Association between anxiety symptoms and Alzheimer’s disease biomarkers in cognitively healthy adults: A systematic review and meta‐analysis

AbstractBackgroundAnxiety has been identified as both a risk factor and prodromal symptom for Alzheimer’s disease (AD) and related dementias, however, the underlying neurobiological correlates remain unknown. The aim of this systematic review and meta‐analysis was to examine the association between anxiety symptoms and two defining markers of AD neuropathology: amyloid‐beta (Aβ) and tau.MethodSystematic literature searches were conducted across 5 databases. Studies investigating the relationship between anxiety and AD neuropathology (i.e., Aβ and/or tau) in cognitively healthy adults were eligible. Where possible, effect sizes were combined across studies, for Aβ and tau separately, using random‐effects meta‐analyses. Sensitivity analyses were performed to assess whether results differed according to anxiety type (i.e., state and trait) and biomarker assessment modality (i.e., positron emission tomography and cerebrospinal fluid). Between‐study heterogeneity was quantified using I 2 with 95% confidence intervals (CI), publication bias evaluated by examining funnel plots, and risk of bias assessed via the National Heart, Lung, and Blood Institute Quality Assessment Tool.ResultTwenty‐seven studies reporting data from 14 unique cohorts met eligibility criteria (Figure‐1). All studies received a quality rating of either ‘good’ (k = 15) or ‘fair’ (k = 12). Random‐effects meta‐analyses revealed no associations between self‐reported anxiety symptoms and either Aβ (13 studies, N = 5141; Fisher’s z = 0.02, 95% CI ‐0.01–0.05, p = 0.194 [Figure‐2]) or tau (4 studies, N = 1126; Fisher’s z = 0.04, 95% CI ‐0.02–0.09, p = 0.235 [Figure‐3]). There was no evidence of publication bias and heterogeneity was low (I 2 = 0.0%). Results remained substantively unchanged across sensitivity analyses assessing the effects of anxiety type and biomarker assessment modality.ConclusionIn cognitively healthy adults, meta‐analytic syntheses revealed no associations between anxiety symptoms and either Aβ or tau. There is a critical need, however, for larger studies with follow‐up periods to examine the effect of anxiety symptom onset, severity, and chronicity on AD neuropathology. An association between anxiety and dementia‐related neurobiological correlates is also likely complex, underpinned by multiple factors, and not restricted to AD neuropathology. Further research investigating other potential neurobiological correlates is crucial to advance understanding of the relationship between anxiety and dementia.