Loneliness Induces Brain Changes That Fuel Cognitive Decline

Gray matter volume, BDNF and cytokine levels, and depressive symptoms partially mediate the cognitive decline associated with loneliness.

Risk Factors for Cognitive Decline

Loneliness contributes to both psychological risk factors for cognitive decline and structural brain changes that are linked to dementia, according to study results published in Brain Behavior and Immunity. Given that older adults are more susceptible to loneliness, targeted interventions for this vulnerable population are needed to prevent adverse health impacts.

Previous research has established a relationship between loneliness and poorer mental and physical health outcomes, particularly among older adults. However, few studies have examined the neurobiological mechanisms underlying loneliness in adults aged 65 and older, and how these changes may impact cognitive function. To investigate this further, researchers used data from the Rush Memory and Aging Project (RMAP) determine whether the psychobiological conditions of loneliness increase the risk for cognitive decline among adults aged 65 and older.

To measure loneliness, participants completed a modified version of the de Jong-Gierveld Loneliness Scale. The researchers assessed 5 cognitive domains: episodic memory, semantic memory, working memory, visuospatial ability, and processing speed. Additionally, the researchers examined levels of proinflammatory cytokines and brain-derived neurotrophic factor (BDNF), depressive symptoms, and total gray matter volume as potential contributing factors to the relationship between loneliness and cognition.

A total of 2130 participants had complete data for loneliness, depressive symptoms, and cognitive measures. Among these participants, 73% were women, 93% were White, 5% were Hispanic, and they were 80.1 years of age, on average. However, the sample size was reduced for the analyses that evaluated cytokines (n=414-423), BDNF (n=272), and gray matter volume (n=664).

The researchers found that loneliness was negatively associated with episodic memory (β= -0.1; SE, 0.01; t = -73; P <.001), semantic memory (β= -0.06; SE, 0.01; t = -5.9; P <.001), working memory (β= -0.06; SE, 0.00; t = -5.9; P <.001), visuospatial ability (β= -0.07; SE, 0.01; t = -7.25; P <.001), processing speed (β= -0.08; SE, 0.01; t = -3.86; P <.001), and global cognition (β= -0.06; SE, 0.01; t = -8.32; P <.001).

The researchers then evaluated potential pathophysiological pathways that may explain the relationship between loneliness and cognition. The researchers observed a significant, positive correlation between BDNF levels and all cognitive domains (all P <.001). When BDNF was added to the linear mixed model, there was a 3-way interaction between BDNF, time, and loneliness (β=0.05; SE, 0.02; P <.05) and a likelihood ratio test indicated that adding BDNF to the model significantly improved the model’s prediction (χ2=6.59; P =.01). Similarly, the researchers observed a 3-way interaction between cytokine levels, time, and loneliness (β= -0.12; SE, 0.05; P <.05)

Total gray matter volume was also a significant mediator of the relationship between cognition and loneliness, with the exception of working memory, accounting for 15% to 25% of the observed relationship. Further, depressive symptoms were a mediating factor for all cognitive domains except visuospatial ability. The mediating effect of depressive symptoms explained 12% of the relationship between loneliness and episodic memory, 17% of processing speed, 41% of visuospatial ability, and 15% of global memory.

Study authors concluded, “As demonstrated in this study, loneliness is related not only to psychological risk factors of cognitive decline, such as depression but also to structural changes in the brain that are significant predictors of dementia.”

Study limitations include the fact that the observed significant associations between longitudinal scores of loneliness and cognitive decline had a small effect size, the sample size was smaller for participants with neuroimaging and measures of loneliness and depressive symptoms, and most MAP participants were White.

Note: This article originally appeared on Psychiatry Advisor