Investigating the impact of hypertension with and without diabetes on progression to Alzheimer’s disease: A clinic‐pathological study

Abstract

AbstractBackgroundHypertension and diabetes have each been associated with an increased risk of progression to Alzheimer’s disease (AD) dementia. Here, we investigated their combined impact on progression from cognitively normal to clinically‐diagnosed AD.MethodCognitively normal individuals from the National Alzheimer’s Coordinating Center were identified as having neither hypertension nor diabetes (HTN‐/DM‐), hypertension without diabetes (HTN+/DM‐), or hypertension with diabetes (HTN+/DM+). The presence of HTN and DM were based on their diagnosis from recent medical history or medication use. This study investigated whether HTN+/DM‐ or HTN+/DM+ were predictors of progression to clinically‐diagnosed AD compared to HTN‐/DM‐. In a subgroup analysis with post‐mortem data, we investigated whether HTN+/DM‐, and HTN+/DM+ were predictors of progression to clinically diagnosed AD due to underlying AD‐ and/or vascular neuropathology.ResultThis study included N = 11074 cognitively normal individuals (mean age: 71.7 (9.0), MMSE: 28.9 (1.4), male: N = 3818 (34%)). Approximately 7% (N = 830) progressed to clinically‐diagnosed AD, and the average duration of follow‐up was 5.2 (3.6) years. Forty‐two percent (N = 4608) were HTN‐/DM‐, 45% (N = 5034) were HTN+/DM‐, and 13% (N = 1432) were HTN+/DM+. Both HTN+/DM‐ (hazard ratio (HR): 1.24 (1.17‐1.32), p<.001), and HTN+/DM+ (HR: 1.31 (1.19‐1.44), p<.001) were significant predictors of progression to clinically‐diagnosed AD. Subgroup analyses with post‐mortem data (N = 919) demonstrated that compared to HTN‐/DM‐, those with HTN+/DM‐ had a higher risk of progressing to clinically‐diagnosed AD with underlying cerebrovascular disease (CVD) neuropathology (HR: 1.54 (1.17‐2.03), p = .002), whereas those with HTN+/DB+ had a higher risk of progression to clinically‐diagnosed AD with underlying AD (HR: 2.10 (1.16‐3.79), p = .01) and cerebral amyloid angiopathy (CAA) neuropathology (HR: 1.52 (1.09‐2.12), p = .01).ConclusionThese findings demonstrate that underlying CVD neuropathology contributes to the risk of clinically‐diagnosed AD in individuals with HTN+/DM‐, while both AD and CAA neuropathology contributes to the risk of clinically‐diagnosed AD in individuals with HTN+/DM+. This suggests that individuals with HTN+/DM‐ and HTN+/DM+ vary phenotypically and may warrant the need for different treatment strategies to reduce the future risk of AD.