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Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a cerebral small vessel disease caused by mutations of the NOTCH3 gene. Marked variations in disease severity have raised the hypothesis that non-genetic factors may modulate the expressivity of the phenotype. The aim of the current study was to evaluate whether atherosclerosis, assessed by carotid duplex ultrasonography, is associated with variations in the clinical and MRI phenotype of CADASIL., Methods: Data from 144 consecutive patients enrolled in an ongoing prospective cohort study were collected. Degree of disability was assessed by the modified Rankin Scale, that of cognitive impairment by the Mattis Dementia Rating Scale (MDRS). The total volume of the brain, of lacunar lesions and of white matter hyperintensities, the number of cerebral microhemorrhages, and parameters derived from histograms of apparent diffusion coefficient were measured on cerebral MRI. Atherosclerosis was evaluated by B-mode ultrasonography of carotid arteries. Both the carotid intima-media thickness (cIMT) and the presence of carotid plaques or stenosis were recorded., Results: Higher cIMT was found to be independently associated with lower MDRS scores when this score was less than the quartile limit (p = 0.02). Only a trend for a positive association was detected between cIMT and the Rankin score (p = 0.06). There was no significant association between carotid markers and the occurrence of stroke or MRI parameters except for diffusion data. The mean and peak values of MRI diffusion histograms were found positively associated with the presence of plaques (p < 0.01)., Conclusion: The results suggest that the severity of atherosclerosis may relate to cognitive decline in CADASIL and that this effect is possibly related to the degree of microstructural cerebral tissue lesions. Longitudinal studies are needed to confirm these results., (Copyright © 2010 S. Karger AG, Basel.)

Objective: This study investigated the relationship between serum levels of two neurotrophic factors, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF), and carotid atherosclerosis and cognitive function in the elderly., Methods: Serum levels of IGF-1 and HGF, carotid artery intima-media thickness (IMT), and Mini-Mental State Examination (MMSE) scores were determined in 60 subjects over 65 years old (35 patients with vascular dementia and 25 without dementia)., Results: In all subjects IGF-1 levels showed a significant positive correlation with the MMSE score (r = 0.262, p = 0.0427) and a negative correlation with the IMT (r = -0.284, p = 0.0277) and the HGF level (r = -0.422, p = 0.0007). HGF levels were significantly correlated with IMT (r = 0.259, p = 0.0455) and lipoprotein(a) levels (r = 0.279, p = 0.0372). Mean MMSE scores and IGF-1 levels were significantly lower in patients with vascular dementia than in the non-demented controls. Mean IMT and the frequency of atherosclerotic plaque in the carotid arteries as well as the serum levels of HGF, LDL cholesterol, lipoprotein(a) and lipid peroxides were significantly increased in the demented patients compared with the non-demented controls., Conclusion: A decrease of IGF-1 along with an increase of HGF may reflect an underlying biological process that influences cognitive decline as well as carotid atherosclerosis in the elderly., (Copyright 2004 S. Karger AG, Basel)