Cortical thickness and low-grade inflammation moderate the association between depressive symptoms and cognitive...

Spousal bereavement is a major life stressor that significantly increases the risk of dementia. However, it remains unclear how the bereavement experience accelerates cognitive aging. In the broader neurocognitive aging literature, depression and cognitive function are closely linked, such that depression is sometimes accompanied by cognitive impairments. Individual differences in depression-related cognitive function may depend on low-grade inflammation and cortical atrophy, two phenomena implicated in cognitive dysfunction and dementia risk. No study to date has examined how psychobiological health relates to cognition in early widowhood. Among recently bereaved spouses, we examined (1) whether depressive symptom severity accounted for variations in cognitive performance and (2) whether the association between depressive symptoms and cognitive function depended on one's biological profile. In a sample of 68 bereaved spouses, depressive symptom severity, cortical thickness in 8 a priori regions, serum proinflammatory composite (IL-6, sIL-6R, TNF-⍺, sTNFRI, and sTNFRII), and a battery of cognitive tests were evaluated at 6 months post-loss. Using multiple linear regression to test hypotheses, we observed a significant negative association between depressive symptoms and performance on global cognitive function, cognitive inhibition, visuospatial processing, and working memory. The interaction between depressive symptoms and the cortical signature composite on global cognition was statistically significant: Depressive symptoms were negatively associated with global cognitive function, only for widow(er)s with average and less than average cortical gray matter. The interaction between depressive symptoms and low-grade inflammation on cognitive inhibition was also statistically significant: Depressive symptoms were negatively associated with cognitive inhibition only for those with average and higher than average levels of the serum inflammatory composite. This suggests that widow(er)s experiencing higher levels of depressive symptoms were more likely to have poorer cognitive function, especially if they presented with a more adverse biological profile (i.e., higher cytokine levels and less cortical gray matter than average); in contrast, for widow(er)s with less adverse biological profiles, there was no evidence for an association between depressive symptoms and cognitive function. This exploratory study identifies psychobiological correlates of cognitive function in early widowhood, offering insight into risk factors for abnormal cognitive aging after profound interpersonal loss.