Diabetes Metab J.  2025 Jan;49(1):60-79. 10.4093/dmj.2024.0117.

Longitudinal Association of Changes in Metabolic Syndrome with Cognitive Function: 12-Year Follow-up of the Guangzhou Biobank Cohort Study

• Tian YM
• Zhang WS
• Jiang CQ
• Zhu F
• Jin YL
• Yeung SLA
• Wang J
• Cheng KK
• Lam TH
• Xu L

• KMID: 2563270
• DOI: http://doi.org/10.4093/dmj.2024.0117

Abstract

Background
The association of changes in metabolic syndrome (MetS) with cognitive function remains unclear. We explored this association using prospective and Mendelian randomization (MR) studies.
Methods
MetS components including high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglycerides were measured at baseline and two follow-ups, constructing a MetS index. Immediate, delayed memory recall, and cognitive function along with its dimensions were assessed by immediate 10- word recall test (IWRT) and delayed 10-word recall test (DWRT), and mini-mental state examination (MMSE), respectively, at baseline and follow-ups. Linear mixed-effect model was used. Additionally, the genome-wide association study (GWAS) of MetS was conducted and one-sample MR was performed to assess the causality between MetS and cognitive function.
Results
Elevated MetS index was associated with decreasing annual change rates (decrease) in DWRT and MMSE scores, and with decreases in attention, calculation and recall dimensions. HDL-C was positively associated with an increase in DWRT scores, while SBP and FPG were negatively associated. HDL-C showed a positive association, whereas WC was negatively associated with increases in MMSE scores, including attention, calculation and recall dimensions. Interaction analysis indicated that the association of MetS index on cognitive decline was predominantly observed in low family income group. The GWAS of MetS identified some genetic variants. MR results showed a non-significant causality between MetS and decrease in DWRT, IWRT, nor MMSE scores.
Conclusion
Our study indicated a significant association of MetS and its components with declines in memory and cognitive function, especially in delayed memory recall.

Keyword

Cognition; Mendelian randomization analysis; Metabolic syndrome; Prospective studies

Figure

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  Fig. 1. Trajectory groups of metabolic syndrome (MetS) index and its components over 12-year follow-up. Values are means and 95% confidence interval (CI) for MetS index and its components. The components of MetS index included high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglyceride (TG). Four trajectory groups for (A) MetS index, (B) HDL-C, (C) SBP, and (D) WC, and two trajectory groups for (E) FPG and (F) TG were identified using group-based trajectory model, with standard of lower Bayesian information criterion and average posterior probability >0.7.

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  Fig. 2. Forest plots for the longitudinal association of the components of metabolic syndrome (MetS) index and their trajectory groups with annual change rates in (A) delayed 10-word recall test (DWRT), (B) immediate 10-word recall test (IWRT) and (C) mini-mental state examination (MMSE), (D) orientation, (E) registration, (F) attention and calculation, (G) recall, and (H) language scores based on linear-mixed effect model over 12-year follow-up. β and 95% confidence interval (CI) were adjusted for sex, age, baseline memory or cognitive function scores, body mass index, education, occupation, marital status, smoking status, drinking status, family income, physical activity, self-rated health, self-reported cardiovascular disease, hypertension, diabetes, hyperlipidemia and drug history. The components of MetS index included high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), waist circumference (WC), fasting plasma glucose (FPG), and triglyceride (TG). MMSE consists of f ive dimensions: orientation, registration, attention and calculation, recall, and language.

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  Fig. 3. (A) Manhattan plot and (B) quantile-quantile (Q-Q) plot for metabolic syndrome in the genome-wide association study involving 2,705 participants of the Guangzhou Biobank Cohort Study (2003 to 2008). The x-axis is chromosomal position, and the y-axis is the significance on a –log10 scale. The red line shows the genome-wide significance level (5×10–6).

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