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

Background: Evidence remains inconclusive regarding plant-based diets preventing cognitive impairment and dementia, as certain plant-based foods, including refined carbohydrates, sweets, sugar-sweetened beverages, and trans fats, may increase dementia risk.

Objectives: To quantitatively synthesize prospective cohort studies on associations between adherence to plant-based diets and the risks of cognitive impairment and dementia.

Design: Systematic review and meta-analysis. This study adhered to the PRISMA guidelines and was registered on PROSPERO (No: CRD42024501334).

Setting: Studies published until December 2025 were systematically identified using AgeLine, CINAHL, Embase, MEDLINE, PsycINFO, Scopus, and Web of Science.

Participants: The study population comprised adults aged ≥ 20 years with no cognitive impairment at baseline.

Intervention: Studies were enrolled if the participants (1) assessed dietary patterns characterized by higher plant-based food consumption and decreased or ceased consumption of animal-based foods or (2) used established dietary indices, including overall plant-based diet index (PDI), healthful plant-based diet index (hPDI), and unhealthful plant-based diet index (uPDI).

Measurements: Data extraction, risk of bias assessment, and the GRADE approach for assessing certainty of evidence were performed independently by three reviewers. A random-effects model with restricted maximum likelihood was used to calculate pooled risk ratios and 95% confidence intervals. The dose-response meta-analysis used two-stage dose-response regression.

Results: The meta-analysis based on seven studies (number of participants: 221,380; number of cases of incident cognitive impairment and dementia: 5668) indicated that participants with greater adherence to plant-based diets had significantly lower risks of cognitive impairment and dementia (pooled risk ratio, 0.74; 95% confidence interval, 0.56-0.97; I² = 92.3%) than those with lower adherence. Dose-response relationships modeled using restricted cubic splines indicated that overall PDI and hPDI were negatively associated with risks of cognitive impairment and dementia, whereas uPDI was significantly positively associated with these risks.

Conclusions: This meta-analysis suggests that adherence to plant-based diets, particularly those rich in healthful plant foods, may be associated with a lower risk of cognitive impairment and dementia. However, given the residual heterogeneity and the inherent limitations of observational study designs, large randomised controlled trials are warranted to establish causality.

Background: Whether healthy lifestyle behaviors are associated with Alzheimer's disease (AD) risk among individuals with hyperlipidemia remains unclear.

Methods: We analyzed 241,642 dementia-free participants from the UK Biobank. A weighted lifestyle score (0-7) was derived from seven factors and categorized into five tiers. Hyperlipidemia was defined as lipid-lowering medication use or LDL-cholesterol ≥ 4.0 mmol/L. Cox regression estimated hazard ratios (HRs) and 95% confidence intervals (CIs).

Results: Over a median follow-up of 14.5 years, 1728 AD cases occurred, including 977 cases among 104,082 individuals with hyperlipidemia. Compared with the intermediate tier, unhealthy lifestyle was associated with elevated AD risk (HR: 1.17; 95% CI: 1.02-1.35), while healtshy and very healthy tiers were associated with progressively lower risk (HR=0.85 and 0.74, respectively). These associations were evident among individuals with hyperlipidemia, but not statistically significant among those without hyperlipidemia.

Conclusions: Healthy lifestyle patterns were associated with lower AD risk among individuals with hyperlipidemia, with greater risk reductions observed for healthier lifestyle tiers.

Introduction: We hypothesize that specific cognitive assessments and plasma biomarkers may exhibit heightened sensitivity during the stage of subjective cognitive decline (SCD). The integration of these plasma biomarkers and cognitive assessments could enhance the ability to predict beta-amyloid (Aβ) pathology in individuals with SCD.

Methods: A total of 231 participants, including 74 normal controls (NC) and 157 SCD, underwent Aβ and tau PET scans and blood testing for Aβ40, Aβ42, p-tau181, p-tau217, NfL, and GFAP. Cognitive assessments, plasma biomarkers, tau PET SUVr, and demographics were compared between Aβ+ and Aβ- groups within NC and SCD. The least absolute shrinkage and selection operator (LASSO) and logistic regression were employed to perform variable selection and develop predictive models.

Results: We observed significantly worse global cognition, visuospatial memory performance, executive function, and metamemory, as well as higher tau PET SUVr, elevated levels of p-tau217, p-tau181, and GFAP, and lower Aβ42/Aβ40 ratios in SCD Aβ+ compared to SCD Aβ-. The model incorporating BVMT-LD and p-tau217 achieved a slightly higher AUC than the model using p-tau217 and Aβ42/Aβ40 (0.94 vs. 0.93). Partial correlation analyses indicated that both auditory verbal memory (AVLT-LD) and visuospatial memory (BVMT-LD) were significantly negatively associated with p-tau217, whereas only AVLT-LD demonstrated a significant negative association with tau pathology severity.

Conclusion: Visuospatial memory deficit and plasma p-tau217 are powerful biomarkers for identifying Aβ+ in SCD. Auditory verbal memory links to tau pathology severity, while visuospatial memory is more sensitive to Aβ deposition, supporting early intervention to prevent AD progression.

Background: Lifestyle factors play a critical role in healthy aging, yet their relationships with aging biomarkers remain insufficiently characterized, particularly in Asian populations. This study aimed to examine the cross-sectional and longitudinal associations between 15 modifiable lifestyle factors and two DNA methylation (DNAm) clocks (GrimAge acceleration [AgeDev] and DunedinPACE) in a cohort of older Asian adults.

Methods: We conducted a cross-sectional analysis of 631 participants (median age 70.0 years; 72.6% female) and a longitudinal analysis of 114 participants (mean follow-up 3.96 years) from the Singapore Diet and Healthy Aging (DaHA) cohort. Lifestyle exposures were assessed using validated self-administered questionnaires. Peripheral blood DNAm profiles were generated using the Illumina MethylationEPIC array. Multivariable linear regression models were applied to evaluate associations between lifestyle factors and DNAm clocks, adjusting for sociodemographic covariates, health status, and immune cell-type proportions.

Results: In cross-sectional analyses, smoking history showed robust positive associations with accelerated epigenetic aging (GrimAge AgeDev: β = 1.45, 95% CI 1.13-1.77, p < 0.0001; DunedinPACE: β = 0.63, 95% CI 0.22-1.05, p = 0.003). Conversely, weekly physical activity was associated with slower aging (GrimAge AgeDev: β = -0.22, 95% CI -0.40 to -0.04, p = 0.02), as was daily engagement in cognitively stimulating activities (GrimAge AgeDev: β = -0.16, 95% CI -0.31 to -0.01, p = 0.04). Weekly feelings of stress were initially associated with greater GrimAge AgeDev, but this relationship was attenuated after full adjustment. No significant longitudinal associations were detected, which may reflect limited statistical power and the stability of long-standing lifestyle behaviors over the follow-up period.

Conclusions: These findings highlight significant cross-sectional associations between key modifiable lifestyle factors, particularly smoking, physical activity, and cognitive engagement, and epigenetic aging in an older Asian cohort. The results suggest that interventions targeting these behaviors may modulate the pace of biological aging. The absence of significant longitudinal associations underscores the need for larger prospective studies with longer follow-up and continued validation of epigenetic clocks in diverse populations to confirm these relationships over time.

Background: Serum β-synuclein is an emerging blood-based biomarker for synaptic integrity in Alzheimer's disease (AD). However, its comparative performance against the established CSF marker neurogranin and its prognostic utility for longitudinal disease progression remain to be fully characterized.

Method: We analyzed 475 participants from the Alzheimer's Disease Neuroimaging Initiative. We compared serum β-synuclein and CSF neurogranin using receiver operating characteristic analysis and Cox proportional hazards models. We also assessed the cross-sectional associations of both biomarkers with cognitive and neuroimaging markers using linear regression. Linear mixed-effects models were applied to determine if baseline serum β-synuclein levels and longitudinal rate of change predicted disease progression. Finally, the trajectory of serum β-synuclein was modeled across the AD continuum.

Results: Serum β-synuclein distinguished clinical AD dementia from controls with high accuracy (AUC = 0.84). Cross-sectionally, it exhibited robust associations with cognitive deficits and neuroimaging markers, comparable to or exceeding those of CSF neurogranin. Higher baseline serum β-synuclein, but not CSF neurogranin, significantly predicted the risk of conversion to dementia (hazard ratio = 1.83). Longitudinally, both elevated baseline levels and faster rates of increase in serum β-synuclein predicted accelerated cognitive decline and neurodegeneration, independent of baseline amyloid or tau pathology. Trajectory analysis revealed that serum β-synuclein levels accelerated significantly over time specifically in individuals with concurrent amyloid and tau pathology.

Discussion: Serum β-synuclein serves as a robust prognostic biomarker for AD, demonstrating diagnostic accuracy for clinical dementia and superior predictive utility for disease conversion compared to CSF neurogranin. Its ability to track synaptic degeneration independent of core proteinopathies highlights its potential as a dynamic outcome measure for monitoring disease progression in clinical trials.

Dementia frequently goes undetected in community settings, particularly among socially disadvantaged populations. Here, we estimated the prevalence of underdiagnosed dementia across diverse sociodemographic determinants of health in the Health and Aging Brain Study-Health Disparities (HABS-HD), a community-based cohort of adults recruited through community outreach in Fort Worth, Texas. We estimated age-specific probabilities of underdiagnosis using Poisson regression models with a log link, including age and sex as covariates. Robust (sandwich) variance estimators were used to obtain standard errors and 95% confidence intervals (CI). Group differences or trends for continuous measures were assessed using robust variance estimates. The prevalence of underdiagnosed dementia was higher among individuals without physician access (98.1% vs. 78.1%, p<.0001), non-English speakers (97.9% vs. 76.8%, p<.0001), and the uninsured (91.5% vs. 79.5%, p=.03). Black and Hispanic participants also showed higher prevalence (85.8% and 90.9%) compared to non-Hispanic White participants (64.9%; p=.02 and p=.002, respectively). Each additional year of education was associated with a 2.5% lower risk of underdiagnosis (p<.0001). No differences were observed by sex, marital status, income or social support. Our results highlight that several sociodemographic factors contribute to the likelihood of living with undiagnosed dementia.

Background: Observational studies have shown associations between immune cells, lipids, and Alzheimer's disease (AD), but their specific causal relationships and the mediating role of lipids remain unclear.

Methods: Within a network Mendelian randomization (MR) framework, we first applied two-sample univariable MR to assess the causal effects of immune cells and lipids on AD. Then, multivariable MR was used in mediation analyses to determine whether lipids mediate the effects of immune cells on AD. Finally, reverse MR analyses were performed to minimize potential bias from reverse causation. The inverse variance weighted method was used as the primary estimator.

Results: The analysis revealed that elevated levels of CD33 on CD33dim HLA DR+ CD11b+ and CD33 on CD33dim HLA DR+ CD11b- were associated with an increased risk of AD. Mediation analysis further indicated that polyunsaturated fatty acids are protective lipid metabolites for AD and partially mediate the effects of the aforementioned immune cells on AD, with mediation proportions of 3.70 % and 3.67 %, respectively.

Conclusion: This study provides new insights into how immune cells may influence AD pathogenesis through lipid metabolism. It also offers a theoretical basis and potential direction for developing immune-lipid-based strategies for AD prevention and intervention.