Published Online
on May 13, 2004

A more recent version of this article appeared on July 1, 2004

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Submitted on September 17, 2003
Accepted on March 18, 2004

Insidious Cognitive Decline in CADASIL

Kaarina Amberla MSc; Minna Wäljas MSc; Susanna Tuominen MD; Ove Almkvist PhD; Minna Pöyhönen MD; Seppo Tuisku MD; Hannu Kalimo MD; and Matti Viitanen MD^*

From the Division of Clinical Geriatrics (K.A., O.A., M.V.), Karolinska Institutet, Stockholm, Sweden; Tampere University Hospital (M.W.), Department of Neurosurgery, Finland; Department of Psychology (O.A.), Stockholm University, Stockholm, Sweden; Department of Medical Genetics (M.P.), Family Federation of Finland, Helsinki, Finland; Keski-Pohjanmaa Central Hospital (S.Tuisku), Kokkola, Finland; Department of Neurology (S.Tuominen) and Department of Pathology (H.K.), Turku University Hospital, Turku, Finland; Department of Pathology (H.K.), Uppsala University and University Hospital, Uppsala, Sweden; Department of Pathology (H.K.), University Hospital of Helsinki, Helsinki, Finland; Department of Geriatric Medicine (M.V.), University of Turku, Finland.

^* To whom correspondence should be addressed. E-mail: matti.viitanen{at}neurotec.ki.se.

Background and Purpose--Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) causes repeated ischemic attacks leading to subcortical vascular dementia. The aim of this study was to characterize cognitive function in subjects with a C475T (R133C) mutation in the Notch3 gene, leading to CADASIL.

Methods--Prestroke (n=13) and poststroke (n=13) mutation carriers and mutation carriers with dementia (n=8) were compared with healthy noncarriers from the same families using a comprehensive set of neuropsychological tests.

Results--Changes in working memory and executive function were observed in the very early phase of the disease before transient ischemic attack (TIA) or stroke. Later, in the poststroke phase, the cognitive impairment concerned also mental speed and visuospatial ability. Finally, the subjects with dementia had multiple cognitive deficits, which engaged even verbal functions, verbal episodic memory, and motor speed. The 2 mutation carrier groups without dementia and the controls could be reliably distinguished using 3 tests that assessed working memory/attention, executive function, and mental speed. Episodic memory was relatively well-preserved late in the disease.

Conclusion--A deterioration of working memory and executive function was already observed in the prestroke phase, which means that cognitive decline may start insidiously before the first onset of symptomatic ischemic episodes.

Key words: CADASIL • neuropsychology • vascular diseases • small vessel disease

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