Susan Hughes

January 07, 2013

The use of beta-blockers for the treatment of hypertension was associated with fewer Alzheimer's-type brain lesions on autopsy than other antihypertensive medications, a new study shows.

The study, which is to be presented at the upcoming American Academy of Neurology meeting in March, was conducted by a team led by Lon White, MD, University of Hawaii, Honolulu.

"These results suggest that beta-blockers may have some special benefits in reducing Alzheimer-type brain lesions," Dr. White told Medscape Medical News.

Honolulu-Asia Aging Study

The findings come from the Honolulu-Asia Aging Study, funded by the US National Institute on Aging, which has followed a large cohort of Japanese-American men who were aged 71 to 93 years at baseline in 1991. They have been examined every 3 years, and now autopsies have started to be performed after the death of the participants.

"One of the key issues to be addressed in the study is how to prevent the development of late-life dementia, which affects about 30-40% of people, the most common form being Alzheimer's," Dr. White explained. "It is now pretty well established that the risk of Alzheimer's is related to mid-life hypertension, more so than late-life hypertension."

In this particular study, they looked at the hypertension-Alzheimer's link in more detail and extended observations to autopsy data.

"With 774 brain autopsies and information on drug use and cognition, this is the largest brain autopsy study ever done in a prospective manner," he said. "And no other study that I am aware of has looked at different treatments for hypertension in relation to Alzheimer's."

Of the 774 patients, both with and without clinical signs of dementia, for whom brain autopsies were available, 610 had been hypertensive or treated with antihypertensive drugs. Drugs used as monotherapy for the treatment of hypertension included beta-blockers (40 patients), angiotensin-converting enzyme inhibitors (n = 35), diuretics (n = 60), calcium blockers (n = 103), and vasodilators (n = 13). In addition, 43 patients were taking beta-blockers in combination with other antihypertensives and 46 were taking other combinations of antihypertensives.

The average age at death was 86 to 87 years in all groups. Education status was similar in all groups, and the incidence of diabetes varied from 17% to 30%. The LPA4 gene was not related to drug treatment. Logistic and linear regression analyses were performed to control for potential biases.

Results showed that patients who had had hypertension and had been taking beta-blockers had fewer Alzheimer-type lesions (both neurofibrillary tangles and amyloid plaques) than those taking no drug therapy or those taking other medications. There was also a significant but less dramatic reduction in infarcts in the small arteries of the brain (a vascular marker of dementia) in patients who had been taking beta-blockers.

The lowest-level Alzheimer's lesions were seen in the patients who did not have hypertension. The group who had been taking beta-blockers had low levels of lesions similar to those of the nonhypertensive group, Dr. White reported. Those who had received beta-blockers plus other medications had intermediate or marginally fewer brain abnormalities.

'First Hint' of Effect

"This is the first hint that different kinds of antihypertensive therapy might have differential effects on Alzheimer's lesions and other brain lesions," Dr. White said. But he cautioned that the numbers are small and nothing definite can be concluded. "This is just a clue that perhaps beta-blockers may be potentially a good choice of antihypertensive for preventing Alzheimer's. But we are obviously a long way from making clinical recommendations."

Speculating on the mechanism, Dr. White noted that beta-blockers reduce pulse rate, which might have an effect on small vessel micro-infarcts in the brain.

"Lifelong exposure of the pulse pressure in the brain might cause some damage," he said. "While we thought beta-blockers may reduce brain micro-infarcts, which they did, we actually saw a larger reduction in the Alzheimer-type lesions which we had not expected. This is somewhat of a mystery at present and may be a chance finding. But if it is a real effect I would think it was something to do with autonomic function."

Dr. White suggested that a reasonable next step could be to test this hypothesis in mice genetically engineered to produce these Alzheimer's lesions. "If we treat these mice with beta-blockers and they develop fewer lesions, then we will know that it is an effect of the drugs," he commented.

The study was supported by grants from the National Institutes of Health. The authors have disclosed no relevant financial relationships.

American Academy of Neurology's 65th Annual Meeting. Abstract 2171. Released January 7, 2013.