Alzheimer's & Dementia最新文献

{"title":"Process evaluation of a digital health intervention for dementia caregivers: Integrating active and passive measurements","authors":"Kang Shen,&nbsp;Y. Alicia Hong,&nbsp;Yixuan (Janice) Zhang,&nbsp;Hae-Ra Han,&nbsp;Jessica Lin,&nbsp;Kenneth Hepburn","doi":"10.1002/alz.70663","DOIUrl":"10.1002/alz.70663","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Research is limited on process evaluation of digital interventions for underserved dementia caregivers. This study reports the design and results from the process evaluation of Wellness Enhancement for Caregivers (WECARE) 2.0, a culturally tailored digital intervention for Chinese American dementia caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>During the 7-week trial of WECARE 2.0, active measurement via weekly surveys and passive measurement via backend tracking were used to assess user engagement, collect timely feedback, and understand intervention mechanisms. These data were integrated to provide complementary insights.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The intervention achieved a 94% follow-up rate and 82% program completion rate. Participants valued the culturally tailored multimedia content, practical resources, and asynchronous delivery, while also providing suggestions for improvement. Key mechanisms driving the intervention's success included improved caregiving skills, stress reduction, and increased social support.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>The study underscores the importance of process evaluation using mixed methods to ensure the usability and effectiveness of digital interventions for underserved dementia caregivers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CLINICALTRIALS ID</h3>\u0000 \u0000 <p>NCT05992467</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Process evaluation was conducted in a digital intervention for dementia caregivers.</li>\u0000 \u0000 <li>Active and passive measurement were integrated in the process evaluation.</li>\u0000 \u0000 <li>Wellness Enhancement for Caregivers (WECARE) demonstrated high retention (94%) and program completion rates (82%).</li>\u0000 \u0000 <li>Data on user experiences, feedback, and intervention mechanisms were presented.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438464/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Performance of 123I-ioflupane SPECT striatal binding in dementia with Lewy bodies","authors":"Emily F. Maly,&nbsp;Frank P. DiFilippo,&nbsp;Brittany Lapin,&nbsp;Yadi Li,&nbsp;Sarah Berman,&nbsp;Andrea C. Bozoki,&nbsp;Jori E. Fleisher,&nbsp;James E. Galvin,&nbsp;David J. Irwin,&nbsp;Carol F. Lippa,&nbsp;Irene Litvan,&nbsp;Debby W. Tsuang,&nbsp;Cyrus P. Zabetian,&nbsp;Angela S. Taylor,&nbsp;Lynn M. Bekris,&nbsp;Oscar L. Lopez,&nbsp;Douglas Galasko,&nbsp;James B. Leverenz","doi":"10.1002/alz.70596","DOIUrl":"10.1002/alz.70596","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>We aimed to determine whether ¹²³I-ioflupane single-photon emission computed tomography (SPECT) striatal binding ratio (SBR) correlated with parkinsonian motor symptoms in dementia with Lewy bodies (DLB) and if SBR predicts worsening of parkinsonism over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>A retrospective cohort study of the U.S. Dementia with Lewy Bodies Consortium dataset including individuals with DLB with baseline ¹²³I-ioflupane SPECT analyzed with DaTQUANT and baseline and 24-month Movement Disorder Society Unified Parkinson's Disease Rating Scale–Part III (MDS-UPDRS-III). A subset had cerebrospinal fluid α-synuclein seed amplification assay (SAA) evaluation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Baseline mean SBRs were significant predictors of baseline and 24-month MDS-UPDRS-III scores, although they did not predict meaningful worsening over time. SAA positivity was associated with lower SBRs; <i>Z</i> score cut-off values are provided.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>In suspected DLB, ¹²³I-ioflupane SPECT, at diagnosis, could be used to confirm underlying dopamine deficiency; it does not predict meaningful worsening of motor parkinsonism. More severe dopamine deficiency increases confidence in presence of synucleinopathy.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>¹²³I-ioflupane single-photon emission computed tomography (SPECT) can confirm underlying dopamine deficiency.</li>\u0000 \u0000 <li>Striatal binding ratio (SBR) <i>Z</i> scores predicted 24-month Unified Parkinson's Disease Rating Scale–Part III (UPDRS-III) scores.</li>\u0000 \u0000 <li>SBR <i>Z</i> scores are not predictive of subsequent meaningful worsening of parkinsonism.</li>\u0000 \u0000 <li>More severe dopamine dysfunction on SPECT is associated with presence of seed amplification assay (SAA).</li>\u0000 \u0000 <li>SBR <i>Z</i> score cut-offs that indicate cerebrospinal fluid SAA positivity are provided.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12438451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donanemab in preclinical Alzheimer's disease: Screening and baseline data from TRAILBLAZER-ALZ 3","authors":"Roy Yaari,&nbsp;Karen C. Holdridge,&nbsp;Melissa Williamson,&nbsp;Alette M. Wessels,&nbsp;Sergey Shcherbinin,&nbsp;Vikas Kotari,&nbsp;Eric M. Reiman,&nbsp;Pierre N. Tariot,&nbsp;Robert Alexander,&nbsp;Jessica B. Langbaum,&nbsp;John R. Sims","doi":"10.1002/alz.70662","DOIUrl":"10.1002/alz.70662","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>TRAILBLAZER-ALZ 3 is investigating donanemab in preclinical Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>This double-blind, placebo-controlled trial used a plasma phosphorylated tau-217 (p-tau217) assay to detect AD pathology for eligibility and a decentralized design to enhance screening and enrollment. After nine monthly infusions, clinical assessments continue every 6 months with a time-to-event primary outcome. A sub-study will evaluate longitudinal changes in amyloid and tau positron emission tomography (PET).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Participants 55–80 years of age were screened (<i>N</i> = 63,124). Plasma p-tau217-eligible participants were enrolled (<i>N</i> = 2196), with Clinical Dementia Rating (CDR) scale-Global score (CDR-GS) of 0 (<i>n</i> = 1202) and 0.5 (<i>n</i> = 664). Plasma p-tau217 eligibility increased with age, differing across races and ethnicities. Mean baseline amyloid levels were 63.2 (CDR-GS: 0) and 70.7 Centiloids (CDR-GS: 0.5). Elevated global tau signal (standardized uptake value ratio ≥1.10) was observed in 15.1% and 26.3% of CDR-GS 0 and 0.5 subgroups, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Utilizing a unique decentralized design, the trial showed baseline data consistent with preclinical AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> TRIAL REGISTRATION</h3>\u0000 \u0000 <p>ClinicalTrials.gov identifier: NCT05026866, TRAILBLAZER-ALZ 3</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>TRAILBLAZER-ALZ 3 screened 63,124 participants in the United States and Japan</li>\u0000 \u0000 <li>Plasma phosphorylated tau-217 (p-tau217) was used to determine Alzheimer's disease pathology for eligibility</li>\u0000 \u0000 <li>A decentralized model was used, including remote raters for clinical testing</li>\u0000 \u0000 <li>Randomized participants had Clinical Dementia Rating scale–Global scores of 0 and 0.5</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145068848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traumatic brain injury, changes in plasma amyloid, tau, and neurodegenerative biomarkers, and dementia risk","authors":"Alexa E. Walter,&nbsp;James R. Pike,&nbsp;Josef Coresh,&nbsp;Ramon Diaz-Arrastia,&nbsp;David Menon,&nbsp;Rebecca F. Gottesman,&nbsp;Priya Palta,&nbsp;Andrea L. C. Schneider","doi":"10.1002/alz.70611","DOIUrl":"10.1002/alz.70611","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Long-term trajectories of plasma biomarkers in relation to incident traumatic brain injury (TBI) and whether TBI modifies associations of biomarkers with dementia risk are unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>One thousand fifty Atherosclerosis Risk in Communities (ARIC) study participants without prior TBI had amyloid beta (Aβ₄₂/Aβ₄₀), phosphorylated-tau181 (pTau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) measured from plasma collected in 1993 to 1995, 2011 to 2013, and 2016 to 2019. Linear mixed-effects models estimated biomarker trajectories associated with TBI and Cox proportional hazards models determined if TBI modified associations of biomarkers with incident dementia through December 31, 2020.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>After the median time of incident TBI, Aβ₄₂/Aβ₄₀ levels remained lower for 9.3 years, and pTau181, NfL, and GFAP remained elevated for 8.5, &gt;13.8, and 12.7 years, respectively. There was evidence of additive interaction by TBI in associations of log₂NfL with incident dementia (<i>p</i> = 0.024).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>TBI alters trajectories of plasma biomarkers of neurodegeneration for approximately a decade after the injury and modifies associations of NfL with dementia risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Our findings provide evidence that TBI fundamentally alters trajectories of plasma biomarkers of AD-related pathology, neuronal degeneration, and astrogliosis for approximately a decade after the injury.</li>\u0000 \u0000 <li>Further, our findings also suggest that an incident TBI event adds to and interacts with ongoing neurodegenerative processes to increase the risk of later life dementia.</li>\u0000 \u0000 <li>These results suggest that the pathologic processes underlying post-TBI dementia are heterogeneous, that individuals with preclinical changes in neurodegenerative biomarkers may be more susceptible to TBI (i.e., that associations are bidirectional), or a combination thereof.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70611","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Effects of single and combined immunotherapy approach targeting amyloid β protein and α-synuclein in a dementia with Lewy bodies-like model”","authors":"","doi":"10.1002/alz.70557","DOIUrl":"10.1002/alz.70557","url":null,"abstract":"<p>Mandler M, Rockenstein E, Overk C, et al. Effects of single and combined immunotherapy approach targeting amyloid β protein and α-synuclein in a dementia with Lewy bodies-like model. <i>Alzheimers Dement</i>. 2025;15(9):1133-1148. doi:10.1016/j.jalz.2019.02.002</p><p>The authors regret that an error occurred during the assembly of Figure 4G, where the incorrect panels were used to represent the APP/α-syn tg AD02 and the AD02/PD-AFF1 conditions in the S. Nigra, and in Figure 5D, where the incorrect panel was used to represent the APP/α-syn tg AD02/PD-AFF1 in the hippocampus. The corrected figures are provided in the attachment below.  </p><p>We apologize for this error.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70557","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1RA comparative effectiveness against dementia onset relative to other antidiabetic medications in a large, multi-site cohort of patients with type 2 diabetes","authors":"Nerissa Nance,&nbsp;Paola Gilsanz,&nbsp;Andrew J. Karter,&nbsp;Holly Finertie,&nbsp;Julie A. Schmittdiel,&nbsp;JaeJin An,&nbsp;Alyce S. Adams,&nbsp;Caryn Oshiro,&nbsp;Andrea E. Cassidy-Bushrow,&nbsp;Sarah Krahe-Dombrowski,&nbsp;Maher Yassin,&nbsp;Sharon Lin,&nbsp;Keanu Izadian,&nbsp;Patrick J. O'Connor,&nbsp;Romain Neugebauer","doi":"10.1002/alz.70621","DOIUrl":"10.1002/alz.70621","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>To address gaps in current research, this study aims to compare the impact of exposure to glucagon-like peptide-1 receptor agonists (GLP-1RA) versus sodium-glucose cotransporter 2 inhibitors (SGLT2i), dipeptidyl peptidase 4 inhibitors (DPP4i), and sulfonylureas (SU) on reducing the risk of dementia, using a rigorous targeted learning causal inference approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using clinical and claims data from four diverse US health-care systems, we emulated three two-arm trials contrasting sustained treatment with GLP-1RA versus SGLT2i, DPP4i, and SU on dementia diagnosis. We included diabetes patients aged ≥ 60 years who initiated medication between 2014 and 2022. We estimated cumulative risk differences at 2.5 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In Cohort 1, there was no evidence of differential dementia risk between sustained exposure to GLP1-RA versus SGLT2i (adjusted risk difference [aRD] −0.001, 95% confidence interval [CI] −0.004, 0.001). In Cohorts 2 and 3, GLP-1RA was associated with reduced risk of dementia diagnosis compared to DPP4i and SU, respectively (aRD −0.013, 95% CI −0.017, −0.009; aRD −0.016, 95% CI −0.018, −0.015).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Rigorous causal inference analysis suggests that sustained exposure to GLP-1RA may modestly reduce risk of dementia, compared to DPP4i or SU exposure—but not compared to SGLT2i.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>We researched the comparative effects of diabetes medications on dementia.</li>\u0000 \u0000 <li>We studied a large, diverse observational cohort of patients with diabetes in the United States.</li>\u0000 \u0000 <li>Glucagon-like peptide-1 receptor agonists (GLP-1RAs) may modestly reduce risk of dementia compared to dipeptidyl peptidase 4 inhibitor or sulfonylurea exposure.</li>\u0000 \u0000 <li>GLP-1RAs do not show evidence of dementia risk reduction compared to sodium-glucose cotransporter 2 inhibitors.</li>\u0000 \u0000 <li>Physicians may consider this when making prescription decisions with patients.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70621","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal changes in white matter hyperintensity volume accelerate across the Alzheimer's continuum in adults with Down syndrome","authors":"Patrick Lao,&nbsp;Natalie Edwards,&nbsp;Lisi Flores-Aguilar,&nbsp;Mohamad J. Alshikho,&nbsp;Anna Smith,&nbsp;Rachel LeMay,&nbsp;Juyoung Hahm,&nbsp;Batool Rizvi,&nbsp;Dana Tudorascu,&nbsp;H. Diana Rosas,&nbsp;Michael Yassa,&nbsp;Bradley Christian,&nbsp;Mark Mapstone,&nbsp;Benjamin Handen,&nbsp;Alzheimer's Biomarkers Consortium–Down Syndrome (ABC-DS) Investigators,&nbsp;Jose Gutierrez,&nbsp;Donna Wilcock,&nbsp;Elizabeth Head,&nbsp;Adam M. Brickman","doi":"10.1002/alz.70679","DOIUrl":"10.1002/alz.70679","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Cerebrovascular disease is elevated across the Alzheimer's disease (AD) continuum in adults with Down syndrome (DS), but regional change within individuals is unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants from the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study (<i>n</i> = 187) had magnetic resonance imaging (MRI) scans quantified for white matter hyperintensity (WMH) volume. Annualized WMH change was assessed across cognitive diagnostic groups defined by progression or stability between two visits (78% remained cognitively stable (CS), 6% progressed from CS to mild cognitive impairment [MCI]-DS, 5% remained MCI-DS, 6% progressed from MCI-DS to AD, 4% remained AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Compared to those who remained CS, WMH changes, particularly in posterior regions, over time were faster in advanced diagnostic groups (i.e., MCI-DS to AD, AD at both timepoints). Monotonic increase across progressive diagnostic groups suggest an acceleration in WMH over time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>Posterior WMH accelerates with AD progression in adults with DS beginning at the progression from MCI-DS to AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>White matter hyperintensity (WMH) volume increased and decreased over time in adults with Down syndrome.</li>\u0000 \u0000 <li>WMH decreased over time in the cognitively stable group.</li>\u0000 \u0000 <li>WMH increased over time in advanced Alzheimer's disease diagnostic groups.</li>\u0000 \u0000 <li>Change in posterior WMH accelerated across progressive Alzheimer's disease groups.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures","authors":"Moonil Kang,&nbsp;Ting Fang Alvin Ang,&nbsp;Sherral A. Devine,&nbsp;Richard Sherva,&nbsp;Shubhabrata Mukherjee,&nbsp;Emily H. Trittschuh,&nbsp;Phoebe Scollard,&nbsp;Michael Lee,&nbsp;Seo-Eun Choi,&nbsp;Brandon Klinedinst,&nbsp;Connie Nakano,&nbsp;Logan C. Dumitrescu,&nbsp;Timothy J. Hohman,&nbsp;Michael L. Cuccaro,&nbsp;Andrew J. Saykin,&nbsp;Walter A. Kukull,&nbsp;David A. Bennett,&nbsp;Li-San Wang,&nbsp;Richard P. Mayeux,&nbsp;Jonathan L. Haines,&nbsp;Margaret A. Pericak-Vance,&nbsp;Gerard D. Schellenberg,&nbsp;Paul K. Crane,&nbsp;Rhoda Au,&nbsp;Kathryn L. Lunetta,&nbsp;Jesse Mez,&nbsp;Lindsay A. Farrer","doi":"10.1002/alz.70681","DOIUrl":"10.1002/alz.70681","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Identifying pleiotropy for blood pressure (BP) and cognitive performance measures may indicate mechanistic links between hypertension and Alzheimer's disease (AD).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We performed a pleiotropy genome-wide association study (GWAS) for paired measures of systolic, diastolic, pulse, and mean arterial pressure with memory, executive function, and language scores using 116,075 exam data from 25,726 participants in clinic-based and prospective cohorts. Significant findings were evaluated by Bayesian colocalization and differential gene expression in brain tissue from pathologically confirmed AD cases with and without clinical symptoms.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Genome-wide significant pleiotropy for BP and cognitive performance with <i>JPH2</i>, <i>GATA3</i>, <i>PAX2</i>, <i>LOC105371656</i>, and <i>SUFU</i> in the total sample; <i>RTN4</i>, <i>ULK2</i>, <i>SORBS2</i>, and <i>LOC100128993</i> in prospective cohorts; and <i>ADAMTS3</i> and <i>LINC02946</i> in clinic-based cohorts. Six pleiotropic loci influence cognition directly, and six genes were differentially expressed between pathologically confirmed AD cases with and without antemortem cognitive impairment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Our results provide insight into mechanisms underlying hypertension and AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Genome-wide significant pleiotropy in blood pressure (BP) and cognitive performance measures were identified with 11 novel loci: <i>JPH2</i>, <i>GATA3</i>, <i>PAX2</i>, <i>LOC105371656</i>, <i>SUFU</i> in the total sample; <i>RTN4</i>, <i>ULK2</i>, <i>SORBS2</i>, <i>LOC100128993</i> in prospective cohorts; and <i>ADAMTS3</i>, <i>LINC02946</i> in clinic-based cohorts.</li>\u0000 \u0000 <li><i>SUFU</i>, <i>RTN4</i>, <i>SORBS2</i>, <i>ADAMTS3</i>, and <i>GATA3</i> affected cognition directly rather than through BP.</li>\u0000 \u0000 <li><i>ACTR1A</i>, <i>HIF1AN</i>, <i>ADAMTS3</i>, <i>RTN4</i>, <i>SORBS2</i>, and <i>SUFU</i> at pleiotropic loci were differentially expressed among controls and pathologically confirmed AD cases with and without clinical symptoms.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70681","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rates of clinical progression according to biological Alzheimer's disease stages","authors":"Lydia Trudel,&nbsp;Joseph Therriault,&nbsp;Arthur C. Macedo,&nbsp;Stijn Servaes,&nbsp;Seyyed Ali Hosseini,&nbsp;Gleb Bezgin,&nbsp;Nesrine Rahmouni,&nbsp;Tevy Chan,&nbsp;Jaime Fernandez-Arias,&nbsp;Étienne Aumont,&nbsp;Yi-Ting Wang,&nbsp;Yansheng Zheng,&nbsp;Brandon Hall,&nbsp;Robert Hopewell,&nbsp;Chris Hung-Hsin Hsiao,&nbsp;Arthur W. Toga,&nbsp;Meredith N. Braskie,&nbsp;Karin L. Meeker,&nbsp;Jean-Paul Soucy,&nbsp;Serge Gauthier,&nbsp;Paolo Vitali,&nbsp;Sid E. O'Bryant,&nbsp;Tharick A. Pascoal,&nbsp;Pedro Rosa-Neto","doi":"10.1002/alz.70624","DOIUrl":"10.1002/alz.70624","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; INTRODUCTION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Predicting the rate of cognitive decline and the likelihood of progression to dementia remains a critical unmet need in clinical settings.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; METHODS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We assessed progression to mild cognitive impairment (MCI) and all-cause dementia in 492 individuals from the TRIAD, ADNI, and HABS-HD cohorts followed for an average of 2.49 years. Amyloid-positive participants were staged according to the Alzheimer's Association biological staging framework (A+T&lt;sub&gt;2&lt;/sub&gt;-/A+T&lt;sub&gt;2MTL&lt;/sub&gt;+/A+T&lt;sub&gt;2MOD&lt;/sub&gt;+/A+T&lt;sub&gt;2HIGH&lt;/sub&gt;+).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; RESULTS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cognitively unimpaired (CU) individuals in the A+T&lt;sub&gt;2MTL&lt;/sub&gt;+, A+T&lt;sub&gt;2MOD&lt;/sub&gt;+, and A+T&lt;sub&gt;2HIGH&lt;/sub&gt;+ biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to non-AD CU individuals. In individuals with MCI, advanced tau stage was associated with an 83% likelihood of developing dementia over 4 years. Biological AD staging demonstrated superior accuracy in predicting clinical progression compared to amyloid-PET (positron emission tomography) status, tau-PET status, and demographic information. All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than non-AD controls, with the A+T&lt;sub&gt;2HIGH&lt;/sub&gt;+ stage showing the steepest rate of decline (&lt;i&gt;p&lt;/i&gt; &lt; 0.001).&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; DISCUSSION&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our results highlight the prognostic value of biological AD staging.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Highlights&lt;/h3&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;ul&gt;\u0000 \u0000 &lt;li&gt;Cognitively unimpaired (CU) individuals in all tau-PET (positron emission tomography)–positive biological Alzheimer's disease (AD) stages were at significantly higher risk of clinical progression compared to individuals without AD.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;In individuals with mild cognitive impairment (MCI), only the A+T&lt;sub&gt;2HIGH&lt;/sub&gt;+ stage reached a point where 50% of individuals had progressed to all-cause dementia, after 2.36 years.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Biological AD staging demonstrated superior accuracy in predicting clinical progression to dementia compared to other PET biomarkers and demographic information.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;All tau-PET-positive individuals showed a significantly faster rate of cognitive decline than in","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70624","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement equivalence of the UDS version 2.0 and 3.0 neuropsychological batteries","authors":"Leslie S. Gaynor,&nbsp;Francesca V. Lopez,&nbsp;Carol A. Van Hulle,&nbsp;Clara Li,&nbsp;Sarinnapha M. Vasunilashorn,&nbsp;Shea J. Andrews,&nbsp;Stephanie M. Simone,&nbsp;Dan M. Mungas","doi":"10.1002/alz.70720","DOIUrl":"10.1002/alz.70720","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The present study examined the dimensional structure of the neuropsychological test batteries from the National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) versions 2.0 and 3.0 and measurement equivalence across UDS versions and race/ethnicity groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>There were 49,895 participants included in the present study. The best-fitting model was developed and tested in separate samples. Multiple group confirmatory factor analysis (CFA) evaluated measurement equivalence across UDS versions and race/ethnicity groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Results identified a best-fitting four-factor model with residual structure. Multiple group CFA supported partial scalar invariance by UDS version and race/ethnicity group. Regarding race/ethnicity groups, the Language and Attention domains had more non-invariant intercepts, which most affected the White group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>A four-factor model effectively summarizes the UDS neuropsychological test batteries across UDS versions and race/ethnicity groups. Crucial differences in measurement parameters must be accounted for in studies using these neuropsychological tests as outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A four-factor model summarizes cognition across Uniform Data Set (UDS) versions and race/ethnicity groups.</li>\u0000 \u0000 <li>Measurement invariance exists across race/ethnicity groups.</li>\u0000 \u0000 <li>Model fit differs between cognitively impaired and unimpaired samples.</li>\u0000 \u0000 <li>Accounting for differences in measurement parameters across groups is essential.</li>\u0000 \u0000 <li>Tailored normative data are crucial for certain UDS tests, including category fluency.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}