How to Treat Alzheimer's & Parkinson's Diseases | Dr. Mark D'Esposito & Dr. Andrew Huberman
00:00:00.000 | As I understand Alzheimer's is a neurodegenerative disorder, impacts the hippocampus, among other
00:00:08.760 | structures.
00:00:09.760 | There's been some debate in recent years as to whether or not the whole amyloid hypothesis
00:00:13.560 | is real or not.
00:00:15.720 | There's a bunch of unfortunately false data accusations and that whole thing.
00:00:21.960 | But my understanding is that if you look at a slice of human brain from a patient that
00:00:26.940 | died with Alzheimer's, maybe even from Alzheimer's, that you see plaques and tangles.
00:00:33.200 | You see these sub-cellular structures and buildup and that our basic understanding of
00:00:41.360 | Alzheimer's that's in the textbook and that most people have heard of is still correct,
00:00:46.320 | right?
00:00:47.320 | Yes.
00:00:48.320 | Okay.
00:00:49.320 | Because I think a couple of years ago it was, you know, unfortunately the way social media
00:00:52.280 | sometimes can work is that, you know, the idea was that it was all wrong, you know,
00:00:55.640 | all wrong.
00:00:56.640 | And somebody fudged data, they made up data and that's terrible.
00:01:01.100 | But Alzheimer's is a neurodegenerative disorder, includes the hippocampus, plaques and tangles
00:01:06.160 | are present in the neurons.
00:01:07.800 | Those are not good for neurons as I understand.
00:01:10.320 | So what's the controversy like and why don't we have a treatment for Alzheimer's yet?
00:01:15.080 | I feel like almost every other psychiatric disease, including Parkinson's, like there
00:01:19.080 | are certain things you can do to at least push the system in the right way.
00:01:22.480 | Why is Alzheimer's and other dementias so tricky?
00:01:26.360 | Yeah, I mean it's very frustrating because the neurodegenerative disorders, it's so many
00:01:33.920 | factors that are probably involved in the pathology that there's not, you know, one
00:01:39.120 | single transmitter.
00:01:41.240 | The Parkinson's disease, it's a decreased dopamine and so one transmitter can make a
00:01:45.320 | very big difference.
00:01:47.680 | Early on in Alzheimer's it was discovered that there was low acetylcholine in the brains
00:01:51.520 | and the only approved treatment for Alzheimer's disease is a drug that boosts acetylcholine.
00:01:57.600 | What's the drug?
00:01:58.600 | It's called Donepezil.
00:01:59.600 | There's a few of them, they're anticholinesterase inhibitors that boost acetylcholine.
00:02:04.560 | They've been around for 20 years or more and, you know, the reality is when you give it
00:02:08.840 | to your patients they don't see much of a difference because it's not the primary deficit.
00:02:14.720 | So the real problem has been trying to find out what is the primary mechanism that's leading
00:02:19.720 | to this wide range of cognitive behavioral issues and there doesn't seem to be at least
00:02:25.640 | one neurotransmitter that can make the difference and so now the push has been is there one,
00:02:30.560 | is there something else that we can do?
00:02:32.560 | Can we block amyloid?
00:02:33.560 | Can we block something in the pathology and again it just has not been successful.
00:02:40.080 | It's very frustrating because I think it was over probably 35 years ago I saw my first
00:02:43.920 | Alzheimer's patients and I don't believe I say that much different to them now, you know,
00:02:50.560 | except that we have a lot more things we can do just on the social side of things.
00:02:54.320 | But unfortunately for drugs we don't have anything that's been really transformative.
00:02:59.400 | But again that's I think part of being a neurologist it sounds very depressing but I think part
00:03:05.060 | of what the family isn't always looking for a cure, of course that's they'd like to have
00:03:09.960 | a cure but I think them understanding what's going on, what to expect, how to handle the
00:03:14.840 | behaviors is what they're really after at least until we find, you know, a cure.
00:03:19.520 | Parkinson's, you mentioned, is a deficit in dopaminergic function due largely to degeneration
00:03:26.640 | of dopaminergic neurons.
00:03:27.880 | There there's some effective treatments, right?
00:03:31.160 | L-Dopa.
00:03:32.160 | Did you know there's this over-the-counter stuff that's sold that a lot of people take
00:03:37.280 | who don't have Parkinson's?
00:03:38.360 | I'm not suggesting they take it called mucuna prurines, it's the velvety bean.
00:03:43.200 | Yeah, I've heard of it.
00:03:44.200 | It's 99% L-Dopa.
00:03:45.200 | I've heard of it, yeah.
00:03:46.360 | It's in present in like some energy drinks and supplements and people can go buy it.
00:03:49.800 | I'm not suggesting they do that.
00:03:51.240 | I actually tried it, boy, I feel being really dopamined out does not, to me doesn't feel
00:03:58.800 | that good.
00:03:59.800 | Yeah, I felt kind of agitated, my vision got a little, you know, twinkly, it did not feel
00:04:05.320 | like a high of any kind and then I felt lousy for a couple hours after it wore off.
00:04:09.680 | Yeah, I don't think you can really get in enough L-Dopa to get enough into your brain.
00:04:14.560 | That happened early in neurology when it was discovered we couldn't give our patients enough
00:04:18.840 | L-Dopa without them feeling bad because it's also metabolized in the periphery.
00:04:24.520 | And so it wasn't until we, Sinemet came along, which has this decarboxylase inhibitor that
00:04:30.960 | blocks sort of the breakdown of dopamine that we were able to sort of get enough dopamine
00:04:35.960 | into the brain.
00:04:36.960 | So I'm not sure, yeah, so that's why I think it's not going to probably get the levels
00:04:41.320 | up high enough in the brain.
00:04:43.940 | So Parkinson's patients are given L-Dopa or bromocriptine or drugs like that.
00:04:51.440 | Going back to Alzheimer's for a moment, I mean, what do you tell somebody who has early
00:04:55.000 | stage Alzheimer's?
00:04:56.000 | You just say, listen, try and get good sleep, try and keep people around you, stay cognitively
00:05:00.080 | engaged, try and keep those circuits going through behavioral induced neuroplasticity.
00:05:04.720 | But we're just going to watch the steepness of the decline.
00:05:10.240 | Is that really all we've got?
00:05:12.360 | - All we've got is to help them with everything that comes up on a day-to-day basis.
00:05:18.000 | A lot of the problems, the memory problems tend to be something that families can help
00:05:24.020 | compensate for, but you do get to a point where you can't be with someone for 24/7.
00:05:31.080 | It's a real burnout for caregivers.
00:05:33.280 | A lot of the behaviors that come up, patients get kind of delusions and agitated, and some
00:05:38.880 | of the medications that we use for other conditions are helpful for treating that.
00:05:45.160 | But it's really just a purely symptomatic therapy.
00:05:48.960 | And the more socialization that patients get, they tend to do better.
00:05:53.040 | There was a study back at Penn, way back, that if you showed patients some family movies
00:05:58.560 | or family albums, it was better than any drug you could give them to sort of help their
00:06:03.880 | behavior.
00:06:04.880 | So there's still those memories that are in there, and they were making some type of contact
00:06:09.600 | that was helping them emotionally that you couldn't turn off with a drug.
00:06:14.040 | So I think the more we do things like that, the more we'll be helpful for them, at least
00:06:19.520 | symptomatically.
00:06:20.520 | - I've seen a number of videos on social media of people with Alzheimer's who listen to a
00:06:26.160 | piece of music, or people with Parkinson's that hear a piece of music, and that seems
00:06:30.560 | to resurrect some at least context-appropriate emotional state, where it kind of brings the
00:06:36.440 | person to the surface again.
00:06:39.360 | Yeah, it's kind of a tragic situation for Alzheimer's right now.
00:06:44.560 | It seems like if ever there was a call to arms for the neurology community and biotech
00:06:50.720 | and behavioral tech, it would be for Alzheimer's, for the treatment of Alzheimer's.
00:06:59.160 | I will never ask a guest to comment on the good or bad behaviors of other people, except
00:07:06.040 | my own.
00:07:08.320 | But there's a Nobel Prize-winning neuroscientist, and I visited him, he's at a Big East Coast
00:07:15.200 | school back in 2010, and during the course of our one-hour meeting, he consumed no fewer
00:07:21.600 | than four pieces of Nicorette gum.
00:07:24.920 | And I said, "I got to ask, what's this about?"
00:07:27.640 | By the way, he's extremely sharp still.
00:07:32.120 | And he said, "Oh, yeah, yeah, yeah, you know, I used to be a smoker, but smoking is really
00:07:35.200 | bad for you because you can get lung cancer, dipping is bad for you because you can get
00:07:39.560 | mouth cancer, but nicotine," these are his words, by the way, "is protective against
00:07:44.480 | Parkinson's and Alzheimer's, and it keeps my brain sharp, so I chew Nicorette all day
00:07:48.800 | long."
00:07:49.800 | And I thought, "Okay, well, he's not, he is an MD, actually."
00:07:55.800 | And I thought, "Oh, that's interesting."
00:07:57.680 | And I did an episode of this podcast on nicotine.
00:07:59.640 | It, by the way, can raise blood pressure.
00:08:01.840 | It's certainly smoking, vaping, dipping, or snuffing, not good, bad, don't do it.
00:08:07.680 | But there is some interest in the use of nicotine as a cognitive enhancer.
00:08:12.720 | So I'd love to know your thoughts on that.
00:08:15.960 | And I'd love to know your thoughts on his statement about nicotine being a potential
00:08:21.060 | way to stave off Parkinson's and Alzheimer's, with the caveat that he just kind of threw
00:08:26.280 | that out there, and this guy's sort of known for just kind of throwing stuff out there
00:08:29.480 | every once in a while.
00:08:30.480 | I have a feeling you know who this person is, but in any event, what gives?
00:08:34.960 | Yeah, well, I don't know anything about nicotine staving off any neurodegenerative disorder,
00:08:40.840 | but nicotine was used, and it was used in a number of early Alzheimer's studies just
00:08:46.000 | because of its effect on the cholinergic system.
00:08:49.000 | So there is some truth to that.
00:08:51.640 | The cholinergic system is dysfunctional in Alzheimer's disease, and boosting the cholinergic
00:08:57.560 | system probably is beneficial.
00:08:59.880 | I mean, the patients that we give the anticholinesterase inhibitors, there are some families that
00:09:04.200 | say, "Yeah, he's remembering more, and he's just doing better."
00:09:07.160 | So I've seen positive things to it.
00:09:11.860 | It doesn't really slow the course of the disease.
00:09:14.240 | That's the problem.
00:09:15.240 | The disease just carries on, even though we're symptomatically improving the symptoms.
00:09:18.400 | But again, I think it's going to take both acetylcholine and something else.
00:09:21.920 | I think we don't know, should we give dopamine with the nicotine or the acetylcholine?
00:09:27.080 | Should we give norepinephrine?
00:09:28.080 | I think it's going to be a cocktail, which, again, pharmaceutical companies have not tried
00:09:33.640 | a cocktail of neuromodulators for Alzheimer's disease.
00:09:36.320 | They've just tried acetylcholine.
00:09:38.480 | [MUSIC PLAYING]