Adipose tissue distribution, cognitive decline and structural brain changes in individuals with cardiovascular disease: the SMART-MR study

Background Individuals with cardiovascular disease (CVD) have an almost 2-fold increased risk of dementia. With no curative therapies available for dementia, prevention is essential. Understanding how CVD risk factors contribute to dementia development in this population could help identify targets for prevention. One of such risk factors that may adversely affect brain health is adiposity. Of all adipose tissue depots, visceral adipose tissue (VAT) may be particularly detrimental and may be more strongly associated with cognitive decline and structural brain changes than other adipose tissue depots. Aim To quantify the relation between visceral adiposity measures, i.e., waist circumference (WC), waist to height ratio (WTHR) and abdominal VAT measured by ultrasound, and non-visceral adiposity measures, i.e., body mass index (BMI) and abdominal subcutaneous adipose tissue (SAT) measured by ultrasound, with cognitive decline and structural brain changes in individuals with CVD. Methods Data were derived from the prospective SMART-MR study (n=1,307), which enrolled participants with CVD or CVD risk factors, who underwent baseline and two follow-up assessments of cognitive function and brain MRI at median intervals of 3.8 years (IQR: 3.3-4.3) and 11.9 years (IQR: 11.4-12.5) after baseline. Linear mixed-effects models were used to estimate the relation between the adiposity measures (per higher SD) and changes in z-scores of executive function, memory, total brain volume (TBV) and white matter hyperintensity (WMH) volume (both corrected for intracranial volume), adjusted for age, sex, smoking status, smoking packyears, alcohol consumption and apolipoprotein E genotype. The age of participants at each visit was chosen as the time variable. Results Among individuals of the same age, those with higher WC, WTHR, abdominal VAT and BMI scored lower for executive function and memory, and individuals with higher WC, WTHR and abdominal VAT had a smaller TBV. Furthermore, individuals with a higher WC, WTHR and BMI had a greater decline in executive function over time (change in z-score per 5 years higher age: WC -0.024 [-0.046;-0.002], WTHR -0.032 [-0.054;-0.010] and BMI 0.026 [-0.048;-0.003]), and individuals with a higher WC, WTHR and abdominal VAT had a steeper decline in TBV (WC -0.011 [-0.016;-0.005], WTHR -0.011 [-0.017;-0.006], VAT -0.008 [-0.014;-0.003]). In contrast, abdominal SAT was not related to any cognition or MRI outcome, and no adiposity measure was related to WMH volume. Conclusion In individuals with CVD, visceral adiposity and total adiposity measures are related to decline in executive function, memory and TBV over time. In contrast, abdominal SAT is not related to any brain outcome. These findings suggest that visceral adiposity may contribute to accelerated brain ageing in individuals with CVD.Figure 1.Executive function over ageFigure 2.