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Social isolation was linked with lower volume in brain areas related to cognition and associated with a higher risk of subsequent dementia as well, a longitudinal study showed.

Among more than 460,000 participants in the , social isolation at age 57 was tied to a 26% increased risk of dementia 12 years later, independent of risk factors like loneliness and depression, reported Jianfeng Feng, PhD, of Fudan University in Shanghai, China, and co-authors.

Socially isolated individuals also had lower gray matter volume in temporal, frontal, and hippocampal regions, the researchers wrote in .

"People who reported high levels of social isolation were more likely to show significant differences in brain volume, in regions that we know as also associated with cognition problems and risk of dementia," said co-author Barbara Sahakian, PhD, of the University of Cambridge, England, in a statement.

"This is very concerning and suggests to us that social isolation may be an early indicator of an increased risk of dementia," she added.

Recent research has shown that lonely older adults who otherwise would be expected to have relatively low risk had a threefold greater risk of dementia than those who weren't lonely. Midlife loneliness also has been tied to late-life dementia and Alzheimer's disease.

Few studies, however, have looked at social isolation separately from loneliness.

"There is a difference between social isolation, which is an objective state of low social connections, and loneliness, which is subjectively perceived social isolation," said co-author Edmund Rolls, PhD, of the University of Warwick in England.

"Both have risks to health, but using the extensive multi-modal data set from the U.K. Biobank and working in a multidisciplinary way linking computational sciences and neuroscience, we have been able to show that it is social isolation, rather than the feeling of loneliness, which is an independent risk factor for later dementia," he noted.

"With the growing prevalence of social isolation and loneliness over the past decades, this has been a serious yet underappreciated public health problem," Rolls added. "Now, in the shadow of the COVID-19 pandemic there are implications for social relationship interventions and care, particularly in the older population."

The study looked at 462,619 people in the U.K. Biobank with a mean baseline age of 57; 45.4% were men and 95.3% were Caucasian. Enrollment in the study started in 2006, and data were collected until Jan. 31, 2021.

At baseline, 41,886 people (9%) said they were socially isolated, and 29,036 people (6%) said they felt lonely.

Compared with controls, both isolated and lonely people had worse cognitive function, after adjusting for age, sex, ethnicity, education, and income. Depressive symptoms also were significantly associated with cognitive function after adjusting for the same variables (P<0.001 for all).

Over a mean follow-up of 11.7 years, 4,998 people developed all-cause dementia. Dementia incidence was 26% higher in people who reported being socially isolated (adjusted HR 1.26, 95% CI 1.15-1.37).

The adjusted HR for dementia related to loneliness was 1.04 (95% CI 0.94-1.16), but 75% of this relationship was attributable to depressive symptoms.

Subgroup analyses showed relationships between social isolation and dementia were consistent for men and women. Analyzed by age, only socially isolated people in an older group (mean age 64.6; 43% of the sample) had a significant association with dementia (adjusted HR 1.28).

A subset of 32,263 participants (mean age 63.5, 52% female) had neuroimaging an average of 8.8 years after baseline. Of these, 2,371 people (7%) reported being socially isolated and 1,503 people (5%) said they were lonely. Gray matter volume partly mediated the association between social isolation at baseline and cognitive function at follow-up.

Preventing age-related neurodegeneration lies at the heart of much clinical research in Alzheimer's disease, noted Lawrence Whalley, MD, of the University of Aberdeen in Scotland, in an . "Older people living socially isolated lives are more likely to be lonely, but loneliness alone is insufficient to increase their dementia risk," Whalley observed.

This research sets new tasks for dementia prevention, Whalley pointed out.

"The first is to show where social isolation appears as a primary agent leading to dementia and is not a consequence of cognitive impairment," he wrote. "What follows becomes an intellectual challenge to reveal the substructure of social isolation and to identify those elements most relevant to dementia risk."

Participants in the U.K. Biobank had fewer self-reported health conditions and were less likely to live alone than the general population, Feng and colleagues acknowledged. How this may influence associations of social isolation and loneliness with dementia risk is unknown.

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