Depression interacts with allostatic load to predict cognitive decline in middle-age

Allostatic load (AL) indicates the cumulative impact of stress on homeostatic mechanisms. Depression and AL have been associated with cognitive deficits, but it is unclear if they do so independently. Using data from middle-aged participants in the observational longitudinal Midlife in the United States (MIDUS) study (n = 704, 57.5 % female, 63.8 ± 10.6 years old in 2014), we assessed whether the effect of prior depression (Composite International Diagnostic Interview Short-Form in 1995) on cognitive decline between 2004 and 2013 (composite Z-scores derived from the Brief Test of Adult Cognition by Telephone and the Stop & Go Switch Task) was moderated by AL Z-scores in 2004 (calculated from biomarkers in blood, urine, and electrocardiography). A significant depression × AL interaction predicted a decline in a composite cognitive score (β = −0.066, SE=0.029, p = 0.024) and executive function (β = −0.068, SE=0.025, p = 0.007). Depression predicted a decline in composite cognition among those with AL Z-scores above − 0.055. AL subdomains of inflammation and lipid metabolism showed evidence of moderation. Middle-aged adults with depression who had higher allostatic load were at greater risk of cognitive decline. Future studies should evaluate whether the interaction predicts incident dementia, and whether interventions targeting depression or elevated AL in people who have both can attenuate cognitive decline.