by Diane Joy Schmidt
Gary Rosenberg, MD, one of the country’s leading researchers in vascular dementia and former chair of the neurology department at the University of New Mexico Health Sciences Center in Albuquerque, took time after a busy day to sit down and explain for the Link’s readers his latest research in dementia, his work in early identification of types of dementia, the important role of high blood pressure, and other risk factors in vascular disease, the promise of treatments for slowing the disease, and how, at the request of UNM Chancellor for Health Sciences Paul Roth, MD, he is now heading up the new UNM Memory and Aging Center that will work to serve the growing population, currently estimated to be 43,000, of people in New Mexico who have some form of dementia.
Link: What do you do to stay healthy? I think this is something everyone wants to know.
Dr. Rosenberg: I try to watch what I eat and to exercise regularly.
Link: First I want to ask you about your research.
Dr. R: I have been fortunate to have almost steady funding for research by the National Institutes of Health. My work has focused on diseases that damage blood vessels in the brain, such as strokes and vascular dementia. With the new center, our group will expand into research and drug studies in Alzheimer’s disease. For the past 10 years, the research has been focused on vascular dementia with the goal of developing better ways to diagnose the illness earlier when treatments would be more effective. We are following about 100 patients for multiple years. We use a number of tests to figure out their diagnosis.
Dementia is a general term, like fever, that is related to many different types of problems with thinking, and there is a lot of different things that cause it.
Our research is focused on vascular causes, such as multiple strokes, which is one large group of patients. Another group of patients has a gradual worsening, which we feel is related to reaction by the brain to the blood vessels damaged by hypertension, diabetes, and elevated lipids. We use the term “inflammation” to denote this type of reaction in the brain. The challenge has been to find the group with this gradually worsening inflammatory process.
There are no specific treatments for vascular dementia so we try control vascular risk factors, by lowering elevated blood pressure and treating diabetes, and also encouraging people to lose weight and take up exercise. For the research studies, we rely on what some call “biomarkers” that suggest an inflammatory process. These come from MRI, psychological testing, and cerebrospinal fluid studies. Since no one test is diagnostic, we use all of the test results for diagnosis. It takes a long time to collect all this information, by following the patients for several years to make sure the diagnosis is correct. We then can look back at the test results to predict the outcome for a new patient.
So, we can start people on treatment trials before extensive damage to the brain has occurred. Our goal is to find drugs that slow the normal course of the disease.
We are also working in the laboratory with animal models to test new drugs, particularly to block the damage done by high blood pressure. To do this we have a rat that develops hypertension, which we make progress faster by feeding it an awful diet – low protein, high salt- which causes damage to the brain’s blood vessels, and they have the same types of changes in the brain that I see in my patients, And we can give that animal anti-inflammatory drugs and block these changes.
Link: So are these drugs in the animal study ones that are readily available or are they highly specialized?
Dr. R: We don’t have a drug yet that we think we can easily translate into people. We have a drug that’s actually an old antibiotic that’s used for acne and it’s an anti-inflammatory and it works well in the animals. There are other drugs being developed at NIH and by drug companies. So although there are some things that are promising, we don’t have a treatment yet.
Link: My family is very long-lived. They probably have this longevity gene that is found among some populations including Ashkenazi Jews. One uncle lived to be 101 with no cognitive issues. Another relative however in his 90s had strokes and then developed memory loss.
Dr. R: That’s exactly the kind of patient we’re interested in.
Link: So, there are new drugs being developed for this group?
Dr. R: Drug are being developed to block this kind of inflammation. We have a population of patients that could participate in clinical trials when there are drugs available. These gradually worsening patients have a disease called Binswanger’s disease, or sub-cortical ischemic vascular disease. We use biomarkers to select this group of patients.
Link: So how do you go about identifying these biomarkers?
Dr. R: First, we use special tests with MRI to show that the white matter is damaged. We can visualize the regions of inflammation with a contrast agent that leaks out of the inflamed blood vessels. Then we use cerebrospinal fluid test for two purposes. One is to look for inflammatory factors – things that show the brain is having inflammation, and the other is to separate out those with Alzheimer’s disease.
That is very important, because we can’t do that so well clinically. So, we can measure the Alzheimer type proteins in the cerebrospinal fluid and we can say this is an Alzheimer patient and then we measure the inflammatory factors, and we say this is an inflammatory process and there’s no Alzheimer factors here; and that suggests that it is a vascular process, which is the patient we are looking for.
Link: So you can separate out the Alzheimer’s patients?
Dr. R: Alzheimer’s patients have a protein called amyloid in the brain and cerebrospinal fluid. It accumulates in the brain in so-called “plaques” and another substance called phosphoTau. Patients with low amyloid and high phosphoTau are likely to have Alzheimer’s disease. To make diagnoses, we use information from multiple sources, including clinical, cerebrospinal MRI findings, in addition to neuropsychological testing. With that amount of information, and following the patient for a couple of years, we know which patients we want for different types of treatment.
Link: People whose parents are now losing their memory, they want to know, of course, am I going to be like that too, is it genetic or is it from strokes?
Dr. R: Alzheimer’s disease can be genetic in some patients with early onset of the disease. Vascular causes of dementia are not clearly genetic, but some families have a tendency for blood vessel disease of the heart and brain.
Link: What led to the development of a new center?
Dr. R: This January, Paul Roth, the medical center chancellor asked me to start a center, which we named the UNM Memory and Aging Center. The purpose was to improve care for the large number of patients in the state with thinking problems. In addition to myself, Janice Knoefel, who is an expert on Alzheimer’s disease, and John Adair, who’s trained in behavioral neurology, see patients in the center. This is the first center for treatment of people with cognitive disorders in New Mexico. We estimate that there are almost 40,000 people with dementia and we will be the only place with dementia specialists in the state.
And it’s even worse than that when you look at it geographically; right now in the United States there are 31 Alzheimer’s centers funded by the National Institute of Aging and these centers are mainly on the coasts with none in the Rocky Mountain states. It was clear that there was a need for such a center and Chancellor Roth recognized that this was important for the state. Now we’ll be able to see a lot more patients, we’ll be able to expand our clinics and research programs and improve teaching.
Link: Does the VA send you patients?
Dr. R: John Adair is at the VA and at the university, so he sees the patients at the VA.
Link: What about costs to the patient?
Dr. R: Medicare and Medicaid covers most of the costs. When they come into one of our studies, the MRIs, the blood tests, the spinal fluid analysis, is paid for by NIH
Link: Would somebody with Parkinson’s be a patient you would see?
Dr. R: Approximately 50% of people with Parkinson’s have some kind of mental impairment. Some people who have Parkinson’s have behavioral problems, such as agitation and hallucinations. A new drug has been approved by the FDA to treat those symptoms. So a trial will be started with that drug to treat those sort of symptoms in Alzheimer’s patients.
Link: If I want to go online and see, well, am I losing my mind, is there a website test I can take?
Dr. R: I think more trouble is caused by the worry created by these searches. It is best if you are concerned to start with your family doctor. They can help rule out thyroid disease, B12 deficiency, congestive heart failure, and a number of other diseases that could cause memory problems. Once they have eliminated those, then we can see them for further evaluation.
Link: For the Jewish community here, many people moved here from the coasts or the Midwest, some to get away from family . . .
Dr. R: It’s a price you pay for that early decision. By moving you often loss your support team.
Link: Is it measurable, having a social network?
Dr. R: Yes, there are studies that show that card playing, regular exercise, using the computer, reading, a good social network, all slow memory loss. You don’t necessarily need to have an intimate family, but a group of supportive friends can compensate. The ideal thing would be for people who live alone to build communities, to build houses close to each other, apartment complexes.
Link: What direction would you like to see the research go?
Dr. R: The focus for most of the dementia research has been Alzheimer’s disease for the last 25 years, and particularly what’s called the amyloid theory, but the recent studies have not supported that. So NIH now is looking at the connection between vascular disease and the Alzheimer-type process. If you have vascular disease it accelerates the Alzheimer process and that’s been pretty well shown in a large number studies. So they’re focusing more on reducing vascular risk factors. We know that if you have hypertension at age 40, by the time you are 60, your brain is seven years older than someone who doesn’t have hypertension – all those years of hypertension have damaged the small blood vessels in the brain.
Link: So what about people with diabetes?
Dr. R: Diabetes is a major vascular risk factor, similar to hypertension. If you have diabetes it can interfere with kidney function, which causes blood pressure to go up, so it’s rare to have one and not the other –
Link: And a growing percentage of the population is obese.
Dr. Rosenberg: It’s an epidemic. The connection between obesity, diabetes and Alzheimer’s disease is not so clear. There seems to be a connection, but it is not as straightforward as hypertension.
Link: I know doctors say one of the biggest problems they have is, how do you change people’s behaviors?
Dr. R: Treatment for hypertension has greatly improved, but not enough people are being treated.
Link: Where is the UNM Memory and Aging Center located and how can a patient be referred?
Dr. R: We are part of the Clinical Neuroscience Center at the University of New Mexico Hospital. Patients can be referred by making an appointment in the Memory and Aging Center in the Clinical Neuroscience Center. Our research center is in the Domenici Hall north of the medical school on Yale next to the golf course. We will soon have a Web site that will allow a patient to make an appointment directly.
This article was written with support from the Journalists in Aging Fellowships, a program of New America Media and the Gerontological Society of America, sponsored by the Retirement Research Foundation.