Causal Associations Between Body Composition and Cerebral Small Vessel Disease

Area of Science:

• Neuroscience
• Genetics
• Cardiology

Background:

• Cerebral small vessel disease (CSVD) impact on brain health is significant but its link to body composition is unclear.
• Cardiovascular risk factors like type 2 diabetes (T2D), blood pressure (BP), and LDL cholesterol are implicated in CSVD pathogenesis.

Purpose of the Study:

• To investigate causal relationships between body composition and CSVD phenotypes using Mendelian randomization (MR).
• To assess the mediating roles of T2D, SBP, DBP, and LDL-C in the association between body composition and CSVD.

Main Methods:

• Genome-wide association study (GWAS) summary statistics were analyzed.
• Univariable MR assessed genetic links between body composition and CSVD (WMH, lacunar stroke).
• Multivariable and mediation MR explored mediating effects of cardiovascular risk factors.

Main Results:

• Increased genetically predicted fat-free mass showed inverse associations with white matter hyperintensity (WMH) and lacunar stroke risk.
• SBP, DBP, T2D, and LDL-C partially mediated the association between fat-free mass and lacunar stroke.
• No mediation by these factors was observed for the WMH association, indicating distinct mechanisms.

Conclusions:

• Fat-free mass appears to have a protective effect against CSVD, partly mediated by cardiovascular risk factors.
• Modulating body composition, specifically increasing fat-free mass, could be a potential strategy for CSVD prevention.
• Understanding these complex interactions is crucial for preserving brain health and preventing cerebrovascular diseases.