Alzheimer's & Dementia最新文献

{"title":"Conversion to Alzheimer's disease dementia from normal cognition directly or with the intermediate mild cognitive impairment stage.","authors":"Xinlin Lu, Yahui Zhang, Yichen Tang, Charles Bernick, Guogen Shan","doi":"10.1002/alz.14393","DOIUrl":"10.1002/alz.14393","url":null,"abstract":"<p><strong>Introduction: </strong>Progression to Alzheimer's disease (AD) dementia from normal cognition (NC) can follow different trajectories, with most progressing through a recognizable mild cognitive impairment stage (NC-MCI-AD), while some individuals transition quickly from NC to AD dementia (NC-AD).</p><p><strong>Methods: </strong>We compared demographic characteristics, health factors, and cognitive and functional assessments across three time points: the first NC visit, the last NC visit, and the first AD dementia visit.</p><p><strong>Results: </strong>The NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis, despite maintaining better cognitive function during the NC stage. Analysis of yearly changes revealed negligible differences during NC. However, the yearly change during the AD dementia stage suggested potentially more rapid functional decline in the NC-AD group.</p><p><strong>Discussion: </strong>These findings highlight the heterogeneity in AD disease progression and emphasize the importance of considering diverse progression patterns in AD research and clinical practice.</p><p><strong>Highlights: </strong>We investigated the disease progression difference between patients who converted to Alzheimer's disease (AD) dementia from normal cognition (NC) directly or through the mild cognitive impairment (MCI) stage. We found that the NC-MCI-AD group showed greater impairment in cognitive and functional scores at AD dementia diagnosis. We discovered that the NC-AD group had rapid functional decline once patients were confirmed with AD onset.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neighborhood physical activity facilities predict risk of incident mixed and vascular dementia: The Cardiovascular Health Cognition Study.","authors":"Kyle D Moored, Michael R Desjardins, Breanna M Crane, Patrick T Donahue, Emily A Richards, Jana A Hirsch, Gina S Lovasi, Andrea L Rosso, Parveen K Garg, Timothy M Shields, Frank C Curriero, Michelle C Odden, Oscar L Lopez, Mary L Biggs, Anne B Newman, Michelle C Carlson","doi":"10.1002/alz.14387","DOIUrl":"10.1002/alz.14387","url":null,"abstract":"<p><strong>Introduction: </strong>Neighborhood environments may promote neurocognitive health in part by providing amenities that encourage physical activity. We examined associations between quantity of walkable facilities, including specifically physical activity facilities (e.g., gyms, recreation centers), with risk of incident dementia.</p><p><strong>Methods: </strong>Participants included 2923 adults ≥ 65 years old from the Cardiovascular Health Cognition Study (1992-1999), with clinically adjudicated dementia classified over a median 6.0 years of follow-up. Walkable facilities were measured within 1 km (Euclidean) of home. Self-reported baseline physical activity was considered a moderator.</p><p><strong>Results: </strong>In adjusted Cox models, participants with ≥ 2 (vs. 0) physical activity facilities had reduced risk of mixed/vascular dementia, but not Alzheimer's disease, particularly after excluding individuals in the bottom 20th percentile of physical activity (hazard ratio = 0.56, 95% confidence interval: 0.35-0.89).</p><p><strong>Discussion: </strong>Neighborhood amenities that encourage physical activity may mitigate dementia risk via improved vascular health, especially for individuals with sufficient baseline mobility to use these resources.</p><p><strong>Highlights: </strong>We examined associations between nearby walkable facilities and incident dementia. Facilities within 1 km were counted via the National Establishment Time Series Database. More physical activity facilities predicted lower risk of mixed/vascular dementia. No associations were found between walkable facilities and incident Alzheimer's disease.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Positron emission tomography harmonization in the Alzheimer's Disease Neuroimaging Initiative: A scalable and rigorous approach to multisite amyloid and tau quantification.","authors":"Susan M Landau, Theresa M Harrison, Suzanne L Baker, Martin S Boswell, JiaQie Lee, Jacinda Taggett, Tyler J Ward, Trevor Chadwick, Alice Murphy, Charles DeCarli, Christopher G Schwarz, Prashanthi Vemuri, Clifford R Jack, Robert A Koeppe, William J Jagust","doi":"10.1002/alz.14378","DOIUrl":"10.1002/alz.14378","url":null,"abstract":"<p><strong>Introduction: </strong>A key goal of the Alzheimer's Disease NeuroImaging Initiative (ADNI) positron emission tomography (PET) Core is to harmonize quantification of β-amyloid (Aβ) and tau PET image data across multiple scanners and tracers.</p><p><strong>Methods: </strong>We developed an analysis pipeline (Berkeley PET Imaging Pipeline, B-PIP) for ADNI Aβ and tau PET images and applied it to PET data from other multisite studies. Steps include image pre-processing, refacing, magnetic resonance imaging (MRI)/PET co-registration, visual quality control (QC), quantification of tracer uptake, and standardization of Aβ and tau standardized uptake value ratios (SUVrs) across tracers.</p><p><strong>Results: </strong>Measurements from 10,105 cross-sectional and longitudinal Aβ and tau PET scans acquired in several studies between 2010 and 2024 can be processed, harmonized, and directly merged across tracers and cohorts.</p><p><strong>Discussion: </strong>The B-PIP developed in ADNI is a scalable image harmonization approach used in several observational studies and clinical trials that facilitates rigorous Aβ and tau PET quantification and data sharing.</p><p><strong>Highlights: </strong>Quantitative results from ADNI Aβ and tau PET data are generated using a rigorous, scalable image processing pipeline This pipeline has been applied to PET data from several other large, multisite studies and trials Quantitative outcomes are harmonizable across studies and are shared with the scientific community.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marmosets as model systems for the study of Alzheimer's disease and related dementias: Substantiation of physiological tau 3R and 4R isoform expression and phosphorylation.","authors":"Hasi Huhe, Sarah M Shapley, Duc M Duong, Fang Wu, Seung-Kwon Ha, Sang-Ho Choi, Julia Kofler, Yongshan Mou, Thais Rafael Guimaraes, Amantha Thathiah, Caroline M Watson, Lauren K H Schaeffer, Gregory W Carter, Nicholas T Seyfried, Afonso C Silva, Stacey J Sukoff Rizzo","doi":"10.1002/alz.14366","DOIUrl":"10.1002/alz.14366","url":null,"abstract":"<p><strong>Introduction: </strong>Marmosets spontaneously develop pathological hallmarks of Alzheimer's disease (AD) including amyloid beta plaques. However, tau expression in the marmoset brain has been understudied.</p><p><strong>Methods: </strong>Isoforms of tau were examined by western blot, mass spectrometry, immunofluorescence, and immunohistochemical staining.</p><p><strong>Results: </strong>3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. Mass spectrometry analysis revealed that tau peptides in marmoset corresponded to the 3R and 4R peptides in human brain, with 3R predominating at birth and an ≈40%:60% 3R:4R ratios in adolescents and adults; tau was distributed widely in neurons, with localization in the soma and synaptic regions. Phosphorylation residues were observed on Threonine (Thr) Thr181, Thr217, Thr231, Serine (Ser) Ser202/Thr205, and Ser396/Ser404.</p><p><strong>Discussion: </strong>Our results confirm both 3R and 4R tau isoform expression and phosphorylation residues in the marmoset brain, and emphasize the significance of marmosets with natural expression of AD-related hallmarks as important translational models for AD. Highlights We report comprehensive characterization of tau isoform expression in marmoset brains across the lifespan. 3R and 4R tau isoforms are expressed in marmoset brains at both the transcript and protein levels across ages. These data emphasize the significance of marmosets with natural expression of primate-specific traits that are important for the study of Alzheimer's disease.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants associated with age-related episodic memory decline implicate distinct memory pathologies.","authors":"Amanat Ali, Sofiya Milman, Erica F Weiss, Tina Gao, Valerio Napolioni, Nir Barzilai, Zhengdong D Zhang, Jhih-Rong Lin","doi":"10.1002/alz.14379","DOIUrl":"10.1002/alz.14379","url":null,"abstract":"<p><strong>Background: </strong>Approximately 40% of people aged ≥ 65 experience memory loss, particularly in episodic memory. Identifying the genetic basis of episodic memory decline is crucial for uncovering its underlying causes.</p><p><strong>Methods: </strong>We investigated common and rare genetic variants associated with episodic memory decline in 742 (632 for rare variants) Ashkenazi Jewish individuals (mean age 75) from the LonGenity study. All-atom molecular dynamics simulations were performed to uncover mechanistic insights underlying rare variants associated with episodic memory decline.</p><p><strong>Results: </strong>In addition to the common polygenic risk of Alzheimer's disease, we identified and replicated rare variant associations in ITSN1 and CRHR2. Structural analyses revealed distinct memory pathologies mediated by interfacial rare coding variants such as impaired receptor activation of corticotropin releasing hormone and dysregulated L-serine synthesis.</p><p><strong>Discussion: </strong>Our study uncovers novel risk loci for episodic memory decline. The identified underlying mechanisms point toward heterogenous memory pathologies mediated by rare coding variants.</p><p><strong>Highlights: </strong>We demonstrated the contribution of the common polygenic risk of Alzheimer's disease to episodic memory decline. We discovered and replicated two risk genes associated with episodic memory decline implicated by rare variants, were discovered and replicated. We demonstrated molecular mechanisms and potential novel memory pathologies underlying interfacial rare coding variants. Molecular dynamics simulations were performed to understand the downstream effects of risk rare coding variants.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Visual read of [F-18]florquinitau PET that includes and extends beyond the mesial temporal lobe is associated with increased plasma pTau217 and cognitive decline in a cohort that is enriched with risk for Alzheimer's disease.","authors":"Ramiro Eduardo Rea Reyes, Karly A Cody, Rachael E Wilson, Henrik Zetterberg, Nathaniel A Chin, Erin M Jonaitis, Melissa Bahr, Olivia Mandel, Madilynn Wintlend, Barbara B Bendlin, Ozioma C Okonkwo, Lindsay R Clark, Matt Zammit, Sanjay Asthana, Bradley T Christian, Tobey J Betthauser, Laura Eisenmenger, Rebecca E Langhough, Sterling C Johnson","doi":"10.1002/alz.14406","DOIUrl":"10.1002/alz.14406","url":null,"abstract":"<p><strong>Introduction: </strong>Patterns of signal from tau positron emission tomography (tau-PET) confined to the medial temporal lobe (MTL) or extended into the neocortex may be relevant for Alzheimer's disease (AD) research if they are linked to differential biomarker levels and cognitive decline.</p><p><strong>Methods: </strong>Visual assessment of Tau-PET [F-18]florquinitau (FQT) exams from 728 initially non-demented older adults yielded four uptake groups: tau-negative (T-), MTL-only (T+_MTL), neocortex-only (T+_Neo), or both (T+_MTL&Neo). Mixed effects models assessed group differences in retrospective cognitive and plasma pTau217 trajectories.</p><p><strong>Results: </strong>T+_MTL&Neo was the most common T+ group (n = 97; 93% A+) and exhibited the sharpest worsening in cognitive and pTau217 trajectories before tau PET.</p><p><strong>Discussion: </strong>The T+_MTL&Neo category represents an intermediate to advanced stage of AD preceded by rising ptau217 and progressive cognitive decline. The pTau217 finding suggests that A+, T+ in MTL or neocortex could represent early AD stages, with a higher likelihood of progressing to more advanced stages.</p><p><strong>Highlights: </strong>Visual assessments of Tau-PET FQT revealed four distinct uptake groups: tau-negative (T-), MTL-only (T+_MTL), neocortex-only (T+_Neo), or both (T+_MTL&Neo). Amyloid positive participants in the T+_MTL and T+_MTL&Neo categories showed a retrospectively faster decline in their cognitive trajectories, and a sharper increase in pTau217 levels in plasma, compared to T-. The T+_MTL&Neo group displayed sharper trajectories compared with the other Tau positive groups in both their cognitive scores and pTau217 plasma levels. Our results suggest that participants with Tau present in both MTL and neocortex represent an intermediate to advanced stage of AD, whereas participants with signals confined to either MTL or neocortex could represent earlier AD stages.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous cerebrovascular reactivity at rest in older adults with and without mild cognitive impairment and memory deficits.","authors":"Allison C Engstrom, John Paul M Alitin, Arunima Kapoor, Shubir Dutt, Trevor Lohman, Isabel J Sible, Anisa J Marshall, Fatemah Shenasa, Aimée Gaubert, Farrah Ferrer, Amy Nguyen, David Robert Bradford, Kathleen Rodgers, Lorena Sordo, Elizabeth Head, Xingfeng Shao, Danny J J Wang, Daniel A Nation","doi":"10.1002/alz.14396","DOIUrl":"10.1002/alz.14396","url":null,"abstract":"<p><strong>Introduction: </strong>Older adults with mild cognitive impairment (MCI) exhibit deficits in cerebrovascular reactivity (CVR), suggesting CVR is a biomarker for vascular contributions to MCI. This study examined if spontaneous CVR is associated with MCI and memory impairment.</p><p><strong>Methods: </strong>One hundred sixty-one older adults free of dementia or major neurological/psychiatric disorders were recruited. Participants underwent clinical interviews, cognitive testing, venipuncture for Alzheimer's disease (AD) biomarkers, and brain magnetic resonance imaging. Spontaneous CVR was quantified during 5 minutes of rest. Respiratory gases analyzed through nasal cannula to quantify end-tidal carbon dioxide (_ETCO₂) levels were used to estimate CVR.</p><p><strong>Results: </strong>Whole brain CVR was negatively associated with age, but not MCI. Lower CVR in the parahippocampal gyrus (PHG) was found in participants with MCI and was linked to worse memory performance on memory tests. Results remained significant after adjusting for AD biomarkers and vascular risk factors.</p><p><strong>Discussion: </strong>Spontaneous CVR deficits in the PHG are observed in older adults with MCI and memory impairment, suggesting medial temporal microvascular dysfunction is observed in cognitive decline.</p><p><strong>Highlights: </strong>Aging is associated with decline in whole brain spontaneous cerebrovascular reactivity (CVR). Older adults with mild cognitive impairment exhibit deficits in spontaneous CVR in the parahippocampal gyrus (PHG). Memory impairment is correlated with reduced spontaneous CVR in the PHG.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of common cardiovascular disease drugs and risk of dementia: A case-control study in Swedish national register data.","authors":"Mozhu Ding, Alexandra M Wennberg, Gunnar Engström, Karin Modig","doi":"10.1002/alz.14389","DOIUrl":"10.1002/alz.14389","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiovascular drug use may help prevent dementia; however, current evidence is mixed. Using a case-control design, we investigated the association between duration and combination of multiple cardiovascular drug classes and incident dementia.</p><p><strong>Methods: </strong>From the Swedish national registers, we included 88,065 incident dementia cases aged ≥ 70 at diagnosis between 2011 and 2016 and 880,650 age- and sex-matched controls. Cardiovascular drug use was ascertained from the Prescribed Drug Register.</p><p><strong>Results: </strong>Long-term users (≥ 5 years) of antihypertensives, diuretics, lipid-lowering drugs (LLDs), and oral anticoagulants (OACs) had statistically significantly fewer dementia diagnoses (odds ratio [OR] 0.75-0.91) than non-users. Antiplatelets use was associated with more dementia diagnoses (OR 1.13-1.25). Use of antihypertensives in combination with diuretics, LLDs, and OACs for ≥ 5 years was associated with fewer dementia diagnoses (OR 0.66-0.84).</p><p><strong>Discussion: </strong>Preventing dementia via cardiovascular drug pathways may be possible. It is however important to consider the potential long-term negative cognitive effect of antiplatelets.</p><p><strong>Highlights: </strong>Use ≥ 5 years of common cardiovascular drugs was associated with lower dementia risk. Common cardiovascular drug combination use was associated with lower dementia risk. Anti-platelet use of any duration was associated with higher dementia risk.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alzheimer's Association workgroup suggests language for clinicians to talk to their patients about new treatments","authors":"","doi":"10.1002/alz.14407","DOIUrl":"10.1002/alz.14407","url":null,"abstract":"&lt;p&gt;The availability of US Food and Drug Administration (FDA)-approved therapies for early Alzheimer's disease (AD) challenges clinicians and health-care providers with effectively communicating the risks, benefits, burdens, costs and available support associated with these treatments to patients, families, and other health-care providers. The task is essential but complex.&lt;/p&gt;&lt;p&gt;The Alzheimer's Association Clinical Meaningfulness Workgroup has developed recommendations and suggested language to help health-care providers explain newly approved AD treatments to patients and caregivers. “Benefits and Risks of FDA-Approved Amyloid-Targeting Antibodies for Treatment of Early Alzheimer's Disease: Navigating Clinician-Patient Engagement” was published online October 15.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The paper focuses on FDA-approved amyloid-targeting antibody therapies for early AD, which offer hope by slowing disease progression. However, these treatments are not cures, and thoughtful management—including ongoing, clear, factual communication—is required.&lt;/p&gt;&lt;p&gt;“The language and guidance in the article emphasizes the need for clear and empathetic communication between clinicians, patients, and caregivers regarding treatment eligibility, risks, benefits, and costs,” said Maria C. Carrillo, PhD, Alzheimer's Association chief science officer and medical affairs lead, and senior author on the article. “It also stresses the importance of genetic testing in advance, ongoing monitoring for side effects, and managing the logistical and financial issues associated with treatment.”&lt;/p&gt;&lt;p&gt;“This effort was catalyzed by Alzheimer's patients and families sharing their enthusiasm, but also their concerns—telling us what they want and need to know about these drugs, and the confusion and discord they have experienced because of the contentious public discussion about the FDA-approved treatments for early Alzheimer's,” Carrillo explained. “The issues are complex, but can be discussed in a way that everyone can understand. We do this for cancer treatment. We can do this for Alzheimer's.”&lt;/p&gt;&lt;p&gt;The Workgroup was formed in 2022 as part of the Alzheimer's Association's efforts to provide resources for clinicians about the benefits and risks of FDA-approved amyloid-targeting therapies for AD. It brought together experts in dementia care, academia, drug development, and the clinical community. The Workgroup received input from experienced clinicians outside the academic and industry communities and from the Alzheimer's Association Early-Stage Advisory Group, which includes individuals with early Alzheimer's dementia or mild cognitive impairment, to incorporate patient perspectives.&lt;/p&gt;&lt;p&gt;“As new Alzheimer's therapies are approved, there may be different risks and expectations,” said Dorene M. Rentz, PsyD, professor of neurology, Harvard Medical School, and lead author of the paper. “Our goal is to update this resource to facilitate those discussions, as needed.”&lt;/p&gt;&lt;p&gt;“The","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"20 11","pages":"8225-8226"},"PeriodicalIF":13.0,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11567858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638461","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":"Additive effects of cerebrovascular disease functional connectome phenotype and plasma p‐tau181 on longitudinal neurodegeneration and cognitive outcomes","authors":"Joanna Su Xian Chong, Fang Ji, Saima Hilal, Joyce Ruifen Chong, Jia Ming Lau, Nathanael Ren Jie Tong, Boon Yeow Tan, Narayanaswamy Venketasubramanian, Mitchell Kim Peng Lai, Christopher Li‐Hsian Chen, Juan Helen Zhou","doi":"10.1002/alz.14328","DOIUrl":"https://doi.org/10.1002/alz.14328","url":null,"abstract":"INTRODUCTIONWe investigated the effects of multiple cerebrovascular disease (CeVD) neuroimaging markers on brain functional connectivity (FC), and how such CeVD‐related FC changes interact with plasma phosphorylated tau (p‐tau)181 (an Alzheimer's disease [AD] marker) to influence downstream neurodegeneration and cognitive changes.METHODSMultivariate associations among four CeVD markers and whole‐brain FC in 529 participants across the dementia spectrum were examined using partial least squares correlation. Interactive effects of CeVD‐related FC patterns and p‐tau181 on longitudinal gray matter volume (GMV) and cognitive changes were investigated using linear mixed‐effects models.RESULTSWe identified a brain FC phenotype associated with high CeVD burden across all markers. Further, expression of this general CeVD‐related FC phenotype and p‐tau181 contributed additively, but not synergistically, to baseline and longitudinal GMV and cognitive changes.DISCUSSIONOur findings suggest that CeVD exerts global effects on the brain connectome and highlight the additive nature of AD and CeVD on neurodegeneration and cognition.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>Effects of multiple cerebrovascular disease (CeVD) markers on functional connectivity were studied.</jats:list-item> <jats:list-item>A global network phenotype linked to high burden across CeVD markers was identified.</jats:list-item> <jats:list-item>CeVD phenotype and plasma phosphorylated tau 181 contributed additively to downstream outcomes.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"98 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}