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Alzheimer S Disease Dementia

 

Alzheimer's Disease Introduction

Alzheimer’s disease is characterized by progressive cognitive decline and memory loss. Individuals who suffer from Alzheimer’s Disease will have difficulties with activities of daily living and need full time assistance in the later stages of the disease.[1] It accounts for 50-60% of all dementia cases in the elderly.[2] Alzheimer’s is a unique condition that is not the result of common aging and natural senility.

The brain tissue in Alzheimer’s patients has a specific pattern of degeneration marked by senile plaques and neurofibullary tangles. There is also a loss of neurons in the cerebral cortex, hippocampus, and subcortical structures, such as the locus caeruleus and nucleus raphe dorsalis.

An increase in beta-amyloid proteins is thought to contribute to the disease as well. This increase is pararlleled with a marked decrease in brain neurotransmitters, with acetylcholine being affected the greatest.[3]

The distinct cause of Alzheimer’s Disease is not completely known. There is a familiar pattern in 15-20% of the cases. For the other 80-85% of cases there are several causal relationships. A genetic etiology is suspected in some individuals, due to findings of an increase in certain proteins in the brain that are coded for specific chromosomes (1, 14, 19, and21).[4] The most significant findings are with the protein apolipoprotein E. Certain forms of the protein (e4-type) are linked with greater incidence, while one form (e2-type) is associated with a more protective effect.[5] Environmental factors are also suspected to play a role in the development of Alzheimer’s disease with specific attention to heavy metal toxicity, oxidative damage, and abnormal hormone metabolism.[6]

Alzheimer’s disease has been called the “disease of the 20th century,” with four million Americans currently affected. The disease affects women twice as much as men, and it is not yet known if female sex is a risk factor. The disease usually strikes individuals over the age of 60, yet 2-7% of cases is early onset and is related to a genetic mutation (Downs Syndrome). The incidence of developing the disease also increases with age.[7]

Alzheimer's Signs & Symptoms

Because the disease progression is gradual there are 4 distinct clinical stages to the disease. Because of the differences in physiology of each individual, a patient may not fit entirely into one single stage.

  • Early stages of Alzheimer’s disease- Characterized by a loss of recent memory, inability to learn and retain new information. Patient may have language problems, mood swings, and personality changes. Difficulties with the activities of daily living develop, judgment is affected, and family members may begin to report strange behaviors.
  • Intermediate stages of Alzheimer’s- At this stage patients are unable to learn and recall new information. They may require assistance with their activities of daily living. Their behavior becomes disorganized; they may begin to wander around, become uncooperative, hostile, and be physically aggressive. They loose sense of time and place.
  • Severe stage of Alzheimer’s- They are completely unable to perform activities of daily living, they may or may not be completely incompetent, and there is complete loss of recent and remote memory. Patients may have loss of some motor skills, be unable to eat or swallow, and are usually placed in a long-term care facility.
  • Final stages of Alzheimer’s- More complete motor and neurological deficits, seizures, coma and death.[8]

Conventional Alzheimer's Treatment

Conventional treatment of Alzheimer’s primarily focus’s on the symptoms of the disease. Drugs such as donepezil are used to enhance cholinergic activity (having physiological effects similar to those of acetylcholine) in the brain. Anti-psychotics and anti-depressants are commonly used for behavioral changes. Anti-histamines and benzodiazepines are also readily used. Prescription drugs are an increasing concern for the individual with Alzheimer’s because of the possible side effects.[9] Because of the side effects caused by conventional treatment, an increasing amount of research is focused on alternative medicine for Alzheimer’s Treatment.

Supplements for Alzheimer's treatment

Ginkgo Biloba

Ginkgo biloba is botanical medicine used for Alzheimer’s Treatment. It is a potent anti-oxidant, increases circulation to the brain, improves mental stamina, and cognitive function. A standardized extract of ginkgo biloba is effective at delaying and reversing mental deterioration in Alzheimer’s.[10]

Studies using a particular standardized extract of Ginkgo Biloba (EGb76) has exhibited neuroprotective properties, is anti-hypoxic (improves oxygen delivery), and is anti-apoptotic (prevents cell death). It is most effective for mild to moderate dementia associated with Alzheimer’s.[11] Another study using the same extract showed definitive results, suggesting Ginkgo is effective at quenching free radicals in the brains affected by Alzheimer’s.[12, 13]

Huperzia serrata

Club moss has been used in China for centuries to treat infection. Huperzine, an isolated alkaloid of club moss is a strong inhibitor of acetylcholinesterase, the enzyme that breaks down acetylcholine in the brain. It enhances memory and is neuroprotective. One of the greatest advantages of huperzine compared to conventional acetylcholinesterase inhibitors is that it has no known side effects or toxicity, even with long term usage. In one study it was shown to increase cognitive function and quality of life in Alzheimer’s patients[14] Another studied produced equally beneficial effects on specific behavioral mechanisms.[15]

Antioxidants to Treat Alzheimer’s

Because oxidative damage contributes to the progression of Alzheimer’s disease dietary supplementation is key. Supplementation is most effective when started in the earlier stages of the disease, though it can also be used as a preventive measure throughout life. The most well known anti-oxidants are Vitamin A, C, and E, although certain trace minerals, like selenium, zinc and botanical constituents such as flavonoids, also possess anti-oxidant ability. Anti-oxidants can be taken alone or in synergistic combinations.

Vitamin E

Vitamin E is a key anti-oxidant and is necessary to replenish glutathione in the body. It is also effective at preventing lipid peroxidation, due to its fat solubility. In Alzheimer’s disease patients have an increase in lipid peroxidation, most notably in the cell membrane, which can ultimately lead to cell death. Persons suffering from this condition also have a decrease in glutathione activity as a quencher of free radicals. In one study of patients with Alzheimer’s disease, blood markers of oxidative stress were measured and found to be extremely high. Supplementation with Vitamin E was shown to decrease oxidative stress and improve cognitive function.[16, 17]

Vitamin B12

Vitamin B12 is key factor in many biochemical reactions in the body. It serves as a methyl donor (carbon and hydrogen) in the building of ATP (energy) and our DNA. If Vitamin B12 is deficient, homocysteine builds up in the tissue and blood. Therefore, it can be used as a marker for Vitamin B12 status. Most (3-42%)[18] elderly individuals have a deficiency of Vitamin B12. Signs of deficiency include numbness or burning in arms and legs, balance difficulty, impaired mental function, and fatigue.

Homocysteine causes damage to the lining of blood vessels. It also induces oxidative injury on neurons in the brain. Homocysteine is elevated in patients with Alzheimer’s disease. The elevation is thought to be caused by oxidative damage to the chemical structure of Vitamin B12, rendering it metabolically inactive. In one particular study the researches speculated that a specific form of Vitamin B12, glutathionylcobalamin, may be most effective decreasing the homocysteine levels.[19] Though the more common forms, cyanocobalamin and methylcobalamin can also be used to decrease homocysteine.[20]

Vitamin B1 (Thiamin)

Thiamin is an important vitamin for the brain because it potentiates and mimics the main neurotransmitter for memory; acetylcholine. In Alzheimer’s disease, acetylcholine activity is diminished due to low levels of this nutrient. Thiamin has been shown to improve mental functioning and intellectual prowess in individuals with mild disease with no side-effects.[21, 22]

Vitamin B3 (Niacin)

A deficiency in niacin causes dementia in otherwise healthy individuals. Supplementation will reverse this dementia without long term damage. In a recent study, the hypothesis that niacin can be protective against the development of Alzheimer’s disease was tested by comparing the dietary intake of niacin of an elderly population and comparing outcome. It was concluded that dietary niacin was protective against the development of Alzheimer’s disease.[23] One could then postulate that supplementing with niacin can give further protection against the disease and further studies may show benefit for treatment.

Choline

Choline is another biochemical component of acetylcholine. Increased levels can promote acetylcholine synthesis and increase the transmission between neurons in the brain. Choline can be taken into the body in several forms; the most recognized are phosphatidylcholine, lecithin, and citicoline. Each of these nutrients donates a choline to an acetyl group to form acetylcholine; a reaction that is mediated by the enzyme, acetylcholine transferase. Levels of acetylcholine transferase are decreased in patients with Alzheimer’s disease.

It is speculated that taking choline may increase availability of acetylcholine. A therapeutic trial is recommended for individual patients to assess efficacy.[24] Citicoline also donates a choline group. It has been shown to assist in the repair and structural integrity of cellular membranes. In a study of patients with early stage Alzheimer’s, citicoline improved cognitive function and increased blood flow over a study period of 12 weeks.[25]

Phosphatidylserine

Phosphatidylserine is the major phospholipid in the brain. It is integral for maintaining structure and fluidity of the cell membrane of neurons. It decreases the effects of aging on neurons. In one study it was shown to restore memory and improve cognitive function in individuals with Alzheimer’s disease.[26, 27]

L-Acetylcarnitine

L-acetylcarnitine is involved in energy production inside brain cells. It assists in the removal of toxic fatty acids from the brain. It is a powerful anti-oxidant which effects the inside of neurons. L-Acetylcarnitine delays the progression of Alzheimer’s disease[28] and reverses the age related decline in the number of acetylcholine receptors on the membrane of neurons.[29] In one study supplementation with phosphatidylserine over a three month period reduced attention deficits in Alzheimer’s disease patients in 50% of cases when combined with an acetylcholinesterase inhibitor. This statistic was compared to only a 38% efficacy with the acetylcholinesterase inhibitor alone.[30]

Essential Fatty Acids

There is growing evidence that abnormal lipid metabolism may play a role in the development of Alzheimer’s disease. Dietary lipids are thought to be a principal risk factor for the development of Alzheimer’s disease. Diets that are high in saturated fats (often found in fatty animal proteins) and those that have higher omega 6 EFA’s (evening primrose oil, borage oil, blackcurrant oil) than omega 3 EFA’s (fish oils, flax seed oil), increase risk factors. Conversely diets high in omega 3 EFA’s and unsaturated fats are protective. This study suggests that simple dietary changes may be effective at preventing and slowing the development of Alzheimer’s disease and other cognitive disorders.[31]

References

[1] Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[2] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[3]Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[4] Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[5] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[6] Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[7] Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[8] Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[9] Beers M and Berkow R. 2004. Merck Manual 17th Ed. Chapter 171

[10] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[11] Ahlemeyer B and Krieglstein J. Pharmacological studies supporting the therapeutic use of Ginkgo Biloba extract for Alzheimer’s disease. Pharmacopsychiatry 2003 Jun; 36(S1):s8-14.

[12] Smith JV and Luo Y. Elevation of oxidative free radicals in Alzheimer’s disease models can be attenuated by Ginkgo biloba extract EGb761. J Alzheimers Dis. 2003 Aug; 5(4): 287-300.

[13] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[14] Zangara A. The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer’s Disease. Pharmacol Biochem Behav. 2003 June; 75(3): 675-686.

[15] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[16] Vina J et al. Molecular bases of the treatment of Alzheimer’s Disease with antioxidants: prevention of oxidative stress. Mol Aspects Med. 2004 Feb-Apr; 25(1-2): 117-123.

[17] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[18] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[19] McCaddon A et al. Functional vitamin B12 deficiency and Alzheimer’s disease. Neurology 2002 May 14; 58(9): 1395-1399.

[20] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[21] Mimori Y et al. Thiamine therapy in Alzheimer’s disease. Metab Brain Dis. 1996 Mar; 11(1): 89-94.

[22] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[23] Morris et al. Dietary niacin and the risk of incident of Alzheimer’s disease and of cognitive decline. J Neuro Neurosurg Psychiatry 2004 Aug; 75(8): 1093-1099.

[24] McDaniel MA et al. Brain specific nutrients: a memory cure? Nutrition 2003 Nov-Dec; 19(11-12): 957-975.

[25] Conant R and Schauss A. Therapeutic applications of citicoline for stroke and cognitive dysfunction in the elderly: a review of the literature. Alternative Med Rev. 2004; 9(1): 17-31.

[26] McDaniel MA et al. Brain specific nutrients: a memory cure? Nutrition 2003 Nov-Dec; 19(11-12): 957-975.

[27] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[28] Pizzorno J, Murray M, and Joiner-Bey H. The Clinician’s Handbook of Natural Medicine. Pp: 28-34. Churchill Livingstone New York.

[29] McDaniel MA et al. Brain specific nutrients: a memory cure? Nutrition 2003 Nov-Dec; 19(11-12): 957-975.

[30] Bianchetti A et al. Effects of acetyl-l-carnitine in Alzheimer’s disease patients unresponsive to acetylcholinesterase inhibitors. Curr Med Res Opin. 2003; 19(4): 350-353.

[31] Cooper JL. Dietary lipids in the aetiology of Alzheimer’s disease: implications for therapy. Drugs Aging 2003; 20(6): 399-418.