Elderly patients who took potassium-sparing diuretics had a 70% lower rate of developing Alzheimer's disease than those who did not take antihypertensive drugs in a population-based study of dementing illnesses, reported Ara S. Khachaturian, Ph.D., and his colleagues.
Antihypertensive agents in general reduced the risk for Alzheimer's disease (AD), but the potassium-sparing diuretics were particularly beneficial, said Dr. Khachaturian of Potomac, Md., and his colleagues.
To assess whether protection against AD might be specific to individual classes of antihypertensive drugs, the investigators analyzed data from the Cache County study, an ongoing investigation of dementias in the elderly population of Cache County, Utah (Arch. Neurol. 2006 March 13 [Epub doi:10.1001/archneur.63.5.noc60013).
They studied medication usage in 3,227 patients who were aged 65 years or older when they enrolled in the study in 1995, including 104 who developed AD during follow-up. Of the 3,217 patients who provided drug information, nearly half of the patients (45.3%) took antihypertensive drugs, including ACE inhibitors (13.0%); β-blockers (11.5%); calcium channel blockers (14.9%); diuretics (26.5%); or some combination of these (18.2%).
The risk of developing AD was significantly smaller in those who took antihypertensive medications than in those who did not (adjusted hazard ratio [aHR] 0.64). When the results were broken down by drug class, diuretics showed the greatest protective effect against AD (aHR 0.61), whereas β-blockers showed a statistical trend toward a significant protective effect (aHR, 0.53); ACE inhibitors (aHR, 1.13) and calcium channel blockers (aHR, 0.86) showed no effect. Closer analysis showed the potassium-sparing diuretics accounted for all the risk reduction attributed to their drug class (aHR, 0.26); thiazide diuretics and loop diuretics were not protective (aHR, 0.72 and 1.45, respectively). Analysis also showed that the dihydropyridine subclass of calcium channel blockers cut the risk of AD (aHR, 0.53), but other subclasses did not, said the researchers.
The finding that antihypertensive agents that protect against AD seem to do so independently of controlling blood pressure was of particular interest. It's not known why the diuretics cut the AD risk. Other diuretics reduce potassium concentrations, and low potassium levels have been tied to oxidative stress, inflammation, platelet aggregation, and vasoconstriction, possible contributors to AD pathogenesis, they said.