Persistent loneliness predisposes adults to cognitive decline

Adults suffering from persistent loneliness are likely to experience worse cognitive function and alterations in brain structure, suggests new evidence from the ongoing Whitehall II cohort study, presented at AAIC 2024.

“Persistent loneliness was associated with both longitudinal cognitive decline and decreased brain regions involved in emotional regulation, suggesting persistent loneliness feelings … could be a risk factor in the neuropathology of Alzheimer’s disease (AD),” said presenting author Ye Zhang from the Department of Aging Research and Geriatric Medicine, Tohoku University, Japan.

“Moreover, recovery from loneliness feeling (transient loneliness) could be protective in future brain structure alterations,” she added.

A total of 5,346 participants (mean age 65 years, 26.68 percent female) were included in this study, which measured loneliness using the Center for Epidemiologic Studies Depression Scale. Longitudinal loneliness changes were then defined from two time points, namely 2002‒2004 and 2007‒2009.

Zhang and her team used linear mixed-effect models to explore the relationship between various types of loneliness and 8-year changes of different cognitive domains (ie, global cognition, verbal fluency, and verbal memory). They also used linear regression models to examine loneliness types and gray matter volumes (GMVs) in selected brain regions 5 years later using the Whitehall II MRI substudy (n=711).

Four types of loneliness changes were identified: no loneliness, transient loneliness, incident loneliness, and persistent loneliness. [AAIC 2024, abstract 641]

After adjustments for age, sex, education, and objective social isolation, persistent loneliness when compared with no loneliness showed a significant association with a decrease in all domains of cognitive function: global cognition (b, ‒0.20; p<0.001), reasoning (b, ‒0.29; p<0.001), verbal memory (b, ‒0.11; p<0.007), and verbal fluency (b, ‒0.15; p=0.001).

Persistent loneliness also contributed to reduced GMVs in the right posterior cingulate cortex (b, ‒0.17; p=0.041) when compared with no loneliness. On the other hand, transient loneliness correlated with higher GMVs in the rostral anterior cingulate cortex (b, ‒0.48; p=0.025).

AD prevention

These findings suggest the development of strategies to help fight loneliness, which could be significant in the prevention of AD, according to the authors.

“Persistent loneliness shows worse cognitive function in all domains ... [and] could be detrimental to both brain health and cognitive function,” Zhang said. “It’s important to alleviate loneliness and identify people with long-term loneliness.”

“Loneliness is a psychosocial stressor that affects both physical and mental health,” said Zhang, noting that loneliness triggers a “self-confirmatory regulation loop,” resulting in … physiological dysregulation.

In addition, Zhang said that feeling lonely may prevent individuals from engaging in social interactions, reducing cognitive stimulation and thereby affecting brain structure.

“Loneliness has been linked to cognitive decline and an elevated risk of AD,” the authors said. “Previous studies measured loneliness at a single point time, which may not accurately capture the longitudinal changes of different loneliness types and their impact in the neuropathology of AD.”