Early memory problems may indicate Alzheimer’s

By: www.ALZinfo.org

In the January 11, 2010 issue of the journal Alzheimer’s and Dementia, Dr. Barry Reisberg and his research team published research showing a significantly higher risk of dementia and Alzheimer’s in people who have experienced subjective memory loss. This condition, called subjective cognitive impairment (SCI), typically occurs in people age 65 and older.

Dr. Reisberg is the director of the Fisher Alzheimer’s Disease Education and Resources Program at New York University Langone Medical Center, and is a professor of psychiatry there. He is also the director of the clinical core at the NYU Alzheimer’s Disease Center.

Preserving Your Memory
magazine spoke with Dr. Reisberg about his team’s findings and what this means for the future of Alzheimer’s research, as well as the importance of these findings for patients and caregivers now.

Preserving Your Memory: What is “subjective cognitive impairment”? Also, how is “mild cognitive impairment” best understood?

Dr. Barry Reisberg: We define subjective cognitive impairment (SCI) as when a person believes that their thinking abilities, including memory, are not as good as they were 5 to 10 years before. It’s a change people notice in themselves, without being told by others. It’s a personal conviction that they see as a problem. The most common complaints are due to memory issues.

Mild cognitive impairment (MCI) is the point at which others begin to recognize that something’s going on with a person’s memory or cognitive functions. It could be from a clinical interview that a doctor could detect deficits, or co-workers could notice a change in performance. These changes become evident from different perspectives.

The next line along the path to Alzheimer’s is “mild dementia,” which is a general deficit that interferes with complex daily activity—things like handling personal finances, paying bills on time, correctly filling out personal documents, etc. That’s the key identifier at this level.

Preserving Your Memory: What do your new findings mean in terms of detecting and diagnosing Alzheimer’s disease and other forms of dementia?

Dr. Barry Reisberg: There are a few things to point out here. I should mention that we’re speaking of SCI, and this phenomenon has already been recognized under various names. Surveys indicate that a big proportion of people—from 25 to 50%—over the age of 65 have SCI symptoms. Classically, these people come to us because they’re convinced they have a problem, and they’re concerned.

So we’ve been studying this entity for a long time. The whole world has had this question, whether these symptoms of early memory loss are truly meaningful. There are various ways to answer that, but the best way is to follow these people and see what happens to them. The study I published was a longitudinal study of people who came to us with these complaints, and we compared them to people who did not have these complaints. We controlled for age, follow-up time, etc. The people who did not have these complaints were a bit younger, typically. Without age control considered, we found that among people who did not have subjective complaints, only 15% went on to MCI or worse after 7 years. But among those who did have complaints, 55% went onto MCI or worse over 7 years.

When we controlled over individual follow-up time and age and some other demographic features, we found that the risk of decline was 4 ½ times as great for people who have SCI. What this means for us, taken with all the data we’ve compiled thus far in other studies, is this: People who did not have SCI, but went on to develop cognitive decline took an average of 3½ years longer to decline than those with SCI.

This study is different in another way. All studies that have been done in this area used much shorter follow-up times, and they also used dementia as an outcome criterion. This study used our definition of MCI and looked at it with a 7-year view, and with that outcome we’re able to see the meaning of the SCI condition. That stage lasts 7 years, as we’ve shown, so it’s a long time before dementia. So you have to follow people for a long time, and if you use dementia as a criterion, you need to use a longer time frame.

MCI is a term I originally defined and is well understood now. Other work we’ve published shows that this stage of MCI lasts about 15 years, and this study confirms that. So, 22 years before mild dementia, you have SCI. It’s a benign condition, depending on one’s age and other risk factors. But it provides an opportunity for us to address the problem when it may be relatively easier to treat.

Our work shows that when Alzheimer’s disease (AD) develops, it does so in certain areas of the brain, and in those areas it continues to progress in nerve cell loss in a linear, continuous fashion in a given region of the brain, such as the hippocampus. At the same time, it spreads outward into other areas of the brain.

In many ways, AD, as it evolves, is like a fire. If you have a little fire, a match, then it’s in an isolated location, and if you pour some water on it the fire is gone. But if you have a forest fire, it spreads outward in all directions, and that cup of water has no effect. It’s the same thing—a chemical reaction— just as AD is a chemical reaction in the body. We think that by catching it early, we can better identify treatments and change the trajectory of the disease, hopefully to the extent that we can prevent it.

This is a very long stage, so it helps that we can identify the trajectory earlier. Even small, significant differences on tests can give us a handle, albeit a small one. We need a bigger handle in order to look at treatment, and that will be one area of focus in the future.

Along with this, we’ve been looking at brain metabolism via PET scans. I did the first PET scans of AD patients in 1979, and we showed a decreased metabolism in the brain in the paper we published in 1980. Now we know that people with SCI have significantly lower metabolism in these areas of the brain than do those who do not have that condition. So we now have markers for this condition at the early SCI stage, an 18 percent decrease from no cognitive impairment at all (NCI). With these markers, we can now try to develop treatments to address these earlier symptoms.

There are a lot of studies showing that in the memory region of the brain, a big proportion of people of around age 65 have these tangles, according to neuropathological studies. So these changes we now know are beginning very early, before the SCI stage. There are other examples of changes occurring early, too, that seem to be a harbinger of the process of AD. Right now, this is the earliest clinical stage we can identify.

It’s like a fulcrum: If you can treat it as its origin, you can have a big effect in terms of the disease’s progress.

Source: www.ALZinfo.org. Preserving Your Memory: The Magazine of Health and Hope; Spring 2010.