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on February 7, 2008

Stroke. 2008
Published online before print February 7, 2008, doi: 10.1161/STROKEAHA.107.507392
A more recent version of this article appeared on March 1, 2008
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Submitted on October 15, 2007
Accepted on November 8, 2007

Gray Matter Atrophy in Patients With Ischemic Stroke With Cognitive Impairment

Glenn T. Stebbins PhD*; David L. Nyenhuis PhD; Changsheng Wang PhD; Jennifer L. Cox PhD; Sally Freels PhD; Katherine Bangen PhD; Leyla deToledo-Morrell PhD; Kumar Sripathirathan PhD; Michael Moseley PhD; David A. Turner MD; John D.E. Gabrieli PhD; and Philip B. Gorelick MD

From the Departments of Neurological Sciences (G.T.S., C.W., L.d.T.-M., K.S.) and Diagnostic Radiology (D.A.T.), Rush University Medical Center, Chicago, Ill; the Department of Neurology and Rehabilitation (D.L.N., P.B.G.), University of Illinois, Chicago, Ill; Buffalo Neuroimaging Center (J.L.C.), Buffalo, NY; the School of Public Health (S.F.), University of Illinois, Chicago, Ill; Neurosciences (K.B.), University of California at San Diego, San Diego, Calif; the Department of Radiology (M.M.), Stanford University, Stanford, Calif; and the Department of Brain and Cognitive Sciences (J.D.E.G.), Massachusetts Institute of Technology, Cambridge, Mass.

* To whom correspondence should be addressed. E-mail: gstebbin{at}rush.edu.

Background and Purpose—Patients with ischemic stroke are at risk for developing vascular cognitive impairment ranging from mild impairments to dementia. MRI findings of infarction, white matter hyperintensities, and global cerebral atrophy have been implicated in the development of vascular cognitive impairment. The present study investigated regional gray matter volume differences between patients with ischemic stroke with no cognitive impairment and those with impairment in at least one domain of cognitive function.

Methods—Ninety-one patients with ischemic stroke participated. Detailed neuropsychological testing was used to characterize cognitive functioning in 7 domains: orientation, attention, working memory, language, visuospatial ability, psychomotor speed, and memory. High-resolution T1-weighted 3-dimensional fast-spoiled gradient recalled structural MRIs were processed using optimized voxel-based morphometry techniques while controlling for lesions. Whole brain voxelwise regional differences in gray matter volume were assessed between patients with stroke with no impaired cognitive domains and patients with stroke with at least one impaired cognitive domain. Logistic regression models were used to assess the contribution of demographic variables, stroke-related variables, and voxel-based morphometry results to classification of cognitive impairment group membership.

Results—Fifty-one patients had no impairments in any cognitive domain and 40 patients were impaired in at least one cognitive domain. Logistic regression identified significant contributions to cognitive impairment groups for demographic variables, stroke-related variables, and cognitive domain performance. Voxel-based morphology results demonstrated significant gray matter volume reductions in patients with stroke with one or more cognitive domain impairment compared with patients with stroke without cognitive impairment that was seen mostly in the thalamus with smaller reductions found in the cingulate gyrus and frontal, temporal, parietal, and occipital lobes. These reductions were present after controlling for group differences in age, education, stroke volume, and laterality of stroke. The addition of voxel-based morphometry-derived thalamic volume significantly improved a logistic regression model predicting cognitive impairment group membership when added to demographic variables, stroke-related variables, and cognitive domain performance.

Conclusions—These results suggest a central role for the thalamus and lesser roles for other cortical regions in the development of cognitive impairment after ischemic stroke. Indeed, consideration of thalamic volumes adds significant information to the classification of cognitive impaired versus nonimpaired groups beyond information provided by demographic, stroke-related, and cognitive performance measures.


Key words: cognition disorders • MRI • vascular cognitive impairment




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