Association of life course adiposity with risk of incident dementia: a prospective cohort study of 322,336 participants
Abstract
Cohort studies report inconsistent associations between body mass index (BMI) and all-cause incident dementia. Furthermore, evidence on fat distribution and body composition measures are scarce and few studies estimated the association between early life adiposity and dementia risk. Here, we included 322,336 participants from UK biobank to investigate the longitudinal association between life course adiposity and risk of all-cause incident dementia and to explore the underlying mechanisms driven by metabolites, inflammatory cells and brain structures. Among the 322,336 individuals (mean (SD) age, 62.24 (5.41) years; 53.9% women) in the study, during a median 8.74 years of follow-up, 5083 all-cause incident dementia events occurred. The risk of dementia was 22% higher with plumper childhood body size (p < 0.001). A strong U-shaped association was observed between adult BMI and dementia. More fat and less fat-free mass distribution on arms were associated with a higher risk of dementia. Interestingly, similar U-shaped associations were found between BMI and four metabolites (i.e., 3-hydroxybutrate, acetone, citrate and polyunsaturated fatty acids), four inflammatory cells (i.e., neutrophil, lymphocyte, monocyte and leukocyte) and abnormalities in brain structure that were also related to dementia. The findings that adiposity is associated with metabolites, inflammatory cells and abnormalities in brain structure that were related to dementia risk might provide clues to underlying biological mechanisms. Interventions to prevent dementia should begin early in life and include not only BMI control but fat distribution and body composition.
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Adiposity is associated with reduced cognitive function.
“Recent evidence has demonstrated an association between adiposity and reduced cognitive function”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [579]
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BackgroundRetractedThe UK Biobank resource with deep phenotyping and genomic data
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- Authors
- Deng, Y.-T., Li, Y.-Z., Huang, S.-Y., Ou, Y.-N., Zhang, W., Chen, S.-D., Zhang, Y.-R., Yang, L., Dong, Q., Feng, J.-F., Suckling, J., Smith, A. D., Cheng, W., & Yu, J.-T.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Qingdao University (CN)
- University of Oxford (GB)
- Fudan University (CN)
- Corresponding author
- Cheng, Wei
- Yu, Jin-Tai
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2022-05-10
- Volume
- 27
- Issue
- 8
- Pages
- 3385-3395
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W4229454380
- Cited by
- 45
- References
- 67
- Citations by year
- 2026: 14 · 2025: 12 · 2024: 14 · 2023: 5
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (submittedVersion)
- Funders
- Medical Research Council (MC_PC_17228)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Oncology › Cancer Risks and Factors
- Keywords
- dementia risk, body mass index, childhood body size, body fat distribution, arm fat, fat-free mass, metabolites, inflammatory cells, brain structure, U-shaped relationship, dementia prevention, UK Biobank
- MeSH terms
- Adult, Child, Dementia, Female, Humans, Life Change Events, Male, Middle Aged, Obesity, Prospective Studies, Risk Factors, Cohort Studies, Body Mass Index, Adiposity
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