Associations of Handgrip Strength and Testosterone With Cerebral White Matter Hyperintensity and Microstructural...

Area of Science:

• Neurology
• Gerontology
• Biomarkers

Background:

• White matter hyperintensity (WMH) is a key marker of cerebral small vessel disease (CSVD).
• Microstructural white matter injury may precede WMH development.
• The relationship between handgrip strength (HGS), serum total testosterone (STT), and WMH/microstructural injury requires further investigation.

Purpose of the Study:

• To explore the associations of HGS and STT with WMH and white matter microstructural injury.
• To analyze neuroimaging outcomes including fractional anisotropy (FA), mean diffusivity (MD), intracellular volume fraction (ICVF), and isotropic volume fraction (ISOVF).

Main Methods:

• Utilized UK Biobank data from 34,832 participants (mean age 64.15 ± 7.75 years).
• Employed cross-sectional linear regression, sensitivity analyses, longitudinal, mediation, and Mendelian randomization (MR) analyses.
• Investigated HGS and STT relationships with WMH and microstructural injury metrics.

Main Results:

• Greater HGS correlated with smaller WMH volume and improved white matter microstructure (p < 0.001).
• STT showed significant associations with WMH and microstructural metrics, varying by sex.
• STT mediated the HGS-WMH association, with MR analysis suggesting causality in males.

Conclusions:

• Increased HGS is associated with reduced WMH and less white matter microstructural damage, partly mediated by STT.
• Enhancing muscle function (HGS) may be a strategy to delay white matter injury.
• This offers a potential secondary prevention approach for CSVD, reducing risks of stroke and dementia.