In the Journals

Blood pressure drug shows promise in Alzheimer’s disease

Nilvadipine, a hypertension drug, increased cerebral blood flow to the hippocampus without affecting other brain regions among people with Alzheimer’s disease, study findings revealed.

These findings, published in Hypertension, indicated that the known decrease in cerebral blood flow (CBF) observed in patients with Alzheimer’s disease (AD) can be reversed in some regions.

“A reduction in CBF has been established as an early marker of AD, predicting disease progression and correlating with cognitive impairment,” Daan L.K. de Jong, PhD, from the Donders Institute for Brain Cognition and Behavior, Radboud University Medical Center, the Netherlands, and colleagues wrote. “There is limited, if any, evidence on how blood pressure lowering treatment will affect cerebral perfusion in older people at risk of AD or with established AD.”

In their randomized, placebo-controlled study, researchers examined whether 6-month treatment with nilvadipine would affect CBF in patients with mild to moderate Alzheimer’s disease.

Overall, 58 older adults (mean age 72.8) were randomly assigned to receive nilvadipine or placebo; of these patients, 22 in both groups were medication compliant over 6 months. The investigators measured CBF using magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest, including the hippocampus.

The results showed nilvadipine significantly reduced blood pressure, as measured at the 6-month follow-up visit, compared with placebo in patients with Alzheimer’s disease (difference in systolic blood pressure = –11.5 mm Hg; 95% CI, –19.7 to –3.2).

After 6 months, nilvadipine also led to an increase in blood flow by 24.4 mL/100 g per minute (95% CI, 4.3-44.5) to the left hippocampus as well as a 20.1 mL/100 g per minute increase to the right hippocampus (95% CI, –0.6 to 40.8), indicating an increase of about 20% in hippocampal cerebral blood flow, the researchers found. However, global CBF remained stable (5.4 mL/100 g per minute; 95% CI, –6.4 to 17.2) as did the CBF in the posterior cingulate cortex (5.2 mL/100 g per minute; 95% CI, –16.5 to 27).

Sensitivity analyses showed comparable results and post hoc analyses of two other regions of interest (precuneus, which is affected in Alzheimer’s disease, and the occipital lobe, which is not) showed stable CBF without major differences between placebo and nilvadipine.

“It would ... be important to investigate, in a larger study with longer follow-up, whether the improvement in hippocampal CBF leads to cognitive benefits in earlier stages of disease (mild cognitive impairment or earlier), where the potential for prevention of cognitive decline may be much higher,” de Jong and colleagues wrote. – by Savannah Demko

Disclosure: de Jong reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Nilvadipine, a hypertension drug, increased cerebral blood flow to the hippocampus without affecting other brain regions among people with Alzheimer’s disease, study findings revealed.

These findings, published in Hypertension, indicated that the known decrease in cerebral blood flow (CBF) observed in patients with Alzheimer’s disease (AD) can be reversed in some regions.

“A reduction in CBF has been established as an early marker of AD, predicting disease progression and correlating with cognitive impairment,” Daan L.K. de Jong, PhD, from the Donders Institute for Brain Cognition and Behavior, Radboud University Medical Center, the Netherlands, and colleagues wrote. “There is limited, if any, evidence on how blood pressure lowering treatment will affect cerebral perfusion in older people at risk of AD or with established AD.”

In their randomized, placebo-controlled study, researchers examined whether 6-month treatment with nilvadipine would affect CBF in patients with mild to moderate Alzheimer’s disease.

Overall, 58 older adults (mean age 72.8) were randomly assigned to receive nilvadipine or placebo; of these patients, 22 in both groups were medication compliant over 6 months. The investigators measured CBF using magnetic resonance arterial spin labeling in whole-brain gray matter and in a priori defined regions of interest, including the hippocampus.

The results showed nilvadipine significantly reduced blood pressure, as measured at the 6-month follow-up visit, compared with placebo in patients with Alzheimer’s disease (difference in systolic blood pressure = –11.5 mm Hg; 95% CI, –19.7 to –3.2).

After 6 months, nilvadipine also led to an increase in blood flow by 24.4 mL/100 g per minute (95% CI, 4.3-44.5) to the left hippocampus as well as a 20.1 mL/100 g per minute increase to the right hippocampus (95% CI, –0.6 to 40.8), indicating an increase of about 20% in hippocampal cerebral blood flow, the researchers found. However, global CBF remained stable (5.4 mL/100 g per minute; 95% CI, –6.4 to 17.2) as did the CBF in the posterior cingulate cortex (5.2 mL/100 g per minute; 95% CI, –16.5 to 27).

Sensitivity analyses showed comparable results and post hoc analyses of two other regions of interest (precuneus, which is affected in Alzheimer’s disease, and the occipital lobe, which is not) showed stable CBF without major differences between placebo and nilvadipine.

“It would ... be important to investigate, in a larger study with longer follow-up, whether the improvement in hippocampal CBF leads to cognitive benefits in earlier stages of disease (mild cognitive impairment or earlier), where the potential for prevention of cognitive decline may be much higher,” de Jong and colleagues wrote. – by Savannah Demko

Disclosure: de Jong reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.