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Hypertension. 2019 Aug;74(2):413-420. doi: 10.1161/HYPERTENSIONAHA.119.12892. Epub 2019 Jun 17.

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

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From the Department of Geriatric Medicine, Donders Institute for Brain Cognition and Behaviour (D.L.K.d.J., R.A.A.d.H., A.R., M.G.M.O.R., J.A.H.R.C.), Radboud University Medical Center, Nijmegen, the Netherlands.
Radboudumc Alzheimer Center, Nijmegen, the Netherlands (D.L.K.d.J., R.A.A.d.H., A.R., M.G.M.O.R., J.A.H.R.C.).
Department of Health Evidence (R.D.), Radboud University Medical Center, Nijmegen, the Netherlands.
Frauenhofer Institute for Medical Imaging Computing MEVIS, Bremen, Germany (M.G.).
Trinity College Institute of Neuroscience, Dublin, Ireland (B.A.L.).
Department of Radiology, C.J. Gorter Center for High Field MRI, Leiden University Medical Center, the Netherlands (M.J.P.v.O.).


Cerebrovascular changes, including reduced cerebral blood flow (CBF), occur early in the development of Alzheimer disease and may accelerate disease progression. This randomized, double-blind, placebo-controlled study investigated how 6 months of treatment with the calcium antagonist nilvadipine would affect CBF in patients with mild-to-moderate Alzheimer disease. CBF was measured with magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined 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 medication compliant over 6 months. Mean age was 72.8±6.2 years, mean mini-mental state examination was 20.4±3.4. Nilvadipine treatment lowered systolic blood pressure (Δ=-11.5 [95% CI, -19.7 to -3.2] mm Hg; P<0.01), while whole-brain gray-matter CBF remained stable (Δ=5.4 [95% CI, -6.4 to 17.2] mL/100 g per minute; P=0.36). CBF in the hippocampus increased (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/100 g per minute; P=0.06). There was no significant change in CBF in the posterior cingulate cortex (Δ=5.2 [95% CI, -16.5 to 27.0] mL/100 g per minute; P=0.63) or other regions of interest. In conclusion, nilvadipine reduced blood pressure and increased CBF in the hippocampus, whereas other regions showed stable or small nonsignificant increases in CBF. These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment. Clinical Trial Registration- URL: . Unique identifier: NCT02017340.


Alzheimer disease; blood pressure; disease progression; hippocampus; nilvadipine

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