Abstract Details

Title Association of Rare NOTCH3 Variants with Prevalent and Incident Stroke and Dementia in the General Population

Topic General Neurology

Presentation(s) P8 - Poster Session 8 (5:30 PM-6:30 PM)

Poster/Presentation
Number 4-003

Objective This study aims to determine the associations of rare NOTCH3 variants with prevalent and incident stroke and dementia, as well as cognitive function changes.

Background Rare NOTCH3 variants have been identified in a considerable proportion of the general population and are associated with imaging changes related to cerebral small vessel disease. In addition, previous studies have found that rare NOTCH3 variants are significantly enriched in Alzheimer’s disease patients compared to controls.

Design/Methods In the prospective community-based Shunyi Study, a total of 1007 participants were included in the baseline analysis. For the follow-up analysis, 1007 participants were included in the stroke analysis and 870 participants in the dementia analysis. All participants underwent baseline brain magnetic resonance imaging, carotid ultrasound, and whole exome sequencing. Rare NOTCH3 variants were defined as variants with minor allele frequency <1%.

Results A total of 137 rare NOTCH3 carriers were enrolled in the baseline study. At baseline, rare NOTCH3 variant carriers had higher rates of stroke (8.8% vs 5.6%) and dementia (2.9% vs 0.8%) compared to non-carriers. After adjustment for associated risk factors, the EGFr-involving rare NOTCH3 variants were associated with a higher risk of prevalent stroke (odds ratio, 2.863 [95% CI, 1.334-6.143]; p=0.028) and dementia (odds ratio, 11.155 [95% CI, 1.601-77.745]; p=0.030). In addition, the rare NOTCH3 variant carriers had a higher rate of carotid plaques (odds ratio, 1.844 [95% CI, 1.158-2.937]; p=0.040). After 5 years of follow-up, we did not find that the rare NOTCH3 variants increased the risk of incident stroke and dementia. There were no statistically significant differences in the cognitive scale scores at baseline or in the changes over the five years.

Conclusions Rare NOTCH3 EGFr-involving variants are genetic risk factors for stroke and dementia in the general Chinese population.

Authors/Disclosures
Pei Wang PRESENTER	Pei Wang has nothing to disclose.
Ming Yao	Ming Yao has nothing to disclose.
Jing Yuan (Peking Union Medical College Hospital)	No disclosure on file
Fei Han	Fei Han has nothing to disclose.
Feifei Zhai	No disclosure on file
Ding-Ding Zhang	Ding-Ding Zhang has nothing to disclose.
Lixin Zhou	Lixin Zhou has nothing to disclose.
Jun Ni	Jun Ni has nothing to disclose.
Shu-Yang Zhang	No disclosure on file
Liying Cui, PhD (Peking Union Medical College Hospital)	No disclosure on file
Yi-Cheng Zhu, MD, PhD (Peking Union Medical College Hospital)	Dr. Zhu has nothing to disclose.

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