Prevention Trials in Alzheimer’s Disease


Dr Eric McDade shares information on different types of prevention trials to manage Alzheimer’s disease.

Marwan Sabbagh, MD: To move into the last part of our conversation, there are a lot of prevention trials, and you’re doing some of those prevention trials. Can you give us an update on some of those?

Eric McDade, DO: Yes, so the prevention space has expanded dramatically in Alzheimer disease over the past decade. Again, the reason being primarily that we see this as a chronic disorder that evolves over a 2-decade period of time. These prevention studies have been focusing on the typical, sporadic Alzheimer disease, the most common forms, as well as the genetic forms, which allow more of a precision approach as far as where you want to intervene for prevention. Then they’re broadly categorized as secondary prevention, meaning they’re defined by amyloid pathology, so people who have amyloid pathology already but don’t have clinical symptoms. So starting and randomizing at that stage of the disease. Or primary prevention, which is a study I’m leading, about to start.

There’s another study with lecanemab that’s getting close to primary prevention. What that means is that you have a high-risk population, in our case, genetic population. And you’re intervening before amyloid pathology develops, and you’re seeing if you can use these therapies that target amyloid and prevent that whole cascade from unfolding. It’s an exciting time. The first 2 prevention studies in the genetic forms of the disease unfortunately were disappointing in the results, using gantenerumab and solanezumab, as well as crenezumab, so 3 different therapies. But they have led to refinements of how we’re either going earlier, or doing things like determining what are the best drugs to use, what dose should we be using, and how long should we be using these. This is the next frontier when we think about Alzheimer disease as a chronic disease, and how we approach chronic disease from a broader health perspective. This is targeting them pharmacologically. Then there are ongoing lifestyle-modifying trials as well that are using multimodal lifestyle approaches to see if you can prevent cognitive impairment in those at risk.

Sharon Cohen, MD, FRCPC: If I could add that at this conference, Miia Kivipelto, [MD, PhD,] who is the queen of lifestyle strategies and has done an amazing job mobilizing countries around the world to look at this, is very importantly now moving to multimodal lifestyle intervention plus drug therapy as a reasonable way to tackle Alzheimer disease. That it’s going to take more than lifestyle, but lifestyle is important. And is it going to be lecanemab, or now that we’re starting to have success in pharmacotherapeutics, it will make it easier to have these combination therapy trials and hopefully better prevention options.


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