Clonal Hematopoiesis of Indeterminate Potential Associated with Covert Cerebral Changes.

Abstract

Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardio-cerebrovascular diseases. This study aimed to investigate CHIP's association with cerebrovascular or glymphatic changes in a community-based population. This study examined Chinese community cohort participants. CHIP mutations were identified through whole-exome sequencing. Intracranial arterial stenosis, silent brain infarcts, cerebral small vessel disease markers, and diffusion along the perivascular space index were identified by magnetic resonance imaging. The correlation between CHIP and neuroimaging outcomes was investigated through univariate and multivariate logistic/linear regression. The multivariate regression model was adjusted for cerebrovascular disease risk factors, including age, sex, body mass index, smoking status, hypertension, diabetes, and hyperlipidemia. In total, 18.2% (224 out of 1,229) participants were identified as carriers of CHIP mutations. The prevalence of CHIP generally increases with age (p = 0.009). After adjusting for vascular risk factors using multivariate regression, CHIP mutations were found to be significantly associated with increased odds of large magnetic resonance imaging-defined infarcts (>15 mm; OR 3.20; 95% CI 1.18 to 8.43; p = 0.018), inversely associated with diffusion along the perivascular space (β = -0.02; 95% CI -0.04 to 0; p = 0.034), and showed a borderline association with intracranial arterial stenosis (OR 1.52; 95% CI 0.99 to 2.30; p = 0.053). Notably, no statistically significant correlations were observed between CHIP and cerebral small vessel disease markers or brain atrophy measures. CHIP was significantly associated with glymphatic dysfunction and large infarcts, and marginally associated with intracranial arterial stenosis. Further research is needed to elucidate the pathophysiology linking CHIP to cerebral covert changes. ANN NEUROL 2025;98:826-836.