New approaches to Alzheimer's Disease

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This post is another pitch for our on-going effort to develop simple, easy, and effective ways to track neurocognitive health through short interactions with a web app.  Why do we want this? Two reasons: first, early detection of neurodegenerative disorders through near-universal tracking; and second, easy large-scale evaluation of interventions, whether those are drugs or lifestyle changes. You can participate by enrolling at https://speechbiomarkers.org, and suggesting it to your friends and acquaintances as well.

Today, diagnosis generally depends on scoring below a certain value on cognitive tests such as the MMSE, which usually won't even be given until you've started experiencing life-changing symptoms — and at that point, the degenerative process has probably been at work for a decade or more. This may well be too late for interventions to make a difference, which may help explain the failure of dozens of Alzheimer's disease drug trials. And it's difficult and expensive to evaluate an intervention, in part because it requires a series of clinic visits, making it hard to fund support for trials that don't involve a patented drug.

If people could accurately track their neurocognitive health with a few minutes a week on a web app, they could be alerted to potential problems by the rate of change in their scores, even if they're many years away from a diagnosis by today's methods. Of course, this will be genuinely useful only when we have ways to slow or reverse the process — but the same approach can be used to evaluate such interventions inexpensively on a large scale.

More background is here: "Towards tracking neurocognitive health", 3/24/2020. As that post explains, this is just the first step on what may be a long journey — but we will be making the data available to all interested researchers, so that the approaches that have worked elsewhere in AI research over the past 30 years can be be applied to this problem as well.

Again, you can participate by enrolling at https://speechbiomarkers.org . And please spread the word!

For an excellent review of the pharmaceutical industry's frustrating history in this area, see Christie Aschwanden, "For Alzheimer's researchers, a long and frustrating struggle to find a drug", Washington Post 4/4/2020:

In February, pharmaceutical companies Roche and Eli Lilly announced that two experimental drugs they had developed for Alzheimer's disease had failed in clinical trials. Roche's drug, gantenerumab, and Eli Lilly's solanezumab joined more than 100 other potential Alzheimer's drugs that have flopped, including aducanumab, a much-heralded drug from Biogen. […]

More than 200 promising leads have fallen through just in the past decade. There has been an ongoing search for Alzheimer's drugs since the 1990s, but "the long and short of it is that it's not been successful," says Lon Schneider, an Alzheimer's researcher at the University of Southern California's Keck School of Medicine. […]

Until relatively recently, the search for a drug largely centered around the idea that Alzheimer's develops and progresses in a specific pattern. Toxic plaques of beta amyloid clump together between neurons in the brain. As these accumulate, they're accompanied by a buildup of tangled masses of tau inside neurons. These changes are accompanied by inflammation and cell death in the brain. Many drug candidates have aimed to clear or disarm beta amyloid, under the logic that eliminating amyloid plaques would halt or reverse the process and thus Alzheimer's itself. […]

The search for Alzheimer's treatments is riddled with failed amyloid drugs, and amyloid has begun to look like an imperfect target. For one thing, about 40 percent of people in their 70s have amyloid plaques but no dementia, Schneider says. At the same time, some people with dementia have not developed amyloid plaques.

Aschwanden's article discusses the possibility that the amyloid physiology is a result rather than a cause:

Rather than being a driver of Alzheimer's disease process, amyloid may represent its aftermath.

"Amyloid plaques might actually be signs of the brain doing its job when it's subject to injury or inflammation," Schneider says. And if that is the case, it would mean that attempts to treat Alzheimer's disease by cleaning up amyloid are futile.

"I compare amyloid plaques to tombstones," Schneider says. You can go into a cemetery and remove tombstones, but it will not make the people buried there any less dead.

In addition to drugs with other physiological targets, the article also cites interest in lifestyle interventions:

For now, some of the most promising approaches to addressing Alzheimer's are non-pharmaceutical. The NIA is sponsoring 86 studies of nondrug interventions that may help, including exercise, diet, cognitive training and sleep. The U.S. Pointer study is a two-year clinical trial examining whether lifestyle interventions can protect older adults from cognitive impairment and dementia.

But oddly, the article doesn't discuss the widespread suspicion that part of the problem lies in diagnostic methods that don't raise a flag until years or even decades into the process of neurological degeneration.

 



2 Comments

  1. Kenny Easwaran said,

    April 8, 2020 @ 3:57 pm

    A related topic was discussed recently in a very poignant way on an NPR podcast:

    https://www.npr.org/2020/03/18/817977005/an-unlikely-superpower

    In the middle of this long story exploring the relationship between smell, memory, prediction, and living with uncertainty, there's some discussion of a method for detecting Parkinson's and Alzheimer's before they become behaviorally manifest, as well as some home for being able to evaluate some interventions.

  2. Martin said,

    April 11, 2020 @ 1:16 pm

    Should one be a native English speaker to participate?

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