Sex differences in the incidence and prevalence of young-onset Alzheimer's disease: A meta-analysis

Objectives: The lifetime incidence of Alzheimer's disease is higher in women than in men, but it remains unclear if similar sex differences exist in young-onset Alzheimer's disease (YOAD). This systematic review test the hypothesis that women have a higher prevalence and incidence of YOAD than men. Methods: We searched Pubmed and Embase (inception to 11 June 2020) for original publications of population-based observational studies with data on the prevalence and/or incidence of YOAD, defined as a medical diagnosis of Alzheimer's disease before the age of 65 years. Data on cross-sectional and/or prospective numbers, percentages, incidences, and incidence rates (in person-years) were derived from included studies. Quality assessment was done using the Nottingham Ottawa Scale. Meta-analyses were done to test the hypothesis that women have a higher prevalence and incidence of YOAD than men. Results: After screening of 3252 titles, 12 articles were included. The pooled prevalence was 0.4% (confidence interval [CI] = 0.1–2.1) in women and 0.2% (CI = 0–1.2) in men (six studies, relative risk [RR] = 1.54, CI = 0.69–3.44, I² = 38%). The pooled incidence was 0.02% (CI = 0.01–0.08) in women and 0.01% (CI = 0–0.05) in men (five studies, RR = 1.50, CI = 0.91-2.48, I² = 0%). The incidence rates per 100,000 person-years ranged from 0 to 132 in women and from 0 to 42 in men. Conclusions: Given the low prevalence and wide CIs, no firm conclusions can be drawn. Large-scale studies are required to verify that women are more likely than men to develop YOAD.