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.