Lou-Ellen Barkan interviews
Dr. Mary Sano

Lou-Ellen Barkan (LEB): Welcome Mary and thank you for joining us. Would you like to tell us something about how you entered the field of Alzheimer’s?

Mary Sano (MS): My training was in neuropsychology. Most people tend to go into either adult or child. I picked adult and was particularly impressed with studying Alzheimer’s disease. Not only are the cognitive aspects scientifically interesting, but the human aspects are impressive. It seems that those who make it to old age, even with late-stage Alzheimer’s disease, also have a personal history – a past that can be used as a reference point from which we can understand their loss of self. Knowing that people had an inner strength from their past was uplifting to me.

The other thing that was very interesting was that Alzheimer’s disease is a disease that is almost always identified by someone else – maybe a family member, maybe the lady who cuts your hair. And these individuals often become caregivers; those who care enough about someone else to get them to a doctor or encourage them to seek medical help. These caring “others” almost always end up helping individuals who have Alzheimer’s with routine daily activities. I found that the disease brought out the humanity of caregiving and that was very impressive. The work was very, very rich, and it made me want to make a career in this field.

LEB: Sounds like your job had a whole level of personal interest and satisfaction beyond the technical and scientific.

MS: It’s a privilege to be able to see how people rise to the need of another human being, and take care of them, even in little ways. The shopkeeper who notices that the person who used to come in regularly can’t handle their change anymore will sometimes report that to a family member. If there’s no family, sometimes they go with the person to the doctor. I’ve met these kinds of people when they bring in patients for an assessment. The person who brings them in may not be related, but they tell you, “I saw this nice person, and they needed a little help.” There are so many situations that are difficult. It’s important to remind yourself that people really do rise to an occasion to help out others.

LEB: It must be frustrating to work so closely with people who are so worthy of your attention, knowing that, right now, there doesn’t seem to be much that we can to do to help them.

MS: Just acknowledging that there’s a problem is a big help. When a person comes to our attention and is diagnosed, that’s the beginning of letting a whole network of others realize that someone needs help and showing them how to get it. Then, rather than working hard to ensure that someone is remembering things, they understand that the person with a cognitive problem can’t manage their regular healthcare, remember to take medications or prepare meals correctly. Identifying the problem is really the beginning of making sure that a person is safe and taken care of. And that’s rewarding.

LEB: There is satisfaction that just comes out of the recognition that there is a problem and having people
understand it.

MS: And leading them to the right resources. Making sure they don’t just say, “Oh it’s okay,” without doing anything about it. Instead, saying, “We should see a doctor.” and “Yes, there are some medications that we can try.”

LEB: We focus a great deal on the challenges of delivering services to so many diverse communities. Do you notice differences between the acknowledgement and acceptance of the problem in the various ethnic and
cultural communities you work with?

MS: That’s an interesting question. I have been doing research with several cultural communities in New York and across the country and there are some economic and demographic issues related to recognition and diagnosis. For example, the risk of dementia seems to be higher with lower education, which may be lower in some ethnic communities, particularly among the elderly of that community. In a national study we completed several years ago, we reported that cognitive and behavioral symptoms reported by caregivers of patients with dementia were similar among English and Spanish-speaking communities across the U.S. In general, I am more struck by the similarities than the differences.

I have been doing research in Mumbai, India, where the community is very poor. As that country has become more modern and industrialized, family members who used to stay at home and help with care for children and elders now have jobs. Adult children leave the village in order to work. They expect to arrange child care but may not have realized that they were also providing care for an older parent or relative. They become aware that these older relatives need help and there are few services to take care of the elderly.

Growing technology affects the whole world, and even in the most remote places, people increasingly need strong cognitive abilities to take care of themselves. Overall,my impression is that cultural differences that interfere with identifying dementia are disappearing, because the world is becoming very homogeneous and the need and expectations for cognitive health at any age is recognized globally.

LEB: Some time ago, estrogen research was very hot and then you moved on to looking at cholesterol and diabetes. Are these still important areas of investigation?

MS: The estrogen story is very interesting. Based on epidemiological observational studies we came to think that estrogen use was associated with many positive things such as improved cardiac function, protection from stroke and protection from Alzheimer’s disease. This impression was confirmed by animal models as well. However, the human observations could be related to coincidental associations (perhaps estrogen users take better care of themselves) rather than the effect of estrogen. The scientific and medical community did the brave and right thing and tested the observation with a well-controlled clinical trial and it is a good thing they did. We now know that not only does estrogen not help cardiac health and does not protect against dementia, but we know it may actually be detrimental for these conditions.

The cholesterol story is also interesting but subtly different. Again, observational studies suggested that those with high cholesterol may have poorer memories and the use of the statins which are cholesterol-lowering drugs was associated with a lower risk of Alzheimer’s disease. Again, we did the important clinical trials with statins and have not found any evidence of protection against dementia. An important difference between these trials and the estrogen studies is that we found no detrimental effect of statins on cognition and the statins not only lower cholesterol, but they prevent heart attacks and strokes. Again, these studies were very important.

It’s important as we think about our cognitive health, to find out how the treatment for anything else affects it. For example, we think that taking care of our cardiac health will improve cognitive health and reduce our risk of Alzheimer’s disease. We don’t know with certainty that taking care of one takes care of the other. Estrogen has a very important role in the health of women at a certain period in their lives, getting them through menopausal symptoms. And, in fact, using it for that purpose is still the right thing to do. But, we were extending it beyond that, thinking that maybe estrogen did other things. This turned out to be wrong. It’s really important to inform the public of the current and future consequences of everything they are doing.

These are complicated stories, not simply, “Do this; it’s good for you forever.” We might better say, “Do this for now, and when this problem goes away, you have to think about a different thing to do.” And I think that “teasing out” the specific times in development when treatments have their affects, and knowing what the consequences are at a later period are important aspects of informing us of how to take the best care of our health.

LEB: Do you believe that there’s a relationship between diabetes and Alzheimer’s or does just having diabetes put you at greater risk?

MS: It’s a really good question and the answer is not clear. In fact, one of the things that we’ve started to identify is that perhaps, at a certain age, there is a relationship between Alzheimer’s and diabetes. That relationship could be anything from diabetes creating a set of increased cognitive risk factors that lower the threshold at which we start to express Alzheimer’s. On the other hand, diabetes affects our vascular system, and that can cause a separate cognitive problem. We do know that vascular disease added to Alzheimer’s disease makes the clinical condition worse. We also know that at older ages, the eighth and ninth decades, vascular and cardiac risk factors may have less effect on the risk of getting Alzheimer’s disease.

We do know for sure that diabetes is associated with cognitive loss, but not necessarily associated with greater potential for Alzheimer’s disease. Alzheimer’s disease patients don’t necessarily have more diabetes. We also know that not only is diabetes itself a complicated issue, but the way you treat it may be an issue. The type of medication used may have a role and how long one takes the medications may also matter.

There is interest in the idea that insulin-resistance may be important to brain function. We know that insulindegrading enzyme (IDE) may also degrade or break down amyloid, the protein that forms plaques in the brain of patients with Alzheimer disease. Some of the drugs used to treat diabetes are being studied as possible treatments for Alzheimer’s disease. At our Center, Dr. Hillel Grossman is conducting a study with a natural product, NIC5-15, which works through this mechanism. He is determining the best dose which might be used in a larger study to treat patients with Alzheimer disease.

LEB: We often ask questions about the effect of various foods on our brain function: red wine, chocolate, blueberries and almonds. We’ve also talked about the effects of general anesthetic and bumps on the head. What we’ve never addressed is the effect of sleep. The reason I’m curious is that I recently met someone who told me about “Sleepy Hollow Syndrome,” where people sleep excessively – often because they’re depressed. Is this associated with greater probability of getting dementia?

MS: I don’t know the data around sleep disturbance itself, but I do know that there are many conditions associated with sleep disruption that are also associated with cognitive loss and dementia. For example, sleep apnea is associated with cognitive loss and treating it can improve memory and thinking. We also know that sleep disturbance can arise from depression, which is associated with an increased risk of Alzheimer disease. But I don’t think we have a good understanding of the effects of sleep – either too much or too little.

The food story is also tricky. For example, observational studies tell us that red wine (or even grape juice) might prevent dementia but how much, what is it in the red wine that will be helpful and how do we get it into the brain effectively. Resveratrol is one of the agents in the red wine that we think might be effective. We are conducting a study in patients with Alzheimer’s disease which is sponsored by the Alzheimer’s Association that uses resveratrol in a formulation that we hope will make it more available to be used by the cells in the body.

LEB: This reinforces the importance of clinical trials. I know that each of us is genetically unique and our life experiences are very different. But even if we all started in the same place, by the time we got to be 18 or 40 or 80, we’d be very different organisms. So the genetic heritage that we bring, combined with our personal habits, dictate how we end up and whether we are going to get diabetes or Alzheimer’s disease or anything else.

I’m part of a clinical study now, categorized as someone who doesn’t have the disease, but has a family history. It was a fascinating experience to go through the cognitive testing, the blood test and some very simple physical exams. They’ll be tracking me over time to see how my cognition holds up. I keep hoping that my participation also encourages others to sign up.

MS: This is really important. A scientist can tell us about a fabulous molecule that takes the amyloid out of the brain of a mouse or makes the mouse swim a maze more quickly. That’s great, but the reality is that we are not mice and the translation from the Petri dish to the mouse to the human being can only be done when we have enough individuals participating in research.

One of the challenges is that, in the laboratory we raise the animals to be genetically identical so we may only need a few to get the same results every time. But humans are not identical, and we need many, many more to understand what the most likely response will be to a given condition or to a new drug. So we go from needing several animals to several hundred humans to get a reliable response. We only get information about people when we test people. We need to convince patients, families and those who are concerned about becoming patients, of the importance of participating in research.We can only get answers when people are committed to providing them by contributing their time to research efforts.

I like to focus on the fact that when it comes to Alzheimer’s disease, not only can you contribute to research yourself, but you can also contribute by helping someone else participate. It’s the one adult disease where every study participant needs a partner. Sometimes a person who would be just right for a study can’t participate because they don’t have a partner. Often the partner is a family member but sometimes they are not available because of geography or work or other commitments. What we have to realize is what we learn in animals at the beginning is an important beginning, but it can’t replace human research.

LEB: What is worrisome is that, even though we know there is an epidemic underway, the length of time to have a drug approved is very, very long. Do we have this kind of time?

MS: I think it is important to get the right answer and that is in part why it takes a long time. However, there is a lot going on. In fact, if you look today on www.clinicaltrials.gov you’ll see many trials that are ongoing right now and the answers from these studies are coming in pretty quickly. There are two drugs that are within two years of approval, if they are effective in the current studies. There are many more that are a bit further away but are using exciting mechanisms.

LEB: So where are we now with treatment, prevention and cure?

MS: It’s important to remember that we have medications that work. They don’t work perfectly, but they do work. And a large number of the elderly who have Alzheimer’s don’t get an opportunity to try these medications. There has been an attempt to suggest that they shouldn’t use them because the effect isn’t great. In fact, the process of approval requires that we demonstrate efficacy in this country, so these drugs have already been established as having efficacy. Hopefully, everyone at least will have a chance to try them. And it’s important to try the medication for the full length of the cycle, in the right dose and regularly. In the course of this, you also need someone who can make sure the person with the disease actually takes the medication. We do have treatments to offer people, which is very important to keep in mind.

In terms of prevention, we don’t really know what prevents the disease. There are studies that suggest that cognition is related to cardiovascular health or mental health. But, the process of going right to the genetic level and understanding how the genetic and environmental risk factors are related is way ahead of us – although we make progress on it every day. We do know more and more about the two proteins we think are important and about how to modify them, but we don’t know if those modifications will change the course of disease. We know more and more about cell regeneration and connectivity. This knowledge is not realized yet in drugs but may help us with modifications to our lifestyles.

In terms of cure, while everybody hopes that we have a preventative agent, the reality of a cure is something we should never forget. Curing people who already have the disease may be the most important thing to focus on. Certainly,we hope that we can prevent Alzheimer’s, but in the absence of being able to do that, there is hope in the treatments that actually target the etiology of the disease.

LEB: What an astonishing outcome if we could prevent the disease in people over the age of 85. This would totally change the way we experience aging in this country.

I know there’s been progress and that there are medications that are available and more new studies, but it still feels disappointingly slow, partly due to funding. So how do you maintain your enthusiasm and optimism in the face of how long we’ve been at this – about 30 years of serious Alzheimer’s research?

MS: It’s a balancing act. The disappointment comes from an awareness that the problem does exist. And it also arises out of people valuing their cognition, not only associated with being young and in the workforce, but understanding that cognition may affect how they spend their free time and retirement. People come to our attention earlier and worry more. And doctors ask questions about your memory during your physical, especially if you are over 50. That is evidence that people know this is important.

LEB: So how do you cope with the pressure of being responsible for such a big agenda at a major institution like Mount Sinai School of Medicine?

MS: I love getting a little bit of physical activity,but it tends to be solo activities. I like to swim and bicycle. I work out in a gym a little bit, but I’m definitely not the competitive type. You won’t see me on a softball team.

I’m blessed with wonderful relationships in both family and friends and I enjoy relaxing with them. Although not in the New York area, most of my family live close enough that I get to see them often. My friends are everywhere. Many people who work with me as well as others around the country who I see quite often have become close friends. So if one of us has a really “down moment,” we can seek each other out, chat, make a meal together, or listen to music.

I’m blessed with wonderful relationships in both family and friends and I enjoy relaxing with them. Although not in the New York area, most of my family live close enough that I get to see them often. My friends are everywhere. Many people who work with me as well as others around the country who I see quite often have become close friends. So if one of us has a really “down moment,” we can seek each other out, chat, make a meal together, or listen to music.

LEB: You are talking about reducing the isolation during the course of the disease.

MS: Yes. But for those who don’t already have the habit of socializing, it will be tough. For those who do, I am hoping our friends will like us even when we don’t think as well.

LEB: In New York, we focus on work. My theory is that to be relevant here, you have to do something meaningful. You have to be engaged. And a lot of our life takes place in the context of a challenging work environment. After people retire, they may have reduced the pressure from work, but they may also be more isolated. It’s the natural outcome of focusing so heavily on our work environment for so much of our lives. In some cities, folks work from 9-5 and then go home and socialize around recreational activities. Here, our work life extends way beyond that.

MS: I think that’s true.

LEB: I would like to go back to your comment earlier about partnering in clinical studies. We’re working with agencies like Share and Care, and United Neighbors of Midtown. These are agencies with the specific mission to take care of people who don’t have any kind of network or family members. These agencies provide invaluable services to those who are isolated in this way.

MS: The most difficult situations will happen to those people in isolation. And we need a way to connect with them. Even if we had a medication, how will those people get it?

LEB: I’ve met some of the clients of these agencies. The retired schoolteacher, who worked very hard, retired without a social network or family and is now living alone in an apartment relying on strangers. She gets sick and the neighbors are all young filmmakers who are never home. She has no social network to protect herself. These terrific agencies play that very important role.

The City’s Department for the Aging has revived the “Carrier Alert” Program. Seniors register with the agency and put a marker in their mailbox. If mail accumulates, the mail carrier calls “311,” the City’s emergency number and is connected to the Department of the Aging. The Agency sends someone out to see if the person needs help. It’s a terrific program.

MS: Well here’s an interesting dilemma. The Alzheimer’s Disease Centers require that everybody have a partner. When you look at the statistics for those over 65, it seems that only about a third of them have ever lived alone. But this number goes up every year, so by age 75 to 85, the percentage of people who live alone is quite high.We need ways to assess these individuals and their needs – and figure out how we are going to deliver services to that community.

LEB: Very frightening to think about these number as the huge population of Baby Boomers age.

Mary, thank you so much for talking with us today. We are so grateful to live in this astonishing City, working with all our brilliant scientists. There is no doubt in my mind that, with all this talent, we will someday conquer all the challenges of Alzheimer’s disease.

Dr. Mary Sano is Professor of Psychiatry and the Director of the Alzheimer's Disease Research Center at Mount Sinai School of Medicine. She is also the Director of Research and Development at the James J. Peters Veterans Administration Hospital. Dr. Sano is a neuropsychologist by training and has been involved in designing and conducting clinical trials for Alzheimer's disease (AD), Parkinson's disease, and mild cognitive impairment of aging. She is the Director of several clinical trials including a multi-center study to determine if lipid lowering drugs can slow the progression of Alzheimer's disease and is co-director of an international study for the treatment of cognitive function in adult individuals with Down syndrome. Currently, she is the Director of a multi-center study to develop Home-Based Assessment of Cognitive Impairment for use in clinical trials for prevention of dementia. Dr. Sano has also directed the development of neuropsychological assessment as outcomes for clinical trials in Spanish speakers in the U.S. and has developed methods for standardizing cognitive outcomes in clinical research in dementia in Europe and Asia.

In 1989, she received the Florence and Herbert Irving Clinical Research Career Award to develop methodologies for the assessment of therapeutic agents in AD. She directed the first ADCS multi-center trial of vitamin E and Selegiline, treatments which delayed the clinical progression of AD, and in 1998, she received the Veris Award for this study. Her research interests are in clinical trial design to treat individuals with cognitive impairment and in the impact of these treatments on functional abilities. She is a member of several prestigeous groups including: the task force to develop guidelines for developing diagnostic criteria for the diagnosis of dementia for the DSM V; the Prevention Research Work Group for the Healthy Brain Initiative sponsored by the Center for Disease Control and Prevention and the National Institute of Aging; and the Veteran Health Administration work group to develop coordinated care for dementia patients. She has been a reviewer for NIA, NINCDS, NCAM and the Merit review. She is also the editor for many scientific journals.

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