Lost Wanderer

In a previous blog I discussed the Cycad Hypothesis of Alzheimer’s, which postulates that excitotoxicity caused by BMAA toxin from cyanobacteria might be the root cause of the disease.  However, there are many other possibilities.

If I had an identical twin who had developed Alzheimer’s, I would consider everything I could think of to prevent it.   The short list would probably include:  I would eat a Paleolithic Diet, intermittently fast, practice good dental hygiene, exercise, take vitamin D supplements, folic acid, omega-3 fats, curcumin, Longevinex, green tea, and resveratrol.  I also would avoid STDs, concussion-risky sports, toxins, radon, electromagnetic fields, heavy cell phone use, and heavy metals. 

Come to think of it, this just sounds a lot like extremely healthy living.  Below are the details:

The disease has an obvious genetic component, since having a family history of Alzheimer’s increases your risk, as does having an identical twin with it (concordance is 59%).

A relatively new theory is that it is a third form of diabetes.  (Alzheimer’s could be diabetes-like illness, study suggests)  It turns out that the brain produces its own insulin.  In Alzheimer’s the brain’s insulin production, as well as its ability to respond to insulin, drops off as the disease becomes more severe.  Brain cells also lose the ability to respond to insulin growth factors, and when rats were treated with related insulin-like growth factors to correct for this lack of response the typical loss of learning and memory was prevented.  Regular diabetes itself is also a risk factor for the disease.

A moderate or severe concussion will roughly double your later risk of Alzheimer’s.  (Study bolsters head injury, Alzheimer’s link)  This is also true of mild repetitive head injuries.  (Fortunately isolated mild concussions don’t seem to increase your risk.) 

Besides avoiding head trauma, having a generally healthy cardiovascular system and avoiding atherosclerosis helps avoid the disease.  Having moderately high cholesterol and a diet higher in saturated fats are risk factors.  Atrial fibrillation makes it 44% more likely you will get it.  Cardiovascular disease increases your risk by 30%.  And if you’ve had a stroke your chances go up by nearly 50%.  Being obese, metabolic syndrome, and smoking during midlife all put you at greater risk.

Researchers suspect that early nutrition, as indicated by various body measurements, might play a role.  Women with short arms have a 50% greater risk, while a longer shin length is protective. 

Various viruses and microbes can worsen your chances.  Viruses in the herpes family (simplex I, Cytomegalovirus V, and simplex VI) are strongly suspected of being causal factors.  One theory holds that the microbe Chlamydia pneumonia might be the main agent responsible.  Lyme disease and Helicobacter pylori bacteria also are both associated with Alzheimer’s.  

A vasectomy might put men at risk for one rare form of dementia, Primary Progressive Aphasia.  

Vitamin D keeps proving its worth, since low levels of vitamin D have been linked to cognitive decline.  (See also Prevalence of vitamin d insufficiency in patients with Parkinson disease and Alzheimer disease)  

The inhaled anesthetics halothane and isoflurane are linked with amyloid beta buildup.  Childhood lead exposure could increase the risk.  Processed food that contains nitrates might be linked to Alzheimer’s, diabetes, and Parkinson’s.  Other possibilities include mercury, aluminum, and zinc exposure, non-wine alcohol consumption, and work related organic solvent exposure.

Although the lines of causation are far from clear, Alzheimer’s correlates with other mental problems.  Being lonely (an active social life is protective), having a history of depression, and having a major psychiatric illness all increase your chances of getting it. 

Additional correlating factors include:  having poor dental health, being exposed to air pollution,  a history of manual work, a family history of Parkinson’s, maternal age at birth, number of pregnancies, (possibly) exposure to low magnetic fields (Qiu et al, 2004) (Occupations with Exposure to Electromagnetic Fields: A Possible Risk Factor for Alzheimer’s Disease, Do Cell Phones Cause Alzheimer’s? By Maggie Spilner), and age.  There have also been concerns about radon’s radioactive daughter products being found in the brains of Alzheimer’s patients at ten times the normal rate. (Alzheimer’s & Parkinson’s – Could the Cause be Radon?)  

In addition to the above list, here are some more controllable factors that people have suggested:  

Exercise has been shown to slow memory loss.

Dietary restriction and intermittent fasting seem to protect against a large variety of diseases, including Alzheimer’s.  (See also Extreme Diet Nixes Alzheimer’s)  A low carbohydrate and high fat diet has been shown to improve Alzheimer’s disease in mice.  In one study drinking fruit and vegetable juices cut risk by 76%.  The Mediterranean diet also seems to be protective.  Although I haven’t seen any studies on it, given all the lines of evidence I’m pointing out in this blog entry, I feel very confident in predicting that The Paleolithic Diet would be protective.

Having proper levels of folic acid reduces your risk by 55%, probably at least in part because of its effect on homocysteine levels.  Curcumin, which is found in the spice turmeric, appears to block amyloid plaques.  Many results suggest that the omega-3 fatty acid DHA is beneficial.  Silica in drinking water might help prevent the disease.  (See also Nature’s Way Silica Gel)  Huge doses of vitamin B3 have been found to stop the progression of Alzheimer’s in mice.  Marijuana has anti-inflammatory effects, and it might limit the memory loss part of it.  There is some speculation that Vitamin K2 could be beneficial.  Vitamin C and E consumption, coffee drinking, resveratrol, huperzine A, and wine consumption all might be somewhat protective.  (Since I am a teetotaler I’d consider using a product like Longevinex, which they claim has red wine’s benefits in a pill, without the alcohol or calories.)

Although it seems a bit extreme to suggest this as a preventive measure, Alzheimer’s does have an inverse association with cancer.  If this is true with those few cancers which are fully curable, and it were possible to somehow induce such a cancer, this suggests an unorthodox treatment option.

Looking in the doctor’s medicine cabinet, non-steroidal anti-inflammatory drugs, statins, antihypertensives (calcium antagonists), and vaccines for diphtheria, tetanus, polio, and the flue all might be protective.

Academic ability is a protective factor which probably indicates that you aren’t as susceptible to the disease.  A Canadian study showed that bilingualism delayed the onset of Alzheimer’s by up to four years.  A lack of schooling and farm upbringing seems to boost your risk.  (Of course, the farm environment suggests the possibility of chemical exposure as an additional risk factor.) 

Researchers are making progress on possible ways to diagnose the disease at earlier stages:

It turns out that the disease manifests tell-tell signs years before it becomes apparent, and that lower levels of abstract reasoning and recall for verbal materials at a young age are good predictors for Alzheimer’s many years later.  One study, the “Nun Study,” has shown that certain aspects of language usage in young adults are 85%-90% accurate in predicting the disease 50 years later.  The rational for focusing on this population of women was that they lived very similar lives; so many possible confounding variables were eliminated.  Researchers found that linguistic features of the essays these women wrote when they were entering the convent, when analyzed properly, were strongly predictive.  They found that grammatical complexity tells how well a person’s memory is functioning, and “Idea density,” which is the number of discrete ideas per 10 written words, predicts educational level, vocabulary, and general knowledge.  It turns out that idea density at a young age is very predictive of Alzheimer’s in old age.   

Researchers have found that normally people do better on a memory test if the words to be remembered are semantically related.  But people who later develop Alzheimer’s don’t do any better at such tasks, suggesting that they no longer have access to deeper semantic meanings.  The same scientists have also found that implicit memory tests are good for diagnosing Alzheimer’s in its early stages.  In one test, participants were required to read words from a computer screen as quickly as possible.  For healthy people if a word is repeated they will be primed and perform better.  This effect doesn’t tend to happen with people who will later develop Alzheimer’s, indicating they aren’t learning implicitly (learning without the awareness of learning, or being primed) when they perform a task.   

Researchers have developed a technique that allows them to image beta amyloid plaques in living mice.  They did this by using a non-toxic compound that binds to the plaques, which is then visible when scanned by using MRI.  It might turn out not be necessary to go to such lengths, because researchers have discovered that beta amyloid proteins also build up in the eye lenses of patients.  It therefor seems likely that a simple eye test will someday be available for the disease.  Some researchers speculate that it might be possible to develop a saliva test which would be able to detect Alzheimer’s.

As for what medicine might eventually have to offer:

British scientists claim that an experimental drug called Rember, which attacks the tangles that form during the disease, can reduce Alzheimer’s progression by about 80%.   In a small study, the anti-inflammatory arthritis drug Etanercept demonstrated remarkable benefits in patients.  Researchers are now testing a patch which delivers a vaccine that causes the immune system to break down beta Amyloid proteins.  If used early in the disease, the epilepsy drug Valproic Acid (VPA) has been shown to reverse memory loss, by inhibiting the production of these proteins.  A drug tested in the UK and Singapore, Methylthioninium chloride (MTC), blocks the accumulation of tau tangles inside brain cells, and slows the progress of the disease by 81%.  Dimebon, a Russian antihistamine, which seems to improve the functioning of mitochondria, stabilized Alzheimer’s in an 18 month study.  In Australia they have developed a drug PBT2 that attacks plaques.  Exelon, a cholinesterase inhibitor, seems to delay development of the disorder.  Researchers have found that they can increase the expression in the brain of the protein transthyretin, which seems to halt the progression of the disease.

Getting further into what sounds like science fiction, there is an experimental helmet which bathes the brain with infra-red light, which it is claimed stimulates the growth of brain cells and could reverse Alzheimer’s symptoms.  Finally, researchers have been experimenting with trepanation, drilling a hole in your head, on the theory that this increases cranial compliance.  This is the elasticity of the brain’s vascular system, and the theory is that increasing this will in turn increase blood flow to the brain. 

Here is an on-line article by William R. Ware that discusses many of the suspected causes that might be involved, in addition to the ones I have listed, they include: emotional stress, oxidative stress, vitamin deficiency, vitamin b12 deficiency, hypotension, hypertension, alcohol abuse, pesticides, and herbicides, low antioxidant levels, and a tendency for thrombosis.  (See also memory and cholesterol, low levels of cholesterol)  He also reviews the relative risk reduction of a number of drugs currently used to treat Alzheimer’s.  What the more successful drugs seem to have in common is antiangiogenic activity, or the inhibition of new vascularization.  Natural compounds which might have antiangiogenic activity include Omega-6 fatty acids, green tea, licorice, quercetin, squalamine, and shark cartilage.

Here are two positively reviewed books:  The Alzheimer’s Answer: Reduce Your Risk and Keep Your Brain Healthy by Marwan Sabbagh, which, at 330 pages, covers a lot of material; and Beyond Alzheimer’s: How to Avoid the Modern Epidemic of Dementia (Hardcover) by Scott D. Mendelson (See also: Beyond alzheimer’s – summary)

Finally, The Myth of Alzheimer’s: What You Aren’t Being Told About Today’s Most Dreaded Diagnosis by Peter J. Whitehouse provides a contrarian view of the disease.