BALTIMORE, March 13-Potassium-sparing diuretics reduce the risk of Alzheimer's by almost 70%, according a study of more than 3,000 persons ages 65 and older.
Other antihypertensive medications, including all diuretics, beta-blockers, and certain calcium channel blockers were associated with a somewhat smaller decrease in Alzheimer's risk, reported Peter Zandi, Ph.D., of Johns Hopkins and colleagues here in the May
Archives of Neurology. The study was posted online today.
The study of 3,297 individuals, age 65 and older, living in Cache County, Utah, included two groups. One group of 1,507 individuals (944 women, 563 men) took antihypertensive medications and 1,790 (975 women, 815 men) did not.
Participants were interviewed at an initial assessment from 1995 to 1997 that included screening for dementia and a detailed inventory of all the prescription and OTC drugs they were taking.
Follow-up assessments were done three years later. Individuals who had Alzheimer's at the first interview were not included.
At the second assessment, there were 104 incident cases of Alzheimer's, the researchers reported. Use of any of these medications at baseline was associated with a lower rate of Alzheimer's (adjusted HR, 0.64, 95% CI, 0.41-0.98).
Analysis of individual drug classes, however, found the greatest risk reduction among patients who took potassium-sparing diuretics (adjusted HR 0.26; 95% CI, 0.08-0.64).
ACE inhibitors (aHR, 1.13, 95% CI 0.60-1.98) and calcium channel blockers (aHR 0.86, 95% CI, 0.45-1.53) had no influence on Alzheimer's risk, the researchers said. However, when they analyzed the dihydropyridine calcium channel blockers separately, they found a benefit for the drugs (aHR, 0.53, 95% CI 0.16-1.34) compared with the nondihydropyridine agents (aHR 1.16, 95% CI, 0.55-2.20).
Beta blockers posted "a trend toward a protective" influence (aHR, 0.53; 95% CI, 0.22-1.09), while the use of diuretics as a whole was associated with a significantly reduced risk of Alzheimer's (aHR, 0. 61; 95% CI, 0.37-0.98), the researchers reported.
These relationships persisted even after controlling for confounding factors including age, gender, education, diabetes, cholesterol, and APOE genotype. Analysis of a sub-sample controlling for blood pressure measurements did not substantially change the findings, the researchers reported.
It is not clear why potassium-sparing diuretics in particular should be associated with a reduced risk of Alzheimer's, the researchers wrote, but it is well known that these drugs lead to increased potassium concentrations. Dr. Zandi said.
As yet unpublished findings suggest that increased potassium levels may be associated with a reduced risk of dementia, the team wrote. In this vein, they suggest that low potassium concentrations are associated with oxidative stress, inflammation, platelet aggregation, and vasoconstriction, all of which are possible contributors to Alzheimer's pathogenesis.
Discussing the possibility that cases in this study were incorrectly diagnosed as Alzheimer's rather than vascular dementia, Dr. Zandi said that the cases were accurately classified according to conventional diagnostic criteria. The investigators also noted that MRI scans were available for 56% of the patients, and in each case the scans failed to reveal vascular pathology sufficient to deter a diagnosis of uncomplicated Alzheimer's.
Other possible limitations noted by the authors included:
- "As is true in all observational studies, our results may also be vulnerable to confounding, i.e., to the possibility that the relation of antihypertensive medication use and Alzheimer's risk reflects the association of both to another variable."
- "Another potential limitation is mortality bias. Users of antihypertensive medications who developed incident dementia might have been more likely than nonusers to die during the interval between [the two assessments] and therefore to have escaped detection. This would in turn lead to an apparent inverse association between antihypertensive use and Alzheimer's risk. Indeed, we found that antihypertensive medication use was associated with increased mortality over the study period."
Because the role of potassium-sparing diuretics is a new finding, Dr. Zandi's team concluded, it requires confirmation in further study. The researchers also called for basic science studies into the possible neuroprotective effects of these drugs.
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