Stroke. 39(7):1999-2005, July 2008

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Nitkunan, Arani ; Barrick, Tom R. ; Charlton, Rebecca A. ; Clark, Chris A. ; Markus, Hugh S.
Multimodal MRI in Cerebral Small Vessel Disease: Its Relationship With Cognition and Sensitivity to Change Over Time.
Abstract
Background and Purpose-: Cerebral small vessel disease is the most common cause of vascular dementia. Interest in using MRI parameters as surrogate markers of disease to assess therapies is increasing. In patients with symptomatic sporadic small vessel disease, we determined which MRI parameters best correlated with cognitive function on cross-sectional analysis and which changed over a period of 1 year.Methods-: Thirty-five patients with lacunar stroke and leukoaraiosis were recruited. They underwent multimodal MRI (brain volume, fluid-attenuated inversion recovery lesion load, lacunar infarct number, fractional anisotropy, and mean diffusivity from diffusion tensor imaging) and neuropsychological testing. Twenty-seven agreed to reattend for repeat MRI and neuropsychology at 1 year.Results-: An executive function score correlated most strongly with diffusion tensor imaging (fractional anisotropy histogram, r=-0.640, P=0.004) and brain volume (r=0.501, P=0.034). Associations with diffusion tensor imaging were stronger than with all other MRI parameters. On multiple regression of all imaging parameters, a model that contained brain volume and fractional anisotropy, together with age, gender, and premorbid IQ, explained 74% of the variance of the executive function score (P=0.0001). Changes in mean diffusivity and fractional anisotropy were detectable over the 1-year follow-up; in contrast, no change in other MRI parameters was detectable over this time period.Conclusion-: A multimodal MRI model explains a large proportion of the variation in executive function in cerebral small vessel disease. In particular, diffusion tensor imaging correlates best with executive function and is the most sensitive to change. This supports the use of MRI, in particular diffusion tensor imaging, as a surrogate marker in treatment trials.