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October 2006

Potassium-Retaining Diuretics and Incident Alzheimer Disease

Arch Neurol. 2006;63(10):1507. doi:10.1001/archneur.63.10.1507-b

The article on antihypertensive medication use and incident Alzheimer disease (AD) in the Cache County Study1 discloses that the use of a potassium-retaining diuretic at baseline, but not the use of a thiazidelike or a loop diuretic, was associated with reduced incidence of AD over the following years in subjects aged 65 years or older.

The set of potassium-retaining diuretics comprises 2 subsets. The epithelial sodium channel blockers amiloride and triamterene cause renal retention of potassium in all circumstances, whereas aldosterone antagonists (eg, spironolactone, eplerenone) act as natriuretics, diuretics, and antikaliuretics only if plasma aldosterone is raised, as happens, inter alia, when a sodium-restricted diet is followed or a thiazidelike or a loop diuretic is used.2 Khachaturian et al1 speculate on the mechanism of the negative relationship between the use of potassium-retaining diuretics and the risk of AD they found by considering several possibilities stemming from renal potassium retention. I would like to expand on their comment. Increases or the avoidance of falls in plasma potassium could have a permissive effect on other metabolic actions of diuretics, ultimately explaining the observed protection. The rise in the serum level of the antioxidant uric acid provoked by all diuretics3 could be 1 such action since oxidative stress appears to participate in the pathogenesis of AD. Heart failure associates with an increased risk of AD in the elderly.4 Hence, the established salutary effect of aldosterone antagonism in heart failure2 could have explained or contributed to the observed positive results in any participants in the study who might have taken spironolactone for this condition.

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