Alzheimer's

Alzheimer's disease—where are we?

Be afraid!

This post was prompted by three things: a friend's experience; my own inexorably advancing age; and regular articles in the Telegraph by nutritional specialists, including this holiday weekend by a neurologist Dr Daniel Gibbs who himself suffers from early Alzheimer's disease. Along with many others, Dr Gibbs uses his professional credentials to promote various brain-friendly lifestyles—a mix of diet, exercise, and social and mental activities. A quick Google reveals hundreds of articles and opinions on this, many presented on slick websites with a scientific veneer and names like "yourhealthylife.com". There is a surfeit of opinion, and vague statistics drawn from canvassing others' opinions: the "Most people, when they discuss brain-friendly diets, agree that fish is good for you" type of thing. There is a glaring lack of references to original research, or indeed any evidence that has any more validity than some buzzwords.

Alzheimer's causes 70% of dementias. Research into Alzheimer's disease is extensive, has been going on for years, and continues to attract massive funding. So what have we found out? Have Alzheimer's researchers established anything genuinely useful? Also have they managed to disprove any of the widespread notions that are out there? I am now on a mission—partly because I would like to know whether, for example, my occasional pizza might be harming my brain (as has been suggested by some).

First, suspicious me needs to find some sources that I trust. What I find will be added to this post. Watch this space...

Dr Daniel Gibbs

• Aerobic exercise
• The MIND diet
• Mentally stimulating activity
• Social engagement
• Good sleep

As mentioned above Dr Gibbs writes in the Telegraph this weekend (promoting his book, £16.99). He cites studies that he claims demonstrate that aerobic exercise slows down the progression of Alzheimer's. What he says is not entirely convincing: exercise certainly, demonstrably and dramatically, clears your head a bit at the time and for a period afterwards. But this may be just extra blood-flow and adrenaline hitting receptors—both reversible phenomena. Exactly how does aerobic exercise slow down plaque formation—if indeed it does? He tells us the more exercise the better and suggests 8000 steps a day. Hmm, this is very light exercise indeed. Really?

There is an ongoing relevant study using cycling as the exercise. The authors point out that multiple meta-analyses of exercise effects on Alzheimer's reveal a large number of studies with inadequate sample size, inadequate levels of exercise, poor study design, and no standard choices of outcome measures. The implication is that many Alzheimer's researchers are happy to take the funding and do amateurish, poor-quality research. So, OK, do people who participate in non-head-impact sports have a lower incidence of Alzheimer's? I've looked and can't find the answer, it's all trendy "head-impact" studies.

There is some fascinating stuff—though rather old news now. Regular exercise increases hippocampal volume. Wow, and does sound relevant. But it also sounds like magic: does an exercise-inflated hippocampus actually perform better?

Dr Gibbs personally follows the MIND diet which he claims resulted in slowing disease progression. The immediately obvious question is, "so what exactly are the therapeutic components of green leafy vegetables?" These are 96% water, plus a little chlorophyl, some folate, and some indigestible fibre. I can find no answers. Perhaps it's the chewing that helps. The microbiome? Lots of opinion, I can find no published research into this.

He says that mental activity helps: using a computer, reading, social activities, and crafts. The cynic in me wonders if this just provides practice of the ability to perform whatever outcome measures the researchers are using. You can practice IQ tests and improve your IQ test scores, that doesn't make you smarter.

He tells us good sleep is important referencing his personal experiences of enhanced performance after sleep. He also quotes sleep as preventing amyloid build up, and it does, and beta-amyloid is certainly a component of the diagnostic brain plaques (the other being tau-protein). But are Alzheimer's plaques caused by chronic poor-quality sleep? He doesn't say and I now know that the research hasn't been done. Well it would be good to even know if there was a correlation.

Dr Gibbs does not suggest mechanisms of action for most of these things, his evidence being based on studies demonstrating a statistically significant slowing of symptom-progression. It would have been nice to see some evidence of effects on the underlying pathology: plaque formation in the brain. If they have looked then please share. Dr Gibbs is refreshingly honest in his summary: "I share my story not as clinical proof, but simply as medical parable, and a call to action for anyone who might be open to encouragement."

Is there really nothing approaching "clinical proof" despite the years of research and all the money spent? Dr Daniel Gibb, a medical expert in the field, doesn't tell us in his two articles. Perhaps his book contains more.

A deeper look

I really hoped to avoid digging in to the published original research. That frustrating world of publication bias (positive studies are far more likely to be published than the balancing negative studies), and flawed research that has slipped past sleepy reviewers. A cynical eye is required.

The Alzheimer's Association Research Page seemed like a good place to begin. The Association was founded in 1980 in the US, and is now part of a large international network. The Bill Gates Foundation is funding relevant research. Famous sufferers like Ronald Reagan raised the disease profile. And the amount of money that has been and continues to be pumped into researching this common and fatal disease is utterly staggering. Rightly so.

Tacrine

The early 1990s saw the first Alzheimer's drug (Tacrine from Pfizer) getting FDA approval in the US. The first major trial (a phase III study) of a number of similar therapeutic drugs began in 2012. This study will take 10 years so is scheduled to be completed in 2022. Next year we should know. Anecdotal results are very promising.

β-amyloid as a vaccine

Used as a vaccine the protein β-amyloid prevents Alzheimer's changes in a mouse model of the disease. There is a human trial under way—IIGs (Intravenous Immune Globulin study). This is actually a very big deal.

Brain-friendly behaviour

The Alzheimer's Association offers a page of general advice backed by what they describe as "growing evidence". 10 ways to love your brain. This is the Dr Gibbs' stuff again, to summarize. Put your heart rate up; challenge your brain (engage in education, eg night classes, and puzzles); basic healthy living (smoking, obesity, head injury avoidance etc); spend time with friends; get plenty of sleep; and eat a low-fat diet (they note that what evidence there is is particularly weak for diet).

I noticed that they say nothing about antioxidants, the role of inflammation (and anti-inflammatory drugs), omega-3 fatty acids, alcohol, and other widespread internet therapeutic advice. You can safely ignore these factors, if they were worthwhile they would already be on their pages.

Many of us are instinctively following these recommendations already. I guess we just do a bit more of the same and cross our fingers. So that's where we are—I'm good for pizza. Bring on that vaccine!