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From the Division of Clinical Neuroscience, St. George’s Hospital Medical School, London, UK.
Address correspondence and reprint requests to Dr. H.S. Markus, Division of Clinical Neuroscience, St. George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK; e-mail: h.markus{at}sghms.ac.uk
Background: Executive dysfunction is an early feature in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) and may progress to a subcortical dementia. The mechanism of cognitive impairment is incompletely understood, and correlations with T2 lesion volumes are not strong. Diffusion tensor imaging (DTI) may provide a better index of white matter tract damage. Previous DTI studies in CADASIL demonstrated abnormalities in normal-appearing white matter, thalamus, and putamen and correlations with the Mini-Mental State Examination (MMSE).
Objectives: To determine whether DTI abnormalities could be identified in nondemented patients with CADASIL and whether these correlated particularly strongly with executive function.
Methods: Eighteen CADASIL subjects underwent DTI and cognitive assessment, including tests of several aspects of executive function. DTI was also performed on 12 age-matched control subjects.
Results: Mean diffusivity was increased in white matter lesions, normal-appearing white matter, and normal-appearing gray matter (thalamus, putamen, and globus pallidus). A composite score of executive function correlated with diffusivity in both normal-appearing gray matter (r = -0.73, p = 0.002) and white matter (r = -0.68, p = 0.004). The strongest correlation for gray matter was for the thalamus (r = -0.66, p = 0.004); this remained after controlling for age, gender, and T2 lesion volumes. Correlations with MMSE were much weaker, and there was no correlation between T2 lesion volume and the executive function score (r = -0.29, p = 0.27).
Conclusions: Abnormalities of normal-appearing white and deep gray matter are present in nondemented CADASIL patients, and these DTI measurements correlate particularly strongly with executive function.
Received April 2, 2003. Accepted in final form September 17, 2003.
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