Event-related potential correlates of recognition memory in asymptomatic individuals with CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common form of hereditary stroke disorder and is caused by mutations of the NOTCH3 gene. Cognitive decline in CADASIL is characterized by early impairments of attention, memory, and executive functions. Studying asymptomatic individuals with CADASIL offers a unique genetic model to understand preclinical vascular cognitive impairment and dementia. This study aimed at examine whether early preclinical physiological changes could be observed in asymptomatic individuals with CADASIL, who will go on to develop vascular cognitive impairment and dementia later in life. Twenty-nine individuals (mean age: 54.1 years old) were included in the study; five CADASIL NOTCH3 mutation carriers and twenty-five age-matched non-carriers. Participants underwent a comprehensive clinical evaluation and neuropsychological testing. Event-related potentials (ERPs) were recorded during a picture recognition memory task. Analyses focused on the early frontal effect and parietal effect ERP components associated with familiarity and recollection memory. There were no differences between groups in behavioral performance during recognition memory discrimination or cognitive performance. Compared to non-carriers, CADASIL carriers had decreased amplitudes in both ERP components for hits and correct rejections. Among mutation carriers, lower amplitude at 500-600 ms in the left parietal region of interest for correct rejections was correlated with worse performance on measures of semantic fluency and inhibitory control. We conclude that cognitively unimpaired CADASIL carriers showed abnormalities in the neural correlates of recognition memory, years before clinical onset. Early disruptions of fronto-subcortical networks may explain preclinical changes in brain function during recognition memory. This work also demonstrates the potential usefulness of ERP brain correlates as preclinical markers of vascular dementia.

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Copyright © 2018. Published by Elsevier B.V.