Blood Pressure Meds May Help Protect Against Alzheimer's
Treatment with angiotensin receptor blocker (ARB) antihypertensive drugs was associated with less Alzheimer's disease-like pathology in the brain, an autopsy study confirmed.
On the criteria for neuropathology established by the Consortium to Establish a Registry of Alzheimer Disease (CERAD), fewer patients who had been treated with ARBs during life had Alzheimer's disease confirmed postmortem compared with those given other antihypertensive agents (37% versus 54%, P=0.005), according to Ihab Hajjar, MD, and colleagues from the University of California Los Angeles.
After adjustment for covariates including age, sex, apolipoprotein E status, and blood pressure, the odds ratio for an Alzheimer's disease pathologic diagnosis at autopsy was 0.47 (95% CI 0.27 to 0.81) for those who had used ARBs compared with those using other blood-pressure lowering agents, the researchers reported online in Archives of Neurology.
Observational studies have suggested that ARB treatment can have protective effects on cognition, and animal studies have shown that these drugs can reduce the accumulation of amyloid-beta in the brain, which is a hallmark event in Alzheimer's disease.
Because the effects of ARBs on amyloid-beta in humans have remained unknown, Hajjar and colleagues performed an analysis of neuropathologic and clinical data from 890 enrollees in the National Alzheimer Coordinating Center, which is a repository of data from 29 Alzheimer's disease centers across the country.
Clinical data included information on medical history and pharmacotherapies, and neuropsychiatric history included findings on multiple tests such as the Mini-Mental State Exam and the Clinical Dementia Rating Scale.
Several measures were used to evaluate neuropathologic status at autopsy, such as the CERAD score, which includes number and makeup of neuritic plaques in each cortical region with adjustment for clinical findings and age, and the National Institute on Aging's Khachaturian criteria, which quantifies both plaques and neurofibrillary tangles, also corrected for age.
Additionally, the Braak and Braak score assessed the stages of neurofibrillary degeneration in the various limbic regions.
Among the study enrollees, almost 80% had received antihypertensive medications. A total of 15% had received ARBs, 64% had been given other types of antihypertensives, and the remainder had not been given treatment.
Almost all the participants were white, and more than 90% had at least a high school education. Fewer than half were women, and the median age at the time of death was 83.
Compared with individuals who had received antihypertensives other than ARBs and those who were untreated, those using ARBs were older when they died (P<0.001) and scored higher on the logical memory test (P=0.01) and the Mini-Mental State exam (P=0.001).
They also scored lower on the dementia rating scale (P=0.01).
Depending on which pathologic criteria were used to identify Alzheimer's disease on autopsy, the likelihood of having the diagnosis was 32% to 35% lower if ARBs were the antihypertensive used, the researchers reported.
On the Khachaturian criteria, the multivariate odds ratio for Alzheimer's pathology was 0.43 (95% CI 0.21 to 0.91) for ARBs versus other antihypertensives, while the odds ratio was 0.52 (95% CI 0.31 to 0.85) using the Braak and Braak scores.
Direct comparison of ARBs with angiotensin-converting enzyme (ACE) inhibitors again found less amyloid deposition (OR 0.43, 95% CI 0.21 to 0.86, P=0.02) and neuritic plaque (OR 0.50, 95% CI 0.28 to 0.89, P=0.02), suggesting that the benefit is ARB-specific.
On vascular-related measures of pathology, ARB use was associated with a greater likelihood of having had a stroke (P=0.03), and also to have infarcts and hemorrhage of the large arteries, although these associations were not significant after adjustment for covariates and exposure to anticoagulants.
This finding of worse vascular pathology among ARB users probably reflects confounding by indication, because this class of drugs is more likely to be prescribed for patients with greater vascular risk, according to the researchers.
They noted that the mechanisms by which ARBs could interfere with the deposition of amyloid-beta have not been fully explored, "but ARB treatment may reduce total [amyloid-beta] content in the brain in part by facilitating membrane-associated insulin degrading enzyme-mediated proteolytic cleavage of [amyloid-beta] peptides."
Limitations of the study included its population, which was largely white and educated and had volunteered to participate in the study, as well as a lack of information on the duration of ARB use.
Future research should focus on antemortem imaging of brain amyloid and the assessment of whether ARB treatment might have beneficial cognitive effects in patients showing clinical signs of dementia.
This work was supported by the National Institute on Aging.
The authors reported no financial disclosures.
From the American Heart Association:
Primary source: Archives of Neurology
Source reference:
Hajjar I, et al "Impact of angiotensin receptor blockers on Alzheimer disease neuropatholog in a large brain autopsy series" Arch Neurol 2012; DOI:10.1001/archneurol.2012.1010.
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