Social genomics, cognition, and well-being during the COVID-19 pandemic.

Introduction: Adverse psychosocial exposure is associated with increased pro-inflammatory gene expression and reduced type-1 interferon gene expression known as the conserved transcriptional response to adversity (CTRA). CTRA is not well-studied in cognitive impairment but may contribute to late-life cognitive decline.

Methods: We examined perceived stress, loneliness, well-being, and the impact of coronavirus disease 2019 (COVID-19) and the relationship to the expression of genes associated with the CTRA. Mixed-effect linear models were used to quantify associations between psychosocial variables and CTRA gene expression.

Results: Eudaimonic well-being (EWB) was inversely associated with CTRA gene expression in participants with both normal cognition (NC) and mild cognitive impairment (MCI). Self-reported coping strategies differed by cognitive status and variably impacted CTRA gene expression.

Discussion: EWB is an important correlate of stress, even in people with MCI. The prodromal cognitive decline appears to moderate the significance of coping strategies as a correlate of CTRA gene expression.

Highlights: Conserved transcriptional response to adversity (CTRA) gene expression is higher with lower eudaimonic well-being.Eudaimonic well-being was important in both participants with normal cognition and those with mild cognitive impairment.Coping strategies and impact on CTRA gene expression differed by cognitive status.Loneliness in a population with relatively low loneliness scores did not impact CTRA gene expression.