Effects of Antihypertensive Drug Treatment on Cognitive Function and the Risk of Dementia
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Hypertension has been associated with an increased risk of stroke, vascular dementia, and Alzheimer’s disease.1-10 Cerebral infarcts, lacunae, and white matter changes are implicated in the pathogenesis of vascular dementia, but also may lead to the development of Alzheimer’s disease.11 Microcirculatory disorders and endothelial dysfunction also may cause a deterioration in cognitive function in persons with hypertension.11 The Epidemiology of Vascular Aging study showed that hypertension is a major risk factor for severe white matter hyperintensities diagnosed by cerebral magnetic resonance imaging (MRI).12 Persons taking antihypertensive drugs to control their blood pressure had a reduced risk of severe white matter hyperintensities.12
Cognitive function is an important determinant of the ability to live independently in the community and of quality of life.13 Cognitive function itself can predict incidence of cardiovascular disease.14 This review article discusses the effect of hypertension treatment on cognitive function and the risk of dementia.
Numerous studies have demonstrated that treatment with antihypertensive drugs reduces the incidence of all strokes in men, women, elderly persons (including those older than 80 years), younger persons, persons with systolic and diastolic hypertension, persons with isolated systolic hypertension, and persons with a history of stroke or transient ischemic attack (TIA)15-27(Table25,28-35). The overall data suggest that reduction of stroke in persons with hypertension is related more to a reduction in blood pressure than to the type of antihypertensive drugs used.36 Reduction of stroke by antihypertensive drugs reduces the incidence of dementia. In the Perindopril Protection Against Recurrent Stroke Study (PROGRESS),25 treatment with perindopril plus indapamide reduced stroke-related dementia by 34% and cognitive decline as assessed by the Mini-Mental State Examination (MMSE) by 45%.
The Medical Research Council trial28 and the Systolic Hypertension in the Elderly Program (SHEP) trial29 did not find any significant difference in the incidence of cognitive decline between persons randomized to antihypertensive drug treatment with diuretics as the primary drug or to placebo. However, a selective dropout in the Medical Research Council and SHEP trials due to nonfatal events might have impaired the recognition of a benefit of antihypertensive treatment on dementia and disability outcomes.37
At 2-year median follow-up in the European Trial on Isolated Systolic Hypertension in the Elderly (Syst-Eur),30 compared with placebo, antihypertensive drug treatment using the calcium channel blocker nitrendipine as the primary drug reduced the incidence of dementia by 50%. Based on this study, if 1000 patients with hypertension were treated with antihypertensive drugs for 5 years, 19 cases of dementia would be prevented.30
Randomized patients in the Syst-Eur trial were offered active study medication for a further period of observation.31 At 3.9-year median follow-up, compared with the control group, antihypertensive drug therapy reduced the risk of dementia by 55%. This study showed that if 1000 patients with hypertension were treated with antihypertensive drugs for 5 years, 20 cases of dementia (95% confidence interval [CI], 7-33) would be prevented.
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In the article “Update on Prevention and Treatment of Influenza in the Elderly” by Richard O. Schamp, MD, and William T. Manard, MD, that appeared in the October 2006 issue, the usual prophylaxis dosage in Table IV for oseltamivir was incorrectly listed as 75 mg twice daily for as long as indicated. The correct amount should be 75 mg once daily for as long as indicated. The corrected Table appears in the online article on the website www.clinicalgeriatrics.com.