Journal of Alzheimer's Disease最新文献

{"title":"How much can biomarkers explain sociodemographic inequalities in cognitive dysfunction and cognitive impairment? Results from a machine learning model in the Health and Retirement Study.","authors":"Eric T Klopack, Mateo P Farina, Bharat Thyagarajan, Jessica D Faul, Eileen M Crimmins","doi":"10.1177/13872877251338063","DOIUrl":"10.1177/13872877251338063","url":null,"abstract":"<p><p>BackgroundBiomarkers may be pathways by which social adversity affects cognitive aging and Alzheimer's disease and related dementias (ADRD) risk.ObjectiveHow much variance in cognitive dysfunction and cognitive impairment onset do blood-based and physiological biomarkers provide above and beyond easily attainable sociodemographic variables, and how much can biomarkers explain differences in cognitive functioning and ADRD by sociodemographic variables?MethodsWe utilize machine learning to generate measures of predicted cognitive dysfunction and cognitive impairment incidence based on 91 biomarkers, identify the relative importance of each biomarker, and examine how much these biomarkers mediate sociodemographic differences.ResultsMarkers related to cellular aging, neurodegeneration, diet and nutrition, immune functioning, and lung function were identified as important. Biomarkers mediated 47.2-77.3% of the variance associated with age, 22.7-35.2% of racial/ethnic differences in cognitive dysfunction, and 12.5-17.6% of educational differences.ConclusionsBiomarkers provide the potential to understand pathways linking sociodemographic characteristics to cognitive functioning and health. Future research should consider additional biomarkers and evaluate the specific systems that put people at risk for cognitive impairment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"54-68"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interaction between neurotransmitter receptor activity and amyloid-β pathology in Alzheimer's disease.","authors":"Yuhan Nong, Jung Soo Kim, Litian Jia, Ottavio Arancio, Qi Wang","doi":"10.1177/13872877251342273","DOIUrl":"10.1177/13872877251342273","url":null,"abstract":"<p><p>The accumulation of amyloid-β (Aβ) peptides is a hallmark of Alzheimer's disease (AD). Central to AD pathology is the production of Aβ peptides through the amyloidogenic processing of amyloid-β protein precursor (AβPP) by β-secretase (BACE-1) and γ-secretase. Recent studies have shifted focus from Aβ plaque deposits to the more toxic soluble Aβ oligomers. One significant way in which Aβ peptides impair neuronal information processing is by influencing neurotransmitter receptor function. These receptors, including adrenergic, acetylcholine, dopamine, 5-HT, glutamate, and gamma-aminobutyric acid (GABA) receptors, play a crucial role in regulating synaptic transmission, which underlies perceptual and cognitive functions. This review explores how Aβ interacts with these key neurotransmitter receptors and how these interactions contribute to neural dysfunction in AD. Moreover, we examine how agonists and antagonists of these receptors influence Aβ pathology, offering new perspectives on potential therapeutic strategies to curb AD progression effectively and improve patients' quality of life.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"391-409"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12283230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pimavanserin safety in adult and elderly patients with neuropsychiatric symptoms related to neurodegenerative disease: An open-label extension study.","authors":"Wiesław J Cubała, Ana Berrio, Katherine Chi-Burris, Gustavo Alva, Lambros Chrones, Sanjeev Pathak","doi":"10.1177/13872877251345162","DOIUrl":"10.1177/13872877251345162","url":null,"abstract":"<p><p>BackgroundAn 8-week, phase 3b, randomized, placebo-controlled trial demonstrated that pimavanserin, a selective 5HT_2A inverse agonist, is generally well tolerated in elderly patients with neuropsychiatric symptoms related to neurodegenerative disease (NDD).ObjectiveThis open-label extension (OLE) study assessed the long-term safety and tolerability of pimavanserin.MethodsPatients from the antecedent double-blind (DB) trial who were treated with oral pimavanserin (34 mg/day) or placebo were enrolled. The safety analysis population included all patients who received ≥1 dose of pimavanserin. The primary endpoint was treatment-emergent adverse events (TEAEs). Exploratory endpoints included change from baseline in Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A), Mini-Mental State Examination (MMSE), Clinical Global Impression-Severity (CGI-S), EuroQoL 5-Dimension 5-Level (EQ-5D-5L), and Sleep Disorders Inventory (SDI) scores.ResultsPatients (N = 595; mean age, 72.2 years) received pimavanserin treatment (mean exposure, 312.4 days). Most patients (95.3%) had dementia (68.7% of whom had Alzheimer's disease), and 70.6% were concomitantly treated with anti-dementia drugs. TEAEs occurred in 238 (40.0%) patients, and 37 (6.2%) had a serious TEAE; 1 (0.2%) was pimavanserin-related. TEAEs resulted in treatment discontinuation in 39 (6.6%) patients. Fatal TEAEs occurred in 11 (1.8%) patients (none considered related to pimavanserin). The mean (standard error) change from DB baseline to OLE Week 52 in MMSE, ESRS-A, CGI-S, EQ-5D-5L, and SDI scores was +0.9 (0.21), -0.3 (0.22), -1.0 (0.05), + 10.7 (0.87), and -0.9 (0.07), respectively. No patients reported suicidal behavior.ConclusionsPimavanserin was generally well tolerated in frail older adults and elderly patients with neuropsychiatric symptoms related to NDD for up to 52 weeks of treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"783-793"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"p53 SUMOylation promotes neurogenesis defects in APP/PS1 mice.","authors":"Anqi Yin, Yuran Gui, Lu Wan, Qinfeng Cai, Yong Luo, Jian-Zhi Wang, Rong Liu, Chenjiang Ying, Xiaochuan Wang, Fumin Yang","doi":"10.1177/13872877251340432","DOIUrl":"10.1177/13872877251340432","url":null,"abstract":"<p><p>Backgroundp53 is a transcriptional factor that regulates numerous cellular processes, the stability and activity of p53 is essential to maintain its function. Post-translational modifications (PTMs), particularly SUMOylation, play a vital role in regulating p53 activity.ObjectiveTo investigate the neurogenesis related genes that downregulated by p53 SUMOylation in APP/PS1 mice, and the protected effect by overexpressing non-SUMOylated p53 (p53 K386R). Furthermore, to provide new clues for the mechanisms of Alzheimer's disease (AD).MethodsCo-immunoprecipitation was used to detect the p53 SUMOylation levels in neuro2a (N2a) cells and APP/PS1 mice overexpressing wild-type p53 (p53 WT) or p53 K386R. In addition, RNA sequencing (RNA-seq) was used to detect the p53 SUMOylation regulated genes. Then we used qPCR, western blot, and immunofluorescence to measure the expression of neuroglobin (ngb) and the effect of neurogenesis defects induced by p53 SUMOylation.ResultsWe verified that overexpression of p53 WT promoted p53 SUMOylation and p53 K386R decreased p53 SUMOylation in N2a cells and APP/PS1 mice. Ngb was related to neurogenesis which dramatically downregulated by p53 SUMOylation. In addition, we found p53 SUMOylation caused neuron reduction and impairment of neurogenesis.ConclusionsOur data support that p53 SUMOylation may lead to neurogenesis defects by downregulating ngb in AD, suggesting that inhibition of p53 SUMOylation may be served as a therapeutic strategy for preventing AD and provide a new target for future researches and interventions.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"352-362"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An inverse association of cerebral amyloid-β deposition and serum docosahexaenoic acid levels in cognitively normal older adults in Japan.","authors":"Akira Sekikawa, Aya Higashiyama, Brian J Lopresti, Masafumi Ihara, Chendi Cui, Jiatong Li, Makoto Watanabe, Mengyi Li, Shatabdi Goon, Howard J Aizenstein, Yuefang Chang, Chikage Kakuta, Zheming Yu, Chester A Mathis, Yoshihiro Kokubo, Sarah Royse, Tetsuya Fukuda, Beth Snitz, Oscar L Lopez, Yoshihiro Miyamoto","doi":"10.1177/13872877251340688","DOIUrl":"10.1177/13872877251340688","url":null,"abstract":"<p><p>BackgroundAlzheimer's disease (AD) is driven by amyloid-β (Aβ) plaque accumulation, but the mechanisms behind this process remain unclear. Omega-3 fatty acids, particularly docosahexaenoic acid (DHA), may offer protective effects, though their relationship with Aβ accumulation is not fully understood.ObjectiveThis study investigated whether serum DHA and eicosapentaenoic acid (EPA) levels, measured 6-9 years before imaging, were inversely associated with cerebral Aβ deposition in cognitively normal older adults in Japan, a population known for high omega-3 intake. We focused on individuals identified as Aβ-positive based on positron emission tomography (PET) scans, as they are at higher risk for AD progression, to assess DHA's potential in mitigating early amyloid pathology.MethodsAn analytical sample of 97 older adults (75-89 years) from the Suita Study was analyzed. Serum DHA and EPA levels were assessed between 2008 and 2012, and amyloid PET was performed between 2016 and 2019. Multiple regression analyses were conducted, adjusting for age, sex, <i>APOE4</i> status, and cardiometabolic disease.ResultsAmong 97 participants (49% males, 8.2% <i>APOE4</i> carriers), 37.1% (n = 36) had cardiometabolic disease, and 29.8% (n = 29) were Aβ positive. In Aβ-positive individuals, higher serum DHA levels were significantly associated with lower Aβ deposition independent of age, sex and <i>APOE4</i> status (standardized β = -0.423, p = 0.030). This became non-significant after additionally adjusting for cardiometabolic disease (β = -0.382, p = 0.059). No significant association was found between EPA and Aβ deposition.ConclusionsHigher long-term DHA levels may help reduce Aβ accumulation in those at risk for AD, supporting its potential role in early prevention.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"378-386"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144019744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic association of social participation with cognitive function: A bidirectional Mendelian randomization study.","authors":"Aoqiang Zhai, Ruiqi Zou, Tianrun Lv, Siqi Yang, Yanjie Zhong, Yang Xiong, Fuyu Li, Haijie Hu","doi":"10.1177/13872877251340078","DOIUrl":"10.1177/13872877251340078","url":null,"abstract":"<p><p>BackgroundCognitive decline poses a significant challenge in aging societies. While some studies suggest that active social participation mitigates cognitive decline, others present conflicting findings.ObjectiveThis bidirectional two-sample Mendelian randomization (MR) study aimed to elucidate the causal relationship between social participation and cognitive function.MethodsThe cognitive performance dataset (n = 257,841) was used as the discovery sample, while cognitive function (n = 22,593) and Alzheimer's disease (AD) datasets (n = 394,705) served as replication samples and proxies for severe cognitive decline. Inverse variance weighting was the primary analytical method, supplemented by weighted median, MR-Egger, MR.RAPS, MR-PRESSO, and maximum likelihood methods for sensitivity analyses.ResultsSocial participation in sports club or gym (β = 0.09, 95% CI: 0.05 to 0.14, p < 0.001), religious group (β = 0.11, 95% CI: 0.08 to 0.14, p < 0.001) and other group activity (β = 0.06, 95% CI: 0.03 to 0.09, p < 0.001) reduced the risk of cognitive decline, while pub or social club (β = -0.06, 95% CI: -0.1 to -0.02, p = 0.005) and social inactivity (β = -0.05, 95% CI: -0.09 to -0.01, p = 0.017) accelerated cognitive decline. Improved cognitive performance promoted participation in beneficial activities and reduced pub or social club participation. Additionally, AD motivated visits to pub or social club (OR = 1.01, 95% CI: 1.00 to 1.03, p = 0.011).ConclusionsSpecific types of social participation may protect against cognitive decline, offering evidence for targeted interventions to prompt cognitive health in aging populations.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"259-270"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Klotho protein in Alzheimer's disease: Diet leading to immortality?","authors":"Kamil Walczak, Weronika Kołodziejczyk, Magdalena Pszczołowska, Magdalena Kozłowska, Jan Aleksander Beszłej, Jerzy Leszek","doi":"10.1177/13872877251350125","DOIUrl":"https://doi.org/10.1177/13872877251350125","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is the most common cause of dementia, leading to progressive cognitive decline and premature death. Despite decades of research, the exact cause of AD remains unknown, and current treatments only slow disease progression without addressing its root cause. Recent studies suggest that endogenous factors such as the Klotho protein may have neuroprotective properties and influence AD progression. This review aims to explore the role of Klotho protein in AD, with a particular focus on its biological functions, expression, and potential therapeutic implications. Additionally, it examines the relationship between Klotho levels and dietary patterns. A literature review was conducted to analyze existing research on Klotho protein, its neuroprotective effects, and its correlation with different dietary factors in the context of AD. Evidence suggests that Klotho protein plays a crucial role in cellular metabolism and neuroprotection. Higher levels of Klotho have been linked to better cognitive function and reduced neurodegeneration. Emerging research also indicates that certain dietary patterns, particularly the Mediterranean diet, may positively influence Klotho expression. Klotho protein represents a promising therapeutic target in AD, potentially slowing disease progression through its neuroprotective effects. Further research is needed to better understand the mechanisms regulating Klotho levels, particularly the impact of diet, and how they can be leveraged for AD prevention and treatment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251350125"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PTEN inhibition induces neuronal differentiation and neuritogenesis in SH-SY5Y cells via AKT signaling pathway.","authors":"Natália Chermont Dos Santos Moreira, Larissa de Oliveira Piassi, Jéssica Ellen Barbosa de Freitas Lima, Geraldo Aleixo Passos, Elza Tiemi Sakamoto-Hojo","doi":"10.1177/13872877251352194","DOIUrl":"https://doi.org/10.1177/13872877251352194","url":null,"abstract":"<p><p>BackgroundPTEN is a key regulator of neuronal differentiation and neurogenesis. Its role in modulating the PI3K/AKT pathway and oxidative stress responses in neuronal models remains an area of active investigation.ObjectiveThis study aimed to assess the effects of PTEN knockdown on neuronal differentiation, neuritic growth, and PI3K/AKT pathway activation in SH-SY5Y cells.MethodsSH-SY5Y cells were treated with PTEN siRNA to induce PTEN knockdown. The level of PTEN inhibition was confirmed, and assays were performed to evaluate neurogenesis and neuritogenesis at 3- and 7-days post-treatment. Protein expression analysis of key components in the AKT/GSK3-β/Tau pathway was conducted to assess their role in neurogenesis. Additionally, the PI3K inhibitor LY294002 was used to examine its impact on PTEN knockdown-induced neuronal differentiation.ResultsPTEN knockdown significantly increased neurite lengths and reduced cytoplasmic size, indicating neuronal differentiation. Protein analysis showed that PTEN inhibition modulated the expression of components in the AKT/GSK3-β/Tau pathway. The PI3K inhibitor LY294002 prevented neuronal differentiation, confirming the involvement of the PI3K/AKT pathway in mediating the effects of PTEN knockdown.ConclusionsOur findings demonstrate that PTEN plays a crucial role in regulating neuronal differentiation in SH-SY5Y cells. The PI3K/AKT pathway mediates the effects of PTEN knockdown, suggesting PTEN as a potential therapeutic target for neurodegenerative diseases where its dysregulation may contribute to disease progression.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"13872877251352194"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BIOmarkers in NEuropsychiatric SYmptoms (BIONESY): A multicenter nation survey and a systematic review.","authors":"Giulia Perini, Matteo Cotta Ramusino, Marco Vergani, Alberto Gatti, Camillo Imbimbo, Silvia Leone, Elena Ballante, Nicola Allegri, Fabrizia D'Antonio, Marta Zuffi, Simone Pomati, Elisabetta Farina, Lucio Tremolizzo, Alfredo Costa","doi":"10.1177/13872877251344631","DOIUrl":"10.1177/13872877251344631","url":null,"abstract":"<p><p>BackgroundBehavioral and psychological symptoms of dementia (BPSD) have poorly understood pathological/morphological correlates.ObjectiveWe aimed to (1) investigate the perception of the utility of different biomarkers in the assessment of BPSD among Italian Memory Clinics and (2) review current literature in this regard.MethodsA multicenter, national survey was launched by the BPSD Study Group of the Italian Neurological Society for Dementia (SINdem). Participants completed a semi-structured questionnaire on their perception of possible associations between the occurrence/severity of different BPSD and different biomarkers, based on their individual knowledge and clinical experience, regarding any type and severity of cognitive impairment. Then, we performed a systematic review according to PRISMA guidelines. Only papers reporting biomarkers correlates of BPSD in neurocognitive disorders were included.ResultsAmong the 53 responders, 94%, 68%, 68%, and 45% perceived neuropsychological testing, MRI, FDG-PET, and EEG, respectively, associated with the total amount of BPSD. EEG alterations were perceived selectively associated with nighttime behavior disturbances and psychosis cluster (p < 0.01). Hallucinations, apathy and delusions were perceived as more correlated with biomarkers. Years of experience using biomarkers for diagnosis were associated with a more selective use of topographical biomarkers (p < 0.01). 91% of participants consider useful increasing the use of biomarkers to predict the occurrence/severity of BPSD. The literature review identified 99 eligible studies. Brain MRI (60 articles) and FDG-PET (12 studies) alterations are the most associated with BPSD.ConclusionsIn clinical practice, topographical biomarkers related to regional consequences of the pathology are perceived as potentially informative in the BPSD's assessment.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"490-511"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144181429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of healthy lifestyle with excess risk of dementia in individuals with hypertension.","authors":"Yuanyuan Lu, Jie Chang, Yiwei Zhao, Peiyang Gao, Yi Tang","doi":"10.1177/13872877251344309","DOIUrl":"10.1177/13872877251344309","url":null,"abstract":"<p><p>BackgroundThe extent to which hypertension-related excess risk of dementia can be mitigated or eradicated through lifestyle factor modification remains unclear.ObjectiveTo explore the association between lifestyle behaviors and hypertension-related excess risk of dementia.MethodsIn this prospective cohort study using data from the UK Biobank, participants were enrolled from 2006 to 2010 and followed up until December 2022. A healthy lifestyle score was constructed by assigning one point for each of the seven selected healthy lifestyle factors. The association of dementia risk in individuals with hypertension according to the healthy lifestyle score was compared to individuals without hypertension.ResultsThis study included 337,378 individuals. During a median follow-up of 13.6 years, 5390 participants developed dementia. A higher healthy lifestyle score was associated with a gradual decrease in the excess risk of dementia for individuals with hypertension compared to individuals without hypertension. Excess dementia risk was not detected among individuals with hypertension who adopted at least six healthy lifestyle factors (hazard ratio (HR) = 1.05 (95% confidence interval (CI): 0.96-1.14)) for six scores; HR = 0.93 (95% CI: 0.82-1.06 for seven scores). The protective association between adhering to all seven healthy lifestyle factors and dementia was significantly stronger for individuals <60 years old than for individuals ≥60 years old.ConclusionsFor individuals with hypertension who adopted at least six healthy lifestyle factors had no hypertension-related excess risk of dementia.</p>","PeriodicalId":14929,"journal":{"name":"Journal of Alzheimer's Disease","volume":" ","pages":"620-633"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}