Cognitive performance in asymptomatic carriers of mutations R1031C and R141C in CADASIL

Area of Science:

• Neurology
• Genetics
• Cognitive Science

Background:

• Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is the primary genetic cause of recurrent ischemic strokes and a model for vascular dementia.
• Identifying cognitive changes in asymptomatic carriers is crucial for early intervention.

Purpose of the Study:

• To assess the cognitive performance of individuals with CADASIL mutations R1031C and R141C before symptom onset.
• To identify potential preclinical cognitive biomarkers associated with CADASIL.

Main Methods:

• An observational, cross-sectional analytical study design.
• Comparison of cognitive function across three groups: asymptomatic R1031C mutation carriers (n=39), R141C mutation carriers (n=8), and non-carriers (n=50).
• Evaluation of cognitive domains including constructional praxis, executive function, abstract reasoning, working memory, mental calculation, and processing speed.

Main Results:

• Significant differences (p < 0.05) were observed between R1031C carriers and non-carriers in constructional praxis, executive function, and abstract reasoning.
• R141C carriers demonstrated lower-than-expected scores in executive function and mental calculation.
• Asymptomatic carriers of both mutations exhibited deficits in working memory, mental abstraction, and processing speed.

Conclusions:

• Asymptomatic carriers of CADASIL mutations R1031C and R141C display cognitive impairments.
• These cognitive deficits may serve as preclinical biomarkers for vascular dementia, preceding clinical manifestation of stroke.
• Early detection of cognitive changes in CADASIL carriers can inform prognosis and therapeutic strategies.