Loneliness Tied to Brain`s Amyloid Levels

By Marilynn Larkin

NEW YORK (Reuters Health) - Loneliness is associated with cortical amyloid burden in cognitively normal adults and thus may be a symptom of preclinical Alzheimer's disease (AD), Massachusetts-based researchers suggest.

"Loneliness is a perceived state of social and emotional isolation that has been associated with cognitive and functional decline and an increased risk of incident AD dementia," write Dr. Nancy Donovan of Brigham and Woman's Hospital in Boston and colleagues in JAMA Psychiatry, online November 2.

"We hypothesized that loneliness might occur in association with elevated cortical amyloid burden, an in vivo research biomarker of AD," they add.

To investigate, the team used data from 79 cognitively normal adults (average age, 76) participating in the Harvard Aging Brain Study, an ongoing observational study aimed at defining neurobiological changes in early AD. As part of their four-year assessment, participants were assessed for loneliness, anxiety and social network.

Cortical amyloid burden was assessed by Pittsburgh Compound B (PiB)-positron emission tomography, and loneliness by the three-item UCLA Loneliness Scale (possible range, 3-12, with a higher score indicating greater loneliness).

The average cortical PiB distribution volume ratio among participants was 1.2 and the average loneliness score was 5.3.

A total of 25 participants were considered "amyloid-positive," with a cortical amyloid burden greater than 1.2, and 22 were carriers of the APOE e4 allele, a genetic risk factor for AD.

After controlling for age, sex, presence of APOE e4, socioeconomic status, depression, anxiety and social network characteristics, a significant association emerged between higher amyloid burden and greater loneliness.

Individuals in the amyloid-positive group were 7.5-fold more likely to be classified as lonely (P=0.002) compared with those in the amyloid-negative group.

In addition, the association between high amyloid burden and loneliness was stronger in those carrying the APOE e4 allele compared with noncarriers. For each 0.1 increase in PiB, the average loneliness score increased by an additional 0.5 units in carriers of the allele versus noncarriers.

Dr. Donovan told Reuters Health, "Our results provide strong evidence that emotional changes, in this case loneliness, are symptoms involved in early AD, even before cognitive impairment sets in."

"From other work we know that psychiatric symptoms, such as depression, are greater in people who go on to develop AD dementia," she said by email. "This study moves us forward in thinking about possible disease processes. We showed that subtle feelings of loneliness were directly related to the abnormal protein accumulation that occurs in AD."

"It is possible that AD brain changes predispose people to loneliness and other psychiatric symptoms such as anxiety and depression," Dr. Donovan suggested. "It is also possible that high levels of loneliness and depression may accelerate AD brain changes. We need longitudinal studies to understand this better."

"Our results do not have clinical implications at this time," she noted. "They are most important in terms of describing subtle clinical changes that may occur in people who are at high risk of going on to develop AD dementia and identifying those who might benefit from early preventative treatments that are now in development."

"Down the road, it may also help us understand the experience of loneliness in aging that may be influenced not only by the size of one's social network and the loss of loved ones but also by one's brain health and capacity for adaptation," she concluded.

Dr. Paul B. Rosenberg of Johns Hopkins University School of Medicine in Baltimore, Maryland, author of a related editorial, commented, "The race to cure Alzheimer's is really a race to prevent Alzheimer's, and prevention involves identifying people in very early stages of the disease or even before the first cognitive symptom."

"In recent years, we have been increasingly aware that psychiatric symptoms such as depression, anxiety, or apathy may be the initial presentation of Alzheimer's," he told Reuters Health by email.

The current study "identifies that loneliness in a cohort of cognitively well older persons was a risk factor for early biological evidence of Alzheimer's, namely amyloid deposition in the brain," Dr. Rosenberg continued. "This was unrelated to depression or to the density of their social networks, and seemed to be a specific symptom related to amyloid."

He concluded, "There may be more such symptoms - relatively few have been explored - and they may help us identify people at risk of Alzheimer's who might be candidates for future preventive therapies."

SOURCE: https://bit.ly/2fy9KgZ and https://bit.ly/2eFWskZ

JAMA Psychiatry 2016.

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