Association of antihypertensive medications and Alzheimer’s disease neuropathology

• Published in: Alzheimer's & dementia Vol. 16
• Main Authors: Xu, Chenjia, Apostolova, Liana G., Oblak, Adrian L, Gao, Sujuan
• Format: Journal Article
• Language: English
• Published: 01-12-2020
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.042283

Background
Previous research has reported that antihypertensive medications are associated with reduced risk of Alzheimer’s disease (AD). The objective of this study is to determine the association between antihypertensive medication use and its subclasses of medications with AD neuropathological measures.
Methods
Autopsy data were obtained from National Alzheimer's Coordinating Center (NACC). This analysis included data from 4,368 individuals. Braak stage for neurofibrillary degeneration, CERAD score for neuritic and diffuse plaques, and cerebral amyloid angiopathy were used as separate outcomes in proportional odds models. Vascular pathology, defined as the total of vascular conditions noted on autopsy forms was also used an outcome in proportional odds models. Any antihypertensive medication use and seven antihypertensive subclasses of medications (antiadrenergic agents, ACE inhibitors, angiotensin II inhibitors, beta‐blockers, calcium channel blocking agents, diuretics, and vasodilators) were independent variables in separate models for each neuropathological outcome while adjusting for age, sex, education, race and other vascular conditions (hypertension, heart disease, diabetes and stroke), blood pressure measures and APOE status.
Results
Mean age at death for this sample was 80.6 (SD=11.6) and 54.0% were male. Sixty percent reported a history of hypertension, 91% of whom were on antihypertensive medications. Any antihypertensive medication use was associated with lower Braak stage of neurofibrillary tangles (proportional OR=0.82, p=0.0085) and lower cerebral amyloid angiopathy (OR=0.80, p=0.0063) while adjusting for demographic variables and other vascular conditions. Among antihypertensive subclass of medications, diuretics were associated with lower Braak stage (OR=0.71, p<0.0001), lower CERAD neuritic plaque density (OR=0.77, p=0.0007), lower CERAD diffused plaque (OR=0.74, p<0.0001), and cerebral amyloid angiopathy (OR=0.75, p<0.0001) while adjusting for demographic variables, other vascular conditions, blood pressure, and APOE. The associations between diuretics and lower pathological measures were unchanged after further adjusting for vascular pathology.
Conclusions
Antihypertensive medication use is associated with decreased AD neuropathology in this large sample of individuals with autopsy. In particular, individuals on diuretics were associated with lower AD pathology after adjusting for blood pressure and APOE. This association appears to be independent of other vascular conditions and is not mediated by vascular neuropathology findings. The mechanism underlying these associations requires further investigation.