Late-life depression, allostatic load, and risk of dementia: The AGES-Reykjavik study

The current study aimed to assess if the relation between depression and dementia could be explained by allostatic load (AL) profiles, as well as assessing their risk on incident all-cause dementia, Alzheimer's disease (AD), and non-AD dementias.

The study included individuals without dementia at baseline from the population-based AGES-Reykjavik Study. Depressive symptoms assessed with the Geriatric Depression Scale-15 and AL markers were collected at baseline. Latent profile analysis (LPA) was performed on the AL markers. Incident dementia was measured during 12-years of follow-up. Cox regressions adjusted for AL profiles were performed to evaluate if AL could explain the relation between depressive symptoms and incident dementia. Additional Cox regressions exploring the interaction with depressive symptoms and AL profiles were also performed.

LPA revealed four profiles based on AL factors: 'Low cardiovascular dysregulation' (43 %), 'Average' (42 % prevalence), 'High cardiovascular dysregulation' (11 %), and 'Multisystem dysregulation' (4 %). Cox regression analyses found an increased risk for dementia in the 'Multisystem dysregulation' group (HR 1.72; 95 % CI 1.26-2.33), as well as for AD (HR 1.75; 95 % CI: 1.12-2.71) and non-AD dementias (HR 1.87; 95 % CI: 1.23-2.84). AL profiles did not mediate the risk of all-cause dementia with depressive symptoms; however, there was evidence of additive interaction with depressive symptoms and the 'Multisystem dysregulation' profile and all-cause dementia (RERI 0.15; 95 % CI 0.03-0.26).

AL profiles and depressive symptoms were independently related to dementia. Individuals with multisystem dysregulation could be more susceptible to the negative effects of depressive symptomology on incident dementia.