Life, the Universe, and Everything

New Dementia Trial Results

There’s a new clinical trial result showing that Bredesen’s approach is able to at least partially cure common forms of Alzheimer-like dementia. (Press release here). It has not received as much attention as it deserves.

The 9 month study seemed a bit less impressive than what I’d hoped for, but the outcomes still support the claim that common forms of dementia are partly curable.

Out of 25 patients, 21 or 19 improved their cognition compared to the start of the trial, depending on which measure I look at, and 2 or 3 declined.

Side effects included occasional improvements in hypertension and diabetes, enough to allow patients to stop taking medications for those conditions.

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Functional Medicine

Mainstream medicine has become increasingly standardized over the past few decades.

Standardization has some benefits: reduced inequality, improved procedures for minimizing mistakes, and increased predictability. Those attributes are often easier to verify than health effects.

Standardization is not so great for promoting innovation (standardizing a few building blocks may promote innovation, but that’s not what medicine has done). Yet medicine is an area where we have a relatively high need for more innovation.

It would be nice if one system of medicine provided everything that I want from medicine. Just like it would be nice if one company could provide all my transportation needs, or every type of food that I want, or an operating system with all the software that I want to use.

Alas, none of those seem close to being feasible this decade. Yet I get the impression that many more people expect it of medicine than is the case for food or transportation.

I’ve reached an age when it’s valuable to ask a good deal from medicine. So in addition to a standard doctor, I’ve engaged with a competing “brand” of medicine.

Specifically, the functional medicine practitioners at Chris Kresser’s Adapt180.

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Book review: The End of Alzheimer’s Program, by Dale Bredesen.

This sequel to The End of Alzheimer’s is an attempt at a complete guide to a healthy lifestyle.

Alas, science is still too primitive to enable an impressive version of that. So what we end up with is this guide that would overwhelm anyone who tries to follow it thoroughly, while still lacking the kind of evidence that would convince a skeptic.

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Last month, I conceded defeat in my bet (with Robin Hanson) that US COVID-19 deaths would be less than 250,000.

My biggest mistake was thinking voters would care about results, and unite against a common enemy as they did in WWII. I should have been more aware of the tendency to treat natural deaths as more acceptable than deaths due to a hostile agent. Robin clearly did better at evaluating this.

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Book review: The Precipice, by Toby Ord.

No, this isn’t about elections. This is about risks of much bigger disasters. It includes the risks of pandemics, but not the kind that are as survivable as COVID-19.

The ideas in this book have mostly been covered before, e.g. in Global Catastrophic Risks (Bostrom and Cirkovic, editors). Ord packages the ideas in a more organized and readable form than prior discussions.

See the Slate Star Codex review of The Precipice for an eloquent summary of the book’s main ideas.

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From The problem with rapid Covid testing, Mayank Gupta writes:

The absolute number of false positives would rise dramatically under slightly inaccurate, broad surveillance testing. At least initially, the number of people going to the doctor to ask what to do would also rise. One can imagine if doctors truly flubbed and didn’t know how to advise patients accurately, a lot of individual patients would lose trust in the medical system (testing, doctors, or both). The consequence of this would be more resistance to health public policy measures in the future.

For a reminder of why rapid testing is valuable, see Alex Tabarrok. Note also the evidence from the NBA that people who need useful tests can be more innovative than the medical system.

This seems like the tip of an important iceberg.

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A new study has provided evidence that a healthy lifestyle can reverse aging, as measured by epigenetic age: Reversal of Epigenetic Age with Diet and Lifestyle in a Pilot Randomized Clinical Trial. This is the second study to show that epigenetic age can be reversed in humans (here’s a reminder to read the first).

They used the Horvath DNAmAge clock.

After a mere 8 weeks of a healthy lifestyle, the subjects’ DNAmAge was 3.23 years younger than the controls (and 1.96 years younger than the pre-trial DNAmAge of the treatment group).

The lifestyle interventions weren’t labeled as paleo, but they closely resemble the lifestyles that are recommended by Chris Kresser, Steven R. Gundry, and Dale Bredesen. The diet comes about as close as the diet of a typical paleo enthusiast to avoiding foods that have been available for less than 10,000 years. The recommended foods that I consider the least paleo are “coconut, olive, flaxseed and pumpkin seed oil”. The diet is more plant-based than the stereotypical paleo diet, but it’s well within the normal range of hunter-gatherer diets.

The study has a bunch of the usual limitations, such as a small sample size (18 people in the treatment group). There are also reasons for mild concerns about conflicts of interest, as some of the researchers work as functional medicine physicians, so their careers are mildly dependent on the popularity of the lifestyle approach being studied. As far as I can tell, that is likely to cause a level of bias that is rather ordinary for nutrition-related research. Oh, and the instructions are listed as “Patent pending”, but it’s unclear why they would meet the novelty requirements for a patent.

My main doubt comes from the difficulty of figuring out whether DNAmAge measures causes of age-related health problems, or whether it’s just measuring symptoms. I’m slightly more than 50% confident that epigenetic changes have some causal influence on aging.

This kind of trial raises questions about how well patients follow the instructions – most would find it difficult to “Avoid added sugar/candy, dairy, grains, legumes/beans”. The paper describes how they checked on patient compliance, but I didn’t see any data indicating what they found about compliance. So there’s some risk that they were especially lucky about getting patients to follow their instructions, and maybe future studies of this nature will show much weaker results due to poor compliance.

Lastly, it’s a bit odd that the control group appeared to age 1.27 years in 8 weeks. Maybe they were depressed about not getting any treatment? (This isn’t the kind of study where blinding is feasible). More likely it was just noise, but that’s a reminder that the small sample size provides lots of opportunity for luck to dominate the results. Even if we assume perfect measurement, there’s plenty of room for variation in lifestyles. Uncontrolled lifestyle changes, such as someone getting fired, could mess with the results enough to matter.

Lifespan

Book review: Lifespan: Why We Age – and Why We Don’t Have To, by David A. Sinclair.

A decade ago, the belief that aging could be cured was just barely starting to get attention from mainstream science, and the main arguments for a cure came from people with somewhat marginal formal credentials.

Now we have a book by an author who’s a co-chief editor of the scientific journal Aging. He’s the cofounder of 14 biotech companies (i.e. probably more than he’s had enough time to work for full time, so I’m guessing some companies are listing him as a cofounder more for prestige than for full-time work). He’s even respected enough by some supplement companies that they use his name, even after he sends them cease and desist letters.

I’m glad that Sinclair published a book that says aging can be cured, since there’s still a shortage of eminent scientists who are willing to take that position.

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