Rebecca J Howe, Lan Jiang, Matthew D Howe, Zachary J Kunicki, John E McGeary, Mindy M Kibbey, Wen-Chih Wu, Catherine Kelso, Samuel Edwards, James L Rudolph, Jane A Driver
{"title":"Electronic Dementia Assessment Score: Screenings and Receipt of Home and Community-Based Services.","authors":"Rebecca J Howe, Lan Jiang, Matthew D Howe, Zachary J Kunicki, John E McGeary, Mindy M Kibbey, Wen-Chih Wu, Catherine Kelso, Samuel Edwards, James L Rudolph, Jane A Driver","doi":"10.1097/WAD.0000000000000752","DOIUrl":"https://doi.org/10.1097/WAD.0000000000000752","url":null,"abstract":"<p><strong>Introduction: </strong>With population aging, ensuring that people living with dementia receive appropriate assessment and services is critical. The objective of this study was to determine whether electronic dementia assessment is associated with increased receipt of home-based and community-based services (HCBS) among Veterans with heart failure and newly diagnosed dementia.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of community-dwelling Veterans with heart failure who received an incident dementia diagnosis between 2010 and 2023. Electronic health record (EHR) data were used to identify completion of cognitive, psychiatric, and functional assessments from 365 days before to 90 days after dementia diagnosis. The primary outcome was receipt of HCBS. Logistic regression with inverse probability of treatment weighting adjusted for demographics, comorbidities, and health care utilization.</p><p><strong>Results: </strong>Among 46,157 Veterans with heart failure and incident dementia, 4% had documented cognitive, 82% psychiatric, and 41% functional assessments. Overall, 25% received HCBS. IPTW-adjusted odds of receiving HCBS significantly increased with electronic health record documentation of cognitive, psychiatric, and functional assessments.</p><p><strong>Conclusions: </strong>Among Veterans with heart failure and newly diagnosed dementia, documentation of cognitive, psychiatric, and functional assessments was associated with greater odds of receiving HCBS. Electronic dementia assessment may support system-level efforts to align dementia care with the goals of aging in place.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229834","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}
Anderson M Pereira da Silva, Maria D V Santos do Nascimento, Giovana Menegucci, Gabriel Caruso Novaes Tudella, Lucas Silva Cabeça, Ocílio Ribeiro Gonçalves, Bernardo Vieira Nogueira, Julia Oliveira Franco, Diogo Haddad Santos, Filipe Silveira Duarte, George Perry, Eryvelton de Souza Franco, Maria Bernadete de Sousa Maia
{"title":"Pioglitazone and Cognitive Outcomes in Mild Cognitive Impairment and Alzheimer Disease: A Systematic Review and Meta-Analysis of Randomized Trials.","authors":"Anderson M Pereira da Silva, Maria D V Santos do Nascimento, Giovana Menegucci, Gabriel Caruso Novaes Tudella, Lucas Silva Cabeça, Ocílio Ribeiro Gonçalves, Bernardo Vieira Nogueira, Julia Oliveira Franco, Diogo Haddad Santos, Filipe Silveira Duarte, George Perry, Eryvelton de Souza Franco, Maria Bernadete de Sousa Maia","doi":"10.1097/WAD.0000000000000744","DOIUrl":"10.1097/WAD.0000000000000744","url":null,"abstract":"<p><strong>Background: </strong>Cognitive impairment is increasingly recognized among older adults with metabolic disorders, including type 2 diabetes. Metabolic dysfunction and insulin resistance have been implicated in neurodegenerative processes. Pioglitazone, an insulin-sensitizing agent widely used in the treatment of type 2 diabetes, has been investigated for potential effects on cognitive outcomes. This systematic review and meta-analysis evaluated the efficacy and safety of pioglitazone on cognitive outcomes in individuals with mild cognitive impairment or Alzheimer disease.</p><p><strong>Methods: </strong>PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched through July 2025 for randomized controlled trials comparing pioglitazone with placebo in adults with mild Alzheimer disease or mild cognitive impairment. Cognitive outcomes included the Mini-Mental State Examination, the Wechsler Memory Scale-Revised, and the Alzheimer's Disease Assessment Scale-Cognitive subscale. Safety outcomes included adverse events, serious adverse events, treatment discontinuation, and peripheral edema. Random-effects meta-analyses were conducted using frequentist and Bayesian approaches.</p><p><strong>Results: </strong>Six randomized trials, including 3680 participants, were analyzed. Pioglitazone was not associated with differences in Mini-Mental State Examination or Wechsler Memory Scale-Revised scores compared with placebo. Alzheimer's Disease Assessment Scale-Cognitive subscale estimates modestly favored pioglitazone, although this finding was not consistent across other cognitive measures. Overall, adverse events and serious adverse events were similar between treatment groups. Treatment discontinuation occurred less frequently with pioglitazone. Peripheral edema was reported more frequently with pioglitazone, although estimates were based on a small number of events and wide CIs.</p><p><strong>Conclusion: </strong>Pioglitazone was not associated with consistent differences in global cognitive outcomes in individuals with mild cognitive impairment or Alzheimer disease. Safety outcomes were broadly comparable to placebo, although peripheral edema occurred more frequently.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"259-267"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820722","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":"Post Hoc Subgroup Analysis by Disease Severity in a Non-Inferiority Trial of Donepezil 27.5 mg Transdermal Formulation in Japanese Patients With Mild-to-Moderate Alzheimer Disease.","authors":"Yu Nakamura, Takuma Tsushio, Masaya Tanahashi, Hideki Suganami, Takumi Omori, Kenichi Nishiyama, Hiroshi Aoki, Naoki Nagakura","doi":"10.1097/WAD.0000000000000738","DOIUrl":"10.1097/WAD.0000000000000738","url":null,"abstract":"<p><strong>Background: </strong>The efficacy of cholinesterase inhibitors varies depending on the severity of Alzheimer disease. We examined the effects of the disease severity on the efficacy of donepezil 27.5 mg patches in Japanese patients with Alzheimer disease.</p><p><strong>Methods: </strong>A post hoc analysis of covariance using per-protocol set in a noninferiority study of donepezil 27.5 mg patches with donepezil hydrochloride 5 mg tablets (JapicCTI-194582) was conducted after imputation of missing data using multiple imputations.</p><p><strong>Results: </strong>No apparent imbalances in the extracted confounding factors were observed between the 2 treatment groups. The baseline value of the Alzheimer Disease Assessment Scale (Japanese version) cognitive subscale was adjusted using analysis of covariance. Least-squares mean of changes from baseline in the Alzheimer Disease Assessment Scale (Japanese version) cognitive subscale at week 24 for each group were -1.661 (-2.681 to -0.640) (donepezil patch) and 0.065 (-0.987 to 1.117) (donepezil hydrochloride tablet). The difference in the least-squares mean (95% CI) between 2 groups was -1.726 (-3.1913 to -0.2602, P =0.021).</p><p><strong>Conclusions: </strong>A post hoc analysis of covariance using the per-protocol set suggested that donepezil patches may be more effective than donepezil tablets in slowing cognitive decline in patients with mild Alzheimer disease.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"212-216"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148400185","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":"Representation of Alzheimer Disease and Related Dementias in a Statewide Population Genomics Cohort: Early Findings from In Our DNA SC.","authors":"Janet Horn, Sara Knox","doi":"10.1097/WAD.0000000000000750","DOIUrl":"10.1097/WAD.0000000000000750","url":null,"abstract":"<p><p>Alzheimer Disease and Related Dementias (ADRD) affect more than 125,000 individuals in South Carolina, yet equitable representation in population genomics initiatives remains a concern. We conducted a cross-sectional descriptive analysis of 247 In Our DNA SC participants aged 50 to 89 years with at least 1 ADRD-related diagnosis, identified using ICD-10 codes, to characterize demographic and clinical features and to compare the cohort with statewide ADRD estimates. Most participants were aged 65 years or older (82.2%), female (52.2%), and White (93.1%), while only 5.3% identified as Black. Nearly half had a Charlson Comorbidity Index score of 4 or greater (48.6%), and 49.5% had at least 10 years of longitudinal electronic health record data. Compared with statewide ADRD estimates, Black individuals were substantially underrepresented despite comprising ∼one-third of ADRD cases in South Carolina. These findings highlight the need for continued efforts to improve representation and support equitable, generalizable precision health research.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"256-258"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868798","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}
Anju Paudel, Elizabeth Galik, Terrence E Murphy, Marie Boltz
{"title":"Content Validity of the Quality of Interactions Inventory (QUALII) in Assisted Living.","authors":"Anju Paudel, Elizabeth Galik, Terrence E Murphy, Marie Boltz","doi":"10.1097/WAD.0000000000000741","DOIUrl":"10.1097/WAD.0000000000000741","url":null,"abstract":"<p><strong>Background/aim: </strong>To promote staff and resident well-being in Assisted Living (AL), it is essential to enhance daily care interactions between staff and older adults with Alzheimer disease and related dementias (ADRD). There is currently no comprehensive instrument that can both guide the process of improving care interactions and appraise the impact of such improvements in AL. We developed a comprehensive instrument, the Quality of Interactions Inventory (QUALII), that accomplishes both tasks. Here, we evaluate its content validity.</p><p><strong>Methods: </strong>An eDelphi study with a convenience sample of N=10 clinical/academic experts in ADRD care and communication. Item-Content Validity Index (I-CVI) and Scale-Content Validity Index (S-CVI) were computed using quantitative ratings; item revisions were based on content analysis of qualitative comments.</p><p><strong>Results: </strong>Following 3 rounds of eDelphi survey, QUALII was reduced to a 19-item tool with I-CVI=0.90 to 1.00 for item relevance, I-CVI=0.80 to 1.00 for item clarity, and S-CVI=0.93 for the overall scale.</p><p><strong>Conclusion and implications: </strong>QUALII demonstrated excellent content validity and will be used for pilot testing in AL communities. Upon pilot testing, QUALII could emerge as a valid, reliable, and comprehensive tool for promoting positive care interactions in ADRD care.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"224-232"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148765737","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}
L Paloma Rojas-Saunero, Natalie Gradwohl, Joseph O Fong, Yixuan Zhou, Yingyan Wu, Taylor M Mobley, Eleanor Hayes-Larson, Roch A Nianogo, Gilbert C Gee, Ron Brookmeyer, Rachel A Whitmer, Paola Gilsanz, Elizabeth Rose Mayeda
{"title":"Hypertension and 10-Year Dementia Risk Among Older Asian American and Non-Latino White Adults in Northern California.","authors":"L Paloma Rojas-Saunero, Natalie Gradwohl, Joseph O Fong, Yixuan Zhou, Yingyan Wu, Taylor M Mobley, Eleanor Hayes-Larson, Roch A Nianogo, Gilbert C Gee, Ron Brookmeyer, Rachel A Whitmer, Paola Gilsanz, Elizabeth Rose Mayeda","doi":"10.1097/WAD.0000000000000742","DOIUrl":"10.1097/WAD.0000000000000742","url":null,"abstract":"<p><strong>Introduction: </strong>Hypertension is a modifiable risk factor for dementia, but its contribution among Asian American ethnic groups remains understudied despite heterogeneity in cardiovascular risk factors.</p><p><strong>Methods: </strong>Participants were Kaiser Permanente Northern California members aged 60 to 90 years without prevalent dementia at baseline, surveyed between 2002 and 2009 [Chinese (n=4,848), Filipino (n=4,130), Japanese (n=2,786), South Asian (n=823), non-Latino White (n=123,593)]. We used ICD-codes to identify hypertension (assessed 5 y before baseline) and incident dementia through 2020. Within strata of race/ethnicity and baseline age group (60 to 75 and 75 to 90 y), we estimated adjusted and standardized 10-year dementia risk, risk ratios, risk differences, and population attributable fractions (PAFs) using pooled logistic regression, treating death as a censoring event.</p><p><strong>Results: </strong>Among Chinese, Filipino, Japanese, and non-Latino White participants aged 60 to 75 years, PAFs (95% CI) were 12% (-3% to 28%), 23% (4% to 40%), 9% (-7% to 27%), and 8% (5% to 10%), respectively. Effect estimates were null for these groups among participants aged 75 to 90. For South Asian participants, point estimates were consistent with protective associations among those aged 60 to 75 and harmful associations among those aged 75 to 90, although estimates were imprecise.</p><p><strong>Conclusion: </strong>Our findings suggest heterogeneity in the effect of hypertension on dementia risk across Asian American ethnic groups and by age.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"175-182"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835815","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":"Factors for Avoiding Counseling Despite Experiencing Cognitive Impairment in South Korea: An Age-Stratified Analysis of the Korea Community Health Survey.","authors":"In Cheol Hwang, Hong Yup Ahn","doi":"10.1097/WAD.0000000000000749","DOIUrl":"10.1097/WAD.0000000000000749","url":null,"abstract":"<p><p>This study examined factors associated with not seeking counseling among 46,156 Korean adults who experienced cognitive impairment in the past year, using data from the 2024 Korea Community Health Survey. Only 8.1% sought counseling. Age-stratified logistic regression showed that counseling-seeking increased with greater disruption of daily activities. Alcohol consumption consistently predicted not seeking counseling across all age groups, while depression was associated with greater counseling seeking. Lower economic status generally increased counseling seeking, though financial barriers limited help-seeking among older adults. Among middle-aged adults, being unmarried and having hypertension were also linked to higher counseling seeking. These findings suggest the need for age-specific strategies to encourage early help-seeking for cognitive impairment.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"253-255"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820769","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}
Dandan Xu, Li Jiang, Qizhi Yang, Roy Rillera Marzo, Zhijuan Peng, Yali Yao, Ruolei Li, Xia Zhang, Linjie Zhu, Jin Qian, Rui Ji, Wenwen Zhao
{"title":"Projected Global and SDI-Region Care Costs for Alzheimer Disease and Associated Dementias, 2023 to 2050: A Stratified Analysis Based on Global Burden of Disease (GBD) Data.","authors":"Dandan Xu, Li Jiang, Qizhi Yang, Roy Rillera Marzo, Zhijuan Peng, Yali Yao, Ruolei Li, Xia Zhang, Linjie Zhu, Jin Qian, Rui Ji, Wenwen Zhao","doi":"10.1097/WAD.0000000000000748","DOIUrl":"10.1097/WAD.0000000000000748","url":null,"abstract":"<p><strong>Objective: </strong>To project the economic burden of Alzheimer disease and associated dementias (ADAD) care globally and across sociodemographic index (SDI) quintiles from 2023 to 2050, explore disparities by age, sex, and region, and provide evidence for targeted care policies.</p><p><strong>Methods: </strong>Based on Global Burden of Disease 2021 data, we estimated ADAD care costs by integrating years lived with disability, caregiving hours, and wage rates. Regions were stratified into 5 SDI levels, with sex- and age-specific subgroup analyses. Direct care labor costs and their proportion in national GDP were quantified, and temporal trends were forecasted and visualized using R software.</p><p><strong>Results: </strong>Global ADAD care costs rose from USD 0.18 trillion in 1990 to USD 0.33 trillion in 2023, and are projected to reach USD 0.53 trillion by 2050. Females sustained 64.7% of the total burden in 2050, with widening gender gaps at advanced ages. High-SDI regions contributed the largest costs (USD 477.6 billion by 2050), while low-SDI regions had the fastest growth rate of 219.4%. Cost peaks shifted to the 80 to 89 age group, with those aged over 80 accounting for over 50% of total costs. The GDP share of care costs increased nearly 15-fold in low-SDI regions, but only 34.8% in high-SDI regions.</p><p><strong>Conclusion: </strong>The global economic burden of ADAD will continue to rise, driven by population aging, female preponderance, and marked regional inequalities. Tailored strategies are urgently needed, including efficiency improvement in high-SDI areas, financial and infrastructure expansion in low- and middle-SDI regions, and early intervention, gender-sensitive support, and long-term care system reform worldwide. All monetary values use the short-scale convention: 1 billion=1000 million (10 9 ), and 1 trillion=1,000,000 million (10 12 ).</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"233-242"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820717","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}
Aliakbar Netterwala, Thomas Mathew, Allen Johnson, Shagun Bhardwaj
{"title":"Dementia With Extensive Giant Perivascular Spaces as a Mimicker of Alzheimer Disease: A Case Report.","authors":"Aliakbar Netterwala, Thomas Mathew, Allen Johnson, Shagun Bhardwaj","doi":"10.1097/WAD.0000000000000745","DOIUrl":"10.1097/WAD.0000000000000745","url":null,"abstract":"<p><p>Giant perivascular spaces (PVS) are usually incidental magnetic resonance imaging findings, but rarely may present with progressive cognitive decline. We report the case of a 70-year-old woman with a 3-year history of gradually progressive amnestic-predominant dementia associated with impairment in instrumental activities of daily living and multidomain deficits on formal cognitive testing. Magnetic resonance imaging of the brain demonstrated extensive bilateral giant cystic spaces in the subcortical, deep, and periventricular white matter following cerebrospinal fluid signal on all sequences with complete FLAIR suppression, consistent with giant PVS. The evaluation for reversible causes was unrevealing, and the plasma p-tau217/Aβ1-42 ratio was negative, arguing against typical Alzheimer-type amyloid pathology. This case highlights giant PVS as an important radiological mimic of Alzheimer disease and supports the consideration of a severe PVS burden as a potential contributor to progressive late-life cognitive impairment.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"246-248"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148805085","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}
Yan Kong, Xian Li, Ruiqian Guan, Xin Wang, Ao Chen, Hongkun Zhang
{"title":"Age-Dependent and APOE-Modified Associations Between Vascular Risk Factor Patterns and Cognitive Function: A Latent Class Analysis of 44,879 NACC Participants.","authors":"Yan Kong, Xian Li, Ruiqian Guan, Xin Wang, Ao Chen, Hongkun Zhang","doi":"10.1097/WAD.0000000000000739","DOIUrl":"10.1097/WAD.0000000000000739","url":null,"abstract":"<p><strong>Introduction: </strong>Vascular risk factors (VRFs) are established contributors to cognitive decline, yet they often co-occur in distinct patterns. Whether VRF pattern-cognition associations are modified by age or apolipoprotein E (APOE) genotype remains unclear.</p><p><strong>Methods: </strong>We analyzed 44,879 participants aged 60 to 90 years from the National Alzheimer's Coordinating Center (NACC) with normal cognition or mild cognitive impairment (MCI). Latent class analysis (LCA) identified VRF patterns from 7 indicators: hypertension, diabetes, hypercholesterolemia, myocardial infarction, atrial fibrillation, heart failure, and stroke. Multivariable linear regression examined associations between VRF patterns and Mini-Mental State Examination (MMSE) scores, with stratification by age and APOE ε4 status.</p><p><strong>Results: </strong>Five VRF patterns were identified: Low Risk (38.4%), Metabolic Predominant (40.5%), Hypertension Predominant (16.0%), Arrhythmia-Cardiac (2.7%), and High Multimorbidity (2.4%). Each additional VRF was associated with 0.056-point lower MMSE ( β =-0.056, 95% CI: -0.072 to -0.039, P <0.001). Significant age × pattern ( P =0.0015) and APOE × pattern ( P =0.0016) interactions emerged. In younger-old adults (60 to 74 y), Metabolic Predominant was associated with lower MMSE ( β =-0.171, P <0.001), but not in older-old adults (75 to 90 y; β =0.020, P =0.53). Among APOE ε4 carriers, the Metabolic Predominant association was substantially stronger ( β =-0.228, P <0.001) compared with noncarriers ( β =-0.053, P =0.025), a 4.3-fold difference in magnitude.</p><p><strong>Conclusions: </strong>VRF-cognition associations show significant heterogeneity by age and APOE genotype. Attenuated associations in older-old adults may reflect survivor bias, while stronger associations in APOE ε4 carriers are consistent with gene-environment interactions.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"202-211"},"PeriodicalIF":0.0,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148842541","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}