Key result
White matter extracellular free water links more closely to deteriorating executive function than standard DTI.
Why the study?
Extracellular free water increases may provide better pathophysiological information in brain aging than conventional MRI biomarkers, but their relationship with executive function is unclear.
Do free water diffusion MRI metrics better correlate with executive function with a speed component compared to conventional MRI biomarkers in healthy aging?
Cross-Sectional (n=226)
Do free water diffusion MRI metrics better correlate with executive function with a speed component compared to conventional MRI biomarkers in healthy aging?
Effect estimate: r = -0.213 to 0.266
In healthy aging, free water in white matter hyperintensities and normal appearing white matter is more closely related to executive function with a speed component than standard DTI and structural measures.
Free water metrics may better track executive function than DTI in aging; hypothesis-generating and requires longitudinal validation.
Extracellular free water (FW) increases are suggested to better provide pathophysiological information in brain aging than conventional biomarkers such as fractional anisotropy. The aim of the present study was to determine the relationship between conventional biomarkers, FW in white matter hyperintensities (WMH), FW in normal appearing white matter (NAWM) and in white matter tracts and executive functions (EF) with a speed component in elderly persons. We examined 226 healthy elderly participants (median age 69.83 years, IQR: 56.99–74.42) who underwent brain MRI and neuropsychological examination. FW in WMH and in NAWM as well as FW corrected diffusion metrics and measures derived from conventional MRI (white matter hyperintensities, brain volume, lacunes) were used in partial correlation (adjusted for age) to assess their correlation with EF with a speed component. Random forest analysis was used to assess the relative importance of these variables as determinants. Lastly, linear regression analyses of FW in white matter tracts corrected for risk factors of cognitive and white matter deterioration, were used to examine the role of specific tracts on EF with a speed component, which were then ranked with random forest regression. Partial correlation analyses revealed that almost all imaging metrics showed a significant association with EF with a speed component (r = -0.213 – 0.266). Random forest regression highlighted FW in WMH and in NAWM as most important among all diffusion and structural MRI metrics. The fornix (R2=0.421, p = 0.018) and the corpus callosum (genu (R2 = 0.418, p = 0.021), prefrontal (R2 = 0.416, p = 0.026), premotor (R2 = 0.418, p = 0.021)) were associated with EF with a speed component in tract based regression analyses and had highest variables importance. In a normal aging population FW in WMH and NAWM is more closely related to EF with a speed component than standard DTI and brain structural measures. Higher amounts of FW in the fornix and the frontal part of the corpus callosum leads to deteriorating EF with a speed component.
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Berger et al. (2022) conducted a cross-sectional in Healthy aging (n=226). Extracellular free water (FW) in brain white matter vs. Standard DTI and brain structural measures was evaluated on Executive functions (EF) with a speed component (r = -0.213 to 0.266). Higher amounts of extracellular free water in white matter hyperintensities and normal appearing white matter are more closely related to deteriorating executive function than standard DTI measures.
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