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

{"title":"Salivary levels of amyloid beta reflect brain amyloid beta burden in cognitively-normal older adults.","authors":"Alison R Bamford, Jenna N Adams, Soyun Kim, Lisa M Taylor, Nandita Tuteja, Liv C McMillan, Negin Sattari, Ivy Y Chen, Miranda G Chappel-Farley, Yuritza Escalante, Alyssa L Lawrence, Novelle J Meza, Destiny E Berisha, Abhishek Dave, Rond Malhas, Mark Mapstone, Bryce A Mander, Michael A Yassa, Elizabeth A Thomas","doi":"10.1016/j.tjpad.2025.100216","DOIUrl":"10.1016/j.tjpad.2025.100216","url":null,"abstract":"<p><strong>Background: </strong>Amyloid beta (Aβ) plaque burden, as measured by positron emission tomography (PET), is increasingly being used as a biomarker for Alzheimer's disease (AD) as well as a screening or monitoring tool for clinical trials with amyloid-lowering drugs. However, PET imaging is expensive, invasive and not widely available for all patients, necessitating alternative means to assess brain Aβ accumulation.</p><p><strong>Objectives: </strong>In this study, we measured levels of Aβ42, Aβ40 and Aβ38 in saliva samples from cognitively unimpaired older adults (n=93; 61.7 % female; mean age = 70.1 ± 6.6 years) using the Mesoscale Discovery platform, carefully considering preanalytical variables, including timing of sample collection, blood contamination and sample concentration. We next determined the relationships between Aβ peptide levels and Aβ plaque burden within the brain, determined using 18F-florbetapir (FBP) PET.</p><p><strong>Results: </strong>We found that salivary levels of Aβ38 and Aβ42, but not Aβ40 nor the Aβ42/Aβ40, were significantly positively correlated with the global mean FBP standardized uptake value ratio (SUVR), before and after adjusting for age, sex and time of day of saliva sample collection (r=0.523/0.544, p=0.001/0.002 and r=0.316/0.32, p=0.031/0.044, for Aβ38 and Aβ42, respectively). Similar results were observed when Aβ values were analyzed as a ratio to the total protein levels in each sample and when tested in saliva samples that were collected during a restricted morning time window. Using composite regions which represent cortical regions vulnerable to Aβ accumulation in early, intermediate, and late stages of AD, we found that Aβ38 showed the most robust correlation with FBP SUVRs from early-accumulating brain regions (r=0.510; p<0.001). In contrast to the observed effects in saliva, plasma levels of Aβ42 measured from a subset of the participants showed a significant negative correlation to mean FBP SUVR. Using logistic regression analysis to determine whether any salivary Aβ species could predict brain Aβ burden, we found that salivary levels of Aβ38 in combination with age, sex, sample timing and APOE genotype could predict Aβ-PET positivity with an area under the curve = 0.950 (95 % confidence interval, 0.876-1.0; p<0.0001).</p><p><strong>Conclusions: </strong>Our findings suggest that salivary Aβ38 and/or Aβ42 could have relevance as a non-invasive, and more widely applicable biomarker, for utility in clinical studies on AD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100216"},"PeriodicalIF":4.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12252581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144267266","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":"Bridging the gap: A conversion framework for CDR-SB and MoCA scores in Alzheimer's disease and related dementia.","authors":"Babak Haji, Quanwu Zhang, Amir Abbas Tahami Monfared","doi":"10.1016/j.tjpad.2025.100226","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100226","url":null,"abstract":"<p><strong>Background: </strong>Accurate assessment of cognitive impairment is essential to effective Alzheimer's disease (AD) management and research. However, the absence of validated methods to translate scores between widely used instruments-such as the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) in trials and the Montreal Cognitive Assessment (MoCA) in clinical practice-poses a significant barrier. This limits data harmonization, impedes cross-study comparability, and complicates the integration of clinical and research evidence. Bridging this gap is critical for consistent staging, longitudinal monitoring, and data-driven decision-making in AD and related dementias.</p><p><strong>Objectives: </strong>To develop and validate bidirectional score conversion tables between CDR-SB and MoCA using a large, diverse cohort spanning the full spectrum of cognitive function.</p><p><strong>Design: </strong>Retrospective, cross-sectional analysis using equipercentile equating with log-linear smoothing. Optimal smoothing parameters were selected by minimizing mean squared error, Akaike Information Criterion, and Bayesian Information Criterion. Concordance was assessed using Spearman's rank correlation and Bland-Altman plots.</p><p><strong>Setting: </strong>National Alzheimer's Coordinating Center (NACC), aggregating standardized assessments from 35 U.S.-based Alzheimer's Disease Research Centers.</p><p><strong>Participants: </strong>23,717 individuals (59,871 visits) with same-day CDR-SB and MoCA assessments from January 2015 to September 2024, spanning normal cognition, mild cognitive impairment (MCI), and dementia.</p><p><strong>Intervention: </strong>None; this was a secondary analysis of existing data.</p><p><strong>Measurements: </strong>Primary measures included CDR-SB (0-18; higher = greater impairment) and MoCA (0-30; higher = better cognition). Bidirectional crosswalk tables were derived using equipercentile equating.</p><p><strong>Results: </strong>CDR-SB and MoCA scores showed strong inverse correlation (Spearman's ρ = -0.68; p < 0.001). Crosswalk tables demonstrated good agreement across the cognitive spectrum and performed consistently in the full cohort and an AD-specific subgroup.</p><p><strong>Conclusions: </strong>This study provides the first validated, bidirectional CDR-SB-MoCA crosswalk, supporting data harmonization and consistent interpretation of cognitive severity across research and clinical settings.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100226"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249689","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":"Physical activity and Alzheimer's disease: a call for evidence incorporation.","authors":"Juan Luis Sánchez-Sánchez, Philipe de Souto Barreto","doi":"10.1016/j.tjpad.2025.100225","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100225","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100225"},"PeriodicalIF":4.3,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249693","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":"Household fuel use and motoric cognitive risk syndrome among older adults: Evidence from cohort study and life course analysis.","authors":"Guanghui Cui, Shaojie Li, Weiwei Li, Xuezhi Zhang","doi":"10.1016/j.tjpad.2025.100227","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100227","url":null,"abstract":"<p><strong>Background: </strong>Motoric cognitive risk syndrome (MCRS) is a predementia syndrome, and its prevention is valuable for reducing the incidence of dementia. However, few studies have focused on the association between indoor air pollution caused by household cooking fuel use and MCRS. This study aimed to investigate whether clean cooking fuel use is associated with reduced MCRS risk and whether the timing of clean fuel adoption across the life span is associated with MCRS prevalence.</p><p><strong>Methods: </strong>We used data from the China Health and Retirement Longitudinal Study. A prospective cohort analysis (n = 4251) examined baseline fuel use (2011) and incident MCRS over four years. A cross-sectional life course analysis (n = 6964) linked retrospective fuel use histories (2014 life history survey) to MCRS status in 2015. Modified Poisson regression was used to estimate relative risks (RRs) and 95 % confidence intervals (CIs), adjusting for covariates.</p><p><strong>Results: </strong>In the cohort study, clean fuel use at baseline was associated with a reduced risk of MCRS (RR = 0.76; 95 % CI: 0.61-0.96). Lower risks were also observed among participants who transitioned from solid to clean fuels and those who consistently used clean fuels. In the life course analysis, clean fuel adoption in early or middle adulthood was linked to lower MCRS prevalence.</p><p><strong>Conclusion: </strong>Clean fuel use for cooking and transitioning from solid to clean fuels decreases MCRS risk among older adults. Moreover, earlier adoption of clean cooking fuels is associated with a lower prevalence of MCRS in later life.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100227"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249692","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 patient pathway for mild cognitive impairment due to Alzheimer's disease in Asia: Current practices, barriers, and expert recommendations for optimization.","authors":"Seong Hye Choi, SangYun Kim, Paulus Anam Ong, Ai Vyrn Chin, Jacqueline Dominguez, Christopher Li-Hsian Chen, Vorapun Senanarong, Chaur-Jong Hu, Manjari Tripathi, Vincent Mok, Gandan Jiang, Amitabh Dash","doi":"10.1016/j.tjpad.2025.100215","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100215","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The age-standardized prevalence of Alzheimer's disease in Asia has increased rapidly in recent years. Disease-modifying treatments that can slow disease progression are now becoming available for patients with early-stage Alzheimer's disease, including those with mild cognitive impairment. However, challenges in diagnosis and assessment for these patients remain.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study characterized the care pathway for mild cognitive impairment due to Alzheimer's disease in Asia, including barriers to care, and considered the future treatment landscape, with the aim of making recommendations for optimizing the care pathway in readiness for the availability of new disease-modifying treatments.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Qualitative study based on semi-structured interviews.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Interviews were conducted with physicians in general/tertiary hospitals in Hong Kong, India, Indonesia, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand. Physicians from mainland China and Japan were not included.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;Physicians managing patients with mild cognitive impairment.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;Number and/or proportion of participants providing a given response, and numerical estimates provided by interview participants.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Forty-four physicians, primarily neurologists (n = 31; 70.5 %), were interviewed. Participants managed a median of 67.5 patients with mild cognitive impairment per month, of whom 24.0-87.5 % had mild cognitive impairment due to Alzheimer's disease. Clinical investigations routinely comprised brief neuropsychological assessments, such as the Mini-Mental State Examination (n = 41), as well as neurological tests (n = 39) and magnetic resonance imaging (n = 40). Except in Korea, comprehensive neuropsychological test batteries and amyloid positron emission tomography were seldom conducted in Asia. Most patients with mild cognitive impairment due to Alzheimer's disease were treated with nootropics and/or acetylcholinesterase inhibitors (Korea, 96 %; all other regions, 69 %), and almost all were recommended a non-pharmacological treatment (Korea, 93 %; all other regions, 100 %). Detection of mild cognitive impairment due to Alzheimer's disease was considered prompt in Korea but suboptimal in other regions (n = 16) owing to low disease awareness among patients. Barriers to assessment and diagnosis included delayed healthcare visits for initial assessment (n = 7), neuroimaging backlogs (n = 6), and insufficient neuropsychology resources (n = 13). Access to amyloid biomarker tests, including amyloid positron emission tomography, cerebrospinal fluid analysis, and blood tests, was limited in regions other than Korea.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The survey findings showed that screening and diagnostic processes for mild cognitive impairment due to Alzheimer's disease in Asia ","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100215"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249703","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":"Erratum to \"Biofluid biomarker changes following treatment with sabirnetug (ACU193) in INTERCEPT-AD, a phase 1 trial in early Alzheimer's disease\" [J Prev Alzheimers Dis 2025;12(4): 100082].","authors":"Erika N Cline, Daniel Antwi-Berko, Karen Sundell, Elizabeth Johnson, Maddelyn Hyland, Hao Zhang, Hugo Vanderstichele, June Kaplow, Robert A Dean, Erik Stoops, Eugeen Vanmechelen, Marleen J A Koel-Simmelink, Charlotte E Teunissen, Gopalan Sethuraman, Todd Feaster, Eric Siemers, Jasna Jerecic","doi":"10.1016/j.tjpad.2025.100217","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100217","url":null,"abstract":"","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100217"},"PeriodicalIF":4.3,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249690","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":"Utility of plasma GFAP as a secondary endpoint for clinical trials in Alzheimer's disease.","authors":"Sarah Abbas, Pamela C L Ferreira, Bruna Bellaver, Guilherme Povala, Francieli Rohden, Cristiano Schaffer Aguzzoli, Hussein Zalzale, João Pedro Ferrari-Souza, Douglas T Leffa, Firoza Z Lussier, Carolina Soares, Guilherme Bauer-Negrini, Markley Silva Oliveira-Junior, Matheus Scarpatto Rodrigues, Pampa Saha, Emma Ruppert, Marina Scop Medeiros, Cécile Tissot, Joseph Therriault, Nesrine Rahmouni, Stijn Servaes, Andrea L Benedet, Nicholas J Ashton, Dana L Tudorascu, Serge Gauthier, Helmet Karim, Chang Hyung Hong, Hyun Woong Roh, Eduardo R Zimmer, Thomas K Karikari, Henrik Zetterberg, Kaj Blennow, Anum Saeed, Sang Joon Son, Pedro Rosa-Neto, Tharick Pascoal","doi":"10.1016/j.tjpad.2025.100205","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100205","url":null,"abstract":"<p><strong>Background: </strong>Clinical trials have recently incorporated plasma glial fibrillary acidic protein (GFAP) as an exploratory endpoint. To include plasma GFAP as a secondary endpoint, it is essential to characterize its longitudinal progression in target populations.</p><p><strong>Objective: </strong>To evaluate the potential use of plasma GFAP changes as a secondary endpoint in Alzheimer's disease trials.</p><p><strong>Methods: </strong>We longitudinally evaluated plasma GFAP in individuals with amyloid-beta (Aβ)-PET scans at baseline in three well-characterized cohorts. Cox proportional hazards regression tested the association between changes in plasma GFAP and cognitive function. Analysis of the 95 % confidence interval of annualized change in plasma GFAP provided statistical inference for a significant longitudinal change. Effect size was calculated as the group mean divided by the standard deviation (SD). We estimated the sample size needed to test a 25% drug effect with 80% power on reducing changes in GFAP.</p><p><strong>Results: </strong>We assessed 487 individuals [176 cognitively unimpaired (CU; 29% Aβ positive) and 311 cognitively impaired (CI; 51% Aβ positive)] with some degree of cerebrovascular disease (Fazekas 1-3), over a mean (SD) follow-up of 1.84 (0.46) years. Changes in plasma GFAP were significantly associated with worsening in Clinical Dementia Rating sum of boxes (CDR-SB) score across the population (p < 0.0001). In CU, only Aβ positive individuals showed significant changes in GFAP (p < 0.001). On the other hand, both CI Aβ positive and negative individuals showed longitudinal progression in GFAP levels (p < 0.0001). The effect size of changes in plasma GFAP was higher in CU Aβ positive (0.44), followed by CI Aβ positive (0.42) and CI Aβ negative (0.38). Clinical trials focusing on CU Aβ positive would require 1320 individuals per study arm, while focusing on CI Aβ positive would require 1440 individuals per study arm.</p><p><strong>Conclusion: </strong>Plasma GFAP increased in parallel with cognitive decline, making it a candidate for monitoring disease progression in trials aimed at mitigating cognitive deterioration. Although Aβ positivity significantly accelerated GFAP progression, the fact that GFAP was increased in CI Aβ negative with cerebrovascular disease supports its potential use as a secondary endpoint in this population as well.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100205"},"PeriodicalIF":4.3,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235313","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":"Sample size estimates for biomarker-based outcome measures in clinical trials in autosomal dominant Alzheimer's disease.","authors":"David M Cash, Katy E Morgan, Antoinette O'Connor, Thomas D Veale, Ian B Malone, Teresa Poole, Tammie Ls Benzinger, Brian A Gordon, Laura Ibanez, Yan Li, Jorge J Llibre-Guerra, Eric McDade, Guoqiao Wang, Jasmeer P Chhatwal, Gregory S Day, Edward Huey, Mathias Jucker, Johannes Levin, Yoshiki Niimi, James M Noble, Jee Hoon Roh, Racquel Sánchez-Valle, Peter R Schofield, Randall J Bateman, Chris Frost, Nick C Fox","doi":"10.1016/j.tjpad.2025.100133","DOIUrl":"10.1016/j.tjpad.2025.100133","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer disease (AD)-modifying therapies are approved for treatment of early-symptomatic AD. Autosomal dominant AD (ADAD) provides a unique opportunity to test therapies in presymptomatic individuals.</p><p><strong>Methods: </strong>Using data from the Dominantly Inherited Alzheimer Network (DIAN), sample sizes for clinical trials were estimated for various cognitive, imaging, and CSF outcomes. Sample sizes were computed for detecting a reduction of either absolute levels of AD-related pathology (amyloid, tau) or change over time in neurodegeneration (atrophy, hypometabolism, cognitive change).</p><p><strong>Results: </strong>Biomarkers measuring amyloid and tau pathology had required sample sizes below 200 participants per arm (examples CSF Aβ42/40: 47[95 %CI 25,104], cortical PIB 49[28,99], CSF p-tau181 74[48,125]) for a four-year trial in presymptomatic individuals (CDR=0) to have 80 % power (5 % statistical significance) to detect a 25 % reduction in absolute levels of pathology, allowing 40 % dropout. For cognitive, MRI, and FDG, it was more appropriate to detect a 50 % reduction in rate of change. Sample sizes ranged from 250 to 900 (examples hippocampal volume: 338[131,2096], cognitive composite: 326[157,1074]). MRI, FDG and cognitive outcomes had lower sample sizes when including indivduals with mild impairment (CDR=0.5 and 1) as well as presymptomatic individuals (CDR=0).</p><p><strong>Discussion: </strong>Despite the rarity of ADAD, presymptomatic clinical trials with feasible sample sizes given the number of cases appear possible.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100133"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674573","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":"A systematic review of targeted dementia risk reduction interventions in middle-aged adults in Primary Care.","authors":"Mary Tullipan, Johnson George, Parker Magin, Kali Godbee, Jane Ferns, Claire Frewin","doi":"10.1016/j.tjpad.2025.100187","DOIUrl":"10.1016/j.tjpad.2025.100187","url":null,"abstract":"<p><strong>Background: </strong>Pathological changes of dementia are thought to commence in mid-life, making mid-life an attractive target for dementia risk reduction. This review assessed the current literature on multidomain dementia risk-reduction interventions in mid-life.</p><p><strong>Methods: </strong>We systematically searched MEDLINE, CINAHL and EMBASE for eligible studies. Studies were included if (i) participants had a mean age between 45 and 65 years, (ii) the intervention was delivered in a primary care setting and targeted two or more dementia risk factors, and (iii) outcomes were change in cognitive function or change in risk score. Data was extracted and assessed for bias using the revised Cochrane risk-of-bias assessment tool.</p><p><strong>Results: </strong>Seven studies were included. Participants' mean age ranged from 45.3 to 64.2 years. Interventions ranged from 10 weeks to 9.8 years and targeted between two and six dementia risk factors. There was a large variation in the type of outcome and statistical tests utilised across the included studies, impacting the ability to draw comparisons between the studies and draw conclusions regarding treatment effects. There was a high risk of bias in three of the studies and some concerns of bias in the other four studies. Two studies assessing dementia risk found a reduction in risk scores at their primary endpoint. None of the included studies found a statistically significant change in cognition from their interventions. This may be attributable in part to not assessing cognition prior to the interventions, limited risk factors being addressed, and the short follow-up/duration of the studies.</p><p><strong>Conclusion: </strong>Current evidence for multidomain dementia risk-reduction interventions in mid-life is not definitive; however, given their substantive potential benefits and likely limited harms, they may be considered for implementation in clinical practice after further evaluation. Future trials that have longer follow-ups, target a broader range of dementia risk factors, and that use consistent outcome measures will be valuable. Strategies to maximise implementation of multidomain interventions and long-term effectiveness will enhance the evidence base for dementia prevention in primary care.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100187"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143987199","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":"Baseline habitual dietary nitrate intake and Alzheimer's Disease related neuroimaging biomarkers in the Australian Imaging, Biomarkers and Lifestyle study of ageing.","authors":"Anjana Rajendra, Nicola P Bondonno, Kevin Murray, Liezhou Zhong, Stephanie R Rainey-Smith, Samantha L Gardener, Lauren C Blekkenhorst, Vincent Doré, Victor L Villemagne, Simon M Laws, Belinda M Brown, Kevin Taddei, Colin L Masters, Christopher C Rowe, Ralph N Martins, Jonathan M Hodgson, Catherine P Bondonno","doi":"10.1016/j.tjpad.2025.100161","DOIUrl":"10.1016/j.tjpad.2025.100161","url":null,"abstract":"<p><strong>Background: </strong>Dietary nitrate, as a nitric oxide (NO) precursor, may support brain health and protect against dementia.</p><p><strong>Objective: </strong>Our primary aim was to investigate whether dietary nitrate is associated with neuroimaging markers of brain health linked with Alzheimer's disease (AD).</p><p><strong>Participants: </strong>Study participants were cognitively unimpaired individuals from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) who had β-amyloid positron emission tomography (PET) scans (n = 554) and magnetic resonance imaging (MRI) scans (n = 335) and had completed a Food Frequency Questionnaire at baseline.</p><p><strong>Methods: </strong>Source-specific nitrate intakes were estimated using comprehensive nitrate food composition databases. Rates of cerebral β-amyloid (Aβ) deposition, measured using PET, and rates of brain atrophy, measured using MRI, were assessed between baseline and 126-months follow-up, at intervals of 18 months. Multivariable-adjusted linear mixed effect models were used to examine associations between baseline source-specific nitrate intake and rates of (i) cerebral Aβ deposition and (ii) brain atrophy, over the 126 months of follow-up. Analyses were carried out following stratification of the sample by established dementia Alzheimer's disease (AD) risk factors including sex and presence or absence of the apolipoprotein E (APOE) ε4 allele.</p><p><strong>Results: </strong>In women carriers of the APOE ε4 allele, higher plant sourced nitrate intake (median intake 121 mg/day), was associated with a slower rate of cerebral Aβ deposition [β: 4.47 versus 8.99 Centiloid (CL) /18 months, p < 0.05] and right hippocampal atrophy [-0.01 versus -0.03 mm3 /18 months, p < 0.01], after multivariable adjustments. Moderate intake showed protective associations in men carriers and in both men and women non-carriers of APOE ε4.</p><p><strong>Conclusions: </strong>Associations were observed between plant-derived nitrate intake and cerebral Aβ deposition, particularly in high-risk populations (women and APOE ε4 carriers). Associations were also observed for brain volume atrophy, however these exhibited subgroup variability without clear patterns relative to sex and APOE ε4 allele carriage. These findings suggest a potential link between plant-sourced nitrate and AD related neuroimaging markers of brain health improved brain health, but further validation in larger studies is required.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100161"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144034963","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}