Loneliness Associated With Increased Risk of Dementia in Older Adults

Summary: Study reports a three-fold increased risk of developing dementia in older adults with no genetic risk factors for Alzheimer’s disease, who experience social isolation and loneliness.

Source: NYU Langone

As social isolation in the United States has been increasing among older adults, a new study shows a notable link between loneliness and dementia risk, and one that is most striking for Americans who represent a large part of the population.

In the study publishing February 7 in Neurology, the medical journal of the American Academy of Neurology, researchers found a three-fold increase in risk of subsequent dementia among lonely Americans younger than 80 years old who would otherwise be expected to have a relatively low risk based on age and genetic risk factors.

The study also found that loneliness was associated with poorer executive function (i.e., a group of cognitive processes including decision-making, planning, cognitive flexibility, and control of attention) and changes in the brain that indicate vulnerability to Alzheimer’s disease and related dementias (ADRD).

“This study emphasizes the importance of loneliness and issues of social connection in addressing our risk of developing dementia as we age,” says lead investigator Joel Salinas, MD, MBA, MSc, the Lulu P. and David J. Levidow Assistant Professor of Neurology at NYU Grossman School of Medicine and member of the Department of Neurology’s Center for Cognitive Neurology.

“Acknowledging signs of loneliness in yourself and others, building and maintaining supportive relationships, providing much-needed support for the people in our lives who are feeling lonely—these are important for everyone. But they’re especially important as we age to increase the chances that we’ll delay or perhaps even prevent cognitive decline.”

Dementia affects more than 6.2 million adults in the United States, according to a 2021 special report by the Alzheimer’s Association. Since the beginning of the coronavirus pandemic, feelings of loneliness have affected an estimated 46 million Americans, and more frequent feelings of loneliness were found in adults aged 60 and older.

“This study is a reminder that, if we want to prioritize brain health, we can’t ignore the role of psychosocial factors like loneliness and the social environments we live in day-to-day,” says Dr. Salinas. “Sometimes, the best way to take care of ourselves and the people we love is simply to regularly reach out and check in—to acknowledge and be acknowledged.”

Dr. Salinas adds, “We can share with each other when we’re feeling lonely, appreciate with each other how loneliness is common, and accept that giving and asking for support can be hard. Fortunately, loneliness can be cured. And although we might need to be vulnerable and creative in figuring out new ways to connect, chances are that even the smallest gesture will have been worth it.”

How the Study Was Conducted

Using retrospective data of the population-based Framingham Study (FS), researchers reviewed 2,308 participants who were dementia-free at baseline, with an average age of 73. Neuropsychological measures and MRI brain scans were obtained at examination and participants were asked how often they felt lonely along with other depressive symptoms, such as restless sleep or poor appetite. Participants were also assessed for the presence of a genetic risk factor for Alzheimer’s disease called the APOE ε4 allele. Overall, 144 of the 2,308 participants reported feeling lonely three or more days in the past week.

The study population was assessed over a decade for dementia using rigorous clinical methods, and 329 of the 2,308 participants were subsequently diagnosed with the disease. Among the 144 lonely participants, 31 developed dementia. While there was no significant association between loneliness and dementia in participants aged 80 years or older, younger participants aged 60 to 79 who were lonely were more than twice as likely to develop dementia. Loneliness was associated with three-fold increased risk among younger participants who did not carry the APOE ε4 allele.

Researchers concluded that the tripling in risk was possibly related to associations between loneliness and early cognitive and neuroanatomical markers of ADRD vulnerability, raising potential population health implications for observed trends in loneliness. Additional findings showed that loneliness was related with poorer executive function, lower total cerebral volume, and greater white-matter injury, which are indicators of vulnerability for cognitive decline.

In addition to Dr. Salinas, researchers from the Boston University School of Public Health, Boston University School of Medicine, University of California Davis, and the Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the University of Texas Health Sciences Center San Antonio were also involved in the study.

Abstract

Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline

Background and Objective: Loneliness is common and its prevalence is rising. The relationship of loneliness with subsequent dementia and the early preclinical course of Alzheimer disease and related dementia (ADRD) remains unclear. Thus, the primary objective of this study was to determine the association of loneliness with 10-year all-cause dementia risk and early cognitive and neuroanatomic imaging markers of ADRD vulnerability.

Methods: Retrospective analysis of prospectively collected data from the population-based Framingham Study cohorts (09/09/1948-12/31/2018). Eligible participants had loneliness assessed and were dementia-free at baseline. Loneliness was recorded using the Center for Epidemiologic Studies Depression Scale; defined conservatively as feeling lonely ≥3 days in the past week. The main outcomes were incident dementia over a 10-year period, cognition, and MRI brain volumes and white-matter injury.

Results: Of 2308 participants (mean age, 73 [SD, 9] years; 56% women) who met eligibility in the dementia sample, 14% (329/2308) developed dementia; 6% (144/2308) were lonely. Lonely (versus not lonely) adults had higher 10-year dementia risk (age-, sex-, and education-adjusted hazard ratio, 1.54; 95% CI, 1.06-2.24). Lonely participants younger than age 80 without APOE ε4 alleles had a three-fold greater risk (adjusted hazard ratio, 3.03; 95% CI, 1.63-5.62). Among 1875 persons without dementia who met eligibility in the cognition sample (mean age, 62 [SD, 9] years; 54% women), loneliness associated with poorer executive function, lower total cerebral volume, and greater white-matter injury.

Discussion: Over 10 years of close clinical dementia surveillance in this cohort study, loneliness was associated with increased dementia risk; this tripled in adults whose baseline risk would otherwise be relatively low based on age and genetic risk, representing a majority of the US population. Loneliness was also associated with worse neurocognitive markers of ADRD vulnerability, suggesting an early pathogenic role. These findings may have important clinical and public health implications given observed loneliness trends.

Classification of Evidence: This study provides Class I evidence that loneliness increases the 10-year risk of developing dementia.