Journal of the International Neuropsychological Society



CADASIL: Neuropsychological findings in three generations of an affected family


JOSETTE G.  HARRIS a1a2c1 and CHRISTOPHER M.  FILLEY a1a2a3
a1 Department of Psychiatry, University of Colorado School of Medicine, Denver
a2 Department of Neurology, University of Colorado School of Medicine, Denver
a3 Denver Veterans Affairs Medical Center

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary brain disease with a variety of neurologic and psychiatric manifestations. We studied 3 members of a family who each had leukoencephalopathy on neuroimaging studies and a characteristic mutation for CADASIL in the notch 3 region of chromosome 19q12. In all 3 cases, neurobehavioral impairment dominated the clinical picture, and a pattern of psychiatric dysfunction heralding cognitive decline emerged. Neuropsychological evaluation revealed diverse deficits, but a profile of frontal lobe dysfunction, declarative memory impairment suggestive of a retrieval deficit, and relatively preserved language was evident. These cases provide a cross-sectional study of the evolution of CADASIL, and suggest that, as in other diseases characterized by white matter dementia, psychiatric dysfunction may occur initially, followed by pervasive cognitive dysfunction later in the course of the disease. CADASIL should be considered in young adults with unexplained leukoencephalopathy on neuroimaging studies, and in those with neurobehavioral dysfunction and a suggestive family history. (JINS, 2001, 7, 768–774.)

(Received January 11 2000)
(Revised July 27 2000)
(Accepted August 29 2000)


Key Words: CADASIL; Neuropsychology; White matter dementia.

Correspondence:
c1 Reprint requests to: Josette G. Harris, Ph.D., Department of Psychiatry, University of Colorado School of Medicine, 4200 East Ninth Avenue, Denver, CO 80262.