Scientists have long believed that loneliness can be hazardous to the health of older adults. But new research suggests there may be another link, as well: Feeling socially isolated (aka lonely) might actually be an early sign of brain changes that can lead to Alzheimer’s disease, according to a study published today by Harvard researchers.

“We were more interested in considering the possibility that there may be a relationship in the opposite direction—that as people age and decline cognitively, they may be more predisposed to loneliness,” says lead author Nancy Donovan, MD, a psychiatrist at Brigham and Women's Hospital and Harvard Medical School.

To test their hypothesis, Dr. Donovan and her colleagues studied 79 men and women with an average age of 76 and no outward signs of memory problems. The participants answered questions designed to assess how lonely they felt; and the researchers used imaging scans to detect the presence of cortical amyloid—a type of protein believed to a precursor of Alzheimer’s—in their brains.

About 32% of the people tested positive for these protein clusters. After the researchers controlled for other factors (such as depression, anxiety, and social network size), they found that the people in this group were 7.5 times more likely to be classified as lonely, compared with those whose scans were negative.

The association between high amyloid levels and loneliness was also stronger in people who carried the gene variant APOEε4, which is an inherited risk factor for Alzheimer’s disease.

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Dr. Donovan says that brain changes in the very early stages of Alzheimer’s disease may cause people to feel lonely even if their social behavior doesn’t change. She notes that, for people in the study, loneliness was not necessarily related to a persons' number of social ties or how often they interacted with friends and family.

In other cases, people experiencing these brain changes might indeed start to withdraw from group activities. “It may be that as people decline both physically and cognitively, they’re less able to successfully socialize and they become less comfortable and have more anxiety in those situations,” Dr. Donovan says.

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Writing in the journal JAMA Psychiatry, the study authors acknowledge that the association between loneliness and memory problems could go either way, and that it’s possible that feelings of loneliness and detachment actually promote amyloid accumulation, rather than the other way round.

Dr. Donovan also says the relationship may go in both directions at the same time. “We don’t have evidence, but it does seem possible that there could be a kind of cycle,” she says.

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In an editorial published along with the study, Paul B. Rosenberg, MD, associate professor of psychiatry and behavioral sciences at Johns Hopkins Bayview Medical Center, called the findings “important and intriguing.”

Doctors are always looking for new and effective ways to screen patients in the early stages of dementia, he writes, and this study suggests that asking about loneliness could potentially be part of that process.

In fact, Dr. Rosenberg says, it’s become increasingly clear that Alzheimer’s disease affects many aspects of mental health—not just memory. “Perhaps other emotions (fear? existential angst? dread? or more positive emotions) might reflect amyloid burden or other biomarkers of preclinical [Alzheimer’s disease],” he wrote.

Dr. Donovan agrees that feelings of social detachment could be “one subtle clue” of Alzheimer’s-related brain changes, but says more research is needed.

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“We’re really trying to understand the full picture, and loneliness could be part of this picture,” she says. “I think it’s difficult to extrapolate and say that someone who’s lonely is absolutely more likely to have Alzheimer’s disease, but it could certainly be part of the characteristics of people who are more vulnerable to it.”

She calls this study a first step, and says it’s too early to give concrete advice based off of the findings. Until more is known, however, there are plenty of other reasons—for your brain, your heart, and your overall health—to keep up with your friends as you age.