Dementia Assessment Should Include Cardiovascular Issues

Controlling the blood pressure and cholesterol level of some patients with dementia might be more beneficial than prescribing costly memory-preserving drugs.

This suggestion comes from a comprehensive review of a condition called mixed dementia, a combination of Alzheimer's disease and vascular dementia, caused in part by problems with blood flow to the brain. A report of the review by researchers from the University of Michigan (UM) Health System, the VA Ann Arbor Healthcare System, and the Group Health Cooperative Center for Health Studies in Seattle appears in the December 15, 2004, Journal of the American Medical Association.

Mixed dementia may affect as many as 20 percent of the 6.8 million Americans with dementia and is particularly common in older patients, who often have memory problems due to a combination of factors. It is now thought that many people with symptoms attributed solely to Alzheimer's may in fact have mixed dementia, according to the authors.

“High blood pressure and high cholesterol damage small blood vessels in the brain and eventually result in cell death,” lead author Kenneth Langa, M.D., Ph.D., told Psychiatric News. “On top of that, Alzheimer's disease can alter the walls of the brain's blood vessels, increasing the chances of stroke.”

Pathological processes that damage the cardiovascular system can also hurt the brain and inflict a further toll on Alzheimer's patients.

The researchers reviewed recent medical studies on mixed dementia, vascular dementia, and Alzheimer's disease and noted any results from drug studies relevant to mixed dementia. They found that drugs designed to slow the progression of Alzheimer's disease, such as galantamine (Reminyl), rivastigmine (Exelon), donepezil (Aricept), and memantine (Namenda), have about the same effect in people with mixed dementia as in people with Alzheimer's disease alone. In some there was a measurable but not dramatic improvement in cognitive function or other values.

The researchers also found significant benefits related to heart-protecting therapy and dementia, however, and concluded that efforts to treat cardiovascular risk factors, especially high blood pressure, may be more effective than memory drugs in protecting brain function.

While more studies are needed for a better understanding of dementia and how to prevent or slow it, Langa said physicians can talk with each patient or family individually about what treatment to pursue. In all patients with dementia who might have a cardiovascular component, that should include advice about lifestyle changes and treatments to address risk factors such as high blood pressure, high cholesterol, diabetes, and physical inactivity. In patients with heart-rhythm problems, blocked neck arteries, or clotting disorders that can greatly increase the risk of stroke, further treatment may be needed.

If a decision is made to prescribe one of the new Alzheimer's drugs, he recommends following up with patients or their families in two to three months to monitor changes in memory, behavior, and cognitive function. Because of the high cost of Alzheimer's drugs, he suggested weighing costs against benefits.

The review focuses both on findings from randomized controlled drug trials and on observational studies based on trends among specific populations. Taken together, the analysis suggests that the cardiovascular system may have a lot more to do with mental function than hitherto believed.

Clinically, paying attention to cardiovascular risk factors could prevent some dementia and decrease the added burden of strokes in those with Alzheimer's disease. One study the researchers reviewed showed a 50 percent reduction in the incidence of dementia in patients with high blood pressure treated over four years with a calcium-channel blocker. Patients had a lower chance of developing Alzheimer's disease, vascular dementia, or mixed dementia.

This corresponds with observational data showing that people with high blood pressure are more likely to develop cognitive impairment, a mild form of dementia that often acts as a warning sign for later dementia. Other observational studies have suggested that treatment for high blood pressure can protect against cognitive decline.

The researchers also looked at evidence relating to drugs that reduce cholesterol or thin the blood. They found that prospective studies on statins have not shown a specific effect on dementia, but follow-up periods have been short. There is other evidence that reducing cholesterol may help brain function, though. Some, but not all, observational studies have shown that people with high cholesterol in middle age are more likely to develop mild cognitive impairment and Alzheimer's disease. And since statins decrease the risk of stroke, they can also decrease the risk of harm to thinking ability that often comes with stroke.

A recent study led by the review's senior author, Eric Larson, M.D., M.P.H., noted that people who have a certain genetic characteristic that puts them at higher risk for both heart disease and dementia may get more cognitive benefit than others from statin therapy. In an observational study, his team found that people with a specific genetic variation that alters production of APOE protein received more cognitive benefit from statins than others.

Aspirin therapy to thin the blood and reduce clotting is another widespread heart-protecting measure. The authors found several studies that attempted to assess the effect of aspirin on vascular dementia. While an observational study in Sweden showed an association between aspirin use and a decreased risk of dementia, there are no data available from randomized controlled trials that included aspirin for vascular dementia. Also uncertain was evidence on the effect of complementary therapies vitamin E and ginkgo biloba, both touted as memory enhancers. More studies are needed to assess whether these compounds have any effect on mixed dementia.

Overall, Langa said evidence is building that mixed dementia can be prevented or slowed by addressing both factors that cause the Alzheimer's disease process and the acute or chronic reduction of blood flow to the brain. The two are intertwined, he said, noting animal research data showing that amyloid protein, the chief sign of Alzheimer's disease, can infiltrate the walls of brain blood vessels and increase the risk of small, bleeding strokes. Other evidence suggests that an undersupply of blood to the brain can stress brain cells and perhaps contribute to Alzheimer's. Chronically high blood pressure also impacts the brain's autoregulation system for its own blood supply.

“Mixed dementia will continue to grow in importance as our society ages and deals with the cardiovascular effects of our current obesity and diabetes epidemics,” Langa said. “We need to help those who have it now and gather the data that will help us take steps to prevent it in the future.”

In addition to Langa and Larson, the study was conducted by Norman Foster, M.D., who is helping to lead a new national study that aims to find more biomarkers, in addition to APOE, that might affect dementia risk and treatment response.

The JAMA study was supported by the National Institute on Aging, Alzheimer's Association, a Paul Beeson Physician Faculty Scholars in Aging Research Award, a John A. Hartford Foundation grant to the Society of General Internal Medicine, and National Institutes of Health.

An abstract of “Mixed Dementia: Emerging Concepts and Therapeutic Implications” is posted online at<http://jama.ama-assn.org/cgi/content/abstract/292/23/2901>.▪