Associations of loneliness with risk of Alzheimer's disease dementia in the Framingham Heart Study

Akhter-Khan, Samia C.; Qin, Tao; Ang, Ting Fang Alvin; Itchapurapu, Indira Swetha; Alosco, Michael L.; Mez, Jesse; Piers, Ryan J.; Steffens, David C.; Au, Rhoda; Qiu, Wei Qiao

doi:10.1002/alz.12327

Cited by 75 publications

(72 citation statements)

References 37 publications

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“…Change in loneliness did not correlate with dementia risk, which is consistent with two recent findings (Akhter-Khan et al, 2021;Lee et al, 2021). In the Framingham Heart Study, for example, only those who reported persistent (i.e., constant) loneliness had increased risk of dementia; participants whose loneliness scores changed across the two waves had decreased or equivalent dementia risk compared to those who reported not feeling lonely at either wave (Akhter-Khan et al, 2021). The average population trajectory in the current study suggests that loneliness is expected to change, with most experiencing worsening levels of loneliness.…”

Section: Discussionsupporting

confidence: 92%

“…We replicated prior findings by showing that mild levels of baseline loneliness predict a 43% increased risk of dementia. Consistent with newly reported findings (Akhter-Khan et al, 2021), change in loneliness did not correlate significantly with dementia risk. Future research should investigate whether chronicity of loneliness is a key feature that increases risk of dementia.…”

Section: Discussionsupporting

confidence: 90%

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A Genetically Informed Longitudinal Study of Loneliness and Dementia Risk in Older Adults

et al. 2021

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Although several studies have shown small longitudinal associations between baseline loneliness and subsequent dementia risk, studies rarely test whether change in loneliness predicts dementia risk. Furthermore, as both increase with advancing age, genetic and environmental selection processes may confound the putative causal association between loneliness and dementia risk. We used a sample of 2,476 individual twins from three longitudinal twin studies of aging in the Swedish Twin Registry to test the hypothesis that greater positive change in loneliness predicts greater dementia risk. We then used a sample of 1,632 pairs of twins to evaluate the hypothesis that effects of change in loneliness on dementia risk would remain after adjusting for effects of genetic and environmental variance. Phenotypic model results suggest that mild levels of baseline loneliness predict greater dementia risk. Contrary to our hypothesis, change in loneliness did not correlate with dementia risk, regardless of whether genetic and environmental selection confounds were taken into account. Worsening loneliness with age may not confer greater dementia risk.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 90%

A Genetically Informed Longitudinal Study of Loneliness and Dementia Risk in Older Adults

et al. 2021

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“…54 The temporal dynamics of social isolation may link to different neural activity and health consequences. Akhter-Khan et al 55 reported that transient loneliness was resilient to dementia risk. Consequently, future research should consider the trajectory of social isolation and loneliness.…”

Section: Discussionmentioning

confidence: 99%

“…54 The temporal dynamics of social isolation may link to different neural activity and health consequences. Akhter-Khan et al 55…”

Section: Discussionmentioning

confidence: 99%

Social isolation, loneliness and all-cause dementia: a longitudinal and imaging-genetic study in the UK Biobank cohort

Shen

Sahakian

Cheng

et al. 2021

Preprint

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INTRODUCTION: Current findings of the relative influence of social isolation and loneliness on dementia are contradictory, and the potential neurobiological mechanisms are unclear. METHODS: We utilized the UK Biobank to investigate the relationships of social isolation and loneliness with dementia (n = 462,619). Neuroanatomical correlates were identified in a subset of participants (n = 32,263). The transcriptomic signatures of related brain changes were characterized by gene enrichment analysis. RESULTS: After full adjustment, social isolation but not loneliness was associated with dementia (hazard ratio: 1.28, 95% confidence interval: 1.17-1.39). Isolated individuals had reduced gray matter volumes in temporal, frontal, occipital and subcortical regions (e.g., hippocampus and amygdala). Relevant brain changes were spatially correlated with genes involved in mitochondrial dysfunction and oxidative phosphorylation, and down-regulated Alzheimer's disease-related genes. DISCUSSION: Social isolation is an independent risk factor for dementia, which could be partly explained by related structural changes coupling with altered molecular functions.

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“…Although longitudinal studies cannot establish causal directionality, these studies consistently demonstrate an association between loneliness and subsequent cognitive decline [ 63 ]. Loneliness has reliably been associated with increased risk of Alzheimer’s disease and related dementias [ 66 , 67 , 68 , 69 ], in addition to worse behavioral and psychological symptoms of dementia [ 70 ]. Moreover, this increase in dementia risk seems to be most relevant for individuals with persistent loneliness compared to individuals with transient loneliness in whom dementia risk remains unchanged [ 67 ].…”

Section: Discussionmentioning

confidence: 99%

The Long-Term Public Health Impact of Social Distancing on Brain Health: Topical Review

Kumar

Salinas

2021

IJERPH

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Social distancing has been a critical public health measure for the COVID-19 pandemic, yet a long history of research strongly suggests that loneliness and social isolation play a major role in several cognitive health issues. What is the true severity and extent of risks involved and what are potential approaches to balance these competing risks? This review aimed to summarize the neurological context of social isolation and loneliness in population health and the long-term effects of social distancing as it relates to neurocognitive aging, health, and Alzheimer’s disease and related dementias. The full scope of the underlying causal mechanisms of social isolation and loneliness in humans remains unclear partly because its study is not amenable to randomized controlled trials; however, there are many detailed experimental and observational studies that may provide a hypothesis-generating theoretical framework to better understand the pathophysiology and underlying neurobiology. To address these challenges and inform future studies, we conducted a topical review of extant literature investigating associations of social isolation and loneliness with relevant biological, cognitive, and psychosocial outcomes, and provide recommendations on how to approach the need to fill key knowledge gaps in this important area of research.

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Associations of loneliness with risk of Alzheimer's disease dementia in the Framingham Heart Study

Cited by 75 publications

References 37 publications

A Genetically Informed Longitudinal Study of Loneliness and Dementia Risk in Older Adults

A Genetically Informed Longitudinal Study of Loneliness and Dementia Risk in Older Adults

Social isolation, loneliness and all-cause dementia: a longitudinal and imaging-genetic study in the UK Biobank cohort

The Long-Term Public Health Impact of Social Distancing on Brain Health: Topical Review

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