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.
Bredesen provides some guidance about which advice is most valuable – primarily the changes needed to reduce insulin resistance. That still leaves lots of ideas for which it’s hard to guess which ones I ought to worry about.
The strength of the evidence is somewhat like the evidence against smoking that was available in 1960, or the evidence in favor of masks in March 2020.
The mainstream medical establishment seems more resistant to imperfect evidence than it was in 1960.
This book pays little attention to convincing skeptics or to motivating readers to care about the health benefits that it offers. Most people should read The End of Alzheimer’s before deciding whether they care enough to wade through this book.
Exercise is one area where his advice is backed by better evidence than I expected. A meta-analysis of 19 studies of people at risk for Alzheimer’s concluded:
Overall, there was a modest favorable effect of exercise on cognitive function (d+ = 0.47, 95% confidence interval (CI) = 0.26–0.68)
Some examples of new ideas in the book that I found interesting:
- we should brew green tea at no more than 170 degrees to maintain its healthy qualities
- canned tomatoes are especially risky due to the effects of their acidity on BPA
- it’s probably healthier to sleep on one’s side. The evidence cited is a rather tenuous, but plausible inference from rats
He’s added more types to his attempts to decompose Alzheimer’s into useful diagnostic categories. That looks like progress, as I can now identify one (vascular) as closely matching my guess about what I’d be at risk for if I were careless about my lifestyle.
Benzodiazepine use is clearly correlated with cognitive decline. It seems unlikely that we’ll get anything resembling an RCT on this, but careful controls lend some support to the concern that benzodiazepine is causing the decline.
Changes in his Protocol
His homocysteine advice seems more plausible now. He’s removed the suspicious advice to try methionine restriction as a last resort. But he sticks with his target of 7 or lower. I have increasing reason to doubt that that target is feasible for me, and likely for many other people. I guess that other, apparently unrelated, parts of his protocol (SIBO treatment?) may end up enabling me to hit that target. Or maybe his advice to try higher doses of TMG and choline will help. But I suspect I’ll end up settling for a target of 8.
He changed his recommended pregnenolone blood levels from a maximum of 100, to a minimum of 100. I’d like to know why.
Bredesen highly recommends Matthew Walker’s “Why We Sleep”. A critic says the book is riddled with scientific and factual errors. OTOH, Bill Gates says This book put me to sleep. I can easily imagine that Walker’s advice helps most of the people who read it, even if his justifications for the advice are crappy. I’m inclined to guess that Bredesen was right to recommend it, but wrong to not qualify that recommendation.
Bredesen encourages prayer: “some research has also demonstrated that prayer can even positively affect outcomes.”, citing a paper which speculates that prayer could produce meditation-like benefits. The paper has good links to support the benefits of meditation, but the link to prayer seems to be just a guess. The paper is mainly about both positive and negative outcomes for people who were prayed for, leaving me confused as to what Bredesen wants us to get out of the paper.
He’s more cautious about fruit than I think is healthy. He lists 22 fruits that he recommends, and discourages us from eating others. Maybe that caution is appropriate for people who are recovering from insulin resistance, but I’m pretty sure it’s healthy for the rest of us to eat almost any type of whole fruit. Bredesen seems to place too much weight on the Glycemic Index, when a more appropriate measure of risk would say it’s safe to eat sugar if accompanied by decent amounts of fiber and other nutrients.
I’m pretty sure these fruits should be considered healthy: baobab, pumpkin, figs, and pretty much any berry. I like berries that he likely hasn’t heard of: saskatoonberries, salmonberries, and cloudberries. However, it’s hard to get those without added sugar.
He has apparently made slow progress at expanding the network of doctors who understand his protocol – see Josh Mitteldorf’s experience. I don’t plan to use that network, as I’m getting health support via a somewhat similar functional medicine group.a
It will require plenty of time and attention to get value out of this book. The risk / reward ratio looks good for pretty much all of Bredesen’s ideas. I expect that most people over about 55 or 60 will be able to get some benefits from trying out his advice, even though some unpredictable fraction will end up being wastes of time. A small fraction of readers will likely get big benefits.
P.S. Ignore the foreword (written by Perlmutter). Medicine is not polarized between reductionism and holism. The dichotomy I see plaguing Alzheimer’s research is closer to the tension between High Modernism and something more Bayesian. Perlmutter is misusing the term reductionism. Bredesen is trying to follow Einstein’s advice that “Everything should be made as simple as possible, but no simpler.”, and is being resisted because the degree of simplicity that he’s been able to achieve so far doesn’t match the demands of standard medical practice. Scientism might be a better word to describe what Perlmutter is trying to oppose.