Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring最新文献

{"title":"Allostatic load dynamics, Alzheimer's disease biomarkers, and progression in individuals with mild cognitive impairment: findings from the Alzheimer's Disease Neuroimaging Initiative.","authors":"Juliana N Souza-Talarico, Yelena Perkhounkova, Maria Hein, Jihye Lee, Marco Hefti, Shireen Sindi","doi":"10.1002/dad2.70140","DOIUrl":"https://doi.org/10.1002/dad2.70140","url":null,"abstract":"<p><p>Allostatic load (AL), reflecting chronic stress, is linked to cognitive decline, but its role in the Alzheimer's disease (AD) continuum needs further study. We examined the relationship between AL, progression from mild cognitive impairment (MCI) to mild dementia due to AD, and AD biomarkers. We analyzed 385 MCI individuals over 36 months using Alzheimer's Disease Neuroimaging Initiative (ADNI) data. AL index (ALI) changes over 12 months were calculated using plasma neuroendocrine, immunological, and metabolic markers. AD biomarkers included plasma amyloid beta 42 (Aβ42), cerebrospinal fluid (CSF) Aβ1-42, tau, and hippocampus volume. A one-point ALI increase was associated with MCI conversion odds by 15%. ALI increased in those progressing to mild dementia due to AD and decreased in MCI stable participants. ALI increases were linked to high CSF tau, plasma Aβ42, and low CSF Aβ1-42, moderated by age, <i>APOE</i> ε4, and baseline tau levels. AL may interact with age and genetic risk, impacting AD biomarkers and MCI progression.</p><p><strong>Highlights: </strong>ALI increase raises MCI to AD conversion odds by 15%.ALI increases in those progressing to AD and decreases in stable participants.Higher ALI was linked to high CSF tau, plasma Aβ42, and low CSF Aβ1-42These associations were moderated by age, <i>APOE</i> ε4 status, and baseline CSF tau.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 3","pages":"e70140"},"PeriodicalIF":4.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12213454/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144555711","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":"Correction to \"Culturally adapted cognitive assessment tool for Indigenous communities in Brazil: Content, construct, and criterion validity\".","authors":"","doi":"10.1002/dad2.70146","DOIUrl":"https://doi.org/10.1002/dad2.70146","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1002/dad2.12591.].</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 3","pages":"e70146"},"PeriodicalIF":4.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12207321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546143","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":"Clinical validation of the Lilly SP-X P-tau217 assay: Performance in underrepresented cohorts.","authors":"Michael E Hodsdon, Adam Abel, Antonio Chambers, Ming Lu, Amanda Morris, Michael J Pontecorvo, Heinz Reiske, Samantha C Burnham, Emily C Collins, Mark Mintun, Andrew Schade, Rose C Beck","doi":"10.1002/dad2.70139","DOIUrl":"10.1002/dad2.70139","url":null,"abstract":"<p><strong>Inroduction: </strong>Plasma phosphorylated tau217 (p-tau217) is a biomarker for the detection of amyloid pathology. We present performance characteristics of the Lilly SP-X P-tau217 assay in a clinical validation cohort, as a whole and divided into subpopulations from traditionally underrepresented groups.</p><p><strong>Methods: </strong>We measured p-tau217 levels in plasma samples from participants with mild cognitive impairment. Assay performance in predicting positivity for amyloid beta (Aβ) positron emission tomography was examined using two numerical cutoffs.</p><p><strong>Results: </strong>Two p-tau217 cutoffs were determined with an upper-level group with 95% positive predictive value for Aβ positivity and a lower-level group with 84% negative predictive value for Aβ negativity, with 91% sensitivity and 90% specificity. The remaining indeterminate group represented 18% of participant samples. Similar performance was observed across validation subgroups.</p><p><strong>Discussion: </strong>The validation data support the potential clinical utility of the SP-X p-tau217 assay in multiple subpopulations to aid in Alzheimer's disease diagnosis.</p><p><strong>Highlights: </strong>The Lilly SP-X p-tau217 assay showed strong concordance with amyloid PET in total cohort and underrepresented groups.Assay performance is in line with guidance from the Global CEOi on AD Working Group.Data support the clinical utility of the assay in multiple cohorts to aid in AD diagnosis.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 3","pages":"e70139"},"PeriodicalIF":4.0,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12206948/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546142","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":"Faster decline of very prodromal dementia with Lewy bodies when amyloid positive.","authors":"Frédéric Blanc, Vincent Bouteloup, Claire Paquet, Marie Chupin, Florence Pasquier, Audrey Gabelle, Mathieu Ceccaldi, Paulo Loureiro de Sousa, Pierre Krolak-Salmon, Renaud David, Clara Fischer, Jean-François Dartigues, David Wallon, Olivier Moreaud, Mathilde Sauvée, Catherine Belin, Claire Roubaud Baudron, Anne Botzung, Alix Ravier, Catherine Demuynck, Izzie Namer, Marie-Odile Habert, Olivier Bousiges, Benoît Schorr, Candice Muller, Nathalie Philippi, Geneviève Chêne, Benjamin Cretin, Jean-François Mangin, Carole Dufouil","doi":"10.1002/dad2.70141","DOIUrl":"10.1002/dad2.70141","url":null,"abstract":"<p><strong>Introduction: </strong>The cognitive and neuroimaging evolution during dementia with Lewy bodies (DLB) from the prodromal phase (Pro-DLB; subjective cognitive impairment [SCI] to mild cognitive impairment [MCI]) according to amyloid beta (Aβ) status is poorly understood.</p><p><strong>Methods: </strong>The decline of Lewy-Memento patients with SCI or MCI was compared according to Aβ status across four groups: Pro-DLB, prodromal Alzheimer's disease (Pro-AD), Pro-DLB+AD, and a group without prodromal DLB and AD (no symptoms [NS]). We observed the evolution of cognitive, functional, quality of life measures, brain volumetry, and metabolism on fluorodeoxyglucose positron emission tomography.</p><p><strong>Results: </strong>In the Pro-DLB and Pro-DLB+AD groups, Aβ+ patients had more cognitive and functional decline than the Aβ- patients. In the Pro-AD and NS groups, Aβ+ patients had more functional decline. Aβ+ Pro-AD showed a greater volume decline of the brain (left insula).</p><p><strong>Discussion: </strong>The presence of amyloid lesions worsens very prodromal DLB patients over time, both cognitively and functionally, but without increasing atrophy.</p><p><strong>Highlights: </strong>Patients at a very prodromal stage, subjective cognitive impairment or mild cognitive impairment, had a clinical diagnosis of either prodromal Alzheimer's disease (Pro-AD), prodromal dementia with Lewy bodies (Pro-DLB), Pro-DLB+AD, or no diagnosis.Amyloid beta positive (Aβ+) patients had more functional decline, whatever the group.Aβ+ DLB patients (Pro-DLB and Pro-DLB+AD) had more global cognitive (Mini-Mental State Examination) decline.Aβ+ Pro-AD patients showed a greater volume decline of the left insula.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70141"},"PeriodicalIF":4.0,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144499123","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":"Associations of abdominal adiposity, lean body mass, and fat body mass with dementia and cognitive change in older age.","authors":"Zimu Wu, Alice Owen, Robyn L Woods, Zhen Zhou, Trevor T-J Chong, Suzanne G Orchard, Raj C Shah, Kerry M Sheets, Anne M Murray, Joanne Ryan","doi":"10.1002/dad2.70135","DOIUrl":"10.1002/dad2.70135","url":null,"abstract":"<p><strong>Introduction: </strong>This study examined whether the waist circumference-body mass index ratio (WBR), lean body mass (LBM), and fat body mass (FBM) were associated with dementia or cognitive change.</p><p><strong>Methods: </strong>We analyzed data from >17,000 individuals aged 65 to 98 years at enrollment. LBM and FBM were estimated using the Hume equation. Dementia was determined according to DSM-IV. Global cognition, verbal fluency, episodic memory, and psychomotor speed were assessed across 11 years. Cox and mixed-effects models were used to examine the associations with dementia and cognitive change.</p><p><strong>Results: </strong>WBR was positively associated with dementia (Q4 versus Q1, hazard ratio [HR]: 1.29, <i>p</i> = 0.004) and cognitive decline (coefficients:-0.122 to -0.025, <i>p</i> < 0.05). Dementia risk was 15% to 38% lower for individuals in higher quartiles of LBM and FBM (Q2 to Q4), compared to Q1 (<i>p</i> < 0.05). Higher LBM and FBM were associated with slower cognitive decline (coefficients: 0.035 to 0.203, <i>p</i> < 0.05), except for verbal fluency.</p><p><strong>Discussion: </strong>Higher LBM and FBM in later life may be associated with better cognition, while abdominal fat could be a risk factor.</p><p><strong>Highligths: </strong>Higher WBR is associated with greater dementia risk, only in men.Higher WBR is associated with faster cognitive decline.Greater LBM and FBM are associated with lower dementia risk.Greater LBM and FBM are associated with slower cognitive decline.Central adiposity may be a risk factor for cognitive impairment in older adults.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70135"},"PeriodicalIF":4.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477804","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 item-level responses to cognitive function index with tau pathology and hippocampal volume in the A4 Study.","authors":"Idris Demirsoy, Elham Ghanbarian, Babak Khorsand, Bhargav T Nallapu, Kellen K Petersen, Richard B Lipton, S Ahmad Sajjadi, Laura A Rabin, Ali Ezzati","doi":"10.1002/dad2.70128","DOIUrl":"10.1002/dad2.70128","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) has a long preclinical phase in which individuals may accumulate amyloid beta (Aβ) and tau pathology without noticeable cognitive impairment. Subjective cognitive impairment reports can provide early insights into cognitive decline.</p><p><strong>Methods: </strong>In the A4 Study, 339 cognitively unimpaired, Aβ-positive individuals underwent tau positron emission tomography imaging. Tau status was classified based on medial temporal lobe tau standardized uptake value ratios (tau_MTL). Participants and study partners assessed cognitive changes using the 15-item Cognitive Function Index (CFI) questionnaire. We explored the relationship among tau_MTL, hippocampal volume (HVa), and CFI reports.</p><p><strong>Results: </strong>Higher tau_MTL was associated with participant-reported concerns about memory and navigation, and with study partner-reported difficulty remembering appointments. Lower HVa showed a marginal association with participant-reported driving difficulty.</p><p><strong>Discussion: </strong>These findings support the utility of participant- and study partner-reported concerns as early indicators of preclinical AD pathology, with potential value for early detection and trial enrichment strategies.</p><p><strong>Highlights: </strong>Higher tau in the medial temporal lobe (tau_MTL) was linked to participant-reported memory and orientation decline such as needing reminders or getting lost.Higher tau_MTL was associated with increased memory-related concerns, such as needing help with appointments and asking repetitive questions.Lower hippocampal volume was associated with spatial memory and navigation such as driving difficulties and greater memory decline as reported by study partners.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70128"},"PeriodicalIF":4.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334399","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":"Retinal vascular biomarkers in mild cognitive impairment and Alzheimer's disease: a comprehensive review and meta-analysis.","authors":"Sunu Mathew, Yen-Ning Huang, Paula Bice, Andrew J Saykin, Shannon L Risacher","doi":"10.1002/dad2.70132","DOIUrl":"10.1002/dad2.70132","url":null,"abstract":"<p><p>Retinal vasculature could be a novel, non-invasive, and inexpensive biomarker for Alzheimer's disease (AD) -related neuropathology. In this comprehensive review and meta-analysis from studies that assessed retinal vasculature using optical coherence tomography angiography in AD dementia, we calculated the pooled standardized mean differences (SMDs) in vascular density (VD)-whole, VD-parafoveal, vessel length density (VLD) and foveal avascular zone (FAZ) between AD and cognitively normal (CN), and between mild cognitive impairment (MCI) and CN. Thirty-six studies were included in the meta-analysis. The pooled SMD between AD and CN in VD-whole, VD-parafoveal, VLD, and FAZ was -0.69 (<i>p</i> < 0.01), -0.38 (<i>p</i> = 0.01), -0.59 (<i>p</i> < 0.01), and 0.33 (<i>p</i> = 0.06), respectively, and between MCI and CN in VD-whole, VD-parafoveal, VLD, and FAZ was -0.36 (<i>p</i> = 0.03), -0.17 (<i>p</i> = 0.44), -0.34 (<i>p</i> = 0.03), and 0.31 (<i>p</i> = 0.07), respectively. We identified a significant reduction in retinal vasculature in AD and MCI compared to CN.</p><p><strong>Highlights: </strong>We performed a meta-analysis of 36 studies using optical coherence tomography angiography to assess the retinal vasculature.These included 4129 participants, of which 1175 had Alzheimer's disease (AD), 1004 had mild cognitive impairment, and 1926 were cognitively normal.We identified a significant reduction in retinal vasculature in AD and mild cognitive impairment compared to cognitively normal.Retinal perfusion measured using optical coherence tomography angiography could be used as a potential biomarker for AD dementia.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70132"},"PeriodicalIF":4.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12168234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144310810","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":"The impact of mild cognitive impairment on healthcare utilization and costs: A UK Biobank study.","authors":"Craig Ritchie, Dominic Trepel, Sophie Edwards, Julie Hviid Hahn-Pedersen, Mei Sum Chan, Benjamin D Bray, Alice Clark, Christian Ahmad Wichmann, Marc Evans","doi":"10.1002/dad2.70065","DOIUrl":"10.1002/dad2.70065","url":null,"abstract":"<p><strong>Introduction: </strong>Mild cognitive impairment (MCI) is common in older adults, but the burden on patients and health systems is not well understood. We aimed to estimate the impact of MCI on healthcare utilization and costs.</p><p><strong>Methods: </strong>This was a matched cohort study in UK Biobank comparing healthcare costs and Alzheimer's disease (AD) dementia incidence rates in participants with MCI to propensity score-matched participants without MCI.</p><p><strong>Results: </strong>Of 164,508 eligible participants, 6605(4%) had cognitive testing scores consistent with MCI. Ten-year inpatient costs were 7.6% higher in MCI versus matched no-MCI participants, while 6-year primary care costs were 9.1% higher. Among MCI participants, AD dementia incidence rates were substantially higher than in non-MCI participants (7.2 5-year incidence rate ratio 95% CI: 3.3 to 15.7), and eventual AD dementia accrued higher additional inpatient costs (mean £20,199) over 10 years.</p><p><strong>Discussion: </strong>MCI is characterized by modestly higher healthcare utilization and costs. Subsequent AD dementia diagnosis was strongly associated with costs.</p><p><strong>Highlights: </strong>Baseline cognitive tests identified individuals with all-cause MCI in the UK Biobank.We compared individuals with MCI to propensity score-matched participants without MCI.Inpatient costs were 7.6% higher over 10 years, and primary care costs were 9.1% higher over 6 years for participants with MCI.AD dementia incidence rate ratio was 7.2 higher in participants with MCI.Among MCI participants, eventual AD dementia was a key driver of costs resulting in higher inpatient costs (mean £20,199) over 10 years.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70065"},"PeriodicalIF":4.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144287119","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":"Automated identification of older adults at risk for cognitive decline.","authors":"Darlene P Floden, Olivia Hogue, Saket A Saxena, Anita D Misra-Hebert, Alex Milinovich, Michael B Rothberg, Elizabeth R Pfoh, Robyn M Busch, Kamini Krishnan, Robert J Fox, Michael W Kattan","doi":"10.1002/dad2.70136","DOIUrl":"10.1002/dad2.70136","url":null,"abstract":"<p><strong>Introduction: </strong>Automated models that predict cognitive risk in older adults can aid decisions about which patients to screen in busy primary care settings.</p><p><strong>Methods: </strong>In this retrospective prediction model development study, we conducted formal cognitive testing on 337 older primary care patients to establish cognitive status. We used up to 5 years of prior discrete-field electronic health record (EHR) data to develop a multivariable prediction model that differentiates patients with impaired versus intact cognition.</p><p><strong>Results: </strong>The final model included seven easily extractable variables with known associations to cognitive decline: age, race, pulse, systolic blood pressure, non-steroidal anti-inflammatory use, history of mood disorder, and family history of neurological disease. The model demonstrated good discrimination of cognitive status (concordance statistic = 0.72).</p><p><strong>Discussion: </strong>The cognitive risk model may be useful clinically to prompt for objective cognitive screening in high-risk patients. The use of common, discrete variables ensures relative ease of implementation in EHRs.</p><p><strong>Highlights: </strong>337 older primary care patients completed full neuropsychological assessment.Risk modeling used data available in a typical primary care record.The model successfully differentiated patients with/without cognitive impairment.This EHR model offers a passive workflow to identify patients at cognitive risk.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70136"},"PeriodicalIF":4.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12162263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144303569","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":"Sex- and age-specific effect of known type 2 diabetes mellitus on incident mild cognitive impairment five years later: Results from the population-based Heinz Nixdorf Recall study.","authors":"Anna Lena Platzbecker, Janine Gronewold, Sara Schramm, Susanne Moebus, Andreas Stang, Börge Schmidt, Christian Weimar, Martha Jokisch","doi":"10.1002/dad2.70130","DOIUrl":"10.1002/dad2.70130","url":null,"abstract":"<p><strong>Introduction: </strong>As studies on the association between type 2 diabetes mellitus (T2DM) and mild cognitive impairment (MCI), including amnestic (aMCI) and non-amnestic (naMCI) subtypes, vary by sex and age, we investigated the sex- and age-specific effects of T2DM on incident MCI after five years in a population-based sample.</p><p><strong>Methods: </strong>A total of 145 participants with T2DM and 1322 without T2DM were included. MCI was defined using established criteria excluding subjective cognitive decline. Adjusted relative risks (aRRs) were calculated considering age, education, body mass index, smoking, and alcohol intake, and stratified by sex and age (middle-aged: 50-65 years; old-aged: 66-80 years).</p><p><strong>Results: </strong>MCI occurred in 39.3% (<i>n</i> = 57) of participants with T2DM versus 27.5% (<i>n</i> = 363) without (aRR: 1.29, 95% confidence interval [CI]: 0.97-1.73). Middle-aged men showed an association with naMCI (aRR: 2.35, 95% CI: 1.26-4.39) and middle-aged women with aMCI (aRR: 2.05, 95% CI: 0.58-7.21).</p><p><strong>Discussion: </strong>T2DM increases MCI risk, particularly in middle-aged individuals with poorly controlled T2DM, emphasizing the need for prevention strategies.</p><p><strong>Highlights: </strong>Longitudinal results from the population-based Heinz Nixdorf Recall study in Germany.Incident mild cognitie impairment (MCI) was more common in type 2 diabetes mellitus (T2DM; 39% vs 28%).T2DM affects incident MCI and subtypes in middle-aged, not old-aged; stronger in men with poorly controlled T2DM.Importance of enhancing age- and sex-specific prevention at the population level.</p>","PeriodicalId":53226,"journal":{"name":"Alzheimer''s and Dementia: Diagnosis, Assessment and Disease Monitoring","volume":"17 2","pages":"e70130"},"PeriodicalIF":4.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12152370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276631","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}