Abstract
OBJECTIVES: Anxiety is an increasingly recognised predictor of cognitive deterioration in older adults and in those with mild cognitive impairment. Often believed to be a prodromal feature of neurodegenerative disease, anxiety may also be an independent risk factor for dementia, operationally defined here as preceding dementia diagnosis by ≥10 years. DESIGN: A systematic review of the literature on anxiety diagnosis and long-term risk for dementia was performed following published guidelines. SETTING AND PARTICIPANTS: Medline, PsycINFO and Embase were searched for peer-reviewed journals until 8 March 2017. Publications reporting HR/OR for all-cause dementia based on clinical criteria from prospective cohort or case-control studies were selected. Included studies measured clinically significant anxiety in isolation or after controlling for symptoms of depression, and reported a mean interval between anxiety assessment and dementia diagnosis of at least 10 years. Methodological quality assessments were performed using the Newcastle-Ottawa Scale. OUTCOME MEASURE: HR/OR for all-cause dementia. RESULTS: Searches yielded 3510 articles, of which 4 (0.02%) were eligible. The studies had a combined sample size of 29 819, and all studies found a positive association between clinically significant anxiety and future dementia. Due to the heterogeneity between studies, a meta-analysis was not conducted. CONCLUSIONS: Clinically significant anxiety in midlife was associated with an increased risk of dementia over an interval of at least 10 years. These findings indicate that anxiety may be a risk factor for late-life dementia, excluding anxiety that is related to prodromal cognitive decline. With increasing focus on identifying modifiable risk factors for dementia, more high-quality prospective studies are required to clarify whether clinical anxiety is a risk factor for dementia, separate from a prodromal symptom.