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  5. Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study.
 
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Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study.
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Published version
Author(s)
Mina, Theresia
Yew, Yik Weng
Ng, Hong Kiat
Sadhu, Nilanjana
Wansaicheong, Gervais
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Type
Journal Article
Abstract
BACKGROUND: Obesity and related metabolic disturbances including diabetes, hypertension and hyperlipidemia predict future cognitive decline. Asia has a high prevalence of both obesity and metabolic disease, potentially amplifying the future burden of dementia in the region. We aimed to investigate the impact of adiposity and metabolic risk on cognitive function in Asian populations, using an epidemiological analysis and a two-sample Mendelian Randomization (MR) study. METHODS: The Health for Life in Singapore (HELIOS) Study is a population-based cohort of South-East-Asian men and women in Singapore, aged 30-84 years. We analyzed 8769 participants with metabolic and cognitive data collected between 2018 and 2021. Whole-body fat mass was quantified with Dual X-Ray Absorptiometry (DEXA). Cognition was assessed using a computerized cognitive battery. An index of general cognition ' g ' was derived through factor analysis. We tested the relationship of fat mass indices and metabolic measures with ' g ' using regression approaches. We then performed inverse-variance-weighted MR of adiposity and metabolic risk factors on ' g ', using summary statistics for genome-wide association studies of BMI, visceral adipose tissue (VAT), waist-hip-ratio (WHR), blood pressure, HDL cholesterol, triglycerides, fasting glucose, HbA1c, and general cognition. FINDINGS: Participants were 58.9% female, and aged 51.4 (11.3) years. In univariate analysis, all 29 adiposity and metabolic measures assessed were associated with ' g ' at P < 0.05. In multivariable analyses, reduced ' g ' was consistently associated with increased visceral fat mass index and lower HDL cholesterol (P < 0.001), but not with blood pressure, triglycerides, or glycemic indices. The reduction in ' g ' associated with 1SD higher visceral fat, or 1SD lower HDL cholesterol, was equivalent to a 0.7 and 0.9-year increase in chronological age respectively (P < 0.001). Inverse variance MR analyses showed that reduced ' g ' is associated with genetically determined elevation of VAT, BMI and WHR (all P < 0.001). In contrast, MR did not support a causal role for blood pressure, lipid, or glycemic indices on cognition. INTERPRETATION: We show an independent relationship between adiposity and cognition in a multi-ethnic Asian population. MR analyses suggest that both visceral adiposity and raised BMI are likely to be causally linked to cognition. Our findings have important implications for preservation of cognitive health, including further motivation for action to reverse the rising burden of obesity in the Asia-Pacific region. FUNDING: The Nanyang Technological University-the Lee Kong Chian School of Medicine, National Healthcare Group, National Medical Research Council, Ministry of Education, Singapore.
Date Issued
2023-04
Date Acceptance
2023-01-26
Citation
The Lancet Regional Health. Western Pacific, 2023, 33, pp.1-11
URI
http://hdl.handle.net/10044/1/103116
URL
https://www.sciencedirect.com/science/article/pii/S2666606523000287?via%3Dihub
DOI
https://www.dx.doi.org/10.1016/j.lanwpc.2023.100710
ISSN
2666-6065
Publisher
Elsevier
Start Page
1
End Page
11
Journal / Book Title
The Lancet Regional Health. Western Pacific
Volume
33
Copyright Statement
Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
License URL
http://creativecommons.org/licenses/by-nc-nd/4.0/
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/36851942
PII: S2666-6065(23)00028-7
Subjects
Adiposity
Aging
Asia
Cardiovascular risk factors
Cognitive function
DEXA
General cognition
Mendelian Randomization
Metabolic syndrome
Visceral adiposity
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2023-02-14
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