Lonely Souls Susceptible to Alzheimer's Disease

CHICAGO, Feb. 5 -- Older men and women who are lonely are twice as likely to develop Alzheimer's-type dementia as their peers with good social networks, researchers have found.

The elevated risk for dementia among the lonely was unrelated to medical causes for Alzheimer's disease or other forms of dementia, suggesting that the social isolation may lead to dementia by another route, wrote Robert S. Wilson, Ph.D., and colleagues at Rush University here and the University of Pennsylvania.

"The basis of the association of loneliness with Alzheimer's disease and cognitive decline is uncertain," the investigators wrote in the February issue of Archives of General Psychiatry. "One possibility is that loneliness is a consequence of dementia, perhaps as a behavioral reaction to diminished cognition or as a direct result of the pathology contributing to dementia."

It's also possible, the authors noted, that loneliness could somehow affect neural systems involved in memory and cognition, making lonely people more susceptible to the effects of age-related changes.

Although other studies have suggested that people who live alone are at greater risk for dementia, "it is uncertain how much feeling alone (i.e., loneliness), as distinct from being alone (i.e., social isolation), contributes to risk of dementia in old age," the authors wrote.

To see whether loneliness itself is associated with increased risk of Alzheimer's disease, the authors conducted a longitudinal study of 823 men and women who were part of the Rush Memory and Aging Project.

The participants, all free of dementia at baseline, were followed for up to four years with annual home clinical examinations. In addition, as per study protocol, participants agree to donate their brains for autopsy, so that investigators could quantify Alzheimer's disease pathology in multiple brain regions, and determine the presence of cerebral infarctions.

They measured loneliness with the de Jong-Gierveld Loneliness Scale, a validated five-item instrument that has been shown to correlate with loss of a spouse, institutional living, and low self-esteem.

The participants were asked to rate, from 1 to 5, their responses to the following statements:

• "I experience a general sense of emptiness"
• "I miss having people around"
• "I feel like I don't have enough friends"
• "I often feel abandoned"
• "I miss having a really good friend."

Item scores were averaged to yield a total score ranging from 1 to 5, with higher values indicating more loneliness.

Each participant's cognitive function and memory were tested at annual visits with 20 different cognitive measures.

The primary outcome measures were a clinical diagnosis of Alzheimer's and changes in previously established composite measures of global cognition and specific cognitive functions.

In all, 76 of the participants developed clinical Alzheimer's disease. When the authors created a Cox proportional hazards model controlling for age, gender, and level of educational attained, they found that the risk of clinical Alzheimer's increased by approximately 51% for each point on the loneliness scale. The relative risk for each one-point increase was 1.51 (95% confidence interval, 1.06-2.14).

People who scored high on the loneliness scale (score 3.2, 90th percentile) had a 2.1-fold risk for Alzheimer's disease than people who said they were not lonely (score 1.4, 10th percentile). When the data were controlled for social isolation, the results remained unchanged.

"Loneliness was associated with lower level of cognition at baseline and with more rapid cognitive decline during follow-up," the authors noted. "There was no significant change in loneliness, and mean degree of loneliness during the study was robustly associated with cognitive decline and development of Alzheimer's disease."

When they performed autopsy on the brains of 90 participants who died during the study, they found that loneliness was unrelated to either summary measures of Alzheimer's disease pathology (such as amyloid plaques) or to cerebral infarction.

"These findings have important limitations," the investigators acknowledged. "They are based on a predominantly white volunteer cohort; the mean observation period was less than three years, and there were only 76 cases of incident Alzheimer's disease and 90 autopsies performed. It will be important to replicate these findings in studies with longer observation periods and more diverse participants."