Insidious cognitive decline in CADASIL.
OBJECTIVE
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.


CONCLUSIONS
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.
Amberla
Kaarina
K
Division of Clinical Geriatrics, Karolinska Institutet, Stockholm, Sweden.
Wäljas
Minna
M
Tuominen
Susanna
S
Almkvist
Ove
O
Pöyhönen
Minna
M
Tuisku
Seppo
S
Kalimo
Hannu
H
Viitanen
Matti
M
D000328:Adult; D003071:Cognition; D003430:Cross-Sectional Studies; D015161:Dementia, Multi-Infarct / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory; D008875:Middle Aged; D009154:Mutation; D009483:Neuropsychological Tests; D010375:Pedigree; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface / Q000235:genetics*; D051880:Receptors, Notch
C499374:NOTCH3 protein, human; D011518:Proto-Oncogene Proteins; D000071656:Receptor, Notch3; D011956:Receptors, Cell Surface; D051880:Receptors, Notch