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

Theresia Mina; Yik Weng Yew; Hong Kiat Ng; Nilanjana Sadhu; Gervais Wansaicheong; Rinkoo Dalan; Dorrain Yan Wen Low; Benjamin Chih Chiang Lam; Elio Riboli; Eng Sing Lee; Joanne Ngeow; Paul Elliott; Konstadina Griva; Marie Loh; Jimmy Lee; John Chambers

doi:10.1016/j.lanwpc.2023.100710

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

Lancet Reg Health West Pac. 2023 Feb 14:33:100710. doi: 10.1016/j.lanwpc.2023.100710. eCollection 2023 Apr.

Authors

Theresia Mina¹, Yik Weng Yew^{1

2}, Hong Kiat Ng¹, Nilanjana Sadhu¹, Gervais Wansaicheong^{1

3}, Rinkoo Dalan^{1

4}, Dorrain Yan Wen Low¹, Benjamin Chih Chiang Lam^{1

5}, Elio Riboli^{1

6}, Eng Sing Lee^{1

7}, Joanne Ngeow^{1

8}, Paul Elliott^{1

6}, Konstadina Griva¹, Marie Loh^{1

2}, Jimmy Lee^{1

9}, John Chambers^{1

6}

Affiliations

¹ Nanyang Technological University Lee Kong Chian School of Medicine, Level 18 Clinical Sciences Building, 11 Mandalay Road, 308232, Singapore.
² National Skin Centre, Research Division, 1 Mandalay Rd, 308205, Singapore.
³ Department of Diagnostic Radiology, Tan Tock Seng Hospital (TTSH), 11 Jalan Tan Tock Seng, 308433, Singapore.
⁴ Department of Endocrinology, TTSH, Singapore.
⁵ Khoo Teck Puat Hospital, Integrated Care for Obesity & Diabetes, 90 Yishun Central, 768828, Singapore.
⁶ Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, 152 Medical School, St Mary's Campus, London, W2 1NY, United Kingdom.
⁷ Clinical Research Unit, National Healthcare Group Polyclinic, 3 Fusionopolis Link, Nexus@one-north, #05-10, 138543, Singapore.
⁸ Division of Medical Oncology, National Cancer Centre, 11 Hospital Drive, 169610, Singapore.
⁹ Research Division, Institute of Mental Health, 539747, Singapore.

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.

Keywords: Adiposity; Aging; Asia; Cardiovascular risk factors; Cognitive function; DEXA; General cognition; Mendelian Randomization; Metabolic syndrome; Visceral adiposity.