The challenge of testing new Alzheimer’s drugs

We Alzheimer’s disease specialists get a lot of free advice. One of the most common recommendations is that we should work on a way to prevent Alzheimer’s in healthy people rather than try to fix people who already have brain damage. As I pointed out in my last blog post, all of our latest research results also point toward prevention as a more plausible goal, and our free advisors ask us: What took you so long?

Here is the scenario: If I had a drug that I was sure would work, I could design a study where one group of people got the drug and a second, similar group of people took a placebo. The proof that the drug worked would be a lower rate of Alzheimer’s in the drug-treated group compared to the placebo-treated group. So let’s say after two years we take a look to see how the treatment is doing. The likelihood, even with a study population over the age of 70, is that the incidence of Alzheimer’s disease will be very low in the placebo group, so that it will be impossible to detect any benefit in the active group. Two options for getting an answer about the drug are to increase the number of study subjects or to increase the duration of the study. Generally speaking, it will take 4,000 subjects treated for five years at a cost of many millions of dollars to get an answer about one drug. And if the answer is “no,” then we  start all over again, five to 10 years later.

The other way to find out if a prevention drug is working is to start with study subjects who are known to be at high risk for developing dementia. That way, the placebo group’s rate of new dementia will be high enough to have a chance of detecting a treatment effect of the drug.

One indicator of increased risk is a memory impairment that is more severe than average (but not as severe as that in dementia, since we are still aiming for prevention). The term now used for people in the category is “mild cognitive impairment”, or “MCI”, and at first we thought we could test prevention strategies in this population.

Unfortunately, the Alzheimer’s rates were still too low in the first several MCI studies, so the research community has worked to identify “biomarkers” that might be used as risk indicators and as a criteria for participation in prevention studies. The most common practice now is to restrict participation in prevention studies to people who initially qualify as having MCI based on memory testing, and then also qualify as “high risk MCI” on the basis of biomarker testing.  The biomarker may be a gene, a brain scan, or test of spinal fluid. At present, the last version is the most practical, even though it involves having a spinal tap.

We are now recruiting for several studies for the prevention of Alzheimer’s disease, with each study taking a slightly different approach to recruiting people who are at increased risk of developing Alzheimer’s.

Joseph Quinn, M.D.
Professor of Neurology
Layton Aging & Alzheimer’s Disease Center
OHSU Brain Institute

2 responses to “The challenge of testing new Alzheimer’s drugs

  1. My sister is worried about her cognition but has not yet been tested. Where (physically) is your study located?

    Thanks you.

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