Are Antihypertensive Agents Protective Against Dementia? A Review of Clinical and Preclinical Data

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Abstract
In the United States, the size of the population of persons aged 65 years or older is expected to double within the next 30 years, resulting in a marked increase in the prevalence of dementia. Hypertension is a risk factor for cognitive impairment and dementia in addition to cerebrovascular morbidity and mortality. The evidence for a connection between high blood pressure in midlife and dementia in late life comes from numerous longitudinal studies. A placebo-controlled, double-blind, randomized trial involving 2,418 patients aged 60 years or older with isolated systolic hypertension demonstrated that active treatment based on the dihydropyridine calcium antagonist nitrendipine with the addition of enalapril, hydrochlorothiazide, or both if needed to control systolic blood pressure to <150 mmHg, significantly reduced not only stroke and cardiovascular complications but also the incidence of vascular dementia and Alzheimer's disease. Several trials of antihypertensive treatment are ongoing to confirm this important finding. The newer dihydropyridine calcium antagonists lacidipine and lercanidipine are effective and well tolerated in the treatment of hypertension. In animal models, these newer agents also have been shown to prevent the progression of hypertensive microvascular damage. Their neuroprotective effects offer possible unique advantages in the management of hypertension.