A Meta-Analysis of the Relationship between Stroke and Alzheimer's Disease: Therapeutic and Prognostic Implications

Several population-based studies have highlighted an association between stroke and dementia. Alzheimer's disease (AD)-related dementia and vascular dementia are the most common causes of dementia, with clear pathophysiological mechanisms for the latter. Given the ongoing debate surrounding the link between stroke and AD, a systematic meta-analysis was performed to determine their relationship and the possible influence of some moderators (sex, age, and region).

We searched five databases (ISI Web of Science, Scopus, PubMed, Elsevier ScienceDirect, and Google Scholar) with no initial publication date restriction, and the last search was conducted in 2022. We included longitudinal population-based studies assessing the stroke-AD association, selecting those with reported effect sizes, standardized AD diagnosis, and an AMSTAR score ≥9. Case reports, reviews, animal studies, and non-English publications were also excluded. The meta-analysis, conducted using Comprehensive Meta-Analysis 3.1, presented pooled log odds ratios (LogOR) with 95% confidence intervals, heterogeneity analysis (Cochran's Q, I2), and moderator analyses by age, sex, and region.

The meta-analysis included 3 meta-analyses and 12 primary studies, comprising a total of 14,207 stroke cases and 1,952 AD cases. Our analysis revealed a significant association between ischemic stroke (IS), hemorrhagic stroke (HS), and microinfarcts (MI) and the risk of AD. Despite some heterogeneity across studies, no significant differences were observed in the stroke-AD association based on age, sex, or region.

Our study describes the risk of AD in patients with episodes of stroke (IS, HS, and MI) and suggests that the risk of AD may be higher in stroke patients than in matched controls without stroke incidence. Moreover, the moderator analysis supports the robustness of our results. The link between stroke and AD suggests that stroke may accelerate cognitive decline. This calls for tighter vascular control and indicates worse prognosis in dementia progression.