Producer: All right, welcome back to Full PreFrontal where we are exposing the mysteries of executive function. I am here as always with our host, Sucheta Kamath.
Good morning, my friend, good to be with you as always. I understand, we are going to talk about aging and Alzheimer’s today.
Sucheta Kamath: Yes, we are, and this reminds me of David Bowie’s quote. He once said that, “If you are pining for youth, I think it produces a stereotypical old man because you’re only living memory. You live in the phase that doesn’t exist. Aging is an extraordinary process where you become the person you always sure have been.” I love that quote and that, of course, is such a nudge for us to age gracefully, but yeah, today’s topic, particularly from cognition and executive function, we will be talking about more towards the sunset years of our life. Not everybody is as lucky to have intact set of skills were thinking and that can cause a great disruption.
Producer: Well, as you know, Sucheta, my mother was diagnosed with Alzheimer’s just over four years ago now. It has been, oh, I’m not going to deny, it has been a very difficult and very painful journey for all of us, but it has also been, to be very frank, a fascinating one to see what this disease has done to her. She is, what we would now classify as late-stage Alzheimer’s, but with organized thinking. So, what that means to those visiting is that yeah, she has, in essence, zero short-term memory, but she has organized thinking which means that she can still dress herself, she can still make her bed, she can still do some personal effects like brushing the teeth and combing hair, and all that, and she still can enjoy social outings, but it is interesting to spend time with a human being who has no short-term memory. It is a real challenge. It has been a very difficult but to be very frank, a fascinating thing to observe, and the disease has not get impacted her general health, so she is still in pre-good health otherwise which is, you know, that brings its own challenges as well, but it has been a fascinating journey, and what’s been really, really fascinating about it is frankly, what we have learned going through it and the little tricks, the little hacks, the strategies that you have come up with that enable you to interact and spend quality time with someone like that. You really can’t talk about the future, you cannot talk about the past. Certainly, the immediate past, and so your whole essence of the time together is to create these present moment of joys, and so that is what you do and that is what you strive for, but it is a horrifying terrible disease. It’s just, I don’t wish that on anyone, but it’s also family, loving family and taking care of each other and it’s what you’re supposed to do, you know?
Sucheta: Absolutely, and I’m so sorry, and I have gotten to know some of your struggles since you and I started working with each other, and I know how taxing it has been on your own relationship with her as well as having to manage personal life, professional life, and now, this added responsibilities of making sure your mother is safe and kind of has that supports that she needs which she may not recognize that you are offering it. I know, do you mind sharing some of the things that you – how did it start? How did you notice the changes in her thinking, her behaviors? What kind of alerted you that this could be Alzheimer’s?
Producer: Yeah, well, and I will be honest, she was exhibiting symptoms of this disease years before she was officially diagnosed, and like I said, that was 2014, four years ago, when she was officially diagnosed, but we had certainly noticed a change in her probably a good two years prior to that, maybe even three, but you know, it manifested itself in some, I guess, not surprising ways, always with meticulous about how she maintained her house and her wardrobe, and if you said, “Mom, we are leaving at 5:30,” she would be ready at 5:25 every time, and then all of a sudden, that just stopped and she would just repeat, “What time are we leaving? What time are we heading out? What do I need to wear? Where are we going? Who are we seeing?” and so it is different than – all of us have a slip of the memory, right? We’ll forget something and, “Hey, honey, remind me about –“ but it becomes a constant thing , and so that was the original real main symptom, was she had always been so careful about her punctuality and knowing exactly when and where, and why she was supposed to be doing something, and then all of a sudden, that just disappeared, and then the notion of misplacing things, so not knowing where the dishwasher soap was or where she would have the right kind of socks, or those little kinds of things – things that she could have done blind and found in the dark, and was always meticulously organized and maintained her house in such a way that everyone always knew where everything was, and that stopped. So, these things had been demonstrated over her entire lifetime all of a sudden end, so that is when you get a real wake-up call that there is definitely something going on.
Sucheta: Got it, got it, and you know, as a speech and language pathologist who specializes in neurological disorders, my work always has centered around helping people build memories and developing organizational skills, and planning, and self-sufficiency or self-awareness skills. Last several years, I have stopped working with people with dementia or any type of memory-related problems with aging, but I have been a lot of work in my earlier career or rather at the start of my career, but when I do see clients with age-related memory challenges, a lot of them come to me because they have had a head injury. So, recently, I saw a woman, she was kind of young, she was only 59 and she had climbed on this drop-down ladder from the attic to get something, and she fell backwards and hit an empty acquire you, home aquarium, that she had and she had her head, the back of the head, and of course, the aquarium broke her fall, and that kind of got her to go to a hospital to the then neurologist, and eventually, she landed in my office for attention, memory and executive function problems, but as they started working with her, my assessment was that she is not showing typical memory problems. They were looking like she’s having significant memory, like what became very evident to me, one day, she called me and she said, “I am trying to get to you. How do I get to you?” so I said, “Oh, I will text you my address. Did you lose my address?” and she said, “No, no, no, I am on my way to get to you. How do I get to you?” and I couldn’t understand that question – what was she trying to say? And so, I said, “Where are you?” so she said, “I am in the parking lot,” and so I said, “Oh, what parking lot?” She said, “Store. Store parking lot,” so I said, “Which start?” So, that was so not – that’s very abnormal and unusual way of describing, post head injury kind of thing. So basically, she, for a moment, had lost bearing of where she was in space and time. She couldn’t figure out that she was in the Target parking lot which was in Roswell and she needed to come to Buckhead area and she needed to take 400, and then take this exit. She kind of lost of the bearing where she was.
Anyway, that was the kind of thing, I said that is extremely unusual, and then I started discussing more about her daily routines, and one of the things I was helping her not be detected or nobody getting suspicious was she was extremely organized, and she had systems and she was not doing a lot of new things. So, anyways, I think this is such an important topic and I noticed this is veering a little bit into more than just executive function, but I do think that a lot of ways that people who are helping people manage family members required this understanding and that is why I thought it would be great for us to talk about this guest I have today.
He is a very special friend and expert, and I’m so excited. So, let me tell you a little bit about him. Today, we have Dr. Ken Kosik. He has served as a professor at the Harvard Medical School from 1996 to 2004, that is where I met him and when he became the Herrmann professor and codirector of the Neuroscience Research Ctr., Institute at the University of California in Santa Barbara. He has received multiple, multiple awards – I’m going to list a few such as Whitaker health science award from MIT, Wilton Foundation Award from Harvard Medical School, More Award from American Association of Neuropathologist, Metropolitan Life Award, Denny Brown Award from American Neurological Associations, and so on and so on. As you can see, he has a prolific career and incredibly celebrated individual who had made a lot of contributions. He has co-authored two important books, one is called Outsmarting Alzheimer’s Disease and second is called The Alzheimer’s Solution: How Today’s Care Is Failing Millions and How Can We Do Better, and we will be talking about what to do in our next segment and I will be referring to that book. It is a great book, everybody should have it.
His work including corrector is a shed in Columbia of the largest family and the world with familial Alzheimer’s has appeared in New York Times, Wall Street Journal, in the New Yorker. It has also been referenced on BBC, CNN, PBS, and even CBS’s 60 minutes. His 2016 UCSP commencement address was archived at the Graduation Wisdom best commencement website, and I really recommend everybody should listen to him. He is extremely inspirational and it is my honor to have him with us today.
Producer: Well, Sucheta, I learn something from every one of your conversations, but goes without saying, I’m particularly looking forward to your conversation with Dr. Kosik, so let us get to it. Here is Sue’s first of two conversations with Dr. Ken Kosik.
Sucheta: Welcome to the podcast, Ken, and I hope you don’t mind calling you Ken instead of Dr. Kosik. I have had the privilege of knowing you and having seen you present and have had many banters with you, so I’m very excited to have you here.
Dr. Kosik: Thank you so much, happy to be here.
Sucheta: Let us dive into your expertise. We are heading towards old age and yet we hardly think about it, or maybe the truth is it that we will be paralyzed if we think too much about it, but the fear of losing one’s mental faculty can be a great concern to everyone. So, for starters, do you mind walking us through the difference between brain farts as I like to call them related to old age versus dementia and Alzheimer’s disease?
Dr. Kosik: Sure. So, the individuals as we get older, we all have some decline in our mental function. It’s really kind of a slowing a little bit. It’s not always necessarily a decrease in intelligence or problem-solving. In fact, some things like problem-solving actually get better as we age, and it is really very common and as we age to develop some retrieval problem, some difficulties in retrieving names, for instance, and memories are not always as accessible, whether they are short-term memories or long-term, but mostly, short-term, and that is very common, then there is the kind of a gray zone where people have those same problems, but they seem to cross over a line that really now begins to be worrisome, and because of that line is a little bit indistinct, we have a lot of trouble about knowing for sure when an elder begins to have memory complaints, whether or not it is the opening shot of Alzheimer’s disease or part of what we might call cognitive aging – it’s a term that is now used. Another termite be normal, normal aging.
There are very small percentage of people that will maintain fair cognition perfectly well into their 90s – there are Pablo Picasso, an amazing artist, painted brilliantly into his 90s. So, it can happen, but this small amount of decline is incredibly common, number one. It would be very nice to give that a boost, and number two is, we want to be really, really increasingly vigilant as to detecting when a person is likely to go over the line and begin to step into an Alzheimer trajectory. Now, when we start to use the term Alzheimer’s, person is already fairly far along. They really have rather frank sense – you can talk to the person and you would very quickly know that there is probably something happening here – it wouldn’t take long. The difficult area, as I mentioned, is this gray zone and we have a word for that. It is called mild cognitive impairments. So, there is a difference between what I called normal cognitive aging a moment ago, and mild cognitive impairment. Mild cognitive impairment is probably on the way to Alzheimer’s disease, whereas normal aging is not.
Sucheta: So, I love the way you kind of sorted it out to get us started. What is that cognitive aging or the normal signs, and you don’t like my unofficial term ‘brain farts,’ but yes, I can –
Dr. Kosik: No, that’s okay too. [0:15:06]
Sucheta: No, I’m just teasing, and I think – if you don’t mind talking a little bit about the difference between, like I think two distinct things stand out for me for me from my cognitive rehabilitation work and training that I do, that the slowing, cognitive slowing, there is a process thing, speed that kind of reduces, and second thing is, as you mentioned, the retrieval in memory, that normal aging is quite – we go to a party and my husband is nudging me already saying that, “Who is that now? What is his name?” or “What is his wife’s name?” Those kinds of things and I’m almost like his name bank. He refers to me to find out relational or some details, and so that part I feel versus the short-term memory developing or managing short-term memory, could you talk a little bit about the distinction between the two, how does that normal person understand it will, to those who don’t understand your science that much?
Dr. Kosik: Yeah. Well, these are often clinical types of decisions that may not require a deep understanding of neuroscience is really more of a very astute clinician. With regard to your going to a party and your husband asking you, there is data that says that memory can be served in a very positive way with a long marriage, and maybe that has something to do with the fact that couples now can double their memory bank by [0:16:38] things that one alone would have forgotten, but I think we can be very descriptive and say there are these retrieval problems, there are these issues, and I think that useful. One, I’m not sure I’m actually answering your question perfectly because we do want up with metrics on this and there are a lot of neuropsychological testing tests that can be done if a person is worried; they should see their neuropsychologist, they can put numbers on it, and if they’re not going to give a clear answer with one visit, they can wait six months, do it again and see if it stays steady, then you have nothing to worry about, or if it’s begun to decline, then you have something to worry about, but I think maybe what you’re getting at is that because when people get older that are not on the path to Alzheimer’s, they would still really like a boost in their memory. I mean, this is something we all want. So, that is a very tricky problem because there is no fountain of youth that we are aware of. How can we really best enhance people who have this normal cognitive aging issue, and I think that we will get to that when we start talking about therapies, but I want to identify that issue as being out there.
I will say one more thing in this vein and that is that in my clinics over the years, when I see individuals, and worried about memory complaints, I would save may be as many as half of the, I’m able to reassure them and tell them, I don’t think it’s Alzheimer’s because number one, we are all worried about Alzheimer’s, number two, cognitive aging is a real thing, people coming wary. It’s nice to get reassurance from a doctor, but it still doesn’t solve the fact that they can’t retrieve a name at a party.
Sucheta: Yes, that’s great. So, can you then define, is dementia same as Alzheimer’s disease, and what is the definition of Alzheimer’s disease?
Dr. Kosik: So, dementia is not the same as Alzheimer’s disease. Alzheimer’s disease is a type of dementia. Dementia simply means that there is an impairment in cognition – you have not just trouble with memory, but there is also trouble in other cognitive spheres such as calculations, executive functions, many things that we can begin itemize. Another sphere that is often affected in dementia and particularly in Alzheimer’s, but in many different types of dementia’s personality. So, we have the cognitive domain and we have more of an emotional personality domain, they both tend to get affected. So, as I suggested now go back, there are many types of dementia. There’s just a long list. When you see a neurologist because you may be concerned about it, the job of the neurologist is to figure out what type of dementia you have, assuming there is a cognitive impairment, and if the neurologist then comes the conclusion that is Alzheimer’s, they are looking for the following things: one, very slow inexorable course in which there has been progression of impairment over years, not over weeks or even months – this is a slowly progressive disease. I’ve had several examples where someone will come into the clinic and say, “Oh, my father went out to the grocery store and he got lost, couldn’t find his way back home,” and now, they are concerned about the onset of a problem because the guy got lost, but all you have to do is ask the person, say, “What happened before?” and it turns out that a year earlier, he may have stopped keeping his checkbook, maybe his wife took about over, and even before that, he might have been communicating a little less. So, there’s many antecedents to these precipitous events that people often pinpoint as the onset – slow inexorable course, number one. Number two, you really want to – I sort of alluded to this a little bit in my discussion of dementia – but it’s particularly apropos for Alzheimer’s where you want to identify impairments in more than one cognitive domain, not just memory as I said before, but if you can also say there is a personality problem, there’s something else going on, that is important because Alzheimer’s disease affects many regions of the brain, and if it is a pure memory problem, short memory problem, it’s probably not Alzheimer’s – there are other conditions that cause pure memory loss, and then there’s a number of tests that can be done; we might want to go into that at some point to pin it down.
I’ll say one last thing which is that often, Alzheimer’s disease, until recently, has been a diagnosis of exclusion, so it’s very important for the clinician to do some simple tests that rule out other possible causes of dementia. There’s a few blood tests and other scans that can be done. We can talk more about that if you like.
Sucheta: Yes, I mean, I was going to come to that part about how do you diagnose Alzheimer’s, so let me just quickly ask you this question areas so, the progression is slow, hence the person experiencing the symptoms of themselves may not be aware of this cognitive change, or maybe chopped off as a normal aging related oopsies, and then second, as you said, that impairments in more than one domain such as executive function, personality, and those are more evident to other people, but a lot of times, many of these elderly folks are isolated or they are interacting with their peers or their spouses in isolation, and it may not be evident clearly. So, do you think we should talk about the neurobiology of Alzheimer’s or do you think – would you like to go and talk about how to evaluate for Alzheimer’s?
Dr. Kosik: Well, we can do both. Let’s first just say a word about neurobiology. The neurobiology really is in some ways simple because from the time of Alois Alzheimer, he very clearly pointed out that the brain fills up with neurofibrillary tangles made up of approaching [0:22:51] and these senile plaques made up of a protein called amyloid, amyloid beta. They are pathological entities that accumulate in the brain. The tau protein accumulates inside neurons to make these tangles and ultimately strangled them, and then the cells die. The amyloid [0:23:13] out around the neurons in the interstices of the brain and ends up creating these plaques that are also damaging, and those are the two entities that were the classic hallmarks. They are easy to see under a microscope. Until recently, they’ve been impossible to see in a living individual. So, this does go neatly into your question about evaluation because now, and I think now, I mean, really only in the last couple of years, we can actually image these two classical hallmarks directly in a living person. These are called PET scans, one PET amyloid, the other, PET tau that allow us to see that pathology and make diagnoses in the living individual if there is some question.
Sucheta: And is it recommended, is essential, or is it more important than relevant in a person who is younger than typical age of onset for Alzheimer’s?
Dr. Kosik: Yeah, very, very good question. So, these tests are actually not recommended, not because they are dangerous or anything like that – they are expensive, and because there would be no treatment implication at this time if your test is positive or negative, they are not widely recommended. They are recommended if one is doing research, if you are trying out a drug and you want to see if that drug is actually affecting the stigmata of Alzheimer’s disease, the plaques and tangles, then it’s mandatory, then you have to do it. So, these tests are important to validate drugs, number one, and that number two is exactly what you said: sometimes, we have cases that it’s really unclear. They are so young, why are they getting a disease that looks like Alzheimer’s. So, if we are perplexed clinically, that would be another reason to order these tests.
Sucheta: What is the age range with somebody gets diagnosed with Alzheimer’s, and when is it too young to be having Alzheimer’s?
Dr. Kosik: Well, as you probably know, there are genetic forms of Alzheimer’s disease where people have gotten as young as in their 20s, that is remarkably young, but there are other families, more commonly, and when I say more commonly, I’m still talking about a rare condition in which there is also a genetic cause and they tend to get it in their 40s or 50s. Let me say a word to sort of unpack that a little bit because the genetics is something that is important to understand in this modern world where genetics is available to all of us. You just send away your saliva or blood and you get your genes back from various companies. So, in the case of Alzheimer’s disease, there are a small group of people, probably less than 1% who have these really bad genes. They are bad in the sense that they have a very high likelihood of causing early onset disease, usually as I say in the 40s and 50s, but as young as in the 20s. If inherited, the technical word is an autosomal dominant, that means it’s inherited from one generation to the next, and each child, if the parent has the gene, each child has a 50% chance of inheriting, just like you have a 50/50 chance of giving birth to a boy or a girl if the mother has it or the father, doesn’t matter which one, the child has a 50/50 chance. So, in a large family, you might see half of the children have it, and these genes are – if you have the gene, we have another technical word here, is that they are highly penetrant. So, if you have one of these genes, you are very likely to go on and get a disease. Fortunately, they are rare. There is, as I say, very low percentage.
Now, let’s go over the remaining 99% or 99.5% of people. We call the rest of the people who get their disease at a later age sporadic disease, but that doesn’t mean they are totally home-free with regard to genes. We do know that if you have a parent with Alzheimer’s disease, your risk goes up a bit. Not hugely, but it does go up, so there is something that can be inherited, and we now know that one of these genes that is now, and, maybe 25% of the Caucasian population, we know less about those numbers and other groups, but it’s probably very similar number in everybody, 25% of people will have a risk factor gene called APOE-4. If you have that gene, your risk goes up, so there are these genetic factors that are going to alter your risk.
Sucheta: Hmm, so wow, so much you have given us to think about. So, if your parent has Alzheimer’s disease, does that mean you are automatically likely to have some risk and is there a way to evaluate that risk?
Dr. Kosik: Well, the first one, I would say no. If you have a parent with a disease, you don’t want to just spend all your time worrying about it because while your risk goes up, goes up a very small amount. If you look at all the people that have a parent with Alzheimer’s disease, the risk for the child is not very much higher than the risk for people whose parents do not have it.
Sucheta: Oh, really?
Dr. Kosik: Yeah. It’s a little bit higher, but not much. So, the first question I would ask is if your parent has it, how old were they when they got it? If they got it when they were well into their 80s, when Alzheimer’s disease is incredibly, then, something like 40% of the population has Alzheimer’s disease among a group that is 85 years old. This is a very common entity among advanced age in people. But then, if I asked that question and the person tells me, “Yeah, my parents had it or one parent had it, and they got it when they were in their 60s,” I’m going to worry a little more. So, it’s still not this extreme case, the very young onset, but if a parent is getting it in their 60s or 70s, I’m going to be a wee bit more concern. Still though, the risk is not going up hugely, but if they want to sort that out and say, they came up to me and I say, okay, your risk goes up a little bit, and this person says, “I’m not satisfied with that, Doc. I want you to tell me exactly how much my risk is going. You’re saying a little bit, but a little bit can be a very little or just a little little,” so than in those cases, we are now able to get genetic testing to assess risk, and one test would be for this APOE gene, APOE-4, and we could then tell the person that yeah, if you have that gene, we can give you a number. We can tell you exactly how much your risk is going to go up if you have that gene.
Sucheta: So, is it worse if you were the person, would you recommend yourself to go into get tested if you have that, is that going to offer the relief that one is looking for by getting this assessment done?
Dr. Kosik: That is the question of the day because we really want – this whole question of disclosure and what people may want to know, how they’re going to use that information, this is the cutting edge question right now in genetics because these genetic tests, I told you one gene, APOE-4 but there are a few others, and so how much you want to know about your fate in life is a very personal matter that we all have to think very carefully about. If a person goes in and wants to have genetic testing for an incurable disease like Alzheimer’s, they must have, and according to the guidelines, they must have some genetic counseling, they must have a companion with them when they get the news, and because these are very wavy matters; they don’t just affect a person who’s getting the test, but it also affects their children, so it’s a very important question you are raising.
Sucheta: Oh, my goodness, you give me so much to think about. So now that you have talked about genetics, can you talk a little bit about nongenetic factors such as person with multiple concussions or person who has not received a high education. Does that impact their chances of getting Alzheimer’s in their old age?
Dr. Kosik: We don’t have super clear answer on your question about multiple concussions, and I’ll come back to that second. First, let me answer your question about education where the answer is a little bit more clear. We have very good statistical epidemiological evidence that people with high levels of education are relatively protected from Alzheimer’s disease. What we have come to learn is that that protection does not mean they are not going to get deep in their brains the plaques and tangles. They will get it like everybody else, but because of their education, they are a little bit more resilient to showing the clinical signs, the memory loss. Over the years, due to their education, they have developed or connections in their brain, more synapses. They can retrieve information in multiple different ways, they may be able to identify a bird, say, not just by its look, but by its song, and these ways, these different routes that you have to memory tend to be a little rigid, perhaps in someone who is – I would say, educated for sure, but education does not just mean formal education. It needs people that have kept their minds active, even if they don’t have a whole stack of degrees. So, bottom line, education can stave off the symptoms but not the underlying pathogenesis.
Now, for your question on concussions. Here is where it’s more murky. We have pretty good evidence now that repeated head trauma, even if that head trauma is not a frank concussion, repeated head trauma can lead to a kind of dementing illness, but we are still unclear whether or not that illness is strictly Alzheimer’s disease because we also know there are other entities that multiple concussions lead to, perhaps more commonly than Alzheimer’s. So, just to rephrase that, multiple concussions may increase your chances of getting Alzheimer’s disease, but more prominently, it increases your chances of getting another type of dementing illness that goes by the name of chronic traumatic encephalopathy or CTE. This has been a very popular topic lately because so many football players have come down with this condition.
Sucheta: Got it. So, is Alzheimer’s disease more common and then all collective types of dementia?
Dr. Kosik: Yes, we can clearly say that the most common form of dementia is Alzheimer’s disease.
Sucheta: And then, is the chronic traumatic encephalopathy, does that affect equally or more than a typical dementia and less than Alzheimer’s, or do we have any understanding of that?
Dr. Kosik: We don’t have good epidemiologic evidence for how prevalent the chronic traumatic encephalopathy is. I don’t think it’s – sure, it’s not as common as Alzheimer’s but how common and it actually is is not known.
Sucheta: Got it. So, as we come to close up this discussion, can you talk a little bit about executive function and aging, as well as executive function and Alzheimer’s disease, because typically, people think about memory as a standalone feature or forgetfulness, but it is also that disconnection between past and present which helps us formulate ideas about the future, that becomes a huge problem for people with these progressive degenerative problems. So, do you mind talking about that?
Dr. Kosik: Of course, those are very intriguing ideas. The idea about the use of the purpose perhaps that we can use such a strong word of memory is not so much to help us recollect the past, but to plan for the future, and when you think about memory in that way, it’s a tool for the future, not necessarily for re-creating the past. There’s really no necessity for memory to be completely accurate. The only people that really expect an answer to questions like what were you doing on May 5, 2016, we don’t have the kind of memory, and the only people that expect an answer to questions like that are attorneys. We really don’t have memories that are video recorders. Our memories are picked up and fragments, they get processed, the information is missing, information can be added, and what the processing is all used for is for us to better plan for the future to be strategic, and to be able to make accurate predictions about the future, that’s all we need because if we have to boil down brain function to one thing, it’s really about making predictions. You have to be able to know that what you’re going to do next is not going to kill you and that is critical.
Sucheta: I love that, and that is actually the essence of executive process which is being able to predict whether it’s the trajectory of your performance, your future outcomes, your current connection to the future self, all those predictions are happening as we speak and that is also the component of [0:37:18] planning, how do we execute, right?
So, as we close today, you have dedicated your career to this studying Alzheimer’s. What drew you to this topic? Because, it is kind of very troubling and you must have seen in your clinical life a lot of sad stories that have weighed on you. What do you see in this that makes you so engaged and hopeful about this?
Dr. Kosik: Well, I would say it’s the science that drives – I am always moved by patients and I like to see patients, but the actual the reason I get up in the morning and ponder these problems is because the scientific problem here, the way it’s all knotted together, it’s the tangles, the plaques, the brain functions, and memory, and all the things we have been talking about is a really challenging fascinating intellectual problem that totally engages me.
Sucheta: Well, thank you so much for coming on the podcast. You have brought your wisdom and deep knowledge, and many, many listeners are going to benefit from it, so I’m really grateful for your time. Thank you, Ken.
Dr. Kosik: Thank you.
[music]
Producer: Alright, so that was Dr. Ken Kosik. As I suspected, Sucheta, especially personally for me, a really great conversation, talking about Alzheimer’s and dementia. An awful lot that I learned from this conversation, I can assure you. Any initial thoughts here you want to share?
Sucheta: Yes, and such an important conversation to have, and Ken is such a wealth of information, and I’m so grateful to know him as a friend. So, here are some of what is triggered in my brain as I was listening to this conversation, that we didn’t get into this, but the idea of normal aging. This didn’t come up, but literature talks about something called crystallized intelligence which refers the accumulation of information or knowledge based on one’s life experience. So, for example, crystallized intelligence is made up of skills and ability, and knowledge that is well practiced, overlearned, and very familiar. So, for example, knowing the capital of a country when we have – or vocabulary items, or knowing the meaning of the words that we have learned early on, and they become crystallized; they become permanently imprinted in the brain. Funny thing is that research shows that what is described as crystallized ability, it either remains stable where it even gradually improves at the rate of 0.2 to almost 0.003 standard deviation per year through the sixth and seventh decades of life. So hence, Brenda younger adults, the older adults tend to perform better on tasks requiring intelligence that is based on knowledge or tasks that require accessing prior knowledge, and that goes into problem-solving, for example.
In contrast then, there is something called fluid cognitive domains which include skills like speed of processing, psychomotor ability, and memory, and even executive function. So, it refers to skills and abilities that involve reasoning, problem solving, teaching decisions, kind of prioritizing, and the set of skills, they are fluent and the reason they are referred to as fluid skills is because they are not dependent on past knowledge or prior learning. It literally refers to application skill: how well do you apply the knowledge that you have. So, simple example which is not the best example, but if you want to open a can, you take a can opener and you use the can opener to open the can. What if you have a can opener that is not yours and you are, let’s say party of visiting me and I give you my can opener, by the way, you will spend extra minutes figuring out how to use that can opener, and knowing how to open cans using a can opener is your prior knowledge, but how to operate in this particular can opener, may be the reason you are processing speed may be slowed down because you are unfamiliar with the task itself, and by the way, I do have a can opener which I use often in my presentations that most people take at least five extra minutes to figure out, or sometimes, we go give up.
So, anyways, what I was saying, that these fluid cognitive domains reflect more the innate ability of how we process and learn information, how we maneuver our own environment and how we solve problems that we are not familiar with. Researchers such as salt house and his colleagues in their 2012 article talked about this that these abilities predominantly speed of processing and psychomotor abilities reach their peak by the third decade of life, and then there is a gradual decline at the estimated rate of 0.02 standard deviation per year. So, these age-related changes are self-evident but may or may not lead to dramatic decline in lifestyle or quality of life. So, as I was having a conversation with Ken, what my thoughts were, that there is like two letters next to each other. One that’s going up which is you become, more knowledge you have, more living you have done, the greater the wisdom, and then the second ladder where the skills decline and that is when your executive function, your memory skills, and your speed of processing. So, together, that is what makes you a wise old fool, so to speak.
Producer: Well, just thinking about the can opener, I mean, I mentioned my mother at the top of the show, she’s at that phase of this disease now where she can open a drawer and she won’t know what that is. She will pull it out and she’ll say, “I don’t know what this is, I don’t know what I was supposed to do with it.” She’s still at this phase felt that when I explained to her or I show her, then she eventually recalls it, and then can use it just fine. She’s also at the phase where any given day, she may know exactly what it is in the next day, she doesn’t. So, it comes and goes which is very common in that disease, so I’m very familiar with understanding what a can opener is or whatever the device is – a toothbrush, from time to time, or an umbrella, even appeared I mean, it’s just been interesting to see what she remembers and what she does not, and then how it changes from day to day. It’s fascinating stuff.
Alright, so continuing on, I think it’s important also to understand that all these age-related changes that you’re talking about, I mean, it goes just beyond forgetting why you walked into a particular room, right?
Sucheta: Yeah, I mean, getting older is certainly not a picnic. We kind of have discussed that and it’s commonsensical, I guess, and there’s a small element of decline in mental function that everybody experiences, and forgetting names comes to mind that we have talked about. So, on the other hand, onset of dementia tends to be gradual and insidious, and the early symptoms can be easy dismissed as normal aging, hence, they can be missed, and my conversation with Dr. Kosik was talking – was about these three distinct categories when we talk about these changes in cognition, and in fact, not just limited to cognition the general social and emotional welfare. There are three distinct processes. One is that normal aging or cognitive aging, and it is a real thing, the second is mild cognitive impairment, and then the third is that actual dementia and Alzheimer’s being one kind of dementia. So, in normal aging, they is certainly slowing of the processing speed, difficulty in word retrieval, short-term memory challenges, but there is no decline in the way we function or the individual functions. The person describes or feels that he’s meeting expectations and going about life perfectly fine. In the mild cognitive impairment, however, there is very, as Ken talked about, there is an indistinct line or the gray zone where the symptoms persist and they become worry some, and then finally, when it becomes extremely detectable which is when, in neurological terms, these are called frank symptoms – they are distinct, they present themselves in lumps, there are more than one area that is affected, and just by talking with such individuals, you can tell there is something wrong. So, it is the mild cognitive impairment and distinguishing that from the normal aging, that is where the art and a science meet, I feel.
Producer: Well, yeah, no doubt about it. I mean, it goes without saying, aging affect your entire body and the brain, and obviously changes in the brain are not visible. Speaking on my mother again, if you were to watch her walk down the hallway in her community, you would not know that she is late stage dementia or Alzheimer’s. She is one of the few residents of that committee that actually can get around without help of a walker or a wheelchair, or even assistance. I mean, so she still physically pretty functional, but we all know her brain is severely diseased. So, talk more about that.
Sucheta: You are right, Todd. Brain is highly wired machine, and the connectivity determines its agility, and we have a few guesses as to what goes inside the brain and researchers like Ken study this, I remember reading his book about ash as he summarized what causes the brain changes, the first component being inflammation which is the response of the immune system, which is to send protein which induces swelling, redness, and in a short quantity and for a short term while, it’s good, but a chronic state of inflammation without any respite is not that great, and then of course, prolonged inflammation speeds up aging, and the second part is the oxidization, the imbalance between the oxidized particles and the antioxidants can alter the brain chemistry, causing damage, and the third thing he describes that the wear and tear that just like the body, the brain injuries that wear and tear. So, for example, like the rest of the body, the damage to the neurons which are the brain cells, that damage is not reversible; it’s not repairable, so they don’t regenerate themselves. So, tearing or strain on these nerve cells causes a breakdown in communication between the neuron’s, resulting in slowing down and it leads to forgetfulness and slowness in processing, so it’s kind of important understand that the brain actually aging can be detected at the brain level, and a funny thing about the brain as you know is the brain is a highly wrinkled body part and that is one body part that you do not want to lose your wrinkles – you want to keep them.
Producer: Yeah, I understand that. I think it was also important that we discussed the difference between dementia and Alzheimer’s. Now, Alzheimer’s is a form of dementia but they are different, right? And, what was striking to me was his comment that if you live long enough, you will likely suffer from dementia, but not necessarily Alzheimer’s – go deeper there.
Sucheta: Yeah, and that was the discussion we were having, right, that I think it’s the presentation of symptoms and how to decipher all that is such a critical part of management too. The Alzheimer’s Association has it on their website that dementia is a general term for loss of memory and other mental abilities severe enough to interfere with daily life, and that’s the critical part, severe enough to interfere with daily life. It is caused by physical changes in the brain. Alzheimer’s is the most common type of dementia, but there are many other kinds of dementia. So, I’m going to put a link there, we have lots of types of dementia, but discussing this Alzheimer’s particularly, as Ken was explaining that it’s the kind of dementia are aware that a few things that are happening. One is, it takes a slow course, that means progression of impairment or decline happens over the years and not overnight. Second was that impairment is in more than one cognitive domain. So, it’s not exclusively limited to memory, and the third is a diagnosis of exclusion. That means the blood tests and the scans rule out other problems which event eventually focuses, zooms into Alzheimer’s, and from then, there are cognitive and emotional domains were the changes appear, and so the most important thing is to not really, I guess avoid having to deal with the challenges that one is noticing. The most important thing for me that again, aren’t you fascinated by our body and brain when they work well, we don’t have any concerns, we become very alerted about things when they are not working? When you are walking well, you don’t think about your legs between your knees hurt, you’re like, what must be the reason? So, similarly, I feel that the two degenerative processes that Ken was talking about in Alzheimer’s is really something that everybody needs to get more information about, is one is that amyloid beta protein that loses out and clumps into flax, and then they accumulate all over the brain causing the disruption in cognition, perception, and processing, and interesting thing about that is it’s all over the brain, and so it’s unlike a brain injury or a gunshot wound. We call that a diffused versus focal injury, so this is a very focal – rather, this is not focal at all. Second thing is that he talked about tau protein which causes the new neurons to misfire and eventually, it causes them to die, and of course, the tau protein help neuron minting their structure and function, and without them, there is a disruption in the way brain functions altogether.
So, most important thing about memory is memory is of course, is the synaptic connection, that means the two brain cells, neurons are communicating to each other through exchange of impulses, electric impulses and more exchange, robust exchange, the greater the communication and the greater cognitive ability and memory, and less and less firing or less and less communication between the neurons, that means less and less chances of that area of the brain being cognitively robust, and that is exactly what happens with Alzheimer’s, and so that, almost like what comes to visualization comes to mind is like a dimming – like that begins to dim and then flicker, and then not work. Similarly, there is a diminished kind of intensity to the volume to that complication that happens between the neurons, and that decline causes the end of one’s robust cognitive functions, I guess.
Producer: Yeah, that is what has been – I don’t want people to get the wrong idea when I say it’s been fascinating to observe those because it has been cruel and horrible, but it has been an amazing process to observe because this dimming process is exactly what my mom has gone through. It has not been this slow, unnoticeable gradual change. It’s like she goes through like these plateaus, right? There’s these stages where she evolves into a staged, and that exists that they for a while, and then there is a noticeable sudden kind of change that and lasts for another while. I don't know how her course will always be, but it’s been – a dimming is an interesting way to think of that. So, fascinating stuff, goodness gracious.
So, gosh, before we go, Sucheta, any concluding thoughts?
Sucheta: Yeah, I’ve been thinking a lot about aging and age-related changes, and recently, there is a book that I was reading, Old Masters: Great Artists in Old Age written by Thomas Dormandy, and he talks about that all the case histories point in one direction: the extraordinary flowering of artistic genius in old age. So, he particularly, in this book talked about these incredible artists who continue to be robust in their practices, and in prolific artists and produce some incredible work. For example, Monet, when we think about Monet, we think about Water Lilies, and you know this, that the Water Lilies is not a name of a single painting, but it’s rather a series of works, and Monet painted about close to 250 water lilies and it was a subject that he kept revisiting throughout his life. When Monet turned 82, he was diagnosed with severe cataract in his right eye and a mild one in his left eye which made it impossible to see, and then Monet underwent three cataract surgeries on his right eye which did not give him any relief. In fact, his eyesight, I think got worse, but he continued to work. He painted water lilies during this time titled Japanese Bridge, and you can look it up on the web, but it’s dominated by reds and oranges which is so beautiful and vibrant which kind of invokes the sense of vibrancy, so even though he wasn’t functioning at his best, he still persisted and produced this incredible thing, and when he died in 1926, the paint on his last waterlily was still not dry.
Why am I talking about this? There’s so many artists including Monet who continued to be wonderfully productive and wonderfully functional to the end. Michelangelo was 89 when he died. Matisse, when he died at 84 was still very artistically engaged. Picasso at 91 was a prolific art producer. O’Keefe, same thing, 98. So, I think at one end, we are discussing Alzheimer’s, then we have this other end of the spectrum where we have these age-related changes impacting people, and get them staying engaged in life, and I feel that what can we do as we have a discussion, even you as a son of a mom who is going through this disease and its impact on her, how do you stay hopeful and connected with your life is what comes to my mind. So, one is, I feel one must be vigilant and one must report symptoms. There is no need to feel shame or fear once you notice things like losing things, getting lost, disoriented, forgetting procedures, or notice that you are avoiding complex thoughts. That is important to address. It is a complex disease. It emerges insidious and subtle, for sure and it takes away the independence and self-worth. It affects family and managing loved ones’ need is a top concern for everybody, and so we must take this seriously, but I think we must stay engaged and as helpful.
The last comment I will make is about executive function. The kinds of executive function symptoms that are evident in cases of Alzheimer’s art difficulty planning and problem solving, difficulty in completing familiar tasks, kind of determining time and place of execution, finding the right words to use to describe ideas, difficulty in making decisions, particularly complex decisions such as planning of location, weighing options, choosing the right insurance, signing up for services, all those require complex abstract comparison and contrasting, and taking multiple factors into consideration, and that can be really, really difficult, but most people are living independently when the spouses die or if you are particularly mobile, you may not be living in a nursing home, so nobody may be interacting with you or you may not be interacting, and so that is why loved ones have such a responsibility to dig deep into the daily lives of these individuals, but I’m very hopeful. I’m hopeful that we as a community can do a lot together, but the first step is to understand, and that is what we try to do today.
Producer: Well, no surprise. I really benefited from the conversation as well, and I like what you just ended at there, yeah, there’s the Alzheimer’s patient that we have to think about, care about, manage their care and look after them, but caregivers are suffering through this as well, and I’m blessed to have the support of family to help me get through that, but that is something we must be very mindful of what you’re going through this for a loved one who is suffering because the caregivers, they have a hard time with this and they need support and care, and love as well, and so that’s almost as equally important, a part of this whole conversation that just the patient. So, great stuff.
Well, I am very much looking forward to our next conversation with Dr. Kosik. I believe he’s going to share with us a couple of hints about how we can do some things now to be proactive in trying to prevent this. So, it’s going to be a great conversation.
Alright, well, that’s it for today. On behalf of our host, Sucheta Kamath and all of us at Cerebral Matters, thank you for tuning it and listening today and we look forward to seeing you again right here next week on Full PreFrontal.