Psychosocial risk factors for dementia and brain age: A systematic review

Abstract Psychosocial factors are linked to increased dementia risk, potentially via accelerated brain ageing. Accelerated brain age, where estimated brain age exceeds chronological age, can be estimated using neuroimaging, epigenetic, and transcriptomic approaches. This systematic review examined associations between psychosocial risk factors (depression, anxiety, post-traumatic stress disorder [PTSD], psychological stress, social isolation, loneliness, neuroticism) and brain age in cognitively unimpaired adults, and whether associations differ by severity (clinical cases, symptoms) and age group (early-, middle-, older-adulthood). After screening, 44 studies were included. Findings were narratively synthesized due to heterogeneity. For depression ( k = 32), relationships with brain age were mixed in early-adulthood (cases: 5 of 8 studies [5/8], symptoms: 3/7) and middle-adulthood (cases: 8/12, symptoms: 2/7), with most studies observing no association in older-adulthood (cases: 1/2, symptoms: 1/5). Anxiety ( k = 5) was associated in early-adulthood (cases: 1/1, symptoms: 2/2) but not middle-adulthood (symptoms: 0/3). PTSD ( k = 4) was not associated in early-adulthood (cases: 0/1, symptoms: 0/1) but associations were evident in middle-adulthood (cases: 2/3). Psychological stress ( k = 4) showed mixed findings across early-adulthood (1/2) and middle-adulthood (1/2). Social isolation ( k = 2) was consistently associated in middle-adulthood (2/2), whereas loneliness ( k = 4) was mixed (1/3) and no association in early-adulthood (0/1). Neuroticism ( k = 4) showed no associations across age groups (0/4). Evidence suggests some psychosocial risk factors are associated with brain age, which varies by risk factor, age group and severity. Research in older-adulthood is limited, yet brain ageing is observed in early- and middle-adulthood. Research is needed to establish whether psychosocial health interventions can modify brain ageing trajectories.