Psychological and neurobiological mechanisms involved in the relationship between loneliness and cognitive decline in older adults

Loneliness, among older adults, is one of the risk factors for developing dementia. Still, little is known about the neurobiological and psychological conditions that link loneliness to cognitive decline. The current study investigated several research aims: First, it sought to identify neurobiological and psychological pathways that may account for the relationship between loneliness and decline across several cognitive domains. These pathways included depressive symptoms, total gray matter volume, and conditional analyses of pro-inflammatory cytokines and brain-derived neurotrophic factor (BDNF) expression. Second, it examined loneliness as a predictor of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Third, it sought to determine whether the relationship between loneliness and cognitive decline is sex-specific in older adults. Longitudinal data were collected from 2130 Rush Memory and Aging Project participants. Participants underwent annual cognitive and psychological assessments and neuroimaging procedures every year. BDNF gene expression was measured in the dorsolateral prefrontal cortex, cytokines were measured in serum, and the final consensus clinical diagnosis was identified at the time of death. All linear mixed and multinomial logistic regression models controlled for age at baseline, education, sex, and APOE genotype. Participants were largely women (73 %), and Caucasian (93 %). The average education was 14.93 (SD = 3.34). The average age at baseline was 80.05 (SD = 7.57). Results showed that gray matter volume and depressive symptoms partially mediated the relationship between loneliness and cognitive decline. There was a significant interaction between loneliness and BDNF expression in relation to cognitive decline. Higher levels of BDNF expression was associated with slower decline in semantic memory and visuospatial ability. Finally, the current study also established that higher levels of loneliness was positively associated with the incidence of AD and other dementias. The present findings support the growing literature, which tends to show that the consequence of loneliness goes beyond the feeling of being isolated. Loneliness may induce physiological changes in our brains, leading to cognitive decline. Future research can explore a wide range of biological and psychological expressions of loneliness to clarify how loneliness relates to dementia.