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Alzheimer's: The State of Prevention, Treatment

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By Matt McMillen

A lot’s happening in Alzheimer’s disease research right now. A recent study suggests that low levels of vitamin D may boost older adults’ risk of Alzheimer’s; a second suggests that up to one-third of cases are preventable.

To walk us through the latest, most exciting developments, we turned to UCLA professor of neurology Dale Bredesen, MD, director of the university’s Mary S. Easton Center for Alzheimer’s Disease Research.

Q: What can you tell us about Alzheimer’s risk? Do factors like diet, exercise, and stress play a role?

A: There are those who take the nihilistic view that there is nothing that can be done to reduce your risk. While you might argue that there’s no guaranteed avoidance of the disease, I think there’s every indication from many studies that one can reduce one’s risk through lifestyle modifications.

Exercise, for example, is a critical piece. So are sleep and chronic stress. Inflammation, of course, is also a huge issue. Look at all the things that feed into inflammation, from your diet to your hygiene to your homocysteine levels. All of these things are critical to Alzheimer’s. My argument — and not everyone agrees — is that, yes, there are things that you can do to reduce your risk, such as exercising and eating a healthy diet.

Of course, you can’t ignore the genetics. Some people have a very strong genetic tendency towards the disease, but even for those people, there are things that do seem to reduce the risk. Diet, sleep, exercise, stress reduction – all of these things are important.

Here’s just one related example: When you eat sugar or simple carbs, you drive up your glucose level, which requires your body to manufacture insulin. Then, your body has to degrade that insulin. To do that, it uses insulin-degrading enzyme. But it turns out that insulin-degrading enzyme is also important for degrading amyloid beta [a protein that builds up in the brains of people with Alzheimer’s disease], and it can’t be doing both things at the same time. That makes diets that are low in simple carbohydrates promising in terms of prevention.

There’s also been discussion about saturated fats and high cholesterol and their association with Alzheimer’s. Type 2 diabetes and metabolic syndrome have a strong correlation with Alzheimer’s. All of these things seem to indicate that one’s diet over the years is going to be important. When we have the optimal treatment program, it will presumably include an important dietary component.

Q: Recent research suggests vitamin D may play a role in Alzheimer’s. How significant is that discovery?

A: You’re going to see some follow-up on this. If we take vitamin D, is it going to be preventive? Is it just an association or is there a causal relationship in terms of risk reduction? There are all sorts of questions that have been brought up by this.

The results also bring into focus a question that is coming up again and again. I think it’s fair to say that many people increasingly believe that the optimal treatment for Alzheimer’s disease and mild cognitive impairment (MCI) will not be a single agent but will be some sort of combination. How do we find that optimal cocktail, that ultimate therapeutic program, which may go beyond pharmaceuticals? Maybe vitamin D is going to be part of that cocktail. That remains to be seen.

As an analogy, look what happened with HIV. With HIV, you had 3 pharmaceuticals, each with a very modest effect. But when you combine them, you have triple therapy, which works very, very well.

Now, let’s turn to Alzheimer’s, which is a more complicated illness. Let’s imagine that the cocktail requires 15-20 drugs rather than three and that none of those drugs by themselves have any statistically significant effect on the disease. If that is the case, then we currently do not have a way forward. After all, once something fails in scientific and/or clinical trials, we’re not going to be adding it to something that also has failed. How, then, are we going to find those 15-20 drugs or agents that work well together, and how are we going to convince the FDA to allow us to test them, and, ultimately, how are we going to convince patients that they are going to have to go through a whole program rather than take a single drug, which is what everyone wants.

Q: What are we now learning about the causes of Alzheimer’s disease ?

A: Genetics and genomics have taught us a lot about this. While we’ve recognized the importance of inflammation for years, there’s now increasing awareness of its role in Alzheimer’s and in the possibility that amyloid beta itself is part of the inflammatory response.

Having said that, you could look at Alzheimer’s as you would other chronic illnesses and see that this is really a network, and there are many ways to feed into this network. In other words, we can’t point to one single cause. So many things can contribute to the development of Alzheimer’s. Inflammation will be part of this. So will metabolism. And, of course, there’s the diabetes connection. All of these things are part of it. One of the interesting questions in the field is, why is it that there are so many different risk factors? If you didn’t go very far in school, if you had head trauma, if you had low levels of vitamin D, if you went through early menopause — you just go on and on and on. How do all these different and apparently disparate risk factors relate to what we call one disease, or what we should probably call one syndrome?

Q: What to you are the most exciting recent discoveries in Alzheimer’s research and how will they influence treatment?

A: There are a lot of interesting things going on. I think the discovery of the Iceland mutation (a gene that may protect against Alzheimer’s) is quite interesting, and the exciting part about it is that it not only seems to reduce risk for Alzheimer’s disease, but it also seems to reduce the risk for non-Alzheimer’s-related cognitive decline.

We’re entering an era now in which there is amyloid beta buildup without dementia and dementia without amyloid. That’s interesting. We used to say that amyloid and dementia go hand in hand, but we’re now seeing these barriers are not as clear as they once were. This is going to lead to new and interesting information about the role of amyloid in dementia, and I think it will help us going forward. Of course, most discoveries like this don’t simply stand on their own, but rather add to a literature that is very large, over 50,000 papers at this point.

I believe that this decade is going to be the most exciting decade for Alzheimer’s disease to date. I think you’re going to see some real changes, and I think you’re going to see changes in the next year or two — you’re going to see people get results that they haven’t before. This is an exciting time. This horrendous illness now affects over 5 million Americans and over 30 million globally and costs the U.S. alone over $ 200 billion a year, not to mention all the disruption to families and all the sadness. However, I think we’re going to see real movement in this area in an exciting direction in the near term.

Q: Where are we in terms of early diagnosis? How will earlier diagnoses impact treatment?

A: We’re getting earlier and earlier markers, with amyloid imaging and tau imaging [types of brain scans] and cerebrospinal fluid markers that have been flagged as abnormal in the 15 years or so before diagnosis.

The general population has also become much more aware. Alzheimer’s disease is in the zeitgeist now. Everybody hears about it every day. That helps. People notice when their memory’s not as good as it once was. They’re good about noticing their own early decline. And we want to foster the notion that you need to come in early and get checked out. You don’t want to wait.

We are working towards the point where if you come in early, your decline can actually be reversed, that you will actually see an improvement. That’s when I think people will really sit up and take notice. There’s nothing like getting an improvement in your health to give you the incentive to stick with a program, and I think we’re on the cusp of that.

Q: What about vaccines?

A: Multiple major trials and hundreds of millions of dollars have been poured into research on passive vaccines, which is the dominant approach. [With passive vaccination, antibodies against a particular condition are given directly to a person.] In the past, there were very significant side effects in trials of active vaccine, and so there has been less interest in these in recent years. Having said that, there is one active vaccine in development with an upcoming trial, and tau vaccine trials are also coming in the not-too-distant future. These may all end up being complementary approaches.

Q: Has recent research provided any useful insights for caregivers?

A: That’s a really good question, because we tend to forget about the caregivers . This is a huge issue. Caregivers are under severe stress, and they have stress-related illness at a higher frequency. In fact, being a caregiver is a risk factor for early demise. The first thing caregivers need to do is make sure that they are taking care of themselves as well. Don’t take too much on yourself, and find ways to relieve stress.

Caregivers might want to introduce music to their regimen. Music is something that brings joy to people, and it seems to improve the behavior and mood of Alzheimer’s patients, though it does not appear to improve their cognition. It can take people who seem lifeless and breathe life back into them. I think that when we have the ultimate cocktail I talked about earlier, however many parts it may have, music and joy are certainly going to be a part of it. That’s going to be important not only for the patient but also for the caregiver.

Malcolm Forbes said that the purpose of an education is to replace an empty mind with an open one. We’re all undergoing this educational process in Alzheimer’s disease. Learning about it is an ongoing process. I’m hoping that we all keep open minds, because that’s going to be an important factor in developing the ultimate treatments for this illness.

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