Journal of Alzheimer's Disease最新文献

{"title":"Cerebrospinal fluid LMO4 as a synaptic biomarker linked to Alzheimer's disease pathology and cognitive decline.","authors":"Yu-Han Chen, Zhi-Bo Wang, Xi-Peng Liu, Zhi-Qi Mao","doi":"10.1177/13872877251326286","DOIUrl":"10.1177/13872877251326286","url":null,"abstract":"<p><p>BackgroundLIM-domain-only 4 (LMO4) is involved in neurodevelopment and synaptic plasticity, but its role in the pathogenesis of Alzheimer's disease (AD) remains unclear.ObjectiveTo investigate the association between cerebrospinal fluid (CSF) LMO4 levels and core AD biomarkers, neurodegeneration, and cognitive decline.MethodsWe included 703 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Associations between CSF LMO4 and AD biomarkers (Aβ₄₂, Ptau181, amyloid PET) and postmortem neuropathology were evaluated. We also explored cross-sectional and longitudinal associations between CSF LMO4 and neurodegeneration and cognitive function. Receiver operating characteristic (ROC) analysis assessed the diagnostic accuracy of CSF LMO4 in distinguishing Aβ-positive from Aβ-negative participants and amyloid PET-confirmed AD cases. Mediation analysis explored the potential mediating role of CSF LMO4 between Aβ pathology and tau pathology.ResultsLMO4 levels were decreased in participants with abnormal Aβ levels and cognitive impairment. Lower CSF LMO4 levels were associated with increased Aβ and tau pathology, brain atrophy, cognitive decline, and postmortem neuropathology. CSF LMO4 partially mediated the relationship between Aβ and tau pathology and demonstrated acceptable discriminative ability in distinguishing Aβ-positive from Aβ-negative participants and amyloid PET-confirmed AD from non-AD cases.ConclusionsCSF LMO4 plays a crucial role in the pathogenesis and progression of AD and may represent a potential therapeutic target for AD treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"216-227"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring interdisciplinary perspectives on the implementation of <i>personalized medicine</i> and <i>patient-orchestrated care</i> in Alzheimer's disease: A qualitative study within the ABOARD research project.","authors":"Tanja J de Rijke, Dianne Vasseur, Wiesje M van der Flier, Mirella Mn Minkman, Hanneke Fm Rhodius-Meester, Nicolaas A Verwey, Ellen Ma Smets, Leonie Nc Visser","doi":"10.1177/13872877251326166","DOIUrl":"10.1177/13872877251326166","url":null,"abstract":"<p><p>BackgroundThe concepts of '<i>personalized medicine</i>' and '<i>patient-orchestrated care</i>' in Alzheimer's disease (AD) lack standard conceptualization, which presents challenges for collaborative and interdisciplinary care.ObjectiveWe explored the interpretations and perspectives of professionals involved in interdisciplinary work on a large-scale project, \"ABOARD\", with the aim to implement <i>personalized medicine</i> and <i>patient-orchestrated care</i> in AD.MethodsSemi-structured interviews were conducted with 30 professionals and audio-recorded. Two researchers independently coded the data inductively, followed by a thematic analysis.ResultsAccording to professionals across different disciplinary backgrounds (mean age 45.7 years; 53.3% female), <i>personalized medicine</i> pertains to the relevant options that an individual has, informed by biomedical and psychosocial factors, whereas <i>patient-orchestrated care</i> captures factors relevant to the decision-making process. Professionals differed in their views on <i>patient-orchestrated care</i> regarding its desirability and feasibility. The concepts were viewed as similar by professionals, as both involve personal preferences while ultimately assigning responsibility to the clinician. However, implementation challenges persist, and no thematic differences were found between clinicians and other AD-related professionals.ConclusionsAD professionals have shared interpretations and perspectives on implementation of <i>personalized medicine</i> but differed in their views on patient-orchestrated care. Personal preferences are seen as part of <i>personalized medicine</i>, but not yet reflected in definitions in the AD field and beyond. Critical discussions on the challenges and existing doubts are necessary for both <i>personalized medicine</i> and <i>patient-orchestrated care</i>. Multi-level implementation changes are needed for both concepts, which warrants stakeholder involvement as well as support and resources from the entire AD field.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"120-133"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 diabetes and late-onset Alzheimer's disease and related dementia: A longitudinal cohort study integrating polygenic risk score.","authors":"Sohyun Jeong, Lisha Lin, Alvaro-Pascual Leone, Yi-Hsiang Hsu","doi":"10.1177/13872877251326107","DOIUrl":"10.1177/13872877251326107","url":null,"abstract":"<p><p>BackgroundThe inherent genetic effects were not established between type 2 diabetes (T2DM) and Alzheimer's disease and related dementia (ADRD).ObjectiveWe aimed to investigate the association between T2DM and ADRD by integrating T2DM polygenic risk score (PRS) and applying matching in every subgroup.MethodsWe utilized UK Biobank First-occurrences datasets. T2DM were 1:1 matched to non-T2DM using propensity scores generated by 8 covariates; age at diagnosis, sex, cerebrovascular disease, ischemic heart disease, hypertensive disorders, lipid disorders, obesity, and mood disorders. T2DM PRS was additionally matched in T2DM PRS matched analysis. Subgroup analyses by age at diagnosis, sex, and <i>APOE4</i> genotype were performed with the same matching criteria within each subgroup. Cox proportional hazard and Fine & Gray competing risk model were utilized.ResultsIn T2DM PRS unmatched cohort, 24,583 T2DM were 1:1 matched to non-T2DM. The mean age at diagnosis was around 62 years old, with females constituting around 40%. Up to 25-year follow-up, ADRD rate/1000 person-years was 0.88 versus 1.52 (Non-T2DM versus T2DM); PRS unmatched (cHR: 1.72, 95% CI: 1.46-2.03) and matched (cHR:1.75, 95% CI: 1.47-2.09). Except for older age onset (≥75 years), the other subgroups demonstrated significantly increased ADRD risks in T2DM. T2DM PRS was higher in non-ADRD group across all subgroups. Contrarily, T2DM PRS was higher in ADRD in younger onset group (<55 years).ConclusionsT2DM is one of the strong risk factors of ADRD but genetic T2DM effect does not contribute to ADRD risk. However, a genetic link might be present in younger age onset group.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"107-119"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143700422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lifespan of male and female APP/PS1 and APP^NL-F/NL-F mouse models of Alzheimer's disease.","authors":"Hannah Roberts, Yimin Fang, Kathleen Quinn, Tiarra Hill, Mackenzie R Peck, Andrzej Bartke, Kevin N Hascup, Erin R Hascup","doi":"10.1177/13872877251325878","DOIUrl":"10.1177/13872877251325878","url":null,"abstract":"<p><p>Alzheimer's disease (AD) disproportionately affects women, yet most preclinical research studies are male-centric. We performed lifespan analyses of male and female AD mouse models (APP/PS1 and APP^NL-F/NL-F) and their shared genetic background control (C57BL/6). Survival curves support significant sex differences between genotypes. Minimal longevity revealed increased age in male APP/PS1, and decreased age in male APP^NL-F/NL-F mice. Maximal longevity revealed an increased average age in males. Furthermore, median lifespan differed between sex and genotype. This study supports dimorphic survival in two mouse models of AD, emphasizing the need to examine mechanisms and treatments in both sexes.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"56-61"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Domestic violence in Lewy body dementia: A national study.","authors":"Emmanuel Morain, Alexandra Fayel, Philippe De Linares, Julien Dumurgier, Emmanuel Cognat, Claire Paquet","doi":"10.1177/13872877251325584","DOIUrl":"10.1177/13872877251325584","url":null,"abstract":"<p><p>A descriptive study using a transversal national online survey to evaluate the prevalence and characteristics of behavioral and psychological symptoms (BPSD) of dementia with Lewy bodies (DLB), and specifically, the perpetration of violent acts against primary caregivers. 196 responses, obtained in one month, were analyzed. Delirium, hallucinations, anxiety, and apathy were the most frequently reported BPSD symptoms (over 80% of responders). Primary caregivers expressed the highest degree of distress from agitation and aggressive behavior. Moreover, 45.9% of primary caregivers reported being the target of violent behaviors from DLB patients. No statistical association was found between the presence of BPSD and violent acts.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"44-48"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The costs of dementia care by US state: Medical spending and the cost of unpaid caregiving.","authors":"Amy Lastuka, Michael R Breshock, Kayla V Taylor, Joseph L Dieleman","doi":"10.1177/13872877251326231","DOIUrl":"10.1177/13872877251326231","url":null,"abstract":"<p><p>BackgroundThere are 5.5 million people living with dementia in the United States (US), with the cost of unpaid care making up a significant portion of the care costs.ObjectiveSummarize variation in the cost of dementia care across the US and examine the association between medical spending and costs of unpaid care at the state level.MethodsWe estimated total cost for dementia by combining recent medical spending estimates from the Disease Expenditure project and unpaid care cost estimates from Lastuka and colleagues. Hours of unpaid care were valued as the hourly wage of a home health aide. We used linear regression to measure the association between the cost of unpaid care and medical spending. The spending that would have occurred if unpaid care had been provided by professional home health care workers was used to measure the cost of unpaid care.ResultsThe annual cost of care attributable to dementia in 2019 was $53,502 (95% uncertainty interval [UI] 46,135-60,594) per case. The contribution of unpaid care to total costs varied by state, ranging from 70.2% (95% UI 64.3-75.4) in the District of Columbia to 89.9% (95% UI 87.8-91.5) in Arizona. We found that higher costs of unpaid care were associated with lower medical spending on nursing facility care.ConclusionsThe large variation in total costs of dementia shows that the economic burden of dementia care is distributed unevenly throughout the US.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"186-196"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered face perception in amnestic mild cognitive impairment: Evidence from representational similarity analysis of event-related potential.","authors":"Yanfen Zhen, Lijuan Gao, Jiu Chen, Lihua Gu, Zhijun Zhang","doi":"10.1177/13872877251326294","DOIUrl":"10.1177/13872877251326294","url":null,"abstract":"<p><p>BackgroundStructural changes in medial temporal lobes including the fusiform gyrus, a critical area in face recognition, precede the progression of amnestic mild cognitive impairment (aMCI) to Alzheimer's disease (AD). However, how the neural correlates of face processing altered in aMCI, as well as their association with cognitive impairments, remain unclear.ObjectiveUsing electroencephalogram (EEG), we explored the electrophysiological markers of face-specific visual processing alterations in aMCI and examined their relationship with cognitive deficits.MethodsWe recruited participants with aMCI (n = 32) and healthy controls (HC, n = 41) and used a passive viewing task to measure the event-related potential (ERP) in response to faces and non-face objects. To compare face processing in aMCI patients and HCs, we adopted mass univariate analysis and representational similarity analysis (RSA) to explore aMCI-related alterations in ERPs.ResultsWe found that face inversion effect (FIE) in P1 amplitudes was absent in aMCI patients. Also, compared to HCs, aMCI patients exhibited a lack of right hemisphere advantage in N170 in response to faces. Furthermore, representation similarity analysis of ERP in posterior-temporal regions revealed that aMCI patients represent face and non-face objects distinctively from HCs in the early processing stage. Additionally, the FIE in P1 amplitude positively correlated to aMCI patients' visuospatial functions.ConclusionsThese findings showed aMCI-related changes in the early perceptual processing of faces and highlights the potential of the FIE in P1 amplitude and ERP patterns over occipital-temporal regions as electrophysiological markers for aMCI and AD.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"268-279"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain and blood transcriptome-wide association studies identify five novel genes associated with Alzheimer's disease.","authors":"Makaela A Mews, Adam C Naj, Anthony J Griswold, Jennifer E Below, William S Bush","doi":"10.1177/13872877251326288","DOIUrl":"10.1177/13872877251326288","url":null,"abstract":"<p><p>BackgroundGenome-wide association studies (GWAS) have identified numerous genetic variants associated with Alzheimer's disease (AD), but their functional implications remain unclear. Transcriptome-wide association studies (TWAS) offer enhanced statistical power by analyzing genetic associations at the gene level rather than at the variant level, enabling assessment of how genetically-regulated gene expression influences AD risk. However, previous AD-TWAS have been limited by small expression quantitative trait loci (eQTL) reference datasets or reliance on AD-by-proxy phenotypes.ObjectiveTo perform the most powerful AD-TWAS to date using summary statistics from the largest available brain and blood <i>cis</i>-eQTL meta-analyses applied to the largest clinically-adjudicated AD GWAS.MethodsWe implemented the OTTERS TWAS pipeline to predict gene expression using the largest available <i>cis</i>-eQTL data from cortical brain tissue (MetaBrain; N = 2683) and blood (eQTLGen; N = 31,684), and then applied these models to AD-GWAS data (Cases = 21,982; Controls = 44,944).ResultsWe identified and validated five novel gene associations in cortical brain tissue (<i>PRKAG1</i>, <i>C3orf62</i>, <i>LYSMD4</i>, <i>ZNF439</i>, <i>SLC11A2</i>) and six genes proximal to known AD-related GWAS loci (Blood: <i>MYBPC3</i>; Brain: <i>MTCH2</i>, <i>CYB561</i>, <i>MADD</i>, <i>PSMA5</i>, <i>ANXA11</i>). Further, using causal eQTL fine-mapping, we generated sparse models that retained the strength of the AD-TWAS association for <i>MTCH2</i>, <i>MADD</i>, <i>ZNF439</i>, <i>CYB561</i>, and <i>MYBPC3</i>.ConclusionsOur comprehensive AD-TWAS discovered new gene associations and provided insights into the functional relevance of previously associated variants, which enables us to further understand the genetic architecture underlying AD risk.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"228-244"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669860","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marijuana use and subjective cognitive decline in middle-aged and older adults: Analysis of the behavioral risk factor surveillance system survey.","authors":"Xiao Chen, Peilu Wang, Yilin Tang, Susan Veldheer, Tingting Geng, Liang Sun, Yaqi Li, Xiang Gao","doi":"10.1177/13872877251327164","DOIUrl":"10.1177/13872877251327164","url":null,"abstract":"<p><p>BackgroundMarijuana impairs the brain development and function among adolescents, but little is known about whether marijuana use is associated with subjective cognitive decline (SCD) among adults.ObjectiveWe investigated the cross-sectional association between marijuana use and past-year SCD in a representative sample of US adults aged 45 years and older.MethodsThe study population included 100,685 participants from five cycles of the Behavioral Risk Factor Surveillance System (BRFSS). Participants self-reported their marijuana use in the past month and whether they experienced SCD or SCD-related functional limitations in the past year. Participants were categorized into past-month marijuana non-users and past-month marijuana users. Among users, they were further classified as occasional (<10 days) and frequent users (≥10 days). The weighted, multivariable logistic regression models were fitted to examine the association between marijuana use and past-year SCD, adjusting for age, sex, educational level, chronic disease status, and other potential confounders.ResultsThe sample included 94.2% (94,818/100,685) of past-month marijuana non-users and 5.83% (5867/100,685) of users. Among the users, 59.3% (3477/5867) were frequent users. Compared with past-month marijuana non-use, past-month marijuana use was significantly associated with higher odds of past-year SCD (OR = 1.70, 95% CI: 1.41, 2.05). The higher frequency was associated with higher odds of having past-year SCD in a dose-response manner (<i>p</i> Trend < 0.001). Similar associations remained for the SCD-related functional limitations.ConclusionsWe found that past-month marijuana users reported higher rates of past-year SCD, a finding consistent with prior literature linking marijuana use with cognitive decline. Future prospective studies are warranted to confirm these findings.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"280-291"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The unsafe profile of lecanemab.","authors":"Poul F Høilund-Carlsen, Thomas J Werner, Abass Alavi","doi":"10.1177/13872877251325891","DOIUrl":"10.1177/13872877251325891","url":null,"abstract":"<p><p>Lack of data from the US Food and Drug Administration (FDA) Adverse Event System makes analyses of the risks of newly approved anti-Alzheimer's antibodies inadequate to determine whether such risks justify the minimal clinical benefits reported. A recent disproportionate analysis in the <i>Journal of Alzheimer's Disease</i> by Ge et al. is a case in point. Among serious adverse effects, it only addresses amyloid associated imaging abnormalities, whereas the even more threatening ones, brain tissue loss and therapy-related death, are not mentioned. We urge the FDA to prioritize monitoring of all adverse effects and encourage transparency from the drug manufacturers.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"62-64"},"PeriodicalIF":3.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}