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. doi: 10.1001/archinte.162.18.2046.


Background: After the double-blind, placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial ended in February 1997, randomized patients were offered active study medication for a further period of observation.

Objective: To refine the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia.

Methods: Eligible patients had no dementia and were at least 60 years old. Their systolic blood pressure at entry was 160 to 219 mm Hg, with diastolic blood pressure below 95 mm Hg. Antihypertensive therapy was started immediately after randomization in the active treatment group, but only after termination of the double-blind trial in the control patients. Treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d), hydrochlorothiazide (12.5-25 mg/d), or both add-on drugs.

Results: Median follow-up increased from 2.0 years in the double-blind trial to 3.9 years overall. The incidence of dementia doubled from 32 to 64 cases, 41 of whom had Alzheimer disease. Throughout follow-up, systolic/diastolic blood pressure was 7.0/3.2 mm Hg higher in the 1417 control patients than in the 1485 subjects randomized to active treatment. At the last examination, the blood pressure difference was still 4.2/2.9 mm Hg; 48.1%, 26.4%, and 11.4% of the control patients were taking nitrendipine, enalapril, and/or hydrochlorothiazide, whereas in the active treatment group these proportions were 70.2%, 35.4%, and 18.4%, respectively. Compared with the controls, long-term antihypertensive therapy reduced the risk of dementia by 55%, from 7.4 to 3.3 cases per 1000 patient-years (43 vs 21 cases, P<.001). After adjustment for sex, age, education, and entry blood pressure, the relative hazard rate associated with the use of nitrendipine was 0.38 (95% confidence interval, 0.23-0.64; P<.001). Treatment of 1000 patients for 5 years can prevent 20 cases of dementia (95% confidence interval, 7-33).

Conclusion: The extended follow-up of Syst-Eur patients reinforces the evidence that blood pressure-lowering therapy initiated with a long-acting dihydropyridine protects against dementia in older patients with systolic hypertension.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / therapeutic use*
  • Calcium Channel Blockers / therapeutic use
  • Dementia / drug therapy*
  • Dementia / epidemiology
  • Dementia / etiology
  • Dementia / prevention & control*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Enalapril / therapeutic use
  • Europe / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrochlorothiazide / therapeutic use
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Incidence
  • Male
  • Middle Aged
  • Nitrendipine / therapeutic use
  • Time Factors
  • Treatment Outcome


  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Hydrochlorothiazide
  • Enalapril
  • Nitrendipine