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

{"title":"Enhancing dementia prediction: A 19-year validation of the CAIDE risk score with insulin resistance and APOE ε4 integration in a population-based cohort.","authors":"Elina Pietilä, Eliisa Löyttyniemi, Seppo Koskinen, Jenni Lehtisalo, Matti Viitanen, Juha O Rinne, Antti Jula, Laura L Ekblad","doi":"10.1016/j.tjpad.2024.100034","DOIUrl":"10.1016/j.tjpad.2024.100034","url":null,"abstract":"<p><strong>Background: </strong>Dementia is a significant cause of disability and dependency. Persons with high dementia risk but intact cognition will benefit from preventive interventions.</p><p><strong>Objectives: </strong>The aim was to validate dementia risk score Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) in a national population-based cohort with data on age, education, hypertension, obesity, hyperlipidemia and physical activity. Secondly, we examined if substituting obesity item with Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) would improve predictive value of CAIDE risk score.</p><p><strong>Design: </strong>Longitudinal, population-based cohort study.</p><p><strong>Setting: </strong>General population, Finland PARTICIPANTS: Representative sample of Finnish adult population aged over 30 years from Health 2000 Survey (n = 5,806).</p><p><strong>Measurements: </strong>CAIDE dementia risk score and substituting BMI with HOMA-IR.</p><p><strong>Results: </strong>Dementia was diagnosed in 571 (9.8 %) participants during the 19 years follow-up. CAIDE risk score predicted dementia well: AUC (area under curve) ROC (receiver-operating characteristic) was 0.78 (95 % CI from 0.76 to 0.79). Secondly, replacing obesity with HOMA-IR in CAIDE risk score generated similar results: ROC AUC 0.78 (95 % CI from 0.76 to 0.80). Adding APOE ε4 status further improved predictive value of risk score: ROC AUC 0.81 (95 % CI from 0.80 to 0.83).</p><p><strong>Conclusions: </strong>CAIDE dementia risk score predicts dementia well in a national population-based cohort. Adding APOE ε4 genotype improved predictive value of risk score. Insulin resistance measured by HOMA-IR is comparable to obesity as part of CAIDE risk score. These findings imply that CAIDE risk score is applicable for assessing risk of dementia and highlight importance of modifiable risk factors of dementia.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100034"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042008","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":"Efficacy of a group-based 8-week multicomponent cognitive training on cognition, mood and activities of daily living among healthy older adults: A two-year follow-up of a randomized controlled trial.","authors":"Patsri Srisuwan, Daochompu Nakawiro, Orawan Kuha, Supatcha Kengpanich, Kulachade Gesakomol, Sirinthorn Chansirikarnjana","doi":"10.1016/j.tjpad.2024.100033","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100033","url":null,"abstract":"<p><strong>Background: </strong>Cognitive training (CT) has been one of the important non-pharmaceutical interventions that could delay cognitive decline. Currently, no definite CT methods are available. Furthermore, little attention has been paid to the effect of CT on mood and instrumental activities of daily living (IADL).</p><p><strong>Objectives: </strong>To assess the effectiveness of a multicomponent CT using a training program of executive functions, attention, memory and visuospatial functions (TEAM-V Program) on cognition, mood and instrumental ADL.</p><p><strong>Design: </strong>A randomized, single-blinded, treatment-as-usual controlled trial.</p><p><strong>Setting: </strong>Geriatric clinic in Bangkok, Thailand.</p><p><strong>Participants: </strong>80 nondemented community-dwelling older adults (mean age 65.7 ± 4.3 years).</p><p><strong>Intervention: </strong>The CT (TEAM-V) Program or the treatment-as-usual controlled group. The TEAM-V intervention was conducted over 5 sessions, with a 2-week interval between each session. A total of 80 participants were randomized (n = 40 the TEAM-V Program; n = 40 the control group).</p><p><strong>Measurements: </strong>The Thai version of Montreal Cognitive Assessment (MoCA), The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog), Thai version of Hospital Anxiety and Depression Scale (HADS) and The Chula ADL were used to assess at baseline, 6 months, 1 year and 2 years.</p><p><strong>Results: </strong>Compared with the control arm (n = 36), the TEAM-V Program (n = 39) was associated with significantly improved general cognition (MoCA, P = 0.02) at 2 years. Compared with baseline, participants receiving the TEAM-V Program were associated with significantly improved immediate recall (word recall task, P < 0.001), retrieval and retention of memory processes (word recognition task, P = 0.01) and attention (number cancellation part A, P = 0.01) at 2 years. No training effects on anxiety (P = 0.94), depression (P = 0.093) and IADL (P = 0.48) were detected.</p><p><strong>Conclusions: </strong>The TEAM-V Program was effective in improving global cognitive function. Even though, the program did not significantly improve anxiety, depression and IADL compared with the control group, memory and attention improved in the intervention group compared with baseline. Further studies incorporating a larger sample size, longitudinal follow-up and higher-intensity CT should be conducted.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100033"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143042007","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":"Associations of early-onset coronary heart disease and genetic susceptibility with incident dementia and white matter hyperintensity: A prospective cohort study.","authors":"Jie Liang, Yanyu Zhang, Wenya Zhang, Yang Pan, Darui Gao, Jingya Ma, Yuling Liu, Yiwen Dai, Mengmeng Ji, Wuxiang Xie, Fanfan Zheng","doi":"10.1016/j.tjpad.2024.100041","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100041","url":null,"abstract":"<p><strong>Background: </strong>The associations of early-onset coronary heart disease (CHD) and genetic susceptibility with incident dementia and brain white matter hyperintensity (WMH) remain unclear. Elucidation of this problem could promote understanding of the neurocognitive impact of early-onset CHD and provide suggestions for the prevention of dementia.</p><p><strong>Objectives: </strong>This study aimed to investigate whether observed and genetically predicted early-onset CHD were related to subsequent dementia and WMH volume.</p><p><strong>Design: </strong>Prospective cohort study.</p><p><strong>Setting: </strong>UK Biobank.</p><p><strong>Participants: </strong>500 671 individuals without dementia at baseline.</p><p><strong>Measurements: </strong>Early-onset CHD (male ≤55 years; female ≤65 years) was ascertained using hospital inpatient records. Incident dementia including all-cause dementia, Alzheimer's disease, and vascular dementia was ascertained using hospital inpatient records, mortality register data, and self-reported data. WMH volume was measured through brain magnetic resonance imaging (MRI). Cox proportional hazards models and linear regression models were used to analyze the associations of early-onset CHD with incident dementia and WMH. Subsequently, a polygenetic risk score (PRS) analysis was conducted to investigate the associations of genetically predicted early-onset CHD with outcomes.</p><p><strong>Results: </strong>Among 500 671 individuals (female: 272 669, 54.5%; mean age: 57.0 ± 8.1 years), 9 294 dementia occurred during a median follow-up of 13.8 years. Compared with the non-CHD group, both early-onset (n = 16 133) and late-onset CHD (n = 43 944) groups had higher risks of developing dementia (hazard ratio [HR]: 1.99, 95% confidence interval [CI]: 1.81 to 2.19 for early-onset group; HR: 1.20, 95% CI: 1.14 to 1.27 for late-onset group). Among CHD participants, early-onset CHD was associated with a significantly higher risk of incident dementia, compared with late-onset CHD (HR: 1.56, 95% CI: 1.39 to 1.75). In a subset of 40 290 individuals who completed brain MRI scans during a median follow-up of 9.3 years, participants with early-onset CHD exhibited the largest WMH volume among the three groups (early-onset CHD, late-onset CHD, and non-CHD, P_trend<0.001). The PRS analysis supported the associations of early-onset CHD with dementia (odds ratio [OR] for the highest quartile: 1.37, 95% CI: 1.28 to 1.46, P_trend<0.001) and WMH volume (β for the highest quartile: 0.042, 95% CI: 0.017 to 0.068, P_trend=0.002).</p><p><strong>Conclusions: </strong>Early-onset CHD and genetic susceptibility are associated with a higher risk of incident dementia and a larger WMH volume. Additional attention should be paid to the neurocognitive status of individuals with early-onset CHD.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 2","pages":"100041"},"PeriodicalIF":4.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041988","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 associations between fresh vegetable and fruit consumption and plasma and PET biomarkers in preclinical Alzheimer's disease: A cross-sectional and longitudinal study of Chinese population.","authors":"Heling Chu, Chuyi Huang, Fang Xie, Qihao Guo","doi":"10.1016/j.tjpad.2025.100076","DOIUrl":"https://doi.org/10.1016/j.tjpad.2025.100076","url":null,"abstract":"<p><strong>Background: </strong>The identification of the modifiable lifestyle factors including dietary habits in older adults of preclinical Alzheimer's disease (AD) and early effective interventions are of great importance.</p><p><strong>Objectives: </strong>We studied whether the consumption of fresh vegetables and fruits was different between cognitively unimpaired (CU) and cognitively impaired (CI) population and mainly investigated the associations between vegetable and fruit consumption and PET and plasma AD biomarkers in older CU adults with higher β-amyloid (Aβ) burden.</p><p><strong>Design, setting, and participants: </strong>Older adults with the age of 50-85 years were enrolled for a cross-sectional and longitudinal study. The groups depended on whether the participants were CU or CI. Partial participants whose habits remained unchanged were followed up.</p><p><strong>Measurements: </strong>The consumption data of vegetables and fruits were collected using a validated self-reported questionnaire. We mainly investigated the associations between vegetable and fruit consumption and various biomarkers in CU participants with positive ¹⁸F-florbetapir PET scan (Aβ-PET), part of whom also underwent plasma AD biomarkers tests and ¹⁸F-MK6240 PET scan (tau-PET). Correlation and multiple linear regression analyses were used to investigate the associations between vegetable and fruit consumption and AD biomarkers.</p><p><strong>Results: </strong>A total of 1433 participants were enrolled, of which CU accounted for 49.4 %. Most of the intake habits of vegetables and fruits was different between CU and CI participants. 177 CU participants with Aβ-PET positive were selected for the following study. Multiple linear regression analysis showed higher consumption of fresh vegetables (>200 g/d), dark vegetables (>100 g/d, ≥2d/week), fruits (>100 g/d), berries (>100 g/d) and grapes (>100 g/d) more or less had associations with the plasma biomarkers including Aβ40, t-Tau, p-Tau-181 and neurofilament light chain as well as amyloid and Tau PET biomarkers. Most of the habits were associated with the change of cognitive function after an approximately two-year follow-up. Especially, higher intakes of fruits and grapes correlated with both lower Aβ and Tau burden and inversely with cognitive decline after follow-up.</p><p><strong>Conclusion: </strong>Our data indicates that higher consumption of vegetables, dark vegetables, fruits, berries and grapes is associated with amyloid and Tau PET and plasma biomarkers in preclinical AD participants and the changes of cognitive function after follow-up. Higher intakes of fruits (>100 g/d) and grapes (>100 g/d) may be more helpful for reducing the risk of AD development.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100076"},"PeriodicalIF":4.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075546","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":"Preventing dementia in Italy: Estimations of modifiable risk factors and public health implications.","authors":"Federica Asta, Guido Bellomo, Benedetta Contoli, Flavia L Lombardo, Valentina Minardi, Simone Salemme, Nicola Vanacore, Maria Masocco","doi":"10.1016/j.tjpad.2024.100055","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100055","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Dementia is a major global public health challenge, with over 50 million cases in 2020, projected to reach 152 million by 2050. Effective prevention strategies are needed to reduce the impact of modifiable risk factors associated with dementia, particularly in countries with ageing populations like Italy. The Population Attributable Fraction (PAF) and Potential Impact Fraction (PIF) are key metrics for understanding and reducing dementia cases through targeted interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aimed to revise and expand PAF estimates for dementia in Italy, integrate them with PIF calculations, and assess the alignment of regional health policies with these risk factors. Additionally, the study explored regional variations in PAFs and evaluated the potential for reducing dementia incidence through feasible public health interventions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;A cross-sectional analysis was conducted using data from two national public health surveillance systems, PASSI and PASSI d'Argento (PdA), to estimate PAFs and PIFs for dementia at both national and regional levels. The study used data collected between 2017 and 2019.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Data were drawn from 19 Italian regions and two autonomous provinces, providing national and subnational estimates of modifiable risk factors for dementia.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Participants: &lt;/strong&gt;The study population included a nationally representative sample of 86,494 individuals aged 18-64 (PASSI) and 48,516 individuals aged 65 and older (PdA).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Measurements: &lt;/strong&gt;PAFs were calculated for 11 of the 12 modifiable risk factors identified by the Lancet Commission in 2021, with data from the PASSI and PdA systems. PIFs were calculated to estimate the potential reduction in dementia cases under different intervention scenarios. Regional variations in PAFs were assessed and aligned with health policies outlined in the Regional Prevention Plans.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The national combined PAF for 11 modifiable risk factors was 39.6 % (95 % CI: 20.8-55.9). Midlife hypertension and physical inactivity were the most significant contributors, accounting for 12.3 % of the total PAF. Cardiovascular risk factors collectively explained over 50 % of preventable dementia cases. Regional PAFs ranged from 31.7 % to 47.5 %, with a clear north-south gradient; southern regions exhibited higher PAFs due to cardiovascular factors. Despite broad consistency between national and regional PAFs, significant variability was found in how regions addressed risk factors, particularly air pollution. At the national level, a 10 % reduction in risk factors would prevent 54,495 dementia cases, with subnational PIFs ranging from 3.7 % to 6.0 %.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This study highlights the substantial potential for dementia prevention in Italy through targeted public health interventions. However, significant regional dispariti","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":" ","pages":"100055"},"PeriodicalIF":4.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984544","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":"Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.","authors":"Sandar Aye, Gunilla Johansson, Christoph Hock, Lars Lannfelt, John R Sims, Kaj Blennow, Kristian S Frederiksen, Caroline Graff, José Luis Molinuevo, Philip Scheltens, Sebastian Palmqvist, Michael Schöll, Anders Wimo, Miia Kivipelto, Ron Handels, Lutz Frölich, Norbert Zilka, Martin Tolar, Peter Johannsen, Linus Jönsson, Bengt Winblad","doi":"10.1016/j.tjpad.2024.100022","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100022","url":null,"abstract":"<p><p>The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists. Additionally, there are logistical concerns related to infrastructure, as well as cost-effectiveness and reimbursement issues. This article brings together insights from a diverse group of international researchers and dementia experts and outlines the potential challenges and opportunities, urging all stakeholders to prepare for the introduction of DMTs. We emphasize the need to develop appropriate use criteria, including patient characteristics, specifically for the European healthcare system, to ensure that treatments are administered to the most suitable patients. It is crucial to improve the skills and knowledge of physicians to accurately interpret biomarker results, share decision-making with patients, recognize treatment-related side effects, and monitor long-term treatment. We advocate for investment in patient registries and unbiased follow-up studies to better understand treatment effectiveness, evaluate treatment-related side effects, and optimize long-term treatment. Utilizing amyloid-targeting therapies as a starting point for combination therapies should also be a priority.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100022"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972239","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":"INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.","authors":"Eric Siemers, Todd Feaster, Gopalan Sethuraman, Karen Sundell, Vladimir Skljarevski, Erika N Cline, Hao Zhang, Jasna Jerecic, Lawrence S Honig, Stephen Salloway, Reisa Sperling, Mirjam N Trame, Michael G Dodds, Kimball Johnson","doi":"10.1016/j.tjpad.2024.100005","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100005","url":null,"abstract":"<p><strong>Background: </strong>Soluble species of multimeric amyloid-beta including globular amyloid-beta oligomers (AβOs) and linear amyloid-beta protofibrils are toxic to neurons. Sabirnetug (ACU193) is a humanized monoclonal antibody, raised against globular species of soluble AβO, that has over 650-fold greater binding affinity for AβOs over monomers and appears to have relatively little binding to amyloid plaque.</p><p><strong>Objectives: </strong>To assess safety, pharmacokinetics, and exploratory measures including target engagement, biomarker effects, and clinical efficacy of sabirnetug in participants with early symptomatic Alzheimer's disease (AD; defined as mild cognitive impairment and mild dementia due to AD).</p><p><strong>Design: </strong>Randomized, double-blind, placebo-controlled, ascending dose first-in-human phase 1 study.</p><p><strong>Setting: </strong>Fifteen study centers in the United States.</p><p><strong>Participants: </strong>Sixty-five participants with early symptomatic AD.</p><p><strong>Intervention: </strong>Participants received one infusion of sabirnetug 2 mg/kg, 10 mg/kg, 25 mg/kg, 60 mg/kg, or placebo (Part A) or three infusions of sabirnetug 10 mg/kg, 25 mg/kg, 60 mg/kg, or placebo (Part B).</p><p><strong>Measurements: </strong>Safety, tolerability, serum pharmacokinetics, and central target engagement of single and multiple doses of sabirnetug, cerebrospinal fluid (CSF) concentrations of sabirnetug, and amyloid plaque load, as determined by positron emission tomography.</p><p><strong>Results: </strong>Sabirnetug was generally well tolerated. A larger percentage of participants receiving sabirnetug (56.3%) versus placebo (42.9%) had at least one treatment emergent adverse event, with approximately 29% in each group considered related to study drug. Most events were mild-to-moderate in severity. Of 48 participants given sabirnetug, five developed amyloid related imaging abnormalities - edema/effusion, including one instance that was mildly symptomatic in a participant who had received one dose sabirnetug 60 mg/kg. Notably, none of the six apolipoprotein E Ɛ4 homozygotes who received sabirnetug developed amyloid related imaging abnormalities - edema/effusion or - hemorrhage/hemosiderin deposition. Infusion reactions, such as rash, pain, or erythema, were not frequent (6.3% for sabirnetug versus 0.0% for placebo). Sabirnetug exposure was dose proportional in both serum and CSF. Target engagement, defined as drug bound to AβOs in CSF, was shown to be dose and exposure dependent. Over three months, approximately 25% and 20% reduction in amyloid plaques, respectively, were observed in participants receiving three infusions of sabirnetug 60 mg/kg every four weeks and 25 mg/kg every two weeks.</p><p><strong>Conclusions: </strong>The Phase 1 INTERCEPT-AD study provided safety, tolerability, dosing, and target engagement data that supported the design of the ongoing ALTITUDE-AD study (NCT06335173).</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100005"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972229","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":"Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.","authors":"Sokratis Charisis, Niki Mourtzi, Matthew R Scott, Eva Ntanasi, Eirini Mamalaki, Alexandros Hatzimanolis, Alfredo Ramirez, Jean-Charles Lambert, Mary Yannakoulia, Mary Kosmidis, Efthimios Dardiotis, Georgios Hadjigeorgiou, Paraskevi Sakka, Claudia L Satizabal, Alexa Beiser, Qiong Yang, Marios Κ Georgakis, Sudha Seshadri, Nikolaos Scarmeas","doi":"10.1016/j.tjpad.2024.100018","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100018","url":null,"abstract":"<p><strong>Importance: </strong>Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.</p><p><strong>Objective: </strong>To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.</p><p><strong>Design: </strong>We analyzed data from the Hellenic Longitudinal Investigation of Aging and Diet (HELIAD). Mean follow-up was 2.9 (SD, 0.8) years. Baseline assessment was from 11/2009 to 11/2016, and cognitive follow-up from 01/2013 to 07/2019. Associations of interest were also examined in the UK Biobank (UKB) for replication purposes (mean follow-up was 12.9 (SD, 2.4) years; baseline assessment was from 12/2006 to 10/2010).</p><p><strong>Setting: </strong>Population-based study.</p><p><strong>Participants: </strong>The HELIAD sample included 622 participants ≥65 years of age without baseline dementia or amnestic mild cognitive impairment (aMCI-the prodromal stage of AD). The UKB sample included 142,637 participants ≥60 years of age without prevalent dementia.</p><p><strong>Exposures: </strong>Genetic predisposition to elevated circulating levels of IL-6 was estimated using a polygenic risk score (PRS), calculated based on the summary statistics of a current GWAS meta-analysis.</p><p><strong>Main outcomes and measures: </strong>AD and MCI diagnoses were based on standard clinical criteria [HELIAD], or hospital records and death registry data [UKB]. Associations with AD or aMCI incidence [HELIAD] and AD incidence [UKB] were examined with Cox regression models.</p><p><strong>Results: </strong>In HELIAD, mean age was 73.4 (SD, 5.0) years; 363 (58%) women. An increase in IL-6 PRS by 1 standard deviation unit (SDU) was associated with up to a 43% increase in the risk for incident AD/aMCI (HR_{GWAS significance threshold of 0.01,} 1.43 [95%CI, 1.14 - 1.80]). In UKBB, mean age was 64.2 (SD, 2.8) years; 73,707 (52%) women. A 1 SDU increase in IL-6 PRS was associated with up to an 8% increase in the risk for incident AD (HR_{GWAS significance threshold of 0.2}, 1.08 [95%CI, 1.04 - 1.12]).</p><p><strong>Conclusions and relevance: </strong>Genetic predisposition to higher circulating levels of IL-6 was associated with an increased risk for AD, supporting the role of IL-6-related pathways in AD pathogenesis, and suggesting that genetic predisposition to proinflammatory states might trigger or accelerate AD-related neuropathology.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100018"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972226","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":"Key considerations for combination therapy in Alzheimer's clinical trials: Perspectives from an expert advisory board convened by the Alzheimer's drug discovery foundation.","authors":"Jeffrey Cummings, Michael Gold, Mark Mintun, Michael Irizarry, Andrew von Eschenbach, Suzanne Hendrix, Donald Berry, Cristina Sampaio, Kaycee Sink, Jaren Landen, Miia Kivipelto, Michael Grundman, Steven E Arnold, Allan Green, Katherine Partrick, Laura Nisenbaum, Aaron Burstein, Howard Fillit","doi":"10.1016/j.tjpad.2024.100001","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100001","url":null,"abstract":"<p><p>There is growing consensus in the Alzheimer's community that combination therapy will be needed to maximize therapeutic benefits through the course of the disease. However, combination therapy raises complex questions and decisions for study sponsors, from preclinical research through clinical trial design to regulatory, statistical, and operational considerations. In January 2024, the Alzheimer's Drug Discovery Foundation convened an expert advisory board to discuss the key considerations in each of these areas. Experts agreed on the need to prioritize a combination therapy approach that encompasses a wide range of targets associated with aging and the underlying biology of Alzheimer's disease. Progress in combination therapy could be accelerated by leveraging preclinical research and Phase 1 and 2A trials to identify the most promising combinations for further development, exploring repurposed agents with available preclinical and clinical data, building collaborations across sectors to support operational challenges, and planning for the likely impact of anti-amyloid beta-protein monoclonal antibody therapies on future clinical trial designs.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100001"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972230","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":"Maintaining level of modifiable dementia risk scores is associated with better cognitive outcomes than increasing risk scores: A population-based prospective cohort study.","authors":"Stephanie Van Asbroeck, Md Hamidul Huque, Scherazad Kootar, Ruth Peters, Nicolas Cherbuin, Moyra E Mortby, Sebastian Köhler, Martin Pj van Boxtel, Kay Deckers, Kaarin J Anstey","doi":"10.1016/j.tjpad.2024.100014","DOIUrl":"https://doi.org/10.1016/j.tjpad.2024.100014","url":null,"abstract":"<p><strong>Background: </strong>A brain healthy lifestyle, consisting of good cardiometabolic health and being cognitively and socially active in midlife, is associated with a lower risk of cognitive decline years later. However, it is unclear whether lifestyle changes over time also affect the risk for mild cognitive impairment (MCI)/dementia, and rate of cognitive decline.</p><p><strong>Objectives: </strong>To investigate if lifestyle changes over time are associated with incident MCI/dementia risk and rate of cognitive decline.</p><p><strong>Design: </strong>Population-based prospective cohort study SETTING: Personality and Total Health (PATH) Through Life Study cohort (Australia).</p><p><strong>Participants: </strong>4,777 participants (50.4% women), recruited between 2000 and 2002, who were 40-44 and 60-64 years old at baseline, without a prevalent dementia diagnosis. Participants had to have cognitive outcome measures available after baseline.</p><p><strong>Measurements: </strong>Various measurements (neurocognitive assessment, blood pressure) and survey responses (demographics, cognitive, social, and physical activity, smoking, alcohol consumption, body height and weight, depression, and previous diagnoses) were collected approximately every four years. A brain-healthy lifestyle was operationalized via two well-validated modifiable dementia risk scores, the LIfestyle for BRAin health (LIBRA) score and the modifiable part of the Australian National University Alzheimer's Disease Risk Index (ANU-ADRI_mod). Their change over time was estimated using latent growth curve modelling, and their association with cognition and incidence of MCI/dementia was investigated using parallel process modelling and Cox regression analysis.</p><p><strong>Results: </strong>Within those aged 60-64 years at baseline (n=2,409), 211 cases of incident MCI/dementia were recorded over a median follow-up time of 12.2 years. On average, individuals' LIBRA and ANU-ADRI_mod increased (i.e., worsened) over time, but individuals whose scores increased one standard deviation (SD) less had a 19.0-24.6% lower risk for MCI/dementia (hazard ratio (95% confidence interval): LIBRA_{change over time}=0.754 (0.664-0.857), ANU-ADRI_{mod, change over time}=0.810 (0.71-0.915)), while controlling for the risk score at baseline and multiple potential confounders. Various associations between dementia risk score trajectories and cognitive performance trajectories were observed.</p><p><strong>Conclusions: </strong>Efforts to maintain a brain healthy lifestyle could reduce the risk for MCI or dementia, and slow cognitive decline.</p>","PeriodicalId":22711,"journal":{"name":"The Journal of Prevention of Alzheimer's Disease","volume":"12 1","pages":"100014"},"PeriodicalIF":4.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972235","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}