Investigating the impact of hypertension with and without diabetes on Alzheimer's disease risk: A clinico‐pathological study

INTRODUCTION Hypertension and diabetes are common cardiovascular risk factors that increase Alzheimer's disease (AD) risk. However, it is unclear whether AD risk differs in hypertensive individuals with and without diabetes. METHODS Cognitively normal individuals (N = 11,074) from the National Alzheimer's Coordinating Center (NACC) were categorized as having (1) hypertension with diabetes (HTN+/DM+), (2) hypertension without diabetes (HTN+/DM‐), or (3) neither (HTN‐/DM‐). AD risk in HTN+/DM+ and HTN+/DM‐ was compared to HTN‐/DM‐. 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‐/DM+ was compared to HTN‐/DM‐. RESULTS Seven percent (N = 830) of individuals developed AD. HTN+/DM+ (hazard ratio [HR] = 1.31 [1.19–1.44]) and HTN+/DM‐ (HR = 1.24 [1.17–1.32]) increased AD risk compared to HTN‐/DM‐. AD risk was greater in HTN+/DM+ with ADNP (HR = 2.10 [1.16–3.79]) and CAA (HR = 1.52 [1.09–2.12]), and in HTN+/DM‐ with CVNP (HR = 1.54 [1.17–2.03]). HTN‐/DM+ also increased AD risk (HR = 1.88 [1.30–2.72]) compared to HTN‐/DM‐. DISCUSSION HTN+/DM+ and HTN+/DM‐ increased AD risk compared to HTN‐/DM‐, but pathological differences between groups suggest targeted therapies may be warranted based on cardiovascular risk profiles. Highlights AD risk was studied in hypertensive (HTN+) individuals with/without diabetes (DM+/‐). HTN+/DM+ and HTN+/DM‐ both had an increased risk of AD compared to HTN‐/DM‐. Post mortem analysis identified neuropathological differences between HTN+/DM+ and HTN+/DM‐. In HTN+/DM+, AD risk was greater in those with AD neuropathology and CAA. In HTN+/DM‐, AD risk was greater in those with cerebrovascular neuropathology.