Abstract
Mobility impairment in older persons is associated with brain white matter hyperintensities (WMH), a common finding in magnetic resonance images and one established imaging biomarker of small vessel disease. The contribution of possible microstructural abnormalities within normal-appearing white matter (NAWM) to mobility, however, remains unclear. We used diffusion tensor imaging (DTI) measures, i.e. fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), radial diffusivity (RD), to assess microstructural changes within supratentorial NAWM and WMH sub-compartments, and to investigate their association with changes in mobility performance, i.e. Tinetti assessment and the 2.5-meters walk time test. We analyzed baseline (N = 86, age ≥75 years) and 4-year (N = 41) follow-up data. Results from cross-sectional analysis on baseline data showed significant correlation between WMH volume and NAWM-FA (r = -0.33, p = 0.002), NAWM-AD (r = 0.32, p = 0.003) and NAWM-RD (r = 0.39, p = 0.0002). Our longitudinal analysis showed that after 4-years, FA and AD decreased and RD increased within NAWM. In regional tract-based analysis decrease in NAWM-FA and increase in NAWM-RD within the genu of the corpus callosum correlated with slower walk time independent of age, gender and WMH burden. In conclusion, global DTI indices of microstructural integrity indicate that significant changes occur in the supratentorial NAWM over four years. The observed changes likely reflect white matter deterioration resulting from aging as well as accrual of cerebrovascular injury associated with small vessel disease. The observed association between mobility scores and regional measures of NAWM microstructural integrity within the corpus callosum suggests that subtle changes within this structure may contribute to mobility impairment.
Highlights
Magnetic resonance images (MRI) of the brain from elderly individuals frequently show areas of white matter damage, characterized by a T2 hyperintense signal and termed white matter hyperintensities (WMH)
Baseline diffusion tensor imaging (DTI) measures and WMH volumes of the dropouts were similar to the completers (p>0.05)
We found a significant increase of axial diffusivity (AD) within genu of corpus callosum (GCC)-normal-appearing white matter (NAWM)
Summary
Magnetic resonance images (MRI) of the brain from elderly individuals frequently show areas of white matter damage, characterized by a T2 hyperintense signal and termed white matter hyperintensities (WMH) Most often these lesions extend outward from the anterior and posterior horns of the lateral ventricles other hemispheric locations including subcortical regions are observed. A multimodal MRI study provided evidence of damage extending from WMH into larger adjacent areas of normal-appearing white matter (NAWM) characterized by reduced blood flow [2] suggesting an underlying ischemic mechanism of WMH expansion. This explanation is supported by epidemiological studies showing associations between WMH and vascular disease risk factors, including hypertension [3,4,5], diabetes [6] and obesity [7]. The predisposition of WMH to occur in frontal areas adjacent to the lateral ventricles likely explains their deleterious effect on mobility, cognition (primarily executive function) and urinary control [10, 12, 17]
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