Middle-Age Loneliness Linked to Alzheimer’s Disease

Midlife loneliness was tied to late-life dementia and Alzheimer’s disease, but the relationship depended on whether loneliness persisted, according to data from the Framingham Heart Study cohort.

People who were persistently lonely via self-report when they were 45 to 64 years old had higher risk of dementia onset later in life compared with people who experienced no loneliness (HR 1.91, 95% CI 1.25-2.90, P<0.01), after adjusting for demographics, social network, physical health, and APOE4 status, reported Wendy Qiu, MD, PhD, of Boston University School of Medicine, and co-authors in Alzheimer’s and Dementia.

Transient midlife loneliness, however, was tied to lower dementia risk (HR 0.34, 95% CI 0.14-0.84, P<0.05). Results were similar for Alzheimer’s disease risk.

“Our study was the first one to find that persistent versus transient loneliness impacted differently for Alzheimer’s disease risk,” Qiu told MedPage Today.

The findings suggest that while “persistent loneliness is a threat to brain health, psychological resilience following adverse life experiences may explain why transient loneliness is protective in the context of dementia onset,” she added.

Loneliness has been linked to Alzheimer’s pathology and cognitive function among older adults, but little research has looked at loneliness as a dementia risk factor for younger people.

In this study, Qiu and colleagues looked at 2,880 cognitively normal participants in the Framingham Heart Study Gen 2 who were age 45 or older in 1998-2001. Participants had health exams about every 4 years and at least two assessments of loneliness using the Center for Epidemiologic Studies Depression Scale (CES-D) that were approximately 3 years apart.

Loneliness scores were based on the number of days that participants reported feeling lonely within the past week on the CES-D. Expert consensus determined dementia and Alzheimer’s disease based on DSM-IV and National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA) criteria, respectively. Participants were followed to the end of 2018 (18 years maximum) with time-to-events being death or onset of dementia or Alzheimer’s.

Of participants, 74.3% reported no loneliness, 8.8% reported persistent loneliness (loneliness at two CES-D assessments), 8.4% reported transient loneliness (loneliness at one but not a subsequent assessment), and 8.4% had incident loneliness (loneliness not seen in previous assessments). Compared with people who reported no loneliness, participants who reported transient, incident, or persistent loneliness were more likely to be female, live alone, be widowed, be depressed, and have smaller social networks. There were no differences in age, education levels, Mini-Mental State Examination (MMSE) scores, rates of APOE4, activities of daily living scores, cardiovascular disease, or diabetes across the four loneliness subgroups.

Of the 2,880 participants, 7.6% developed dementia, with 81.2% of those diagnoses being Alzheimer’s disease. Compared with participants who reported no loneliness, people with persistent loneliness had higher risk of developing both dementia (13.4% vs 7.5%, P<0.01) and Alzheimer’s disease (10.6% vs 6.0%, P<0.01). People with transient loneliness had lower risk of dementia (2.1% vs 7.5%, P<0.01) and Alzheimer’s disease (2.1% vs 6.0%, P<0.01). Loneliness appeared to be a risk factor independent from midlife depression.

The study had several limitations, Qiu and co-authors noted. Loneliness was measured as a single item on the CES-D, which is not multi-dimensional and may not account accurately for real-life experience. Lack of more frequent data collection limited the assessment of how persistent or transient the feeling of loneliness actually was. It was unclear whether participants who reported incident loneliness would belong to the transient or persistent group if follow-up had continued. In addition, unmeasured confounders may have influenced results.