Khachaturian AS, Zandi PP, Lyketsos CG, Hayden KM, Skoog I, Norton MC, Tschanz JT, Mayer LS, Welsh-Bohmer KA, Breitner JC. Antihypertensive medication use and incident Alzheimer disease: the Cache County Study. Arch Neurol. 2006 May;63(5):686-92. PubMed.
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In this study, Khachaturian and colleagues compared a group of elderly, nondemented subjects who used antihypertensive medication (AH) with non-users for their risk of developing Alzheimer disease (AD) 3 years after they were first examined and declared dementia-free. The study found that the use of antihypertensive medication (AH) was associated with a lower risk of developing AD. These findings add to the literature supporting the benefits of AH medication in the prevention of dementia. However, as for all observational studies, there could be potential biases influencing the results.
The authors compared subjects based on their treatment status, not on their hypertensive status. The reference group of non-treated subjects could include people with a worse health profile (untreated hypertensives and subjects who have low blood pressure resulting from pathological conditions such as heart failure or incipient dementia). In this case, the observed protective effect of AH medication could be due in part to the comparison with a group that is at high risk for cognitive impairment resulting from other reasons than not being treated. More information on the comparison group would help to clarify this.
The study was sufficiently powered to test the main hypothesis about the overall protection of AH against AD. The power was reduced when the different subclasses of AH were tested separately. Additional analyses reported by the authors seem to provide support that, among the drugs tested, the potassium-sparing diuretics are the most effective against AD, but the numbers of AD cases in these sub-analyses is very small. The reduced power could explain the lack of significance for the β-blockers and the calcium channel blockers.
The question remains whether the observed protective effect is the result of a better control of blood pressure among the potassium-sparing AH users or if this drug category has a specific effect on AD, as the authors suggest. Although this hypothesis should not be excluded, at present the sample sizes are not sufficient to test it. Previous clinical trials found that other categories of AH drugs, such as ACE inhibitors and the calcium channel blockers, were protective against cognitive decline, dementia and AD (1-3). Some of the benefits from these drugs may reflect protection against vascular damage rather than AD pathology per se. Vascular damage is often present in cases diagnosed with AD, and the presence of vascular damage worsens the clinical presentation of dementia (4-6).
References:
Tzourio C, Anderson C, Chapman N, Woodward M, Neal B, MacMahon S, Chalmers J, . Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease. Arch Intern Med. 2003 May 12;163(9):1069-75. PubMed.
Forette F, Seux ML, Staessen JA, Thijs L, Birkenhäger WH, Babarskiene MR, Babeanu S, Bossini A, Gil-Extremera B, Girerd X, Laks T, Lilov E, Moisseyev V, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Fagard R. Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998 Oct 24;352(9137):1347-51. PubMed.
Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MR, Babeanu S, Bossini A, Fagard R, Gil-Extremera B, Laks T, Kobalava Z, Sarti C, Tuomilehto J, Vanhanen H, Webster J, Yodfat Y, Birkenhäger WH, . The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) study. Arch Intern Med. 2002 Oct 14;162(18):2046-52. PubMed.
Jellinger KA. Alzheimer disease and cerebrovascular pathology: an update. J Neural Transm. 2002 May;109(5-6):813-36. PubMed.
Launer LJ. Demonstrating the case that AD is a vascular disease: epidemiologic evidence. Ageing Res Rev. 2002 Feb;1(1):61-77. PubMed.
Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR. Brain infarction and the clinical expression of Alzheimer disease. The Nun Study. JAMA. 1997 Mar 12;277(10):813-7. PubMed.
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