Perceived social isolation is correlated with brain structure and cognitive trajectory in Alzheimer’s disease

Abstract

Both objective and perceived social isolations were associated with future cognitive decline and increase risk of Alzheimer’s disease (AD). However, the impacts of perceived social isolation depending on different clinical stages of AD have not been elucidated. The aim of this study was to investigate the influence of perceived social isolation or loneliness on brain structure and future cognitive trajectories in patients who are living with or are at risk for AD. A total of 176 elderly patients (mean age of 78 years) who had complaint of memory problems (39 subjective cognitive decline [SCD], 53 mild cognitive impairment [MCI], 84 AD) underwent structural MRI and neuropsychological testing. Loneliness was measured by one binary item question “Do you often feel lonely?.” Voxel-based morphometry was conducted to evaluate regional gray matter volume (rGMV) difference associated with loneliness in each group. To evaluate individual differences in cognitive trajectories based on loneliness, subgroup analysis was performed in 51 patients with AD ( n = 23) and pre-dementia status (SCD-MCI, n = 28) using the longitudinal scores of Alzheimer’s Disease Assessment Scale - cognitive component-Japanese version (ADAS-Jcog). Whole brain VBM analysis comparing lonely to non-lonely patients revealed loneliness was associated with decreased rGMV in bilateral thalamus in SCD patients and in the left middle occipital gyrus and the cerebellar vermal lobules I − V in MCI patients. Annual change of ADAS-Jcog in patients who reported loneliness was significantly greater comparing to these non-lonely in SCD-MCI group, but not in AD group. Our results indicate that perceived social isolation, or loneliness, might be a comorbid symptom of patients with SCD or MCI, which makes them more vulnerable to the neuropathology of future AD progression. Supplementary Information The online version contains supplementary material available at 10.1007/s11357-022-00584-6.

Contributions of loneliness to cognitive impairment and dementia in older adults are independent of other risk factors and Alzheimer’s pathology: a narrative review

“…This lack of AD pathology is similar to what is observed with chronic stress, i.e., neuroticism, where cognitive change or dementia is greater than in controls but there is no clear relationship to AD pathology ( Wilson et al, 2003 , 2007a ; Chapman et al, 2020 ; Franks et al, 2021 ). This lack of AD pathology even extends to neuroimaging where medial temporal lobe changes have not been consistently related to loneliness, even as other areas have demonstrated changes ( Salinas et al, 2022 ; Zhang et al, 2022 ). While not completely consistent, there is evidence that the risk of loneliness contributing to cognitive decline or dementia may be greater in those with fewer conventional risks of AD dementia, such as lower age or being APOE4 negative.…”

“…There was no significant association between loneliness and hippocampal volume. A small exploratory study of people with cognitive complaints revealed no relationship between loneliness and brain regions typically involved with AD (e.g., hippocampus and medial temporal lobe) ( Zhang et al, 2022 ).…”

Loneliness in Posttraumatic Stress Disorder: A Neglected Factor in Accelerated Aging?

“…At an organ system level there is strong evidence for increased cardiovascular disease and morbidity, as well as metabolic morbidity including high LDL cholesterol, triglycerides, and reduced HDL as well as type 2 diabetes in loneliness [91][92][93][94] and PTSD [95][96][97][98][99][100]. Both conditions have also been reported to be associated with impaired cognitive functioning [1,[101][102][103][104][105][106].…”

Dementia and the History of Disease in Older Adults in Community

“…It is related to aging and degeneration of the nervous system, featuring amyloid plaques, neuro brillary tangles and neuronal loss in the temporal lobe and neocortex of the brain. [8] Known risk factors for dementia included heredity, aging, gender, social isolation, [9] socioeconomic status, [10] abdominal obesity, [11] physical inactivity, [11] excessive intake of saturated fat, [12] cardiovascular diseases, [13] cerebrovascular diseases, [13] dyslipidemia, diabetes, [14] brain trauma [15] and depression [16].…”