The introduction is done by Dr. Steven Flanagan, Chairperson of the Department of Rehabilitation at NYU Langone Health. His remarks ended at the 2 minute: 24 second mark.
Dr. Darryl Kaelin is the Endowed Chair of Stroke and Brain Injury Rehabilitation at the University of Louisville. In this Grand Rounds session, he speaks about Traumatic Brain Injury and its Association with Neurodegenerative Disorders.
Part 2
Repetitive mild brain injuries also can result in the same kinds of findings. So, it is not just moderate to severe, but repetitive mild injuries that increase the risk. Although there may not be a direct causal relationship, certainly having a brain injury, multiple mild brain injuries or a moderate to severe brain injury increases the risk of developing neurodegenerative processes like Alzheimer’s and Parkinson’s. He tells his patients that the likelihood of developing a neurodegenerative process may be there, but in each individual it can be different. We don’t know specifically what it might mean for you. On average the risk may go up, but it still is very small. He talked about some potential neuro-protective treatments that might exist out there or are in the process of being looked at. He stated that this patient population is heavily heterogeneous, especially in how it presents and responds to trauma. Additionally, patients in the U.S. don’t all receive exactly the same treatment after their trauma, which is a confounding variable that results in a very different outcome for each of those kinds of patients. Nutrition is a highly important factor when it comes to recovery and outcomes. Parenteral nutrition goes a long way in helping their outcomes. It also is important to keep an eye on vitamin and mineral levels. Zinc is a key supplement for many patients and magnesium can help in recovery. He closed by describing a disorders of consciousness program at his institution called the Emerge Program.
A Question &Answer period followed.
[MUSIC] >> Welcome to Rusk Insights on Rehabilitation Medicine, a top podcast featuring interviews with thought leaders in the field of PM and R from Rusk Rehabilitation at NYU Langone Medical Center and other prominent rehab medicine institutions. Your host for these interviews is Dr. Tom Elwood. He will take you behind the scenes to look at what is transpiring in the exciting world of rehabilitation research and clinical services through the eyes of those involved in making dynamic breakthroughs in healthcare. So listen, learn, and enjoy. [MUSIC] >> Hello, and welcome back to part two of a presentation by Dr. Darryl Kailen in the Rusk Rehabilitation Institute podcast series. He concluded part one of his presentation by discussing how moderate to severe brain injuries increase the risk of developing Alzheimer's disease. In part two, he discussed how having a brain injury, multiple mild brain injuries are a moderate to severe brain injury, increases the risk of developing neurodegenerative processes like Alzheimer's and Parkinson's. >> So we're talking about instead of maybe having a 2% chance of having developing Alzheimer's dementia in your life, you might have a 6% chance. So it's still a small number, even though it's three times the likelihood. Repetitive mild brain injuries also can result in these same kinds of findings. So it's not just a moderate and severe, but sometimes repetitive miles that increase the risk. And brain injury is an additional risk factor for Parkinson's disease as well. And it typically brain injury lowers the age of onset, a potential neurocognitive degeneration as well. So we'll talk about that next. So a study that was published in 2019 of the Journal of Neurotrauma showed that there were 68 studies that were identified looking at brain injury or risk factor for dementia and Alzheimer's. This was a study that had some weakness in that many of these patients were self-identified as having a brain injury. So they would have said something to the fact of, yeah, I had a head injury when I fell out of a tree, when I was 12, or I was in a car accident a few years ago and had a bad concussion, that would have identified them as having had a brain injury as opposed to having a medical diagnosis that was made in the medical literature or in the electronic record, I should say. 55% had a poor definition of brain injury. 86 had a risk of reverse causality, meaning that instead of saying you had Alzheimer's, did you have a brain injury? They said you have a brain injury, now do you have Alzheimer's? And then there was also in many of these studies poor, controlled, confounding variables. So these were not the best studies, they weren't great studies. But when you have 68 of them and you pull all the data together, you start to see some ideas and trends. And so the association of brain injury with subsequent neurologic and psychiatric disease has also been looked at in a meta-analysis. And what it basically showed in reviewing studies from '95 to 2012 and narrowing it down to the 57 best studies based on their criteria is that the odds ratio for mild brain injury developing Alzheimer's type dementia was about 1.4. The odds ratio of getting mild cognitive impairment was quite a bit higher, almost twice as high, 2.69. And then the odds ratio of mild brain injury getting Parkinson's disease was about 1.45. So definitely an increased risk. Although again we're talking about relatively small numbers. And so this study focused primarily on Parkinson's disease and the effects of neural trauma on the development of that. And this was done in a VA population with mild brain injury versus age match controlled vets without mild brain injury. And they looked at a very large number, as you can see here, 325,000 in the comparison groups. And the incidence of Parkinson's disease without brain injury was 0.3 with mild brain injury 0.47 and with moderate to severe brain injury 0.75. So you got basically two to two and a half times more likely to develop Parkinson's with a moderate to severe brain injury and about one and a half times more likely if you developed, if you had a mild brain injury. And so the hazard ratio is Parkinson's disease with mild brain injury coming out to about 1.56 and it was for severe brain injury about 1.8. So again, we're starting to mount evidence here that suggests that although there may not be a direct causal relationship, certainly having a brain injury, multiple mild brain injuries or a moderate to severe brain injury does increase your risk of developing neurodegenerative processes like Alzheimer's and like Parkinson's. And then was mentioned at the age of dementia onset after brain injury has been looked at and this was studied and published by Schafford at all in neuropsychology in 2018. And this was done in 2133 autopsy confirmed Alzheimer's participants. And there was a self-reported brain injury with loss of consciousness and at least a year or more before the diagnosis of Alzheimer's. And so both the onset and the diagnosis were 3.6 years earlier in the brain injury group than in the non-traumatic brain injury group. Or I should say in the non-brain injury group. And so certainly this is starting to suggest that maybe some of these chronic neuroinflammatory processes do contribute to the development and degeneration of the central nervous system at a faster rate than have they not experienced it. And then of course the age of onset of Alzheimer's with brain injury versus APOE4 has been looked at. This was published in clinical neuropsychology in 2017. And this was a pretty large study using the national Alzheimer's coordinating centers. It looked over 7,600 patients. And again, self-reported brain injury with loss of consciousness was looked at. This is always a little concerning because people's recollections and accuracy are not always good. And then these patients were lab tested for the presence of the APOE4 allele. And the brain injury group had a 2.5 year earlier onset of Alzheimer's disease, which was statistically significant. And the APOE4 opposite group had a 2.3 earlier age of onset. So if you have an APOE4, if you're going to develop Alzheimer's, you're likely to develop it a little bit earlier. If you've had a brain injury and you're going to develop Alzheimer's, you're likely to develop it a little bit earlier. And so both brain injury and APOE4 together actually resulted in an even earlier onset. So together, APOE4, brain injury versus brain injury alone, was 2.8 years earlier, versus APOE4 alone, was 2.7 years earlier. So if you have both an APOE4 and a brain injury, you're going to develop the Alzheimer's even earlier than if you just had either of those by themselves. So starts to give us an idea of the likelihood of somebody is developing this. And in the time frame that we might want to be keeping an eye out for this, right? These studies are particularly valuable both from a clinical perspective, but also as we enter into the legal world, we're seeing more and more attorneys now asking these kinds of questions. And historically, we've just not been able to give them very good answers about it. Now we're starting to see evidence that supports that maybe we can give them some reasonable answers as to the likelihood that something's going to occur. And then the onset of dementia was looked at in post-9/11 vets. These are soldiers coming back from OIFOEF. And the rates of vets and non-vets greater than 65 who develop Alzheimer's disease are about the same. So vets over 65 versus non-vets over 65, the development of Alzheimer's is approximately the same. But in looking at those who had early onset dementia, a total of 689, and this whole study, there were 689 that had early onset dementia, 284 who developed frontal temporal dementia. That age, gender, race match controls, without early onset dementia or frontal dementia, there was comparison there. And the odds ratio of developing early onset dementia with brain injury was about three times and that of developing absolutely, epilepsy, almost five times, where the increased severity of brain injury increased the risk of early onset dementia. So in summary, that's with verified brain injuries who are about three times more likely to develop early onset dementia or frontal temporal dementia than their age match controls. Now, that sounds like a lot. But again, we're talking about a relatively small number. And so I think this is the key factor of all these things. It's twice as likely does not mean more likely than not. And for those who are not familiar with legal terms, we're generally asked as physicians to speak in terms of medical certainty or feel medically very confident this is more likely to happen than not. So 50% or more in this case. So if a person doubles their chances of getting Alzheimer's disease, it may only go from 3% to 6% if they've had a moderate severe brain injury. But it still means they're very unlikely to develop it. So there's not a 50% chance of developing Alzheimer's. It's still only up maybe 6% or 7%. But it may be two or three times more than what it would have been have they not developed before. So just an important thing to remember, less important probably for the legal terms that you may get involved in. But more important for the patient to understand that you don't want to scare them with these terminologies of three times more likely or five times more likely when you're really talking about a very small percentage anyway. So what I typically am telling my patients is, yes, the likelihood of developing a neurodegenerative process may be there. In each individual, it can be different. We don't know specifically what it might be for you. But on average, it may go up, but it's still very small. So don't sit around every day wondering, is today the day I develop Alzheimer's or is today the day I want to develop Parkinson's? Because that day may never come. And it's important for patients to not sit around and worry about those kind of things when the risk remains small. Now for some patients, they may say, well, I want to do everything I can to reduce those risks, and they also want to know, you know, are my risk higher because I have those genetic predispositions. And in those cases, you could certainly test them and have those things looked at. But what we'll get into here in the next couple of minutes is talking a little bit about some of the potential neuroprotective treatments that might exist out there or that are in the process of being looked at. So that when patients ask about what they can do, you can give them some education around that process. So we talked earlier about this AQP4 gene and how it has an impact on lymphatics and drainage and the moving of extracellular neurotoxins into the CSF. So what we know is if you silence that gene, then you get alleviation and improvement of brain edema, improvements in neurologic deficits, reduction in neuronal apoptosis, and inhibited astrocyte activation. And so all of those things ultimately lead to some improvement. So these AQP4 minus mice, the ones that have had that affected show less neural inflammation, better blood brain barrier integrity, and better amyloid beta clearance, therefore they end up with better cognitive and functional outcomes. Now, of course, this is mouse studies, not human studies. But since we know that the pathway is very similar, it certainly might make sense that things that we can do to help lymphatics or to reduce neural inflammation might ultimately result in a better outcome. So we ourselves, in the process of trying to recover, produce what we call neurosteroids, right? So neuroinflammation is a normal protective response to an infection or an injury. But if it's left chronic in nature, can ultimately not drive neurodegeneration. So the CSF in itself is highly steroidogenic, meaning it's actually will produce its own endogenous steroids in order to help reduce inflammation and improve function and outcome. And so what we know is that this process is substantially affected and reduced in people who have chronic neural inflammation. So we want to really try to reduce those inflammatory responses from becoming chronic so that we don't end up having some of these long-term complications and problems. And so ultimately, the development of neurosteroids starts with a transfer of cholesterol into the mitochondria. Steroidal genesis takes place in the neurons and in the glia. Even astrocytes produce things like pregnant alone, regesterone, DHEA, androstendyndione, testosterone, estradiol, estranone. So all of these precursors to the steroids that we're aware of are being produced and are available within our cell structures of the brain. So this tells us that the brain is accustomed to having to fend off against infection and against trauma. And in doing so, it has been able to produce its own endogenous steroids. What we do know from historical research is that animal studies and even some human studies have shown that female animals have done better as far as responding and recovering from brain injury because of what is assumed to be their estrogen and compared to male counterparts. A study that was also looked at progesterone a number of years ago that I was fortunate enough to be very involved in down at Emory, where Dr. Wright and some of his partners down at Emory were looking at progesterone. And in an early single site study, they showed a significant improvement in individuals who were given progesterone at the time of trauma within the first 24 hours. There was an improvement in those who lived in an improvement in the function of those who were given the steroid over not, or the progesterone in this case over not. Unfortunately, they got a much larger NIH grant. They had a multi-center study and that study was stopped about halfway through because it didn't show to have any improvement in outcome. So this always speaks to something I think it's important for a rehab population to understand, especially as it relates to brain injury, spinal cord injury, and things of that nature. This population is very heterogeneous, especially in how it presents and how it responds to their trauma. And in addition to that, patients in America don't all receive exactly the same treatment after their trauma. So if you go into a major trauma center in Atlanta, New York, Chicago, where you're going after you've left the trauma center is not necessarily going to be the same for all patients, right? Not all patients in Chicago go to Shirley Ryan. Not all patients in New York get to go to Rusk. And so when you have patients that are going home, patients that are going to nursing homes, patients that are going to acute rehab, are going to multiple levels of different post-acute services, LTCH, et cetera, then that in itself is a confounding variable that results in a very different kind of outcome for each of those kinds of patients. And so I think that was a big weakness of this study because we were the receivers of many of these patients and we felt like our patients got very good outcomes of course we're biased in that we're seeing only the ones that were able to get to us at Shepherd Center and we were providing them with a very high level of rehabilitative care for a long period of time, often one to two months as opposed to two or three weeks that you might get in other centers, et cetera. And so I think that if they were able to stabilize the post-acute care that these patients received, they might actually see that the intervention was more favorable than what it looked like initially. Of course, nutrition is a very important factor and I think anybody who works in the rehabilitation environment understands that when we have patients that come to us that have low pre-albumin levels, low vitamin D levels, low vitamin C levels sometimes, that nutrition is a big, big factor when it comes to recovery and outcome. And so multi-center cohort study published in 2012 found that patients receiving enteral nutrition within 48 hours of injury had better survival rates and approved Glasgow coma scores. Other studies recommended an increased caloric intake with anywhere from one to one and a half grams per kilogram of protein for the first two weeks post-injury. So certainly we see many of our patients unfortunately missing out on good nutrition in the first several days after injury. So just be very watchful and very encouraging of trying to get parental nutrition into these patients. It really goes a long way to helping their outcomes. Brain injury patients who were malnourished at the time of admission exhibited lower albumin and pre-albumin levels were correlated with poor neurological outcomes. So it doesn't take a lot to understand that a well-fed person with good nutrition is going to do better than those that aren't. Dietary supplements, we have a number of them that are listed here in bold won't go into great detail on these you can read through the examples here. But each of these has what we think are some potentially beneficial effects at either reducing inflammation, improving blood, brain barrier, integrity, reducing oxidative stress and inflammation. All of these kinds of things could be potentially helpful. So looking at you know, increasing intake of leafy green vegetables, looking at increasing the intake of grapes and berries and things of that nature obviously could have a beneficial effect and we all have seen and studied curcumin for a long time and it does seem to have a very nice anti-inflammatory effect that is seen both in the neuro as well as the musculoskeletal population. The course is important to note that we need to keep an eye on vitamin and mineral levels. We check vitamin D levels in all of our patients when they're admitted to Fraser and I would say 50% or more of them are low, especially in the wintertime. So very important to keep an eye on that and zinc obviously is also very important as a supplement that's been shown to reduce inflammation, apoptosis, autophagy, etc. So we don't put all of our patients on zinc but certainly I think it's not a bad idea especially if you see some early depression or mood issues maybe check zinc levels or at least put a person on a short-term supplement of zinc would not be harmful. Magnesium has also been shown to improve recovery from brain injury and free clinical models, mouse and other animal models and so again not something that I think we're using here regularly at Fraser but it doesn't seem to cause much harm and as long as you're keeping an eye on magnesium levels could potentially be helpful. And then of course we always talk about doing things to reduce inflammation right and of course inflammation or the inflammation process is the cyclooxygenase system and how do we go about inhibiting that and which things that we use are safe toward that or not safe whether we want to use a Cox2 inhibitor like Celebrex that's currently on the market things of that nature to reduce inflammation certainly could be potentially helpful. Study looking at car profen and anti-inflammatory drug also improve brain injury outcome and lesion size and rodent studies. So there may come a time where there's a quote "brain injury cocktail" that we're giving people that ultimately helps to reduce neural inflammation improve their nutritional outcomes and ultimately hopefully reduce cell death and improve their recovery. And as we mentioned earlier omega-3 fatty acids are being studied pretty regularly there are individuals throughout the country who really are pushing these hard as being kind of the the savior for brain injury. I'm not convinced of it yet but I certainly have had patients take them. I don't think they're harmful. I think in some cases patients feel better whether that's a placebo effect or not. I'm not sure but again it may find its way into that neurotropic soup or that brain injury cocktail in the early phases of brain injury in the first few weeks and probably wouldn't be harmful if it happened. Of course anybody who's spent any time rotating on a brain injury rotation or spending time working with brain injury patients knows that sleep/wake cycle is very important. Melatonin has its role. It's not always effective for everybody but making sure that people are getting adequate sleep. Melatonin can be an effective way of helping with that. Colleen has been looked at in some large studies and unfortunately did not show to be create much of a difference as far as those are concerned. But again I think that study may have also been affected by the variability and post-acute care and where patients went when they were discharged. So I think there were some problems with that study as it was created. Almost every study that's been used to look at what we call laseroids, drugs that help bring people back from the dead or back from severe brain injury have almost all been found to be negative studies primarily because of two factors. One is they're too precise in where they work in a biochemical system and so dirtier drugs things like progesterone that work in many places might be better but beyond that managing the confounding variables of post-acute care also are very difficult and so I think once those can can be better controlled for we can have better studies. And so here you can see another one looking at a flavonoid in pine bark extract that may have some beneficial effects in reducing their own inflammation won't go into too much detail there. So hopefully what we've accomplished today in this last 45-48 minutes is to kind of give you a little bit of an idea of what is the process that goes into secondary brain injury insult. You know the ischemia, the edema, the development of scar tissue and ultimately whether that neural inflammation goes through a normal process and stops or whether that neural inflammation persist and if it persists is it causing ongoing damage. Secondarily looking at the pathophysiology between neurodegenerative disorders like Alzheimer's and Parkinson's and having a better understanding of how they are similar in many ways to what happens in brain injury and how the initial insult of brain injury can lead to neuroinflammation and inflammatory responses and immunologic responses that ultimately can lead to the problems that create Alzheimer's and Parkinson's. And then also looking at what those correlations are, right? Not necessarily causality but risk in saying that yes there probably isn't increased risk of developing neurodegenerative processes like Alzheimer's and Parkinson's if you've had a moderate to severe brain injury or maybe even multiple mild brain injuries but that risk still remains very small and so really it's more important to see what we can do to prevent the ongoing neuroinflammation and ultimately try to come out with a better outcome. As mentioned earlier and I'll say this as an aside note we're not quite in the publishable stage yet but we are looking at the data. We have a Disorders of Consciousness program here in Louisville we call the Emerge program and historically over my career these Disorders of Consciousness programs have popped up around the country. There are many good ones you may have one there at Rasker in New York. There are some that are kind of average or not as good and so typically we would say an average program has an emergence rate of a person going from a Rancio 3 minimally responsive state to a more responsive Rancio 4, 5 level of about 50 or 60 percent. A really good program may have about a 70 or 75 percent emergence rate. We've been fortunate here at our program called the Emerge program of having about an 85 to 90 percent rate and so we do not handpick our patients we take young and old multiple kinds of insurances. We do require that all of our patients have family members that have agreed to take them home even if they don't get better because obviously our program can't stay alive and well if we're sending all of our patients to long-term care facilities after discharge insurances eventually going to give up on our program. But one of the things that we've done that's very unique is that we have a very close relationship with our neurosurgery department and with our trauma center which is just two blocks from our rehab hospital and in doing that we have trained our neurosurgeons to start a mantidine in the ICU setting with our brain injury patients and our severe neurologic impaired patients and we believe that that has resulted in some component of the improvement that we're seeing. Our program is a very good program but I wouldn't say that we're doing anything dramatically different here than I did in Atlanta or I did in Indianapolis but our outcomes are clearly better. Now is it because I'm smarter or I'm using new drugs that I didn't use before? Maybe but I honestly think is that because we're getting a drug that reduces neural inflammation and has NMDA receptor antagonism and dopamine agonism like an amantidine early on in the patient's recovery I think is resulting in a reduction in cell death, a reduction in neural inflammation and ultimately maybe a better outcome. So just we'll leave you with that and I'll open up things for questions if anybody has it. Thanks Daryl, great overview of neurodegenerative conditions associated with traumatic brain injury. Really appreciate that and you know I would reiterate the you know the trouble with existing studies looking at neurodegeneration at the traumatic brain injury or just you know they have so many flaws you mentioned you know the reverse causality you know that folks have you know early onset neurodegenerative conditions, fall had a brain injury and then blamed the you know what was already a pre-existing early stage neurodegenerative condition on the fall. You know the the variable severity, the variable treatments. I mean even taking a look at you know CTE which I think got a lot of press you know recent data coming out of Boston really indicates that there are so many factors in the phenotypes of what we attribute folks with TTE to have including no drug abuse, alcohol abuse and not particularly leading a healthy lifestyle it's so complex. I'm just curious you know in any of your research and prep for this you know have any of the the newer studies been better in controlling for any of this and I suspect the answer is no but I figured I'd ask the question anyway. Yeah good question and correct answer really it looks like you know you have some some well controlled studies within the larger number but those studies are so small that you really can't derive any convincing decision-making from them. You also have some mediocre and some poor studies but in the long run if you try to take the better-than-average studies and put them together there's certainly as you can see in my discussion evidence leaning toward the relationship that exists between neuro trauma and neuro degeneration but there are so many variables that play into this as you've mentioned. You know if you're bringing in patients if they all come from one trauma center they all go through one rehab hospital they're all followed up by the same doctors they get to some kind of therapies you might be able to produce a study that's actually pretty pretty good but because that isn't how a lot of our studies are done it's unfortunate that we really can't can't say that with any convincing evidence that there is definitely a causal relationship I think there's a risk factor involved and that the best you can do is just try to reduce all your confounding variables as much as possible and be aware of them before you go into the study. The trouble with TBI research is such a heterogeneous group and on some of these folks who have a brain injury they go on to lead potentially not such healthy lifestyles which I think is also a contributing factor. I'll ask one more question before the I'll pass it on to others I don't want to be too greedy here. You know in your opinion given the you know proposed pathophysiology of TBI related neurodegeneration particularly in the in the dementia realm you know is it your thought or what do you think with regards to you know TBI related dementia you know is that a distinct you know pathophysiological or distinct condition do you think from Alzheimer's or frontotemporal dementia or is it you know a role is it all the same? Yeah that's a great question my inclination is to say that it's all the same in that once you've kind of started down that Alzheimer's type dementia pathway the clinical presentation is almost indistinguishable with what I've seen right meaning you know you you wouldn't be able to if you didn't know the background you wouldn't be able to distinguish a brain injury related Alzheimer's type versus a non-brain injury Alzheimer's type. Now that's different for frontotemporal dementia for those who've seen that that's a very unusual very distinct clinical presentation often thought to be associated with pre-existing trauma I've seen a handful of those over my career and almost in all of those cases there's been some trauma involved and so I think that probably is the one type of dementia that I would distinguish from the other types that probably has a clear brain injury phenotype so to speak but I don't know that I would say the Alzheimer's types are much different I think there it may actually be the fact that the brain injury created or are pushed or promoted that cascade of events that was going to happen anyway to just happen earlier and so that's really what we're seeing is maybe a three to five year earlier onset with a similar kind of presentation. Thanks for that I think there's a question in the in the chat Gary Fang asked if you know daily aspirin was popular for cardiovascular purposes for a long time is there any evidence to suggest that folks who take aspirin have reduced Alzheimer's occurrence as a whole? I am not aware of any studies saying that taking aspirin over a long period of time carries a cost risk ratio that's beneficial toward reducing Alzheimer's. Certainly we know that there is a gut brain connection that making sure that our gut flora is well maintained making sure that our type of diet is better and healthier fewer additives into our foods more natural foods fewer red less red meat which is my big weakness that I think those things can contribute to our reduction certainly reducing anticholinergic agents and antihistamines over a period of time has been shown to be helpful in reducing the development of dementia and mild and mild cognitive impairment but I haven't seen aspirin as effective for preventing Alzheimer's and actually not even shown in non-cardiac patients to be a cost effective in preventing cardiovascular disease so if you're 40 and have risk factors starting aspirin has not been shown to be any more effective than not taking it certainly working on all the other risk factors cholesterol weight exercise can be very helpful. Any other questions for Dr. Kaylin? Yes we actually have one from Dr. Karen he directed me so I'll share with the group he's asking is exercise exclusive of that for specific motor weakness especially aerobic been found to be effective in prevention and/or reduction of dementia post TBI? So that's a great question my understanding is that exercise in the reduction of risk for developing Alzheimer's exclusive of it's whether it's brain injury related or non-brain injury related has been shown to be beneficial so we want our aging individuals and when I say aging we're all aging so that's our 30s 40s 50s 60s we want to be exercising we want to be eating right we want to be challenging ourselves cognitively those things reduce the likelihood of developing dementia in a brain injury specific population we know that patients with brain injuries who exercise do better both cognitively and functionally than those who don't but hey that's the same for the general population right so it's not magic to say any of these things so it might make sense that if you have a brain injury and you you're more active in your exercise your likelihood of developing dementia may go down but I don't think that study specifically has been done. Daryl it's Jonathan here I'll just add to that nice to a great talk by the way thank you so much and good to see you you know it's what wants to exercise an Alzheimer's disease there's no convincing evidence that exercise will prevent Alzheimer's or prevent the progression of Alzheimer's disease but in the general context many people with dementia's have other reasons for cognitive impairment and other dementia's going on as well and just like you're implying the good nutrition and the good exercise reduces vascular insult to the brain and reduces vascular type dementia so in general we should be recommending aerobic exercise you know as Dr. Karen I think is alluding to all of our patients with TBI we know it's helpful but also specifically in terms of reducing the risk of all dementias but there's no convincing evidence that it reduces Alzheimer's dementia. Thank you John. All right with that Daryl thank you so much for coming to New York virtually it's one o'clock I think we all have worked to do but great review thanks so much for an excellent lecture and I'm looking forward to seeing you in our next meeting. Thanks to you Steve and to everybody there at NYU if you're in the neighborhood stop by and we'll have the bourbon together. Thank you again for joining us you can learn more about RUSC at NYULangone.org/RUSC also be sure to follow this podcast on Twitter at RUSC Podcast.
