed with the increasing number of multimorbid conditions across these outcomes. A disease cluster driven by cardiometabolic conditions was consistently associated with poorer brain health across all outcomes. Disease clusters driven by respiratory, mental health and other conditions showed less consistent associations.</p><p><strong>Conclusions: </strong>Multimorbidity was strongly associated with poorer brain health, particularly within the cardiometabolic disease cluster. Given that UK Biobank participants are, on average, healthier than the general population, future studies in more diverse and representative cohorts would be valuable.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100208"},"PeriodicalIF":4.3,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144161114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}