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Loneliness increased the risk for all-cause dementia, a meta-analysis that included more than 600,000 people showed.

Feeling lonely was tied to a 31% higher risk of overall dementia (HR 1.306, 95% CI 1.197-1.426), according to Martina Luchetti, PhD, of Florida State University in Tallahassee, and co-authors.

Loneliness was associated with both Alzheimer's disease (HR 1.393, 95% CI 1.290-1.504) and vascular dementia (HR 1.735, 95% CI 1.483-2.029), Luchetti and colleagues said.

Moreover, it was linked with cognitive impairment that was not dementia (HR 1.150, 95% CI 1.113-1.189), they reported in .

The study was the largest meta-analysis on the associations between loneliness and dementia, the researchers said. Relationships persisted when models controlled for depression, social isolation, and other modifiable risk factors.

Loneliness differs from being alone or isolated, noted Elizabeth Necka, PhD, of the National Institute on Aging, which supported the study.

"You can be lonely, but socially integrated in terms of having interactions with people. You also can be socially isolated but really enjoy it," Necka told 番茄社区.

Both loneliness and isolation are included in the review of modifiable dementia risk factors, Necka pointed out. The commission estimated that "if we could address loneliness and social isolation, we could reduce the prevalence of dementia cases by 5%," she observed.

"The effect sizes are pretty comparable to more traditional dementia risk factors, like physical activity or smoking," she added. "This is really something that we should be paying more attention to."

Several researchers are exploring ways to integrate in clinical care, she noted. Last year, U.S. Surgeon General Vivek Murthy, MD, MBA, took steps to address loneliness and isolation by proposing a national strategy to .

"In the past years, and particularly after the social restrictions due to the [COVID-19] pandemic, there has been an increasing interest in the consequences of loneliness, with numerous new publications and attempts to identify risks for cognitive health," Luchetti and colleagues noted.

One recent study showed that dementia incidence was tripled in lonely older adults who otherwise would be expected to have relatively low risk based on age and genes. Another suggested that persistent midlife loneliness was tied to late-life dementia and Alzheimer's disease. Loneliness also has been linked with incident Parkinson's disease independently of genes, depression, and other major risk factors.

In their meta-analysis, Luchetti and co-authors assessed relationships between loneliness and all-cause dementia in 608,561 individuals pooled across 21 samples that included articles from published literature and ongoing aging cohort studies.

Five articles assessed Alzheimer's disease risk (492,967 people) and three articles assessed risk for vascular dementia (489,467 people). To analyze cognitive impairment that wasn't dementia, the researchers used 16 samples that included both articles and ongoing studies.

There was large heterogeneity across the studies, partly due to differences in loneliness measures and ascertainment of cognitive status, the researchers said.

The meta-analytic effects for dementia and cognitive impairment were weaker but significant in models that accounted for depression, social isolation, or other modifiable risk factors, they noted. "In particular, depression and social isolation emerge as possible mediators underlying the associations," they wrote.

"Loneliness is closely associated with depressive symptomatology, which in turn increases the risk for cognitive decline," Luchetti and colleagues added. "Loneliness, however, is not simply a symptom of depression, and this research suggests that loneliness has an independent relation with dementia when controlling for depressive symptoms."

Interventions that target social isolation and depressive symptoms may alleviate loneliness and support cognitive health, but other mechanisms may be involved, they suggested.

Lonely individuals may engage in unhealthy behaviors or experience elevated stress and immune dysfunction, they noted. While loneliness is related to cardiovascular risk, incorporating variables like diabetes, hypertension, and obesity into the current analysis had negligible effects on associations with dementia and cognitive impairment.

"Other modifiable risk factors for dementia (for example, hearing function and air pollution) were not considered in the current analysis because such variables were not available across all studies," the researchers acknowledged. "These risk factors could have an important role in the association between loneliness and cognitive risk in later life."

Studies in this meta-analysis assessed loneliness at one point in time, and most reported only the presence or absence of loneliness, Luchetti and co-authors noted. "The large heterogeneity across study estimates points to the need to better identify moderators that explain differences across studies," they added.

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