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Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study

Machado-Fragua, Marcos D; Sabia, Séverine; Fayosse, Aurore; Hassen, Céline Ben; van der Heide, Frank; Kivimaki, Mika; Singh-Manoux, Archana; (2023) Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study. BMC Medicine , 21 (1) , Article 436. 10.1186/s12916-023-03155-4. Green open access

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Abstract

BACKGROUND: Metabolically healthy obesity is hypothesized to be a benign condition but whether this is the case for dementia remains debated. We examined the role of age at assessment of metabolic-obesity phenotypes in associations with incident dementia. METHODS: Obesity (body mass index ≥ 30 kg/m2) and poor metabolic health (≥ 2 of elevated serum triglycerides, low HDL-C, elevated blood pressure, and elevated serum fasting glucose) were used to define four metabolic-obesity phenotypes (metabolically healthy (MHNO) and unhealthy non-obesity (MUNO), metabolically healthy (MHO) and unhealthy obesity (MUO)) at < 60, 60 to < 70, and ≥ 70 years using 6 waves of data from the Whitehall II study and their associations with incident dementia was examined using Cox regression. RESULTS: Analyses with exposures measured < 60, 60 to < 70, and ≥ 70 years involved 410 (5.8%), 379 (5.6%), and 262 (7.4%) incident dementia cases over a median follow-up of 20.8, 10.3, and 4.2 years respectively. In analyses of individual components, obesity before 60 years (HR 1.41, 95% CI: [1.08, 1.85]) but not at older ages was associated with dementia; unhealthy metabolic status when present < 60 years (HR 1.33, 95% CI: [1.08, 1.62]) and 60 to < 70 years (HR 1.32, 95% CI: [1.07, 1.62]) was associated with dementia. Compared to the metabolically healthy non-obesity group, the risk of dementia was higher in those with metabolically healthy obesity before 60 years (1.69; 95% CI: [1.16, 2.45]); this was not the case when metabolic-obesity phenotype was present at 60 to < 70 years or ≥ 70 years. Analyses at older ages were on smaller numbers due to death and drop-out but inverse probability weighting to account for missing data yielded similar results. CONCLUSIONS: Individuals with metabolically healthy obesity before age 60 had a higher risk of incident dementia over a 27-year follow-up; the excess risk dissipates when metabolic health and obesity are measured after 70 years.

Type: Article
Title: Is metabolic-healthy obesity associated with risk of dementia? An age-stratified analysis of the Whitehall II cohort study
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12916-023-03155-4
Publisher version: https://doi.org/10.1186/s12916-023-03155-4
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Keywords: BMI, Cardiometabolic risk factors, Dementia, Metabolic status, Obesity, Phenotypes
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry > Mental Health of Older People
URI: https://discovery.ucl.ac.uk/id/eprint/10181800
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