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

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.

Clinically relevant anxiety and risk of Alzheimer's disease in an elderly community sample: 4.5 years of follow-up.

OBJECTIVES: To investigate whether clinically relevant anxiety increased the risk for developing Alzheimer's disease (AD) while controlling for the presence of depression and other confounders; and to report the population attributable fraction (PAF) associated with anxiety disorder. METHOD: We used data from the longitudinal, community-based Zaragoza Dementia and Depression (ZARADEMP) study. A random sample of 4057 dementia-free community dwellers aged ≥55 years were followed for 4.5 years. The Geriatric Mental State-Automated Geriatric Examination for Computer Assisted Taxonomy package was used for the diagnosis of clinically significant cases and subcases of anxiety; and AD was diagnosed by a panel of research psychiatrists according to DSM-IV criteria. Multivariate survival analysis with competing risk regression model was performed. RESULTS: We observed a significant association between anxiety cases at baseline and AD risk in the univariate analysis that persisted in the fully adjusted model (SHR: 3.90; 95% CI: 1.59-9.60; p = 0.003), with a PAF for AD of 6.11% (95% CI: 1.30%-16.17%). No significant association between 'subcases' of anxiety at baseline and AD risk was found. LIMITATIONS: Data on apolipoprotein E were not available. The hospital-based diagnosis was not completed in all cases of dementia. CONCLUSION: Late-life, clinically significant anxiety (but not subclinical anxiety) seems to increase the risk of AD, independently of the effect of several confounders, including depression. Taking into account the high prevalence of anxiety among the elderly, future studies are warranted to determine potential risk reduction of AD.

Clinically significant anxiety as a risk factor for dementia in the elderly community.

OBJECTIVE: To evaluate whether clinically significant anxiety is an independent risk factor for dementia, taking into account both depression among potentially confounding factors and the competing risk of death. METHOD: During the Zaragoza Dementia and Depression (ZARADEMP) study, a random sample of community dwellers aged 55 years or older was assessed (n = 4803), and a two-wave, 4.5-year follow-up was completed. Geriatric Mental State (GMS)-AGECAT criteria were used to diagnose anxiety and DSM-IV criteria were applied to diagnose incident dementia. The multivariate Fine and Gray regression model was implemented to calculate dementia risk. RESULTS: Compared with non-cases (GMS-AGECAT criteria), the incidence rate of dementia was significantly higher in subcases of anxiety, and particularly significant in the cases of anxiety (incidence rate ratio (IRR): 2.77; P = 0.010). Cases of anxiety, but not subcases, at baseline were significantly associated with dementia risk (adjusted subdistribution hazard ratio (SHR): 2.7; P = 0.019). CONCLUSION: Clinically significant anxiety is associated with an almost threefold increase in the risk of dementia in the population, even when controlling for depression and considering mortality in the competing risks model.