Non-Genetic Risk Factors for Degenerative and Vascular Young Onset Dementia: Results from the INSPIRED and KGOW Studies

Background: Several brain reserve, vascular risk, and other modifiable factors have been associated with late-onset dementia, but their association with young onset dementia (YOD) has not been adequately explored. Objective: To examine the association of cognitive reserve enhancing factors, cardiovascular risk factors (including smoking), depression, alcohol use, and traumatic brain injury (TBI) with non-autosomal dominant degenerative and/or vascular YOD. Methods: Data for this matched case-control study were taken from two larger studies conducted in NSW, Australia. One comprised all people with YOD within a geographical region, while the other exclusively included Aboriginal and Torres Strait Islander participants. Dementia diagnosis was confirmed by clinical consensus, and risk exposure was retrospectively self- and/or informant-reported. Results: Participants were 96 people with YOD (58.4% with probable Alzheimer's disease) and 175 age-group, sex, and sample matched control participants. Poor educational attainment, low participation in cognitive leisure activity, stroke, transient ischemic attack, and self-reported very heavy alcohol use were related to the risk of primary degenerative and/or vascular YOD. The effect of hypertension and depression varied depending on when they occurred relative to dementia onset. Current smoking was significantly associated with risk in univariate analyses but did not retain significance in multivariate modelling. There was no association with hypercholesterolemia, diabetes, or TBI of any kind. Some compensation for low educational attainment was possible via a complex occupation later in life. Conclusion: Non-genetic factors have a role in YOD, though the relative importance of each factor may be different to late onset dementia. The timing and severity of exposure, as well as the potential for compensation with later protective exposures, are important considerations for potential prevention strategies.