BP drug nilvadipine could benefit Alzheimer’s patients

The antihypertensive drug nilvadipine may benefit Alzheimer’s patients by encouraging blood flow to the brain, slowing the progression of the disease while reducing blood pressure in the hippocampus, researchers reported in Hypertension June 17.

Daan L.K. de Jong, PhD, of Radboud University Medical Center, the Netherlands, and colleagues said in the journal a reduction in cerebral blood flow (CBF) was previously established as an early marker of Alzheimer’s disease and has proven useful as a prognostic tool. Even in a study of cognitively healthy patients undergoing MRI arterial spin labeling, reduced CBF in the posterior cingulate cortex predicted patients’ risk of future cognitive decline.

“Whether these early changes in CBF are truly a manifestation of cerebrovascular pathology, or whether they are simply a consequence of reduced metabolic demand leading to reduced CBF, has been the topic of debate for decades,” de Jong et al. wrote.

Since midlife hypertension is a major risk factor for cerebrovascular disease, de Jong’s team tested the effect of BP-lowering drugs on CBF in patients with mild-to-moderate dementia. The project—a substudy within a larger randomized controlled trial of nilvadipine—enrolled 44 patients, half of whom were randomized to six months of treatment with the calcium antagonist. At baseline, most patients were in their seventies.

The researchers measured all study participants’ CBF with magnetic resonance arterial spin labeling in whole-brain gray matter and in several a priori defined regions of interest, including the hippocampus. They found treatment with nilvadipine lowered systolic blood pressure in the therapy group by an average of 11.5 mmHg.

Whole-brain gray matter CBF remained stable throughout the study and there weren’t any significant changes in CBF in the posterior cingulate cortex or other regions of interest, but de Jong and colleagues said CBF in the hippocampus increased. The left hippocampus saw an average CBF increase of 24.4 mL/100 g per minute; the right saw an increase of 20.1 mL/100 g per minute.

“The posterior circulation may be more sensitive to the effects of hypertension on CBF, leading to paradoxical reductions in CBF with increases in BP,” de Jong et al. wrote. “If this circulation is more sensitive to high BP, it may also benefit more from BP lowering. This could explain why we observed changes in the hippocampus and not in global cortical CBF.

“The increase in hippocampal CBF could theoretically also be driven by a specific effect of nilvadipine on amyloid-beta.”

The authors said they didn’t have the resources or sample sizes to determine if the observed benefit of nilvadipine translated to better clinical outcomes. They said it will be important, in future studies with larger populations and longer follow-up, to determine whether the improvement in hippocampal CBF leads to cognitive benefits in earlier stages of Alzheimer’s.

The team also noted that current hypertension guidelines lack specific advice for patients with Alzheimer’s disease. It makes sense, they said, since there isn’t enough existing evidence on which to base a ratio between safety and benefit for these patients.

“One of the risks of BP lowering in this patient group is to compromise CBF, since cerebral autoregulation might be affected,” de Jong and co-authors wrote. “However, we previously showed that dynamic cerebral autoregulation remains effective in Alzheimer’s disease, and the present study confirms that BP lowering was achieved without causing cerebral hypoperfusion.”