Synergistic associations of CD33 variants and hypertension with brain and cognitive aging among dementia‐free older adults: A population‐based study

Abstract INTRODUCTION CD33 rs3865444 and hypertension (HTN) are related to cognitive impairment, individually. However, little is known about their combined effects on cognitive function in older adults. METHODS This population‐based study included 4368 dementia‐free participants (age ≥65 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND‐China), with data available in 1044 persons for gray matter volume and 85 persons for cerebral blood flow (CBF). We used general linear regression and mediation models to examine the associations of rs3865444 and HTN with cognition, brain atrophy, and CBF. RESULTS Among rs3865444 CC carriers, HTN and late‐life HTN were significantly associated with impaired cognition. Midlife and late‐life HTN were correlated with brain atrophy. CD33 rs3865444 CC moderated the mediation effect of gray matter volume on the association between HTN and global cognition. HTN was correlated with low CBF in rs3865444 CC carriers. DISCUSSION There are synergistic associations of CD33 rs3865444 and HTN with brain and cognitive aging in dementia‐free older adults.