The Journal of Prevention of Alzheimer's Disease最新文献

{"title":"Serum BDNF and progression to MCI in cognitively normal older adults: A prospective cohort study.","authors":"Kyungtae Kim, Min Soo Byun, Dahyun Yi, Joon Hyung Jung, Bo Kyung Sohn, Gijung Jung, Hyejin Ahn, Jun-Young Lee, Yun-Sang Lee, Yu Kyeong Kim, Kwangsik Nho, Dong Young Lee","doi":"10.1016/j.tjpad.2025.100210","DOIUrl":"10.1016/j.tjpad.2025.100210","url":null,"abstract":"<p><strong>Background: </strong>Brain-derived neurotrophic factor (BDNF) is the most abundant neurotrophin in the mammalian brain. Preclinical studies suggest that BDNF influences the pathophysiology of Alzheimer's disease. In humans, higher blood BDNF levels have been associated with a lower risk of dementia. However, the relationship between serum BDNF levels and the progression to mild cognitive impairment (MCI) in cognitively normal (CN) individuals remains uncertain.</p><p><strong>Objectives: </strong>To examine whether higher serum BDNF levels in CN older adults are associated with a reduced incidence of MCI over a 4-year follow-up period and to identify potential moderators of this relationship.</p><p><strong>Design: </strong>Longitudinal analyses were conducted using follow-up data from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's Disease, an ongoing prospective cohort study. Data were collected from January 1, 2014, to May 31, 2021, and analyzed from May 1, 2023, to September 30, 2023.</p><p><strong>Setting: </strong>Community and memory clinic setting.</p><p><strong>Participants: </strong>A total of 274 CN older adults aged 55-90 years were included at baseline.</p><p><strong>Measurement: </strong>Progression to MCI over the 4-year follow-up period.</p><p><strong>Results: </strong>Among the 274 participants, 26 developed MCI during follow-up. The high BDNF group had a significantly lower incidence of MCI compared to the low BDNF group (hazard ratio [HR], 0.27; 95 % confidence interval [CI], 0.11-0.69; P = 0.006). This association persisted even after adjusting for BDNF Val66Met polymorphism, amyloid PET positivity, vascular risk factors, cholesterol levels, triglycerides, homocysteine, BMI, smoking, alcohol, TBI history, CES-D, and MMSE scores (HR, 0.14; 95 % CI, 0.05-0.40; P < 0.001). Subgroup analyses further revealed that the association was significant only in women (HR, 0.12; 95 % CI, 0.03-0.48; P = 0.002), individuals aged <75 years (HR, 0.16; 95 % CI, 0.03-0.77; P = 0.022), those with less than a college degree (HR, 0.23; 95 % CI, 0.07-0.74; P = 0.013), and amyloid PET-negative (HR, 0.29; 95 % CI, 0.11-0.72; P = 0.014) individuals.</p><p><strong>Conclusions: </strong>These findings suggest a protective role of BDNF against clinical progression to MCI in cognitively healthy older individuals. This effect appears to be more prominent in women, as well as in relatively younger, less educated, and amyloid PET-negative individuals.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100210"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144143589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum BDNF and progression to MCI in cognitively normal older adults A prospective cohort study.","authors":"Gary A Rosenberg","doi":"10.1016/j.tjpad.2025.100254","DOIUrl":"10.1016/j.tjpad.2025.100254","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100254"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma p-tau217 predicting brain-wide tau accumulation in preclinical AD.","authors":"Hasom Moon, Xi Chen","doi":"10.1016/j.tjpad.2025.100252","DOIUrl":"10.1016/j.tjpad.2025.100252","url":null,"abstract":"<p><strong>Background: </strong>Recently developed blood test of Alzheimer's disease (AD) has been recognized as a promising alternative to CSF and PET, as it is noninvasive, cost-effective, and more accessible. Particularly, plasma p-tau217 shows high sensitivity in detecting β-amyloid (Aβ) and tau positivity in early AD. However, the potential value of p-tau217 in revealing Aβ and tau distribution and predicting future development has not been studied.</p><p><strong>Objectives: </strong>We investigated the dose-response associations between p-tau217 and regional Aβ and tau measured by PET, as well as the longitudinal prediction of p-tau217 for prospective Aβ and tau accumulation measured by longitudinal PET.</p><p><strong>Design: </strong>Cross-sectional and longitudinal analyses.</p><p><strong>Setting: </strong>We used data in Anti-Amyloid Treatment in Asymptomatic Alzheimer's disease (A4) study (N = 333) for primary analyses and Alzheimer's Disease Neuroimaging Initiative (ADNI) (N = 410) for validation.</p><p><strong>Participants: </strong>Cognitively unimpaired older adults (N = 333) from A4 study and cognitively unimpaired older adults (N = 222), mild cognitive impairment (N = 114), and dementia (N = 74) from ADNI.</p><p><strong>Measurements: </strong>Plasma p-tau217 was measured using Lilly (A4) and Fujirebio (ADNI) assays. ^18-FFlorbetapir PET and ^18-FFlortaucipir PET measured regional Aβ and tau.</p><p><strong>Results: </strong>Plasma p-tau217 was associated with concurrent Aβ in most cortical regions and tau in temporo-parietal cortices. Longitudinally, p-tau217 predicted brain-wide tau accumulation in widespread cortical regions in preclinical AD, but not Aβ change anywhere.</p><p><strong>Conclusions: </strong>Plasma p-tau217 shows dose-response, brain-wide relationships with concurrent Aβ and future tau development in preclinical AD, suggesting its potential in disease trajectory monitoring and large-scale screening for individuals approaching certain biological stages of AD in clinical trials.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100252"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321616/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to letter regarding \"hearing loss, diet, and cognitive decline: Interconnections for dementia prevention\".","authors":"Xiaoran Liu, Uzma S Akhtar","doi":"10.1016/j.tjpad.2025.100188","DOIUrl":"10.1016/j.tjpad.2025.100188","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100188"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321632/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic alterations in peripheral blood B Lymphocytes of patients with Alzheimer's Disease.","authors":"Meng-Ting Wang, Ye-Ran Wang, Gui-Hua Zeng, Xiao-Qin Zeng, Zhang-Cheng Fei, Jia Chen, Jin Zhou, Xin-Peng Li, Zhi-Qiang Xu, Yan-Jiang Wang, Yu-Hui Liu","doi":"10.1016/j.tjpad.2025.100135","DOIUrl":"10.1016/j.tjpad.2025.100135","url":null,"abstract":"<p><strong>Introduction: </strong>Dysfunction of humoral immunity has been implicated in the pathogenesis of Alzheimer's disease (AD). The distribution of B lymphocyte subsets and their clinical relevance in AD remain unclear.</p><p><strong>Objective: </strong>In this study, we aimed to investigate the distribution of peripheral blood B lymphocyte subsets and their relevance with cognition and biomarkers in AD.</p><p><strong>Design, setting, and participants: </strong>We evaluated the immunophenotype of peripheral B lymphocytes in 27 AD patients confirmed by PET-Amyloid scan and 32 cognitively normal controls.</p><p><strong>Results: </strong>The phenotype of B lymphocytes is altered in AD patients. AD patients exhibit a decrease in both the numbers and proportions of switched memory (SwM) B cells and double-negative (DN) B cells. The proportion of unswitched memory (USwM) B cells was increased after in vitro stimulation. Additionally, B cells that produce proinflammatory cytokines including GM-CSF, IFN-γ, and TNF-α are increased, while those that produce the anti-inflammatory cytokine IL-10 are decreased in AD patients after in vitro stimulation. These alterations in B cell populations were linked to cognitive functions and biomarkers, including Aβ42/40 and pTau181, in AD patients.</p><p><strong>Discussion: </strong>This study reveals an altered B-lymphocyte phenotype in AD patients, marked by functional and compositional dysregulation. Further research incorporating mechanistic, longitudinal, and functional studies is needed to determine whether these immune perturbations directly contribute to AD pathogenesis or arise as secondary effects of neurodegeneration.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100135"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143693314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain photobiomodulation: a potential treatment in Alzheimer's and Parkinson's diseases.","authors":"Guillaume Blivet, Benjamin Touchon, Hugo Cavadore, Sara Guillemin, Frédéric Pain, Michael Weiner, Marwan Sabbagh, Cécile Moro, Jacques Touchon","doi":"10.1016/j.tjpad.2025.100185","DOIUrl":"10.1016/j.tjpad.2025.100185","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) and Parkinson's Disease (PD) are common neurodegenerative diseases, characterized by the progressive loss of synapses and neurons, leading to cognitive and motor decline. Their pathophysiology includes cerebral lesions, oxidative stress, neuroinflammation as well as brain-gut axis microbiota dysbiosis. Preclinical investigations demonstrated that brain photobiomodulation (bPBM) reduces oxidative stress and inflammation, increases cerebral blood flow and enhance neurogenesis and synaptogenesis, which makes bPBM a promising treatment in AD and PD. This review focuses on the clinical application of bPBM in AD and PD. It aims to provide a scientific overview of the current clinical knowledge, review recent clinical studies findings, and describe future directions and upcoming clinical studies. So far, several clinical studies investigated bPBM therapy, at various parameters, both in patients with AD and related dementia, and PD. All demonstrate bPBM safety and bring valuable clinical information regarding efficacy, with particularly promising results in AD. However, their exploratory design and inconsistent quality lead to a low level of evidence, which currently does not support the widespread use of bPBM in clinical practice. Future clinical research should address two gaps: the need for robust double-blinded RCTs vs sham with a higher number of patients and a longer follow-up, and the need for research focusing on dosimetry to determine which bPBM parameters are optimal. The ongoing or unpublished clinical studies on bPBM should fill in this gap.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100185"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using machine learning and electronic health record (EHR) data for the early prediction of Alzheimer's Disease and Related Dementias.","authors":"Sonia Akter, Zhandi Liu, Eduardo J Simoes, Praveen Rao","doi":"10.1016/j.tjpad.2025.100169","DOIUrl":"10.1016/j.tjpad.2025.100169","url":null,"abstract":"<p><strong>Background: </strong>Over 6 million patients in the United States are affected by Alzheimer's Disease and Related Dementias (ADRD). Early detection of ADRD can significantly improve patient outcomes through timely treatment.</p><p><strong>Objective: </strong>To develop and validate machine learning (ML) models for early ADRD diagnosis and prediction using de-identified EHR data from the University of Missouri (MU) Healthcare.</p><p><strong>Design: </strong>Retrospective case-control study.</p><p><strong>Setting: </strong>The study used de-identified EHR data provided by the MU NextGen Biomedical Informatics, modeled with the PCORnet Common Data Model (CDM).</p><p><strong>Participants: </strong>An initial cohort of 380,269 patients aged 40 or older with at least two healthcare encounters was narrowed to a final dataset of 4,012 ADRD cases and 119,723 controls.</p><p><strong>Methods: </strong>Six ML classifier models: Gradient-Boosted Trees (GBT), Light Gradient-Boosting Machine (LightGBM), Random Forest (RF), eXtreme Gradient-Boosting (XGBoost), Logistic Regression (LR), and Adaptive Boosting (AdaBoost) were evaluated using Area Under the Receiver Operating Characteristic Curve (AUC-ROC), accuracy, sensitivity, specificity, and F1 score. SHAP (SHapley Additive exPlanations) analysis was applied to interpret predictions.</p><p><strong>Results: </strong>The GBT model achieved the best AUC-ROC scores of 0.809-0.833 across 1- to 5-year prediction windows. SHAP analysis identified depressive disorder, age groups 80-90 yrs and 70-80 yrs, heart disease, anxiety, and the novel risk factors of sleep apnea, and headache.</p><p><strong>Conclusion: </strong>This study underscores the potential of ML models for leveraging EHR data to enable early ADRD prediction, supporting timely interventions, and improving patient outcomes. By identifying both established and novel risk factors, these findings offer new opportunities for personalized screening and management strategies, advancing both clinical and informatics science.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100169"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the difference between cystatin C- and creatinine-based estimated glomerular filtration rate with cerebral small vessel disease: A large prospective cohort study.","authors":"Zhiming Li, Fei Wang, Jincheng Liu, Benbo Xiong, Han Wang, Zijie Wang, Xiao Hu, Qi Li","doi":"10.1016/j.tjpad.2025.100190","DOIUrl":"10.1016/j.tjpad.2025.100190","url":null,"abstract":"<p><strong>Background and objective: </strong>It remains unclear whether the difference between the estimated glomerular filtration rate based on cystatin C and creatinine (eGFRdiff) is associated with cerebral small vessel disease (CSVD). We investigated the correlation of eGFRdiff with SCVD and further evaluated the mediating role of blood pressure.</p><p><strong>Methods: </strong>This prospective cohort study included 35,590 neurologically healthy participants at baseline (2006 to 2010) from the UK Biobank. eGFRdiff is divided into two indicators: absolute difference (eGFRabdiff) and ratio (eGFRrediff) based on the calculation between cystatin C and creatinine. CSVD was assessed by calculating white matter hyperintensity volume (WMHV) from T2-FLAIR brain MRI scans (conducted between 2014 and 2021), with values normalized to intracranial volume and log-transformed. Multiple linear regression models and mediation analysis was used to evaluate the associations of eGFRdiff with WMHV.</p><p><strong>Results: </strong>Participants with negative eGFRabdiff had higher WMHV (β = 0.07, 95 % confidence interval [CL] = 0.04 ∼ 0.10), while participants with positive eGFRabdiff had smaller WMHV (β = -0.05, 95 %CL = -0.09 ∼ -0.02), compared to midrange eGFRabdiff group. Meanwhile, participants with eGFRrediff ≤ 0.7 had higher WMHV compared with participants with eGFRrediff > 0.7 (β = 0.08, 95 %CL = 0.01∼ 0.15) .In addition, hypertension mediated the associations between eGFRdiff and WMHV (12.6 % ∼13.2 %).</p><p><strong>Conclusion: </strong>eGFRdiff was independently associated with WMHV. Our findings suggested that monitoring eGFRdiff has potential benefits in identifying the burden of CSVD in the general population in future.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100190"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytes provide a unique biomarker for Alzheimer's and other pathologies.","authors":"Eric Siemers","doi":"10.1016/j.tjpad.2025.100233","DOIUrl":"10.1016/j.tjpad.2025.100233","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100233"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monitoring of amyloid related imaging abnormalities: SWI vs T2*-GRE.","authors":"Diana M Sima, Thanh Vân Phan, Ana M Franceschi, Wende N Gibbs, Frederik Barkhof, Philip Scheltens, Stephen Salloway, Jeffrey Cummings, Wim Van Hecke, Dirk Smeets","doi":"10.1016/j.tjpad.2025.100220","DOIUrl":"10.1016/j.tjpad.2025.100220","url":null,"abstract":"<p><p>Amyloid-β-directed monoclonal antibody therapies may lead to amyloid-related imaging abnormalities (ARIA). Clinical trials that formed the basis for the ARIA radiographic severity grading scale adopted by the approved drugs' labels utilized T2* gradient recalled echo (T2*-GRE) images for ARIA-hemorrhagic (ARIA-H) assessment. Little is known about the application of susceptibility-weighted imaging (SWI) to ARIA-H assessment. We exploited comparative studies on the usage of SWI instead of 2D T2*-GRE and simulated the impact of SWI's higher sensitivity on the derived ARIA-H severity distribution for three approved drugs. The simulations indicated that the two sequences are not equivalent when grading ARIA-H severity and that the rate of therapy discontinuation would increase by more than 50% compared to the rates reported in the drugs' prescribing information. This should be taken into consideration whenever SWI is applied for ARIA safety monitoring. Appropriate imaging guidelines are needed to enhance management of amyloid-β-directed antibody therapies.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100220"},"PeriodicalIF":7.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12321608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}