Current Series: Advances Treatment Alzheimers Disease

Jeffrey L. Cummings, MD, ScD: Richard, I’d like to have you discuss brain health strategies that could be integrated into a diagnostic and therapeutic approach to Alzheimer disease.

Richard Isaacson, MD: Before answering this, first of all it’s tremendous that we can now start talking about brain health and how to integrate it into an Alzheimer disease plan. I think first it’s important to understand the spectrum of Alzheimer disease. So Alzheimer disease dementia is when a person has developed cognitive impairment, specifically memory as well as other domains, where someone can no longer take care of themselves and thus they qualify for Alzheimer disease dementia. Mild cognitive impairment is predementia stage where mild symptoms are occurring, but they can still take care of themselves.

Now rather than treating Alzheimer disease dementia, it’s more preventing or trying to reduce risk of progressing to Alzheimer disease dementia. That would be called tertiary prevention. Secondary prevention of Alzheimer disease is when someone has amyloid in the brain but no symptoms. So that would be a construct called the preclinical Alzheimer disease, or secondary prevention. And in primary prevention it’s a little murkier, but it’s maybe where we need to go at some point, and that’s primary prevention of Alzheimer disease as a pathophysiologic feature.

The terminology here is confusing. But brain health strategies may be preferentially effective, or less effective, depending on where a person is in the spectrum. So when it comes to lifestyle changes—a Mediterranean style diet, exercise on a regular basis, cognitive engagement and cognitive training—some of these interventions were preferential much earlier in the spectrum. But when someone has Alzheimer disease dementia, for example, moderate to severe or even mild to moderate, there are even studies that show more rigorous exercise on a regular basis leads to poorer outcomes.

So I think sometimes this stuff is a little bit unclear, but integrating aspects of physical activity, cognitive training, Mediterranean style diet, music therapy and music activities, the list goes on and on, I think every person with Alzheimer disease needs to think about nonpharmacological approaches as much as pharmacological approaches. And I think the evidence for these approaches is evolving rapidly.

Jeffrey L. Cummings, MD, ScD: Very good. Anybody else have a strategy for brain health in their practice?

Marwan Sabbagh, MD: I’ve heard some statistic recently that up to a third of cognitive impairment or dementia could be delayed, postponed, or prevented with lifestyle intervention. This is an area of tremendously rapidly growing interest. We’ll prove it over time, but it is of great interest.

Alireza Atri, MD, PhD: Yes, and actually I believe the data, the level of evidence, need to be supported more. But it does make sense. Some of it may be directly involving the disease mechanisms, but other ones are just improving your brain reserve. And so I encourage people to read The Lancet commission paper from 2017, read the evidence for themselves.

I talk a lot about lifestyle changes as a part of what individuals can do who are symptomatic who have let’s say mild Alzheimer disease. Regarding the benefits, I think it’s the sweet spot, “how much?” If you say over-rigorous exercise, if they’re overdoing it and they’re dehydrated all the time or they’re getting rhabdomyolysis or something, that’s a different story. But there are tremendous benefits for sleep and mood, and I don’t know what it is, but I think we’ll know eventually how this combination of the medicines we have and lifestyle changes are going to be beneficial and be synergistic to individuals.