UC Riverside

The aims of this dissertation were to compare associations between baseline and longitudinal loneliness and performance and change in four specific cognitive abilities and to explore whether DNA methylation at specific locations in blood leukocytes may play a role in the association between loneliness and cognition. In Study 1, we assessed effects of baseline loneliness and two measures of longitudinal loneliness (time-varying loneliness and geometric means for loneliness across waves) on cognitive performance and change across up to 28 years of follow-up in a large pooled sample from the Consortium on Interplay of Genes and Environment Across Multiple Studies (IGEMS). Results showed small effects of loneliness on cognition that varied across cognitive domains, with faster processing speed at age 65 and faster decline in processing speed and spatial ability. In Study 2, we evaluated loneliness and longitudinal methylation and cognitive data in a subsample from the Swedish Adoption/Twin Study of Aging (SATSA) to evaluate associations between loneliness and methylation at 1,586 CpG sites within genes linked with the conserved transcriptional response to adversity (CTRA) using both phenotypic and co-twin control approaches. For sites with associations between loneliness and methylation, regression models were used to explore relations between loneliness, methylation, and cognition. Results showed associations between loneliness and methylation level at age 70 at cg00403457 in PTPN12 and change in methylation with age at cg00619097 in CPT1B and cg26661481 in IL10RA, with partial confounding of these relations by genetic or common environmental factors indicated by co-twin control results. Although direct effects of loneliness on cognition were not significant, indirect associations of perceived loneliness to methylation of cg00403457 in PTPN12 to change in processing speed were observed, indicative of a potential role of methylation at this site in the loneliness—cognition relation. Overall, across study1 and study 2, results indicate that feelings of loneliness predict faster cognitive decline with small albeit meaningful effects that play out across age with hints of indirect mediation via methylation pathways that may be partly genetically moderated. Additional work is needed to further clarify how loneliness relates to cognition change.