Fluke or Trend: ARBs vs Alzheimer's Disease

Alvin B. Lin, MD, FAAFP
Dr. Lin is an associate professor of family and community medicine at University of Nevada School of Medicine and an adjunct professor of family medicine and geriatrics at Touro University Nevada College of Medicine. He also serves as an advisory medical director for Infinity Hospice Care and as medical director of Lions HealthFirst Foundation. Dr. Lin maintains a small private practice in Las Vegas, NV. The posts represent the views of Dr. Lin, and in no way are to be construed as representative of the above listed organizations. Dr. Lin blogs about current medical literature and news at


Recently, I reviewed a meta-analysis that concluded that ACE inhibitors decreased all-cause mortality but ARBs did not. That should make it pretty clear which anti-hypertensive to choose, right? Well, to muddle things up, I stumbled upon an observational study published early online this week in Archives of Neurology in which the authors concluded that use of ARBs was associated with less pathology consistent with Alzheimer's disease upon autopsy.

Granted, the authors only studied 890 volunteers, average age at death 81 years old, 43% female, almost all Caucasian. As noted in yesterday's study on spin, that makes the results of this study less generalizable to a more ethnically diverse population. Moreover, this study was performed upon death so to some extent, it's useless for the living. In fact, they only looked for neuropathological evidence of Alzheimer's disease but there was no mention of clinically relevant outcomes, eg cognition or function. On the other hand, it wouldn't be so difficult to consider an ARB in treating someone with hypertension who is deathly afraid of dementia (not that we all aren't). But I think we're jumping the gun since we have no trials demonstrating clinical benefit.

Or do we? A prospective cohort analysis published January 2010 in BMJ of 819, 491 men older than 65 years old withheart disease followed for 4 years concluded that ARBs are associated with significant reduction in Alzheimer's disease, both incidence or progression, when compared to ACE inhibitors! In a small short randomized controlled trial published May 2008 in Neurology of the ARB, candesartan, vs placebo, 257 participants, average 76 years old were randomized to candesartan vs placebo. After 44 months, the authors concluded that use of candesartan was associated with less decline in attention or episodic memory. Unfortunately, we can't conclude from this particular study whether any anti-hypertensive would have achieved the same effect.

But certainly the trend is there. I guess I'll have to reconsider using ARBs in my hypertensive patients who value preventing dementia over all-cause mortality.