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

{"title":"Enhancing statin research for Alzheimer's prevention: Suggestions for future studies and policy implications.","authors":"Yumei Zhong, Shanshan Liu, Xiaofeng Lv","doi":"10.1016/j.tjpad.2025.100118","DOIUrl":"10.1016/j.tjpad.2025.100118","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100118"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LMTK2 and CRB1 are two novel risk genes for Alzheimer's disease in Han Chinese.","authors":"Xuewen Xiao, Hui Liu, Rui Yao, Yunni Li, Xinxin Liao, Yingzi Liu, Yafang Zhou, Junling Wang, Beisha Tang, Bin Jiao, Jinchen Li, Lu Shen, Shilin Luo","doi":"10.1016/j.tjpad.2025.100087","DOIUrl":"10.1016/j.tjpad.2025.100087","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's disease (AD) is the most prevalent neurodegenerative disease with a substantial genetic background. However, its underlying genetic architecture remains to be elucidated.</p><p><strong>Methods: </strong>In this study, we performed whole-exome sequencing in 282 familial and/or early-onset AD patients and 1086 cognitively normal controls in the Han Chinse populations. According to minor allele frequency, variants were divided into common variants (MAF ≥ 0.01) and rare variants (MAF < 0.01). Common variant-based association analysis and gene-based association test aggregating rare variants were performed by PLINK 1.9 and Sequence Kernel Association Test-Optimal, respectively. We replicated the significant results by using the same AD samples and controls from whole genome sequencing (n = 1879). Furthermore, we determined the functions of the novel AD risk genes in vitro.</p><p><strong>Results: </strong>Common variants association analysis revealed that APOE rs429358 reached statistical whole-exome significance. Gene-level aggregation testing identified that rare damaging variants in LMTK2 and CRB1 conferred risk to AD. All variants are located in highly conserved amino acid regions and are predicted to be damaging. Furthermore, functional studies showed that LMTK2 rare damaging variants (R234P and S974G) enhanced tau phosphorylation levels, tau aggregates formation, and Aβ generation. Meanwhile, the CRB1 Y556X variant caused incomplete translation of CRB1 protein and increased the Aβ42 level and Aβ42/Aβ40 ratio.</p><p><strong>Conclusion: </strong>Our findings indicated that LMTK2 and CRB1 are two novel AD risk genes in Han Chinese, which may provide promising targets for diagnosis and intervention.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100087"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143373992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of dietary fatty acids with longitudinal change in plasma-based biomarkers of Alzheimer's disease.","authors":"Serena S Hoost, Lawrence S Honig, Min Suk Kang, Aanya Bahl, Annie J Lee, Danurys Sanchez, Dolly Reyes-Dumeyer, Rafael A Lantigua, Jeffrey L Dage, Adam M Brickman, Jennifer J Manly, Richard Mayeux, Yian Gu","doi":"10.1016/j.tjpad.2025.100117","DOIUrl":"10.1016/j.tjpad.2025.100117","url":null,"abstract":"<p><strong>Background: </strong>Elevated intake of omega-3 polyunsaturated fatty acids is linked to a reduced risk of dementia in some prospective studies. However, few studies have examined the relationship between nutrient intake and plasma biomarkers of Alzheimer's disease.</p><p><strong>Objectives: </strong>We explored whether omega-3, omega-6, and monounsaturated fat intakes were associated with changes in plasma biomarkers of Alzheimer's disease over time.</p><p><strong>Design: </strong>The Washington Heights-Inwood Columbia Aging Project is a prospective cohort study (1994-2021); the data set used here includes a mean follow-up of 7.0 years.</p><p><strong>Setting: </strong>Community-based in New York City.</p><p><strong>Participants: </strong>599 dementia-free individuals at baseline who completed a 61-item food frequency questionnaire and had biomarkers measured in plasma from at least two different time points.</p><p><strong>Measurements: </strong>Fatty acid intake tertiles were computed from participant-completed 61-item Willett semi-quantitative food frequency questionnaires (Channing Laboratory, Cambridge, Massachusetts) obtained once at their baseline visit. Plasma-based biomarker assays were performed, using the single molecule array technology Quanterix Simoa HD-X platform, at baseline and follow-up visits. Generalized Estimating Equations (GEE) models were used to evaluate the association between baseline nutrient intake tertile and changes in biomarkers including phospho-tau181, amyloid-beta 42/40 ratio, phospho-tau181/amyloid-beta42 ratio, glial fibrillary acidic protein, neurofilament light chain, and two biomarker patterns derived from Principal Component Analysis (PCA1 and PCA2), with higher scores indicating a high level of neurodegeneration and low level of Alzheimer's disease burden, respectively). Models were adjusted for age, sex, race/ethnicity, education, and calculated total energy intake initially, and additionally for cerebrovascular risk factors.</p><p><strong>Results: </strong>Higher baseline omega-3 intake tertile was associated with lesser decline in PCA2 (β = 0.221, p < 0.001) and amyloid-beta 42/40 ratio (β = 0.022, p = 0.003), and a lesser rise in phospho-tau181 (β = -0.037, p = 0.001). Higher omega-6 intake tertile was linked to a lesser rise in phospho-tau181 (β = -0.050, p < 0.001) and glial fibrillary acidic protein (β = -0.028, p = 0.002). Most associations persisted after adjusting for cardiovascular risk factors.</p><p><strong>Conclusions: </strong>Higher relative baseline intake of omega-3 and omega-6 fatty acids is associated with lesser progression of blood-based biomarkers of Alzheimer's disease. Consuming healthy fatty acids may help prevent accumulation of Alzheimer's disease-related pathological changes.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100117"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12094269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664026","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 health services for the secondary prevention of cognitive impairment and dementia: Opportunities, challenges, and the business case for existing and future facilities.","authors":"Giovanni B Frisoni, Federica Ribaldi, Gilles Allali, Théophile Bieth, Andrea Brioschi Guevara, Stefano Cappa, Lisa Cipolotti, Kristian Steen Frederiksen, Jean Georges, Frank Jessen, Giacomo Koch, Hugh Masters, Augusto J Mendes, Lutz Frölich, Valentina Garibotto, Oriol Grau-Rivera, Federico E Pozzi, Dorota Religa, Ayda Rostamzadeh, Lenny Shallcross, Susan D Shenkin, Wiesje M van der Flier, Meike W Vernooij, Leonie N C Visser, Jeffrey L Cummings, Philip Scheltens, Bruno Dubois, Elena Moro, Claudio L A Bassetti, Miia Kivipelto","doi":"10.1016/j.tjpad.2025.100098","DOIUrl":"10.1016/j.tjpad.2025.100098","url":null,"abstract":"<p><p>A European Task Force has recently developed and published the concept and protocols for the setup of the innovative health offer of Brain Health Services for the secondary prevention of dementia and cognitive impairment (dBHS). dBHS are outpatient health care facilities where adult persons can find an assessment of their risk of developing cognitive impairment and dementia, have their risk level and contributing factors communicated using appropriate language supported by adequate communication tools, can decide to participate to programs for personalized risk reduction if at higher risk, and benefit from cognitive enhancement interventions. This health offer is distinct from that of currently active memory clinics. The ultimate aim of dBHS is to extend healthy life, free from cognitive impairment. Here, we (i) discuss the pertinent opportunities and challenges for those persons who want to benefit from dBHS, professionals, and wider society, (ii) describe the concepts, protocols, organizational features, and patient journeys of some currently active dBHS in Europe, and (iii) argue in favor of the business case for dBHS in Europe.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100098"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143658662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning to detect Alzheimer's disease with data on drugs and diagnoses.","authors":"Johanna Wallensten, Caroline Wachtler, Nenad Bogdanovic, Anna Olofsson, Miia Kivipelto, Linus Jönsson, Predrag Petrovic, Axel C Carlsson","doi":"10.1016/j.tjpad.2025.100115","DOIUrl":"10.1016/j.tjpad.2025.100115","url":null,"abstract":"<p><strong>Background: </strong>Integrating machine learning with medical records offers potential for early detection of Alzheimer's disease (AD), enabling timely interventions.</p><p><strong>Objectives: </strong>This study aimed to evaluate the effectiveness of machine learning in constructing a predictive model for AD, designed to predict AD with data up to three years before diagnosis. Using clinical data, including prior diagnoses and medical treatments, we sought to enhance sensitivity and specificity in diagnostic procedures. A second aim was to identify the most important factors in the machine learning models, as these may be important predictors of AD.</p><p><strong>Design: </strong>The study employed Stochastic Gradient Boosting, a machine learning method, to identify diagnoses predictive of AD using primary healthcare data. The analyses were stratified by sex and age groups.</p><p><strong>Setting: </strong>The study included individuals within Region Stockholm, Sweden, using medical records from 2010 to 2022.</p><p><strong>Participants: </strong>The study analyzed clinical data for individuals over the age of 40. Patients with an AD diagnosis (ICD-10-SE codes F00 or G30) during 2010-2012 were excluded to ensure prospective modeling. In total, AD was identified in 3,407 patients aged 41-69 years and 25,796 patients aged over 69.</p><p><strong>Measurements: </strong>The machine learning model ranked predictive diagnoses, with performance assessed by the area under the receiver operating characteristic curve (AUC). Known and novel predictors were evaluated for their contribution to AD risk.</p><p><strong>Results: </strong>AUC values ranged from 0.748 (women aged 41-69) to 0.816 (women over 69), with men across age groups falling within this range. Sensitivity and specificity ranged from 0.73 to 0.79 and 0.66 to 0.79, respectively, across age and gender groups. Negative predictive values were consistently high (≥0.954), while positive predictive values were lower (0.199-0.351). Additionally, we confirmed known risk factors as predictors and identified novel predictors that warrant further investigation. Key predictors included medical observations, cognitive symptoms, antidepressant treatment, visit frequency, and vitamin B12/folic acid treatment.</p><p><strong>Conclusions: </strong>Machine learning applied to clinical data shows promise in predicting AD, with robust model performance across age and sex groups. The findings confirmed known risk factors, such as depression and vitamin B12 deficiency, while also identifying novel predictors that may guide future research. Clinically, this approach could enhance early detection and risk stratification, facilitating timely interventions and improving patient outcomes.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100115"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Enhancing Statin Research for Alzheimer's Prevention: Suggestions for Future Studies and Policy Implications.","authors":"Zirong Ye, Jiahe Deng, Xiuxia Wu, Jingwen Cai, Sicheng Li, Xiaochun Chen, Jiawei Xin","doi":"10.1016/j.tjpad.2025.100119","DOIUrl":"10.1016/j.tjpad.2025.100119","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100119"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term cumulative physical activity associated with less cognitive decline: Evidence from a 16-year cohort study.","authors":"Suhang Song, Meng Hsuan Sung, Diana Diaz, Zhuofan Lin, Allan D Tate, Zhuo Chen, Janani Rajbhandari-Thapa, Grace Bagwell Adams, M Mahmud Khan, Ye Shen, Lisa M Renzi-Hammond, Yinzi Jin","doi":"10.1016/j.tjpad.2025.100194","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100194","url":null,"abstract":"<p><strong>Introduction: </strong>Physical activity (PA) has been reported to delay cognitive decline. However, the role of long-term, cumulative PA (cPA) in cognitive decline remains unclear.</p><p><strong>Methods: </strong>This longitudinal study obtained data from Health and Retirement Study, 2004-2020. Global cognition was operationalized as the sum of memory and executive function scores on a battery of cognitive tests. cPA was operationalized as the area under the curve of the metabolic equivalent of tasks (MET) adjusted PA. Generalized linear mixed models were fitted to examine the associations between cPA and cognitive change.</p><p><strong>Results: </strong>This study included 13,450 cognitively healthy participants, with a mean follow-up duration of 11.06 (SD=4.91) years. Higher cPA was associated with delayed declines in global cognition (p<.001), memory (p<.001) and executive function (p<.001), and such protective benefits grew over the 16-year study period. Longer PA engagement was associated with progressively delayed cognitive decline.</p><p><strong>Conclusion: </strong>PA engagement over long timeframes may better maintain cognitive performance.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100194"},"PeriodicalIF":4.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":"https://doi.org/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":4.3,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":"https://doi.org/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":4.3,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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":"https://doi.org/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":4.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}