Can the same actions that help prevent a heart attack or stroke also prevent or slow the memory loss, confusion and thinking problems of dementia? A new study suggests that for many people, primarily senior citizens, the answer could be yes.
And for some, the impact of steps like controlling blood pressure and cholesterol might be greater than the effect of high-priced memory-preserving drugs.
Doctors now think that many people with symptoms attributed solely to Alzheimer's - memory loss, confusion, wandering, trouble following instructions - may in fact have mixed dementia.
Mixed dementia is a combination of Alzheimer's disease and vascular dementia, caused in part by problems with blood flow in the brain. It may affect as many as 20 percent of the 6.8 million Americans with dementia. It is particularly common in older patients, who often have memory problems due to several conditions at once.
In the December 15 issue of the Journal of the American Medical Association, researchers from the University of Michigan Health System, the VA Ann Arbor Healthcare System and the Group Health Cooperative Center for Health Studies in Seattle present a comprehensive review of what's known - and what's not - about a condition called mixed dementia.
"Having risk factors like high blood pressure and high cholesterol does damage to small blood vessels in the brain and can cause death of brain cells over time," says lead author Kenneth Langa, M.D., Ph.D. "In addition, the Alzheimer's disease process itself can affect the walls of blood vessels in the brain, making strokes more likely. Strokes can cause dementia through the death of large areas of brain tissue, or through the build-up of damage from multiple small strokes cased by athero-sclerosis in small arteries in the brain or the larger carotid arteries in the neck."
In other words, processes that hurt the cardiovascular system also hurt the brain, and inflict a further toll on those with Alzheimer's disease.
For the new paper, the researchers reviewed all recent medical studies on mixed dementia, vascular dementia and Alzheimer's. They analyzed hundreds of articles, noting any results from drug studies that were relevant to mixed dementia.
The review shows that drugs designed to slow the progression of Alzheimer's disease have about the same effect in people with mixed dementia as in people with Alzheimer's alone. That is, in some people they cause a measurable but not dramatic improvement on tests of cognitive function or other measures, or slightly slow an inevitable decline. The authors looked at drugs like galantamine (Reminyl), rivastigmine (Exelon), donepezil (Aricept) and memantine (Namenda).
But when the authors reviewed the evidence relating to heart-protecting therapy and dementia, they found significant benefits. They conclude that efforts to treat cardiovascular risk factors, especially high blood pressure, may be more effective than memory drugs in protecting brain function.
Still, the authors note that more studies are needed to give doctors a full picture of mixed dementia, and to show them what works, and what doesn't, in preventing and slowing it.
"Until those studies are completed, physicians should talk with each patient or family individually about the treatment route to pursue," says Langa. That discussion, in all patients with dementia that might have a cardiovascular component, 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, the authors recommend that doctors follow up with patients or their families in two to three months, to see if there has been any improvement in memory or behavior, or whether the patient's cognitive decline has slowed. A discussion of costs and benefits, because of the high monthly cost of the drugs, is also advised.
Langa says that the review's findings have changed the way he handles his patients with dementia and cardiovascular risk factors, in the primary care clinic of the VA Ann Arbor Healthcare System. He is also an assistant professor of general medicine at the U-M Medical School, a research investigator at the Ann Arbor VA, and a faculty associate at the U-M Institute for Social Research.
The new review focuses on findings from randomized controlled drug trials, and 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 many people realize. Paying attention to cardiovascular risk factors could prevent some dementia and decrease the added burden of strokes in those with Alzheimer's disease.
For example, one study that the authors reviewed showed a 50 percent reduction in the incidence of dementia in a group of patients with high blood pressure who were treated over four years with a calcium-channel blocking blood pressure drug. And patients who received the blood pressure drug 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. And other observational studies have suggested that treatment for high blood pressure can protect against cognitive decline.
The authors also looked at evidence relating to drugs that reduce cholesterol or thin the blood. To date, they find, prospective studies on cholesterol drugs called statins haven't shown a specific effect on dementia, but follow-up periods in such studies have been short.
There's 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 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 new paper's senior author, Eric Larson, M.D., MPH, of the Group Health Cooperative, notes 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 a protein called APOE 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 yet available from randomized controlled trials (the gold standard of clinical research) that included aspirin for vascular dementia.
Also uncertain, the authors found, was evidence on the effect of complementary therapies vitamin E and ginkgo biloba, both often touted as helping memory. More studies will be needed to assess if these compounds have any effect on mixed dementia.
In all, says Langa, evidence is building that mixed dementia can be prevented or slowed by addressing both factors that cause it: the Alzheimer's disease process and the acute or chronic reduction of blood flow to the brain.
The two are intertwined, he says, 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. And other evidence suggests that an under-supply of blood to the brain can stress brain cells and perhaps jump-start the Alzheimer's disease process. Chronically high blood pressure also impacts the brain's auto-regulation 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," he says. “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 co-authored by Norman Foster, M.D., a professor of neurology at U-M who directs the Cognitive Disorders Clinic and 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. Langa, meanwhile, hopes to use ISR data to look at the relationship between cardiovascular risk and dementia in an ongoing national study of older Americans.
The study was funded by the National Institute on Aging, the Alzheimer's Association, the Hartford Foundation and the Paul Beeson Physician Faculty Scholar program.
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