16 March 2006. They have been used for decades to lower blood pressure, but evidence now suggests that some specific forms of diuretic drugs may help stave off Alzheimer disease (AD). In the March 13 Archive of Neurology online, John Breitner, University of Washington School of Medicine, Seattle, and researchers of the Cache County Study Group report that potassium-sparing diuretics reduce the risk of developing AD by around 70 percent. The finding helps explain conflicting data on the potential benefit of hypertension medicines for incipient AD and suggests that this particular subtype of blood pressure medication should be more thoroughly explored as a prophylactic.
Previous epidemiological studies have examined the effect of hypertension medications on dementia but, as is often the case in AD epidemiology, the results have been confusing. The Kungsholmen Project found that antihypertension medication reduced the incidence of AD in the elderly (see Guo et al., 1999), but while the Rotterdam study found that blood pressure medication reduced rates of vascular dementia, it also found that the same meds did not alter the chances of getting AD (see in’t Veld et al., 2001). The reasons for these discrepancies are unclear. Because other studies reported that cognitive performance in the elderly improved only on specific types of hypertension drugs, Breitner and colleagues decided to examine if the incidence of AD is altered among those taking different classes of hypertension agents.
First author Ara Khachaturian of Khachaturian and Associates, Potomac, Maryland, and colleagues followed up with more than 3,000 elderly people who had taken part in Utah’s Cache County Study in the late 1990s. Nearly 1,500 of the volunteers were using hypertension medication at that time. The drugs used fall into four main classes: angiotensin converting enzyme (ACE) inhibitors; β-adrenergic blockers; calcium channel blockers; and diuretics.
When Khachaturian and colleagues parsed the data according to drug type, they found that only diuretics and β-blockers decreased the odds of getting Alzheimer’s. After correcting for age, education, sex, number of ApoE4 alleles, and other potential confounding factors, they found that hazard ratios (HRs) for AD were 0.53 and 0.61 for those patients on β-blockers and diuretics, respectively. But when the authors delved a little deeper, they found that hazard ratios were even lower for some specific types of drugs, namely potassium-sparing diuretics (HR, 0.26), and the calcium channel blocker dihydropyridine (HR, 0.53). The findings suggest that potassium-sparing diuretics, which help the body lose water without also losing potassium, and possibly the β-blockers and dihydropyridine may protect against AD.
These findings corroborate results from some previous trials. SHEP (Systolic Hypertension in the Elderly Project), the Medical Research Council trial, and SCOPE (the Study on Cognition and Prognosis in the Elderly) all found that β-blockers, thiazide diuretics (which are not potassium-sparing), and angiotensin II type I receptor blockers have no effect on cognition in the elderly. But the Syst-Eur (Systolic Hypertension in Europe) trial found that the dihydropyridine calcium channel antagonist nitrendipine reduced the incidence of dementia by 50 percent. No other trial has examined the effects of potassium-sparing drugs on cognition, and the authors suggest that further studies should be carried out to evaluate the epidemiology and also the potential mechanism whereby these drugs may protect against AD.—Tom Fagan.
Khachaturian A, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, Breitner JCS. Antihypertensive medication use and incident Alzheimer Disease. Archive of Neurology online. March 13, 2006. Abstract