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Updated: Sep 23, 2025
Diffusion Tensor Magnetic Resonance Imaging in the Analysis of Neurodegenerative Diseases
Published on: July 28, 2013
Free water diffusion MRI and executive function with a speed component in healthy aging
Martin Berger1, Lukas Pirpamer1, Edith Hofer2
1Department of Neurology, Division of Neurogeriatrics, Medical University of Graz, Auenbruggerplatz 22, Graz 8036, Austria.
Abstract:
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.
Insights
Extracellular free water (FW) increases in white matter lesions and normal-appearing white matter are more closely linked to executive functions (EF) in older adults than traditional MRI measures. Specific white matter tracts, like the fornix and corpus callosum, significantly impact EF speed.
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.
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