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However, little is known about their combined effects on cognitive function in older adults.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>This population\u2010based study included 4368 dementia\u2010free participants (age \u226565 years) in the Multimodal Interventions to Delay Dementia and Disability in Rural China (MIND\u2010China), 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Among rs3865444 CC carriers, HTN and late\u2010life HTN were significantly associated with impaired cognition. Midlife and late\u2010life HTN were correlated with brain atrophy. <jats:italic>CD33<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>There are synergistic associations of <jats:italic>CD33<\/jats:italic> rs3865444 and HTN with brain and cognitive aging in dementia\u2010free older adults.<\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14209","type":"journal-article","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T02:39:05Z","timestamp":1725071945000},"page":"7193-7204","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Synergistic associations of <i>CD33<\/i> variants and hypertension with brain and cognitive aging among dementia\u2010free older adults: A population\u2010based study"],"prefix":"10.1002","volume":"20","author":[{"given":"Min","family":"Zhu","sequence":"first","affiliation":[{"name":"Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education, Department of Neurology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan Shandong P.R. 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