Previous research has suggested loneliness may be associated with Alzheimer's disease among older adults. A new study supports this link, after identifying a marker of early Alzheimer's in the brains of seniors with greater self-reported loneliness.

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Researchers suggest loneliness in older age might represent brain changes related to Alzheimer's.

Study co-author Nancy J. Donovan, of Brigham and Women's Hospital and Harvard Medical School in Boston, MA, and colleagues report their findings in JAMA Psychiatry.

According to a 2010 survey from the American Association of Retired Persons (AARP), around 32 percent of adults aged 60-69 and 25 percent of adults aged 70 and older in the United States report feeling lonely.

As well as increased risk of depression, heart disease, and stroke, loneliness in older adults has been associated with greater risk of cognitive decline and Alzheimer's disease.

For their study, Donovan and team set out to determine whether loneliness is associated with pathological brain changes that might be a marker of Alzheimer's.

Specifically, they looked at whether loneliness might be associated with levels of amyloid proteins in the brain. These proteins can form clumps called plaques, which are considered a hallmark of Alzheimer's.

Loneliness 7.5 times more likely in adults with high amyloid levels

The research included 79 adults - 43 women and 36 men - of an average age of 76 years with normal cognitive functioning.

The team used the UCLA Loneliness Scale to assess how lonely each participant felt. This tool asks three questions: "How often do you feel left out?," "How often do you feel isolated from others?," and "How often do you feel you lack companionship?"

The answer to each question is scored on a 4-point scale, with 1 representing "never" and 4 representing "often." In total, participants' average loneliness score was 5.3 out of 12.

Using brain imaging, the researchers measured amyloid protein levels in cortical areas of the participants' brains, including the frontal, lateral temporal and lateral, and medial parietal regions.

Compared with participants with low cortical amyloid levels, subjects with high amyloid levels were 7.5 times more likely to report feeling lonely, the researchers found.

This association was stronger for participants who were carriers of APOEε4 - a gene that is associated with increased risk of Alzheimer's.

The results remained after accounting for a number of potential confounding factors, including age, sex, anxiety, depression, and socioeconomic status.

Donovan and colleagues say their results point to loneliness as a sign of early Alzheimer's, after showing loneliness can be reflected in pathological brain changes related to the disease.

Commenting on their findings, the authors write:

"We report a novel association of loneliness and cortical amyloid burden in cognitively normal older adults and present evidence for loneliness as a neuropsychiatric symptom relevant to preclinical AD [Alzheimer's disease].

This work will inform new research into the neurobiology of loneliness and other socioemotional changes in late life and may enhance early detection and intervention research in AD."

Future implications for Alzheimer's disease

Alzheimer's is the most common form of dementia, affecting around 5.4 million people in the U.S. This number is expected to reach 13.8 million by 2050, unless new prevention and treatment strategies are discovered.

In an editorial linked to the study, Dr. Paul B. Rosenberg, of the Department of Psychiatry and Behavioral Sciences at Johns Hopkins Bayview Medical Center in Baltimore, MD, says the results from Donovan and team may advance the development of early screening methods for Alzheimer's.

"One can imagine a future landscape of treatment in which older persons are screened for AD risk with a mix of self-report measures (mood and memory concerns), cognitive screens performed on a tablet or smartphone, and genetics including APOEε4 and future studies with whole-genome sequencing; the genetics is still costly but in a decade should become inexpensive," says Dr. Rosenberg.

"We might calculate a risk index and use this to stratify older persons for biomarker assessment and interventions," he adds. "This approach would be beneficial not only for public health in developing countries but also for low- and middle-income countries where the majority of the world's persons with AD already live and where the at-risk populations are huge."

"In this endeavor, measures such as loneliness and mood symptoms yet to be identified may loom large, and Donovan et al. have contributed a significant advance in this regard," concludes Dr. Rosenberg.

Read about how loneliness might alter the immune system to cause illness.