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

{"title":"Plasma amyloid-β precursor protein _669-711/amyloid-β_1-42 ratio is associated with cognition in Alzheimer's disease.","authors":"Moeko Noguchi-Shinohara, Yasuhiro Sakashita, Hiroto Nakano, Daiki Muramatsu, Sadao Hikishima, Junji Komatsu, Hidetomo Murakami, Yukiko Mori, Kenjiro Ono","doi":"10.1016/j.tjpad.2024.100003","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100003","url":null,"abstract":"<p><p>Plasma amyloid-β (Aβ) markers are significant predictors of Aβ pathology. However, their prognostic value for cognition in patients with Alzheimer's disease (AD) is unknown. We compared plasma amyloid-β precursor protein (APP)_669-711 and Aβ_1-42 levels between cognitively unimpaired participants (CU) and those with MCI due to AD and AD dementia. The CU group was divided into CU+ or CU- groups according to presence of Aβ pathology. All patients with AD exhibited Aβ pathology. The plasma APP_669-711/Aβ_1-42 ratio was significantly elevated in patients with CU+, MCI+, and AD+ compared with those with CU-. Furthermore, the plasma APP_669-711/Aβ_1-42 ratio was significantly correlated with the MMSE score (rs = -0.544, p < 0.001). Analysis of the Aβ+ group revealed that the significant relationship between MMSE score and plasma APP_669-711/Aβ_1-42 ratio remained unchanged (rs = -0.244, p = 0.027). Therefore, we conclude that the plasma APP_669-711/Aβ_1-42 ratio is associated with cognition in patients with AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100003"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972238","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":"17th Clinical Trials on Alzheimer's Disease (CTAD) Madrid, Spain, October 29 - November 1, 2024: Symposia, Oral Communications.","authors":"","doi":"10.1016/j.tjpad.2024.100043","DOIUrl":"10.1016/j.tjpad.2024.100043","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1S","pages":"100043"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979564","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":"17th Clinical Trials on Alzheimer's Disease (CTAD) Madrid, Spain, October 29 - November 1, 2024: Poster Presentations.","authors":"","doi":"10.1016/j.tjpad.2024.100044","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100044","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1S","pages":"100044"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979259","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":"Dietary supplementation and the role of phytochemicals against the Alzheimer's disease: Focus on polyphenolic compounds.","authors":"Rayees Ahmad Naik, Roshni Rajpoot, Raj Kumar Koiri, Rima Bhardwaj, Abdullah F Aldairi, Ayman K Johargy, Hani Faidah, Ahmad O Babalghith, Ahmed Hjazi, Walaa F Alsanie, Abdulhakeem S Alamri, Majid Alhomrani, Abdulaziz Alsharif, Anastasiia Shkodina, Sandeep Kumar Singh","doi":"10.1016/j.tjpad.2024.100004","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100004","url":null,"abstract":"<p><p>Alzheimer's disease is a complicated, multifaceted, neurodegenerative illness that places an increasing strain on healthcare systems. Due to increasing malfunction and death of nerve cells, the person suffering from Alzheimer's disease (AD) slowly and steadily loses their memories, cognitive functions and even their personality. Although medications may temporarily enhance memory, there are currently no permanent therapies that can halt or cure this irreversible neurodegenerative process. Nonetheless, fast progress in comprehending the cellular and molecular abnormalities responsible for neuronal degeneration has increased confidence in the development of viable prevention and treatments. All FDA-approved anti-AD medications have merely symptomatic effects and cannot cure the illness. This necessitates the pursuit of alternate treatments. Accumulating data shows that systemic neuroinflammation, oxidative stress and associated mitochondrial dysfunction play crucial roles in the etiology of AD and precede its clinical presentation. Therefore, innovative therapeutic approaches targeting these pathophysiological components of Alzheimer's disease are being explored aggressively in the present scenario. Phytochemicals such as resveratrol, curcumin, quercetin, genistein and catechins are prospective therapies owing to their capacity to alter key AD pathogenetic pathways, such as oxidative stress, neuroinflammation, and mitochondrial dysfunction. The use of new phytochemical delivery strategies would certainly provide the possibility to solve several issues with standard anti-AD medicines. In this review, the roles of phytophenolic compound-based treatment strategies for AD are discussed.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100004"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972224","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":"Liver function and Alzheimer's brain pathologies: A longitudinal study: Liver and Alzheimer's pathologies.","authors":"Jee Wook Kim, Min Soo Byun, Dahyun Yi, Joon Hyung Jung, Nayeong Kong, Yoon Young Chang, Gijung Jung, Hyejin Ahn, Jun-Young Lee, Koung Mi Kang, Chul-Ho Sohn, Yun-Sang Lee, Yu Kyeong Kim, Dong Young Lee","doi":"10.1016/j.tjpad.2024.100012","DOIUrl":"10.1016/j.tjpad.2024.100012","url":null,"abstract":"<p><strong>Importance: </strong>The neuropathological links underlying the association between changes in liver function and AD have not yet been clearly elucidated.</p><p><strong>Objective: </strong>We aimed to examine the relationship between liver function markers and longitudinal changes in Alzheimer's disease (AD) core pathologies.</p><p><strong>Design: </strong>Data from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a longitudinal cohort study initiated in 2014, were utilized.</p><p><strong>Setting: </strong>Community and memory clinic setting.</p><p><strong>Participants: </strong>Three hundred forty-seven older adults.</p><p><strong>Main outcome and measures: </strong>Participants underwent baseline and 2-year follow-up evaluations, including liver function assessments and various brain imaging techniques, such as amyloid and tau PET, FDG-PET, and MRI). Liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin] were examined as exposure variables.</p><p><strong>Results: </strong>Higher baseline ALT levels were associated with a greater increase in beta-amyloid deposition over 2 years [β = 0.166, Bonferroni-corrected P (P_B) = 0.012], while lower total bilirubin levels were associated with a greater increase in tau deposition over the same period (β = -0.570, P_B < 0.001). In contrast, AST alone showed no significant association with changes of AD pathologies.</p><p><strong>Conclusions and relevance: </strong>The findings suggest a possible link between lower liver function and the accumulation of core AD pathologies in the brain. These results also support the possibility that the liver-brain axis could be a potential target for therapeutic or preventive strategies against AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100012"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972234","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":"Artificial intelligence-enabled safety monitoring in Alzheimer's disease clinical trials.","authors":"Gustavo A Jimenez-Maggiora, Michael C Donohue, Michael S Rafii, Rema Raman, Paul S Aisen","doi":"10.1016/j.tjpad.2024.100002","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100002","url":null,"abstract":"<p><strong>Background: </strong>Investigators conducting clinical trials have an ethical, scientific, and regulatory obligation to protect the safety of trial participants. Traditionally, safety monitoring includes manual review and coding of adverse event data by expert clinicians.</p><p><strong>Objectives: </strong>Our study explores the use of natural language processing (NLP) and artificial intelligence (AI) methods to streamline and standardize clinician coding of adverse event data in Alzheimer's disease (AD) clinical trials.</p><p><strong>Design: </strong>Our quantitative retrospective study aimed to develop a gold standard AD adverse event data set, evaluate the predictive performance of NLP-based models to classify adverse events, and determine whether automated coding is more efficient, accurate, reliable, and consistent than clinician coding.</p><p><strong>Setting: </strong>Our study was conducted at the University of Southern California's Alzheimer's Therapeutic Research Institute (ATRI). ATRI serves as the clinical and data coordinating center for the Alzheimer's Clinical Trial Consortium (ACTC).</p><p><strong>Participants: </strong>We collected demographic and adverse event data from eight completed clinical trials in participants (n=1920) with symptomatic AD conducted between 2005 and 2020.</p><p><strong>Measurements: </strong>Original expert clinician-confirmed codes were used for all model performance comparisons. F1 score was used as the primary model selection metric. Final classifier performance was evaluated using predictive accuracy. Clinician effort was measured in time to code, review, and confirm coded adverse events.</p><p><strong>Results: </strong>In a sample of 1000 adverse events, AI-based AE coding achieved higher accuracy (∼20% increase in accuracy) and was more cost-effective (∼80% cost reduction) than traditional clinician coding.</p><p><strong>Conclusions: </strong>Our study results demonstrate how approaches that effectively combine AI and human expertise can improve the efficiency and quality of adverse event coding and clinical trial safety monitoring.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100002"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971971","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":"Expert opinion on Centiloid thresholds suitable for initiating anti-amyloid therapy. Summary of discussion at the 2024 spring Alzheimer's Association Research Roundtable.","authors":"Gill Farrar, Christopher J Weber, Gil D Rabinovici","doi":"10.1016/j.tjpad.2024.100008","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100008","url":null,"abstract":"<p><p>A 24-30 Centiloid (CL) threshold was collectively considered by a group of global dementia experts as a practical and implementable cut-off for anti-amyloid therapy intervention, in Alzheimer's disease patients who have been diagnosed at the mild cognitive impairment or mild dementia stage of their disease. Though additional validation is needed, knowledge of this threshold would be valuable to those involved in diagnosing and treating patients in the new AD care pathways, as well as entry into clinical trials. Therapy monitoring to determine future treatment response and assess amyloid clearance can be accomplished with amyloid PET with some technical details still to be elucidated.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100008"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972225","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":"Informal care for people with dementia in Europe.","authors":"Ron Handels, Somboon Hataiyusuk, Anders Wimo, Anders Sköldunger, Christian Bakker, Anja Bieber, Alfonso Ciccone, Carlo Alberto Defanti, Andrea Fabbo, Sara Fascendini, Lutz Frölich, Chloé Gervès-Pinquié, Manuel Gonçalves-Pereira, Kate Irving, Raymond Koopmans, Patrizia Mecocci, Paola Merlo, Bernhard Michalowsky, Oliver Peters, Yolande Pijnenburg, Óscar Ribeiro, Geir Salbaek, Larissa Schwarzkopf, Hilde Verbeek, Marjolein de Vugt, Bob Woods, Orazio Zanetti, Bengt Winblad, Linus Jönsson","doi":"10.1016/j.tjpad.2024.100015","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100015","url":null,"abstract":"<p><strong>Introduction: </strong>Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.</p><p><strong>Methods: </strong>A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia. A mixed regression model was fitted to time spent on instrumental or basic activities of daily living using disease severity and demographic characteristics.</p><p><strong>Results: </strong>Daily informal care time was 0.5 hours higher in moderate compared to mild and 1.3h higher in severe compared to mild cognitive impairment. Likewise, this was 1.2h and 2.7h for functional disability and 0.3h and 0.6h for behavioral symptoms in the same directions.</p><p><strong>Discussion: </strong>Estimates can be used in both single- and multi-domain health-economic models for dementia in European settings.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100015"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972227","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":"The impact of hypertension prevention and modification on dementia burden: A systematic review of economic studies.","authors":"Marie Lan, Ava John-Baptiste, Cassandra Curran, Feben W Alemu, Abolfazl Avan, Kelly K Anderson, Shehzad Ali","doi":"10.1016/j.tjpad.2024.100017","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100017","url":null,"abstract":"<p><strong>Aim: </strong>Neurological disorders account for the largest proportion of disability-adjusted life years globally, with dementia being the third leading cause. Hypertension has been identified as a priority, targetable risk factor for dementia. This study aimed to systematically review economic studies that examine the impact of hypertension prevention and control on the costs and outcomes of dementia.</p><p><strong>Methods: </strong>An electronic literature search was conducted using MEDLINE, EMBASE, Scopus, Web of Science, EconLit, and grey literature sources. The inclusion criteria were: 1) economic evaluation studies, including both full and partial evaluations; 2) a primary focus on dementia; and 3) evaluation of the impact of preventing or modifying hypertension on the burden of dementia. The quality of included studies was assessed using the Consensus on Health Economic Criteria (CHEC) list.</p><p><strong>Results: </strong>Twelve studies were included in the final review. Four studies were full economic evaluations, while eight were partial evaluations, with one reporting costs and seven reporting the impact on dementia prevalence. Nine studies considered hypothetical reductions in hypertension rate, while three evaluated applied hypertension-related interventions. Hypertension modification was associated with higher life expectancy and a higher average age of dementia onset. Full economic evaluations of specific hypertension modification interventions found that these interventions dominated (i.e. had lower costs and higher quality-adjusted life-years (QALY)) the status quo scenario or had an acceptable incremental cost-effectiveness ratio (ICER).</p><p><strong>Conclusions: </strong>Hypertension modification has the potential to reduce the burden of dementia in a cost-effective way. However, further economic evaluations of applied interventions are needed to determine real-world feasibility and cost-effectiveness.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100017"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972240","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":"Microglial activation states and their implications for Alzheimer's Disease.","authors":"Zachary Valiukas, Kathy Tangalakis, Vasso Apostolopoulos, Jack Feehan","doi":"10.1016/j.tjpad.2024.100013","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100013","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) of tau protein in the brain. Microglia, key immune cells of the central nervous system, play an important role in AD development and progression, primarily through their responses to Aβ and NFTs. Initially, microglia can clear Aβ, but in AD, chronic activation overwhelms protective mechanisms, leading to sustained neuroinflammation that enhances plaque toxicity, setting off a damaging cycle that affects neurons, astrocytes, cerebral vasculature, and other microglia. Current AD treatments have been largely ineffective, though emerging immunotherapies focusing on plaque removal show promise, but often overlook the role of neuroinflammation. Activated microglia display a complex range of phenotypes that can be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe the significant overlap between states. Aβ can strongly induce inflammatory activity, triggering the production of reactive oxygen species, inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, and impaired Aβ clearance. These processes contribute to neural tissue loss, manifesting as cognitive decline such as impaired executive function and memory. Conversely, anti-inflammatory activation exerts neuroprotective effects by suppressing inflammatory pathways and releasing neurotrophic factors that aid neuron repair and protection. Induction of anti-inflammatory states may offer a dual therapeutic approach to address both neuroinflammation and plaque accumulation in AD. This approach suggests potential strategies to modulate microglial phenotypes, aiming to restore neuroprotective functions and mitigate disease progression by simultaneously targeting inflammation and plaque pathology.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100013"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972236","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}