The Peter Attia Drive - #251 - AMA #46： Optimizing brain health： Alzheimer's disease risk factors, APOE, prevention strategies, and more

00:00:00.000 hey everyone welcome to a sneak peek ask me anything or ama episode of the drive podcast

00:00:16.400 i'm your host peter atia at the end of this short episode i'll explain how you can access

00:00:20.840 the ama episodes in full along with a ton of other membership benefits we've created

00:00:25.460 or you can learn more now by going to peter atia md.com forward slash subscribe so without further

00:00:32.140 delay here's today's sneak peek of the ask me anything episode welcome to ask me anything

00:00:41.260 episode 46 i'm once again joined by my co-host nick stenson in today's episode we have compiled

00:00:48.100 a lot of recent questions that we've received around brain health this has been in response

00:00:53.300 two recent podcasts on brain health alzheimer's disease neurodegeneration and the recent series

00:00:59.320 on limitless where i worked closely with chris hemsworth during a time when he learned that he

00:01:06.160 had two copies of the apo e4 gene so needless to say over the past call it four or five months we

00:01:11.380 have been overrun by questions on all things that pertain to brain health in today's ama we discuss

00:01:16.620 the following how alzheimer's disease is diagnosed what we need to know about it based on blood-based

00:01:21.920 biomarkers how these predict risk of disease what the various apo e genes mean in terms of a person's

00:01:27.780 risk of developing alzheimer's disease and why i believe it's important for everyone to know their

00:01:31.300 apo e gene which is really code for i believe we can do something about it regardless of the outcome

00:01:36.900 from there the conversation shifts over into what someone can do to prevent alzheimer's disease

00:01:42.440 and neurodegeneration now we do this in kind of two formats we spend a lot less time on the no

00:01:49.080 regret moves so there are a handful of things that are really stone cold obvious and there's really

00:01:54.320 nothing to talk about frankly we can talk a little bit about the dose so for example we talk a little

00:01:59.480 bit about exercise but really only in the context of minimum effective dose the evidence is overwhelming

00:02:06.680 that exercise is beneficial so i don't really want to delve too much into that instead what i want to

00:02:11.600 focus on are things that are less obvious and really scrutinize the data in nutrition supplementation

00:02:18.840 again minimum effective dose of exercise but not overall lipid management brain games saunas oral

00:02:24.880 health hearing loss all of these things i think this episode is kind of relevant to anyone who has a

00:02:28.960 brain if i'm just going to be blunt and kind of paraphrase richard isaacson because anyone with a

00:02:33.560 brain regardless of their apo e genotype or family history is at risk if you're a subscriber and you want to

00:02:38.720 watch the full video of this podcast you can find it on the show notes page again i think that's

00:02:42.780 valuable because we do go through a number of figures which of course are also available on the

00:02:47.100 show notes page if you're not a subscriber you can watch a sneak peek of the video on our youtube page

00:02:52.180 so without further delay i hope you enjoy ama number 46

00:02:55.860 here welcome to another ama how you doing good this is gonna be a good one it is gonna be a good one

00:03:06.720 before we get to it how are you faring out there in the cold weather and the icy climate of austin texas

00:03:11.800 i'm faring pretty well but i can't say the same for the trees is school out today or are they back

00:03:17.580 in no it's been out for a week yeah so for those listening any chance they're going to see any little

00:03:22.620 guys running behind you today i would go with 50 50 on that for those listening the kids have been

00:03:29.620 out for the past few days while austin's been a nice storm and every now and then on some zoom

00:03:34.600 calls you see some extra special guests behind peter so we'll see if any make an appearance today

00:03:39.660 but what we're gonna do today is something we're pretty excited about which is really talk about

00:03:46.220 something we haven't talked about on the ama before so we've had no shortage of podcast content

00:03:52.280 on the brain dementia alzheimer's you know most recently with kelly ann chris hemsworth delved into it

00:04:00.520 and then you have podcasts with richard isaacson lauren rogan hussein yasin amanda smith so it's a

00:04:06.980 topic that we've talked a lot about on the podcast but recently we kind of did an analysis and we

00:04:12.660 realized we haven't really covered it on the ama so what we did is we went collected all the questions

00:04:17.460 that have come through organized them and put together what we think is a really interesting ama for

00:04:24.360 anyone who kind of is worried about their brain worried about alzheimer's neurodegeneration

00:04:30.140 whenever i say that i always think of what richard isaacson said which is anyone who has a brain should

00:04:35.920 care about this so no matter who you are it should be really applicable and so actually i think what

00:04:41.760 richard said is anyone who has a brain is at risk for this which maybe is even a more pointed statement

00:04:47.920 yeah and it speaks to whether you have this in your family history whether you don't know if you have

00:04:53.780 this in your family history or whether you know what your risks are everything we'll cover today

00:04:57.920 should be of interest for everybody so i think with that unless you have anything you want to add

00:05:04.260 we'll just start getting into it because i know we have a lot to get through let's do it we do have a

00:05:07.980 lot i think to start off it'd be helpful just to kind of set the stage as this applies to how we talk

00:05:13.940 about things later is it would be really helpful for people just understand even how is alzheimer's

00:05:19.260 disease diagnosed so at the outside i'll say that a lot of what we're going to talk about today is

00:05:24.460 around alzheimer's disease because alzheimer's disease is both the most common neurodegenerative

00:05:30.240 disease and the most common cause of dementia but it's worth pointing out that there are other

00:05:35.240 causes of dementia for example vascular dementia which would be quite prevalent lewy body dementia

00:05:41.440 and there are other neurologic neurodegenerative diseases such as lewy body dementia which is not

00:05:47.160 alzheimer's it's distinct from that and obviously parkinson's disease so anyway a lot of what we're

00:05:51.040 going to talk about is alzheimer's disease and so as it pertains to the diagnosis you know unfortunately

00:05:56.080 it's not a neat and tidy diagnosis the way we would have for say breast cancer right if we're going to

00:06:01.160 diagnose breast cancer we might have some radiographic or physical findings that would you know rouse

00:06:06.260 suspicion and that would be confirmed with a physical biopsy when it comes to alzheimer's disease

00:06:11.980 it really starts with a clinical diagnosis so that's made by typically neurologists and they

00:06:18.500 work with the patient and people who are very close to the patient so you know friends or family members

00:06:23.760 and they will assess various symptoms symptoms such as you know difficulty remembering events difficulty

00:06:29.560 concentrating planning or problem solving confusion with location or temporal confusion so confused about

00:06:36.740 different events over time language problems reduction in vocabulary speech writing things like

00:06:42.080 that all of those are kind of clinical then there may be some sort of mental status exam or

00:06:47.320 neuropsychological tests generally there will also be some lab tests done to rule out other causes and

00:06:54.360 i personally because i'm not a neurologist just haven't got a lot of experience with this but

00:06:58.240 certainly have read case studies of patients where gosh it looks like they have all of the signs and

00:07:03.800 symptoms of alzheimer's disease but you come to find out that they're profoundly hypothyroid or they have

00:07:09.760 b12 and b6 deficiencies or things like that so you want to kind of rule out things like that but the bottom

00:07:15.740 line is this diagnosis really isn't definitively made or at least if we want to conclude it until an

00:07:22.420 autopsy now today there are other biomarkers that are increasing in the sensitivity for this so we now have

00:07:31.360 the ability to look at serum amyloid and tau and those can be coupled with the things i've described above in addition

00:07:41.300 to things like amyloid pet such that a really good diagnostician can probably be almost assured that a

00:07:49.680 patient indeed has alzheimer's disease based on the presentation it's really interesting and i know one of the

00:07:54.820 questions we see come through is you know when you talk about cardiovascular disease you have apob as

00:08:01.140 kind of a biomarker that's kind of a predictor of risk and something that people can easily run and

00:08:05.560 understand where they're at is there anything equivalent to that for alzheimer's or neurodegeneration

00:08:12.240 no i would say that alzheimer's is much more complicated in this regard and i don't think we have

00:08:19.020 something that's as neat and tidy that said we do have biomarkers like i said a second ago right we

00:08:23.920 have amyloid we have tau historically and for the purposes of research these were typically drawn from

00:08:30.200 csf so cerebral spinal fluid which can be accessed via a lumbar puncture would certainly be a way to

00:08:37.460 determine the presence of amyloid and tau again very impractical in the real world right these are

00:08:44.540 not benign procedures and they're certainly not things that we want to subject patients to rapidly

00:08:49.480 so as we now look at other scores like the c2n which i can't remember if we talked about that on a

00:08:56.960 previous podcast if not i know we have a newsletter that'll be coming out on this at some point but the

00:09:02.460 c2n developed amyloid score uses a couple of things it uses a patient's apo e variant so it sort of

00:09:11.720 says is this patient a three a three four four four etc and then it looks at the ratio of two

00:09:18.820 variants of amyloid beta so amyloid beta 42 and amyloid beta 40 and then also looks at their age

00:09:24.820 so it takes apo e status ab 40 to 42 ratio as measured in the plasma and patient age and then

00:09:32.440 it predicts the probability of ad pathology now this is a test we have been using i would say there's

00:09:40.420 probably like six or seven patients in our practice that we are using this test in and i would argue

00:09:46.720 that we are still in very early days of knowing what to make of these data so there's two reasons

00:09:52.500 we kind of look at that one is it's one more piece of information that helps us understand risk and it

00:09:58.280 goes into kind of our overall risk assessment that includes everything we talked about before so family

00:10:03.840 history genotype metabolic health apo e status cognitive testing and it allows us to say okay

00:10:12.700 is risk high or lower and more importantly and this is where i think it's too soon to say if it's

00:10:17.400 valid as we make interventions as we take steps to reduce risk we would look to see what happened to

00:10:23.780 that c2n score did it go up or down now think about it if it goes down it's not going down because

00:10:28.920 their apo e status changed and it's not going down because their age got younger it can only go down

00:10:34.320 because the ratio of ab 42 to ab 40 changed so what we're basically saying is we do have a biomarker

00:10:40.960 that measures the change in amyloid 42 to 40 and potentially tau eventually and is that predictive

00:10:50.080 of an improvement i don't know the answer the other thing i think i'll just say for the sake of

00:10:54.680 completeness is we do have amyloid pet scans these are not something we use clinically we've probably

00:11:01.140 done three or four of these in total and they're typically done in a research setting i'll probably

00:11:06.180 not say much more about those right now and for the c2n is that something you know you mentioned you

00:11:11.900 only have used it on a handful of patients is that something that it's just too new for you to kind of

00:11:18.240 roll out with everybody or are you really only using that on very high risk based on all the other

00:11:23.240 factors it's really the latter so you remember with every test you have to think every test has

00:11:29.820 a sensitivity and a specificity and when you take a sensitivity and specificity you want to be able

00:11:36.880 to say this has high positive predictive value and high negative predictive value so if it comes back

00:11:42.460 positive i want to believe that it means something and it comes back negative i want to believe it means

00:11:46.700 something and in addition to the sensitivity and specificity which are fixed for a test the way

00:11:53.120 that you as a physician or person administering the test can increase the odds in your favor is by

00:11:59.060 applying this test to patients with what we would call the highest pre-test probability so in other words

00:12:04.780 if you applied the c2n test willy-nilly across everybody my fear is you would probably get a lot of noise

00:12:13.640 and you would this isn't an arbitrary fear it's just mathematics you're going to get a lower positive

00:12:18.920 predictive value the test will mean less and you'll get lower negative predictive value as well so the

00:12:24.060 goal here is to say look we have tremendous uncertainty about this test unlike for example apob where we have

00:12:30.380 really clear relationship between at least population risk and marker and therefore i feel you know much

00:12:38.120 more comfortable checking apob on everybody but when it comes to this test the answer is no i don't i think

00:12:42.600 we have to reserve this for people who are at the highest risk that makes sense and i think for

00:12:46.340 anyone who wants to dive deeper on the sensitivity specificity positive negative predictive value

00:12:51.460 ama25 one you and bob did which really dove into although it was cancer screening spent a lot of time

00:12:58.860 talking about those metrics and those terms and what they mean so anyone who wants to learn more on

00:13:04.220 that it's going to be a great resource the next question we see come through a lot you kind of

00:13:09.840 mentioned already with the apo e status what do we know about genetic testing and what those results

00:13:16.460 can mean in someone's long-term risk of developing ad or dementia well we know that there is a strong

00:13:23.600 genetic component to alzheimer's disease and we know that there are several genes that are implicated in

00:13:28.620 this i think we can start with the three most penetrant genes or the three genes for which if you

00:13:37.300 have the gene you are most likely to indeed get alzheimer's disease so these three genes are as close

00:13:44.080 to what we would call deterministic as any genes are and fortunately they're very uncommon so the three

00:13:51.980 genes we're going to talk about i'm not going to say much about them other than to state what they are

00:13:55.680 one is psen1 psen2 and app so those three genes collectively account for one percent of patients

00:14:05.780 with alzheimer's disease those patients get alzheimer's disease very early not uncommon for

00:14:11.500 these patients to be afflicted in their 50s in fact we now know that the incident case of alzheimer's

00:14:18.820 disease in other words the patient for whom the disease i mean it was named after the first physician

00:14:23.880 who identified it but his first patient was indeed a woman that had i believe she had the app mutation

00:14:30.020 but it might have been one of the presenilin mutations again i just want to put that out there

00:14:34.320 as an aside we do see that gene from time to time fortunately it's incredibly rare let's focus on the

00:14:40.940 other 99 of cases of ad so 99 of patients who go on to develop alzheimer's disease do not have one of

00:14:48.260 the quote-unquote deterministic genes of those patients about two-thirds have at least one copy

00:14:56.600 of the apo e4 gene now to put that in context about 25 percent of the general population has at least

00:15:05.420 one copy of the apo e4 gene so 25 percent of the population has at least a copy of one copy of e4 and

00:15:13.540 by the way most of them are just one copy two copies is pretty rare that's about two percent of

00:15:18.260 the population but that 25 percent of the population makes up two-thirds of all cases of alzheimer's

00:15:24.840 disease so out of the gate you realize before you jump into the minutiae on this which we'll do in a

00:15:30.940 second clearly this gene is highly associated with alzheimer's disease but as i've stated many times

00:15:38.940 before including stated this obviously when we discussed this on limitless this is not a

00:15:44.420 deterministic gene so there are plenty of patients with apo e4 one copy or even two who never go on

00:15:53.500 to develop dementia in fact as i think i write about briefly in the book there are even centenarians

00:16:00.280 walking around with e4s meaning there are people who make it to a hundred with no signs of dementia

00:16:06.040 who are carrying e4s so there are other genes at play and some of those genes amplify and some of

00:16:13.280 those genes attenuate risk again we've discussed this on some of the previous podcasts so i won't go

00:16:19.160 so deep into it other than to say other genes like clotho so there's one variant of clotho klvs

00:16:28.020 which attenuates risk in e4s so an e34 carrier that has the clotho klvs variant their risk returns to

00:16:38.680 that of a 3-3 a 4-4 carrier who has a clotho klvs their risk returns to almost a 3-3 it's still

00:16:47.200 slightly higher but nowhere near the 4-4 risk conversely the wrong mitochondrial haplotype

00:16:54.320 will amplify risk tgf beta would be another one that amplifies risk tom 40 would be another one

00:17:01.580 that amplifies risk although it's not clear how much tom 40 functions and that's two m's by the way

00:17:07.020 on tom 40 t-o-m-m-40 not clear how much that factors into risk independent of e4 some of these

00:17:14.500 genes and snips can be identified on regular kind of call it commercial over-the-counter tests such as 23 and

00:17:22.760 me but truthfully nick for most of our patients we're doing whole genome sequencing on this

00:17:28.220 particular topic the error rate is lower and frankly most of the genes that we care about are

00:17:34.100 not genes that are showing up on the shorter snip tests that was one of my questions was just how

00:17:39.920 easily available are some of those other tests because we know for someone to find their apoe that's

00:17:46.080 just a blood-based test that is fairly readily available and i know we've kind of mentioned

00:17:52.200 apoe 4s but if someone gets their apoe check do you kind of just want to run through here are the

00:17:59.900 options of what the results could be and then in a second we'll get to kind of what that means but i

00:18:04.600 think just for people to understand who maybe aren't familiar just what are the different combos that

00:18:09.260 they could even see on that test two things that i want to say so to answer your question

00:18:12.980 there are three alleles for the apo e4 gene so just to be clear apo e is a gene it codes for a protein

00:18:23.900 unsurprisingly called apo e but we have three different versions of that gene circulating in

00:18:31.240 our gene pool and to be clear none of these are called mutations these are all three wild type

00:18:37.400 alleles so one is e2 one is e3 and one is e4 e3 is the most common and e4 is the next most common and e2

00:18:46.980 is quite rare these genes can therefore be combined in up to six ways because you're going to get one

00:18:54.820 copy from your mom and one copy from your dad so you can have a 2 2 2 3 3 4 3 3 3 4 4 i hope i got

00:19:04.540 those all right but it's pretty easy to do the math on that right two two two two three three four

00:19:09.720 three three three three four four four the general prevalence of these is i think 50 to 55 percent are

00:19:17.080 three three about 25 percent are three four two four i think is the next most common not that common

00:19:27.300 probably about five to ten percent and two two is the rarest four four is is the second rarest you can

00:19:36.520 sort of do the math but the majority of cases you're seeing are three three oh and then two three is not

00:19:42.540 that uncommon so anyway going back to your question i think you asked a question about do we how easy is

00:19:48.900 it to go about getting these other genetic tests to look for genes beyond apo e4 because apo e4 is pretty

00:19:54.000 easy to get checked the short answer is it's really hard and to my knowledge there is still no turnkey

00:20:00.440 solution for looking at the entire suite of genes that are involved in alzheimer's disease even kind of

00:20:07.620 the 12 most relevant so right now we work with richard isaacson and his team and brute force it meaning

00:20:15.640 richard and a team of folks literally go through the whole genome sequence trying to identify these there's a

00:20:23.380 huge opportunity there to streamline this process which again wouldn't be interesting if not for what

00:20:28.780 we're about to talk about today in other words i don't know that this would matter a whole heck of a

00:20:32.940 lot unless you believed you could do something about it which i think comes back to kind of a broader issue

00:20:36.820 around apo e4 testing when the limitless thing came out there was a surprising amount at least to

00:20:43.820 my naive view of i don't know what the word is but call it just sort of backlash against like how

00:20:50.540 irresponsible it was to test for apo e in chris i found that to be a baseless and meritless criticism

00:20:57.400 truthfully but at the same time i can understand where it came from if you believed that having a

00:21:04.260 copy of an apo e4 gene or two copies was deterministic and it was all a fait accompli in other words if you

00:21:10.900 believe that having those genes means you're going to get alzheimer's disease and nothing can be done

00:21:15.700 about it then at least you could entertain the argument why know it now but even if that were

00:21:21.560 the case i still think that's incorrect i think knowing something allows you to plan accordingly

00:21:26.280 but i don't even believe that premise i do believe there's a lot that can be done to delay onset and or

00:21:33.120 reduce risk so let's talk a little bit about what the prevalence means of these right so globally the

00:21:38.580 prevalence of ad is two to one in favor of women to men so women are literally twice as likely to get

00:21:46.380 alzheimer's disease as men and of course we see the reverse in parkinson's disease so it's sort of

00:21:52.220 interesting where does that 2x difference come from it's kind of a combination of individual risk for

00:21:59.480 the women so for any combination of genotype so actually let's pull up figure one nick this will be

00:22:04.720 easier to explain there perfect got it pulled up so what you're looking at here this is a bit of a

00:22:10.040 complicated figure until you sort of orient yourself to it each figure is showing you men and women so

00:22:15.340 the women are in red the men are in green the first column is showing you the risk of alzheimer's

00:22:25.140 disease the 10-year risk so for a given age what is the subsequent decades risk so in the first column

00:22:31.360 that's for alzheimer's disease in the second column that's for vascular dementia which is the second

00:22:36.740 most prevalent form of dementia and the final column is just 10-year risk of all dementias so

00:22:41.800 that would include alzheimer's plus vascular plus lewy body etc frontal etc i think that's the first way

00:22:48.900 to orient then if you go by rows you're just looking at the decade in which we look so the top row is

00:22:54.940 people in their 60s the next row is people in their 70s the final row is people 80 and up so

00:23:01.260 not surprisingly as you move down the rows the numbers get bigger and not surprisingly the third

00:23:08.340 column has to be greater than the sum of the first two columns because it includes both of them plus

00:23:14.000 other things lastly each box shows the six genotypes the six combinations so it always goes the same

00:23:23.520 direction e22 32 33 42 43 and 44 which is more or less in the order of risk although you'll see

00:23:34.540 that when it comes to alzheimer's disease specifically the 32 is the lowest risk in all-cause dementia

00:23:45.880 22 is the lowest risk that probably has to do with the impact of the e2 genotype in lewy body and other

00:23:54.140 dementias but we'll put that aside for a moment so what's really obvious when looking at this is that

00:24:00.100 the 44 has a significantly higher risk than everything else and then the 34 and the 42 are kind of next we

00:24:09.340 think of the 33 as the baseline since that's the most common genotype we see in the population

00:24:14.480 so in general everything gets compared to the 33 you'll also notice that at any point in time

00:24:20.720 women seem about 20 percent more likely in a given decade to get alzheimer's disease than men

00:24:27.320 and what that suggests is that the two-to-one prevalence is probably a function of that coupled

00:24:35.360 with the fact that women are living longer that would be my interpretation of this

00:24:39.340 and peter you kind of hinted at there with what you kind of loosely called some backlash around

00:24:44.600 the idea of testing for someone's apoe status and why they would want to do it is there anything

00:24:51.120 more we can say because we do see a lot of questions come through on how robust is the idea

00:24:56.260 that prevention is possible for ad and what more do we know about that side of it again i think this

00:25:03.220 is a very important part of what we're going to talk about today so the bulk of today's ama is going

00:25:09.060 to be around what are the measures that we can take what are the modifiable behaviors that factor

00:25:15.760 into risk reduction or prevention here's the problem really difficult to do this directly with

00:25:23.300 controlled trials given the time course you're going to see a couple of examples where we can talk

00:25:28.420 about that and where we can i think pretty convincingly take a causal view but unfortunately

00:25:36.220 much of the data here is epidemiologic so if you look at something called the chicago health and aging

00:25:43.820 project it followed nearly 4 000 individuals who underwent regular clinical and cognitive assessment

00:25:50.620 from the early 90s to about 2012 i think these patients were 65 and older they had no alzheimer's

00:25:58.760 disease at the outset they were all cognitively tested and the bottom 10 percent of non-ad patients

00:26:07.320 in terms of cognition were excluded so we're trying to take out what we think were the most susceptible

00:26:13.260 they also excluded any patients who were four fours so if a patient is e4 you're going to see that the

00:26:21.740 data are divided between e4 and non-e4 so the e4 segment is just two fours and three fours and that was

00:26:28.260 about a third of the sample so a third of the sample had two four or three four and a third of the sample

00:26:35.240 had no e4 so interesting population to study there was no intervention i want to just state that we're

00:26:43.560 full of limitation here they looked at how these patients did over the subsequent what was it 20

00:26:52.960 years roughly 15 to 20 years based on the number of healthy lifestyle factors they engaged in so healthy

00:27:01.720 lifestyle factors are all the usual stuff i don't need to restate the obvious right so not smoking

00:27:05.960 getting good sleep exercise nutrition etc etc and they broke these folks into two buckets you either

00:27:13.620 were doing zero to one or four to five so they wanted to kind of create a gap so if you looked at those

00:27:22.900 let's pull up the graph nick if you don't mind here i got it pulled up so what you're looking at on the

00:27:27.800 x-axis is time what you're looking at on the y-axis is cognitive score on the left hand side you see

00:27:37.720 the apo e cohort that means these are the third of the patients who were e4s and then on the right hand

00:27:46.680 side you see the patients who had no e4 the solid line shows you the people who were in the zero to one

00:27:55.400 healthy lifestyle factors and the dotted line is the four to five the line you might be asking well

00:28:02.760 why is this such a straight line well it's because this is a linear model of cognitive decline based

00:28:07.560 on this global cognition score done from four tests over the 17 years the shaded area is your 95 confidence

00:28:15.560 interval these models were adjusted for all the usual suspects age sex race ethnicity total education

00:28:22.920 presence of other diseases such as cardiovascular disease etc what's the takeaway here well let's put

00:28:29.320 aside for the moment that there's confounders that can never be undone here so we know for example that

00:28:37.000 education is a huge predictor of cognitive decline meaning high education is less than low education

00:28:45.560 but it's also a marker for socioeconomic status and socioeconomic status has its other reasons that it

00:28:51.000 might factor into this so if you put all that aside for a moment two things at least to me stand

00:28:55.240 out when i look at this graph the first is at the beginning of the study both groups all four groups if

00:29:02.120 you think about it the e4s and the non e4s and the healthy lifestyle versus the non-healthy lifestyle

00:29:07.640 you see how they all had about the same cognitive score yeah it's pretty interesting what happens is

00:29:13.800 is two things the e4s even with healthy behaviors still fall faster than the non e4s with healthy

00:29:24.200 behaviors so it really speaks to the risk of e4 later in life but the other thing of course that stands out

00:29:32.520 is healthy behaviors offset much of that risk so in other words the rate of decline of the e4s doing the

00:29:42.920 healthy things seems to be slightly less maybe it's not statistically significant in fact it's not

00:29:49.080 so you would just say seems to be identical to the non e4s who are not engaging in the healthy behaviors

00:29:56.360 in other words this suggests that you have some control over this this is malleable again i want to

00:30:02.600 restate that right if you look at the left hand graph in the dotted line including that confidence

00:30:08.760 interval it's basically identical to the solid line on the right so another way to look at this is

00:30:14.920 healthy behaviors have a greater impact on e4s than non e4s the space between the lines on the left

00:30:23.240 is greater than the space between the lines on the right that's what that means the lift that you can

00:30:28.600 get with healthy behaviors seems to be even greater as an e4 than as an e3 it is really interesting to see

00:30:34.520 kind of that graph that way and it really leads to what you hinted at just a second ago which is

00:30:39.560 we're now going to spend the rest of this ama with the true focus of what are these things that you can

00:30:44.840 do to prevent alzheimer's dementia to really try and work to keep your brain as healthy as possible

00:30:52.280 and we'll cover a ton of questions that we get but i think what would be really helpful is even though

00:30:58.120 we're going to spend more time than less on some of these different preventions just because we don't

00:31:04.760 have the time in the day to cover them all in detail do you just want to give people that kind

00:31:10.360 of quick list of hey here are all the factors that you should think about before we kind of start

00:31:15.480 picking them apart thank you for listening to today's sneak peek ama episode of the drive if you're

00:31:21.640 interested in hearing the complete version of this ama you'll want to become a member we created the

00:31:26.600 membership program to bring you more in-depth exclusive content without relying on paid ads

00:31:32.840 membership benefits are many and beyond the complete episodes of the ama each month they

00:31:37.640 include the following ridiculously comprehensive podcast show notes that detail every topic paper

00:31:43.800 person and thing we discuss on each episode of the drive access to our private podcast feed the

00:31:50.200 qualies which were a super short podcast typically less than five minutes released every tuesday

00:31:55.560 through friday which highlight the best questions topics and tactics discussed on previous episodes

00:32:00.600 of the drive this is particularly important for those of you who haven't heard all of the back

00:32:05.800 episodes it becomes a great way to go back and filter and decide which ones you want to listen to in

00:32:10.680 detail really steep discount codes for products i use and believe in but for which i don't get paid to

00:32:16.440 endorse and benefits that we continue to add over time if you want to learn more and access these

00:32:22.120 member-only benefits head over to peter atia md dot com forward slash subscribe lastly if you're

00:32:29.000 already a member but you're hearing this it means you haven't downloaded our member-only podcast feed

00:32:33.800 where you can get the full access to the ama and you don't have to listen to this you can download that

00:32:39.160 at peter atia md dot com forward slash members you can find me on twitter instagram and facebook all

00:32:47.000 with the id peter atia md you can also leave us a review on apple podcasts or whatever podcast player

00:32:53.560 you listen on this podcast is for general informational purposes only and does not constitute the practice

00:32:59.320 of medicine nursing or other professional health care services including the giving of medical advice

00:33:05.720 no doctor patient relationship is formed the use of this information and the materials linked to

00:33:10.760 this podcast is at the user's own risk the content on this podcast is not intended to be a substitute

00:33:17.160 for professional medical advice diagnosis or treatment users should not disregard or delay in obtaining

00:33:24.440 medical advice from any medical condition they have and they should seek the assistance of their

00:33:29.480 health care professionals for any such conditions finally i take conflicts of interest very seriously

00:33:35.960 for all of my disclosures and the companies i invest in or advise please visit peter atia md dot com

00:33:43.080 forward slash about where i keep an up-to-date and active list of such companies

00:33:59.480 you

The Peter Attia Drive - April 17, 2023

#251 - AMA #46： Optimizing brain health： Alzheimer's disease risk factors, APOE, prevention strategies, and more

Episode Stats

Length

Words per Minute

Word Count

Sentence Count

Hate Speech Sentences

Summary

Transcript