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Prevalence and Predictors of Vascular Cognitive Impairment in Patients With CADASIL
Amy A Jolly1, Stefania Nannoni2, Hayley Edwards2
1From the Stroke Research Group, Department of Clinical Neurosciences (A.A.J., S.N., H.E., H.S.M.), University of Cambridge, Cambridge Biomedical Campus, United Kingdom; and Department of Psychology (R.G.M.), King's College Institute of Psychiatry, Psychology and Neurosciences, Institute of Psychiatry, London, United Kingdom. aj602@medschl.cam.ac.uk.
Insights
Vascular cognitive impairment (VCI) affects nearly half of CADASIL patients. Stroke history and MRI-detected lacunes are key predictors of VCI in this genetic stroke disorder.
Area of Science:
- Neurology
- Genetics
- Neuroimaging
Background:
- Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic cause of stroke and early-onset dementia.
- Understanding the prevalence and predictors of vascular cognitive impairment (VCI) in CADASIL is crucial for patient management.
Purpose of the Study:
- To determine the prevalence of VCI in patients with genetically confirmed CADASIL.
- To identify clinical, genetic, and MRI factors associated with VCI risk in CADASIL.
Main Methods:
- Cognitive function was assessed in 176 CADASIL patients and 265 controls using the Brief Memory and Executive Test (BMET) and Montreal Cognitive Assessment (MoCA).
- VCI was defined using validated cutoffs.
- Associations between VCI and clinical factors, mutation location, and MRI markers of small vessel disease were analyzed.
Main Results:
- VCI prevalence was significantly higher in CADASIL patients (39.8% on BMET, 47.7% on MoCA) compared to controls (10.2% on BMET, 19.6% on MoCA).
- CADASIL patients exhibited poorer performance across all cognitive domains.
- A history of stroke independently predicted VCI (BMET: OR 2.12, MoCA: OR 2.55).
- Lacune count on MRI was the sole independent MRI predictor of VCI (BMET: OR 1.63).
- No association was found between VCI and mutation site.
Conclusions:
- VCI affects nearly half of CADASIL patients, even at a mean age of 50.
- Stroke history and the number of lacunes on MRI are significant independent predictors of VCI in CADASIL.
Background And Objectives:
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common monogenic form of stroke and early-onset dementia. We determined the prevalence of vascular cognitive impairment (VCI) in a group of patients with CADASIL and investigated which factors were associated with VCI risk, including clinical, genetic, and MRI parameters.
Methods:
Cognition was assessed in patients with genetically confirmed CADASIL (n = 176) and healthy controls (n = 265) (mean [SD] age 50.95 [11.35] vs 52.37 [7.93] years) using the Brief Memory and Executive Test (BMET) and the Montreal Cognitive Assessment (MoCA). VCI was defined according to previously validated cutoffs. We determined the prevalence of VCI and its associations with clinical risk factors, mutation location (epidermal growth factor-like repeats [EGFr] 1-6 vs EGFr 7-34), and MRI markers of small vessel disease.
Results:
VCI was more common in patients with CADASIL than in controls; 39.8 vs 10.2% on the BMET and 47.7% vs 19.6% on the MOCA. Patients with CADASIL had worse performance across all cognitive domains. A history of stroke was associated with VCI on the BMET (OR 2.12, 95% CI [1.05, 4.27] p = 0.04) and MoCA (OR 2.55 [1.21, 5.41] p = 0.01), after controlling for age and sex. There was no association of VCI with mutation site. Lacune count was the only MRI parameter independently associated with VCI on the BMET (OR: 1.63, 95% CI [1.10, 2.41], p = 0.014), after controlling for other MRI parameters. These associations persisted after controlling for education in the sensitivity analyses.
Discussion:
VCI is present in almost half of the patients with CADASIL with a mean age of 50 years. Stroke and lacune count on MRI were both independent predictors of VCI on the BMET.
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