Reduction of dementia by calcium-antagonist-based antihypertensive treatment

Aims The purpose of the vascular dementia project, set up in the framework of the double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial, was to investigate whether antihypertensive drug treatment based on calcium-channel inhibitor as first step could reduce the incidence of dementia. Methods and Results The study was run on nondemented patients, at least 60 years old, with isolated systolic hypertension. Treatment was initiated with nitrendipine (10-40 mg . day(-1)) possibly associated with enalapril (5-20 mg . day(-1)) and/or hydrochlorothiazide (12.5-25 mg . day(-1)). Cognitive function was assessed by the Mini Mental State Examination. The diagnosis of dementia was based on the DSM-III-R criteria. The aetiology of dementia was established using either the Modified Ischaemic Score with brain imaging or the Hachinski score. Median follow-up was 2.0 years. By intention-to-treat, the incidence of dementia was reduced by 50% from 7.7 in the placebo group (n = 1180) to 3.7 cases per 1000 patient-years in the active treatment one (n=1238) (21 vs II patients, P=0.05). At the last available evaluation, systolic and diastolic blood pressure were 8.3 mmHg and 3.8 mmHg lower (P<0.001) in the active-treatment group. Conclusion In older people with isolated systolic hypertension, antihypertensive treatment started with nitrendipine reduced the incidence of dementia. In the mechanism of dementia prevention a neuroprotective role of calcium-channel blockers may be suggested. Reversing alterations in calcium homeostasis may represent a new opportunity to prevent the development of Alzheimer's disease. This mechanism, associated to the antihypertensive action of calcium inhibitors, makes this class of drugs a logical candidate for future trials in the area of dementia prevention.