ARBs May Curb Amyloid Deposition in the Brain

Megan Brooks

September 13, 2012

September 13, 2012 – Angiotensin-receptor blocker (ARB) therapy may cut the risk of Alzheimer's disease (AD) by reducing amyloid deposition in the brain, a new study hints.

The study, based on aggregated data and brain autopsies from 890 patients from 29 AD centers in the United States, showed that ARB treatment correlated with less amyloid accumulation and AD-related abnormality independent of other AD risk factors.

"To our knowledge, this is the first human evidence to suggest that treatment with ARBs may have a selective beneficial effect on amyloid metabolism," Ihab Hajjar, MD, and colleagues from University of Southern California, Los Angeles, report.

Their findings were published online September 10 in Archives of Neurology.

"This is an important finding, and something that is significantly different than what was done before," Benjamin Wolozin, MD, PhD, from the departments of pharmacology and neurology, Boston University School of Medicine in Massachusetts, who was not involved in the study, told Medscape Medical News.

Mounting Evidence That ARBs Protect the Brain

Several research teams have found evidence that ARB therapy may protect against cognitive decline and dementia.

In 2010, as reported by Medscape Medical News, an observational study by Dr. Wolozin and colleagues found a significant reduction in the incidence of AD and dementia among ARB users compared with users of angiotensin-converting enzyme (ACE) inhibitors or other cardiovascular drugs.

In 2011, a large British study confirmed this result, finding a 53% lower risk for AD in older adults prescribed an ARB compared with those prescribed other antihypertensive agents. As reported by Medscape Medical News, in that study, the risk for AD was 24% lower in those prescribed ACE inhibitor.

Earlier this year, Dr. Hajjar's group reported results of a small study suggesting that ARB therapy may improve cognitive function in older adults with early cognitive impairment.

However, until now, the mechanism for the apparent protective effect of ARBs on the brain was unclear. "The current paper provides key evidence that the benefit of the ARBs might come from actions directly on the brain, by reducing beta-amyloid," Dr. Wolozin said. "This result is consistent with our findings, where we observed that ARBs that get into the brain were more effective than ARBs that don't get into the brain. So, all in all, this strengthens the ARB story considerably."

Dr. Hajjar and colleagues included in their sample 890 hypertensive patients with available brain autopsy data. The patients' mean age at death was 81 years, 43% were women, and 94% were white. The researchers excluded patients with normal cognitive function as assessed by the clinician on the last assessment and those with a pathologic diagnosis of normal brain as assessed by the neuropathologist.

Of the 890 patients, 710 (80%) were treated with antihypertensive medications, 133 (15%) with ARBs, and 577 (64%) with other antihypertensive medications. The remaining 180 patients (20%) were untreated.

The researchers report that ARB-treated patients were less apt to have received a neuropathologic diagnosis of AD using various pathologic criteria, including Consortium to Establish a Registry for Alzheimer's Disease (P = .005), AD and Related Disorders Association score (P = .04), and the overall neuropathologist diagnosis (P = .06).

They say the association between ARB therapy and a lower likelihood of AD diagnosis remained significant in covariate-adjusted analysis. Compared with use of other antihypertensive medications, use of ARBs was associated with a 32% to 35% lower likelihood of AD diagnosis, depending on the criteria used. This was also true when the researchers compared patients treated with ARBs vs untreated patients.

Patients treated with ARBs, with or without a diagnosis of AD, also had significantly less amyloid deposition than untreated patients and those treated with non-ARB antihypertensive medications.

Implications

"The implications of our results are that ARBs may offer an advantage over other antihypertensive agents in regard to AD risk and pathology," the authors note in their paper.

In comments to Medscape Medical News, Dr. Hajjar said, "It is too early to make clinical recommendations based on this study."

However, he said it's "probably not a bad idea to include an ARB as part of the hypertension management in older adults since they have proven cardiovascular safety and efficacy in many clinical trials."

The study was supported by author grants from the National Institute on Aging. The authors and Dr. Wolozin have disclosed no relevant financial relationships.

Arch Neurol. Published online September 10, 2012. Abstract

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