All of the excitement ... and cautious optimism ... in Alzheimer's research has been around aducanumab. While there are other possibilities out there, aducanumab has achieved something quite remarkable -- even if it failed to improve cognition. Researchers have shown that the malformed protein we call beta amyloid can actually be removed from the brain. Research on the treatment was halted because it did not appear to be improving cognition, but that conclusion is being revisited.
What's interesting to me is that the strategy aducanumab employs (using a monoclonal antibody to destroy the amyloid) is being applied in other treatments. Gantenerumab, donanemab, and BAN2401 all have been shown to remove amyloid plaques, and with BAN2401, this has been maintained for several years. We discussed BAN2401 back in July 2018. These treatments are all in phase 2 or phase 3 trials. (Another one, crenezumab, appears to be flaming out...)
As with aducanumab, the question remains whether these treatments will actually improve cognition or slow the progress of the disease. At one time it seemed a slam dunk that, if you can get rid of the beta amyloid, you can stop the disease and improve cognition. But now, not so much.
The question of cognitive improvement as a consequence of amyloid removal was addressed at the Clinical Trials on Alzheimer’s Disease conference we discussed on December 6, and the discussions were reviewed this week in an article in ALZForum. The article was "Amyloid Clearance: Check. Cognitive Benefit: Um ... Maybe." Presentations at the conference discussed in the article addressed the successes in amyloid removal, but were quite cautious about claiming improvement in cognition. In their words, "There are hints—though that is all they are at this point in time—that amyloid clearance correlates with preserved memory, as well." The ALZForum interviewed one researcher who said, "The totality of evidence now suggests anti-amyloid antibodies will work as a preventative treatment to delay AD progression."
So, stay tuned.
We are currently in Hawaii spending the holidays with family. The temperature is pleasant, but a bit wetter than we'd hoped. We are hopeful that you had a wonderful Christmas, Hanukkah, or whatever you celebrate, and you have a prosperous 2020!
In my book, "Beating the Dementia Monster," I describe what has occurred since 2015 when I first knew I had memory problems. (You can find it on Amazon.com.) I have experienced remarkable improvement, and I’m certain that I can share valuable information with many others. In this second edition I continue my story to 2020 and provide greater understanding of how Alzheimer's advances and why what I did worked.
Monday, December 30, 2019
Saturday, December 21, 2019
Vitamins Are Bad for You ... Maybe Kill You?
When I was in high school -- or maybe it was college -- I remember Linus Pauling making news on several fronts. He had won the Nobel Prize in chemistry and he was a political activist. But then he was saying that he'd taken supplements with a high vitamin C concentration for an extended period of time and it had kept him from getting a cold.
It was kind of big in the news, and a lot of people started taking vitamin C supplements to keep from getting sick. But my skepticism antenna went up right away. As near as I could tell, he was committed to a scientific conclusion based only on his own anecdotal evidence. As it turns out, the idea that Vitamin C prevents or cures sickness has been scientifically discredited, but the mythology persists to this day. This has stained Pauling's legacy as a remarkable scientist.
In the 1970s, the idea that vitamin E had increased fertility in rats generated a lot of consumption of vitamin E supplements on the belief that it might have aphrodisiac properties. This ended abruptly when a study claimed to have found that people taking vitamin E were more likely to die younger than those not taking them.
Vitamin B-12 deficiency can lead to dementia, although not Alzheimer's dementia. With the exception of supplements that can be generated from yeast, we normally acquire it from animal products, so vegans must take extra precautions to ensure they get adequate B-12.
Vitamin C and vitamin E are antioxidants that can fight oxidation damage in the brain, and oxidation is part of the Alzheimer's disease process. This is why foods with antioxidant properties, like blueberries and strawberries, are included in the MIND diet. (We wrote about this back in June.) We anticipate the results of a large study of the MIND diet that may confirm its benefit with respect to Alzheimer's disease.
As we discussed in Beating the Dementia Monster, sometimes we extract nutrients and chemical products from beneficial foods and consume them as supplements. If they benefit our health in the food, then the supplements should convey the same beneficial properties. But they don't.
The other day, I saw a BBC article about vitamins ("Why Vitamin Pills Don’t Work, and May Be Bad for You") that was saved by Pocket. The article smacked Pauling up side the head and described a lot of research about vitamin supplements. Several studies suggested premature deaths resulted from consumption of vitamin supplements. The authors noted that we don't understand all the dynamics of nutrition, and different nutrients and chemicals in the food may act in concert to produce their benefit. So consuming red wine (moderately) may have a beneficial effect, but consuming the active ingredient (resveratrol) as a supplement does not.
The article was interesting reading, but the bottom line was: skip the supplements and eat your fruits and vegetables.
It was kind of big in the news, and a lot of people started taking vitamin C supplements to keep from getting sick. But my skepticism antenna went up right away. As near as I could tell, he was committed to a scientific conclusion based only on his own anecdotal evidence. As it turns out, the idea that Vitamin C prevents or cures sickness has been scientifically discredited, but the mythology persists to this day. This has stained Pauling's legacy as a remarkable scientist.
In the 1970s, the idea that vitamin E had increased fertility in rats generated a lot of consumption of vitamin E supplements on the belief that it might have aphrodisiac properties. This ended abruptly when a study claimed to have found that people taking vitamin E were more likely to die younger than those not taking them.
Vitamin B-12 deficiency can lead to dementia, although not Alzheimer's dementia. With the exception of supplements that can be generated from yeast, we normally acquire it from animal products, so vegans must take extra precautions to ensure they get adequate B-12.
Vitamin C and vitamin E are antioxidants that can fight oxidation damage in the brain, and oxidation is part of the Alzheimer's disease process. This is why foods with antioxidant properties, like blueberries and strawberries, are included in the MIND diet. (We wrote about this back in June.) We anticipate the results of a large study of the MIND diet that may confirm its benefit with respect to Alzheimer's disease.
As we discussed in Beating the Dementia Monster, sometimes we extract nutrients and chemical products from beneficial foods and consume them as supplements. If they benefit our health in the food, then the supplements should convey the same beneficial properties. But they don't.
The other day, I saw a BBC article about vitamins ("Why Vitamin Pills Don’t Work, and May Be Bad for You") that was saved by Pocket. The article smacked Pauling up side the head and described a lot of research about vitamin supplements. Several studies suggested premature deaths resulted from consumption of vitamin supplements. The authors noted that we don't understand all the dynamics of nutrition, and different nutrients and chemicals in the food may act in concert to produce their benefit. So consuming red wine (moderately) may have a beneficial effect, but consuming the active ingredient (resveratrol) as a supplement does not.
The article was interesting reading, but the bottom line was: skip the supplements and eat your fruits and vegetables.
Thursday, December 19, 2019
How Early Can the Latent Dementia Be Identified?
It's becoming clearer and clearer that the earlier you can identify someone who will develop dementia, the more relief you can provide. The evidence suggests that the earlier you begin treatment with aducanumab, the more success you're likely to have in slowing the advance of symptoms. So it's increasingly important to find ways of the identifying appearance of Alzheimer's and other dementias. Recall that the disease process may actually begin 20 years before dementia and well before the first cognitive symptoms are recognized. So there ought to be ways of seeing if something ominous is going on in someone's head well before even the onset of mild cognitive impairment.
So there's a lot of interest in early diagnosis, and we anticipate acceptance of some very sensitive blood tests in the coming months. And then there was a recent article in the journal Alzheimer's and Dementia regarding another way in which the probability an individual will develop dementia can be assessed eight years before the a conventional diagnosis.
The article was entitled "Stratifying risk for dementia onset using large-scale electronic health record data: a retrospective cohort study." Essentially the researchers reviewed the discharge notes for about 270,000 hospital patients and correlated statements in the notes with the incidence of subsequent development of dementia. They concluded that they could identify an increased probability of a discharged patient developing dementia as much as eight years before an actual diagnosis.
So there's a lot of interest in early diagnosis, and we anticipate acceptance of some very sensitive blood tests in the coming months. And then there was a recent article in the journal Alzheimer's and Dementia regarding another way in which the probability an individual will develop dementia can be assessed eight years before the a conventional diagnosis.
The article was entitled "Stratifying risk for dementia onset using large-scale electronic health record data: a retrospective cohort study." Essentially the researchers reviewed the discharge notes for about 270,000 hospital patients and correlated statements in the notes with the incidence of subsequent development of dementia. They concluded that they could identify an increased probability of a discharged patient developing dementia as much as eight years before an actual diagnosis.
Wednesday, December 18, 2019
Virtual Reality for Alzheimer's Patients
At a conference where I was speaking not long ago, there was a vendor showing off a virtual reality device for dementia. I had seen such a device used to give people a sense for what it was like to have dementia and thought this was the same. I knew nothing else about virtual reality in the context of dementia.
But during the Q&A for my talk, someone asked me what I thought about the use of virtual reality to help people with dementia, and I was caught off guard. I hadn't thought about a person with dementia using virtual reality. I don't remember what I said, but I'm sure the person with the question went away dissatisfied.
Recently, Paul, a friend of mine, sent me an article on various technological approaches to helping with dementia. Some of the approaches included items like GPS ankle bracelets to help find people who have wandered, but others were intended to enhance the lives of people suffering from dementia. This included robots, but also a virtual reality device, likely the one I saw at the conference.
The virtual reality device is manufactured by a company called MyndVR that leases the devices to assisted living facilities. The company claims that the device provides people suffering from dementia with experiences that reduce anxiety and depression, stimulate memory and cognition, and increase socialization. The article describes the experience of a man in the late stage of dementia watching a sunrise in Costa Rica, a place where he and his family had memorable vacations. This and other devices play music from when the users were younger to stimulate memory. (For what it's worth, I've tried playing familiar music to someone with serious dementia, and it wasn't able to stimulate the person.)
So how would I answer the conference question now? Can a virtual reality device actual improve the quality of life for someone suffering from dementia? I doubt I'd have a better answer now, since I can't find any information to back up the company's claims. But it is an intriguing idea.
But during the Q&A for my talk, someone asked me what I thought about the use of virtual reality to help people with dementia, and I was caught off guard. I hadn't thought about a person with dementia using virtual reality. I don't remember what I said, but I'm sure the person with the question went away dissatisfied.
Recently, Paul, a friend of mine, sent me an article on various technological approaches to helping with dementia. Some of the approaches included items like GPS ankle bracelets to help find people who have wandered, but others were intended to enhance the lives of people suffering from dementia. This included robots, but also a virtual reality device, likely the one I saw at the conference.
The virtual reality device is manufactured by a company called MyndVR that leases the devices to assisted living facilities. The company claims that the device provides people suffering from dementia with experiences that reduce anxiety and depression, stimulate memory and cognition, and increase socialization. The article describes the experience of a man in the late stage of dementia watching a sunrise in Costa Rica, a place where he and his family had memorable vacations. This and other devices play music from when the users were younger to stimulate memory. (For what it's worth, I've tried playing familiar music to someone with serious dementia, and it wasn't able to stimulate the person.)
So how would I answer the conference question now? Can a virtual reality device actual improve the quality of life for someone suffering from dementia? I doubt I'd have a better answer now, since I can't find any information to back up the company's claims. But it is an intriguing idea.
Tuesday, December 17, 2019
More Aducanumab and Biogen...
... and more on the San Diego Clinical Trials Conference.
This week's issue of ALZForum reported on the early December conference and discussed Biogen's presentation on aducanumab. The article contained a few insights I hadn't seen previously.
One thing I hadn't seen reported previously was that, not only did aducanumab clear beta amyloid plaques, but it also appears to remove tau tangles. Amyloid plaques and tau tangles are the two pathologies that define a dementia as Alzheimer's disease. Both are products of the disease, but both appear to participate in propagating the disease. Aducanumab was to remove the amyloid, but it's a bonus that it also appears to clear tau.
In Beating the Dementia Monster, we provide an overview of where these come from and what we understand about their role in Alzheimer's disease.
Apparently there were some naysayers at the conference, but the article reported the encouraging conclusion that, "It robustly removes amyloid, possibly clears tau tangles as well, and, at sustained high doses, may modestly slow decline."
The big question mark now is whether the FDA will consider the data clean enough to approve the drug. The issue will be how the unplanned changes to dosing that were made part way through the trial complicate analysis of the data.
This week's issue of ALZForum reported on the early December conference and discussed Biogen's presentation on aducanumab. The article contained a few insights I hadn't seen previously.
One thing I hadn't seen reported previously was that, not only did aducanumab clear beta amyloid plaques, but it also appears to remove tau tangles. Amyloid plaques and tau tangles are the two pathologies that define a dementia as Alzheimer's disease. Both are products of the disease, but both appear to participate in propagating the disease. Aducanumab was to remove the amyloid, but it's a bonus that it also appears to clear tau.
In Beating the Dementia Monster, we provide an overview of where these come from and what we understand about their role in Alzheimer's disease.
Apparently there were some naysayers at the conference, but the article reported the encouraging conclusion that, "It robustly removes amyloid, possibly clears tau tangles as well, and, at sustained high doses, may modestly slow decline."
The big question mark now is whether the FDA will consider the data clean enough to approve the drug. The issue will be how the unplanned changes to dosing that were made part way through the trial complicate analysis of the data.
Friday, December 6, 2019
The Aducanumab Drama Continues...
As I write, The12th Clinical Trials Conference on Alzheimer's Disease is in progress in San Diego, and it's in the news. It's in the news because everyone wants to know what's going on with aducanumab, and Biogen was there to talk about it. The PowerPoint for their presentation is here.
As we discussed previously, back in March Biogen suspended trials of aducanumab when a futility study found that the results were not sufficiently promising to justify continuing. But in October, they did an about face, saying they would be applying to the FDA for approval after all. They had reassessed the data and found the the treatment was actually working for some people.
What happened? When I originally auditioned for the trial, the researchers disclosed that earlier trials found that aducanumab was causing brain inflammation and micro-hemorrhages in some subjects. At the time (early-mid 2016) these were not believed to be life threatening, and the researchers monitored test subjects with relatively frequent MRIs. Nevertheless, dose levels appeared to be a risk factor, and they cut back the dose in the study populations receiving the higher dose in the middle of the trial. (Two different doses were administered to different populations.) Review of the data found that subjects on the higher dose were improving while they were on the higher dose. But this effect was diluted in the data after their dose was reduced. (Subjects on the lower dose had marginal improvement.)
So what does this mean? Obviously the idea that removing beta amyloid from the brain can slow cognitive decline is exciting, and it encourages further exploration of this path. It had looked very much like a dead end. But, so far, aducanumab has neither reversed nor stopped the advance of Alzheimer's disease. By some interpretations of the data, it has slowed the advance by an average of 30%. A lot better than nothing, but some are observing that insurance companies and others will be asking if that's enough to justify the (so far unknown) cost of the treatments.
And it won't just be the insurance companies. The researchers found that not everyone was willing to be persistent in showing up for the monthly, hour-long infusions. Regular MRIs will undoubtedly be a feature of the treatment process, and this could be a further inhibition to encouraging people to receive the treatment. Aducanumab won't be a pill you can take at bedtime.
Should the FDA approve aducanumab as a treatment for Alzheimer's disease? Depends on who you ask. Some say yes, others say it needs another trial that applies what we learned in the previous three trials.
Here is Biogen's aducanumab web page.
As we discussed previously, back in March Biogen suspended trials of aducanumab when a futility study found that the results were not sufficiently promising to justify continuing. But in October, they did an about face, saying they would be applying to the FDA for approval after all. They had reassessed the data and found the the treatment was actually working for some people.
What happened? When I originally auditioned for the trial, the researchers disclosed that earlier trials found that aducanumab was causing brain inflammation and micro-hemorrhages in some subjects. At the time (early-mid 2016) these were not believed to be life threatening, and the researchers monitored test subjects with relatively frequent MRIs. Nevertheless, dose levels appeared to be a risk factor, and they cut back the dose in the study populations receiving the higher dose in the middle of the trial. (Two different doses were administered to different populations.) Review of the data found that subjects on the higher dose were improving while they were on the higher dose. But this effect was diluted in the data after their dose was reduced. (Subjects on the lower dose had marginal improvement.)
So what does this mean? Obviously the idea that removing beta amyloid from the brain can slow cognitive decline is exciting, and it encourages further exploration of this path. It had looked very much like a dead end. But, so far, aducanumab has neither reversed nor stopped the advance of Alzheimer's disease. By some interpretations of the data, it has slowed the advance by an average of 30%. A lot better than nothing, but some are observing that insurance companies and others will be asking if that's enough to justify the (so far unknown) cost of the treatments.
And it won't just be the insurance companies. The researchers found that not everyone was willing to be persistent in showing up for the monthly, hour-long infusions. Regular MRIs will undoubtedly be a feature of the treatment process, and this could be a further inhibition to encouraging people to receive the treatment. Aducanumab won't be a pill you can take at bedtime.
Should the FDA approve aducanumab as a treatment for Alzheimer's disease? Depends on who you ask. Some say yes, others say it needs another trial that applies what we learned in the previous three trials.
Here is Biogen's aducanumab web page.
Wednesday, December 4, 2019
What a Difference a Day Can Make
Immediately after posting "Watching Dementia," I hopped in my car and drove over to the memory care facility to visit my friend there. The person I met today was someone completely different from yesterday.
My friend usually talks quite a bit, but he just rambles. He speaks in complete sentences (not "word salad"), but he will be incoherent. He may seem to have something on his mind, but one sentence does not logically follow from the previous, and he does not express specific ideas.
Yesterday, he seemed depressed, but there was one theme in his speech he could follow -- uncertain he was about who he was and where he was. He could also talk about how frightened he was. He said he didn't know who I was.
Today, he recognized me and spoke as coherently as I've ever heard him. Perhaps more coherently. He stuck with a topic and actually reasoned about it at length. I can't say I've ever heard him reason about a topic before.
Many caregivers that I've met speak about how people with dementia have good days and bad days. I've experienced this to a lesser extent with my own condition. I'm wondering if there's something in this phenomenon that might be useful to study, but I haven't seen anything about it in the research literature.
My friend usually talks quite a bit, but he just rambles. He speaks in complete sentences (not "word salad"), but he will be incoherent. He may seem to have something on his mind, but one sentence does not logically follow from the previous, and he does not express specific ideas.
Yesterday, he seemed depressed, but there was one theme in his speech he could follow -- uncertain he was about who he was and where he was. He could also talk about how frightened he was. He said he didn't know who I was.
Today, he recognized me and spoke as coherently as I've ever heard him. Perhaps more coherently. He stuck with a topic and actually reasoned about it at length. I can't say I've ever heard him reason about a topic before.
Many caregivers that I've met speak about how people with dementia have good days and bad days. I've experienced this to a lesser extent with my own condition. I'm wondering if there's something in this phenomenon that might be useful to study, but I haven't seen anything about it in the research literature.
Watching Dementia
I mentioned before that I would visit two friends who lived in elder care facilities. One of these was a good friend that I'd known for more than 25 years but was in his late 90s. I would visit him two or three times a week. In years gone by, he and I would meet for dinner in a diner we liked that seemed to cater to older people. On those evenings, he would tell me stories about growing up on a dryland wheat farm along the Snake River as one of the younger of 10 children. He would also tell me about his service in WWII, when he fought in the Battle of the Bulge. He was born two years before my own father.
More recently I tried to get him to tell me those stories again for my video camera, and he could still remember the earlier ones. However, he had a hard time recalling later periods, even from the 1960s. While he had days when he was quite confused, he clearly did not have Alzheimer's disease or any neurodegenerative disease -- he was simply old. And most days he was quite coherent, even if he had trouble recalling specific memories of events that had been readily available to him a couple of years ago.
A couple of weeks ago, his wife called to tell me that he had fallen and broken his hip. This was the day after I finished filming his video autobiography, what of it we were going to get. The next day she called to tell me that he had died.
The other friend is in a memory care facility that is much closer to our home. I'm able to see him pretty much every day. He's in his mid-80s and does have significant dementia. His wife is a friend of my wife's, and I didn't know him before he had dementia. His cardiologist judges it is vascular dementia, but I don't believe he's ever had any brain imaging to support that.
While the second friend has serious dementia, he is very pleasant to speak with most days, and is always happy to see me. Some days he recognizes me as a familiar face, while other days we are introduced to each other as if for the first time. Some days he knows his name, some days he knows only his first and middle name, and other days he can't recall his name at all. Unlike my first friend, he (apparently) had no religious background or upbringing, but nevertheless is always happy for me to read to him from the Bible.
What prompted me to write today is that, when I visited him yesterday, he was much more confused than I'd seen him in the past. He has always been confused to some level, but yesterday he seemed much more uncertain of who he was or where he was. He spends a lot of time in bed, but he's usually pretty lively when I'm there talking with him. Yesterday seemed different.
In visiting these facilities, I've come to learn a little about some of the other residents. If you're sitting in the common area talking, others are likely to come up and start talking with you, usually nonsense. One theme that came up with both of my friends, and also with other residents, is their fear that they have no money. They need to find a job so that they can pay their expenses. I hadn't heard that for a while, but my friend brought it up yesterday. My sense is that question may signal depression, based on their apparent mood at the time they bring it up.
My friend recently began to hallucinate. Apparently, he had some kind of issue over a car he owned that he may have given away or sold for less than it was worth. I don't know if anything like that happened in his life, but he seemed obsessed with it for a couple of days. I'll have to ask his wife about it. He once pointed across the room from his bed and was surprised that I didn't see the car there. Perhaps we were in a garage The issue of the car seems to have passed, but two days ago he was surprised that I didn't see a couple of other people in the room with us.
What I'm trying to discern in the time I'm spending with my friend are the ways in which his disease progresses. I'm not always sure if, when I see something I hadn't seen before, whether it is evidence of decline. I am curious about whether the four syndromes will manifest themselves, although these are largely peculiar to Alzheimer's disease. I'm also curious about how quickly he is declining and whether there are factors that can be associated with either retarding or accelerating his decline. For example, sleep and social connection, although I can't measure these objectively.
More recently I tried to get him to tell me those stories again for my video camera, and he could still remember the earlier ones. However, he had a hard time recalling later periods, even from the 1960s. While he had days when he was quite confused, he clearly did not have Alzheimer's disease or any neurodegenerative disease -- he was simply old. And most days he was quite coherent, even if he had trouble recalling specific memories of events that had been readily available to him a couple of years ago.
A couple of weeks ago, his wife called to tell me that he had fallen and broken his hip. This was the day after I finished filming his video autobiography, what of it we were going to get. The next day she called to tell me that he had died.
The other friend is in a memory care facility that is much closer to our home. I'm able to see him pretty much every day. He's in his mid-80s and does have significant dementia. His wife is a friend of my wife's, and I didn't know him before he had dementia. His cardiologist judges it is vascular dementia, but I don't believe he's ever had any brain imaging to support that.
While the second friend has serious dementia, he is very pleasant to speak with most days, and is always happy to see me. Some days he recognizes me as a familiar face, while other days we are introduced to each other as if for the first time. Some days he knows his name, some days he knows only his first and middle name, and other days he can't recall his name at all. Unlike my first friend, he (apparently) had no religious background or upbringing, but nevertheless is always happy for me to read to him from the Bible.
What prompted me to write today is that, when I visited him yesterday, he was much more confused than I'd seen him in the past. He has always been confused to some level, but yesterday he seemed much more uncertain of who he was or where he was. He spends a lot of time in bed, but he's usually pretty lively when I'm there talking with him. Yesterday seemed different.
In visiting these facilities, I've come to learn a little about some of the other residents. If you're sitting in the common area talking, others are likely to come up and start talking with you, usually nonsense. One theme that came up with both of my friends, and also with other residents, is their fear that they have no money. They need to find a job so that they can pay their expenses. I hadn't heard that for a while, but my friend brought it up yesterday. My sense is that question may signal depression, based on their apparent mood at the time they bring it up.
My friend recently began to hallucinate. Apparently, he had some kind of issue over a car he owned that he may have given away or sold for less than it was worth. I don't know if anything like that happened in his life, but he seemed obsessed with it for a couple of days. I'll have to ask his wife about it. He once pointed across the room from his bed and was surprised that I didn't see the car there. Perhaps we were in a garage The issue of the car seems to have passed, but two days ago he was surprised that I didn't see a couple of other people in the room with us.
What I'm trying to discern in the time I'm spending with my friend are the ways in which his disease progresses. I'm not always sure if, when I see something I hadn't seen before, whether it is evidence of decline. I am curious about whether the four syndromes will manifest themselves, although these are largely peculiar to Alzheimer's disease. I'm also curious about how quickly he is declining and whether there are factors that can be associated with either retarding or accelerating his decline. For example, sleep and social connection, although I can't measure these objectively.
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