BP Reduction May Have Positive Effects in Alzheimer's

June 18, 2019

Antihypertensive treatment appears to have beneficial cerebrovascular effects in patients with Alzheimer's disease, a new study suggests.

The study, a sub-study of the larger NILVAD trial, analyzed cerebral blood flow in 44 patients with mild to moderate Alzheimer's who had been randomly assigned to receive the calcium antagonist nilvadipine or placebo for 6 months.

While nilvadipine treatment lowered systolic blood pressure by an average of 11 mm Hg, it did not affect cerebral blood flow apart from in the hippocampus, where blood flow was increased. 

The study was published online yesterday in Hypertension.

"These findings not only indicate preserved cerebral autoregulation in Alzheimer disease but also point toward beneficial cerebrovascular effects of antihypertensive treatment," the researchers conclude.

"We wanted to look at the effect of lowering blood pressure on cerebral blood flow in Alzheimer's, with a particular interest in the hippocampus, which is involved in Alzheimer's disease," senior author Jurgen Claassen, MD, PhD, Radboud University Medical Center, Nijmegen, the Netherlands, told Medscape Medical News.

"We found cerebral blood flow in general remained stable when blood pressure was lowered," he added. "This is an important finding in itself, but blood flow to the hippocampus actually increased when blood pressure was lowered."

Claassen explained that there is a widespread assumption that lowering blood pressure will cause cerebral blood flow to be compromised, and this is a particular concern in the elderly.

"Clinicians seem to want blood pressure to be a bit higher in the elderly, but we think the reason behind this is incorrect," he said. "It has been thought that the brain needs blood pressure to be higher to maintain cerebral blood flow, but we have shown this not to be the case."

He believes this is particularly important for Alzheimer's patients. "Some clinicians don't like to treat raised blood pressure in Alzheimer's patients as they believe this may reduce cerebral blood flow and exacerbate memory loss," Claassen noted. "Our results suggest the opposite may be true — lowering blood pressure does not do any harm and may actually benefit Alzheimer's as it appears to increase blood flow to the hippocampus."

On the mechanism, Claassen speculated that high blood pressure might trigger reduced blood flow to the brain and hippocampus, with the blood vessels becoming thicker to withstand the higher pressures.

"Possibly an overreaction might take place resulting in blood flow being compromised somewhat, and we believe the hippocampus might be particularly sensitive to this in Alzheimer's patients," he said.

He noted that previous studies have shown lowering blood pressure improves cerebral blood flow in patients with hypertension and cardiovascular disease.

"Now we have shown a similar result in Alzheimer's patients," he said. "We know amyloid accumulates in the hippocampus in Alzheimer's and it also deposits in blood vessels. The vessels to the hippocampus may be most affected, which may make them more sensitive to a lowering of blood pressure."

Half the patients in the current study had hypertension at baseline, with the others having high/normal blood pressure, but the effects on cerebral blood flow appeared similar regardless of baseline pressures.  

"What we think of as 'normal' blood pressure is probably still too high when it comes to negative effects on the cardiovascular system and the brain," Claassen commented. "Even mildly elevated pressure could lead to cerebral blood vessels adapting."

He said the current results have several potential therapeutic implications.

"First of all, for patients with Alzheimer's who also have hypertension, there is no reason not to treat with antihypertensives. Lowering blood pressure does not compromise cerebral blood flow," he said. "And secondly, lowering blood pressure may have a benefit in Alzheimer's from enhanced blood flow to the hippocampus."

While the larger NILVAD (Nilvadipine in AD) study did not show a benefit of nilvadipine on cognition, there was a signal of a slowing in cognitive decline in those at milder stages, Claassen noted. "It may be too late to see any clinical benefits once Alzheimer's is established, so lowering blood pressure before the disease develops may be the best approach," he said. 

He cautioned that because the current study is small, the results are not enough for clinical recommendations, but there are other studies that also point to similar conclusions.

"Several observational studies have shown high blood pressure in middle age to be a risk factor for dementia in later life, and the SPRINT MIND trial suggested that reducing blood pressure may lead to a reduction in the risk of developing mild cognitive impairment. Our results may explain these observations," he suggested.  

"And together, I think we do have enough data to suggest that lowering blood pressure in middle age may be beneficial in preventing cognitive impairment later," he said. "We know lowering blood pressure is beneficial for preventing cardiovascular events, but now we have another reason to do this."

Good for the Heart, Good for the Brain

Commenting on the study for Medscape Medical News, Rebecca Edelmayer, PhD, director of scientific engagement at the Alzheimer's Association, said the findings add to the body of evidence that controlling blood pressure may play a role in decreasing the pathological changes contributing to dementia that occur in the brain. 

"This study should be replicated in a larger, more diverse population, and more research is also needed to understand how blood pressure control affects individuals who are on different points of the Alzheimer's disease continuum," she noted.  

"What we know from years of research is what is good for the heart is good for the brain," Edelmayer added. "Research reported last year at the Alzheimer's Association International Conference found lowering blood pressure to 120 mm Hg systolic significantly reduced the occurrence of mild cognitive impairment."

Earlier this year, the Alzheimer's Association offered more than $800,000 in seed funding to extend this clinical trial in hopes of determining whether continued blood pressure control could reduce risk of probable dementia, she added.

The NILVAD main study was funded by the European Commission Framework 7 Program Health Theme. This NILVAD cerebral blood flow sub-study was funded by the Alzheimer's Drug Discovery Foundation and the Dutch Alzheimer Society.  One of the study coauthors reports a pending patent for nilvadipine. The other authors have disclosed no relevant financial relationships. Edelmayer has disclosed no relevant financial relationships.

Hypertension. Published online June 17, 2019. Abstract

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