Alzheimer's & Dementia最新文献

{"title":"Predicting amyloid beta accumulation in cognitively unimpaired older adults: Cognitive assessments provide no additional utility beyond demographic and genetic factors","authors":"Shu Liu,&nbsp;Paul Maruff,&nbsp;Martin Saint-Jalmes,&nbsp;Pierrick Bourgeat,&nbsp;Colin L. Masters,&nbsp;Benjamin Goudey,&nbsp;for the Alzheimer's Disease Neuroimaging Initiative, and the Australian Imaging Biomarkers and Lifestyle Flagship Study of Ageing","doi":"10.1002/alz.70036","DOIUrl":"10.1002/alz.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> BACKGROUND</h3>\u0000 \u0000 <p>Integrating non-invasive measures to estimate abnormal amyloid beta accumulation (Aβ+) is key to developing a screening tool for preclinical Alzheimer's disease (AD). The predictive capability of standard neuropsychological tests in estimating Aβ+ has not been quantified.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>We constructed machine learning models using six cognitive measurements alongside demographic and genetic risk factors to predict Aβ status. Data were drawn from three cohorts: Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4), Alzheimer's Disease Neuroimaging Initiative (ADNI), and Australian Imaging, Biomarker &amp; Lifestyle (AIBL) study. Internal validation was conducted within A4 with external validations in ADNI and AIBL to assess model generalizability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>The highest area under the curve (AUC) for predicting Aβ+ was observed with demographic, genetic, and cognitive variables in A4 (median AUC = 0.745), but this was not significantly different from models without cognitive variables. External validation showed no improvement in ADNI and a slight decrease in AIBL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Standard neuropsychological tests do not significantly enhance Aβ+ prediction in cognitively unimpaired adults beyond demographic and genetic information.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Standard neuropsychological tests do not significantly improve the prediction of amyloid beta positivity (Aβ+) in cognitively unimpaired older adults beyond demographic and genetic information alone.</li>\u0000 \u0000 <li>Across three well-characterized cohorts, machine learning models incorporating cognitive measures failed to significantly improve Aβ+ prediction, indicating the limited relationship between cognitive performance on these tests and the risk of pre-clinical Alzheimer's disease (AD).</li>\u0000 \u0000 <li>These findings challenge assumptions about cognitive symptoms preceding Aβ+ screening and emphasize the need for developing more sensitive cognitive tests for early AD detection.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660863","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":"Blood biomarkers differentiate AD-related versus non-AD-related cognitive deficits","authors":"Kelsey R. Sewell,&nbsp;Lauren E. Oberlin,&nbsp;Thomas K. Karikari,&nbsp;Marcos Olvera-Rojas,&nbsp;Lu Wan,&nbsp;Jill K. Morris,&nbsp;Paul J. Kueck,&nbsp;Xuemei Zeng,&nbsp;Haiqing Huang,&nbsp;George Grove,&nbsp;Yijun Chen,&nbsp;Tara K. Lafferty,&nbsp;Anuradha Sehrawat,&nbsp;M. Ilyas Kamboh,&nbsp;Anna L. Marsland,&nbsp;Arthur F. Kramer,&nbsp;Edward McAuley,&nbsp;Jeffrey M. Burns,&nbsp;Charles H. Hillman,&nbsp;Eric D. Vidoni,&nbsp;Chaeryon Kang,&nbsp;Kirk I. Erickson","doi":"10.1002/alz.14619","DOIUrl":"10.1002/alz.14619","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The utility of blood-based biomarkers for discriminating Alzheimer's disease (AD)-related versus non-AD-related cognitive deficits in preclinical populations remains poorly understood. Here, we tested the capability of blood markers to detect and discriminate variation in performance across multiple cognitive domains in a cognitively unimpaired sample.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Participants (<i>n </i>= 648, aged 69.9 ± 3.8, 71% female) underwent a comprehensive cognitive assessment and assays for plasma-based biomarkers amyloid beta (Aβ)1-42/1-40 by mass spectrometry, phosphorylated tau (p-tau) 181 and 217, p-tau217/Aβ1-42, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Greater p-tau217 was exclusively associated with poorer episodic memory performance (β = −0.11, SE = 0.04, <i>p </i>= .003), and remained so after covarying for NfL. Higher NfL was non-specifically associated with poorer performance across a range of cognitive domains and remained so after covarying for p-tau217.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Blood-based biomarkers may differentiate non-AD-related versus AD-related cognitive deficits. This characterization will be important for early intervention and disease monitoring for AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>There is heterogeneity in the causes of cognitive decline in aging.</li>\u0000 \u0000 <li>AD-related blood biomarkers may help characterize these causes.</li>\u0000 \u0000 <li>Elevated p-tau217 was exclusively associated with poorer episodic memory.</li>\u0000 \u0000 <li>Elevated NfL was associated with poorer cognition in a broad range of domains.</li>\u0000 \u0000 <li>Blood biomarkers may help differentiate AD- and non-AD-related cognitive deficits.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14619","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660322","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":"Metabolic stress and age drive inflammation and cognitive decline in mice and humans","authors":"Sarah E. Elzinga,&nbsp;Kai Guo,&nbsp;Ali Turfah,&nbsp;Rosemary E. Henn,&nbsp;Ian F. Webber-Davis,&nbsp;John M. Hayes,&nbsp;Crystal M. Pacut,&nbsp;Samuel J. Teener,&nbsp;Andrew D. Carter,&nbsp;Diana M. Rigan,&nbsp;Adam M. Allouch,&nbsp;Dae-Gyu Jang,&nbsp;Rachel Parent,&nbsp;Emily Glass,&nbsp;Geoffrey G. Murphy,&nbsp;Stephen I. Lentz,&nbsp;Kevin S. Chen,&nbsp;Lili Zhao,&nbsp;Junguk Hur,&nbsp;Eva L. Feldman","doi":"10.1002/alz.70060","DOIUrl":"10.1002/alz.70060","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Metabolic stressors (obesity, metabolic syndrome, prediabetes, and type 2 diabetes [T2D]) increase the risk of cognitive impairment (CI), including Alzheimer's disease (AD). Immune system dysregulation and inflammation, particularly microglial mediated, may underlie this risk, but mechanisms remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Using a high-fat diet-fed (HFD) model, we assessed longitudinal metabolism and cognition, and terminal inflammation and brain spatial transcriptomics. Additionally, we performed hippocampal spatial transcriptomics and single-cell RNA sequencing of <i>post mortem</i> tissue from AD and T2D human subjects versus controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>HFD induced progressive metabolic and CI with terminal inflammatory changes, and dysmetabolic, neurodegenerative, and inflammatory gene expression profiles, particularly in microglia. AD and T2D human subjects had similar gene expression changes, including in secreted phosphoprotein 1 (<i>SPP1</i>), a pro-inflammatory gene associated with AD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These data show that metabolic stressors cause early and progressive CI, with inflammatory changes that promote disease. They also indicate a role for microglia, particularly microglial <i>SPP1</i>, in CI.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Metabolic stress causes persistent metabolic and cognitive impairments in mice.</li>\u0000 \u0000 <li>Murine and human brain spatial transcriptomics align and indicate a pro-inflammatory milieu.</li>\u0000 \u0000 <li>Transcriptomic data indicate a role for microglial-mediated inflammatory mechanisms.</li>\u0000 \u0000 <li>Secreted phosphoprotein 1 emerged as a potential target of interest in metabolically driven cognitive impairment.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660601","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":"Rethinking biological biomarkers to track treatment efficacy in Alzheimer's disease: Focus on brain connectivity","authors":"Lorenzo Pini,&nbsp;Bruno P Imbimbo","doi":"10.1002/alz.70083","DOIUrl":"10.1002/alz.70083","url":null,"abstract":"&lt;p&gt;In a recent issue of &lt;i&gt;Alzheimer's &amp; Dementia&lt;/i&gt;, Bittner and colleagues published a comprehensive evaluation of brain positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers from two, 116-week, double-blind, placebo-controlled Phase 3 studies (GRADUATE I and II) investigating gantenerumab, an anti-amyloid beta (Aβ) monoclonal antibody. The studies included 1965 participants with early Alzheimer's disease (AD).&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The authors measured a wide range of imaging and fluid biomarkers, including markers of amyloid pathology (amyloid PET, Aβ40, Aβ42), tau pathology (tau PET, p-tau181, p-tau217), neurodegeneration (volumetric magnetic resonance imaging (MRI), total tau, neurofilament light chain [NfL]), synaptic dysfunction (neurogranin, neuronal pentraxin-2 [NPTX2], and alpha-synuclein [α-syn]), and glial activation and neuroinflammation (soluble triggering receptor expressed on myeloid cells 2 [sTREM2], glial fibrillary acidic protein [GFAP], S100 calcium-binding protein B [S100B], and chitinase-3-like protein 1 [YKL-40]). Amyloid PET measurements were performed in 237 participants, tau PET in 201 participants, MRI volumetric assessments in 1952 participants, and CSF biomarker assessments in 315 participants.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Treatment with gantenerumab significantly affected Aβ-PET burden and CSF levels of Aβ40, Aβ42, total tau, p-tau181, GFAP, neurogranin, S100B, NfL, α-syn, and NPTX2. Although the effects of gantenerumab on these biomarkers were consistent with putative effects on brain Aβ deposition, neurodegeneration, and neuroinflammation, the drug did not show significant cognitive, clinical, or functional benefits for patients.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The apparent discrepancy between biomarker improvements and lack of clinical efficacy raises an important question: why does gantenerumab, despite positively influencing several AD biomarkers, fail to translate these effects into cognitive or functional benefits?&lt;/p&gt;&lt;p&gt;This discrepancy is not unique to gantenerumab. Other anti-Aβ monoclonal antibodies have shown similar inconsistencies. Lecanemab, approved by the U.S. Food and Drug Administration (FDA) in 2023 for early AD, significantly slowed cognitive and clinical decline but did not significantly affect CSF NfL levels, a marker of neural injury.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Similarly, donanemab, another FDA-approved anti-Aβ monoclonal antibody, reduced the rate of cognitive and clinical decline&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; but did not significantly decrease plasma NfL levels compared to placebo,&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; whereas its effects on CSF NfL levels were not investigated. In addition, its impact on CSF Aβ40 or Aβ42 remains unknown.&lt;/p&gt;&lt;p&gt;Given these findings, we must question whether traditional AD biomarkers, tracking Aβ load, neurodegeneration, and neuroinflammation, are reliable predictors of cognitive and functional outcomes. Recently, we proposed that brain connectivity could rep","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661914","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":"Association between healthy lifestyle and cognitive decline, all-cause mortality, and mortality from cardiovascular and cerebrovascular diseases: a 10-year population-based prospective cohort study","authors":"Chun Li,&nbsp;Chaobo Bai,&nbsp;Lijun Wang,&nbsp;Mei Zhang,&nbsp;Maigeng Zhou,&nbsp;Jing Chen,&nbsp;Danhua Zhao,&nbsp;Baoyu Chen,&nbsp;Qi Wang,&nbsp;Yuan Li,&nbsp;Junyi Chen,&nbsp;Xintong Guo,&nbsp;Jinjin Wang,&nbsp;Zhe Zhao,&nbsp;Hongqiang Sun,&nbsp;Limin Wang,&nbsp;Junliang Yuan","doi":"10.1002/alz.70021","DOIUrl":"10.1002/alz.70021","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>The association between cognitive function, healthy lifestyle, and mortality remains understudied in large Chinese cohorts.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In this nationwide 10-year prospective study of 24,657 older adults, we assessed Mini-Mental State Examination (MMSE) categories (&lt;18, 18 to 23, 24 to 27, 28 to 30) and a seven-component lifestyle score (0 to 7) for their relationships with all-cause, cardiovascular, and cerebrovascular mortality.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>Compared with individuals scoring 28 to 30 on the MMSE, lower scores were linked to elevated all-cause and cerebrovascular mortality but not cardiovascular mortality. Participants with lifestyle scores of 4 or 5 had a higher risk of all-cause mortality. Even optimal lifestyle practices did not fully mitigate the heightened mortality risk associated with declining cognitive performance.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>A healthy lifestyle is beneficial but cannot fully offset the impact of cognitive impairment. Therefore, integrating routine cognitive assessments and targeted interventions with healthy lifestyle practices is crucial for effectively reducing mortality risk.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>A nationally representative, 10-year prospective cohort in China was employed to investigate the combined effects of lifestyle behaviors and cognitive function on all-cause, cardiovascular, and cerebrovascular mortality.</li>\u0000 \u0000 <li>Both healthy lifestyle and better cognitive function were associated with a reduced risk of all-cause mortality.</li>\u0000 \u0000 <li>Even among individuals practicing optimal lifestyle behaviors, cognitive impairment significantly elevated the risk of all-cause and cerebrovascular mortality.</li>\u0000 \u0000 <li>These findings underscore the necessity of incorporating routine cognitive assessments and targeted interventions with healthy lifestyle practices aimed at reducing mortality risk in aging populations.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660325","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":"Relationships between hypometabolism and both β-amyloid and tau PET in corticobasal syndrome","authors":"Alma Ghirelli,&nbsp;Austin W. Goodrich,&nbsp;Yehkyoung C. Stephens,&nbsp;Jonathan Graff-Radford,&nbsp;Farwa Ali,&nbsp;Mary M. Machulda,&nbsp;Chistopher G. Schwarz,&nbsp;Matthew L. Senjem,&nbsp;Federica Agosta,&nbsp;Massimo Filippi,&nbsp;Clifford R. Jack Jr.,&nbsp;Val J. Lowe,&nbsp;Keith A. Josephs,&nbsp;Jennifer L. Whitwell","doi":"10.1002/alz.70018","DOIUrl":"10.1002/alz.70018","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Alzheimer's disease (AD) pathology causes corticobasal syndrome (CBS) in 21%–50% of patients. Studies have assessed hypometabolism in CBS according to β-amyloid (A) positron emission tomography (PET), but the understanding of the association of both AD-tau (T) and A with hypometabolism is incomplete.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>Thirty-three CBS patients and 45 controls underwent fluorodeoxyglucose (FDG), flortaucipir, and Pittsburgh compound-B PET and were classified as A± and T±. FDG-PET uptake was extracted for 12 regions-of-interest in dominant (most affected) and non-dominant hemispheres and compared across A/T groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>A+T+ patients had greater hypometabolism in temporo-parieto-occipital cortices than A+T- and A-T- groups, with no differences observed between the A+T- and A-T- groups. FDG asymmetry was more accentuated in A+T+ patients. Medial temporal and basal ganglia metabolism were similar across AT groups.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>Amyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in temporo-parieto-occipital cortices in CBS, with AD-like patterns of hypometabolism observed only in A+T+ patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Amyloid (A) and tau PET (T) status can be used to stratify CBS patients.</li>\u0000 \u0000 <li>A+T+ CBS patients show more hypometabolism in temporo-parieto-occipital cortices.</li>\u0000 \u0000 <li>Medial temporal metabolism (typical AD pattern) is similar across AT groups.</li>\u0000 \u0000 <li>Parieto-occipital cortices should be assessed when investigating AT pathology in CBS.</li>\u0000 \u0000 <li>Amyloid and tau positivity contribute synergistically to hypometabolism and asymmetry in CBS.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70018","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660926","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":"Accuracy of plasma biomarkers to detect Alzheimer's disease proteinopathy prior to dementia","authors":"Karly A. Cody,&nbsp;Lianlian Du,&nbsp;Rachel L. Studer,&nbsp;Erin M. Jonaitis,&nbsp;Sanjay Asthana,&nbsp;Bradley T. Christian,&nbsp;Nathaniel A. Chin,&nbsp;Kris M. Kirmess,&nbsp;Matthew R. Meyer,&nbsp;Kevin E. Yarasheski,&nbsp;Tim West,&nbsp;Philip B. Verghese,&nbsp;Joel B. Braunstein,&nbsp;Tobey J. Betthauser,&nbsp;Rebecca E. Langhough,&nbsp;Sterling C. Johnson","doi":"10.1002/alz.14570","DOIUrl":"10.1002/alz.14570","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> INTRODUCTION</h3>\u0000 \u0000 <p>Plasma biomarkers sensitive to Alzheimer's disease (AD) proteinopathy prior to the onset of dementia have significant implications for early detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> METHODS</h3>\u0000 \u0000 <p>In 304 individuals without dementia, we investigated whether C₂N Diagnostics’ mass spectrometry (MS)-based plasma biomarkers (amyloid beta 42/40, %phosphorylated tau [p-tau]181, and %p-tau217) and amyloid probability scores (APS, PrecivityAD and APS2, PrecivityAD2) are associated with brain amyloid, brain tau, or preclinical cognitive decline.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> RESULTS</h3>\u0000 \u0000 <p>In this cohort study, %p-tau217 and the APS2 had high discriminative accuracy (area under the curve &gt; 0.93) for identifying elevated brain amyloid and tau and were associated with faster preclinical cognitive decline. Using %p-tau217 or the APS2 in a theoretical AD trial screening scenario reduced amyloid positron emission tomography imaging costs up to 41% or 45%, respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> DISCUSSION</h3>\u0000 \u0000 <p>These findings suggest that C₂N Diagnostics’ MS-based plasma biomarkers can detect brain amyloid and tau with high accuracy prior to dementia and could aid in identifying candidates for clinical trials or therapeutic intervention.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>C₂N plasma biomarkers differentiated Alzheimer's disease proteinopathy status prior to dementia.</li>\u0000 \u0000 <li>Plasma %phosphorylated tau (p-tau)217 and the C₂N Diagnostics PrecivityAD2 (APS2) were concordant with amyloid and tau positron emission tomography status.</li>\u0000 \u0000 <li>Plasma %p-tau217 and the APS2 were associated with preclinical cognitive decline.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14570","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660323","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":"Optimizing mealtime care and outcomes for people with dementia and their caregivers: A systematic review and meta-analysis of intervention studies","authors":"Wen Liu,&nbsp;Kyuri Lee,&nbsp;Heather Suh,&nbsp;Junxin Li","doi":"10.1002/alz.14522","DOIUrl":"10.1002/alz.14522","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Interventions addressing modifiable personal and environmental factors are critical to optimize dementia mealtime care, caregiving, and outcomes. This review synthesized the characteristics and effects of non-pharmacological interventions on mealtime care and outcomes in people with dementia and their caregivers. Five databases were searched from January 2012 to October 2024. Eligible studies were accessed for study quality and graded for level of evidence. Meta-analyses were performed for studies within the same intervention type that tested the impact on same outcomes. 33 studies were identified and categorized into five intervention types. Five studies were strong, 7 moderate, and 21 weak in quality. The levels of evidence varied from very low to moderate, with most being very low to low. Meta-analyses showed “resident training/therapy” decreased eating difficulties and increased food intake; “Nutritional supplement” improved cognition and depression; “environmental/food modification” increased food intake. Further research using rigorous designs is needed to increase evidence quality and determine effects of multi-component interventions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Highlights</h3>\u0000 \u0000 <div>\u0000 <ul>\u0000 \u0000 <li>Five intervention types were identified from the 33 included studies: nutritional supplements, resident training/therapy, caregiver training and/or mealtime assistance, environmental/food modification, and multiple component interventions.</li>\u0000 \u0000 <li>One-third of the included studies were strong to moderate, and two-thirds were weak in study quality.</li>\u0000 \u0000 <li>“Resident training/therapy” showed effects in reducing eating difficulties and increasing food intake.</li>\u0000 \u0000 <li>“Environmental/food modification” showed effects in increasing food intake.</li>\u0000 \u0000 <li>“Nutritional supplements” showed effects in improving cognitive function and depression.</li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14522","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660321","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":"Obfuscation via pitch-shifting for balancing privacy and diagnostic utility in voice-based cognitive assessment","authors":"Meysam Ahangaran,&nbsp;Nauman Dawalatabad,&nbsp;Cody Karjadi,&nbsp;James Glass,&nbsp;Rhoda Au,&nbsp;Vijaya B. Kolachalama","doi":"10.1002/alz.70032","DOIUrl":"https://doi.org/10.1002/alz.70032","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;Digital voice analysis is an emerging tool for differentiating cognitive states, but it poses privacy risks as automated systems may inadvertently identify speakers.&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 developed a computational framework to evaluate the trade-off between voice obfuscation and cognitive assessment accuracy, using pitch-shifting as a representative method. This framework was applied to voice recordings from the Framingham Heart Study (FHS, &lt;i&gt;n&lt;/i&gt; = 128) and the DementiaBank Delaware (DBD, &lt;i&gt;n&lt;/i&gt; = 85) corpus, both featuring responses to neuropsychological tests. Speaker obfuscation was measured via equal error rate (EER), and diagnostic utility was assessed through machine learning models distinguishing cognitive states: normal cognition (NC), mild cognitive impairment (MCI), and dementia (DE).&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;With the top 20 acoustic features, our framework achieved classification accuracies of 62.2% (EER: 0.3335) on the FHS dataset for NC, MCI, and DE differentiation, and 63.7% (EER: 0.1796) on the DBD dataset for NC and MCI differentiation, using obfuscated speech files.&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 demonstrate the feasibility of privacy-preserving voice markers, offering a scalable solution for voice-based cognitive assessments.&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;We developed a computational framework using pitch-shifting and acoustic transformations to balance speaker privacy and diagnostic utility in voice-based cognitive assessments.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;We evaluated the framework on two independent datasets, Framingham Heart Study (FHS, &lt;i&gt;n&lt;/i&gt; = 128) and DementiaBank Delaware (DBD, &lt;i&gt;n&lt;/i&gt; = 85) corpus, assessing the trade-off between privacy (measured by equal error rate [EER]) and classification accuracy.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Our framework achieved classification accuracies of 62.2% (EER: 0.3335) for distinguishing normal cognition (NC), mild cognitive impairment (MCI), and dementia in the FHS dataset and 63.7% (EER: 0.1796) for NC and MCI differentiation in the DBD dataset, using obfuscated speech files.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Our framework demonstrates that pitch-shifting levels can preserve diagnostic utility while protectin","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612569","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":"Visual-somatosensory integration as a novel behavioral marker of amyloid pathology","authors":"Jeannette R. Mahoney,&nbsp;Emmeline Ayers,&nbsp;Joe Verghese","doi":"10.1002/alz.14561","DOIUrl":"https://doi.org/10.1002/alz.14561","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;The ability to integrate information across sensory modalities is a vital aspect of everyday functioning and is linked to cognition. Increasing evidence suggests that Alzheimer's disease (AD) pathology manifests in sensory association areas before appearing in higher-order cognitive areas. We examined the role of visual-somatosensory integration (VSI) as a novel behavioral marker of AD-associated amyloid pathology.&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;This cross-sectional study included 243 adults (77 ± 6.5 years; 52% female) who completed the VSI test and AD biomarker assays. The &lt;i&gt;magnitude of VSI&lt;/i&gt; was the &lt;i&gt;independent variable&lt;/i&gt; and amyloid-beta probability scores (APS; PrecivityAD&lt;sup&gt;TM&lt;/sup&gt;) were the &lt;i&gt;dependent variable&lt;/i&gt;. Cognitive status (normal, mild cognitive impairment, or AD) was assigned during case conferences.&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;Linear regression revealed an inverse association between the &lt;i&gt;magnitude of VSI&lt;/i&gt; and APS (&lt;i&gt;β&lt;/i&gt; = −0.16; &lt;i&gt;p&lt;/i&gt; ≤ 0.01). As cognitive impairment increased from normal to dementia, the &lt;i&gt;magnitude of VSI&lt;/i&gt; decreased (&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;Findings provide support for VSI impairment as a new behavioral marker of AD-associated amyloid pathology.&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;Here we provide support for the &lt;i&gt;magnitude of VSI&lt;/i&gt; as a novel behavioral marker of AD-associated amyloid pathology given its significant association with an established, accurate, and reliable biomarker of AD pathology.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Adults with normal cognition maintained the highest &lt;i&gt;magnitude of VSI&lt;/i&gt; and brain amyloid negative scores.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;As cognitive impairment increased, the mean &lt;i&gt;magnitude of VSI&lt;/i&gt; significantly decreased while amyloid probability scores (APS) increased. In fact, individuals with dementia revealed the lowest &lt;i&gt;magnitude of VSI&lt;/i&gt; and the highest APS.&lt;/li&gt;\u0000 \u0000 &lt;li&gt;Our research continues to emphasize the importance of successful multisensory integration in aging, where the establishment of future novel multisensory-based interventions aimed at preventing disability and optimizing independence could prove valuable.&lt;/li&gt;\u0000 &lt;/u","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"21 3","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/alz.14561","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143564654","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}