Supplementary Material for: A META ANALYSIS OF THE RELATIONSHIP BETWEEN STROKE AND ALZHEIMER’S DISEASE: THERAPEUTIC AND PROGNOSTIC IMPLICATIONS

Background: Several population-based studies have highlighted the association between stroke and dementia. Alzheimer’s disease (AD) related dementia and vascular dementia are the most common causes of dementia, with clearer pathophysiological mechanisms for the latter. Given the ongoing debate surrounding the link between stroke and Alzheimer’s disease, to determine their relationship and the possible influence of some moderators (sex, age, and region), a systematic meta-analysis was performed.
Methods: We searched five databases (ISI Web of Science, Scopus, PubMed, Elsevier Science Direct, and Google Scholar) with no initial publication date restriction, with the last search 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 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, gender, and region.
Results: The meta-analysis included three meta-analyses and twelve primary studies, comprising a total of 14,207 stroke cases and 1,952 AD cases. Our analysis found a significant association between ischemic stroke (IS), hemorrhagic stroke (HS), and microinfarcts (MI) with 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.
Conclusion: 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 patients that suffer stroke when compared to matched controls without incidence of stroke. Moreover, moderator analysis supports the robustness of our results. The link between stroke and Alzheimer's suggests that stroke may speed up cognitive decline. This calls for tighter vascular control and points to a worse prognosis in dementia progression.