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Loneliness may indicate preclinical Alzheimer’s disease

Cognitively normal older adults with higher cortical amyloid burden or apolipoprotein E 4 were more likely to report loneliness, suggesting it may be a neuropsychiatric symptom of preclinical Alzheimer’s disease.

“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 [Alzheimer’s disease] dementia. As such, loneliness may be a sensitive clinical marker of pathological brain changes in older people,” Nancy J. Donovan, MD, of Brigham and Women’s Hospital, Harvard Medical School, Boston, and colleagues wrote. “Importantly, loneliness is a specific construct that can be reliably measured and distinguished from depression, anxiety, and objective social isolation through the use of well-established instruments,”

To assess associations between cortical amyloid burden and greater loneliness among cognitively normal older adults, researchers conducted cross-sectional analyses of data from the Harvard Aging Brain Study for 79 community-dwelling participants. Cortical amyloid burden was measured by Pittsburgh Compound B-positron emission tomography (PiB-PET). Loneliness was determined by the 3-item UCLA Loneliness Scale, where a higher score indicates greater loneliness. Study participants had a mean age of 76.4 years.

Mean cortical amyloid burden was 1.23 and mean loneliness score was 5.3.

Twenty-eight percent of the cohort had positive apolipoprotein E 4 (APOE 4) carrier status and 32% were in the amyloid-positive group with a cortical distribution volume ratio greater than 1.2.

When adjusting for age, sex, APOE 4, socioeconomic status, depression, anxiety, and social network, higher amyloid burden was significantly associated with greater loneliness. Individuals in the amyloid-positive group were 7.5 (95% CI, 1.7-34) times more likely to be classified as lonely, compared with those in the amyloid-negative group (P = .002).

The association between high amyloid burden and loneliness was stronger among APOE 4 carriers than non-carriers.

“Could self-reported loneliness be associated with brain amyloid burden and [Alzheimer’s disease] risk? The results reported by Donovan [and colleagues] indicate that they could,” Paul B. Rosenberg, MD, of Johns Hopkins University School of Medicine, Baltimore, wrote in an accompanying invited commentary. “These are novel findings, and the construct of loneliness merits a closer look. It is a self-reported symptom and not obviously associated with the participants’ social engagement and networks, and it is not associated with depression. Instead, the authors hypothesize that loneliness may be a specific symptom or construct related to brain amyloid burden itself, and this novel idea merits replication in larger samples and longitudinal designs.” – by Amanda Oldt

Disclosure: Donovan reports salary support from Eisai Inc and Eli Lilly and that her spouse is employed by Alkermes PLC. Please see the study for a full list of relevant financial disclosures.