Vascular Intervention Useful in Preventing Non-Alzheimer's Dementia?

Pauline Anderson

August 01, 2016

TORONTO — A multidomain intervention that targets vascular risk factors, including hypertension, does not reduce incident all-cause dementia in an unselected population, but results suggest it may have some benefit in reducing vascular dementia.

Known as the Prevention of Dementia by Intensive Vascular Care (pre-DIVA), the results of a cluster-randomized clinical trial showed that while the intervention did not reduce incidence of all-cause dementia, disability, or mortality, the results "do not rule out clinically meaningful effects in people with untreated hypertension who are adherent to the intervention," the investigators note.

The study was presented here at the Alzheimer’s Association International Conference (AAIC) 2016 and simultaneously published online July 26 in The Lancet.

Nurse-Led Intervention

The nurse-led intervention was largely based on Dutch primary care and guidelines for vascular risk management for secondary prevention, said study investigator Edo Richard, MD, Department of Neurology, Academic Medical Center, Amsterdam, the Netherlands.

"So in the case of hypertension, the nurse advised lifestyle changes and also prescribed medication in conjunction with the primary care practitioner. If patient was a smoker, they were advised to quit smoking. If they were inactive, they were advised to be physically active. If they were overweight, they were referred to a dietitian. In cases of dyslipidemia, they were started on a statin and in cases of diabetes or prediabetes, they were treated accordingly," Dr. Richard added.

For the study, researchers recruited 3526 patients aged 70 to 78 years from 116 primary care practices in the Netherlands to participate in the study.

After baseline assessments, patients were randomly assigned to the intervention (n = 1890) or standard of care (n = 1636).

The primary outcome was all-cause dementia. Dementia was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, and classified into Alzheimer’s disease, vascular dementia, dementia with Lewy bodies, and other dementia types. In cases where the diagnosis wasn’t clear, it was confirmed by an expert panel blinded to treatment allocation.

Secondary outcomes included stroke, myocardial infarction, cognitive decline, dementia subtype, and mortality.

During a median follow-up of 6.7 years, 7% of patients in the standard care group and 6.5% in the intervention group developed dementia (hazard ratio [HR], 0.92, confidence interval [CI], 0.71 - 1.19; P = 0.54).

There was a small but significant difference in blood pressure change for the intervention group: an average adjusted mean difference in systolic blood pressure of –2.6 mm Hg (P = .0005), with the biggest decline among those with the highest baseline levels.

There were no significant treatment effects of other vascular risk factors, although there was a "slight improvement in dietary habits and more people quit smoking" in the intervention group than in the control group, said Dr Richard.

A sensitivity analysis suggested that patients in the intervention group who attended at least two thirds of the planned visits benefited the most. This, said Dr Richard, provided "some interesting signals of a potential effect in adherent persons."

Interpret With Caution

When the researchers looked at dementia subtypes, there was no effect on Alzheimer’s disease dementia ((HR, 1.05; CI, 0.78 - 1.14; P = .74), but there was a significant effect on combined non-Alzheimer’s dementia, most of which was vascular dementia (HR, 0.37; 95% CI, 0.18 - 0.76; P = .007).

"We have to interpret this with great caution," said Dr Richard. "These are small numbers (1% in the intervention and 2% in the control groups), and this is a secondary outcome analysis."

However, Dr Keith Fargo, PhD, director, Scientific Programs and Outreach, Alzheimer’s Association, was more enthusiastic.

"I would consider these to be among the most dramatic results to come out of this conference; they have the potential for saving millions of lives, if they pan out," he told Medscape Medical News.

"There appears to be something here that is important and that could inform future studies," he said. "It certainly calls for additional research designed specifically to target people who have hypertension et cetera to see if this can be replicated," Dr Fargo added.

As for other secondary effects, the investigators found no differences on myocardial infarction, stroke, mortality, or cognition as measured by the Mini-Mental State Examination.

Dr Richard said this speaks to the safety of the intervention.

"People thought this intervention would be dangerous due to the age of the participants, but we did not see any excess mortality, or excess hospitalizations in the intervention vs the control group."

Dr Richard noted that in many ways, the two groups were very similar, probably because the level of healthcare in the Netherlands is already very good.

"It’s very difficult to improve an already high level of healthcare," he said.

The fact that the study was carried out in the Netherlands "makes it all the more exciting" because people there already have a very high standard of care, said Dr Fargo.

He also noted that the intervention was "very modest," so it may be easy to introduce.

"You’re not talking about giving someone a drug candidate, and you’re not talking about making someone run on a treadmill for 2 hours a day 5 days a week; you’re talking about 3 visits to a nurse per year. Anyone can do that, and you can deploy that relatively cheaply virtually anywhere in the world."

Indeed, according to Dr Richard, such an intervention might have a greater effect on low- and middle-income countries because of the projected increase in hypertension and cardiovascular disease and low levels of risk management in these areas.

During a question period following his presentation Dr Richard was asked whether there was an element to the intervention that patients particularly disliked that might have explained why some dropped out. Dr Richard said he and his colleagues "should explore that more in-depth" in future trials.

Dr Richard and Dr Fargo have disclosed report no relevant financial relationships.

Alzheimer’s Association International Conference (AAIC) 2016. Abstract 04-05-01. Presented July 27, 2016.

Lancet. Published online July 26, 2016. Abstract

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