Protect Brain Function by Enhancing Neurotransmission
      by Will Block

There is recent evidence, from a Canadian study, that life expectancy in people suffering from dementia is much shorter than had previously been believed.¹ The study found that the median survival rate for elderly dementia patients was 3.3 years after the onset of the disease.  Previous, less carefully controlled studies had suggested that the survival rate was anywhere from 5 to 9.3 years. The clear implication is that dementia shortens lifespan.

But should we resign ourselves to that fact and let Mother Nature take her course, doling out the seeds of dementia to the unlucky among us, while sparing the rest for no apparent reason?  No way!  First of all, it's not so much a matter of luck as of lifestyle - making the right choices.  In that sense, we can manufacture our own "luck," and we are fools if we don't - especially when we consider that the means are all around us, sometimes even in the flowers growing at our feet.

Some of those flowers contain galantamine, a compound that has been found to be as effective in treating Alzheimer's disease as synthetic drugs.  But there are other natural compounds that are also valuable in this regard, as we will see.

THE PROGNOSIS FOR ALZHEIMER'S IS POOR
Alzheimer's disease is one of the two dominant types of dementia, which is defined as a progressive loss of memory accompanied by significant impairment in other areas of mental function or behavior.*  The slow, inexorable fading away of a once vibrant personality - and with it, of life itself - is a terrible thing to endure or to witness, especially in someone we love.  As the Canadian study has shown, the prognosis for patients with dementia is similar to that for patients with such malignant diseases as cancer and heart disease.²

Alzheimer's is a degenerative disease of the brain tissue itself (in certain parts of the brain). It entails the atrophy or dysfunction of certain cell groups that underlie the normal neural mechanisms associated with higher cognitive functions. This is often accompanied by the development of pathological changes in the brain called plaques and tangles.

The other dominant type of dementia, vascular dementia, is caused by cerebrovascular disease, or diseased blood vessels in the brain. This leads to impaired blood flow and thus diminished delivery of such vital nutrients as oxygen and glucose to the brain's cells. It is important to realize that many cases of Alzheimer's may be complicated by some degree of vascular dementia, simply because cerebrovascular disease is so common in the elderly.

HEALTHY NEUROTRANSMISSION IS VITAL
Whatever it takes to stave off the threat of Alzheimer's is worth doing.  The primary objective is to enhance neurotransmission so as to retain memory and other higher cognitive functions.  Neurotransmission is the mechanism by which information travels in the brain - zipping from nerve cell to nerve cell by jumping across the tiny gaps (called synapses) between them.  This is effected via molecules called neurotransmitters, among the most important of which is acetylcholine (ACh).  One of the hallmarks of Alzheimer's is a marked reduction of Acetylcholine levels in certain regions of the brain.

 

Acetylcholine Is Much More Than a Neurotransmitter Acetylcholine's role as a neurotransmitter is by no means limited to the brain. On the contrary, Acetylcholine is synthesized in the majority of human cells and is found throughout the entire body, where it serves as the primary neurotransmitter for stimulating muscle cells and the cells of various internal organs. Furthermore, it has been discovered that Acetylcholine also plays a role in a variety of fundamentally important non-neuronal cellular functions as well, including cellular homeostasis, the mechanism by which a cell maintains equilibrium by adjusting its physiological processes to compensate for the effects of disruptive outside forces. (For a discussion of this newly understood aspect of Acetylcholine function, see "What's Old With Acetylcholine Is New to Us"  Thus, Acetylcholine is much more than "just" a neurotransmitter, and maintaining optimal Acetylcholine levels may be beneficial for more than just the prevention of Alzheimer's disease.

There are three approaches to enhancing neurotransmission by acetylcholine:

1. Stimulation of Acetylcholine production. This is the most direct (but not necessarily the best) approach. The idea is to boost the brain's synthesis of Acetylcholine by using chemical precursors - compounds whose reactions with other molecules in the body lead, eventually, to more Acetylcholine molecules.

2. Protection of existing Acetylcholine. This is the approach most widely used in medical practice, because it has been found to be the most effective. At all times, the brain's Acetylcholine molecules are subject to a natural regulatory mechanism in which they are attacked and destroyed by an enzyme called acetylcholinesterase (AChE).  Compounds that suppress AChE are called acetylcholinesterase inhibitors, and these compounds are the primary agents for treating Alzheimer's disease.

3. Sensitization of nicotinic receptors. The brain's nerve cells (neurons) are equipped with different kinds of molecular receptor sites for the Acetylcholine molecules jumping across the synapses.  Among the most important of these are ones called nicotinic receptors, and sensitizing them to make them more receptive to Acetylcholine enhances the efficiency of neurotransmission.

THE DOUBLE BENEFIT OF GALANTAMINE
Mother Nature's bounty includes a variety of natural compounds that can enhance neurotransmission by Acetylcholine, and one of them, as mentioned above, rivals the best synthetic drugs that pharmaceutical companies have to offer.  That compound is galantamine, which has a history of medicinal use in Europe that goes back many centuries.  The flowers from which it is extracted include snowdrops, daffodils, spider lilies, and a few others. It takes huge amounts of these flowers to get a little galantamine, so it cannot be made inexpensively.

Galantamine is a first-rate AChE inhibitor, and, unlike other AChE inhibitors, it is also a potent sensitizer of nicotinic receptors, giving it a double whammy against Alzheimer's disease.  Many research studies documenting these attributes have been published in the international medical literature in recent years. Now a meta-analysis - a thorough, critical review of the literature - has been published, with results that confirm the role of galantamine as an effective treatment for Alzheimer's.³

The authors combed medical journals and monographs, databases of clinical trials, and directories of Ph.D. theses for all available information on galantamine's role as a treatment for Alzheimer's.  To ensure that only high-quality research was included in the meta-analysis, the authors screened the studies for the following factors: 
1) they had to be randomized, double-blind, placebo-controlled, and unconfounded (i.e., galantamine had to be tested alone, not in combination with any other agent); 
2) they had to have covered a treatment period of more than 4 weeks for patients with Alzheimer's disease; and 
3) they had to meet additional criteria regarding the study protocol and the reporting of data. Of the 30 studies examined, seven made the grade.

GALANTAMINE WORKS AS WELL AS SYNTHETIC DRUGS
From the combined results of these seven studies - all of which involved patients with mild to moderate Alzheimer's, none severe - the authors concluded that

 ". . . this review shows consistent positive effects for galantamine in trials of 3 months, 5 months, and 6 months duration. . . . there is evidence demonstrating efficacy for galantamine on global ratings, cognitive tests, assessments of ADLs [activities of daily living], and behavior. The magnitude of the effect on cognition is similar to other acetylcholinesterase inhibitors, including donepezil, rivastigmine, and tacrine." (These are the three most widely used synthetic drugs for treating Alzheimer's disease.)

In other words, in terms of cognitive function (memory and learning), galantamine works as well as the synthetic drugs.  The dosages most commonly used in these studies were either 24 or 32 mg per day, but the authors concluded that 16 mg per day is probably preferable because its efficacy is equal to that of the higher doses, and it is less likely to cause gastrointestinal upset, a possible side effect of galantamine.  The synthetic drugs can cause GI upset too but are also notorious for more serious side effects, such as liver toxicity and heart-rate irregularities.

HUPERZINE A ALSO WORKS WELL
Another acetylcholinesterase inhibitor with a long history of use - but primarily in China - is huperzine A, a compound extracted from the Chinese plant Huperzia serrata. This compound is effective in improving memory and cognitive abilities in humans, including those with dementia.*

For example, Chinese scientists studied the effects of huperzine A (HupA for short) on the mental functions of elderly Alzheimer's patients.⁴  Sixty patients aged 52 to 80 with impaired faculties were treated with synthetic HupA (200 micrograms twice daily) or placebo for 60 days.  They were evaluated with psychological and physiological tests to determine their mental and physical health before and after the treatment.  Based on four of the most important psychological tests, including memory function, the improvement rates in both groups ranged from 43% to 70%.  The only side effects of HupA noted in this study were mild to moderate nausea and insomnia.

OTHER SUPPLEMENTS CAN HELP TOO
Other natural supplements that may help to enhance neurotransmission include choline, which is a chemical precursor of acetylcholine. Some of the choline in our diet is used by the body to manufacture the Acetylcholine  it needs (most of the rest goes into the building of cell walls).  Choline works best in this regard if accompanied by another compound called a cofactor - in this case, vitamin B5 (pantothenic acid).   A larger and more complex version of choline that also serves as a precursor to Acetylcholine  is CDP-choline (also known as citicoline), which has been shown to be effective in treating Alzheimer's disease.⁵

For enhanced neurotransmission, galantamine rivals the best
synthetic drugs that pharmaceutical companies have to offer.

Yet another Acetylcholine precursor is DMAE (dimethylaminoethanol), which is similar in molecular structure to choline.  Although DMAE does not appear to improve memory or to be of benefit in Alzheimer's disease, it may help produce positive behavioral changes, such as improvements in mood and motivation, in elderly patients with dementia.⁶

The herb Ginkgo biloba has been shown to have beneficial effects in dementias of the Alzheimer's type and other types as well - probably through different mechanisms of action.^7-9 It is known to improve cognitive function by enhancing neurotransmission and to improve circulatory function by inhibiting platelet aggregation, the process that produces blood clots. Both of these functions may be related to the antioxidant properties of flavonoid compounds in the ginkgo extract. This is significant because it is believed that some of the conditions associated with Alzheimer's disease (as well as with many other aspects of aging) may be due, in part, to oxidative damage caused by free radicals.¹⁰

Antioxidant properties are the hallmark of two other agents in this compendium of anti-Alzheimer's supplements: vitamin C and vitamin E.  These are widely viewed as among the most important antioxidants for human health in many of its aspects, and this extends to the protection of brain cells from oxidative damage.

References              www.AlzheimersTreatments.com

1. Wolfson C, Wolfson DB, Asgharian M, M'Lan CE, Østbye T, Rockwood K, Hogan DB. A reevaluation of the duration of survival after the onset of dementia. N Engl J Med 2001 Apr 12;344(15):1111-6.
2. Kawas CH, Brookmeyer R. Aging and the public health effects of dementia. N Engl J Med 2001 Apr 12;344(15):1160-1.
3. Olin J, Schneider L. Galantamine for Alzheimer's disease (Cochrane review). In The Cochrane Library, Issue 2, 2001. Oxford: Update Software.
4. Xu SS, Cai ZY, Qu ZW, Yang RM, Cai YL, Wang GQ, Su XQ, Zhong XS, Cheng RY, Xu WA, Li JX, Feng B. Huperzine-A in capsules and tablets for treating patients with Alzheimer's disease. Acta Pharmacol Sin 1999 Jun;20(6):486-90.
5. Alvarez XA, Mouzo R, Pichel V, Perez P, Laredo M, Fernandez-Novoa L, Corzo L, Zas R, Alcaraz M, Secades JJ, Lozano R, Cacabelos R. Double-blind placebo-controlled study with citicoline in APOE genotyped Alzheimer's disease patients. Effects on cognitive performance, brain bioelectrical activity, and cerebral perfusion. Methods Find Exp Clin Pharmacol 1999;21(9):633-44.
6. Ferris SH, Sathananthan G, Gershon S, et al. Senile dementia. Treatment with Deanol. J Am Ger Soc 1977;25:241-4.
7. Le Bars PL, Katz MM, Berman N, et al. A placebo-controlled, double-blind, randomized trial of an extract of Ginkgo biloba for dementia. North American EGb Study Group. JAMA 1997;278:1327-32.
8. Hofferberth B. The efficacy of EGb 761 in patients with senile dementia of the Alzheimer type, a double-blind, placebo-controlled study on different levels of investigation. Human Psychopharmacol 1994;9:215-22.
9. Kanowski S, Herrmann W, Stephan K, et al. Proof of efficacy of the Ginkgo biloba special extract EGb 761 in outpatients suffering from mild to moderate primary degenerative dementia of the Alzheimer type or multi-infarct dementia. Pharmacopsychiatry 1996;29:47-56.
10. Harman D. Free radical theory of aging: a hypothesis on pathogenesis of senile dementia of the Alzheimer's type. Age 1993;16:23-30.

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