Can Vitamins Prevent Age-Related Cognitive Decline?

[Music] I'm going to start out by saying that as a scientist it's kind of hard to figure out how best to present some of the information that I'm going to give to you tonight you know how much how many how much graphs how many data do I show and well your eyes glaze over and that sort of thing so but they're also know in these groups because I've done this before is that there are some people who want to see that stuff there you know that that's that's what that's what they're here for and so I'm trying to get a balance I hope I get the balance right but what you are gonna see graphs and numbers but then I'm gonna show all right and this is what it means so you don't have to necessarily totally understand what I'm talking about so today's title is chem vitamins prevent age-related cognitive decline now the media and the lay public people like you want a simple story a causes B Alzheimer's disease causes dementia for instance C prevents or cures B this vitamin this miracle drug or whatever will cure you of Alzheimer's disease well I have to tell you that it really is rarely that simple and that's what we need to remember is there's no miracle here but when you're when we're done there's gonna be a basic message a basic take-home message that I think you you'll be able to use even if the rest of it in between you don't understand okay all right so you know we have science and the thing is and what's lost often on the the general public and the media is that science often is nuanced it's contextual it has caveats and sometimes you get apparent contradictions you get one headline that says one thing and then a month later there's a headline that says no that was wrong or it says something completely different and this leads to confusion okay and what I want to try when we're going to attempt to do tonight is to give you a little inside view of of science and how it actually works so you can see why this sometimes happens and then when we come out the other end as an expert I may be able to give you okay so this is what I think really is the case all right and and hopefully that's that's your message you'll get so here are some headlines that are some of the confusion so on here we have Time magazine the real power of vitamins new research shows that they'll help fight cancer heart disease aging but then over here are a bunch of other headlines some of them are consistent vitamin supplements compact cancer but then there are others that say all those vitamin pills doing are they doing you more harm than good all right and then one of my favorites up here one a healthy pregnancy forget the vitamins and have a tipple instead I have no idea what that means I don't know where the temple is yeah but you know I don't know but but I totally advise against that all right so what I wanted to point out to you sorry about the graphic images but up until the mid 1900s a little history lesson in nutrition is that was the golden period of when we discovered and that's the Royal we not me but we discovered the the vitamin deficiency diseases there were these diseases that we knew were really bad and it was then that we discovered oh they're due the deficiencies so you have things like night blindness and the severe case what's called zeroth Almia that's vitamin A deficiency these are the bleeding gums of scurvy which is vitamin C deficiency here are the bowed legs of rickets a vitamin D deficiency and kids this is a disease called berry berry which is b1 thiamine deficiency there's various versions of that pellagra [Music] nice and efficiency this is the dermatitis the characteristic dermatitis and then folic acid and vitamin b12 particularly b12 will be important tonight they produce this big cell anemia or macrocytic anemia so we've discovered that if you are deficient outright deficient you will get these diseases all right this is a clear cause and effect but where we are now we've discovered all those diseases and now we've moved into a new era and that new era is moving from the certainty of disease if you are deficient in a vitamin to the risk of disease when you are sub-optimal okay and so what we mean by that is if you have low levels but not enough to be deficient you might be an increased increased risk of say vascular disease or heart attacks or strokes or cancer or that sort of thing tonight we're going to talk about the risk of Alzheimer's disease and dementia and cognitive decline when vitamin certain vitamins are sub optical but not necessarily what we'd call deficient and here is the problem is that these kinds of studies are really really hard so risk reduction studies particularly with vitamins are very hard to do why is that they're expensive and because pharmaceutical companies can't patent vitamins or or corner of the market on vitamins they don't pay for the studies so we have to go to the NIH and these days we're having a hard time getting things funded okay so that's hard simply paying for them they often take many many years to do the right participants need to be recruited into these studies and that's going to be a big topic tonight in my talk those participants need to be compliant they need to do what they were asked to do and often that they don't here's another thing that's not appreciated a vitamin is not a drug and every one of you has some sort of status say of by them in b12 some or some of them this room might be low some gonna be pretty good so might be high nobody has zero unlike in drug studies where you don't have that drug in you until it's given to you and so we're starting people in these studies at different levels and that makes it hard right and then we have ethics to come into play if you are low in the vitamin and you go into one of these studies and they're called randomized clinical trials right and you know that people some people are going to get a placebo and some people are gonna get the vitamin but how do we ethically withhold a vitamin from somebody who's low that we know they're low and so we can't really use people who are really deficient and so we're using people who are sort of deficient and that makes it hard as well all right so this is something you need to remember when you see that headline where some Reporter has said that has just distilled everything down to do this and this will work you know it doesn't it doesn't really work that way and that's what the scientists know and then what I want to impart to you tonight a little bit so I would tell you that I think the most successful recent version of a vitamin reducing the risk of something rather than preventing deficiency but actually just reducing happens to be what we call neural tube defects and neural tube defects are things like spina bifida all right the March of Dimes as has been a big institution trying to prevent spina bifida and other birth defects and what we discovered in the late 1980s early 90s is that women if they take folic acid and the earliest parts of pregnancy before what's called the neural tube closes that this is very effective in reducing the risk of having a child with a spina bifida or more even more serious birth defects and what these des this graph is showing you is that in different parts of the world some of them had high rates of neural tube defect pregnancies some not so high but then every one of those locations locations there was a reduction in risk when folic acid was given to the population so this is one of the most dramatic public health interventions that has come along in recent years we have added folic acid to the food supply it's all in your breads and your cereals and your and and pastas and things like that we're all getting this extra folic acid and it has significantly reduced the numbers of these birth defects but what I want to tell you is that that's pretty rare these days there's there is very little low-hanging fruit left where we can say oh yeah it's very obvious that if you take this vitamin your risk of something is going to go down alright there's still that all the rest of it has all these nuances and caveats and all that so what I would tell you though that this science and I think this is where maybe you guys can be advocates and talk to your legislators and and and things this we doing these kinds of studies even though they're hard even though they sometimes give ambiguous answers sometimes they give positive answers sometimes negative answers they're really really important to do and we need to get them funded and that's what we need you to tell your legislators and so let me give you a an idea of why particularly for brain aging this is important this is a graph showing you what's happening to the world population alright so this was this is from the United Nations and in 1950 the world population looked like this so the pink are women or females and the blue or males and these are the age groups from the youngest to the oldest and you could see that in 1950 most people were would be very young most people were less than 20 years of age and there were very few of the very old in 1995 what you see was an expansion of the young younger age groups but now you started to see more middle aged people and you started to see the rise of older people and in 2050 when I'll be in my 80s I hope okay you see that this our pyramid is turning into a rectangle so the fastest growing groups are the oldest of the old all right so that's really really important when you take into account these sobering statistics which are by the year 2050 the number of people who are over 85 years of age will be about 220 million plus or minus and that right now the estimates are that almost 50% of that age group has some level of Alzheimer's disease so this is a coming epidemic that we need to deal with on all different levels healthcare a hospice care this sort of thing but also in trying to find cures but in the meantime cures are hard but in the meantime is there something that we can do to maybe slow this down maybe make it so that the disease comes on later in life or perhaps never if you know maybe some other disease gets you before you get Alzheimer's disease but this is really really important and we believe that nutrition can be a major player in slowing this down maybe preventing and that's and that's why we're here today so this is just to give you an idea this is what we're fighting against this is what Alzheimer's disease looks like in a whole brain what you can see here is the folds of the brain you see this little gap here this gap here those are much wider than they're supposed to be that's indicating that there's been loss of brain this brain is is to Orosz on the outside there's loss of brain on the outside it's not as nice and circular as it should be and then this is something perhaps most of you rarely see this is the microscopic amyloid plaques that occur you may have heard of the plaques in the brain and these are the tangles that occur in the brain so this is the microscopic indication of Alzheimer's disease so that's about 70 percent of dementia cases is Alzheimer's disease the about 15 more percent is vascular disease and so what you're seeing here are different versions of vascular disease in the brain this is a major impart that's affected a lot of the brain this is probably was very dramatic but over here we have little tiny holes and and sometimes you can have developed vascular disease in little tiny spots and then and that can just slowly over time degrade your brain and then this is the microscopic view this is a blood vessel and you can see here that all this blank space is where the cells have died okay so this is because there was probably an obstruction of some kind in this blood vessel so this is what we're fighting against and it's it's very serious and we need to really try and prevent this from happening so you may see a lot of advertisements on the internet and things for instance on the left here is seven ways to cut your Alzheimer's disease risk and at list these sevens it's it's really small you probably can't read it but I want to point out to you that it says number four is making vitamin b12 a priority number five is choose your multivitamin wise so there are people out there saying hey you can cut your Alzheimer's disease risk through supplements but is it really true okay up here we have vitamin b12 and memory folic acid these kind of work together to some extent down here we have vitamin D which I'm going to touch on a little bit here tonight I think but mostly what I'm going to talk to you and I'm gonna teach you a new word and that's a word called homocysteine so homocysteine is an amino acid and the way you should think about it is that when this amino acid becomes elevated in your blood it's very much like cholesterol so you all know that high cholesterol is related to heart attacks and strokes and vascular disease and that sort of thing well you should think of homocysteine in the same way when it becomes elevated it is a risk factor not only for vascular disease but for Alzheimer's disease and dementia and cognitive decline but I'm gonna but I'm gonna tell you the story because the story is very interesting and nuanced and I want you to hear it it's so you that you understand a little better about how to to think about these things and the Keith one of the key things to remember is that one of the main one of the main reasons homocysteine goes up in your blood is that certain B vitamins if they are low or deficient will cause this to happen alright so but I'm going to start with the the downer all right and this was a what you have to understand is that and I realized this when I was preparing this talk is that my first academic publication on homocysteine and cognitive function and dementia was 25 years ago right and I was like wow we've been doing this for 25 years that's a lot of effort to put in to have somebody come along with a press release that says taking B vitamins won't prevent Alzheimer's disease and looking at that going no that's not right I know I've been doing it for 25 years but you know this press release said taking B vitamins doesn't slow mental decline as we age nor is it likely to prevent Alzheimer's disease conclude Oxford University researchers who have assembled all the best clinical trial data involving many many people for the final answer on this debate and I'm the time here to tell you that this is well I won't use the word I wanted to do by the way this is the publication from the American Journal of Clinical Nutrition that that is behind this press release this journal is one of the top nutrition journals in the world okay so they don't publish usually bad things but that's the case so then later on in 2014 there was another press release this time from BBC News dementia study questions advice on taking supplements this is the the references in a journal called neurology which is one of the top journals in the field also and again we have this story so if Oxford and the BBC proclaim it then it must be true right well no so the question for us tonight is do be vitamin supplements prevent cognitive decline and the answer I believe probably but the devil is in the details so let's look at some of the details hopefully I'll keep you awake now some of you may be biochemically inclined most of you are probably not biochemically inclined however I will tell you something I'll just digress here for a second when I teach my students I tell them that they are all biochemists even though most of some of them are English majors and that's the right thing and the reason I tell them that by their biochemists is because nutrition is actually applied to biochemistry every time you stick something in your mouth and digest it and it goes into your body you are playing with your biochemistry and sometimes that sets off a light bulb in their heads are like wow you know it actually means something that what we're learning so I just so some of you may be interested in the arrows in the words this is homocysteine this is amino acid it gets metabolized but the important thing to take away from this is that if that folate a be the vitamin b9 om v12 which is also Co cobalamin vitamin b6 which is also called paradox in if you are low in there vitamins homocysteine will build up in your cells it will spill out in your blood and become elevated in your blood and we can measure that and when we do we can say oh way there's something there's something wrong here and that this might prompt us to give you B vitamins and also it's an increase in creases your risk of vascular disease like heart attacks and strokes now this is where the 25 years come in this is the article that I and and one of my mentors Irv Rosenberg published when I was a gret published when I was a graduate student at Tufts University we wrote a review article and in there we made the statement it turns out to be one of the first statements if not the first statement in the literature that connects vitamin b12 b6 and folate deficiencies and homocysteine this amino acid I'm going to tell you about - what we call cerebrovascular disease so vascular disease in your brain and that this might be behind the cognitive disturbances that are associated with low levels of these vitamins and so I'm going to show you September it's going to show you some graphs this is one of the highlights or the seminal publications in this field from 1998 and you know what's really ironic about this this was published by doctor Clark who was the same person who published that paper that said there's no there's no benefit so he was one of the first people who showed this relationship and what this is telling you is that if your homocysteine is high the odds of you having Alzheimer's disease at that time so this is what we call a case control study we compared people who don't have Alzheimer's to people who have Alzheimer's and we say what is your homocysteine level and more people with Alzheimer's disease have high homocysteine in their blood 4.6 times higher older adults with high homocysteine are more likely to have Alzheimer's disease and vice versa and the reason I say vice versa is we don't know in that kind of study what's caused and what's effect you could get high homocysteine because you have Alzheimer's disease rather than high homocysteine causing Alzheimer's disease but this was really important because it was the first study that actually verified on autopsy that the people had Alzheimer's disease when they were alive and that's a really important thing because the definitive decision on whether you have Alzheimer's disease is at autopsy right in the time of this study I would say that the clinicians like John were probably about 70% accurate in predicting whether you had Alzheimer's disease by 85 for John maybe but that will tell you but I'll tell you that now they're probably in the 90 the 95 percent range getting it right but you still need that autopsy the beat to be perfect to get it exactly right so anyway high homocysteine associated with this this disease all right so the next seminal study I wanted to show you was this one by a group led by dr. Seshadri and what this is telling you is when you take older adults who don't have a diagnosis of Alzheimer's disease and you follow them over time in this case all the way up to almost 12 years and ask who gets Alzheimer's disease what you find is this dark the the solid line these are the people with the highest homocysteine and they get Alzheimer's disease at a higher rate than the people who have low homocysteine all right so to put that into words older adults with high homocysteine are more likely to be diagnosed with Alzheimer's disease or dementia in the future so this is starting to get more towards cause-and-effect right that this is something that happens before the disease all right so now I want to tell you about the salsa study and this is an appropriate name study because it's the Sacramento area Latino study on Aging is a community-based cohort study blah blah blah but what you should know is that this study was done right here in the Sacramento area with a woman named Mary han was the PI of that study many members of the Alzheimer's Institute here were involved in this study it actually kind of is going on still at this point in fact I think she's moved on to what she calls the Nino study which is the offspring of the of these people and the salsa study has been very very good to me these are the many publications that we have put out on this population many of them related to B vitamins homocysteine cognition dementia in this population so I wanted to show you some of these data so that you can get a sense of why I think this is this area is important so breaking a lot of work down into one table what you're looking at here is data from two studies me on was the lead author and one one of my graduate students Marissa Ramos who now works for the California Department of Health was the author on the other and what you're looking at here is different cognitive function tests so we have the neuropsychologists have a way of assessing how well your brain is working at a psychological level so the first test is just a global test this is mainly a screen you come in and they ask you a bunch of questions actually to do a bunch of things and you get a score and the higher the score the better your cognitive function and then they have other tests that drill down into specific cognitive functions so delayed recall is a short-term memory test so it's something like I might give you three words to remember and then distract you with some other tasks and then come back and ask what were those three words I'm not gonna try that on you tonight right but that's that's short-term memory where you have to remember something after after a little bit of time ability to name objects so they give you a bunch of pictures and you have to say oh that's a chair and that's a building and that's a tree and then then there's more there's long-term memory tests there's attention and visual spatial skills all certain all different domains an executive function was just probably the more the most challenging tests because this requires you the sort of followed directions and do one thing lead to another and that sort of thing so these are all different kinds of tests and what we found just to break this these studies down very simply both your folate or folic acid status and your homocysteine level are both associated with your global cognitive functioning that if your as your folate level goes up you have better folate status you have better cognition and as your homocysteine goes up you have poorer cognition all right but notice that when we look at the subdomains folate was associated with memory short-term memory homocysteine was not well homocysteine was associated with some of the others so basically what this is saying is that both of these things are important and they while they are related to each other biochemically they are associated with different things they're independent of each other as well we then went and asked what hat what about dementia that was cognitive functioning but without what about clinical dementia and we found that without going through those numbers just get to the point is that both Bowie and homocysteine were important so older adults with low folate status so low vitamin status or high homocysteine are more likely to have cognitive impairment and dementia we then ask the question what about over time whether if we took the people who didn't have dementia or some sort of clinical cognitive impairment and asked does homocysteine or folate predict this the development of cognitive impairment or dementia and so what you see here what is being shown here is that older adults with high homocysteine just like we saw before in the Sheshadri study but not low folate are more likely to be diagnosed with cognitive impairment in the future so you might ask well why not low folate well what happened in 1998 was we put all this folic acid in the food supply and here's your memory test why did we do that there are two defects right okay so it seems to us based on our data that that not only prevented Norrell team defects but now Foley wasn't associated with dementia prevent dementia later in life we think that that folic acid being put in the food supply actually reduced some of the dementia in our population that's we haven't proven that that we think that these data are consistent with that however the Homa cysteine was still important and what this these day they're showing I'll just this one's even more cut that graph is even more complicated I'll just avoid even going into it but the the bottom line is that vitamin b12 comes into play so older adults with high homocysteine because of low vitamin b12 are more likely to be diagnosed with cognitive impairment in the future okay so what this is telling us is that high homocysteine and low b12 may be really important and now I want to show you some data from a collaboration we had with University of California at San Francisco and this is a really interesting study because the people in this study were chosen even though their average age is about 72 years and their education level was very very high all right college and post college education level they were very very healthy they were chosen for being very very healthy no apparent cognitive impairment very little disease like diabetes and heart disease that's our thing this was a healthy aging study they wanted to see what were the characteristics and you can see here that they're full eight levels nobody was deficient very few people were deficient in vitamin b12 so that goes along with their healthiness their home a cysteine level I can tell you this number it is is relatively low however there was a small percentage who had high homocysteine and also down here this this number here creatinine some of you may know that from maybe getting it measured this is a measure of your renal function your kidney function and there was a as expected in an age group this high there was some renal dysfunction going on but in the screening test for cognitive function they on average scored 9 out of 30 which is really really good if you scored 29 out of the 30 on this test the neurologists would send you home you're doing good we'll see you next year right so these were really healthy cognitive cognitively what I can tell you is even in these really healthy people we found associations with homocysteine and the volume of brain in certain regions so using MRI we were able to see that very important regions related to Alzheimer's disease and dementia memory and the sort of thing things like the hippocampus which is here the amygdala the basal ganglia the thalamus these are all regions they're really really important and we found that as homocysteine went up in this population the volume in these areas of the brain went down so this is a really early indicator we also found that there's some things called ventricles in your brain which are really kind of holes in your brain there is supposed to be there they're filled with cerebral spinal fluid right but they shouldn't be too big and when they're too big that means you're losing brain and we also found the homocysteine was correlated with that so these are the numbers I'm just going to skip that but we then went on to ask ok is this associated with cognitive functioning alright so so maybe they've lost a little bit of brain but maybe their cognition is still pretty good well we found that when we looked at global cognitive function there was no relationship with homocysteine just sort of general scream some basic things like being able to process words basic memory tests none of that was associated but when we got to the harder cognitive functions what we call executive functions we started to see significant correlations in a bad way so what we think is happening here is first of all high homocysteine serves as a very early indicator of brain atrophy lose loss of brain and cognitive impairment and apparently healthy older adults and we think that homocysteine can serve as a canary in a coalmine are you all familiar with that concept in coal mines they'd have a little canary and the canary fate fainted you better run because they were gases being released that was going to because the the bird was so small it would be affected first before the humans well we think that homocysteine might be one of these Canaries so if you go to your doctor and you have it measured and it's elevated that might be an early indication that something's going on or will be going on with your cognition and and your brain now I depict this here I use this this figure that I found from the internet that this canary as a pickaxe and the other question is whether or not this homocysteine is actually causing the damage or if it's just a marker we don't really know so that's that's why the the canary has a pickaxe alright so now I'm going to take you through this figure because this figure is the most exciting thing that I think I can show you tonight and I want you that I want you to appreciate what's being shown here so I'm gonna take a few minutes to go through this this is a study by dr. Smith and dr. Smith actually came to visit UC Davis a few years ago and presented these data he's from the the UK and they took a group of people who have what we call mild cognitive impairment so they're not normal but they wouldn't be classified as having Alzheimer's disease or dementia but they're probably on their way okay so they're in decline and what they were doing was that they were they were taking MRI images of the brain and the first thing they did was they they said how much brain do you have what's your total volume of brain and then they said how is that related to your homocysteine level and if you look on the left side of this figure and they'll try to take it take it through take you through it slowly on the bottom is your homocysteine level in your blood increasing okay and on the left is the rate at which your brain is being lost each year in percent and then this group of people they ranged in a loss of brain over a per year of around 0.5 percent all the way up to 3 and above 3% think about that if you're losing 3% of your brain every year in 10 years 30% of your brain is gone that is serious stuff right and and so what's really fascinating about this is that your homocysteine level is predicting how fast it's going so if you have a low homocysteine a normal home Assisting level you're at the point five percent so in 10 years it's 5% loss but if you're at the higher levels of homocysteine now you're at 2% 3% and that's 20% 30% over 10 years but what was really really cool about this study is it they took people half of the people they gave them B vitamins and those B vitamins lowered their homocysteine level and oops sorry and what you see here is what their home Assisting level was at baseline and what you can see with some variation is that whether they were low at baseline or high now they're flat okay which means that the B vitamins were slowing that loss of brain even for the people with the highest soma cysteine levels at the beginning of the study and that is really really important really really dramatic it says there are some people who will benefit from these B vitamins now to give you a sense of what we're talking about this is the likes a little bit right you may not be able to appreciate this but this is comparing to people who started with high homocysteine of about the same 22 or 24 this person got placebo and their home and cysteine actually went up this person got the B vitamins there homocysteine was cut in half and this person's loss of brain per year was two and a half percent and this person's was only 0.46% and the way the way you look at this this is an overlay this is a the baseline picture of the brain and then everywhere that you see color is loss of brain over two years and you can there and if you look closely if you were the those in the back of you came up you'd see there's a lot more color in this one and a lot less color in this one all right so that gives you an image and then this is probably a little too complicated but then when they looked at specific regions they were able to confirm their finding so B vitamin supplements slow brain atrophy in older adults with mild cognitive impairment and high homocysteine now I want you to understand these this is the nuance these are the caveats right it's not all of you it's not all older people it's people with these specific characteristics they're going to benefit and that's what's lost when it goes to the press but before I get to that more on that I just wanted to show you that this also plays a role in cognitive function people with I'll just go to the final result here the people with high homocysteine so above 11.3 those have got B vitamins maintain this their memory on this memory test over the two year period that's the blue lines but the dark lines the black line is showing you that the ones who got placebo after two years have started to loss lose their cognitive function so there's an association between this loss of brain and loss of cognitive function so B vitamins supplements low cognitive decline in older adults with mild cognitive impairment and high homocysteine this is dr. de Carly's graph that it gives you an idea of what is happening to your brain over time as you age the doctor de Carly is the head of the Alzheimer's Center here at UC Davis and he would be here tonight that he's celebrating his birthday so he needed to go home so what I wanted to show you I'm sorry I want jumped ahead a little bit what I want you to appreciate is that this is time at the bottom and in black is what we're calling brain injury so that could be Alzheimer's disease vascular disease it could be being punched in the head a lot concussions this sort of thing over time we will develop injuries to our brain for region reasons some people develop less of that injury as they get to be 89 years old and some people develop a lot more and they cross a threshold and they're impaired cognitively or they have dementia and then looking on the left the the blue cognitive ability and the red lines this is what happens to your cognitive function over time and some of you I hope everybody in this room will have this line or maybe a little loss of cognition when you get older but it will remain fairly good and you probably all know people like this there are 90 years old and there they're clear and lucid as you as can be then there are others who may decline a little more quickly and they might when they're they're fairly old may have you know fairly minor cognitive problems they forget this or forget that but they're doing fairly well then there are other people who follow these trajectories where they're declining quickly and then they fall off the table and they become into in dementia and Alzheimer's disease and so what I just showed you in all those data that I showed you the Clark study the other the other studies Sheshadri that salsa study by Mary Han dr. Smith and then the study that we did with UCSF which I hope to write up and published this summer at every stage of this homocysteine was important it was high at every one of these stages okay so all of these data all together really are really good circumstantial evidence that this is important and that you should conclude that we should be taking B vitamins to lower homocysteine and we can maybe prevent or slow things down so taken together these data suggest taking B vitamins lower homocysteine prevents low cognitive decline in all the dotes so I'd ask you are you convinced yes well I remind you that of this of this paper this this press release right and and so what what I wanted to explain to you is what's going on here is what's called a meta-analysis and a meta-analysis what is when they take many many different studies and they put them all together and in fact it's funny you can make quite a good living in science being somebody who who doesn't do any of the research at all just takes everybody else's and stuck it stick it together and analyzes it statistically and writes papers like this okay but the power of these studies is that there are a lot of people the more people subjects that you can put together in these statistical analyses the more power you have to see associations and see connections and make definitive decisions on whether something is real or true or not okay and that's why they're done and they're really important without what I'm here to tell you is that when they're not done well or if they're done well but they're asking the wrong question or they're using the wrong people wrong studies they can give you the entirely the wrong answer and in this case I actually think it's a bit dangerous what happened okay so let me show you yeah again sorry about these graphs but basically these are the studies that they put together and then they they get a an average of all the studies and what you're seeing here is that if this symbol that they came up with the represent all the studies was to the left of this center line or to the right it tells you that b-vitamins are better or worse under these circumstances and what you can see here is because this symbol is straddling the line it's telling you that they believe that the vitamins don't work they don't do anything they don't make you worse they don't make you better and then there's a second aspect to this study where they're looking at the different cognitive domains like memory and thinking speed and executive function and again all of these things that their conclusion is that they don't do anything a colleague and I from Wales Andrew McCadden got really kind of pissed off myth yes thank you myth and so we did with academics do we write a paper her that if you look at the title you know we're talking about somebody called Bradford Hill and meta-analyses and causality it's very academic right but what it truly is is an ex Corey ation of head study alright and what and there are a lot of things we found wrong with the study and but I underlined in our abstract to this paper the the most important thing I want to get across to you and that is careful examination of the trials in the meta-analysis indicates that no conclusion can be made regarding the effects of homocysteine lowering on cognitive decline since the trials typically did not include individuals poor actually experienced such decline so let me give you an idea of that that remember this second press release well if we look at that study carefully I'm sorry about the low numbers but the small the small type but basically there are there are four different cognitive function tests and they're comparing the placebo versus the B vitamins and it's over two years and what if you look very carefully at this all of the subjects who are receiving placebo none of them were declining in their cognitive function and so you can't prevent something that isn't happening right so this is the nuance this is the the caveat right you have to pick the right people there are not everybody you could we could throw vitamins at all of you and there be a percentage probably a minority of you who might actually benefit because you are of the characteristics that would benefit from those vitamins that could be you have low B vitamin status you have high homocysteine you're beginning to decline in cognitive function but the rest of you who are doing fine and if there's some unfortunate folks who actually already are at the dementia or Alzheimer's disease stage we don't think that's it's going to benefit you and so that is the nuance that's lost in that press release that says it doesn't work alright so probably but the devil is in the details now key consideration we so I've already gone through this just to reiterate we need to know what your cognitive status is we need we have to ask the right question what truly was asked in that study that we excoriated was not whether it would prevent cognitive decline or prevent Alzheimer's disease what was actually asked in that study was whether or not B vitamins will improve your cognitive function and that is a very different question okay and I would tell you that in most cases that is not the the the question that we're interested in we're interested in preventing decline all right and then of course it matters what your B vitamin homocysteine status is all right so we're back to here and what I wanted to just point out to you so there's a difference between treatment and prevention okay and what I want to tell you is that the Alzheimer's disease process and the dementia and and vascular disease in your brain once it's progressed very far it's it's asking a lot for vitamins to help you at that point and what really important is that we're talking about prevention we want to get you early we want to get you filled up with the good status of vitamins at that point all right and I think maybe there's one other version of this coming up and there we go and then one more click and so this is what we've been talking about your homocysteine level your B vitamins level will it help you at this stage so conclusions B vitamins supplements best protect against cognitive decline taken prior to the development of brain damage due to Alzheimer's or cerebrovascular disease B vitamin supplements may only be effective in those individuals with metabolic evidence of deficiency such as high homocysteine technical term being hyper home assistant emia so now here's your take-home message my practical advice for older adults 60-plus go to your doctor have your b12 status measured you want to have what's called a total b12 that's a measure of all the b12 in your blood but you also probably want to have something else measure that's turned the the science particular I've been involved in this the science in establishing your vitamin b12 status has progressed in recent years to say that measuring just your total b12 isn't enough you need to measure some other things there's something called methylmalonic acid but we would recommend in this case because we're talking about cognition a b12 and a homocysteine your doctor very likely these days if you go to ask them you asked your doctor please measure my b12 if they haven't already done it they very likely will do it in this day and age the homocysteine measurement they might wait they might say let's look at your b12 first okay now I haven't talked about vitamin D but I'm now going to talk about it briefly but I also recommend that you have your vitamin D status measured turns out the deficiency even in this region of the country where you're exposed to so much sunlight and you know that Sun creates synthesizes vitamin D in your skin even in this area there is a lot of vitamin D deficiency and insufficiency so the recommendation now your doctor will very likely measure your vitamin D even if you don't ask but if you do ask probably will measure it all right and what I wanted to tell you is it - vitamin D deficiency like b12 deficiency is associated with increased rates of cognitive decline and that is a paper that we published in 2015 there's a it was it came out of the Alzheimer Center here and basically we've been collecting for like 10 12 years lots of blood samples there's some of the folks some of the folks from the Alzheimer's center in the room were involved in the collection of those samples they got sent over to my lab when I was here I froze them away and we built this big Bank of samples we got over a thousand samples it's probably much higher now and then we started measuring stuff and the first thing we started was starting with was measuring vitamin D in those samples and we published his paper and with a journal called JAMA and neurology and it got a lot of press and we're very excited about this study so I just wanted to give you a little sense of it there were 382 people in the study about 76 years of age as usual there were more women than men fairly good education at least the high school graduates on average what was really important about this study was that it was ethnically and racially diverse most of the work that has occurred in the last ten years on vitamin D and the brain has been from northern Europe and very very to be blunt about it very very white okay and and so what was really what is really great about the Alzheimer Center around here is that they're recruiting other people right so there's African American and their Hispanics so about half the population than or more than half of the population were these two ethnic racial groups and a few others some agents not very many and so that was really really important also there were people about half we're cognitively normal some had what we call mild cognitive impairment and some had outright dementia and what you can see here which was really amazing to us is that the average level of vitamin D in the blood was actually in the insufficient range so that was really amazing and 26% of the population we would call deficient even living in Northern California with all the Sun that's probably due to the fact that when it really is sunny out we we stay inside right because it's too hot we also spend a lot of time working inside and we all know we don't want skin cancer so we slather ourselves with with a Sun sunblock and that actually blocks the conversion of vitamin D in your skin plus the fact that our sources of vitamin D in the diet are dairy products and many of you are probably not eating dairy products because you have lactose intolerance or that you know you don't you just ordered maybe even don't even like milk right plus fish some lot of people don't like fish and most people don't eat enough fish another source of vitamin D so you put all those things together there's a lot of deficiency even here in Northern California okay so long story short what we found was if you were adequate in vitamin D let me let me show you what's going on here we have four different cognitive function tests that we did this is memory another kind of memory it's what's called visual spatial ability that's kind of like moving thing objects around in your mind you know in three three dimensions and then executive functions and what we found for all of them and significantly for for memory and executive function was that if you were insufficient or too efficient in vitamin D your cognition was declining more quickly than if you were adequate in vitamin D back to the practical advice if deficient in vitamin b12 if your doctor finds you deficient then you can have intramuscular injections okay but a lot of people don't like that and usually those are reserved for people who have really severe b12 deficiency due to a malabsorption condition called pernicious anemia there may be one or two in the room who have this but only about two to three percent of people over age 60 have actual pernicious anemia that requires inner muscular injections on a monthly basis for the rest of us oral supplements are probably sufficient but it's really important to check your b12 and your homocysteine levels with your doctor don't let your doctor measure your v-12 in your homocysteine and say oh I'm going to give you b12 and then never check it again alright because it's quite possible that the dose you're taking might not be good enough might not be high enough to get you to where you need to be so you need to follow up and make sure that you're you're getting there all right and so that the same advice is goes for vitamin D if you're deficient oral supplements but this is important you can take as much b12 as you want as far as we know and it's fine there's really no toxicity but there can be toxicity the vitamin D and so the upper what we call the upper tolerable level you should not take more than 4-thousand what we call international units for dead per day so you want to work with your doctor to figure out what dosage you should take to bump up your vitamin D levels into the normal range now the caveat to all this is that we have no idea at the moment whether vitamin D supplements I showed you the vitamin that the B vitamin data where supplements actually helped but we have no idea at this point whether giving those vitamin D supplements will actually help your brain actually slow things down because those studies have not been done John dr. John over here is the the principal investigator on a grant that is at NIH that got scored pretty well and we're hoping we're crossing our fingers that any day now they'll say you are funded and if that's funded we will be doing a intervention trial here at UC Davis to see if vitamin D will actually be beneficial and we will be we will do our best to actually pick the right people to put into that study it's to give ourselves the best chance of seeing an effect if it if it actually occurs so I just want to end to acknowledge these studies take lots and lots of people there are actually many people not even listed here but there are people from here at UC Davis from the Department of Medical pathology where where I was before I went to Rutgers the UC Davis Alzheimer's the center Center here's dr. John right here okay dr. de Carli the head of the center the nursing staff really important component here the Department of nutrition and the USDA nutrition center on the Davis campus the leader of that was involved in a lot of salsa studies dr. Allen the leader of the salsa study itself Mary Han the nursing staff there and then the UCSF people and then all of the grant funding that comes into play here so that's the end of my presentation and I am open to take questions at this time there's been a lot of controversy about vitamins versus eating food yes and so I wanted to ask you because you were about the absorption of b12 and vitamin D yes should we be getting it from our food instead of supplements because also most of vitamin b12 is found in meat yes going vegan and vegetarian how is that affecting right so the question in case you didn't hear in the back was about the difference between supplements and foods as nutritionists we say it is always best to get your nutrition from foods okay because foods come with all sorts of other things that we don't really you know necessarily know what they're doing but particularly fruits and vegetables and things like that so we really urge people to try and get all of their nutrition from foods but the truth of the matter is for various reasons you might not eat well you might not like things you might have a physiological problem with absorption you might have have chosen to be vegetarian or vegan there are all sorts of reasons why you may not acquire certain nutrients at high enough levels and we know that b12 and vitamin D in particular particularly for older adults are too problematic vitamins and we recommend supplements under those circumstances but if as a 20 year old we might not recommend them because you just be sort of throwing your money away because you don't need them at that point so in a practical sense or level if a patient is presented to a neurologist and says oh by the way I saw this whiz-bang presentation on b12 what's the status among the practicing clinicians in the area when presented with this kind of data so I would say I might I'll make a comment but dr. Lucini might make a comment because he actually sees patients but I would say that in the last couple of decades there's been increasing awareness in the medical profession of nutrition and that more and more when you go through a doctor they're like oh yeah yeah b12 vitamin B yeah we should be looking at that but it's not 100% do you want to make a comment on it I would say that b12 has been more established and accepted as an appropriate lab for any patient with dementia to rule out a metabolic treatable cause vitamin D is still kind of a new kid on the block and there's it's not as widely published as being a standard test for all patients with with dementia now MCI my lack of impairment my recommendation is those patients also be considered for metabolic and nutritional deficiencies and it even makes more sense as you want to prevent dementia rather than wait for dementia and again that's not uniformly done but it should but it's generally done that the same test would be done if you if you have mild cognitive impairment if you have objective cognitive impairment of most neurologists will quite uniformly check of b12 most primary cares will even check of b12 in those situations vitamin D is probably more likely to be thought of by the neurologist for for causing cognitive impairment the primary care might think about it in terms of osteoporosis I just had a question about the vitamins can you just get by with taking a multivitamin or do you have to take a multivitamin plus b12 plus your vitamin D pill because I think I have a calcium pill that has vitamin D in it yeah so can I get by with the multivitamin pill yeah so alright so the question is what kind of supplements should you be taking so you have your multivitamins multivitamins are usually formulated for maintenance right they're providing the RDA or a little bit higher to keep you at a normal level but in these problematic vitamins like b12 well you may be mal absorbing it from food or from pills you need to take a lot higher and that and under those circumstances you would consider taking a separate b12 supplement the I think the same thing is true with vitamin D and but the but uh you know I'm a bit conservative I think you should go to your doctor and actually have them measure these things I think just throwing vitamins that somebody is is is a shortcut and you may be just throwing away your money well so you know it's a plus or minus though all right well then I'm insisting as a blood test as well so yeah is that uncommon is my is my MD going to say yeah maybe maybe I think it depends on you know who you go to here at UC Davis there's a lot of people who a lot of a lot of the docs know about homocysteine and they would probably say okay we'll do that but other places not and so sometimes you may have to educate your doctor you know I'm not a scientist so I'm just putting this out there because I don't understand is there a is there or is there not a DNA marker for Alzheimer's or something like that could be something that you screen people for before you put them in a study so then there would be something then right or is it not so there's what's called a PO II okay and it turns out not to get too complicated about it but it comes in different forms there's a to form a three form and a four-four okay and most of us have a three form it turns out that if you have the four form you are at significantly increased risk of developing Alzheimer's disease later in life and that is proud that is the strongest genetic marker scientists in more recent years have been looking for other genetic markers and there's they're they have smaller risks associated with them but when you add them all up you know they can have larger risk so somebody who has the a PO for a pony for it's it's unclear what to do with that information and whether it's even worthwhile telling the patient because there's no real treatment other than to tell you oh you're at higher risk and we know there's not much we can do about it but there are drugs to help in Alzheimer's disease but I think under those circumstances maybe the answer is nutrition in the sense that okay you are at higher risk but maybe we can slow this down maybe maybe we reduce all that saturated fat that you're eating maybe we get you to lose some weight maybe we get some supplements into you like b12 and vitamin D and maybe we can sort of ameliorate some of that slow it down give you more years but where it starts to come into play oh yeah we could studies are done that way yeah certainly are that can be done the marker is fairly straightforward to measured genetically particularly these days dr. vitamin b12 orally liquid or pill one is better than the other and also the amount taken right okay so again a lot of nuance to this question but the the simple answer is the liquids and the pills are probably very good it turns out though that more isn't necessarily better because the amount that we can absorb of any given dose is limited so it turns out there's some evidence that if you take smaller doses more often you know a small dose in the morning and the afternoon and the evening you might actually do better than taking one large dose at a given time but more importantly is is your ability your physiological ability to absorb the b12 in general and that's where the remember I mentioned this disease called pernicious anemia there's also something called atrophic gastritis which is loss of stomach acid and that leads to the inability to get b12 out of food so if you eat a piece of steak for instance it's hard for you to extract the b12 out of that and so these cause malabsorption and under those circumstances you you want to take higher doses and in fact for pernicious anemia where you can get intramuscular injections the alternative is to take very large doses every day and that sort of shoves b12 into you just by diffusion but pills and liquids should be about the same you'd have to look on the bottle and and say and ask okay how much how much b12 is in there and you may look at that go you know that's that it's it's not a problem for toxicity but you know if you take half of that you're probably just as good and you your it lasts longer right so you don't have to keep buying as much right hi a couple questions if I can one and I want to say my mom's been diagnosed with mild cognitive impairment and she's being screened for a study with dr. Kyle at Sutter neurology and they are definitely and they have checked her b12 levels and vitamin DS and now the homocysteine I'm not sure yeah but they did just check her blood yesterday the Didache courtesy draw Sutter to send off to Lilly so I'm gonna get results of that even though it's not an epoch and I'm gonna see if that was checked uh-huh on D my levels are very low I've had mine checked the lab slip will say something like twenty to thirty is normal but I've had my mom's cardiologist for instance dr. van at Sacramento heart want to see it above 50 and I saw your screen said normal what's up 250 yeah so what would be the ideal level and there's d2 and d3 one is plants one is Sun not clear on that which are we talking about yeah okay so a lot of a lot of good so again nuances and caveats right okay where to start so there is significant debate in the among the scientists studying vitamin D about whether or not there's a too high level and I think everybody thinks that you can gets up too high right but what that cut off when you measure it in the blood what that cut off is nobody's really sure at this point so I would say conservatively you want to be in the maybe in the 40 to 50 range but maybe not go much higher than 50 until further notice you know what I mean until we figure this out because you can get too much and it can be toxic so that wouldn't be good for you so that's where it gets a little interesting because what you need to take as a supplement may be higher or lower than somebody else so it's okay yes so that's that's the second thing that you have to consider what what the level that we were talking about was a daily dose but you can also take a very large dose but only once a week right and then that can sort of slowly supplement yes and so that so you want to be careful you want to make sure it's not too high yeah yes and they can they can do what we call titrating it they can look at it said okay this is working or oh you're you're too high we can cut your dose down yeah that's right yeah so d3 is what is synthesized in your skin when the Sun shines on it d2 is typically found in supplements and maybe in some other sources from from what we know there's not much difference between the two I think most of the time when you're getting I think it's studies use d3 so I don't have much else to say about that I've now seen Alzheimer's at autopsy yeah to see the plaques yeah but from what I understand now also my mom is going to be doing a PET scan yeah and that the PET scans have gotten to the point can they indeed diagnose the plaques yeah I'll let dr. Alessi answer that right right those those have been of research studies until very recently it's actually the amyloid PET scans and also CSF a beta levels from spinal taps are two ways to diagnose abnormal amyloid however while FDA's improve that as a diagnostic for Alzheimer's dementia Medicare and insurance will not pay for it yet so we're actually doing a study called the idea study in national UC Davis is participating it's run out of UCSF and that's looking for imaging dementia evidence for amyloid scanning and Medicare and the government and the Alzheimer's Association are Co funding this to say will it change outcomes change survival and healthcare dollars spent for example and so it might be reimbursed in the future right it's about it's about a four thousand dollar cost so it's quite and so we don't know that it's you know till there's a prevention therapy and it's proven then it's not clear if it's cost-effective I heard that people with and I'm not sure if I'm going to pronounce it right but the MTHFR gene mutation can't use all forms of b12 and that it's possible that their b12 test would appear normal but it might be in a form that they can't use I'm one and then you mention the methyl malonic acid test yeah would that take that into consideration with that okay all right so first of all those two things are completely separate from each other all right the MTHFR story let me try to explain it as simply as possible there's a gene that makes an enzyme that's involved in metabolizing folic acid and there's a genetic difference that some of us have that reduces the activity of that enzyme and those people need more folic acid to have as good metabolism as somebody else what sticks in my craw because I'm an expert in this is there's a lot of disinformation and misinformation around this genetic difference and one of the misinformation is what you just said it really does not affect the b12 at all okay and I could really go into a whole lecture on you know what goes on biochemically and all that but the beach well the kind of b12 that you take really should not be affected by that enzyme defect now what might be different is the type of folate or folic acid that you take so we typically have we typically take as supplements or what's been added to food is what's called folic ass but there's another form which is called methylfolate and there is some suggestion and some theoretical basis that if you have that gene that we're talking about that taking methylfolate would be better than taking folic acid but I have to tell you you'll look on the internet and you'll hit here and you'll see people saying definitively oh you have to take methylfolate and not folic acid and I let me tell you the science there's there's just no science to back that up right now it hasn't been done it's not that there's a yes/no answer to this question it just hasn't been done and so you're getting misinformation from these sources and it's really frustrating when you know that that's happening however on the other hand the the problem that you know the biggest problem with taking methylfolate instead of folic acid it's probably it's significantly more expensive but I don't think you're going to hurt yourself at least as far as we know yes that's right so folic acid unless we added it to the food which we've done but in most foods like spinach green leafy vegetables broccoli orange juice it's in these methylfolate form right and again very quickly methylmalonic acid is a separate separate thing it's something that gets elevated in your blood when your b12 deficient and it's a market so you have that measure then it can help you understand what your b12 status would you give me your opinion on the quality of vitamins say purchased at a health food store as opposed to Costco thank you for asking that question I was waiting I was waiting for that question so these are the slides I show our students there was a dietary supplement act called Desha in 1994 it means that dietary supplements aren't drugs they're treated differently importantly they the difference between a drug and a supplement very quickly is that a drug requires FDA approval a supplement does not drugs the burden is on the company to prove that they are safe and effective they cannot sell it if they are not safe and not effective but a supplement the burden is on the FDA to gather the evidence that they are not safe and you do not have to prove that they are effective which is why it's a wild-west snake oil world out there that you have to be aware of the reason the rationale is that not requiring the drug proof for supplements is that there's freedom of choice for consumers and it reduces the FDA's ability to enforce unreasonable regulatory barriers so you know we're fighting this battle all the time you know between Republicans and Democrats just to be blunt about it right government regulation and and freedom and all that sort of thing so it comes into play here and the difference between drugs and supplements right so ramifications there are thousands of untested unregulated supplements sold every day there's little safety data little assurance that was supposed to be in the bottle is actually in the bottle of content or amount so snake oil salesman caveat emptor let the buyer beware alright but there is something there is something to help you and that is what's called the u.s. Pharma kapiel convention that's a really strange name but the bottom line is this is a group that looks at supplements and if they can show if they think the evidence is good that what's in the bottle is what is said is in the bottle and it's that the amount that said that's in the bottle and they put their seal on it they put the USP seal on it and you should look for that on your supplements if it's not there maybe you should be go look for some other brand that has that on there okay and and then this is more of what I've already said basically bottom line here is that there are specific circumstances where supplements are called for such as you have a limiting availability of food maybe you're not taking dairy lactose intolerant or vegan vegetarian rat-like for young kids rapid growth development and various other reasons happy oat st that was maybe six because what these basics depends is a kind in crates homocysteine and is there any association yeah so the vitamin b6 question is less certain than the b12 and folate question so vitamin b6 deficiency will cause your homocysteine to go up but it's really unclear how much b6 deficiency there is around and it seems that when we do give B vitamins to people it's really the Foley than the b12 that lower your homocysteine typically so it's sort of a stay tuned on b6 there's still a lot of research going on you said that you know we're trying to reduce the homocysteine in our systems to prevent the or slow the decline of cognitive decline are there other ways besides taking vitamins okay so one of the ways would be to avoid getting diabetes so that means maintaining a normal weight because obesity associated with diabetes it turns out that that's a big risk factor you want to avoid trying to get cardiovascular disease so you want them you want to get a good lipid profiles so that that's that can be dietary not supplements but through you know good healthy eating lots of fruits and vegetables limiting your saturated fat you know all the basic stuff that most people should know now okay exercise comes into play and maybe even bother it alcohol intake for instance it turns out you may be you know a glass of wine a night yeah a glass of wine a night is supposed to be pretty pretty good what I'm avoiding saying the one thing that I'm avoiding saying is saying anything about other supplements because I don't think for most of the other supplements the science and the brain on the food the brain isn't very good it's it still bit of wishy-washy and may suffer from some of the problems that I was talking about in the studies but there are things like omega-3 fatty acids beta-carotene and it was going to say one other blanking on it what but there are some where I'd say yeah maybe and then there are others I would say I don't know and I wouldn't recommend because I just don't I just don't know you

Channel: UC Davis Alzheimer’s Disease Research Center

Views: 26,791

Keywords: vitamins, alzheimers, brain, health, vitamin D, vitamin b12, aging, vitamin b6, dementia, Prevention, Cognitive Decline, Joshua Miller, healthy aging

Id: td_sSJ5cyME

Length: 81min 7sec (4867 seconds)

Published: Fri Oct 27 2017