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The Relationship Between Infection and Alzheimer Disease Risk

In this video, Paul Schulz, MD, discusses the relationship between infection and Alzheimer disease risk and what health care practitioners can recommend to patients to reduce their risk for Alzheimer disease development. This is part two in a three-part series.

Additional resource:

  • Harris K, Ling Y, Bukhbinder AS, et al. The impact of routine vaccinations on Alzheimer's disease risk in persons 65 years and older: a claims-based cohort study using propensity score matching. J Alzheimer's Dis. 2023;95(2):703-718. doi:103233/JAD-221231. 

Watch part one of this three-part series here.

Watch part three of this three-part series here.


TRANSCRIPT: 

Paul Schulz, MD:My name is Dr Paul Schultz, and I'm a professor of neurology at the University of Texas Health Science Center in Houston.

C360: Could you briefly discuss what else is known on the relationship between infections and the risk of Alzheimer disease among older adults?

Dr Schulz: I see people every day. I get calls from my patients every day. "My husband got acutely worse today, did his Alzheimer get a lot worse?" And Alzheimer and all the other neurodegenerative diseases are slow. And over 6 months they'll say to me, yeah, he's doing this a little bit less. And then 6 months later, a little bit less of that. But when they call acutely, I know it's going to be an infection. Once in a while it's something else like a new medication that has a side effect. Yeah. So number one, to answer your question about infections, they tend to really aggravate the Alzheimer disease. Now, sometimes people get an infection and they get a lot worse, but 2 months later they get back to where they were. But a lot of times, honestly, they're not as good as they were 2 months prior. So there is a permanent effect of having turned on the white blood cells of the brain.

So in that case, we think that whether it's a pneumonia or a cough or a urinary tract infection, when they turn on the peripheral inflammatory cells, they actually seem to turn on the central ones. And so the guys in the brain start getting overly active. And since they're the ones that are killing brain cells, they actually seem to do that. Yeah, so step number one is that infections generally make things a lot worse. Now for Alzheimer, very interesting question is whether or not infections of the brain are relevant. And over the years, there have been a lot of findings that have made the suggestion that some infections may actually be in the brain.

If you look at someone postmortem, a little macabre to talk about. But when people pass away we often look in the brain to try to understand what's going on in their disease. In Alzheimer patients, it's very common to find bacteria and other remnants of infection. What's been really difficult to figure out though is whether those were present during life or whether when we pass away and we don't have an immune system, everything on our skin tries to go in and do nasty things. I don't want to be explicit about it. But the point is that there have been a lot of theories of direct infection of the brain precipitating Alzheimer, but it's been really tough to show that over the years. In the other direction, the fact that these vaccines are working leads to the question, is it effect of the vaccine on the immune system, turning it off for example, or does the flu vaccine prevent the flu and the flu makes Alzheimer worse? So maybe what we're doing is we're just preventing infections. And that's certainly possible

Because all of those four infections that we mentioned, for which we've shown the vaccinations are helpful, they do prevent disease and that's why we get them.

C360: In addition to routine vaccinations, what other medical or lifestyle measures might health care practitioners recommend to their older adult patients for reducing their risk of Alzheimer disease?

Dr Schulz: Everybody asks that of me in clinic every day, even if I tell them they're normal, then the question is, "okay, if I'm normal and don't need Alzheimer treatment, what can I do to prevent it?" And it's a wise thing to pursue. So it turns out that there are many, many studies of this, and they all have findings between a 20% and 80% reduction in the risk of Alzheimer. So quite significant. So I think most of us in the field quote a figure of you can reduce the risk of Alzheimer about 50% with lifestyle changes. 50% being a number in the middle we can all agree on; okay, it's a little less than the 80% this person thought, a little more than the 20% this one thought. But since there is that broad range there, we can kind of all agree on 50%.

Well, 50% is huge. For a disease that we can't cure yet, reducing someone's risk 50% is really a big deal. And it turns out it's a lot of the things that you know as cardiovascular risk factors. So we and others have papers for example, showing that if we lower our cholesterol, lower our blood sugar lower, our triglycerides, lower our blood pressure, all of those things have a significant impact on reducing the risk of Alzheimer's disease. It turns out one of the most efficacious ways to reduce the risk is actually physical exercise. Believe it or not, it's our most effective tool. And there's a lot of reasons for that. Probably we don't understand all of 'em, but it does increase blood flow to the brain a lot. It may literally clear the plaques out, we don't know. But it also increases growth factors and other things that could have a positive effect.

The other thing, there's a couple more risk factors that are a little less direct. For example, if someone smokes, I tell 'em to stop smoking. That's a big risk factor for dementia. It doubles or triples the risk of dementia. Also, getting bumped on the head is a big precipitant for Alzheimer. If it's something you got when you were young, it could actually be causal. But if you were going to get Alzheimer 5 years from now and you're in a car accident today or a bike accident and hit your head, you could start getting the symptoms next month. So wearing a helmet, in the car wearing your seatbelt, wearing a helmet when you're skiing, everything to prevent getting bumped on the head is really valuable.

Dr Schulz: There's another couple of things that we've shown over the years, and one of them is PTSD which obviously is very common in veterans and other people that have been exposed to a big trauma.

It looks like PTSD; we have a paper and another group has a paper showing that that increases the risk of Alzheimer 2.3 times. So if your risk was X, it's more than double that If you have PTSD. So we suggest treating PTSD and there's also data not of ours, but of other people that major depressive disorder if untreated is a risk for Alzheimer's. So we recommend getting treated for those things. We don't know if treating them prevents the risk, but certainly it makes sense that it would. So all of those things are factors that we've discovered.

There's one more that we can't quite recommend as a prevention, but it seems to be. There's about 30 epidemiologic studies already showing that if you take nonsteroidals at any point in your life for a year or more, it significantly reduces or it's associated with a reduction in the risk of Alzheimer. People who take them for a year or more often have another disease. So technically we don't know if it's the rheumatoid arthritis that reduces the risk of Alzheimer or if it's the nonsteroidal that someone takes for their rheumatoid arthritis that reduce the risk. But a lot of us neurologists take nonsteroidals thinking there's a chance that it's not the rheumatoid arthritis that's preventive, but actually the nonsteroidal. Every nonsteroidal that's been tested for a year or longer has had the same effect. So I think it's probably a real effect. And of course it's for different diseases. The chance of all of them reducing the risk of Alzheimer's seems slim. So anyway, if you have a reason to take a nonsteroidal, don't take it if you don't because there are side effects of them. But if you have a reason like arthritis or I'm a jogger and I constantly pull muscles and I'm sore so I take nonsteroidals a lot. If there's a reason to take it, take it because that could be another reducing factor.

So there's about 10 or more risk factors that you can reduce through lifestyle and other related things, taking medications prophylactically, that we recommend to people to reduce the risk of Alzheimer. Again, about 50% or more.


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