Alzheimer's & Dementia最新文献

{"title":"A short version of the Everyday Cognition scale can predict clinical progression and cognitive decline.","authors":"Manchumad Manjavong, Adam Diaz, Miriam T Ashford, Anna Aaronson, Melanie J Miller, Jae Myeong Kang, Scott Mackin, Rachana Tank, Michael Weiner, Rachel Nosheny","doi":"10.1002/alz.14309","DOIUrl":"10.1002/alz.14309","url":null,"abstract":"<p><strong>Background: </strong>The Everyday Cognition scale (ECog-39) scores are associated with future cognitive decline. We investigated whether the 12-item ECog (ECog-12), which is being collected in Alzheimer's Disease Neuroimaging Initiative (ADNI)4, can predict progression.</p><p><strong>Methods: </strong>Baseline self (PT)- and study partner (SP)-ECog-12 data were extracted from the 39-item version collected in the ADNI. Weibull analysis examined the relationship between baseline ECog-12 and future clinical progression (change in Clinical Dementia Rating Sum of Boxes [CDR-SB] scores and diagnostic conversion).</p><p><strong>Results: </strong>Higher PT- and SP-ECog-12 scores were associated with faster CDR-SB worsening, with hazard ratios in cognitively unimpaired (CU) 3.34 and 9.61, mild cognitive impairment (MCI) 1.44 and 2.82, and dementia 0.93 and 1.82. They were associated with conversion from CU to MCI 3.01 and 6.24 and MCI to dementia 1.61 and 3.07.</p><p><strong>Discussion: </strong>SP-ECog-12 provided a higher prognostic value for predicting clinical progression, so this can help identify and monitor patients at risk in research and health-care settings.</p><p><strong>Highlights: </strong>The 12-item Everyday Cognition scale (ECog-12) data obtained from both raters increased diagnostic conversion risk from cognitively unimpaired to mild cognitive impairment (MCI) and from MCI to dementia. ECog-12, rated by study partners, was associated with an increased risk of Clinical Dementia Rating Sum of Boxes worsening in all diagnostic groups. Our results provide novel information about the specific scoring outputs and rater types (participant vs. study partner) of ECog-12 that can facilitate screening, prioritization, and longitudinal monitoring of the clinical progression of participants in Alzheimer's Disease Neuroimaging Initiative 4 and other Alzheimer's disease clinical studies, clinical trials, and in health-care settings.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520704","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":"2024 AA criteria for Alzheimer's disease diagnosis: Mainly anchored at Aβ not tau.","authors":"Alexis Moscoso, Nicolas Villain","doi":"10.1002/alz.14340","DOIUrl":"10.1002/alz.14340","url":null,"abstract":"","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520703","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":"Retrosplenial hypometabolism precedes the conversion from mild cognitive impairment to Alzheimer's disease.","authors":"Dylan J Terstege, Liisa A M Galea, Jonathan R Epp","doi":"10.1002/alz.14258","DOIUrl":"10.1002/alz.14258","url":null,"abstract":"<p><strong>Introduction: </strong>Not all individuals who experience mild cognitive impairment (MCI) transition through progressive stages of cognitive decline at the same rate, if at all. Previous observational studies have identified the retrosplenial cortex (RSC) as an early site of hypometabolism in MCI which seems to be predictive of later transition to Alzheimer's disease (AD).</p><p><strong>Methods: </strong>We examined N = 399 MCI subjects with baseline ¹⁸F-fluorodeoxyglucose positron emission tomography. Subjects were classified based on whether their diagnosis converted from MCI to AD.</p><p><strong>Results: </strong>Whole-brain metabolism was decreased in converters (MCI-AD). This effect was more prominent at the RSC, where MCI-AD subjects showed even greater hypometabolism. Observations of RSC hypometabolism and its utility in predicting transition from MCI-AD withstood statistical analyses in a large retrospective study.</p><p><strong>Discussion: </strong>These results point to the utility of incorporating RSC hypometabolism into predictive models of AD progression risk and call for further examination of mechanisms underlying this relationship.</p><p><strong>Highlights: </strong>Not all individuals who develop MCI will progress to AD. Individuals with MCI who progress to AD show early whole-brain hypometabolism. Early hypometabolism is particularly prominent at the RSC.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520708","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":"Latent change-on-change between amyloid accumulation and cognitive decline.","authors":"Hannah M Klinger, Brian C Healy, Bernard J Hanseeuw, Rich N Jones, Rory Boyle, Diana L Townsend, Michael J Properzi, Gillian T Coughlan, Mabel Seto, Colin Birkenbihl, Michelle E Farrell, Kathryn V Papp, Jasmeer P Chhatwal, Hyun-Sik Yang, Aaron P Schultz, Rebecca E Amariglio, Heidi I L Jacobs, Julie C Price, Keith A Johnson, Dorene M Rentz, Reisa A Sperling, Rachel F Buckley","doi":"10.1002/alz.14326","DOIUrl":"10.1002/alz.14326","url":null,"abstract":"<p><strong>Introduction: </strong>While the influence of cross-sectional β-amyloid (Aβ) on longitudinal changes in cognition is well established, longitudinal change-on-change between Aβ and cognition is less explored.</p><p><strong>Methods: </strong>A series of bivariate latent change score models (LCSM) examined the relationship between changes in ¹¹C-Pittsburgh Compound-B (PiB) positron emission tomography (PET) and the Preclinical Alzheimer's Cognitive Composite-5 (PACC-5) while adjusting for covariates, including cross-sectional medial temporal lobe (MTL) tau-PET burden. We selected 352 clinically normal older participants with up to 9 years of PiB-PET and PACC-5 data from the Harvard Aging Brain Study (HABS).</p><p><strong>Results: </strong>Aβ accumulation was associated with subsequent cognitive decline beyond the effects of cross-sectional Aβ burden. Within this model including covariates such as age, sex, and apolipoprotein ε4 (APOEε4) status, we found no evidence supporting previously published associations between cross-sectional tau-PET and cognitive intercept/slope.</p><p><strong>Discussion: </strong>Short-term Aβ changes are significantly associated with cognitive decline in clinically normal older adults and may eclipse the effect of cross-sectional Aβ and MTL tau.</p><p><strong>Highlights: </strong>Aβ accumulation is associated with subsequent cognitive decline. High Aβ burden is not the sole metric signaling impending cognitive decline. Contrary to prior work, MTL tau-PET and cognition were not associated in our models. Models of bivariate latent Aβ and cognitive change may eclipse the effects of MTL tau.</p>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520706","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":"Synaptic and extrasynaptic distribution of NMDA receptors in the cortex of Alzheimer's disease patients","authors":"Sergio Escamilla, Raquel Badillos, Joan X. Comella, Montse Solé, Isabel Pérez‐Otaño, Jose V. Sánchez Mut, Javier Sáez‐Valero, Inmaculada Cuchillo‐Ibáñez","doi":"10.1002/alz.14125","DOIUrl":"https://doi.org/10.1002/alz.14125","url":null,"abstract":"BACKGROUNDSynaptic and extrasynaptic distribution of N‐methyl‐D‐aspartate receptors (NMDARs) has not been addressed in the brain from Alzheimer´s disease (AD) subjects, despite their contribution to neurodegeneration.METHODSWe have developed a protocol to isolate synaptic and extrasynaptic membranes from controls and AD frontal cortex. We characterized the distribution of the NMDAR subunits GluN2B, GluN2A, GluN1, and GluN3A, as well as post‐translational modifications, such as phosphorylation and glycosylation.RESULTSLower levels of synaptic GluN2B and GluN2A were found in AD fractions, while extrasynaptic GluN2B and GluN1 levels were significantly higher; GluN3A distribution remained unaffected in AD. We also identified different glycoforms of GluN2B and GluN2A in extrasynaptic membranes. Synaptic Tyr1472 GluN2B phosphorylation was significantly lower in AD fractions.DISCUSSIONReduction of synaptic NMDAR subunits, particularly for GluN2B, is likely to contribute to synaptic transmission failure in AD. Additionally, the increment of extrasynaptic NMDAR subunits could favor the activation of excitotoxicity in AD.Highlights<jats:list list-type=\"bullet\"> <jats:list-item>New protocol to isolate synaptic and extrasynaptic membranes from the human cortex.</jats:list-item> <jats:list-item>Low GluN2B and GluN2A levels in Alzheimer´s disease (AD) synaptic membranes.</jats:list-item> <jats:list-item>High GluN2B and GluN1 levels in AD extrasynaptic membranes.</jats:list-item> <jats:list-item>Specific glycoforms of extrasynaptic GluN2B and GluN2A.</jats:list-item> <jats:list-item>Low phosphorylation at Tyr1472 in synaptic GluN2B in AD.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"236 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489595","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":"Associations of semaglutide with first‐time diagnosis of Alzheimer's disease in patients with type 2 diabetes: Target trial emulation using nationwide real‐world data in the US","authors":"William Wang, QuangQiu Wang, Xin Qi, Mark Gurney, George Perry, Nora D. Volkow, Pamela B. Davis, David C. Kaelber, Rong Xu","doi":"10.1002/alz.14313","DOIUrl":"https://doi.org/10.1002/alz.14313","url":null,"abstract":"INTRODUCTIONEmerging preclinical evidence suggests that semaglutide, a glucagon‐like peptide receptor agonist (GLP‐1RA) for type 2 diabetes mellitus (T2DM) and obesity, protects against neurodegeneration and neuroinflammation. However, real‐world evidence for its ability to protect against Alzheimer's disease (AD) is lacking.METHODSWe conducted emulation target trials based on a nationwide database of electronic health records (EHRs) of 116 million US patients. Seven target trials were emulated among 1,094,761 eligible patients with T2DM who had no prior AD diagnosis by comparing semaglutide with seven other antidiabetic medications. First‐ever diagnosis of AD occurred within a 3‐year follow‐up period and was examined using Cox proportional hazards and Kaplan–Meier survival analyses.RESULTSSemaglutide was associated with significantly reduced risk for first‐time AD diagnosis, most strongly compared with insulin (hazard ratio [HR], 0.33 [95% CI: 0.21 to 0.51]) and most weakly compared with other GLP‐1RAs (HR, 0.59 [95% CI: 0.37 to 0.95]). Similar results were seen across obesity status, gender, and age groups.DISCUSSIONThese findings support further studies to assess semaglutide's potential in preventing AD.HIGHLIGHTS<jats:list list-type=\"bullet\"> <jats:list-item>Semaglutide was associated with 40% to 70% reduced risks of first‐time AD diagnosis in T2DM patients compared to other antidiabetic medications, including other GLP‐1RAs.</jats:list-item> <jats:list-item>Semaglutide was associated with significantly lower AD‐related medication prescriptions.</jats:list-item> <jats:list-item>Similar reductions were seen across obesity status, gender, and age groups.</jats:list-item> <jats:list-item>Our findings provide real‐world evidence supporting the potential clinical benefits of semaglutide in mitigating AD initiation and development in patients with T2DM.</jats:list-item> <jats:list-item>These findings support further clinical trials to assess semaglutide's potential in delaying or preventing AD.</jats:list-item> </jats:list>","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"235 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488803","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":"Pathway enrichment in genome-wide analysis of longitudinal Alzheimer's disease biomarker endophenotypes.","authors":"Thea J Rosewood,Kwangsik Nho,Shannon L Risacher,Shiwei Liu,Sujuan Gao,Li Shen,Tatiana Foroud,Andrew J Saykin,","doi":"10.1002/alz.14308","DOIUrl":"https://doi.org/10.1002/alz.14308","url":null,"abstract":"INTRODUCTIONThe genetic pathways that influence longitudinal heterogeneous changes in Alzheimer's disease (AD) may provide insight into disease mechanisms and potential therapeutic targets.METHODSLongitudinal endophenotypes from the Alzheimer's Disease Neuroimaging Initiative (ADNI) representing amyloid, tau, neurodegeneration (A/T/N), and cognition were selected. Genome-wide association analysis was performed using a linear mixed model (LMM) approach, followed by gene and pathway enrichment with significant and functionally relevant SNPs.RESULTSA total of 33 and 19 statistically significant pathways were identified associating with the intercept and longitudinal trajectory, respectively. The longitudinal intercept pathways represent eight groups: immune, metabolic, cell growth and survival, DNA maintenance, neuronal signaling, RAS/MAPK/ERK signaling pathways, vesicle and lysosomal transport, and transcription modification. Longitudinal trajectory pathways represented six groups: Immune, metabolic, cell signaling, cytoskeleton, and glycosylation.DISCUSSIONLongitudinal enrichment identified pathways that uniquely associate with trajectories of key AD biomarkers and cognition, providing new insight into AD course-related mechanisms and potential new therapeutic targets.HIGHLIGHTSA systematic genome-wide analysis with longitudinal AD biomarker endophenotypes was performed. Enriched pathways were identified with functionally derived SNP to gene analysis. Fifty-two pathways were associated with longitudinal trajectory and intercept. Many of the identified pathways are specific steps in larger pathways implicated in AD. The identified pathways may provide therapeutic targets and areas for further study.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"34 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488292","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":"Enrichment for clinical trials of early AD: Combining genetic risk factors and plasma p-tau as screening instruments","authors":"Xin Wang, Xinran Wang, Steven D. Edland, Iris J. Broce, Anders M. Dale, Sarah J. Banks","doi":"10.1002/alz.14284","DOIUrl":"https://doi.org/10.1002/alz.14284","url":null,"abstract":"Identifying low-cost, minimally-invasive screening instruments for Alzheimer's disease (AD) trial enrichment will improve the efficiency of AD trials.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"93 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487840","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":"Effectiveness of psychological therapies for depression and anxiety in atypical dementia","authors":"Celine El Baou, Rob Saunders, Joshua E. J. Buckman, Marcus Richards, Claudia Cooper, Natalie L. Marchant, Roopal Desai, Georgia Bell, Caroline Fearn, Stephen Pilling, Nikki Zimmermann, Val Mansfield, Sebastian Crutch, Emilie Brotherhood, Amber John, Joshua Stott","doi":"10.1002/alz.14332","DOIUrl":"https://doi.org/10.1002/alz.14332","url":null,"abstract":"People with dementia may benefit from psychological therapies for depression or anxiety, but evidence of their effectiveness in atypical dementia is limited.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"13 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142487838","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":"Associations between AHA's Life's Essential 8 and cognition in midlife and older adults.","authors":"Lindsay Master,Yuqi Shen,Alexa C Allan,May A Beydoun,Alan B Zonderman,Michele K Evans,Orfeu M Buxton,Alyssa A Gamaldo","doi":"10.1002/alz.14294","DOIUrl":"https://doi.org/10.1002/alz.14294","url":null,"abstract":"INTRODUCTIONThis study evaluated the associations between Life's Essential 8 (LE8) and cognitive performance, and compared the strength of the relationships of Life's Simple 7 (LS7) and LE8 to cognition in midlife and older adults.METHODSParticipants (N = 1539) were from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Cross-sectional multivariable regression examined the associations between LE8 and cognition. Secondary analyses compared model performance between LE8 and LS7 measures on cognition from the same available sample.RESULTSHigher LE8 scores were associated with better global cognitive performance, working memory, and attention. The LS7 model outperformed the LE8 model on global cognitive performance, but the LE8 model outperformed the LS7 model for the working memory domain.DISCUSSIONBetter cardiovascular health (CVH) was associated with better cognitive performance among US middle-aged and older adults. However, the association between CVH and specific cognitive domains varies when using LE8 versus LS7.HIGHLIGHTSCardiovascular health (CVH) is associated with cognitive performance. Life's Essential 8 (LE8) is a new construct to quantify CVH. Associations between LE8 and cognition were assessed. Higher LE8 was associated with better global cognitive performance. Higher LE8 was also associated with better working memory and attention.","PeriodicalId":7471,"journal":{"name":"Alzheimer's & Dementia","volume":"235 1","pages":""},"PeriodicalIF":14.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489733","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}