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 (Sys t-Eur) trial, was to investigate whether antihypertensive drug treatment ba sed on calcium-channel inhibitor as first step could reduce the incidence o f dementia. Methods and Results The study was run on nondemented patients, at least 60 years old, with isolated systolic hypertension. Treatment was initiated wit h nitrendipine (10-40 mg . day(-1)) possibly associated with enalapril (5-2 0 mg . day(-1)) and/or hydrochlorothiazide (12.5-25 mg . day(-1)). Cognitiv e 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 imagi ng 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 treatme nt one (n=1238) (21 vs II patients, P=0.05). At the last available evaluati on, 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, antihyperte nsive 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 homeos tasis may represent a new opportunity to prevent the development of Alzheim er's disease. This mechanism, associated to the antihypertensive action of calcium inhibitors, makes this class of drugs a logical candidate for futur e trials in the area of dementia prevention.