Journal of Alzheimer's Disease最新文献

{"title":"Brain and Ocular Nutrition Conference 2025, Lecture Abstracts June 17th - 20th 2025, Endicott College, Massachusetts, USA.","authors":"","doi":"10.1177/13872877251345099","DOIUrl":"https://doi.org/10.1177/13872877251345099","url":null,"abstract":"","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":"106 1_suppl","pages":"S1-S33"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316989","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":"Association between cardiovascular-kidney-metabolic syndrome and risk of low cognitive function in older adults: Data from the NHANES 2011-2014.","authors":"Xinde Zheng, Shuzhi Lin, Zefeng Cai, Jilin Li","doi":"10.1177/13872877251352204","DOIUrl":"https://doi.org/10.1177/13872877251352204","url":null,"abstract":"<p><p>BackgroundCardiovascular-kidney-metabolic (CKM) syndrome was associated with high risk of adverse health outcomes. However, the relationship between CKM syndrome and risk of low cognitive function remains underexplored.ObjectiveTo evaluate the association between CKM syndrome and low cognitive function risk among older adults.MethodsThis study included 2158 participants aged 60 years or older from the NHANES 2011-2014. Cognitive function was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test, Digit Symbol Substitution Test (DSST), and Animal Fluency Test. Weighted multivariable logistic regression models were used to examine the association between different stages of CKM syndrome and low cognitive function risk.ResultsAmong the 2158 participants, 486 (22.5%) for the CERAD test, 492 (22.8%) for the DSST, and 456 (21.1%) for the Animal Fluency Test were diagnosed with low cognitive function. Compared with participants at CKM syndrome Stage 0, the multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) for low cognitive function assessed by CERAD test in Stages 1 to 4 were 0.76 (0.23, 2.98), 1.56 (0.79, 3.72), 1.72 (1.02, 4.10), and 2.97 (1.15, 5.42), respectively. For the DSST, the OR and 95% CI in Stages 1-4 were 0.75 (0.34, 3.42), 1.21 (0.65, 2.95), 1.30 (1.04, 3.23), and 2.21 (1.05, 4.92), respectively. No significant association was found between CKM syndrome and low cognitive function for the Animal Fluency Test.ConclusionsOlder adults at CKM stages 3-4 showed poorer cognitive performance, particularly in episodic memory, processing speed, and attention, compared to those at stage 0.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352204"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505692","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":"Impact of type 2 diabetes mellitus on differential cerebellar volume reduction in Alzheimer's disease trajectory.","authors":"Suhyung Kim, Sheng-Min Wang, Dong Woo Kang, Sunghwan Kim, Jong-Hyun Jeong, Hyukjin Yoon, Hyun Kook Lim, Yoo Hyun Um","doi":"10.1177/13872877251352208","DOIUrl":"https://doi.org/10.1177/13872877251352208","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder linked to cognitive decline. Type 2 diabetes mellitus (T2DM) is a known risk factor for AD and may contribute to cerebellar atrophy, but their relationship remains unclear.ObjectiveThis study investigated the impact of T2DM on cerebellar gray matter (GM) volume across normal cognition (NC), preclinical AD, and AD mild cognitive impairment (AD MCI) groups to explore its role in AD progression.MethodsMedical records of patients visiting St. Vincent's Hospital (September 2019-April 2024) were analyzed. Cerebellar GM volume was analyzed using voxel-based morphometry with SPM12. Group differences in cerebellar GM volume were assessed using rank analysis of covariance. Spearman's partial correlation was used to explore associations between cerebellar GM volume and cognitive function, and HbA1c levels in patients with T2DM.ResultsAD MCI patients with T2DM showed greater GM atrophy, particularly in the posterior lobe. In NC, T2DM was associated with Vermis VI volume reduction, while preclinical AD showed increased Left VIIIb volume. Amyloid-β positive (Aβ+) group has negative correlation HbA1c level and right Crus I volume. Cerebellar GM volume correlated with cognitive scores, particularly episodic memory in AD MCI patients with T2DM.ConclusionsT2DM and AD pathology contribute to cerebellar changes linked to cognitive decline. Managing T2DM may mitigate its impact on AD progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352208"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505754","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":"Comparative analysis of brain-derived tau oligomer interactomes in Alzheimer's disease, non-demented with Alzheimer's neuropathology, and primary age-related tauopathy: Implications for neurodegeneration and cognitive resilience.","authors":"Danielle Jamison, Shrinath Kadamangudi, Batbayar Tumurbaatar, Wen-Ru Zhang, Lee Palmer, Steve Kunkel, Rakez Kayed, Agenor Limon, Giulio Taglialatela","doi":"10.1177/13872877251352382","DOIUrl":"https://doi.org/10.1177/13872877251352382","url":null,"abstract":"<p><p>BackgroundIn Alzheimer's disease (AD), soluble tau oligomers are central to neurodegeneration and cognitive decline. Resilient individuals, such as those with non-demented Alzheimer's neuropathology (NDAN) or primary age-related tauopathy (PART), offer critical insights into protective mechanisms against tau-mediated neurodegeneration. NDAN individuals exhibit AD neuropathology without cognitive impairment or neurodegeneration, while PART, characterized by hippocampal- and entorhinal-restricted tau pathology, manifests with minimal-to-no amnestic changes. Brain-derived tau oligomers (BDTO) from these cohorts provide a unique platform to explore molecular pathways underlying both vulnerability and resilience to tau pathology.ObjectiveTo identify vulnerability- and resilience-associated pathways by comparing BDTO interactomes across AD, NDAN, and PART.MethodsBDTO were isolated from AD (<i>n</i> = 4; 2M, 2F), NDAN (<i>n</i> = 4; 2M, 2F), and PART (<i>n</i> = 4; 1M, 3F) hippocampal autopsy specimens using co-immunoprecipitation. Proteins were identified via liquid chromatography-tandem mass spectrometry, and non-specific interactors were filtered using SAINTq. Interactome networks and enrichment analyses were performed using Metascape. Findings were cross-referenced with the Neuropro database and existing literature on tangle-associated proteins. Key interactors were validated through reverse co-immunoprecipitation.ResultsA total of 203 proteins were identified, including eight novel interactors not previously linked to AD. All interactomes were enriched in proteins related to tau physiology and lysosomal degradation. NDAN and PART interactomes showed unique enrichment in proteins involved in cellular responses to reactive oxygen species.ConclusionsOne vulnerability-associated and 18 resilience-associated pathways that may mitigate tau-mediated neurodegeneration were identified, laying the groundwork for novel diagnostic and therapeutic strategies targeting pathological tau oligomers.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352382"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505693","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":"LCN2 of cerebrospinal fluid: A potential biomarker for diagnosis and disease progression in Alzheimer's disease.","authors":"Qing-Ning Zhang, Lan-Ke Yu, Xin-Yuan Zhang, You Wu, Heng Zhang, Jia-Lin Wu, Zhao-Hui Yao","doi":"10.1177/13872877251352411","DOIUrl":"https://doi.org/10.1177/13872877251352411","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is a neurodegenerative disorder with complex pathological features and pathogenesis, involving aspects such as amyloid-β (Aβ) deposition and neuroinflammation. AD lacks the specific biomarkers for diagnosis, which restricts diagnosis. Recent studies have indicated that Lipocalin-2 (LCN2) plays a direct or indirect role in the occurrence and development of AD. However, whether LCN2 can serve as a biomarker for AD diagnosis remains unclear.ObjectiveThis study aims to investigate the role of LCN2 in AD and its potential as a biomarker for diagnosis from a clinical perspective.MethodsWe analyze the participant demographic information, LCN2 and Aβ₄₂ levels in cerebrospinal fluid (CSF), and cortex thickness from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database with Welch ANOVA, Linear regression models and other statistical methods.ResultsLCN2 levels in the CSF of AD patients were significantly higher than those in individuals with mild cognitive impairment and no cognitive impairment. The LCN2 levels were closely associated with cognitive decline and pathological features of AD, including Aβ deposition, and reduced cortical thickness, but no tau protein phosphorylation. Age was an important confounding factor affecting the relationship between LCN2 and Aβ₄₂, while gender, years of education, and <i>APOE</i> carrier status did not have a significant impact. Furthermore, LCN2 was linked to the upregulation of inflammatory markers, indicating its potential involvement in the neuroinflammatory processes of AD.ConclusionsLCN2 is not only a potential biomarker for the early diagnosis of AD but may also play a significant role in the neurodegenerative processes associated with the disease.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352411"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505755","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":"Utility of machine learning algorithms in classification of progressive cognitive impairment in Alzheimer's disease: A retrospective cohort based on China.","authors":"Feilan Chen, Hainan Deng, Qingyu Zhang, Yanmei Liu, Yujie Zhang, Yan Zhang, Dan Li, Xinling Meng","doi":"10.1177/13872877251352510","DOIUrl":"https://doi.org/10.1177/13872877251352510","url":null,"abstract":"<p><p>BackgroundDistinct risk factors influence Alzheimer's disease (AD) stage stratification, yet effective tools for early diagnosis and prognosis remain limited, especially in middle-aged populations.ObjectiveTo develop machine learning models for predicting cognitive decline and identifying early markers of stage stratification in a middle-aged Chinese cohort.MethodsWe conducted a retrospective study on 451 patients from 2017 to 2021 (aged 45-90 years, 47.7% male). All participants were classified into normal, mild cognitive impairment (MCI), AD. Neuropsychological scale, epidemiological and laboratory parameters were collected. Four machine learning algorithms, the Least Absolute Shrinkage and Selection Operator (LASSO) regression, Random Forest, Support Vector Machine (SVM), and Extreme Gradient Boosting (XGBoost), were employed with 10-fold cross-validation. Model performance was measured using area under the receiver operating characteristics curve (ROC-AUC) and area under precision and recall curves (PR-AUC), classification confusion matrices, sensitivity, accuracy, precision, recall, F1 Score.ResultsModels demonstrated high ROC-AUC and satisfactory PR-AUC, with LASSO and SVM excelling in the MCI group (recall: 85.3% and 93.1%; F1 score: 78.4% and 78.3%, respectively). Mini-Mental State Examination (MMSE) scores differed significantly across stages, except for advanced-stage items such as naming, language repetition, and language understanding.ConclusionsThese multi-dimensional machine learning models show promise as effective tools for predicting AD stage stratification, enabling targeted monitoring and early intervention for at-risk patients.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352510"},"PeriodicalIF":3.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505756","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":"Associations of chronic stress and social support with cognition: The role of gender and race/ethnicity in the HABS-HD study cohort.","authors":"Jillian K Lee, Leigh Johnson, James R Hall, James R Bateman, Sid O'Bryant, Michelle M Mielke","doi":"10.1177/13872877251352110","DOIUrl":"https://doi.org/10.1177/13872877251352110","url":null,"abstract":"<p><p>BackgroundFew studies have examined whether chronic stress and social support are potential modifiable risk factors for Alzheimer's disease and related dementias.ObjectiveTo examine the associations of chronic stress and social support with domain-specific cognitive z-scores (attention, memory, executive functioning, and language) and assess whether gender or race/ethnicity modify these associations.MethodsParticipants included 3005 older adults (age range: 50-92) enrolled in the Health and Aging Brain Study-Health Disparities. Social support was measured using the Interpersonal Support and Evaluations List, and chronic stress measured with the Chronic Burden Scale. Linear regression models evaluated associations of chronic stress and/or social support with domain-specific cognitive z-scores, adjusting for age, education, gender, race/ethnicity, and symptoms of anxiety. Interactions between chronic stress or social support and gender or race/ethnicity in relation to cognition were assessed. Additional analyses examined the interrelationship between chronic stress and social support in relation to cognition.ResultsHigher chronic stress was associated with lower cognitive z-scores; results differed by race/ethnicity. Higher social support was associated with higher cognitive z-scores; results differed by gender and race/ethnicity. In models incorporating both chronic stress and social support, associations between social support and cognition remained, however associations between chronic stress and cognition were attenuated. A combination of high chronic stress/low social support, compared to low chronic stress/high social support, was associated with lower cognitive z-scores.ConclusionsHigh chronic stress and low social support is associated with worse cognition. Future studies are needed to understand the underlying mechanisms, with consideration of gender and race/ethnicity.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352110"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496714","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":"Estimation of events in cohort studies based on probability of cognitive impairment.","authors":"Jiyeon Park, Erin L Abner, Pei Wang, Changrui Liu, Gregory Jicha, Jordan P Harp, Frederick A Schmitt, Richard J Kryscio","doi":"10.1177/13872877251351337","DOIUrl":"https://doi.org/10.1177/13872877251351337","url":null,"abstract":"<p><p>BackgroundDementia and Alzheimer's disease-causing pathologies progress slowly over decades, and participants are recruited cognitively intact, so designing studies to observe enough cases within a feasible timeframe is important.ObjectiveIn this study, we used readily available basic predictors, age, family history, sex, and apolipoprotein E (<i>APOE</i>) 4 allele carriership, to generate cumulative incidence functions for serious cognitive impairments over years of follow-up.MethodsThe data were taken from the University of Kentucky Alzheimer's Disease Research Center longitudinal cohort established in 1989. The participants were recruited cognitively unimpaired and aged 60+. The probability of serious cognitive impairment was assessed using a multinomial logistic model, with age, the number of risk factors (family history and <i>APOE</i>4 allele) and sex as predictors.ResultsWe estimated that when two or more risk factors are present, the long-term incidence of clinical mild cognitive impairment and dementia is 2.3 to 2.7 times higher than that of the 0-risk group for both sexes, whereas the 0-risk group experienced approximately 7.9% to 11.6% longer observation times for female and 0.9% to 4.8% for male compared to the two or more risks group.ConclusionsThis study presents the expected cumulative incidence functions over varying follow-up times, and the expected observation time of serious cognitive impairment for given family history, carriership of <i>APOE</i>4, age and sex.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251351337"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496752","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":"Astrocytic lipidopathy and bioenergetic failure in ApoE4-associated late-onset Alzheimer's disease: A unifying hypothesis.","authors":"James P Garrahy","doi":"10.1177/13872877251350338","DOIUrl":"https://doi.org/10.1177/13872877251350338","url":null,"abstract":"<p><p>Late-onset Alzheimer's disease (LOAD) is traditionally attributed to amyloid-β (Aβ) accumulation and tau pathology as primary drivers of neurodegeneration. However, growing evidence suggests these may be secondary events arising from earlier disturbances in brain metabolism and lipid homeostasis. The ε4 allele of apolipoprotein E (ApoE4) remains the strongest genetic risk factor for LOAD, with carriers exhibiting both increased lifetime risk and earlier age of onset compared to ε2 or ε3 carriers. ApoE4 disrupts lipid metabolism and is associated with increased lipid droplet accumulation within astrocytes, implicating astrocytic lipidopathy in disease pathogenesis. Here, we propose a self-reinforcing pathogenic feedback loop-driven by dysregulated lipid homeostasis, chronic neuroinflammation, impaired glucose-handling, and cerebrovascular dysfunction-that culminates in astrocytic bioenergetic failure. This framework helps explain why ApoE4 carriers reach a critical bioenergetic threshold earlier in life, triggering the clinical onset of LOAD. Targeting astrocytic lipid homeostasis, through interventions such as blood-brain barrier-permeable statins, choline supplementation, or metabolic therapies, may offer novel strategies to delay disease progression or onset. Beyond AD, the framework proposed here, if validated, may have broader implications for unifying the cellular origins of age-related degenerative diseases and cancer through a shared vulnerability to progressive bioenergetic collapse.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251350338"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496715","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":"Diagnostic and prognostic multimodal prediction models in Alzheimer's disease: A scoping review.","authors":"Xin Xia, Lukas A Duffner, Christophe Bintener, Angela Bradshaw, Daphné Lamirel, Linus Jönsson","doi":"10.1177/13872877251351630","DOIUrl":"https://doi.org/10.1177/13872877251351630","url":null,"abstract":"<p><p>BackgroundMultimodal prediction models for Alzheimer's disease (AD) are emerging as promising tools for improving detection and informing prognosis.ObjectiveTo summarize the predictive objectives, constituting predictors and algorithms, and performance of existing multimodal prediction models.MethodsWe performed a systematic literature search in Medline, Embase, and Web of Science up to January 15, 2024, to identify prediction models covering the full spectrum of AD, from the preclinical stage to subjective cognitive decline (SCD), mild cognitive impairment (MCI), and AD dementia. The predictors, algorithms, and model performance of prediction models were summarized narratively by their predictive objectives. The review protocol was registered with the Open Science Framework (osf.io/zkw6g).ResultsPredicting the future progression from MCI to AD dementia was the most common objective of prediction models for AD. The second most common objective was to classify AD stages (SCD versus MCI versus AD dementia), followed by detecting the presence of amyloid, tau, or neurodegeneration. More than half of the prediction models reported an area under the receiver operating characteristic curve exceeding 0.8 and an accuracy exceeding 70%. However, 66.7% of the prediction models were developed using data from the ADNI study, and only 10.1% of the models went through external validation.ConclusionsExisting multimodal prediction models have mainly focused on the prediction of current or future AD stages and reported good performance. However, these models need to be validated using data other than the data used for model training before being considered for practical applications.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251351630"},"PeriodicalIF":3.4,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144496751","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}