Contributions of modifiable risk factors to increased dementia risk in depression

Background. Individuals with depression have an increased dementia risk, which might be due to modifiable risk factors for dementia. This study investigated the extent to which the increased risk for dementia in depression is explained by modifiable dementia risk factors. Methods. We used data from the English Longitudinal Study of Ageing (2008-2009 to 2018-2019), a prospective cohort study. A total of 7460 individuals were included [mean(standard deviation) age, 65.7 +/- 9.4 years; 3915(54.7%) were women]. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale-8 (score >= 3) or self-reported doctor's diagnosis. Ten modifiable risk factors for dementia were combined in the 'LIfestyle for BRAin health' (LIBRA) score. Dementia was determined by physician diagnosis, self-reported Alzheimer's disease or the shortened version of the Informant Questionnaire on Cognitive Decline in the Elderly (average score >= 3.38). Structural equation modelling was used to test mediation of LIBRA score. Results. During 61 311 person-years, 306 individuals (4.1%) developed dementia. Participants aged 50-70 years with depressive symptoms had higher LIBRA scores [difference(S.E.) = 1.15 (0.10)] and a 3.59 times increased dementia risk [HR(95% CI) = 3.59(2.20-5.84)], adjusted for age, sex, education, wealth and clustering at the household level. In total, 10.4% of the dementia risk was mediated by differences in LIBRA score [indirect effect: HR = 1.14(1.03-1.26)], while 89.6% was attributed to a direct effect of depressive symptoms on dementia risk [direct effect: HR = 3.14(2.20-5.84)]. Conclusions. Modifiable dementia risk factors can be important targets for the prevention of dementia in individuals with depressive symptoms during midlife. Yet, effect sizes are small and other aetiological pathways likely exist.