Alzheimer's Disease
and other Dementias

Unless your doctor says that supplementation is contraindicated, Dr. Weyrich recommends that ALL patients, especially including patients with Alzheimer's or dementia, take a supplement containing the B vitamins (see below) in their methylated forms, and avoid all vitamins that have the synthetic (folate, folic acid) forms. The product that Dr. Weyrich personally uses is "Country Life Coenzymated B" (take one daily). Talk to your doctor to determine what is best for you.

It is well known that a number of different B vitamins are important for healthy brain and nerve function. Some of these will be highlighted below. There are a number of tests for adequate vitamin B status, but insurance coverage may be a problem for some of the better, but more expensive tests. It is generally more cost-effective to simply take an appropriate vitamin B supplement than it is to test for deficiency. B vitamins are water soluble, and generally excess intake is simply excreted in the urine, leading to low risk of overdose toxicity. The most notable side effects of excess B-vitamin supplementation is that the patient's urine turns bright yellow. This is harmless. In addition, vitamin B3 may cause flushing ("hot flashes"), which can be mitigated by careful adjustment of dosage and other strategies.

Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease [Evatt2008].

This is one of the interventions used by [Bredesen2014]. This vitamin is particularly important for nervous system health, and has been shown to protect against Alzheimer's Disease [Hooshmand2010] and cognitive decline [Tangney2009]. Unfortunately the patient's ability to absorb this vitamin tends to decline with age. This situation is further exacerbated by patients taking prescription or over-the-counter antacid preparations such as H2-blockers and Proton Pump Inhibitors. Since vitamin B12 is only found in animal products, vegans are particularly at risk for vitamin B12 deficiencies [Pacholok2011].

Note that excessive supplementation with folic acid (Vitamin B9) can create a relative deficiency of vitamin B12, and thereby accelerate cognitive decline [Tangney2009].

In some cases, proper consideration of diet and food sensitivities can eliminate the need to take B12 depleting drugs.

In order to assure adequate B12 status, sublingual administration of the methyl form of B12 is recommended. In some cases, vitamin B12 injections may be indicated. A commonly used vitamin therapy used by naturopathic medical doctors is called the "Myer's Cocktail"; some allopathic doctors also prescribe what they call a "banana bag" IV injection, which is similar but lower in dose.

This vitamin is also important for nervous system health, and works hand-in-hand with vitamin B12. Unfortunately, many commercial vitamins, supplements, and "enriched" food products are made with a synthetic form of the vitamin called "folic acid" or "folate". In many individuals, the body is able to convert this inactive synthetic folic acid into the active form "5-methyltetrahydrofolate" (5-MTHF). However, a substantial number of people have a genetic deficiency that does not allow their body to convert the synthetic folic acid into 5-MTHF. For these people, taking folate may be harmful (block necessary enzymes), so taking the more natural 5-MTHF is necessary. Again, it is possible to test for Vitamin 9 deficiency or the genetic defect, but it is generally more cost-effective to simply take an appropriate 5-MTHF supplement than it is to test for deficiency or genetic polymorphism.

This vitamin is also important for nervous system health. Again, the vitamin is available in both synthetic and methylated forms that are sometimes more effective.

This vitamin is required for synthesis of the neurotransmitter Acetyl Choline. Deficiency of this neurotransmitter has been associated with Alzheimer's Disease. It is also necessary for the synthesis of the energy metabolism intermediate acetyl-CoA.

These two vitamins (B2 and B3) are also known as riboflavin and niacin. Both are important cofactors for energy metabolism. Since the brain has high metabolic rate, these two vitamins are essential to support proper brain function.

This is one of the interventions used by [Bredesen2014]. Serum Vitamin D (also known as calcifediol, 25OHD or 25(OH)D) concentrations have been shown to be 1.4 standard deviation units lower in Alzheimer's Disease cases compared to cognitively healthy controls [Annweiler2013]. If renal disease prevents conversion of 25OHD into the bioactive form calcitriol (1,25(OH)D), preformed Calcitriol must be supplemented.

A number of researchers have noted that low dose naltrexone (LDN) has a beneficial effect on reducing neuroinflammation. Preliminary studies are mixed; some show some benefit from higher doses of naltrexone over a prolonged period (over a month) [Knopman1986].

[LDN] reports that all patients with autoimmune processes who were treated by the late Dr. Bihari [Bihari2003] using LDN "have experienced a halt in progression of their illness. In many patients there was a marked remission in signs and symptoms of the disease." Dr. Bihari suggests a 50% to 70% overall response rate [Bihari2003].

According to [LDN], "given the repeated demonstration of LDN's efficacy in halting progression in all cases of MS, and the possibility of its having a therapeutic effect in [Parkinson's disease], it now may be timely to consider LDN in treating the full spectrum of neurodegenerative diseases whose etiology is unknown - all of which may well have a significant underpinning of immunodeficiency/autoimmunity causing the neurological syndromes. Alzheimer's disease ... [is a ] prominent [possibility] that spring[s] to mind."

In fact, [Dudley_conditions] does report that Alzheimer's disease is responsive to LDN.

Dr. Weyrich is following this research carefully and recommends a therapeutic trial of the compounded prescription form of Low Dose Naltrexone for Alzheimer's and other dementia patients.

Dr. Weyrich has been trained in the use of Low Dose Naltrexone (LDN). However, Dr. Weyrich has not treated any cases of Alzheimer's Disease or other Dementias with LDN.

Please see What is Low Dose Naltrexone? for more information.

HPN has been reported to be useful for treating the symptoms of Alzheimer's disease [Snook], [Willis]. Dr. Weyrich has been trained in the use of Neuro-Gen High Performance Neuromodulation system by it's inventor, Corey Snook. However, Dr. Weyrich has not treated any cases of Alzheimer's disease with this technique.

Please see What is Neuro-Gen High Performance Neuromodulation? for more information.

Neurofeedback may be useful for treating or preventing Alzheimer's disease. Some researchers, however have reported that neurofeedback as a mono-therapy does not appear to be effective in treating Alzheimer's Disease. (But one of the main points of this article is that combinations of monotherapies may be synergistic, and therefore more effective than any single therapy). Dr. Weyrich has been certified in neurofeedback since 2008, and more recently completed an additional residency training program at ADD Clinic of Scottsdale, AZ. While at the ADD clinic, he treated several cases of age-related mental decline.

Please see What is Neurofeedback? for more information.

This is one of the interventions used by [Bredesen2014]. Stress increases inflammation and reduces the repair mechanisms of the body. Stress reduction can reduce corticotropin-releasing factor (CRF) production in the hypothalamus, adrenocorticotropic hormone (ACTH) production in the pituitary, and excessive cortisol production by the adrenal glands. There are many methods of stress reduction, ranging from prayer, meditation, yoga, breathing exercises to biofeedback. Dr. Weyrich is trained in the application of "Heart Rate Variability" biofeedback training for stress reduction.

This is one of the interventions used by [Bredesen2014]. Considerable evidence suggests that controlling the inflammatory marker "homocysteine" (which is easily measured by an inexpensive blood test, and can be controlled with targeted nutritional supplements) is important not only for reducing risk of Alzheimer's Disease [Hooshmand2010], but also for cardiovascular health. In fact, elevated homocysteine levels are considered as important a predictor of future cardiovascular events as elevated cholesterol. Unlike cholesterol, there are no patented drugs that lower homocysteine, but over the counter supplements that are "Generally Regarded as Safe" (GRAS) by the FDA are effective without the toxic side effects of statin drugs.

Note that the common diuretic hydrochlorothiazide (HCTZ) increases homocysteine levels [Westphal2003].

Dr. Weyrich highly recommends that all patients be tested for elevated homocysteine levels, which Dr. Weyrich can treat using nutritional methods.

Note that homocysteine is also elevated when there is renal failure [Allen1993].

Elevated methylmalonic acid levels, which is a marker for vitamin B12 deficiency, have been correlated with faster rates of cognitive decline [Tangney2009]. The serum level of methylmalonic acid should be monitored and vitamin B12 supplementation considered if methylmalonic acid is elevated.

Note that methylmalonic acid is elevated when there is renal failure [Allen1993].

Since both methylmalonic acid [Allen1993] and homocysteine [Hooshmand2010] are elevated when there is renal failure, and elevated levels of each are associated with cognitive decline [Tangney2009], renal disease should be addressed. While conventional medicine has little to offer other than dialysis, there are certain herbs that have been reported which benefit kidney function, and should be considered.

There is some evidence linking statin drug use with transient memory loss (see the book "Lipitor: Thief of Memory" by NASA flight surgeon and former astronaut Duane Graveline [Graveline2006]). In fact, cholesterol is necessary for proper brain function, as well as making a number of hormones. Statins also suppress the body's production of the cofactor CoQ-10, which is necessary for mitochondrial energy production.

A cause-effect relationship between cholesterol and cardiovascular disease has not been proven (association does not prove causation). Nor has the possibility been ruled out that the cholesterol plaques are a marker of another disease process (such as inflammation) rather than a cause of disease per-se, or even a protective response to another disease process (such as inflammation). The Naturopathic Medical principle "Find and treat the cause" (e.g. inflammation) is applicable here.

Since homocysteine and cholesterol are both independent risk factors for cardiovascular disease, it may make more sense to target reducing homocysteine using vitamin therapy instead of reducing cholesterol levels with statin drugs.

While you should never discontinue medications without discussing the matter with your prescribing doctor, there are some important questions to ask:

1. Given my current age and life expectancy, is there any actual evidence that continuing statin drug therapy will allow me to live longer (reduce all-cause mortality)?
2. Given my current age and life expectancy, is there any actual evidence that continuing statin drug therapy will slow the progression of my dementia?

It is highly unlikely that the prescriber will be able to cite an actual clinical trial that answers either of these questions in the affirmative. However, there is "expert opinion" that will say yes; but keep in mind that in the past "expert opinion" has recommended replacing butter with trans-fat containing margarine. This is now known to be very bad advice.

Note that the above advice is different than the current standard of care endorsed by conventional medicine - you must decide whom to trust.

This is one of the interventions used by [Bredesen2014]. Treat hypothyroidism if present. Test free T3 and free T4 (and maybe reverse T3), and not just TSH. There are anecdotal reports that geriatric patients treated for hypothyroidism had much lower incidence of Alzheimer's than age-matched peers [Starr2005, pg 57].

In addition to optimizing thyroid function (see above), vitamins B2 (riboflavin), B3 (niacin), and B5 (pantothenic acid) are components of the cofactors FAD, NAD, and CoA that are essential for mitochondrial energy production. CoQ-10, PQQ, D-ribose, and carnitine are also necessary for mitochondrial energy production.

This is one of the interventions used by [Bredesen2014]. Balance Cortisol, Estradiol, Testosterone, and their precursors DHEA and pregnenolone.

Estrogen use in Medicare-eligible women was associated with about a 50% slower rate of cognitive decline (1.5 point decline/6 years for estrogen users versus 2.7 point decline/6 years for non-users) among ApoE4-negative women; ApoE4-positive women did not display any benefit from estrogen use [Yaffe2000].

Testosterone use improves verbal learning and memory in healthy postmenopausal women [Davison2011]. Small-scale clinical trials of elderly men suggest that some cognitive deficits may be reversed, at least in part, by testosterone supplementation, although these researchers found no benefit for women [Hogervorst2005].

This is one of the interventions used by [Bredesen2014]. It has been said "all disease begins in the gut." While this may seem to be hyperbole, it is well known that problems such as dysbiosis can aggravate both autoimmune diseases that may attack the nervous system, promote systemic inflammation that negatively impacts neuroplasticity, and also produce neurotoxins that can adversely affect brain function. H. pylori, Food Allergy, Stool Analysis, Intestinal Permeability, and Organic Acid Testing may be appropriate; Treatments may include probiotics, prebiotics, natural and pharmaceutical antimicrobials, and healing nutrients. Dr. Weyrich highly recommends testing before planning an intervention in the digestive system.

This is one of the interventions used by [Bredesen2014]. This is important because Alzheimer's disease is sometimes referred to as "Diabetes of the Brain." The low-glycemic diet helps reduce insulin resistance.

This is one of the interventions used by [Bredesen2014]. Medium-chain triglycerides are processed differently by the body, and tend to promote thermogenesis and provide the brain with ketone bodies to use as an alternate fuel in the case of "Diabetes of the Brain". Dr. Weyrich recommends a trial of the prescription-only medical food Axona (caprylidene) or else integrating MCT oil or coconut oil into the daily diet. The medical food Axona can be prescribed by Dr. Weyrich.

This is one of the interventions used by [Bredesen2014]. This is important because many grains are high in carbohydrates, and may contain gluten, which may aggravate auto-immune conditions that may lead to neurodegeneration [Perlmutter2013].

This is one of the interventions used by [Bredesen2014]. See also "Get an Oil Change" below.

A healthy diet contains an adequate supply of essential fatty acids, and minimizes the consumption of "bad" fats that cause inflammation. Contrary to popular belief, not all fat is bad, and in fact fat is an important building block of the brain. Saturated fats are NOT necessarily bad. However, modern agricultural practices can lead to many animal products containing "bad fats" that can cause inflammation. On the other hand, organic farming practices can produce very healthy animal fats.

You should replace the "bad fats" in your diet with "good fats" as follows:

Bad Fat	Replace with Good Fat
Margarine and trans fats	Butter
Corn-fed beef products	Grass-fed beef products and pasture-fed chicken eggs
Omega-6 rich oils (corn, safflower, sunflower, canola, etc)	Coconut, Palm, Olive oils, Omega-3 rich oils (Cod Liver)
Farm-raised fish (including Atlantic salmon)	Wild-caught cold water fish (preferably smaller fish)

Note that the above advice is different than the current standard of care endorsed by conventional medicine - you must decide whom to trust.

This is one of the interventions used by [Bredesen2014]. Insulin resistance is characterized by normal fasting blood glucose levels but elevated fasting insulin levels; or mildly elevated HbA1C levels. There are many treatments for this condition, but most involve dietary modification. [Bredesen2014] recommends Fasting Insulin < 7; HbA1c < 5.5.

This is one of the interventions used by [Bredesen2014]. By fasting at least 12 hours each day (mostly at night), insulin levels may be lowered, ketogenesis and autophagy enhanced, and perhaps Aβ may be reduced.

This is one of the interventions used by [Bredesen2014]. Curcumin has been reported to attenuate cognitive deficits, neuroinflammation, and amyloid plaque deposition in Alzheimer's Disease rat [Frautschy2001] and mouse [Yang2005] [Garcia_Alloza2007] models. The later reference also reports partial regression of neuronal damage. The properties of Curcumin have been reviewed by [Aggarwal2007].

Dr. Weyrich notes that benefits seen in animal models do not always translate to humans; and in particular pharmaceutical trials that directly target amyloid plaque formation in Alzheimer's Disease have not been successful, and may even be counter-productive. While Curcumin is reported to directly target plaque formation [Garcia_Alloza2007], it also has other immunomodulatory effects on inflammation, which may provide a benefit not found in the pharmaceutical agents targeting the plaque formation more directly.

This is one of the interventions used by [Bredesen2014]. Highly-sensitive C-Reactive Protein (hs-CRP) is a sensitive marker of inflammation. Since inflammation plays a significant role in neuroinflammation and consequent neurodegeneration, the root cause of elevated hs-CRP should be identified and treated. Treatments aimed at directly reducing hs-CRP are not likely to be useful, as they essentially "shoot the messenger" rather than addressing the problem that hs-CRP serves as a marker for. Approaches to lowering hs-CRP include (but are not limited to) Low-inflammatory and Oil-change diets (see above), curcumin, and optimize hygiene (especially dental).

This is one of the interventions used by [Bredesen2014]. Low Albumin/Globulin (A/G) Ratio is a marker of inflammation. Since inflammation plays a significant role in neuroinflammation and consequent neurodegeneration, the root cause of low A/G ratio should be identified and treated. Treatments aimed at directly increasing A/G ratio are not likely to be useful, as they essentially "shoot the messenger" rather than addressing the problem that low A/G serves as a marker for. Approaches to lowering the A/G ratio include (but are not limited to) Low-inflammatory and Oil-change diets (see above), curcumin, and optimizing hygiene (especially dental).

This is one of the interventions used by [Bredesen2014]. Good sleep (8 hours of sound sleep) is necessary for minimizing inflammation and optimizing repair of all parts of the body, including the brain. Supplements such as melatonin or tryptophan may be helpful (ask your doctor about appropriate dosing). In addition to benefiting sleep, melatonin has been reported be protective in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, Huntington's disease and Amyotrophic Lateral Sclerosis [Polimeni2014]. Many sleeping pills disrupt sleep architecture, and are therefore counter-productive.

This is one of the interventions used by [Bredesen2014]. An extension to the idea of optimizing sleep is the diagnosis and treatment of sleep apnea. Not only can sleep apnea disrupt sleep, but it can also lead to anoxia (loss of oxygen to the brain), which both can be damaging and also can inhibit repair. If you snore or stop breathing at night, ask your doctor for a referral for a sleep study.

This is one of the interventions used by [Bredesen2014]. In an 18-month study, individuals at genetic risk for Alzheimer's Disease (who are positive for the apolipoprotein epsilon 4 (ApoE4) and who engaged in (self-reported) physical activity are protected from hippocampal atrophy, while those with similar genetic risk who did not engage in physical activity experienced a 3% decline in hippocampal volume over the same period [Smith2014].

This is one of the interventions used by [Bredesen2014]. Forty hours of computerized brain training was found to yield a statistically significant improvement in generalized measures of memory and attention over a control group. The magnitude of the effect sizes suggests that the results are clinically significant [Smith2009].

Neuro Research [Hinz2015] reports that Alzheimer's disease and dementia can be benefited by balancing neurotransmitter levels in the body.

Dr. Weyrich has been trained in neurotransmitter balancing protocols, but has not treated Alzheimer's disease and dementia using this technique.

Please see What is Neurotransmitter Balancing? for more information.

While everybody does not have heavy metal toxicity, it is well known that environmental toxins such as lead and mercury can cause serious disruption of mental function. Consider for example the "Mad Hatter" syndrome, which was caused by the mercury compounds used to make felt hats. Here in Arizona, the "Dreamy Draw" area of Phoenix (near Northern and Arizona 51) was formerly a mercury mine, and was given its name because of the mental disruption observed in the miners.