Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts

Background: Loneliness is often accompanied by depression and is associated with an increased risk of dementia. However, evidence remains limited regarding how loneliness and depression jointly relate to future dementia risk, and whether depression may help explain the observed association between l...

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Main Authors: Luping Wang, Jinye Ma, Nanyang Liu, Lina Ma, Hui Pei, Shan He, Hao Li
Format: Article
Language:English
Published: Elsevier 2025-10-01
Series:The Journal of Nutrition, Health and Aging
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Online Access:http://www.sciencedirect.com/science/article/pii/S1279770725001782
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author Luping Wang
Jinye Ma
Nanyang Liu
Lina Ma
Hui Pei
Shan He
Hao Li
author_facet Luping Wang
Jinye Ma
Nanyang Liu
Lina Ma
Hui Pei
Shan He
Hao Li
author_sort Luping Wang
collection DOAJ
description Background: Loneliness is often accompanied by depression and is associated with an increased risk of dementia. However, evidence remains limited regarding how loneliness and depression jointly relate to future dementia risk, and whether depression may help explain the observed association between loneliness and dementia. Method: We conducted a study using prospective cohort data from three multinational populations. The association between loneliness, depression, and dementia risk was evaluated using Cox proportional hazards models. Mediation analysis was conducted to evaluate the potential contribution of depression to the observed association between loneliness and dementia risk. Additionally, both multiplicative and additive interaction methods were employed to assess the interaction between loneliness and depression with dementia risk, quantifying their combined associations. Results: At baseline, a total of 133,388 participants were included in the study. Our study revealed a significant independent association between loneliness or depression and increased dementia risk. Additionally, compared to the group without loneliness or depressive symptoms, the other three groups had significantly higher risks of dementia during follow-up (loneliness only: HR = 1.26, 95% CI: 1.15–1.38; depression only: HR = 1.58, 95% CI: 1.41–1.78; loneliness with depression: HR = 1.98, 95% CI: 1.81–2.17).Mediation analysis showed that depression accounted for 36% of the loneliness-dementia association. Furthermore, we observed a significant additive interaction between loneliness and depression on dementia risk. Conclusions: This study examined the combined association of loneliness and depression with the risk of developing dementia, underscoring the importance of addressing loneliness and depression as potentially related factors in dementia prevention.
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spelling doaj-art-7d27c81cfd6a478a891aa1c73ebc2af92025-08-20T03:47:06ZengElsevierThe Journal of Nutrition, Health and Aging1760-47882025-10-01291010065310.1016/j.jnha.2025.100653Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohortsLuping Wang0Jinye Ma1Nanyang Liu2Lina Ma3Hui Pei4Shan He5Hao Li6Department of Geriatrics, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing, 100102, ChinaDepartment of Geriatrics, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing, 100102, ChinaDepartment of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan Playground, Haidian District, Beijing, 100091, ChinaDepartment of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan Playground, Haidian District, Beijing, 100091, ChinaDepartment of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan Playground, Haidian District, Beijing, 100091, ChinaPharmacological Laboratory, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing, 100102, China; Corresponding authors.Department of Geriatrics, Wangjing Hospital, China Academy of Chinese Medical Sciences, No. 6 Wangjing Zhonghuan South Road, Chaoyang District, Beijing, 100102, China; Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, No.1 Xiyuan Playground, Haidian District, Beijing, 100091, China; Corresponding authors.Background: Loneliness is often accompanied by depression and is associated with an increased risk of dementia. However, evidence remains limited regarding how loneliness and depression jointly relate to future dementia risk, and whether depression may help explain the observed association between loneliness and dementia. Method: We conducted a study using prospective cohort data from three multinational populations. The association between loneliness, depression, and dementia risk was evaluated using Cox proportional hazards models. Mediation analysis was conducted to evaluate the potential contribution of depression to the observed association between loneliness and dementia risk. Additionally, both multiplicative and additive interaction methods were employed to assess the interaction between loneliness and depression with dementia risk, quantifying their combined associations. Results: At baseline, a total of 133,388 participants were included in the study. Our study revealed a significant independent association between loneliness or depression and increased dementia risk. Additionally, compared to the group without loneliness or depressive symptoms, the other three groups had significantly higher risks of dementia during follow-up (loneliness only: HR = 1.26, 95% CI: 1.15–1.38; depression only: HR = 1.58, 95% CI: 1.41–1.78; loneliness with depression: HR = 1.98, 95% CI: 1.81–2.17).Mediation analysis showed that depression accounted for 36% of the loneliness-dementia association. Furthermore, we observed a significant additive interaction between loneliness and depression on dementia risk. Conclusions: This study examined the combined association of loneliness and depression with the risk of developing dementia, underscoring the importance of addressing loneliness and depression as potentially related factors in dementia prevention.http://www.sciencedirect.com/science/article/pii/S1279770725001782LonelinessDepressionAgingDementiaMediation analysisInteraction analysis
spellingShingle Luping Wang
Jinye Ma
Nanyang Liu
Lina Ma
Hui Pei
Shan He
Hao Li
Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts
The Journal of Nutrition, Health and Aging
Loneliness
Depression
Aging
Dementia
Mediation analysis
Interaction analysis
title Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts
title_full Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts
title_fullStr Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts
title_full_unstemmed Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts
title_short Associations of loneliness and depression with increased risks of incident dementia: A prospective study from three older adult cohorts
title_sort associations of loneliness and depression with increased risks of incident dementia a prospective study from three older adult cohorts
topic Loneliness
Depression
Aging
Dementia
Mediation analysis
Interaction analysis
url http://www.sciencedirect.com/science/article/pii/S1279770725001782
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