Alzheimer''s and Dementia: Translational Research and Clinical Interventions最新文献

{"title":"Memantine, acetylcholinesterase inhibitors, and quality-of-care outcomes among patients with cognitive impairment: an emulated trial design.","authors":"Erin L Ferguson, Jingxuan Wang, Justin S White, Katherine Possin, Anna Chodos, Fan Xia, Eva Raphael, Alexander K Smith, M Maria Glymour","doi":"10.1002/trc2.70306","DOIUrl":"10.1002/trc2.70306","url":null,"abstract":"<p><strong>Introduction: </strong>We evaluated the effect of acetylcholinesterase inhibitors (AChEIs) and memantine on non-cognitive outcomes by implementing emulated trials in electronic health records.</p><p><strong>Methods: </strong>Individuals diagnosed with cognitive impairment who initiated AChEIs or memantine were matched to up to five non-initiators. Associations of medication initiation with 11 non-cognitive outcomes were estimated using Cox proportional hazards models. We calculated e-values for each hazard ratio (HR) and compared their magnitude to socioeconomic predictors of memantine and AChEI use in a US-based cohort.</p><p><strong>Results: </strong>AChEI initiation was associated with nine of 11 adverse outcomes. For example, the HR for antipsychotic use = 1.67 (95% confidence interval [CI]: 1.51 to 1.84) and depression HR = 1.86 (1.67 to 2.06). Results for memantine were similar. E-values varied from 1.45 to 2.11 for memantine and 1.40 to 2.44 for AChEIs. Many potential confounders had odds ratios (ORs) > 1.4 for initiation, including marital status (ORs = 1.36 to 6.67).</p><p><strong>Discussion: </strong>Memantine and AChEIs were associated with adverse outcomes, and residual confounding was unlikely to fully account for all the observed associations.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70306"},"PeriodicalIF":7.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13598552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149041867","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":"Dementia progression with GLP-1 receptor agonists in people with mild cognitive impairment and type 2 diabetes: target-trial emulation study.","authors":"Meir Schechter, Dvora R Sehtman-Shachar, Alisa Fishkin, Ofri Mosenzon, Tali Cukierman-Yaffe, Ronit Sharon, Gil Leibowitz, David Arkadir, Genya Aharon-Hananel","doi":"10.1002/trc2.70315","DOIUrl":"10.1002/trc2.70315","url":null,"abstract":"<p><strong>Introduction: </strong>In people with type 2 diabetes (T2D) without dementia, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) improved cardiovascular, kidney, and mortality outcomes, with multiple real-world studies suggesting reduced risk of dementia onset. However, the EVOKE/EVOKE+ randomized-controlled trials (RCTs) found that oral semaglutide did not slow cognitive decline in individuals with early Alzheimer's disease (AD), most (86%) without T2D. It is unclear whether GLP-1 RA therapy influences progression to dementia in people with both T2D and mild cognitive impairment (MCI).</p><p><strong>Methods: </strong>In a target-trial emulation hypothesis-generating study using TriNetX global collaborative network data, we compared incident dementia (including AD) in adults with MCI and T2D without dementia, who were new users of GLP-1 RAs versus dipeptidyl peptidase-4 inhibitors (DPP4i).</p><p><strong>Results: </strong>We included 1320 propensity-score-matched (1:1) individuals who initiated GLP-1 RAs or DPP4i in the period 2010 to 2021 (702 women; mean age 67.2 years). Over up to 5 years of follow-up, incident dementia occurred in 101 and 132 participants initiating GLP-1 RAs and DPP4i, respectively (Cox proportional hazard ratio 0.74 [95% confidence interval [CI]: 0.57 to 0.95]). At a mean follow-up of 3.9 years, the respective Kaplan-Meier-derived cumulative incidences were 15.5% and 20.4% (absolute difference -4.9% [95% CI -9.4 to -0.4], number needed to treat of 21 [11 to 234] individuals to prevent one event). Various sensitivity analyses supported the primary analysis: comparing GLP-1 RAs with basal insulin, using alternative outcome definitions, repeating the analyses across baseline subgroups, and using a negative control outcome.</p><p><strong>Conclusion: </strong>In this hypothesis-generating study, initiation of GLP-1 RAs versus DPP4i in people with T2D and MCI without dementia was associated with a lower risk of incident dementia.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70315"},"PeriodicalIF":7.4,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018785","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":"What is new in delirium: A vascular etiology outlook.","authors":"Niccolò Terrando, Mervyn Maze, Ting Yang","doi":"10.1002/trc2.70324","DOIUrl":"10.1002/trc2.70324","url":null,"abstract":"<p><p>Emerging studies have highlighted the vascular contributions to cognitive impairment and dementia (VCID), especially in the context of neurodegenerative disorders that cause cognitive decline (i.e., Alzheimer's disease and related dementias [ADRD]). More recent research on perioperative neurocognitive disorders, including postoperative delirium, is describing a potential role of neurovascular dysfunction in the pathogenesis of these common complications for many older adults. These findings support an expanded conceptual framework in which delirium is not simply a transient disorder of neuronal function but may represent an acute neurovascular phenotype that links systemic inflammation, blood-brain barrier injury, and VCID. Delirium is characterized by acute and fluctuating disturbances in attention, awareness, and cognition. It is a common, costly, neurologic complication in patients, especially critically ill patients, patients with chronic metabolic disorders, or older adults. In older adults, delirium is among the most consequential complications of hospitalization. A 2025 national cohort of > 5.5 million older adults undergoing major non-cardiac surgery found that postoperative delirium was associated with markedly higher odds of death or major complications, and 30-day mortality. These contemporary data reinforce a shift in framing: delirium should be treated as acute brain failure and as a quality target for perioperative and critical care systems, not merely as a temporary behavioral syndrome. In addition to the acute negative impacts, delirium significantly escalates the risk of persistent cognitive decline, presaging the potential onset of neurodegenerative disorders. Despite substantial research into delirium epidemiology, prevention, and control, its management is complicated by the elusive nature of its pathophysiological mechanisms. Here, we propose a vascular etiology outlook for delirium, with emphasis on the neurovascular unit as a key interface in determining the onset of this complication and potentially jump-starting permanent brain dysfunction and ADRD.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70324"},"PeriodicalIF":7.4,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148992366","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":"Effect of choline supplementation in presymptomatic <i>APOE ε4</i> carriers: a pilot study.","authors":"William J Ray, Yaima L Lightfoot, Ronnie T Trinh, Janelle Fawver-Kahle, Susan Cooper, Li-Huei Tsai, Jonathan Bortz, Isis Trujillo-Gonzalez, Tianheng Zhang, Hulin Wu, Guadalupe J Ortiz Iv, Paul E Schulz","doi":"10.1002/trc2.70323","DOIUrl":"10.1002/trc2.70323","url":null,"abstract":"<p><strong>Introduction: </strong>With the advent of early detection biomarkers, it is possible to envision testing preventive strategies that delay the onset of Alzheimer's disease (AD). The ε4 allele of apolipoprotein E (<i>APOE</i> ε4) is the strongest genetic risk factor for late-onset AD; approximately 50% of all patients are <i>APOE</i> ε4-positive.¹ APOE is the major central nervous system (CNS) lipoprotein, and studies have linked APOE4-dependent deficits in lipid metabolism to disease-relevant processes.^2-6 Choline, the precursor for phosphatidylcholine (PC), normalizes <i>APOE</i> ε4-mediated lipid dysfunction in human model systems,⁶ and low dietary choline intake correlates with increased disease risk or progression in mouse models and humans.^7-17 We therefore tested whether biomarkers and omics provided early evidence of choline CNS target engagement in an at-risk population.</p><p><strong>Methods: </strong>In a 6-month open-label phase 1 study (NCT05880849), asymptomatic <i>APOE</i> ε4 carriers (<i>n =</i> 13; age 70 ± 5.5 years) received 2200 mg/day oral choline, with plasma and cerebrospinal fluid (CSF) collected before and after treatment.</p><p><strong>Results: </strong>Choline was well tolerated with no serious adverse events. Treatment increased plasma and CSF choline and betaine, indicating systemic and CNS exposure. Exploratory lipidomics identified changes in plasma PC species and, in CSF, increases in ceramides and cholesterol esters. Although this study was not powered to assess biomarker efficacy, CSF neurofilament light (NfL) was lower at the end of treatment, and CSF phosphoserine-181 tau (pTau181)/amyloid beta (Aβ)42 and plasma pTau217 showed directionally similar trends.</p><p><strong>Discussion: </strong>These findings support randomized placebo-controlled trials of choline in at-risk populations and illustrate how fluid biomarkers and omics can de-risk AD prevention studies.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70323"},"PeriodicalIF":7.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575335/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978782","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":"Effects of long-term daily supplementation with vitamin D3 and marine omega-3 fatty acids on change in ADRD biomarkers: A secondary analysis of a randomized clinical trial.","authors":"Chirag M Vyas, Beth L Ostaszewski, Amirah K Anderson, Nancy R Cook, Jae H Kang, David Mischoulon, Charles F Reynolds, Grace Chang, Jennifer R Gatchel, JoAnn E Manson, Dennis J Selkoe, Olivia I Okereke","doi":"10.1002/trc2.70312","DOIUrl":"10.1002/trc2.70312","url":null,"abstract":"<p><strong>Introduction: </strong>Vitamin D3 and omega-3 supplementation may slow outcomes related to Alzheimer's disease and related dementias (ADRD), with variation by sex or race, but their effects on ADRD-associated biomarkers are unknown.</p><p><strong>Methods: </strong>In this secondary analysis of a randomized clinical trial (RCT), we included 929 participants from the in-clinic subcohort of the VITamin D and OmegA-3 TriaL - a completed, placebo-controlled, 2×2 factorial trial testing vitamin D3 (2000 IU/day) and omega-3s (1 g/day) for cardiovascular disease and cancer prevention. Plasma ADRD biomarkers were assayed at baseline and 2- and/or 4-year follow-up. Study outcomes were longitudinal change in four ADRD biomarkers: N-terminal tau fragment (NT1), amyloid beta (Aβ)40:42, neurofilament-light (NfL), and glial fibrillary acidic protein (GFAP). Repeated-measures models were used, with sex and race were pre-specified effect modifiers.</p><p><strong>Results: </strong>The sample mean (SD) age was 65.0 (6.6) years; 49.2% were female, and 8.2% were Black adults. Neither vitamin D3 nor omega-3s, compared to placebo, significantly reduced ADRD biomarkers over 4 years. Pre-specified subgroup analyses suggested potential interactions by sex and race. Vitamin D3 supplementation resulted in a reduction in NT1 among males (-2.7%) but not females (<i>p</i>-interaction = 0.08). Among Black participants, vitamin D3 supplementation resulted in a 16.2% reduction in NfL levels [95% CI: -30.5% to 1.1%; <i>p</i>-interaction = 0.06], while omega-3 supplementation showed a 12.4% reduction in GFAP levels [95% CI: -21.5% to -2.2%; <i>p</i>-interaction = 0.049].</p><p><strong>Discussion: </strong>In this secondary analysis of a RCT, neither vitamin D3 nor omega-3s significantly reduced selected plasma ADRD biomarkers over 4 years. Potential differences were observed by sex and race in reductions of ADRD biomarkers in response to these supplements; however, these analyses were uncorrected for multiple hypothesis testing and should be interpreted cautiously as hypothesis-generating signals requiring replication.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifiers: c (VITAL); NCT01696435 (VITAL-DEP).</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70312"},"PeriodicalIF":7.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977997","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":"Alzheimer's disease heterogeneity and co-pathologies: Defining novel targets, biomarkers, modalities, and research methodologies.","authors":"Malú Gámez Tansey, Sasha Bozeat, Peter Ackerman, Alireza Atri, Christopher J Barnum, Patrik Brundin, Carlos Abreu de Carvalho, Adam S Fleisher, Ana Graf, Elizabeth Head, Geoffrey A Kerchner, Hartmuth C Kolb, Akihiko Koyama, Mariel Kozberg, Cheryl E G Leyns, Jorge J Llibre-Guerra, Niklas Mattsson-Carlgren, David McKissock, Melissa E Murray, Liana S Rosenthal, Carrie Rubel, Suzanne E Schindler, Julie A Schneider, Adam J Schwarz, Kirsten M Scott, Tamara Seredenina, Duygu Tosun, Rebecca L Wallings, Hong Wang, Donna M Wilcock, Maria Carrillo, Simin Mahinrad, Christopher J Weber","doi":"10.1002/trc2.70287","DOIUrl":"10.1002/trc2.70287","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a biologically heterogeneous condition with vascular, proteinopathic, metabolic, and immune processes jointly shaping its clinical expression, trajectory of progression, and response to therapeutic intervention. Common AD co-pathologies such as cerebral amyloid angiopathy, Lewy body pathology, α-synuclein, and transactive response DNA-binding protein of 43 kDa (TDP-43)/limbic-predominant age-related TDP-43 encephalopathy are also increasingly connected with cognitive decline and therapeutic response. Significant advances in biomarkers, including seed amplification assays, proteomic signatures, and emerging positron emission tomography tracers bolster the field's understanding of a biological staging model and discovery of previously unrecognized co-pathologies. The Fall 2025 Alzheimer's Association Research Roundtable (AARR) brought together academic, clinical, and industry leaders to discuss and explore the current advances in the heterogeneity and co-pathologies of AD, and their implications for diagnosis, clinical trial design, and precision treatment strategies. This paper presents key takeaways from the Fall 2025 AARR meeting.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70287"},"PeriodicalIF":7.4,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13573319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148972360","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":"Factors associated with phlebotomy failure in an Alzheimer's Disease Research Center cohort.","authors":"Mary Catherine Pawlus, Anna Gorham, Claudia Suarez-Rodriguez, Ilisa Risal, Maria A Galvez, Beata-Gabriela K Simpson, Johanna Celedon, Ayush Noori, Liliana Ramirez-Gomez, Sudeshna Das, Steven E Arnold, Pia Kivisäkk, Alberto Serrano-Pozo","doi":"10.1002/trc2.70322","DOIUrl":"10.1002/trc2.70322","url":null,"abstract":"<p><strong>Introduction: </strong>Venous blood collection through phlebotomy is critical for biomarker development and genetics research on Alzheimer's disease (AD) and related dementias. In this research setting, phlebotomy is often performed by clinical research coordinators (CRCs) rather than professional nurses or phlebotomists. Even though phlebotomy in older adults with cognitive impairment can be empirically challenging, data on the factors associated with phlebotomy failure in this special population are lacking. We addressed this question in the Massachusetts Alzheimer's Disease Research Center (MADRC) Longitudinal Cohort.</p><p><strong>Methods: </strong>We applied mixed-effects logistic regression with phlebotomy failure as the dependent variable; age at visit, sex, education, body mass index (BMI), under-represented minority (URM) status, and Clinical Dementia Rating (CDR) scale global score as fixed effects; and participant ID as a random effect to account for multiple visits per participant.</p><p><strong>Results: </strong>Full data were available for a total of 1365 visits from 659 individual participants (average 2.1 visits/participant, range 1-7). Greater BMI (odds ratio [95% confidence interval]: 1.10 [1.05-1.16], <i>P</i> < 0.001) and CDR global score (1.51 [1.13-2.03], <i>P</i> = 0.005), but not age, sex, or education, were independently associated with higher odds of phlebotomy failure. URM participants had twice the odds of a phlebotomy failure compared to non-Hispanic Whites, although this trend did not reach statistical significance due to insufficient power (2.07 [0.97-4.41], <i>P</i> = 0.059).</p><p><strong>Discussion: </strong>Greater BMI and CDR as well as URM status are independently associated with higher odds of phlebotomy failure. Potential strategies to maximize participation of these subpopulations in biomarker and genetics research are discussed.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70322"},"PeriodicalIF":7.4,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13569986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957198","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":"Hippocampal mediation in the lipid-Alzheimer's disease pathway: A high-dimensional mediation analysis stratified by <i>APOE</i> and sex.","authors":"Yunjia Cao, Yuwei Fan, Qingtao Meng, Jiajia Wang, Rui Chen","doi":"10.1002/trc2.70314","DOIUrl":"10.1002/trc2.70314","url":null,"abstract":"<p><strong>Introduction: </strong>Systemic lipid dysregulation is a modifiable risk factor for Alzheimer's disease (AD), yet the neuroanatomic pathways through which specific lipids influence AD progression remain poorly delineated. We investigated whether brain structure mediates the relationship between plasma lipids and AD progression, and whether this pathway is modified by apolipoprotein E (<i>APOE</i>) genotype and sex.</p><p><strong>Methods: </strong>This retrospective cohort study included 1019 non-demented participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Baseline plasma lipidomics (781 species) and subsequent T1 magnetic resonance imaging (MRI)-derived brain volumes and cortical thickness (198 features) were analyzed. Cox models identified lipids and brain regions associated with time-to-AD progression. High-dimensional mediation analysis (HIMA) was employed to identify significant mediators, followed by stratified analyses by <i>APOE</i> ε4 carrier status and gender and sensitivity analyses adjusting for cerebrospinal fluid (CSF) biomarkers and comorbidities.</p><p><strong>Results: </strong>Thirty-five lipids were associated with AD progression. High-dimensional mediation analysis across all 198 imaging features uniquely identified left hippocampus volume as the sole significant mediator for 14 specific lipids, including lysophosphatidylcholines and phosphoinositols. Stratified analyses revealed that this mediation pathway was predominantly driven by <i>APOE</i> ε4 carriers. Furthermore, gender differences were observed: female participants exhibited a more isolated indirect effect through the hippocampus for key lipids, whereas male participants often showed concurrent direct and indirect effects. Sensitivity analyses confirmed robustness after adjusting for CSF amyloid beta (Aβ)42/phosphorylated tau (p-tau) and revealed white matter hyperintensities as an additional mediator when accounting for comorbidities, supporting a dual neurodegenerative-vascular pathway.</p><p><strong>Discussion: </strong>The left hippocampus is a critical mediator linking specific plasma lipids to AD progression, with an additional vascular pathway via white matter hyperintensities emerging after comorbidity adjustment. This pathway is strongly modified by both <i>APOE</i> genotype and sex, highlighting the potential for precision-medicine interventions targeting lipid metabolism to preserve brain structure and slow disease progression, particularly in genetically susceptible individuals.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70314"},"PeriodicalIF":7.4,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13562603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957245","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":"Understanding dementia in Filipino Americans: risk factors, research gaps, and the role of community-based participatory research.","authors":"Rochelle-Jan Dionisio Reyes, Ariel Guevarra, Eugenie Mamuyac, Alexander Ivan B Posis, Laura María Calderón Cuevas, Luis Martinez Roman, John Matthew Suntay, Lolita Kintanar, Michelle Caunca, Boon Lead Tee, Charles Windon, Serggio Lanata, Ivan Bondoc, Eduardo Europa, Jessica de Leon","doi":"10.1002/trc2.70319","DOIUrl":"10.1002/trc2.70319","url":null,"abstract":"<p><p>Filipino Americans are the third-largest Asian American, Native Hawaiians, and Pacific Islander (AANHPI) group in the United States. Previous studies showed that they have high incident rates of Alzheimer's disease and related dementias (AD/ADRD) compared to other AANHPI groups. However, they are often aggregated into the \"Asian\" category in AD/ADRD research, masking distinct risk and mitigating factors. To date, no studies have directly explored AD/ADRD factors in Filipino Americans, a community that has unique characteristics from life experiences, immigration, historical and cultural context, and differential burden of genetic risk. In this perspective, we review known AD/ADRD risk and mitigating factors through the lens of the National Institute on Aging's Health Disparities Research Framework, spanning environmental, sociocultural, behavioral, and biological domains, and discuss their relevance to the Filipino American community. By identifying current knowledge gaps and contextualizing AD/ADRD risk and resilience through this framework, we aim to improve understanding of the complex, multifactorial pathways contributing to AD/ADRD outcomes across communities. Lastly, we discuss our experiences and strategies in the recruitment of Filipino Americans for AD/ADRD research studies, outlining challenges, successes, and future directions.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70319"},"PeriodicalIF":7.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921733","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":"Remote digital cognitive assessment in a trial-ready Alzheimer's disease cohort: A scalable approach for early intervention studies.","authors":"Andrew J Aschenbrenner, Hannah Wilks, Matthew Welhaf, Samhita Katteri, Sarah H Stout, Martin J Sliwinski, Tammie L S Benzinger, Brian Gordon, Yan Li, Richard J Perrin, Alan Renton, Guoqiao Wang, Chengjie Xiong, Christopher H van Dyck, Ricardo Allegri, William S Brooks, Jacob A Bechara, Suman Jayadev, Johannes Levin, Catherine J Mummery, Raquel Sanchez-Valle, David Aguillon, Eric M McDade, Randall J Bateman, Jason Hassenstab","doi":"10.1002/trc2.70311","DOIUrl":"10.1002/trc2.70311","url":null,"abstract":"<p><strong>Introduction: </strong>Early detection of cognitive decline in Alzheimer's disease (AD), particularly in preclinical stages, is critical for evaluating therapeutic interventions. Traditional cognitive assessments often require lengthy in-person visits, and may therefore limit scalability for younger, trial-ready populations for primary and secondary prevention studies. We evaluated the feasibility, reliability, and validity of high-frequency remote digital cognitive assessments in individuals with autosomal dominant AD (ADAD).</p><p><strong>Methods: </strong>One hundred twenty-three mutation carriers and non-carriers from the Dominantly Inherited Alzheimer Network Trials Unit from 20 international sites (Ages 19-66 years) completed remote assessments via personal smartphones, prompted four times daily for 7 days (≈ 3 minutes per session), and conventional in-clinic cognitive testing at baseline. Adherence, between-person reliability, test-retest reliability (intraclass correlation coefficients [ICCs]), construct validity (confirmatory factor analysis), and sensitivity to clinical disease progression were evaluated.</p><p><strong>Results: </strong>Remote measures demonstrated excellent reliability (ICCs > 0.90 after just 10 sessions) and strong construct validity, with tasks loading onto memory, attention, and executive function domains. A composite of the remote tests slightly outperformed a traditional composite at separating mutation carriers from non-carriers. Average adherence to the study protocol was 42%, lower that observed in previous studies of older adults.</p><p><strong>Discussion: </strong>High-frequency remote cognitive assessment is feasible, reliable, and valid in a relatively young international ADAD cohort. This approach offers substantial utility for clinical trials, including improved accessibility and enhanced reliability, supporting its integration into early-intervention studies.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"12 3","pages":"e70311"},"PeriodicalIF":7.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13554964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921713","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}