Clonal Hematopoiesis of Indeterminate Potential and the Risk of Cognitive Impairment in the Women’s Health Initiative Memory Study
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INTRODUCTION
Clonal hematopoiesis of indeterminate potential (CHIP) confers an increased risk of several chronic aging-related diseases. Paradoxically, CHIP was associated with lower risk of dementia in recent studies.
METHODS
We examined associations between baseline CHIP and incident mild cognitive impairment (MCI) and/or probable dementia in the Women’s Health Initiative Memory Study. CHIP was detected using blood-based targeted sequencing. Cox proportional hazards models examined time to onset of cognitive impairment, adjusting for traditional risk factors.
RESULTS
Using a conventional variant allele fraction (VAF) threshold of 2%, CHIP was not associated with incident cognitive impairment. The presence of larger CHIP clone (VAF≥8%) was associated with a lower incidence of adjudicated probable dementia (HR=0.62 [95% CI=0.41-0.94], p =0.025), while the association with the composite outcome MCI/probable dementia was weaker and overlapped 1.0.
DISCUSSION
The association of CHIP with lower risk of cognitive impairment in postmenopausal women may be dependent on VAF and impairment severity.
