Risk of hemorrhagic and ischemic stroke in patients with Alzheimer disease: A synthesis of the literature

Objective To assess the risk of hemorrhagic and ischemic stroke in patients with Alzheimer disease (AD) compared to non-AD subjects with similar risk profiles. Methods A search was conducted on Embase and Medline for reports published up to September 26, 2018. Studies were included if they: 1) assessed incidence of stroke in patients diagnosed with AD; 2) included patients with no history of stroke; and 3) reported outcomes by stroke subtype. The main outcome was relative risk of ischemic or hemorrhagic stroke. Further, the rate of stroke occurrence per 1000 person-years was assessed. A random effects meta-analysis was undertaken. The risk of bias in included studies was assessed in terms of selection, comparability and outcome. Results 3,605 studies were screened in the title and abstract phase after removing duplicates, and 88 eligible studies were screened for full text. Eight studies met the inclusion criteria representing 121,719 subjects (AD=73,044; non-AD=48,675). Five studies were included in the relative risk analysis, among which four studies applied formal matching criteria of 44,544 AD and 44,660 non-AD subjects. The included studies were based on nation-wide registries from Finland, Sweden, Taiwan (2), UK (2), one clinic-based study from the Netherlands and one US population-based cohort. Among AD patients, the incidence rate of hemorrhagic stroke was 3.41/1000-person years (95% CI 2.70, 4.32) and 2.23 (95% CI 1.72, 2.88) among AD-cases and non-AD controls respectively. This is in contrast to 13.98 (95% CI 9.86, 19.81) and 12.12 (95% CI 7.55, 19.46) for ischemic stroke among AD-cases and non-AD controls respectively. Compared to non-AD subjects with similar risk profiles, AD patients had a relative risk of 1.42 (95% CI 1.23, 1.64) for hemorrhagic stroke and 1.15 (95% CI 0.89, 1.48) for ischemic stroke. Conclusion Compared to non-AD subjects with similar risk profiles, AD patients are likely at higher risk of hemorrhagic, but not ischemic stroke