Free water diffusion MRI and executive function with a speed component in healthy aging.

Area of Science:

• Neuroscience
• Radiology
• Gerontology

Background:

• Conventional biomarkers for brain aging, such as fractional anisotropy, may be less informative than extracellular free water (FW) increases.
• Understanding the relationship between brain imaging metrics and cognitive function is crucial for assessing aging-related cognitive decline.

Purpose of the Study:

• To investigate the association between conventional MRI biomarkers, FW in white matter hyperintensities (WMH) and normal-appearing white matter (NAWM), and executive functions (EF) with a speed component in elderly individuals.
• To determine the relative importance of various MRI metrics, including FW and diffusion metrics, in predicting EF performance.

Main Methods:

• The study included 226 healthy elderly participants who underwent brain MRI and neuropsychological testing.
• Partial correlation analyses were used to assess the relationship between imaging metrics (FW in WMH/NAWM, FW-corrected diffusion metrics, conventional MRI measures) and EF.
• Random forest analysis and regression models were employed to identify key determinants of EF and the role of specific white matter tracts.

Main Results:

• Nearly all imaging metrics showed a significant association with EF, with FW in WMH and NAWM identified as the most important predictors among diffusion and structural MRI metrics.
• Tract-based regression analyses revealed that the fornix and specific regions of the corpus callosum (genu, prefrontal, premotor) were significantly associated with EF with a speed component.
• Higher FW in the fornix and frontal corpus callosum correlated with deteriorating EF speed.

Conclusions:

• In a healthy aging population, extracellular free water in both white matter hyperintensities and normal-appearing white matter is more strongly associated with executive functions involving speed than standard diffusion tensor imaging and structural MRI measures.
• Specific white matter tracts, notably the fornix and corpus callosum, play a critical role in maintaining executive function speed in older adults.