Health Matters 2024: Brain Power - How Science Is Revolutionizing Cognitive Health

good morning and Welcome to our second Health Talk of the morning as Karen said it's great to see such a full house today on a beautiful Saturday morning and I'd like to welcome all of you who are joining us online my name is Dana Hayes and I am a local resident here in the Bay Area and a member of the Stanford medicine Community Council before we get started I want to remind everyone that there will be a live Q&A after our presentation you can submit your questions using the QR code in your program or if you're watching online there should be a QR code on your screen and for all of our attendees both in person and online the slid shown during this presentation will be available to view after the event at Health matters. stanford.edu now I'm pleased to introduce Dr Frank Longo he's a professor of Neurology and neurological Sciences here at Stanford and the former chair of that department today Dr longa will be talking about the groundbreaking work that's taking place in the area of cognitive Health including here at Stanford he will share how fortunate we are to be living in a time of a neuroscience Revolution with more ways to detect and treat neurological conditions than at any other time in history he'll also share information and practical tips that we can use starting today to keep our brains healthy into the future now please well join me in welcoming Dr Frank Longo thank you thank you okay well thank you Dana for that nice introduction and thank you everyone for being here it's a it's a pleasure for me to be here at at Health matters I'd like to thank Carla and the team that has made this event possible i' also like to thank Dr katsumoto for her wonderful talk that she just gave it helps me uh discuss a few areas about about the brain so for centuries the brain has been this black box and we really didn't know what was going on in the brain in living people and during the past few years technologies have become available that are rapidly changing that so we're in an explosion of brain science two of the drivers are that are imaging technology some of which was developed here at Stanford and another technology we call omix genomics proteomics the ability to measure thousands of genes and thousands of proteins in the blood or the spinal fluid all at the same time in living people and with those Technologies we finally have a window inside the brain and that's allowing us to accelerate uh strategies to uh promote brain health and to come up with therapies and I'll share some of those new developments uh with you today so let's look at our cognitive Health span all of us are on the Spectrum if we're lucky many of us start with normal cognition and at some point around age 30 most of us start to develop what we call age related cognitive impairment what does that mean that means a little bit of more challenge in short-term memory and some more challenges in what we call Executive function ability to multitask now it's not all bad with aging some cognitive functions can improve for example judg or Association or verbal abilities can actually improve all the way into our 80s but we're all on this journey of of age related cognitive impairment at a minimum now starting in our 60s in between age say 65 and 75 a little over 20% of people will have mild cognitive impairment what does that mean that means some cognitive impairment often involving short-term memory that's decreased compared to your AG match controls but not severe enough to affect day-to-day functions that's called MCI mild cognitive impairment you'll hear that term quite a bit now if you have mild cognitive impairment for each year you have a 10 or 15% chance of going on to develop a full dementia dementia is a broad term it means enough cognitive impairment to significantly affect day-to-day function that's what a dementia is there are many kinds of Dementia I've listed three of the most common here Alzheimer's vascular and Louis body dementia today today I'll be speaking about Alzheimer's quite a bit but the principles of Alzheimer's apply to these other forms of Dementia in many ways uh as well Alzheimers is by far the most common form of dementia it accounts about for about 2third of the dementias that we see in our Clinic let's look inside the brain of an Alzheimer's patient there are three critical processes here one is the accumulation of the substance called amalo what's ameloid ameloid is the fragment of a normal protein uh and it's an abnormal fragment that accumulates with age but especially with Alzheimer's we don't know why it accumulates uh but it's damaging to the connections between neurons the second pathology or there's a protein called toao it has some normal functions inside the nerve cells or neurons but but abnormal forms of it that dark substance inside those neurons will start accumulating that causes the neurons to degenerate and the third process is neuroinflammation Dr katsumoto talked about the importance of inflammation the brain has its version of inflammation and there are cells in the brain called microa cells those are the brains inflammatory cells um and in the upper picture there on the right is a normal microgo cell in a in a happy non-activated healthy state but when it gets activated by brain injury by poor diet whatever it is it has this plumped up uh appearance that you can see there and when when it's in that state it's secreting cyto kindes and inflammatory chemicals that again affect these connections between the nerve cells these three pathologies will come up over and over again if you're a student of brain health so remember what these look like okay and the bottom line is that we want to protect our synaptic connections so synapses are the connections between the nerve cells we might have about a 100 trillion of them in our brain and the most delicate part of that synaptic connection is called the spines those little Nubs there so there's a dendrite or an axon it has those little Nubs or spines and those that's the heart and soul of the synaptic connection so if you're interested in brain health what your interest is is not losing these synaptic connections that's the bottom line how do what's that have to do with Alzheimer's so we talked about amalo and Tow and inflammatory cells all three of these processes cause degeneration and failure of the synaptic connections so this this is what we're dealing with so let's delve a little deeper into this concept of of the synaptic spine on the left here is a picture again of that synaptic connection and the spine's shown in green there and on the right is this fascinating study one of my favorite studies where they looked inside human brain and they're looking along the dendrite or the ax on there on the top panel and they're looking at those little Nubs are the spines and the top panel are just aged m match people with normal cognition and then the lower two panels are people whose brains are filled with amalo and towel like a typical Alzheimer's patient but a small number of those patients with amalo and Tow in the brain have normal cognition about 5% or so so about 5% of people can have amalo and Tow in the brain and have normal cognition the rest the other 95% have a dementia but if you look carefully you can see that people with a normal cognition have a normal number of spines a normal density of spines whereas if you look at the lower panel at the patients with dementia their spines are almost gone so it's that ability to keep that keep that spine uh that's important for preserving cognition and we think we have strategies uh for protecting these spines so one of the ultimate therapeutic goals now uh if you're developing a treatment to prevent or treat Alzheimer's dementia is find a way to protect the synapse and really to protect those spines that's our goal the other uh uh thing I find fascinating about this observation is Nature's done the experience experiment for us what nature is telling us is that there are a small number of people that have amalo and toao in their brains but with normal cognition they're resilient so this introduces the concept of resilience now these are a small number of lucky people but can we create Therapeutics that confer resilience so that everyone can have the resilience rather than just a few if you were to come to the Stanford memory Clinic uh today we have a you know big uh great Stanford memory Clinic here I'm privileged uh to be one of the neurologists working there this is how we assess you if you're worried about cognitive loss or getting it or do you have it we take a careful history because we need to know the time course of any symptoms that might be there we do a careful neurologic exam we're looking for subtle Clues maybe there are subtle clues of Parkinson's for example we need to know that uh we do a careful cognitive exam that's very quantitative we compare to your aged match uh appear we do a brain MRI scan as shown in the picture here a normal and Alzheimer's patient now the MRI scan cannot detect Alzheimer's cannot detect Louis body dementia why are we doing the brain scan it can show a little shrinkage uh but that's not specific to any particular process we get a little shrinkage with age we're doing the brain scan to look for other things that can affect cognition is there a brain tumor there did this patient have a series of small Strokes we didn't know about does this patient have too much fluid on the brain all of those things can affect cognition uh we wouldn't want to miss those that's why we're doing the MRI scan and then we'll do a few blood tests a low B12 can affect cognition low thyroid can affect cognition that's been the traditional workup for a number of years but recently we have these newer Technologies one are ameloid and Tow pet scans I'll show you some images of those uh we can do a spinal tap and get spinal fluid and get a more precise diagnosis but we we try to avoid doing spinal taps unless we have to do them and then finally we can measure amalloy or tow in the blood and this is a recent technology that we'll talk a little bit more of let's look at the tow in amalo pet scans so on the left hand side is an amalo pet scan we have an Alzheimer's patient above and a normal patient below the bright the yellow and red colors are the accumulations of amalo in this patient and then on the right hand side we have the towel pet scan same thing the bright colors are the accumulation of abnormal tow in this patient one of the most notable aspects of this technology is that that amalo we can see it start to accumulate 10 or 15 15 or 20 years before the change in cognition starts this startled the whole field we had no idea this was happening because we had no way of looking inside the brains and living patients right so just think about that if you're destined to have your dementia start at age 70 it was during your early 50s that this amalo started accumulating and some people it's accumulating during their 40s right this process has already started and the tow is is later it starts accumulating right before the symptoms start what about the blood test this is a technology just coming out now it will really change many aspects of Health Care so this is the ability just to with blood to measure certain abnormal forms of tow in the blood and if those forms are abnormal there's a greater than 95% chance that this process is already started in the brain and and there are two main applications of a blood test uh we can see patients who are already having cognitive symptoms and use the blood test to help us figure out what's the cause of those cognitive symptoms is it Alzheimer's or not or and here's the big implication in healthcare people that have normal cognition and they just want to get this blood test as a screening tool what are the implications of that in other words you're only age 45 or 50 your cognition is perfectly fine and you can go to your primary care doctor and get this blood test done do you want to do that do you want that information what would you do with that information what will this do to the Healthcare System overnight we'll have 20 or 30 million people in the United States wanting to see a neurologist uh when this when this comes back abnormal we're all we're all worried about this in fact there are several clinics in in both us and Europe that are have research programs to study what are the impacts in the primary care setting of ordering this test getting the results we really don't know so you're you're living through an experiment now I listed four companies or probably more now that are offering this this is already available there's one company where as a patient you can initiate this uh they'll have a doctor put the order in for you a physician has to order this but you're the one initiating that you don't even have to deal with your own doctor and you'll get the results back what do we do with that information do you want to know that information we can talk more about that so what are the risk factors uh for coming down to dementia there are many other I don't want to overwhelm you with this slide I I put a square around four that we'll talk a little bit more about today the physical activity the diet social engagement and sleep but there are other ones uh that people ask us about in our Clinic stress depression hearing loss interest inly smoking excessive alcohol consumption I I just want to put a note about alcohol because I get asked about this all the time can I drink or not and it's there's no agreement in the field uh it's you'll find it under a a a list of risk factors but I saw a study recently from the past year where any amount of alcohol in the in the reasonable range was thought to be protective of not getting a dementia so it's it's we really don't know yet um there there are medical issues that can contribute to getting a dementia certain what we call anti-cholinergic medications these are the first generation bladder medications or early generation anti-depressive um or some of the allergy medications the older forms uh increased risk of Dementia by about two-fold um and then these medical issues hypertension diabetes all of these things can uh promote dementia and then traumatic brain injury earlier in our life nothing we can do about that at that point low education that cut points about seventh or eighth grade people that have less of that are more likely to come down with a dementia air pollution I grew up in Los Angeles so I'm waiting for that one um and and then finally genetics things that we can't do much about there but we'll talk about genetics let's in fact that's what I have next okay so genetics is important when we're thinking about brain health and in thinking about Alzheimer's there's a there's a rare form under 2% of people that comes on early during the 40s typically we call it familial Alzheimer's where there's one gene that if a parent has it each child has a 50% of getting it and if they get that Gene they will 100% sure come down with Alzheimer's is if they live a normal lifespan so that's called familial Alzheimer's but it's fairly rare the more general form of Alzheimer's that we're dealing with we call spartic the onsets typically in the late 60s it starts or so but the MOG impairment earlier stage can start much earlier that's probably a result of many genes and lifestyle and environment but there's one gene that that is a big risk factor for sporadic Alzheimer's that's called the apoe gene and that Gene makes a protein that carries cholesterol around the body there are three forms of that Gene E2 E3 and E4 if you have the E4 version of this Gene you're at higher risk for Alzheimer's now you can get this a doctor can order this is a blood test you can find out if you have the E4 on on 23 and me so if you have no family history of Alzheimer's your lifetime risk for all of us if we live a full lifespan is about 15% so 15% of every everyone here will come down with Alzheimer's on average however if you do not have the E4 high-risk Gene you're down to 9% so less likely to get Alzheimer's if you do have the E4 Gene you've just doubled your risk now you're up to 30% now let's add in if you've have one parent with Alzheimer's because now your risk go up by about twofold by having a parent with Alzheimer's and you can see if you have both a parent with Alzheimer's and you have one copy of E4 you're up to 45% risk if you have two copies of E4 I have 60% here but a study just came out if you have two copies of the E4 you might be at 80 or 90% likely to come down with Alzheimer's this is a a powerful effect here now do you want to know this information so if you've been on 23 and me you have to do a few extra clicks to find this out because they kind of warn you do you really want to know why would you know or not want to know well I've had patients say I want to know if I have the high-risk apoe Gene for Life planning purposes when I'll retire Etc the problem is this is not real precise you could have the E4 never get Alzheimer's and if you're going to get it we don't know so it's it's not that easy uh risk management I'll I'll you know how people manage that um uh how there's a a risk here that you can be under more stress by knowing that you have the high-risk Gene knowing you have the highrisk gene can affect your relationships with your family and friends it can affect trying to get disability insurance for example you'll be asked do you are you aware of any risks for diseases and how do you answer that when you know you have the E4 Gene and then are treatment implications so far no that if you had the high-risk Gene there's not a drug we can offer you yet we hope we're close but there is a study going on called the A45 study where people who have the E4 high-risk Gene and their still normal cognition can enroll in this study and start to get treated with one of the treatments that removes ameloid from the brain and I'll be talking about those those treatments so let's talk about four four basic uh prevention strategies exercise diet cognitive exercise and sleep we'll start with exercise and there are multiple studies uh uh showing that people who exercise have less risk for dementia the UK biobank because they have a public health system in the UK lots of data here are 78,000 people that they looked at um and they volunteer to wear wrist Accel accelerometer uh over seven years to measure their steps the people that had the relatively lower number of steps each day um still some exercise had a 25% risk reduction of getting out of getting a dementia but the people that did 9800 steps look at that 50% uh risk reduction this is a powerful effect uh the the biology of exercise is very powerful uh a metaanalysis means that somebody summarized 29 research uh uh projects on exercise uh and cognition and they distill this down to the bottom line that moderate to vigorous exercise on average cause a 25% risk reduction during the 15-year follow-up period an important message here is because I'm often asked well how much exercise um the light exercise and examples are leisurely walking or gardening had no effect unfortunately so you do have to get your heart rate up to at least a moderate uh level we can talk more about what does moderate exercise uh mean but so the am of exercises the dose is important and here's an example of another study looking at physical activity and seen if people come down with a a dementia so they look follow people over about an eight-year period And as the line goes down people are coming down with the dementia and you can see that the people that had low amalo in their brain um were were pretty stable they weren't coming down with dementia very often but the people that had the high amalo on the Pet Scan uh they were coming down with Alzheimer's much more frequently that's in the low exercise group The 2900 step group but what about the people who are more active you can see that even the people with high amalo if they were Physically Active were not coming down with dementia nearly as often again powerful biology of exercise this is like a powerful drug basically um we want to know more about does exercise really cause a protection in the brain and these are two big studies that came out of Stanford recently where we work with mice mice love to run um and if you if you put a running wheel in their cage that's they'll go straight to that one running wheel and start to run and then some mice we we lock the running wheel so they can't run so those are the sedentary mice right and then we could take blood from those mice and inject it into elderly mice now if you take blood from a a couch potato Mouse and injected an elderly Mouse You Don't See Much happen but if you take the blood from an exercising mice and in Ed into an elderly mice the elderly Mouse will have improved memory function and decreased brain inflammation that to me is really powerful biology there's something in that blood when you exercise that has big effects on the brain another more sophisticated study the mice like to run on these treadmills you can put the treadmills at different inclines and do a whole uh getting in shape program uh for the mouse by changing the incline and the speed of the treadmill same findings and here they looked at male and female mice separately but in in the mice that succeeded in in or that did the training versus the sary uh they had decreased immune uh action in their brain improved metabolic function and better mitochondrial function the energy source in our cells and for the female mice the effects on inflammation were particularly notable the the benefits were particularly notable there um Dr katsumoto did a wonderful job talking about Mediterranean the different kinds of diets here's the Mediterranean diet uh uh pyramid you're familiar with anyway overall it's associated with a 20 to 40% risk reduction in dementia and this has been looked at from many angles people uh can follow this study they followed people over about 10 years looking at diet compliance to the Mediterranean diet and there as the lines go down they're coming down with dementia the people that had the high compliance with the Mediterranean diet were less likely to come down with dementia versus the people that were on the low compliance so what Dr katsumoto talked about in the body and the joints appears to be applying to the brain as well and then again the UK biobank uh they have many subjects there 60,000 subjects overall uh people on this kind of diet had a 23% risk reduction for dementia and now that's the symptom of dementia what happens inside the brain and that's what the rush memory and aging project looked at so uh these patients volunteer to be followed and then when they pass away they donate their brains and they're all rated with a Mediterranean diet score and you could see the higher the Mediterranean diet score the lower the Alzheimer brain pathology and the lower the amalo load in the brain so they're they're presumably influencing the amalo load based on whether they're having Mediterranean diet or not um and finally uh a prospective trial there aren't many of these in the in the dietary field because it's hard to change diets over many years in a study but this was a study it's the Mind diet It's a combination of the Mediterranean diet and the DASH diet the dash is a little more of a strict diet um and they enrolled 604 subjects with normal cognition and then they followed them to see if they would come down with a cognitive impairment um and the control group and these the body mass index was 35 or higher so these are relatively overweight uh volunteers uh the control group had advice on color caloric restriction and then the treatment group had the same advice same coach on chloric restriction but then they added the diet in and they wanted to see if adding the mine diet would do anything differently and it did not you could see a similar uh both had some improvement in cognitive score and they speculated that maybe it was just the mild caloric restriction that helped um so we still have more work to do on the effect of these diets um and then finally I'd like to talk about ultr processed food uh this is the Framingham heart study and they followed people over about 20 years they looked at cumulative incidents of a dementia and you could see the people that high uptakes of ultr processed food were about 50% more likely to come down with the dementia so again we're seeing this ultrapress food effect and then the the graph on the right shows servings per day and we can see between two to four servings per day as we get to that and higher uh the incidence of dementia is going up sleep has been a big factor lately uh people that have sleep issues have more likelihood of having a dementia come on and the theory is that during sleep uh we get more fluid flux through the brain so more cleaning out of amalo uh uh theoretically compared to when we're awake um but the big question in sleep is which came first some people argue that it's a very early brain degeneration disrupts sleep patterns and it's the it's the degeneration of the brain and Alzheimer's that causes poor sleep before cognition starts but other people argue no it's the other way around it's the poor sleep came first and that's contributing to the dementia we really don't know which one is is first now but I still recommend to people to try to get the six or seven hours of of healthy sleep and then healthy lifestyle overall again these studies try to integrate multiple Health factors the Mind diet Etc and people that have zero or one healthy Factor only you can see they're more likely over at each age range to the Blue Line there more likely to come down with a dementia versus people with four or five healthy factors the red dotted line uh almost almost 50% less likely to come down with a dementia so it might be a combination of these lifestyle uh factors and there's a study called the finger study finished geriatric intervention study that again combines all these lifestyle issues because people we want to focus on exercise and diet separately to learn what they do but in the end it might be the combination of these lifestyle uh factors so let's get to Therapeutics for the last few minutes uh we have a number of drugs that have been around for a long time I've listed them here these boost the neurotransmitters in that synapse they make the synapses work a little bit better but they don't slow down degeneration unfortunately so what we don't have in the field yet is a drug that can slow down degeneration alth there's one that recently came out we'll talk about uh people ask me about supplements all the time uh this graph is just comparing people who are low in vitamin D versus higher vitamin D a vitamin D deficiency might increase the risk of dementia but adding more vitamin D to people won't necessarily help or treat it the bottom line with supplements is and I can summarize thousands of websites for you in one sentence probably unfortunately the bottom line is there is no supplement proven in a well-designed trial to delay onset of dementia or slow it down that that's the bottom line you can talk about any supplement there're these endless products like Prevagen you could buy at CVS no good evidence whatsoever I hate taking hope away from people but these products don't have any effects okay metformin is an old diabetes drug it's touted to maybe slow down aging people ask me if they should be taking it uh it might it's touted to maybe it'll slow down or reduce chances of getting dementia uh no EV no consistent evidence for that this was a big huge uh study here they looked at thousands of people no evidence whatsoever for metformin so here's one drug that is FDA approved lanam this is an an amalo antibody that's given intravenously and this antibody goes inside the brain and clears amalo out of the brain you can see on the Pet Scan here the reduction in amalo uh by lanam um and it you can see the graph in the middle there uh over this drug was this in this trial they were treated for 18 months and the cognition still gradually got worse in the placebo group and it still got worse lcab group but a little bit less worse so 27% less worse on lanam and people are debating now is this clinical effect meaningful enough because it's a really small slowing of clinical loss unfortunately it's a very small effect and at the same time this drug has significant side effects about 20% of the people got a form of a swelling of the brain or edema of the brain some had had some hemorrhages of the brain they're getting intervenous treatment every two weeks they have to be monitored frequently MRI scans so it's it's a personal and difficult decision whether or not somebody uh with um my early stage Alzheimers would want to be on this drug we can talk about that that more and finally I'd like to share a little bit of our experience developing a drug for Alzheimer's it kind of highlights what this like to create a treatment that will prevent or slow down Alzheimer's we created a drug that affects all three of these mechanisms I talked about and beyond our control this drug ended up on the cover of Time Magazine a few week a few years ago just cuz our journey in developing this has been unusual um so we created a small molecule that can be taken orally that protects the synapses and neurons from ameloid and these other features so we can take a neuron from a mouse uh grow it in a dish and if we expose it to amalloy its processes get this successive curvature that's a sign of a degenerating uh neurite uh neuron due to the amalo but if we add the drug called c31 there it protects the neurites from the amalo in a dish and then we can go uh into mice and look at neurons as well and you can see those little fine H uh hubs those are the spines there those little black um little Nubs there and we expose them to amalo in the middle panel uh we lose those spines but if we have our drug present the ameloid is no longer able to damage th those spines remember I said if we want to save anything in the brain it's those spines right so here's a drug protecting those spines from amalo and protecting them from tow that's been the goal and so we uh did all the studies necessary to bring this drug to humans and that's my colleague Steve mass and I visiting the FDA and going through all the testing uh get to get to human we did a phase 2 trial in Alzheimer's patients in Europe five different countries there um this is my wife an Longo and I at a clinic in Barcelona um and we had a start a company to get these trials done and an's the founding CEO of our company and made all this possible on the financial end we also had ni funding and this was a blister pack that one of the patients and their families brought back when we were visiting that day it was very emotional seeing a family come back with this empty blister pack because they were taking a drug you know that we created in our lab very very meaningful for us anyway the good news was that this drug is significantly slowing degeneration in the brain this is a f what we call an fdg pet scan and if everywhere in the red is in the brain where the placebo patients were having degeneration and those parts of the brain that are critical uh these are the parts that degenerate in Alzheimer's but the placebo group unfortunately had that degeneration like we expect but in the purple down below those are the parts of the brain where there's a statistically significant slowing of that degeneration for the patients that that took this drug so we're really excited about that finding and finally um I know this is a complicated slide but that black line under the zero is uh these are abnormal proteins that are accumulating in the spinal fluid of patients way before their dementia starts so 10 year minus 10 minus 20 years before the dementia starts their abnormal proteins already accumulated in the spinal fluid um and then the dementia starts and what we found about about our drug is those abnormal proteins that are accumulating 10 and 20 years before the dementia starts our drug is normalizing those so we think that maybe this could be a drug that you would take 10 or 20 years before your dementia starts and delay the onset if we can delay dementia onset by only 10 years we reduce we eliminate 90% of all Alzheimer's uh it's just a very highly leveraged effort if we can delay it by 10 years which I think we can do we eliminate 90% of Alzheimer's in the world so potentially big impact there um and then so now we've designed a big trial that that could go for FDA approval uh there would be a placebo group a drug group treated for 18 months and then after the blinded period everybody gets to be on the drug for 12 months so we're we hope to be able to start this trial soon so I want to thank everybody in our Stanford uh uh Alzheimer's research group uh we have a lot of great stuff going on at Stanford uh this is the ikbal FR and Assa Jamal Alzheimer's center it's our families and patients that make a lot of this uh possible and we're continuing to work on age related mechanisms better even better Imaging and blood test and really coming up with additional uh treatment so I'd like to thank everybody for your attention thank you thank you Dr Longo wow what a lot of great information lot of hopeful information yes some a little not so much but I I'm very positive about what we can do yeah exactly so so as expected we have a lot of questions just reminder please submit your questions using the QR code okay our first question I've heard that you can't definitively diagnose Alzheimer's until after someone has died is that still true that's been true throughout history all the way up to until very recently so I I think it used to be that at autopsy we would look in the brain and that's when we really knew if somebody had Alzheimer's or not um and that would create a lot of confusion for amilies because they would hear about a parent or relative that died of a with a dementia they're never sure if it was Alzheimer's or not a lot of speculation but I think now with the some of the tests I mentioned the blood tests or the pet scans especially the blood test that'll revolutionize things that tells us with more than 95% accuracy that there's Alzheimer's pathology in the brain so that'll really changed the the discussion okay can you address how crossword puzzles and creative activities like art music and writing affect cognition uh yes yeah important question crossword puzzles and these other activities I think um I think being sedentary and doing a cognitive activity might not be enough um so you know there are companies that market software to do so-called brain exercises so you sit in front of your computer on your phone and you do so-called brain exercises right it's been very controversial you'll probably get better at that particular activity but most of the studies suggest it won't delay getting Dementia or it won't make your cognition better it's been controversial in fact the Federal Trade Commission filed a lawsuit against one of these companies for marketing that brain exercises would would improve your cognition I've had patients in my clinic uh I think these these brain exercises can be fun I've never really done them I've had my patients tell me about them they are excited about them I don't want to take away that but then I say okay that's great now tell me about your exercise and there's no exercise um and and the sitting in front of that computer is not going to do it uh it's just exercise is so much more powerful now the Alzheimer's Association says well do your crossword puzzles um I don't even like crossword puzzles um I'm not very good at them and so I I think cognitive activity is important but I don't think it ranks up there with exercise and Nutri but there is one cognitive activity that does register That's What I Call cognitive engagement um the the social engagement the most complicated thing in your environment is another human being um so social engagement um having a mission people have formerly studied people who have some kind of mission that might be their grandkids or their volunteer job or the boards they're on some kind of mission maybe it's their family's just survival but a mission and being on a mission reduces dementia risks as well that's the kind of cognitive exercise I think can be helpful okay very helpful next question my husband has depression and anxiety do these conditions or the medications he takes for them increase his risk for cognitive impairment yeah depression and anxiety so we do know that people with you know chronic depression um are some higher risk for dementia and if if the anxiety is AC chronic stress there can be some increased risk one of the theories is that with forms of stress there's a hormone called cortisol that's increased and we know that cortisol is hard on the neurons in the hippocampus a part of the brain that's important for memory so there is some basis for that but it tends to be fairly chronic uh severe uh um conditions in terms of the medications that are used uh for depression uh at least the newer medications that don't have the anti-cholinergic effects they're generally probably safe in terms of I'm not aware of any significant increased risk of those medications and coming down with the dementia okay that's promising what should we anticipate regarding Long CO's chronic brain inflammation and its effect on health yeah um long covid important area one of our faculty here at Stanford invented a kind of pet scan that can identify uh inflammation in the brain remember I shared those microa cells so she came up with a a pet scan that can detect those micral cells from being overactivated and we're using that kind of strategy what people are seeing now that in long covid there's some active inflammation uh in the brain right now having chronic active inflammation in the brain I think will be hard on this synapsis so long Co has not been around long enough yet but I wouldn't be surprised if five years from now or so we're we're seeing okay long Co might be a risk factor right how is C coffee beneficial or harmful to memory and cognitive function are we sure you want to hear the answer to this yeah so I'm well with alcohol I'm always disappointed because there are studies saying it might be harmful right um they're mixed as I said but coffee is the one last substance I'm aware of that I've never seen a negative study on it um so just great so I I think acutely coffee can enhance cognition as most of us know um coffee you know has like most plants has flavonoids in it besides you know not just the caffeine and so in general these flavonoids are antioxidants and so that can be beneficial in terms of brain inflammation so I look at lot of epidemiologic studies and I would say a coffee if anything would be a plus but it's not known to be a big huge one it won't save you okay but we can still enjoy our exercise is still more important yeah so maybe maybe we should do crossword puzzles while running on a treadmill and have coffee after well you know there was a study where they put people on a treadmill and then they put a screen in front of them and they had to do computer games while they were on the treadmill um and luckily none got hurt but I was just G to say the orthopedic surgeons like that one right but the people that were doing both they think had a little more benefit than just treadmill only uh so but don't try that at home I don't okay this might apply to lots of people if I have a family history of Alzheimer's when should I see a neurologist to have my cognition tested yeah this this is this question is so complex now and it's changing I think in an exciting way um okay you have a f if you have a parent with Alzheimer's you're two times increased risk if it's a grandparent or an aunt or Uncle it it's less of of an effect on risk it's really having the parent okay twofold risk if you have a parent with Alzheimer's right um and then if your cogn is normal what do you do if you're at twice as much risk now traditionally I'd say well there's not much you could do just make sure your lifestyle and exercise try to optimize that but now that we actually have a trial going on treating people that have normal cognition so if you were in this situation you might get the apoe gene tested or you might get this new blood test this too 217 that tells you if you have amalo pathology you might and so so you might say I'm going to get the blood test the problem is I think it's a little too soon to act on these blood tests this is a really important question who should get this blood test right so if you have a family history and you're worried about it you might be thinking about getting this blood test but when people get tests I always say to them is there's something actionable you will do right now some people say to me well if I have an abnormal blood test I'm going to start working out um um I'd say you should be exercising anyway um right or I'm going to start eating a healthy diet I say you should do that anyway you don't need a blood test to tell you that but if you get this blood test and had uh evidence that you have the brain pathology until recently i' said well there's not much you can do with that um in terms of actionable thing but now we've got this study going on right where people are enrolling to take one of these amalo antibodies to clear the amalo out of their brain even though their cognition is still normal and the hypothesis of this study is that while your cognition is still normal if we can clear that amalo out you're going to be much less likely to come down with a dementia that's the theory that this and we're offering the study here at Stanford it's not an easy study to be in you're going to be in it for years you're going to be coming into a lot of visits you're going to be getting intervenous treatments with antibody I talked about the risks of this antibody so it's a personal decision but your question is so important because it is changing the how we think about these questions and we don't have all the answers yet right I just know I mean typically you don't do a screening tool unless there's something you can do about it right but right um now yeah you typically don't screen unless there's an actual item now if if people are do have some symptoms though that changes screening so I like to think of screening in two different categories either you're normal and you just want this information that's one context and that's the one you're talking about you sure you want to get screening if you're normal and there's nothing you can do about it or if you're having symptoms and I I I would see a neurologist to really know if cognitive symptoms are significant or not if they're mild because they're not always significant um but if there's clearly a cognitive issue going on it changes the context of the screening and and and the value of of the information right okay does the use of a Statin increase the incidence of dementia yeah or reduce it yeah Statin complex question the two levels with Statin um in a in a very small percentage of people on a Statin when Statin first came out and this was maybe 1 or two% of people on the stat um they were thought to have some little bit of impairment of cognition and some muscle inflammation as well so you know people ask about muscle pain when you're when you're on a Statin um but then the pattern has not been so clear so um I don't worry too much about acute use of Statin now in the long term it was hoped that Statin AC quiet some of this inflammation in the brain and the taking a Statin would uh slow down dementia right and so there were two big trials by the large Farmers that that uh make statins and both trials unfortunately were negative so statins had no effect on big Trials of slowing down cognitive loss so that's why we don't use it as a dementia treatment per se I mean to the extent it inhibits inflammation it could theoretically be helpful I wouldn't feel badly if I were on a Statin right but we can't call it a treatment okay thank you can meditation or mindfulness practices help prevent or improve cognitive impairment and then what is the impact of stress on cogn the way I look at mindfulness or meditation practices is um those have been studied um and to the extent that they reduce stress I think that could be helpful I mean the question's also about stress and we talked about high levels of stress chronically uh can impair cognitive function uh uh function so the so meditation and mindfulness I think can be uh helpful there um there are small what I call associative studies and people who meditate or practice mindfulness might be a little bit less likely to get a dementia but those are small studies and the effects aren't huge they aren't as large as say we see with exercise and diet so I say it's some benefit uh but not at the level of say exercise and diet okay and are there any studies on the use of stem cells to reduce or reverse mild cognitive impairment or Alzheimer's yeah so stem cells uh get asked about and there there have been some studies especially at the pre preclinical level at the mouse level um there haven't been uh human Trials of putting stem cells in the brain for uh cognition um and I think application of stem cells is somewhat uh limited for our problem because this is not a problem of losing the cells that we need to replace for example in Parkinson's there's a part of the brain where you're losing the cells that are important for motor control and you may want to replace those cells so we talk about stem cells in Parkinson's quite a bit but in Alzheimer's it's not so much losing the cells so we don't have cells to replace it's losing those connections right and a stem cell is probably not going to help us deal with losing these connections okay so stem cells are not a big part of the Alzheimer's field if you were to go to a 5-day international meeting on Alzheimer's disease where there are hundreds of sessions you might barely find one session talking about stem cells for that reason it's not a big part of the field so they don't help preserve those spikes or those spines no okay oh and our last question how can I learn more about participating in your study do you have a website where we can follow your progress yeah so two things there so um there's the Standford studies and then there's a study we're doing so the study that we are planning has not started yet uh we have to uh you know do all the Preparatory work and if you know fundraising to make it possible we're hoping it'll start maybe in about a year or something like that it takes a lot to get these studies started when the study starts typically a big phase three trial in Alzheimer's will be in 80 or 100 locations and they're typically both in North America and Europe so there will be sites in the Bay Area probably at Stanford when it starts but it it's at least a year away but if people are interested in studies in General on our uh Stanford Alzheimer's Research Center website and our department memory Clinic website there is a information there on studies at any one time at Stanford we have four five six Active trials going on okay either I mentioned the one to prevent getting a Dementia or if people already have early stages of a dementia we have trials going on here at Stanford and what there's uh a contact info on that website and what you want to do is talk to a study coordinator and just figure out if you're eligible for a study or not um my patients and families we talk about studies all the time and the just generalities about studies almost all of them will have a placebo group um that's just unfortunately the only way we can do a study to know if a drug works but but the good thing is most studies are designed so that at the end of the what we call the blinded portion of the study everybody it's then we do the open label part where everybody gets to be on the drug so even if you're on Placebo you get to be on the drug that's not generally available so we try to reward people for taking that risk of bleeding on the placebo and when you see studies in the news I always pay attention to Placebo I can't tell you how powerful placebo effect is there's good and bad to that and we've done studies here at Stanford where we've had patients respond had miraculous res responses to various things uh Parkinson studies all kinds of studies I mean they'll come in and say you've changed my life know I'm not on the placebo the family test testifies to that obviously my husband is not on the placebo thank you so much and then the stud's over we unblind it and it's really hard to let somebody know you were on Placebo um and so and the reason why I say this is for two reasons um the brain is a very powerful plastic system you know we can really influence our brain and so maybe that's a good thing that people can you know do something um and but it it just tells you how important placebos are and I see studies in the news all the time where people said this changed my life this cured me guess what no placebo group we'll never know if that treatment worked or not good point um could you say so the Stanford Alzheimer's research department is that where well there's the yeah Alzheimer's disease Research Center adrc okay or you could just go into Stanford neurology and you'll find the memory Clinic the Stanford memory Clinic thank you and thanks so much for all that incredible information and help okay thank you everybody so

Channel: Stanford Medicine

Views: 12,930

Keywords: medical school, medical research, biomedical research, patient care, medicine lectures, medical education, covid-19

Id: 4DgfG7850V4

Length: 51min 13sec (3073 seconds)

Published: Thu May 23 2024