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However, it is unclear whether AD risk differs in hypertensive individuals with and without diabetes.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>Cognitively normal individuals (<jats:italic>N<\/jats:italic>\u00a0=\u00a011,074) from the National Alzheimer's Coordinating Center (NACC) were categorized as having (1) hypertension with diabetes (HTN+\/DM+), (2) hypertension without diabetes (HTN+\/DM\u2010), or (3) neither (HTN\u2010\/DM\u2010). AD risk in HTN+\/DM+ and HTN+\/DM\u2010 was compared to HTN\u2010\/DM\u2010. This risk was then investigated in those with AD neuropathology (ADNP), cerebral amyloid angiopathy (CAA), cerebrovascular neuropathology (CVNP), arteriolosclerosis, and atherosclerosis. Finally, AD risk in HTN\u2010\/DM+ was compared to HTN\u2010\/DM\u2010.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Seven percent (<jats:italic>N<\/jats:italic>\u00a0=\u00a0830) of individuals developed AD. HTN+\/DM+ (hazard ratio [HR]\u00a0=\u00a01.31 [1.19\u20131.44]) and HTN+\/DM\u2010 (HR\u00a0=\u00a01.24 [1.17\u20131.32]) increased AD risk compared to HTN\u2010\/DM\u2010. AD risk was greater in HTN+\/DM+ with ADNP (HR\u00a0=\u00a02.10 [1.16\u20133.79]) and CAA (HR\u00a0=\u00a01.52 [1.09\u20132.12]), and in HTN+\/DM\u2010 with CVNP (HR\u00a0=\u00a01.54 [1.17\u20132.03]). HTN\u2010\/DM+ also increased AD risk (HR\u00a0=\u00a01.88 [1.30\u20132.72]) compared to HTN\u2010\/DM\u2010.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>HTN+\/DM+ and HTN+\/DM\u2010 increased AD risk compared to HTN\u2010\/DM\u2010, but pathological differences between groups suggest targeted therapies may be warranted based on cardiovascular risk profiles.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>AD risk was studied in hypertensive (HTN+) individuals with\/without diabetes (DM+\/\u2010).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>HTN+\/DM+ and HTN+\/DM\u2010 both had an increased risk of AD compared to HTN\u2010\/DM\u2010.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p><jats:italic>Post mortem<\/jats:italic> analysis identified neuropathological differences between HTN+\/DM+ and HTN+\/DM\u2010.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In HTN+\/DM+, AD risk was greater in those with AD neuropathology and CAA.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In HTN+\/DM\u2010, AD risk was greater in those with cerebrovascular neuropathology.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.13717","type":"journal-article","created":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T01:49:40Z","timestamp":1709257780000},"page":"2766-2778","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Investigating the impact of hypertension with and without diabetes on Alzheimer's disease risk: A clinico\u2010pathological study"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0308-2593","authenticated-orcid":false,"given":"Myuri","family":"Ruthirakuhan","sequence":"first","affiliation":[{"name":"Dr. Sandra Black Centre 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