Diffusion tensor MRI correlates with executive dysfunction in patients with ischaemic leukoaraiosis

Background: Cerebral small vessel disease is a common cause of vascular dementia. Both discrete lacunar infarcts and more diffuse ischaemic changes, seen as confluent high signal (leukoaraiosis) on T2 weighted magnetic resonance imaging (MRI), occur. However, there is a weak correlation between T2 lesion load and cognitive impairment. Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage. Objectives: To determine whether DTI measures are correlated more strongly with cognitive performance than lesion load on T2 weighted images, and whether these correlations are independent of conventional MRI parameters. Methods: 36 patients with ischaemic leukoaraiosis (leukoaraiosis plus a previous lacunar stroke) and 19 healthy volunteers underwent DTI, conventional MRI, and neuropsychological assessment. Results: On DTI, diffusivity was increased both within lesions and in normal appearing white matter. Mean diffusivity of normal appearing white matter correlated with full scale IQ (r = -0.46, p = 0.009) and tests of executive function. These correlations remained significant after controlling for age, sex, brain volume, and T1/T2 lesion volumes. No significant correlation was identified between T2 lesion load and IQ or neuropsychological scores. Of conventional measures, brain volume correlated best with cognitive function. Conclusions: Diffusion tensor measurements correlate better with cognition than conventional MRI measures. They may be useful in monitoring disease progression and as a surrogate marker for treatment trials. The findings support the role of white matter damage and disruption of white matter connections in the pathogenesis of cognitive impairment in cerebral small vessel disease.