Published Online
on February 1, 2007

A more recent version of this article appeared on March 1, 2007

This Article Full Text (PDF) All Versions of this Article: 38/3/923    most recent 01.STR.0000257968.24015.bfv1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liem, M. K. Articles by Lesnik Oberstein, S. A.J. Search for Related Content PubMed PubMed Citation Articles by Liem, M. K. Articles by Lesnik Oberstein, S. A.J. Related Collections Cerebral Lacunes Computerized tomography and Magnetic Resonance Imaging

Submitted on September 28, 2006
Accepted on October 11, 2006

Lacunar Infarcts Are the Main Correlate With Cognitive Dysfunction in CADASIL

Michael K. Liem MD^*; Jeroen van der Grond PhD; Joost Haan MD, PhD; Rivka van den Boom MD, PhD; Michel D. Ferrari MD, PhD; Yvette M. Knaap MSc; Martijn H. Breuning MD, PhD; Mark A. van Buchem MD, PhD; Huub A.M. Middelkoop PhD; and Saskia A.J. Lesnik Oberstein MD, PhD

From the Departments of Radiology (M.K.L., J.v.d.G., R.v.d.B., M.A.v.B.), Clinical Genetics (M.H.B., S.A.J.L.O.), Neurology (J.H., M.D.F.), and Neuropsychology (Y.M.K., H.A.M.M.), Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology (J.H.), Rijnland Hospital, Leiderdorp, The Netherlands; Department of Psychology (H.A.M.M.), Neuropsychology unit, Leiden University, The Netherlands.

^* To whom correspondence should be addressed. E-mail: m.k.liem{at}lumc.nl.

Background and Purpose--Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy is caused by mutations in the NOTCH3 gene and is clinically characterized by recurrent stroke and cognitive decline. Previous studies have shown an association between white matter hyperintensities on brain MRI and cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. In the general population the presence of lacunar infarcts and microbleeds is also associated with cognitive dysfunction. The objective of this study was to determine to what extent lacunar infarcts and microbleeds on MRI contribute to cognitive decline in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Methods--NOTCH3 mutation analysis was performed in 62 symptomatic and asymptomatic members of 15 cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy families. Neuropsychological tests were performed on the same day as the MRI examination. MRI was semi-quantitatively scored for white matter hyperintensities, infarct lesion load, and microbleeds. Regression analysis was performed to test the association between MRI abnormalities and neuropsychological test results.

Results--Forty individuals had a NOTCH3 mutation and 22 did not. Severity of cognitive dysfunction in mutation carriers was independently associated with MRI infarct lesion load (P<0.05). In contrast, WMH lesion load and microbleeds were not associated with cognitive dysfunction after correcting for age.

Conclusions--Lacunar infarct lesion load is the most important MRI parameter associated with cognitive dysfunction in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

Key words: CADASIL • cognition • lacunar infarction • MRI

This article has been cited by other articles:

				M.K. Liem, S.A.J. Lesnik Oberstein, J. Haan, R.v.d. Boom, M.D. Ferrari, M.A.v. Buchem, and J.v.d. Grond Cerebrovascular Reactivity Is a Main Determinant of White Matter Hyperintensity Progression in CADASIL AJNR Am. J. Neuroradiol., June 1, 2009; 30(6): 1244 - 1247. [Abstract] [Full Text] [PDF]

				M. Dichgans Cognition in CADASIL Stroke, March 1, 2009; 40(3_suppl_1): S45 - S47. [Abstract] [Full Text] [PDF]

				M. K. Liem, S.A.J. Lesnik Oberstein, J. Haan, I. L. van der Neut, M. D. Ferrari, M. A. van Buchem, H. A.M. Middelkoop, and J. van der Grond MRI correlates of cognitive decline in CADASIL: A 7-year follow-up study Neurology, January 13, 2009; 72(2): 143 - 148. [Abstract] [Full Text] [PDF]

				M L Stromillo, M T Dotti, M Battaglini, M Mortilla, S Bianchi, K Plewnia, L Pantoni, D Inzitari, A Federico, and N De Stefano Structural and metabolic brain abnormalities in preclinical cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy J. Neurol. Neurosurg. Psychiatry, January 1, 2009; 80(1): 41 - 47. [Abstract] [Full Text] [PDF]

				M. K. Liem, S. A. J. Lesnik Oberstein, J. Haan, I. L. van der Neut, R. van den Boom, M. D. Ferrari, M. A. van Buchem, and J. van der Grond Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy: Progression of MR Abnormalities in Prospective 7-year Follow-up Study Radiology, December 1, 2008; 249(3): 964 - 971. [Abstract] [Full Text] [PDF]

				P. B. Gorelick and J. V. Bowler Advances in Vascular Cognitive Impairment 2007 Stroke, February 1, 2008; 39(2): 279 - 282. [Full Text] [PDF]

				R. N. Kalaria Rounding up the usual suspects: Lacunar infarction and impairment in CADASIL Neurology, July 10, 2007; 69(2): 131 - 132. [Full Text] [PDF]