Summary
Background and Objective:
Loneliness is common and its prevalence is increasing. The relationship of loneliness to later dementia and the early preclinical course of Alzheimer’s disease and related dementia (ADRD) remains unclear.
Therefore, the primary objective of this study was to determine the association of loneliness with 10-year all-cause dementia risk and early cognitive and neuroanatomical 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 were screened for loneliness and did not have dementia at the start of the study.
Loneliness was recorded using the Center for Epidemiological Studies Depression Scale; conservatively defined as feeling lonely ≥3 days in the past week.
Primary 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% female) who met criteria in the dementia sample, 14% (329/2308) developed dementia; 6% (144/2308) were alone.
Lonely adults (vs. those who were not lonely) had a higher 10-year risk of dementia (hazard ratio adjusted for age, sex, and education, 1.54; 95% CI, 1.06-2.24 ).
Solitary participants younger than 80 years without APOE ε4 alleles had a threefold increased risk (adjusted hazard ratio, 3.03; 95% CI, 1.63-5.62).
Among 1875 eligible people without dementia in the cognition sample (mean age, 62 [SD, 9] years; 54% female), loneliness was associated with poorer executive function, lower total brain volume, and greater white matter injury.
Discussion:
During 10 years of close clinical surveillance for dementia in this cohort study, loneliness was associated with an increased risk of dementia; this was tripled in adults whose baseline risk would be relatively low based on age and genetic risk, representing the 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 the observed loneliness trends.
Classification of evidence : This study provides Class I evidence that loneliness increases the risk of developing dementia at age 10.
Comments
As social isolation in the United States has increased among older adults, a new study shows a notable link between loneliness and dementia risk, and one that is most surprising for Americans who make up a large portion of the population.
In the study that was published in Neurology , the medical journal of the American Academy of Neurology, researchers found a threefold increase in the risk of later dementia among lonely Americans under age 80 who would otherwise be expected to were at 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 attention control) and changes in the brain that indicate vulnerability to Alzheimer’s disease and related dementias (AKI).
"This study emphasizes the importance of loneliness and social connection issues in addressing our risk of developing dementia as we age," says lead researcher Joel Salinas, MD, MBA, MSc, Lulu P. and David assistant professor of neurology. J. Levidow. at NYU Grossman School of Medicine and a member of the Center for Cognitive Neurology in the Department of Neurology.
“Recognizing the signs of loneliness in oneself and others, building and maintaining supportive relationships, providing much-needed support to the people in our lives who feel lonely, are important for everyone. But they are especially important as we age to increase our chances of delaying or even preventing cognitive decline.”
Dementia affects more than 6.2 million adults in the United States, according to a 2021 special report from the Alzheimer’s Association. Since the start of the coronavirus pandemic, feelings of loneliness have affected approximately 46 million Americans, with more frequent feelings of loneliness found in adults age 60 and older.
“This study is a reminder that if we want to prioritize brain health, we cannot ignore the role of psychosocial factors such as loneliness and the social environments we live in every day,” says Dr. Salinas. “Sometimes the best way to take care of ourselves and the people we love is to simply reach out and check in regularly, to recognize and be recognized.”
Dr. Salinas adds: “We can share with each other when we feel alone, appreciate with each other how loneliness is common, and accept that giving and asking for support can be difficult. Fortunately, loneliness can be cured. And while we may need to be vulnerable and creative to discover new ways to connect, even the smallest gesture is likely to have been worth it.”
How does the study was realized
Using retrospective data from the population-based Framingham Study (FS), researchers reviewed 2,308 participants who did not have dementia at the start of the study, with an average age of 73 years.
Neuropsychological measures and brain MRIs were obtained at screening and participants were asked how often they felt lonely along with other depressive symptoms, such as restless sleep or poor appetite.
Participants were also tested 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 on three or more days in the past week.
The study population was assessed for dementia over a decade 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 and older, younger participants aged 60 to 79 who felt lonely were more than twice as likely to develop dementia. Loneliness was associated with a threefold increased risk among younger participants who did not carry the APOE ε4 allele.
The researchers concluded that the tripling of risk was likely related to associations between loneliness and early cognitive and neuroanatomical markers of vulnerability to Alzheimer’s and related dementias, raising the potential population health implications of trends observed in loneliness.
Additional findings showed that loneliness was related to poorer executive function, lower total brain 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, the University of California Davis, and the Biggs Institute for Alzheimer’s and Neurodegenerative Diseases at the Center for Disease Control and Prevention also participated. Health Sciences at the University of Texas at San Antonio. in the study.
