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Wednesday, January 10, 2007

How to Prevent Alzheimer's Disease:
Light up a cigarette.
No, seriously. Light up a cigarette.

Alzheimer’s Disease (AD) is Hell. It’s pretty close to my own personal definition of a literal Hell.

I’ll do just about anything to avoid AD. Chances are, because my three living grandparents are all over 88 years old, I’m going to live a while, assuming I avoid stepping in front of busses. Recent evidence suggests that damage due to the APOE4 allele only kicks in after the age of 80. Before that, it’s just laziness (or due to other neurodegeneration.)

So I’ve been incorporating all those prim little lifestyle changes that are supposed to guarantee a long, healthy, happy life. I’ve cut down on coffee and chocolate. I’ve never smoked and rarely have a drink. I try to minimize the number and amount of painkillers and other drugs that I take. I’m a vegetarian and eat lots of pretty colors of food every day and take my multivitamin.

If I don’t live forever, it will certainly seem that way.

Here’s the joke: My heart may be in pretty decent shape, but that Baptist nun approach to life is a recipe for Alzheimer’s Disease.

That’s right. The best and latest research shows that the best way to avoid, slow, or delay Alzheimer’s disease and preserve your brain is to pickle it with booze, cigarettes, caffeine, ibuprofen, and the occasional fish. Oh, and eating your vegetables doesn’t help at all.

First of all, the biggest shocker: smoking reduces your chances of getting AD.
Ref1 Ref2

Seriously, it’s true. It’s not widely publicized because it’s terribly politically incorrect.

Smoking also reduces your chance of getting Parkinson’s Disease.

Actually, to maximize your chance of avoiding AD and living a long life: smoke for a while, then stop. (Easier said than done.)

Before we go any farther, I don’t think anyone is recommending that you take up smoking. That particular device, the cigarette, has thousands of other compounds that cause heart disease, cancer, halitosis, body odor, and wrinkles. Smoking also vastly increases your chances of getting a vascular form of dementia caused by many small strokes. So, it’s really not a good idea. I don’t smoke. Never have. Never will.

I have considered the nicotine patch or gum, however.

But there’s good evidence that smoking reduces your risk of AD. The studies are pretty good, and they’re not sponsored by the tobacco companies. They have controlled for other risk factors, including the “Hardy Survivor” effect, which basically means that if smoking doesn’t kill you, nothing will. Ref1 Another study controlled for weight of the subjects, which is important because smokers generally aren’t as chubby as non-smokers, and being overweight is associated with AD. Ref2.

One theory as to why smokers are less susceptible to AD involves nicotinic acid receptors. When you smoke, your brain makes more receptors for the nicotine. Ref1. However, people who have dementia with Lewy bodies (DLB) have fewer nicotinic acid receptors. Ref2 People with AD also have fewer nicotinic acid receptors in their brains. Ref3

But can nicotine or smoking reduce your chances of getting AD?

First, some basic neuroscience. One of the most supported theories for the cause of AD (and we aren’t sure what causes AD) is a protein called beta-amyloid, also called Ab, A-beta, or bAP. (Thus, the folks who espouse this theory are called bAP-tists.)

Beta-amyloid protein occurs naturally in your brain, though no one knows what it does. The normal form is soluble, which means that it dissolves in water. Forms of beta-amyloid that are less soluble and tend to form clumps (aggregate) are thought to be more pathogenic. The forms that may be associated with AD are called Ab40 and Ab42. Ab42 is thought to be worse for your brain (more pathogenic) than Ab40.

The more pathogenic forms Ab40 and Ab42 are found in higher amounts in non-smokers’ brains than in smokers, Ref1 especially in areas of the brain that are associated with age-related dementia. Ref2. In general, higher concentrations of Ab40 and Ab42 have been found to be associated with AD.

Now can smoking reduce your chances for AD? In a mouse model of AD (and mouse models are imperfect for a whole variety of reasons, but that’s another essay,) mice who produce a mutated human gene for amyloid (that is associated with getting AD in humans) make amyloid plaques in their little mousy brains. When you feed them nicotine, they make fewer gunky amyloid plaques in their little mousy brains.

How can that happen? Well, it’s been found in humans that the chemical that nicotine turns into in your body, (called Nornicotine,) bonds to amyloid and reduces it’s gunking into plaques.

Nicotine also breaks down fibrils of amyloid, which are thought to be what the plaques are made of.

Some recent studies, however, have found that smoking increases your chances of dementia. Ref1. Ref2. Yet, the molecular evidence suggests that Ab disposition is less in smokers and in nicotine-ingesting mice. Why is that?

Well, there’s a whole host of possible reasons.

(1) Alzheimer’s Disease, like all “lifestyle” diseases, is multi-causal. Slightly changing the way you pick your subjects will drastically change your results. Different model. Different study.

(2) Many of the studies found positive links between smoking and dementia, not smoking and AD. You can’t definitively diagnose AD unless you autopsy the brain. (This is contraindicated in people who are still using their brains.) Therefore, these studies may be finding vascular dementia, which is very common and associated with smoking.

(3) The last possibility is that the beta-amyloid hypothesis of Alzheimer’s Disease is wrong, or at least the Ab42-is-bad hypothesis is wrong. This means that all the studies are correct. Smoking, therefore, increases your risk of AD while decreasing your load of Ab42-associated plaques.

One hypothesis suggests that the plaques are formed to keep the Ab42 (or a precursor, like ADDLs) from floating around. The floating Ab42 kills brain cells. Therefore, tying up the Ab42 in plaques is actually a defense mechanism. Thus, smokers have fewer defensive plaques, more floating Ab42, and more AD.

1 comment:

Nickie said...

Judge Judy says, "If it doesn't make sense, it isn't true." Years of research on both animals and humans have shown a protective effect of smoking against AD and Parkinsons; and suddenly in the past 8 years or so, research starts "proving" that smoking causes AD. Hmmm... Speaking of study design and bias, Pub Med brought up a reference related to yours (Arch Neurol. 2002 Feb;59(2):223-7) which mentions that use of lipid-lowering agents is associated with a history of smoking. Might it be the smoking, and not the statin use that is prevening the AD?