Effects of Nilvadipine on Cerebral Blood Flow in Patients With Alzheimer Disease

摘要

Cerebrovascular changes, including reduced cerebral blood ?ow (CBF), occur early in the development ofAlzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled studyinvestigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mildto-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain graymatter and in a priori defned regions of interest including the hippocampus. Fifty-eight patients were randomly assigned(29 in each group), of whom 22 in both groups had no magnetic resonance exclusion criteria and were medicationcompliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipinetreatment lowered systolic blood pressure (Δ=?11.5 [95% CI, ?19.7 to ?3.2] mm Hg; P<0.01), while whole-brain graymatter CBF remained stable (Δ=5.4 [95% CI, ?6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampusincreased (left: Δ=24.4 [95% CI, 4.3–44.5] mL/100 g per minute; P=0.02; right: Δ=20.1 [95% CI, ?0.6 to 40.8] mL/100g per minute; P=0.06). There was no signifcant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, ?16.5to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressureand increased CBF in the hippocampus, whereas other regions showed stable or small nonsignifcant increases in CBF.These fndings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward benefcialcerebrovascular effects of antihypertensive treatment.