Frailty associated with higher odds of incident all-cause dementia and Alzheimer's disease in 835,992 participants.

BackgroundFrailty and dementia are critical geriatric syndromes that pose a substantial global public health burden. While the association between frailty and increased dementia risk is widely recognized, the magnitude of this association, its consistency across populations, and the influence of frailty subtypes remain inadequately synthesized and quantified.ObjectiveTo address this gap, we conducted a systematic review and meta-analysis to precisely estimate the association between frailty and the risk of incident all-cause dementia and Alzheimer’s disease (AD), and to explore sources of heterogeneity through comprehensive subgroup analyses.MethodsWe systematically searched PubMed, Embase, and the Cochrane Library for cohort studies published from inception to March 8, 2025. Data from eligible studies were pooled using random-effects models to calculate summary odds ratios (ORs) with 95% confidence intervals (CIs). Pre-specified subgroup analyses were performed based on geographic region, study design, and frailty subtype. Heterogeneity was assessed using the I2 statistic.ResultsThirteen cohort studies comprising 835,992 participants were included. The meta-analysis showed that frailty was associated with significantly higher odds of all-cause dementia (pooled OR = 1.76, 95% CI: 1.48–2.10). For Alzheimer’s disease, the pooled estimate suggested increased odds but did not reach statistical significance (OR = 1.91, 95% CI: 0.86–4.20), and the evidence was limited by the small number of contributing studies (k = 4) and substantial heterogeneity.ConclusionThis study provides robust, quantitative evidence that frailty is a major independent risk factor for dementia, with the strength of association varying by population and frailty domain. These findings underscore the imperative of integrating standardized, multi-domain frailty assessments into clinical practice to identify high-risk individuals and inform targeted, personalized prevention strategies for dementia.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, CRD420251008804.