Updating the evidence for an association between anxiety and risk of Alzheimer's disease: A meta-analysis of prospective cohort studies.

ABSTRACT

OBJECTIVES: Anxiety is postulated to be a modifiable risk factor for Alzheimer's disease (AD). Our primary aim was to conduct a meta-analysis of prospective cohort studies investigating the association between anxiety and AD risk. DESIGN: We searched multiple scientific databases to identify relevant papers published up to March 2019. Inclusion criteria were prospective cohort studies with a minimum follow-up period of 1 year, baseline anxiety assessment, absence of dementia at baseline, investigated the association between anxiety and AD incidence, and reporting Relative Risks (RRs), or equivalents (HRs and SHRs), for the association between anxiety and AD risk. We excluded studies that focused on subjective memory or mild cognitive impairment samples, review and meta-analyses, not reporting original, published peer-reviewed results. We used a random-effects model that accommodated the differences in association statistics. RESULTS: 7 prospective cohorts (reported in 6 studies), with a total of 24,528 participants, were included in our meta-analysis. A marginally significant association between anxiety and AD risk was found, with a pooled RR of 1.45 (95% CI 1.00-2.12), and a population attributable fraction for AD of 2.8% (95% CI 1.2%-4.3%). LIMITATIONS: There was a high level of heterogeneity across the studies, which may be associated with differences in the covariates adjusted for. Studies also differed considerably in how they measured anxiety. CONCLUSION: Anxiety is marginally associated with an increased risk of AD in this meta-analysis. Future research is needed to determine the extent to which anxiety might be a cause of AD rather than a prodrome or marker.