Why Enhancing Metabolic Health Could be the Key to Preventing Alzheimer's Disease

[Applause] [Music] hello everyone I'm Dr David pearlmutter we live in a world that really wants to convince us that we should basically live our lives Come What May and that there will be wonderful ways to pull us out of our various types of problems that we get into well as it relates to our brains that just isn't the case what makes a good brain go bad uh ultimately turns out to be a metabolic change and we are in fact The Architects of our brain's Destiny in that we absolutely control our brain's metabolism by the lifestyle choices that we make each and every day let's explore this a bit further I've decided to call this presentation Mind Over metabolism because we really need to get our arms around the notion that what makes a good brain go bad and even as it relates to Alzheimer's disease are metabolic changes that occur within the brain uh but how exciting it is that uh We've now seen headlines that there are breakthrough drugs momentous breakthroughs in the treatment of Alzheimer's we we see this uh in uh November of 2022 that this new drug LMI or laab is hailed as a uh momentous breakthrough as uh per the BBC uh here in the Washington Post the FDA giving Pro a full approval to the first drug that clearly but modestly slows Alzheimer's even though when you read the small print uh even it's administered every other week and it can cause brain bleeding and swelling well that's not necessarily a good thing so we're told this is the start of a new era a wonderful new era in the treatment of Alzheimer isn't that exciting let's look at the data and just see what all this excitement is about from the New England Journal of Medicine this is the drug lmbi or lanam and this is their study published in January of 2023 looking at 1,800 individuals participants half received the drug half were Placebo uh an 18-month study this is a drug designed to Target beta ameloid the so-called cause of of am uh Alzheimer's disease this is a drug designed to Target that drug because as we all know and I'm being facius that is the cause of Alzheimer's disease when we look at the uh cognitive function During the 8mon period of time of the placebo group the group that did not receive uh the drug we see a pretty dramatic decline in 18 months but in the those receiving this LMI or lamap drug uh what did we see well we actually saw a very similar decline in their cognitive function as well when we look at at the actual graph from the study what we see is an interesting thing that again both uh the placebo group and lanam ab group do Decline and uh at the 15mon point it's as if both groups basically fall off a cliff with a much more dramatic uh drop in cognitive function whether they're receiving this wonder drug or not between 15 and 18 months a dramatic loss of cognitive function but be that as it may the the other part of the story that I just hinted to is that there are consequences of using this drug as an intervention we call these uh hemorrhages in the brain and swelling the brain amalo related Imaging abnormalities or Aras and a significant increase risk of these changes in the brain which can be devastating uh in the group receiving the drug versus placeo this is what these things look like um swelling in the brain hemorrhaging into the brain far more likely in the group treated with this amalo modifying type of drug uh of which there are now several the other thing that we weren't told with all this excitement and these breakthrough announcements is that there is brain shrinkage actually associated with the use of these drugs uh another uh research group looked at the MRI scans of the individuals in the studies and uh compared them and actually determined that there was a significant loss of brain volume caused by the anti- amid beta drugs they actually went back and looked at the original researchers uh data and images and found that in fact there was a dramatic loss of brain volume now there are two classes of anti- ameloid drugs there are the ameloid drugs that inhibit HIIT a certain enzyme that's involved in the production of beta amid we call these secretase Inhibitors and there's another group of drugs targeting amalo that uh Target the actual amalo that's existing in the brain by creating a group of what called monocle antibodies that Target that uh ameloid and help the brain get rid of it here are a couple of the names Adu Helm and lmbi these are really in the spotlight these days for a number of reasons we'll see why and they looked at these uh patients who were on the drugs versus placebo and they looked at the volumetric MRI data in various areas of the brain and what they discovered was in those individuals using the secretase Inhibitors there was significant loss of tissue in the brain's Memory Center called the hippocampus as well as in the entire brain in general in those drugs that targeted the uh amalo itself using antibody uh therapy there was a loss in uh in brain mass such that the areas within the brain called the ventricles actually increased in size and what they stated was that these mild cognitively impaired participants uh treated with these anti- amid drugs were projected to have a material regression towards brain volumes that were seen in Alzheimer's dementia 8 months earlier than if they were untreated so something we need to think about this was the the headline that appeared in Med page today the other thing that I think is really important as it relates to these drugs is according to this new study appearing in the well-respected peer-reviewed uh Journal neurology that when we look at who qualifies for the use of these drugs uh based upon you know making sure we don't have people with other medical problems Etc that might be worsened uh by the use of these drugs fewer than 10% of Alzheimer's patients in this real world real world cohort would actually qualify for these drugs costing 60 to 80,000 a year but we do have the sudden uh news a release of yet a third uh type of drug um called uh Gan or Rab in early assim this study just came out in the New England Journal of of medicine again November of 2023 a very well-respected peerreview journal and how this drug Works similarly is it's the creation of a monoclonal antibod that's that three-winged purple uh image in the middle of the screen that then targets is directed against the existing ameloid in the brain with the notion that this is going to Target that amalo and rid the brain of of amloid because again that is thought to be the cause if you will of Alzheimer's disease again looked at about a thousand each of treated and untreated patients average age 72 years follow these people over 116 weeks and what did the study show first let's look at what happened in the brains as we did as we look at the pet scans of people that uh first the untreated group what happens to the amalo levels in their brains It Go go up with time what happens to the amalo levels in the brains treated with the drug a pretty robust decrease in amalo in their brains well if ameloid is causing this cognitive decline we would expect to see a pretty significant difference then in the cognitive function comparing the placebo to the treatment group what did these researchers find as we look at uh the first trial no difference in uh changes over time uh in their cognitive function and the second trial similarly no difference when we look at the composite uh chart graph uh comparing the intervention drug that get tenor Raab through to Placebo what do we see virtually no change in terms of their cognitive decline both groups decline quite dramatically despite the fact that one group had a significant lowering in their brains of beta ameloid but here's what is also fundamentally important when we look again at these amalo related Imaging abnormalities or the brain hemorrhaging and swelling that occurs a pretty dramatic difference that's the placebo group and this is the treatment group so you know I I think when we have the notion of above all Do no harm premium non noair uh that this is something we should be thinking about that we're not gaining any benefit here as you look at the risk benefit ratio there is no benefit but look at what the risk may very well be dramatic increase risk in these brain hemorrhages and edema these authors concluded that among persons with early Alzheimer's the use of this new drug led to a lower amalo plaque burden than Placebo at 116 weeks but was not associated with slower clinical decline as Albert Einstein has reminded us uh many times the the definition of insanity is doing the same thing over and over and expecting different results well here's the latest news on one drug Adu Helm that the company manufacturing it is going to stop uh its manufacturing and uh selling of this drug and beyond that quite interesting to note uh that the drug maker is going to stop developing and selling Adu Adel an anti- amid monoclonal antib body that did receive FDA accelerated approval in 2021 and they're also going to terminate the confirmatory trial which was a requirement of the Drug's accelerated approval in other words the drug got approved here in the United States by the FDA although all of the studies confirming that it did anything uh had not been completed um that's kind of interesting so where are we where are we getting this messaging that we should be so dependent upon drugs well let's see what the Alzheimer's Association is telling us that there are 6.7 million Americans living with Alzheimer's dementia that among people uh age 70 61% of those with Alzheimer's are expected to die before the age of 80 so it's it's a life-threatening issue compared with only 30% of people without alamer dementia and finally and this is very important remember this that Alzheimer's begins 20 years years or more before the memory loss and other symptoms then develop and this is again taken from the uh this organization on the far left of your screen a person experiences memory or thinking problems on the far right of your screen treatment is started as a person goes through the Continuum let me just bring these together so it'll make it easy what I'm the point I'm trying to make that the cognitive concerns begin and then ultimately at the end of the Continuum you get treatment and on which is ongoing under the care of a specialist who is able to do these intravenous infusions of drugs that basically with all due respect do not work and are associated with significant morbidity and yes mortality so again this is the Continuum and I'm going to challenge I'm going to augment it now myself uh and make room for what should be on the left side of your screen I'm cognitively intact and plan to keep it that way thank you very much yes the notion of prevention needs to be something we look at as it relates to Alzheimer's disease Dr Michael merenich uh a good friend and who who's been called the father of neuroplasticity uh made us aware of of really how ineffective these drugs are a recently appearing a report um and he commented saying that these the trial of these drugs do not support the hypothesis that amalloy is the primary neuropathological agent underlying the progressive neurobehavioral decline in Alzheimer's disease uh and furthermore the more obvious path to winning the battle against this human Scourge is prevention prevention uh this is so important because as he made clear 80 to 90% of prospective cases can be either delayed or prevented 80 to 90% of a number that's 55 million in our on our planet today so I want to take a step back then and look at what we understand is really going on in the brains of Alzheimer's patients that it is a a bioenergetic issue it is a failure of the brain's ability to supply blood to itself and to use the fuel in that blood which is glucose to power its cell it cannot uh it's failing as it relates to its bioenergetics and this is not recent data this dates back to October 2017 where they looked at the metabolism in the brain and indicated getting back to an earlier slide that this hypom metabolism occurs decades before clinical manifestations of Alzheimer's and that individuals with insulin resistance or have difficulty using glucose or type 2 diabetes have an increased risk for developing Alzheimer's disease moreover we may be able to characterize the brain metabolic fingerprints that may be used to offer patients and research participants more personalized therapeutic options in other words therapy that targets brain metabolism yes in days gone by we we saw differences in the MRI scans uh comparing controls to Alzheimer's disease but now using pet scan and even more recently MRI we can see that the brains of Alzheimer's p s even prior to the diagnosis of Alzheimer's uh even when there's no clinical issue like memory failure we can detect and predict who's going to have Alzheimer's based on the loss of uh energy utilization that is so obvious on these pet scans when we look at even mild Alzheimer's brain glucose update is significantly reduced and along the Continuum of an older person versus mild cognitive impairment and full-blown Alzheimer's a dramatic reduction in glucose uptake so what we're seeing now is that journals like the Journal of the American Medical Association are letting us know that it's glucose and brain metabolism that is as per this title moving to Center Stage as they indicate at the same time researchers are exploring ways to slow or prevent dementia using drugs and importantly for all of us lifestyle modifications typically prescribed for metabolic disorders like diabetes or obesity and these uh inquiries have new urgency as several anti-id targeting therapy disease uh drugs have failed in clinical trials so what are these lifestyle issues that they're talking about and where is the data that would indicate that there may be some uh relationship to memory decline for example well let's start looking at some of this research here's a study following individuals for 10 years looking at their lifestyle choices and noting that a healthy lifestyle was associated with a slower rate of memory decline in cognitively normal older adults adults including people who are genetically susceptible to memory decline a huge study of 30,000 individuals followed for 10 years and yes they even even looked at the whether or not they carried the so-called Alzheimer's gene or the apo4 AP E4 alil they did cognitive evaluations and assessed their activities over the course of this 10-year study looking at things like what foods do you eat how much exercise are you getting are you interacting with others are you interacting with things challenging your brain were you ever a smoker or did you quit and well how much alcohol you're consuming and what they found was really quite fascinating that the rate of cognitive decline memory function specifically over 10 years was dramatically increased on the right side of your screen uh in those who had unfavorable lifestyle choices and these are people who do not carry the Alzheimer's Gene those who did carry the Alzheimer's Gene look at that same results meaning that the gene really is less important than we had thought that carrying the so-called apoe for alil does not condemn an individual to having a cognitive decline that lifestyle choices are so important we don't have a lot of time to go through them all I'm going to go through physical exercise I think this is uh certainly something that's within everyone's grasp and let's look at some of the the data to help us understand what is the relationship between activating our muscles during exercise and brain uh in both health and disease and I think it's great to uh explore this because we know that exercise is good for us we know that exercise is good for the brain but how does it work what's going on so this is a an interesting study report that makes it clear that our muscles are an endocrine organ think about that that the muscle are an endocrine organ they secrete chemicals uh that have activity throughout the body much like other endocrine organs that you are familiar with pituitary the pineal uh and thyroid uh to name a few when we recognize the muscles and endocrine organ we embrace the notion that we can activate that endocrine organ and have it do its job when we exercise so when we exercise we're activating muscles and muscles are now creating myocin and what are myocin these are chemicals or cyto kindes that are synthesized released by muscles during muscular contraction and they are the molecular mediators of the great things that happen to our bodies and our brains when we exercise and we now are embracing a no a notion of looking at all the things involved with these muscle chemicals and what they do as we talk about a new term called the myome and the myome then looks at all of this activity of the various myokines like interlukin 6 which we used to characterize as being purely pro-inflammatory Ketone bodies many of you have heard of being in a ketogenic diet why that's good for the brain lactate irisin cathepsin B and of course brain derived neurotropic Factor being so good for the brain these are active um these are active Regulators of our Focus which is the metabolism of the brain and importantly that these are increased in muscular activity even when there isn't inflammation it increases the ability to use GL uh glucose or blood sugar the breakdown of fat in muscle and the utilization of fatty acids in muscle and importantly activates something called amk This is a pathway that allows us to use fat as a fuel uh that allows us to grow new mitochondria or energy producers uh even in the brain so that helps our metabolism so we're now looking at the notion of proper muscle Tob brain signaling as an important mechanism uh as it relates to brain health and that when we don't utilize this process we may set ourselves up for brain disease exercise actually improves insulin sensitivity and this uh was a study looking at sedentary or non-exercising adults who are overweight uh and obese overid or obese and it was a relatively small study 14 women seven men uh elevated body mass index and they did a study of their brain utilization uh of glucose brain metabolism if you will after and before and after giving them a blast of insulin in their nose and compared that to what happened when uh some of them did an exercise program and let me just walk through again what the study involved they each had a baseline functional MRI that looks at brain metabolism then they had a blast of insulin in their uh noses that does get into the brain 30 minutes later they underwent another functional MRI so looking at the uh utilization metabolism uh in a part of the brain called the paman uh a specific area that was studied here shows that comparison uh group this is the group not exercising uh after the 30 minutes of receiving after receiving insulin no real change in the activity in this particular part of the brain but when we look at what happens in the group over the 8 week uh period that exercise then got the insulin and then had to repeat functional MRI a dramatic increase in how insulin works in the brain to increase metabolism another thing they looked at is this notion of functional connectivity how one part of the brain relates to another part of the brain the connectivity the connections pretty dramatic increased uh presence of functional connectivity in the group that exercise and also doing a a mental test called a trail making the lower score the better the means the faster you're doing this study uh this test uh that shows that their brains are working better and even looking at metabolism looking at how their mitochondria work a dramatic increase in the exercisers in comparison to those uh who did not uh who still received the insulin but did not exercise from the Journal of the American Medical Association looking at 880,000 adults followed for seven years they put a wrist accelerometer on them and they wanted to determine in this group of 80,000 people who got dementia what did they find dramatic um um uh association between risk of getting dementia and lower levels of exercise but importantly their quote that there's no minimal threshold to the beneficial association of Step counts with incident dementia meaning any exercise is good more is better in this study 9800 steps per day was optimal for being in the lowest uh risk group for developing dementia but again any level of activity is going to benefit your brain so we need to consider brain metabolism which involves really two things the um utilization of sugar and of course its delivery in the first place blood supply Central to this is a chemical recently discovered uh in the brain and in the body it's actually a gas called nitric oxide abbreviated n o and nitric oxide is actually a powerful mechanism whereby exercise does its beautiful stuff in the brain that exercise increases our ability to use glucose and improves blood supply because it goes through this nitric oxide Channel could nitric oxide be something that relates to alzheimer's could we maybe just say no nitric oxide to Alzheimer's and in fact we're now seeing uh studies that show a significant reduction in risk for developing Alzheimer's in drugs uh in people who use drugs that increase blood supply by increasing nitric oxide Viagra a drug for erectile dysfunction was designed to increase nitric oxide and therefore increase blood supply it does so throughout the body not just as it relates to rectile dysfunction nitric oxide again does two things it improves glucose utilization by enhancing how insulin works and it improves blood supply glut glucose utilization and Vascular profusion are the difference between uh a normal brain and the Alzheimer's brain and nitric oxide is a central mechanism now I'm certainly not um advocating that we all begin taking this drug we'll look at what we can do to improve nitric oxide in just a moment uh this study looked at what nitric oxide bioavailability bioavailability does uh on Progressive um uh changes in the body and in the brain with respect to alzheimer's looking at uh cereal blood flow Young on the left uh and the endstage Alzheimer's on the right dramatic reduction in blood flow to the brain one might assume that perhaps they don't have as much nitric oxide we'll get there in a moment when we look at uh blood flow in the internal cored artery that brings blood into the brain dramatic reduction in going from young to old and to end stage on the far right of your screen Alzheimer's looking at blood supply to the cortex the top of the brain which we can measure now again the same Decline and we look at nitric oxide availability a very very interesting similar curve that we see this strong correlation of reduction in blood flow with reduction in nitric oxide by bio availability in the brain as we age but certainly worse as it relates to developing the development rather of inage Alzheimer's so these uh authors demonstrated that in patients with Alzheimer's that these changes are directly associated with Alzheimer's and not to aging that nitric oxide bioavailability is the link between cardiovascular and central nervous systems degenerative processes in patients at different levels of severity of Alzheimer's again related to the depletion of nitric oxide nitric oxide plays a central role in brain metabolism where does it come from a lot of it is from recycling nitric oxide and uh those chemicals that make it but a lot of it actually 50% comes from foods that are rich in something called nitrate nitrate rich foods are converted by bacteria in the mouth to nitrite and that becomes nitric oxide I recently did a an interview uh with a Doctor Mark barena uh that's available on YouTube that covers this that interview went uh viral uh because I think the way he explained this relationship and the important role of our mouth bacteria was really very stunning so again he is calling attention as many have to the role of the bacteria in the mouth well we're told that we want to do everything we can to kill the bacteria in our mouth right so we don't have problems like who knows what bad breath and and uh tooth decay but is there a relationship if we kill these bacteria between glucose utilization and Vascular profusion in other words could killing off these bacteria have systemic issues could using mouthwash for example be related to risk for diabetes and in this really fascinating study from from 2017 these researchers looked at about a thousand individuals overweight obese adults non-diabetic how often used mouthwash they followed for three years what did they find using mouthwash two or more times a day associated with a 49% increased risk of pre-diabetes or diabetes what about high blood pressure If nitric oxide is involved in blood pressure regulation a very similar study 540 individuals again 3 years risk of developing high blood pressure a powerful risk factor for Alzheimer's risk of high blood pressure 117% increase and that's just from Two Times Daily so what else should we consider as we think about what's going on how do we increase nitrate and then nitrite and nitric oxide by eating nitrat rich foods colorful vegetables like beets we know that uh we can actually change uh the the bacteria in the mouth they respond with higher levels of nitrate again the notion is if we eat nitrat rich foods in this study a dramatic reduction in blood pressure by using a specific supplement that reduced rather that improved nitric oxide by giving nitrate bacteria converted to nitrite your body turns it on into nitric oxide that lowers blood pressure one of the Pioneers is Dr Nathan Brian who has done a variety of studies demonstrating dramatic changes in patients with cardiovascular disease uh in individuals who received a a pharmaceutical way orally uh of increasing their nitrate and therefore nitric oxide production uh I had the opportunity to meet with him and uh I will be with him um actually beginning a study of uh increasing nitric oxide as a way of treating individuals with existing Alzheimer's Disease by for the very first time targeting their metabolism well I hope you enjoyed that presentation again metabolism is Central uh to brain health and resistance to things like Alzheimer's disease metabolism is highly influenced by the various lifestyle choices we make uh each and every day thank you bye-bye [Applause] [Music]

Channel: DavidPerlmutterMD

Views: 80,192

Keywords: david perlmutter, dr. david perlmutter, grain brain, dr. perlmutter, brain maker

Id: 5LU_XY0z2ZY

Length: 32min 36sec (1956 seconds)

Published: Fri Feb 23 2024