Impact of Angiotensin receptor blockers on Alzheimer disease neuropathology in a large brain autopsy series

Abstract

BACKGROUND Angiotensin II may be involved in amyloid metabolism in the brain. Angiotensin receptor blockers (ARBs) may also prevent cognitive decline. OBJECTIVE To evaluate the impact of treatment with ARBs on the neuropathology of Alzheimer disease (AD) in the National Alzheimer Coordinating Center database, which includes aggregated data and brain autopsies from 29 AD centers throughout the United States. DESIGN Multiple logistic regression was used to compare the pathologic findings in hypertensive subjects taking ARBs with those taking other antihypertensive treatments as well as with hypertensive subjects who did not receive antihypertensive medications. SETTING Neuropathologic data included neuritic plaque and neurofibrillary tangle measures and vascular injury markers. PATIENTS Data were collected from participants who were self-referred or provider-referred and included those with and without cognitive disorders. Our sample included only hypertensive participants and excluded cognitively and neuropathologically normal participants (N = 890; mean age at death, 81 years [range, 39-107 years]; 43% women; 94% white). RESULTS Participants with or without AD who were treated with ARBs showed less amyloid deposition markers compared with those treated with other antihypertensive medications (lower Consortium to Establish a Registry of Alzheimer Disease score: odds ratio, 0.47, 95% CI, 0.27-0.81; Alzheimer Disease and Related Disorders Association score: odds ratio, 0.43, 95% CI, 0.21-0.91; Braak and Braak stage: odds ratio, 0.52, 95% CI, 0.31-0.85; neuritic plaques: odds ratio, 0.59, 95% CI, 0.37-0.96). They also had less AD-related pathology compared with untreated hypertensive subjects. Participants who received ARBs were more likely to have had a stroke; hence, they had more frequent pathologic evidence of large vessel infarct and hemorrhage. CONCLUSION Treatment with ARBs is associated with less AD-related pathology on autopsy evaluations. The effect of ARBs on cognitive decline in those with dementia or AD needs further investigation.

Figure 1

Description of sample sizes from the original NACC 2011 dataset to our final sample of 890 hypertensive participants.

Figure 2

AD neuropathological scores (2A and 2B), vascular brain injury measures (2C), and Athero/arteriosclerosis (2D) in the three groups: those exposed to ARBs, other antihypertensive medications, or no antihypertensive medications.