Alzheimer's & Dementia最新文献

{"title":"Neuropsychiatric symptom subtypes and dementia-associated neuropathologic change","authors":"Brenna A. Cholerton,&nbsp;Gary W. Beecham,&nbsp;Christiane Reitz,&nbsp;Alyssa N. De Vito,&nbsp;Michael Cuccaro,&nbsp;Walter A. Kukull,&nbsp;Thomas J. Montine,&nbsp;Edward D. Huey","doi":"10.1002/alz.70622","DOIUrl":"10.1002/alz.70622","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Neuropsychiatric symptoms (NPS) are prevalent in clinically diagnosed Alzheimer's disease (AD), yet their etiology remains unclear. We assessed associations between NPS and neuropathologic features in dementia patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Logistic regression analyses estimated associations between neuropathologic lesions and retroactively assigned NPS phenotypes (early and late psychosis [EPS, LPS], early and late affective symptoms [EAS, LAS]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>EPS was associated with Lewy body (odds ratio [OR] = 2.4, <i>p</i> &lt; 0.0001) and white matter (OR = 1.7, <i>p</i> &lt; 0.0001) pathology. LPS was associated with moderate/severe neurofibrillary tangles (OR = 2.8, <i>p</i> &lt; 0.0001), moderate/frequent neuritic plaques (OR = 2.3, <i>p</i> &lt; 0.0001), Lewy bodies (OR = 1.9, <i>p</i> &lt; 0.0001), and cerebral amyloid angiopathy (OR = 1.6, <i>p</i> &lt; 0.0001). EAS was associated with white matter injury (OR = 3.4, <i>p</i> &lt; 0.0001); EAS and LAS were associated with moderate/severe neurofibrillary tangles (ORs = 1.7, 1.9, <i>p</i> &lt; 0.005). Risk for EPS, LPS, and EAS increased with total neuropathologic burden.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>NPS subtypes are differentially associated with AD/non-AD neuropathologic features, suggesting that efficiency of interventional targets may depend upon timing and type of NPS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Timing/nature of neuropsychiatric symptoms (NPS) had distinct associations with brain autopsy findings in the National Alzheimer's Coordinating Center.</li>\u0000 \u0000 <li>Increased odds for psychosis symptoms was associated with both Alzheimer's disease neuropathologic change (ADNC) and Lewy body dementia (LBD).</li>\u0000 \u0000 <li>Late psychosis symptoms (PS) was most strongly associated with ADNC, early PS most strongly with LBD.</li>\u0000 \u0000 <li>Early PS and affective symptoms were both associated with white matter disease.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70622","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127325","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":"Neuroimaging markers of dementia across race/ethnicity and sex/gender using an intersectional approach within the HABS-HD cohort","authors":"Michelle R. Caunca,&nbsp;Amber Bahorik,&nbsp;Xiaqing Jiang,&nbsp;Meredith N. Braskie,&nbsp;Sid O'Bryant,&nbsp;Kristine Yaffe","doi":"10.1002/alz.70733","DOIUrl":"10.1002/alz.70733","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Racial/ethnic and sex/gender differences in neuroimaging markers of dementia have been previously explored, but rarely with an intersectional approach.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using data from the Health and Aging Brain Study–Health Disparities cohort, we examined neuroimaging markers of dementia using both interaction between race/ethnicity and sex/gender and effect modification of race/ethnicity by sex/gender.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We analyzed data from 3433 dementia-free participants with either magnetic resonance imaging or positron emission tomography (PET) data at baseline (mean [standard deviation] age: 65 [9] years, 36% non-Hispanic White [NHW], 27% Black, 37% Hispanic, and 63% women). Compared to NHW, Black men had lower global amyloid PET standardized uptake value ratio (SUVR; β [95% confidence interval]: –0.32 [–0.53, –0.11]), and Hispanic (0.65 [0.39, 0.91]) and Black women had greater medial temporal lobe tau SUVR (0.49 [0.30, 0.69]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>We observed that the distribution of neuroimaging markers of dementia differed across racial/ethnicity groups by sex/gender. An intersectional approach can aid in tailoring research and clinical efforts in preventing and treating dementia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Hispanic and Black women had greater medial temporal lobe tau deposition, compared to their non-Hispanic White counterparts.</li>\u0000 \u0000 <li>Black men had lower global amyloid deposition compared to non-Hispanic White men.</li>\u0000 \u0000 <li>Black men and women had higher burden of cerebral small vessel disease compared to their non-Hispanic White counterparts, with stronger associations in Black men.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70733","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127349","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":"Multimodal prognostic modeling of individual cognitive trajectories to enhance trial efficiency in preclinical Alzheimer's disease","authors":"Viswanath Devanarayan,&nbsp;Michael C. Donohue,&nbsp;Reisa A. Sperling,&nbsp;Keith A. Johnson,&nbsp;Yuanqing Ye,&nbsp;Arnaud Charil,&nbsp;Thomas Doherty,&nbsp;Lu Tian,&nbsp;Rema Raman,&nbsp;Paul S. Aisen,&nbsp;Lynn D. Kramer,&nbsp;Michael C. Irizarry,&nbsp;Shobha Dhadda","doi":"10.1002/alz.70702","DOIUrl":"10.1002/alz.70702","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;Cognitive decline in asymptomatic preclinical Alzheimer's disease (AD) is slow and variable, limiting detection of treatment effects. This study developed models to forecast trajectories and improve trial efficiency.&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;Models were trained on longitudinal Preclinical Alzheimer's Cognitive Composite (PACC) data up to 240 weeks from the Phase III A4 study of solanezumab. Baseline inputs included demographics, apolipoprotein E (&lt;i&gt;APOE&lt;/i&gt;) ε4, clinical scores, amyloid positron emission tomography (PET), plasma pTau217, magnetic resonance imaging (MRI), and tau PET (sub-study). Stochastic gradient boosting was used, with evaluation via cross-validation and trial simulations.&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;The best model without tau PET used pTau217, clinical, and MRI data (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.32; area under the receiver operating characteristic curve (AUROC) for classifying a 0.5-point PACC decline = 78.6%). Replacing MRI with tau PET improved performance (&lt;i&gt;R&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.42; AUROC = 83.1%). Predicted trajectories as a prognostic covariate reduced sample sizes by 35% and increased power from 80% to 94.7%.&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;Prognostic models can predict decline in preclinical AD and improve trial efficiency.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; CLINICALTRIALS.GOV IDENTIFIERS&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;NCT02008357 (Clinical Trial of Solanezumab for Older Individuals Who May be at Risk for Memory Loss (A4))&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;Models forecast 4.5-year cognitive decline in amyloid-positive preclinical Alzheimer's disease (AD).&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Plasma pTau217 and tau positron emission tomography (PET) standardized uptake value ratios (SUVRs) in early-accumulating regions are key predictors.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Tau PET improves prediction beyond plasma, magnetic resonance imaging (MRI), and clinical measures.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Forecasted decline as a prognostic covariate improves power and cuts sample size in trial simulations.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Alternative models underperform yet retain practical utility wh","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70702","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127331","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":"PINK1 deficiency permits the development of Lewy body dementia with coexisting Aβ pathology","authors":"Tong-Yao Gao,&nbsp;Xu-Zheng Wang,&nbsp;Yu-Han Xie,&nbsp;Tong Wang,&nbsp;Yun-Bi Lu,&nbsp;Lu-Long Huang,&nbsp;Cong Chen,&nbsp;Ming Zhang,&nbsp;Xin Ma,&nbsp;Ya-Ling Chen,&nbsp;Fu-Xiang Liang,&nbsp;Zhi-Ling Lou,&nbsp;Jin-Sheng Li,&nbsp;Yi-Fan Yu,&nbsp;Jian-Bin Wu,&nbsp;Xiao-Ru Ma,&nbsp;Hua-Li Wang,&nbsp;Chun Tang,&nbsp;Wei-Ping Zhang","doi":"10.1002/alz.70730","DOIUrl":"10.1002/alz.70730","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Dementia with Lewy bodies (DLB), a prevalent neurodegenerative dementia, involves α-synuclein (α-syn) aggregates and frequent amyloid beta (Aβ) co-pathology, but mechanistic drivers remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We crossed <i>pink1</i> knockout with <i>APP/PS1</i> mice, and assessed behavioral and pathological phenotypes of the resulting animals. We also performed biochemical and biophysical characterizations of PTEN-induced kinase 1 (PINK1) phosphorylation of α-syn.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>DLB brains show PINK1 deficiency alongside α-syn and Aβ co-pathology. Mirroring human DLB patients, <i>APP/PS1::pink1-/-</i> mice spontaneously develop Lewy pathology at endogenous α-syn levels, affecting both central and peripheral nervous systems with heterogeneous phenotypes. Mechanistically, PINK1 phosphorylates α-syn at Thr44, suppressing Aβ-induced α-syn aggregation. Moreover, pT44-α-syn levels are correlated with PINK1 expression and activity in human brains.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>PINK1 deficiency synergizes with Aβ to promote Lewy pathology via loss of protective α-syn phosphorylation. The <i>APP/PS1::pink1-/-</i> model recapitulates key DLB features without α-syn overexpression, offering a valuable tool for future mechanistic and therapeutic studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>PTEN-induced kinase 1 (PINK1) deficiency, either through reduced expression or impaired activity, is found in human dementia with Lewy bodies (DLB) patients with amyloid beta (Aβ) co-pathology.</li>\u0000 \u0000 <li>PINK1 specifically phosphorylates α-synuclein at Thr44, inhibiting Aβ-induced aggregation and preventing the development of Lewy pathology.</li>\u0000 \u0000 <li>The <i>APP/PS1::pink1-/-</i> mouse model recapitulates key features of human DLB, exhibiting widespread Lewy pathology and heterogeneous phenotypes.</li>\u0000 \u0000 <li>PINK1 alterations emerge as a novel genetic risk factor for DLB, opening new avenues for diagnosis and therapeutic intervention.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70730","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127324","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":"Sociodemographic traits as early indicators of AD, FTD, and VaD up to 10 years before diagnosis","authors":"Ave Kivisild,&nbsp;Iina Rinnankoski,&nbsp;Mikko Aaltonen,&nbsp;Kalle Aho,&nbsp;Sami Heikkinen,&nbsp;Adolfina Lehtonen,&nbsp;Laura Leppänen,&nbsp;Helmi Soppela,&nbsp;Laura Tervonen,&nbsp;Kaijus Ervasti,&nbsp;Päivi Hartikainen,&nbsp;Annakaisa Haapasalo,&nbsp;Kasper Katisko,&nbsp;Johanna Krüger,&nbsp;Eino Solje","doi":"10.1002/alz.70616","DOIUrl":"10.1002/alz.70616","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;We aimed to investigate early differences in sociodemographic factors before the onset of Alzheimer's disease (AD), frontotemporal dementia (FTD), vascular dementia (VaD), and mixed dementia (AD + VaD).&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;Lifetime sociodemographic factors were collected from Statistics Finland for 1238 AD, 274 FTD, 343 VaD, and 402 AD + VaD patients with a diagnosis and visit at Kuopio and Oulu University Hospitals between January 2010 and December 2021. Comparisons were performed between dementia groups and matched controls.&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;All patient groups showed decreased employment status compared to controls already 10 years prior to diagnosis. In particular, individuals with early-onset FTD (EOFTD; 66.9% vs. 77.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) and early-onset VaD (EOVaD; 49.0% vs. 76.5%, &lt;i&gt;p&lt;/i&gt; &lt; 0.001) had significantly lower employment rates than controls. Similarly, 10 years prior to diagnosis the proportion of married individuals was lower in the VaD (60.1% vs. 65.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and EOVaD (50.0% vs. 61.6%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) groups versus controls, while single status was more common in early-onset AD (EOAD; 23.2% vs. 17.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.01) versus controls. Patients with VaD and AD + VaD had lower levels of education than controls: basic education only in 51.9% of VaD (vs. 45.0%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05) and 65.7% of AD + VaD (vs. 60.2%, &lt;i&gt;p&lt;/i&gt; &lt; 0.05).&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 findings may aid in the early recognition or potential risk factor evaluation for different types of dementia. Screening cognitive symptoms in individuals with unexplained long-term unemployment may help detect prodromal dementia.&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;Employment rates were already reduced 10 years before the diagnosis of Alzheimer's disease, frontotemporal dementia, and vascular dementia.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The association between education level and dementia risk appears to be subtype specific.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Lower employment may serve as an early “social marker” of subtle cognitive decline.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Social markers could help inform models predicting progression to cognitive impairment.&lt;/li&gt;\u0000 &lt;/ul&gt;","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70616","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127317","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":"Everyday functioning in young onset dementia: differences between diagnostic groups","authors":"Emma Weltings,&nbsp;Merel C. Postema,&nbsp;Maureen van Dam,&nbsp;Mark A. Dubbelman,&nbsp;Mukrabe E. Tewolde,&nbsp;Flora H. Duits,&nbsp;Afina W. Lemstra,&nbsp;The LEADS consortium,&nbsp;Bradford C. Dickerson,&nbsp;Maria C. Carrillo,&nbsp;Gil D. Rabinovici,&nbsp;Dustin B. Hammers,&nbsp;Wiesje M. Van der Flier,&nbsp;Liana G. Apostolova,&nbsp;Yolande A. L. Pijnenburg,&nbsp;Sietske A. M. Sikkes","doi":"10.1002/alz.70711","DOIUrl":"10.1002/alz.70711","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>The aim of this study was to examine differences in Instrumental Activities of Daily Living (IADL) among young-onset dementia (YOD) diagnoses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants were included from Amsterdam Dementia and Longitudinal Early-Onset Alzheimer's Disease (LEADS) cohorts, with diagnoses of typical Alzheimer's disease (AD), behavioral variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), posterior cortical atrophy (PCA), or dementia with Lewy bodies (DLB) established in multidisciplinary meetings. We compared overall IADL scores and item level scores between groups using multiple regression analyses, adjusted for cohort, demographics, and disease severity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>We included 582 YOD patients (58.4 ± 4.2 years; 59%F), with overall moderate IADL problems (47.5 ± 8.57). DLB patients showed the most IADL difficulties (41.8 ± 7.8) compared to PCA, typical AD, bvFTD, and PPA (adjusted β range 4.62 to 14.14, all <i>p</i> &lt; 0.01), whereas PPA patients showed the least IADL difficulties (55.8 ± 9.83), with item-specific differences.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> CONCLUSION</h3>\u0000 \u0000 <p>We found differences in everyday functioning between YOD types. Understanding IADL in YOD types will assist in care planning.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Patients with DLB showed the most IADL difficulties compared to PCA, typical AD, bvFTD, and PPA</li>\u0000 \u0000 <li>Patients with PPA showed the least IADL difficulties compared to DLB, PCA, typical AD, and bvFTD</li>\u0000 \u0000 <li>We identified diagnostic group-specific activity challenges. While ‘working’ was among the most commonly impaired activities across al groups, distinct functional challenges emerged per diagnosis: for example, DLB had high impairment in financial tasks, PCA patients in visual-spatial tasks, and bvFTD with planning and organizational activities (e.g. making appointments).</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70711","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129844","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":"The Brain Health Index: Integrating vulnerability, resilience, and cognitive function into a unified measure of cognitive health and risk of neurodegenerative disease","authors":"Michael J. Kleiman,&nbsp;Gregory Gibbs,&nbsp;Mahesh S. Joshi,&nbsp;James E. Galvin","doi":"10.1002/alz.70723","DOIUrl":"10.1002/alz.70723","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;Assessing brain health and identifying cognitive impairment risk remains challenging, with only 11.4% of MCI cases receiving timely diagnoses. We developed the Brain Health Index (BHI), integrating the Vulnerability Index, Resilience Index, and Number Symbol Coding Task into a unified metric.&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 evaluated 469 participants (258 congnitively normal [CN], 140 mild cognitive impairment [MCI], 49 Alzheimer's disease and related dementias [ADRD]) using comprehensive clinical, cognitive, and biomarker assessments. After empirically-derived weighting, BHI thresholds were developed. Cross-sectional associations and longitudinal analyses were performed, with threshold validation for risk stratification.&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;BHI demonstrated strong correlations with cognitive (Montreal Cognitive Assessment [MoCA] &lt;i&gt;r&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.408), functional (Functional Activities Questionnaire [FAQ] &lt;i&gt;r&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.278), and biomarker (neurofilament light chain [NfL] &lt;i&gt;r&lt;/i&gt;&lt;sup&gt;2&lt;/sup&gt; = 0.073) measures. Complete mediation was observed for NfL and glial fibrillary acidic protein (GFAP) changes over 1 year. Threshold analysis revealed 89.2% of low BHI participants had cognitive impairment, with only one ADRD case in the high BHI group.&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;The BHI provides a brief, validated, comprehensive brain health metric with clinical utility for risk stratification and intervention monitoring.&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;Assessing brain health status and identifying individuals at risk for cognitive impairment remains a significant challenge, particularly in early prodromal and symptomatic stages when current therapies may be most effective and patients may be eligible for clinical trials.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We created a unified metric, the Brain Health Index (BHI), combining resilience and vulnerability factors with cognitive performance that divided individuals into high, indeterminant, and low risk groups.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The BHI demonstrated strong correlations with cognitive, functional, and biomarker measures.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;The BHI had a 16-fold increase in identifying individuals who were likely to have ","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70723","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127347","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":"Cognitive trajectories among English- and Spanish-test-takers in the NACC","authors":"Carlos E. E. Araujo-Menendez,&nbsp;Rubi A. Carpio,&nbsp;Wassim Tarraf,&nbsp;Alyssa L. Lawrence,&nbsp;Armando Lemus,&nbsp;Rachel Membreno,&nbsp;Carmen J. W. Chek,&nbsp;Ursula G. Saelzler,&nbsp;Elsa Baena,&nbsp;Alejandra Morlett Paredes,&nbsp;Ariana M. Stickel","doi":"10.1002/alz.70721","DOIUrl":"10.1002/alz.70721","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Cognitive assessments were traditionally developed using English-speaking populations, creating a potential disadvantage and misrepresentation for non-English speakers. We aimed to determine whether English- and Spanish-test-takers have similar or different cognitive trajectories.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants included 931 Hispanic/Latino adults from the National Alzheimer's Coordinating Center. Using mixed-effects regression analyses, we examined baseline differences and longitudinal changes in memory, attention/working memory, executive functioning, and language between Spanish- and English-test-takers. Models controlled for age at baseline, education, sex, Hispanic/Latino heritage, and cognitive status.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>English-test-takers performed significantly better than Spanish-test-takers across all domains at baseline. No differences in cognitive trajectories were detected, except for attention/working memory, in which Spanish-test-takers declined at a slower rate than English-test-takers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Despite baseline differences, both groups exhibited largely similar cognitive aging trajectories. These findings suggest that cross-sectional differences may reflect measurement bias rather than differences in cognitive aging and an underestimation of cognitive abilities among Spanish speakers.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Baseline disparities in cognition were observed across all domains, except for language, with Spanish-test-takers scoring significantly lower than English-test-takers.</li>\u0000 \u0000 <li>Despite baseline differences, rates of cognitive decline were largely similar across language groups, suggesting potential measurement bias rather than differences in cognitive aging.</li>\u0000 \u0000 <li>Spanish-test-takers showed greater maintenance in attention over time, pointing to possible benefits from repeated testing or cultural factors that warrant further investigation.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70721","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127323","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":"Facets of language performance in early-onset and late-onset Alzheimer's disease dementia","authors":"Jeanne Gallée,&nbsp;Laura E. Gibbons,&nbsp;Seo-Eun Choi,&nbsp;Michael Lee,&nbsp;Phoebe Scollard,&nbsp;Emily H. Trittschuh,&nbsp;Jesse Mez,&nbsp;Andrew J. Saykin,&nbsp;Nancy S. Foldi,&nbsp;Shubhabrata Mukherjee,&nbsp;Paul K. Crane","doi":"10.1002/alz.70705","DOIUrl":"10.1002/alz.70705","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Early-onset Alzheimer's disease dementia (EOAD) is characterized by more pronounced cognitive decline than late-onset AD dementia (LOAD). Characteristic performance in spoken language remains undefined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHOD</h3>\u0000 \u0000 <p>A cross-sectional analysis of 1189 people with EOAD and 4646 with LOAD from the National Alzheimer's Coordinating Center (NACC) was conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULT</h3>\u0000 \u0000 <p>Based on data from their first NACC visit with AD, there was considerable heterogeneity in language performance across people with EOAD and LOAD. The distribution of naming ability was similar across these groups. On average, people with LOAD performed better than those with EOAD in category fluency, letter fluency, and spoken lexical retrieval, and had lower Clinical Dementia Rating (CDR) Language scores, although there was considerable overlap in the distributions for participants with EOAD and those with LOAD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>At diagnosis, the language profiles of EOAD and LOAD are distinct. There is substantial variability in both groups in multiple aspects of language.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Early-onset Alzheimer's disease (EOAD) is associated with significantly poorer category and phonemic fluency and global spoken lexical retrieval compared to late-onset Alzheimer's disease (LOAD) at time of diagnosis.</li>\u0000 \u0000 <li>Participants with EOAD dementia show greater severity and variability in clinician-rated language functioning, as measured by Clinical Dementia Rating (CDR) Language scores.</li>\u0000 \u0000 <li>No significant group differences were observed in confrontation naming performance between EOAD and LOAD dementia.</li>\u0000 \u0000 <li>Findings support that there are distinct profiles of language performance in EOAD and LOAD at time of dementia diagnosis.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70705","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127350","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":"Alzheimer's Association releases its first clinical practice guideline for blood-based biomarker tests","authors":"","doi":"10.1002/alz.70701","DOIUrl":"10.1002/alz.70701","url":null,"abstract":"&lt;p&gt;At the Alzheimer's Association International Conference 2025, the Association released release of its first clinical practice guideline (CPG) on the use of blood-based biomarker (BBM) tests.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The CPG provides clear, evidence-based, brand-agnostic recommendations to support more accurate and accessible diagnosis of Alzheimer's using BBM tests. The recommendations are linked to a systematic review using a robust and transparent methodology and will be updated regularly as evidence evolves.&lt;/p&gt;&lt;p&gt;“This is a pivotal moment in Alzheimer's care,” said Maria C. Carrillo, PhD, Alzheimer's Association chief science officer and medical affairs lead, and a co-author of the guideline. “For the first time, we have a rigorously evidence-based guideline that empowers clinicians to use blood biomarker tests confidently and consistently. Adoption of these recommendations will lead to quicker, more accessible, more accurate diagnoses — and better outcomes for individuals and families affected by Alzheimer's.”&lt;/p&gt;&lt;p&gt;The guideline cautions that there is significant variability in diagnostic test accuracy and many commercially available BBM tests do not meet these thresholds.&lt;/p&gt;&lt;p&gt;“Not all BBM tests have been validated to the same standard or tested broadly across patient populations and clinical settings, yet patients and clinicians may assume these tests are interchangeable; they are not,” said Rebecca M. Edelmayer, PhD, Alzheimer's Association vice president of scientific engagement and a co-author of the guideline. “This guideline helps clinicians apply these tools responsibly, avoid overuse or inappropriate use, and ensure that patients have access to the latest scientific advancements.”&lt;/p&gt;&lt;p&gt;Compared to standard-of-care PET imaging and CSF tests, BBM tests are typically less costly, more accessible, and more acceptable to patients. The guideline emphasizes that BBM tests do not substitute for a comprehensive clinical evaluation by a health care professional, and should be ordered and interpreted by a health care professional in the context of clinical care.&lt;/p&gt;&lt;p&gt;This is the first evidence-based guideline in the Alzheimer's space that uses Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. The use of GRADE ensures a transparent, structured, and evidence-based process for evaluating the certainty of evidence and formulating recommendations. This strengthens the credibility and reproducibility of the guideline and allows for explicit linkage between evidence and recommendations.&lt;/p&gt;&lt;p&gt;This guideline's primary audience is specialists involved in the diagnostic evaluation of cognitive impairment in specialized care settings. A specialist is defined as a health care provider, typically in neurology, psychiatry, or geriatrics, who cares for adults with cognitive impairment or dementia. It also applies to primary care providers, nurse practitioners, and physician assistants in specialized care settings.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 9","pages":""},"PeriodicalIF":11.1,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://alz-journals.onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70701","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145127321","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}