Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study

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 t...

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Main Authors: Mina, Theresia, Yew, Yik Weng, Ng, Hong Kiat, Sadhu, Nilanjana, Wansaicheong, Gervais, Dalan, Rinkoo, Low, Dorrain Yan Wen, Lam, Benjamin Chih Chiang, Riboli, Elio, Lee, Eng Sing, Ngeow, Joanne, Elliott, Paul, Griva, Konstadina, Loh, Marie, Lee, Jimmy, Chambers, John
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
Subjects:
Online Access:https://hdl.handle.net/10356/165808
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Institution: Nanyang Technological University
Language: English
id sg-ntu-dr.10356-165808
record_format dspace
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Medicine
Adiposity
Visceral Adiposity
spellingShingle Science::Medicine
Adiposity
Visceral Adiposity
Mina, Theresia
Yew, Yik Weng
Ng, Hong Kiat
Sadhu, Nilanjana
Wansaicheong, Gervais
Dalan, Rinkoo
Low, Dorrain Yan Wen
Lam, Benjamin Chih Chiang
Riboli, Elio
Lee, Eng Sing
Ngeow, Joanne
Elliott, Paul
Griva, Konstadina
Loh, Marie
Lee, Jimmy
Chambers, John
Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study
description 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.
author2 Lee Kong Chian School of Medicine (LKCMedicine)
author_facet Lee Kong Chian School of Medicine (LKCMedicine)
Mina, Theresia
Yew, Yik Weng
Ng, Hong Kiat
Sadhu, Nilanjana
Wansaicheong, Gervais
Dalan, Rinkoo
Low, Dorrain Yan Wen
Lam, Benjamin Chih Chiang
Riboli, Elio
Lee, Eng Sing
Ngeow, Joanne
Elliott, Paul
Griva, Konstadina
Loh, Marie
Lee, Jimmy
Chambers, John
format Article
author Mina, Theresia
Yew, Yik Weng
Ng, Hong Kiat
Sadhu, Nilanjana
Wansaicheong, Gervais
Dalan, Rinkoo
Low, Dorrain Yan Wen
Lam, Benjamin Chih Chiang
Riboli, Elio
Lee, Eng Sing
Ngeow, Joanne
Elliott, Paul
Griva, Konstadina
Loh, Marie
Lee, Jimmy
Chambers, John
author_sort Mina, Theresia
title Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study
title_short Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study
title_full Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study
title_fullStr Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study
title_full_unstemmed Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study
title_sort adiposity impacts cognitive function in asian populations: an epidemiological and mendelian randomization study
publishDate 2023
url https://hdl.handle.net/10356/165808
_version_ 1764208131852730368
spelling sg-ntu-dr.10356-1658082023-04-16T15:37:47Z Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study Mina, Theresia Yew, Yik Weng Ng, Hong Kiat Sadhu, Nilanjana Wansaicheong, Gervais Dalan, Rinkoo Low, Dorrain Yan Wen Lam, Benjamin Chih Chiang Riboli, Elio Lee, Eng Sing Ngeow, Joanne Elliott, Paul Griva, Konstadina Loh, Marie Lee, Jimmy Chambers, John Lee Kong Chian School of Medicine (LKCMedicine) National Skin Centre Tan Tock Seng Hospital Khoo Teck Puat Hospital National Healthcare Group Polyclinic National Cancer Centre Institute of Mental Health Science::Medicine Adiposity Visceral Adiposity 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. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Ministry of Health (MOH) Nanyang Technological University National Medical Research Council (NMRC) Published version This work was supported by intramural funding from Nanyang Technological University, Lee Kong Chian School of Medicine, and the National Healthcare Group. J.C. is supported by: the Singapore Ministry of Health and National Medical Research Council STaR funding scheme [NMRC/StaR/0028/2017], LCG funding [MOH-000271], and Phase 2 National Precision Medicine Programme (Research Platform and Data Enablers) [NMRC/PRECISE/2020]; and the Singapore Agency for Science Technology and Research IAF-PP National Precision Medicine Program Phase 1A (A Population Level Genomic Infrastructure) [H17/ 01/a0/007] and IAF-PP Asian Skin Microbiome Programme [H18/01/ a0/016]. T.M. received postdoctoral fellowship from the Singapore Ministry of Education – Research Scholarship Block and Lee Kong Chian School of Medicine. 2023-04-11T01:54:58Z 2023-04-11T01:54:58Z 2023 Journal Article Mina, T., Yew, Y. W., Ng, H. K., Sadhu, N., Wansaicheong, G., Dalan, R., Low, D. Y. W., Lam, B. C. C., Riboli, E., Lee, E. S., Ngeow, J., Elliott, P., Griva, K., Loh, M., Lee, J. & Chambers, J. (2023). Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study. The Lancet Regional Health - Western Pacific, 33, 100710-. https://dx.doi.org/10.1016/j.lanwpc.2023.100710 2666-6065 https://hdl.handle.net/10356/165808 10.1016/j.lanwpc.2023.100710 36851942 2-s2.0-85147994215 33 100710 en NMRC/StaR/0028/2017 MOH-000271 NMRC/PRECISE/2020 H17/ 01/a0/007 H18/01/ a0/016 The Lancet regional health - Western Pacific © 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/). application/pdf