Don’t Forget Your Galantamine

Galantamine—The Earlier, the Better

Don’t Forget Your Galantamine
New evidence shows that it may be helpful in
mild cognitive impairment, a precursor to Alzheimer’s
By Will Block

I never forget a face, but in your case I’ll make an exception.
— Groucho Marx

hy is it that many men forget their anniversary (hello, doghouse), but their wives never do? And why is it that many women forget . . . uh, what is it that women forget, anyway? I can’t seem to remember right now. The point is that, although men and women differ in the kinds of things they are most likely to forget, we all forget some things from time to time: the value of π, perhaps, or Marilyn Monroe’s real name, or the capital of Nebraska. These “tip-of-the-tongue” incidents are harmless, because the things forgotten are things that we know we know, and they will soon come back to us.

But what if, someday, we start noticing (or others start noticing) that some things don’t come back to us? What if we seem to have really forgotten some things? We used to celebrate Beethoven’s birthday, for example, and now December 16 comes and goes without notice. We used to have no trouble remembering our grandchildren’s names and ages, but now . . . .

MCI—A Slippery Slope to Dementia

What is happening to us? Is it a benign memory loss, or could it be something more sinister? If the degree of loss significantly affects our quality of life (which is hard to quantify, but we know it when we feel it, and others know it when they see it), our condition could be mild cognitive impairment (MCI). This form of chronic memory loss stands uneasily between two other conditions, one a precursor and the other a successor.

The precursor is normal, age-related memory loss, to which all people are subject to some degree. This condition does not impair our quality of life to any significant extent, nor does it necessarily lead to MCI—in fact, it usually does not—so it’s considered to be benign. On the “downstream” side of MCI, however, things are very different: although MCI does not necessarily lead to the dread sequel, Alzheimer’s disease (AD), it usually does, so MCI is far from benign. It’s not a death sentence, as AD is, but it’s a major warning of potential trouble ahead—AD or perhaps one of the other two main types of dementia, Lewy body dementia and vascular dementia.

Typically, the memory impairment in MCI is noticeably worse than that associated with normal aging, but unlike that of dementia, it’s largely unaccompanied by other cognitive deficits. A common description of MCI invokes the so-called Petersen criteria:1 (1) memory complaints; (2) normal or close to normal activities of daily living; (3) normal general cognitive functioning; (4) abnormal memory for one’s age; and (5) no dementia. Alzheimer’s disease, a true dementia, is characterized by increasingly severe deficits in many aspects of cognitive and executive function, activities of daily living, and global function, as well as behavioral aberrations.

Early Diagnosis Is Difficult

Trying to distinguish clearly between normal, age-related memory loss and MCI, or between MCI and dementia, is like trying to draw a precise line between any two adjacent colors in the rainbow—they blend into each other so subtly that the best we can do is to recognize when we’re well inside one color and not in either of the adjacent ones. Psychiatrists have developed increasingly sophisticated psychometric tests for making these distinctions, but it’s still a challenge. Once there is visible evidence of Alzheimer’s disease, however (e.g., through neuroimaging techniques), all doubt is removed. (For news on a possible breakthrough in early detection of Alzheimer’s, see the sidebar.)

The Eyes Have It—Alzheimer’s, That Is

The eyes, it is said, are the mirror of the soul. Less romantic, perhaps, but of greater practical value, is the idea, based on recent discoveries, that the eyes are the mirror of the brain itself—at least in people with Alzheimer’s disease. Scientists at the Center for Ophthalmic Research at Brigham and Women’s Hospital in Boston have found that deposits of the protein amyloid-beta, the primary constituent of senile plaque and a hallmark neuroanatomical feature of AD, are found not just in the brains of AD victims, but in the lenses of their eyes as well.1

This is the first time that Alzheimer’s-type amyloid-beta has been found outside the brain. It indicates that what is occurring in the brains of AD victims is also occurring in the lenses of their eyes—a startling discovery. Since it’s much easier to look into an eye than into a brain, it should soon be possible to see (literally) the development of the disease, in a way that has hitherto been unimaginable. “Seeing” in this case involves the use of sophisticated laser-optical and optochemical techniques for the detection and identification of the virtually invisible particles. The researchers note too that amyloid-beta in the lens produces a very unusual type of cataract, which is formed in a different place than common cataracts.

If this method is approved by the regulatory authorities, it offers the exciting prospect for earlier and more definitive diagnosis of AD, which would be a blessing—but not as great a blessing as preventing this terrible disease in the first place.

Reference

  1. Gardner A. Eyes Might Hint at Alzheimer’s. New York Times syndicate, Oct. 18, 2005.

If Alzheimer’s Can Be Treated, Why Not Lesser Problems?

We expect conditions to have treatments, so let’s start with normal, age-related memory loss. Is it curable? If by curable we mean totally reversible, the answer is probably not, because humans gradually lose brain neurons throughout their adult lives, so some degree of brain function must inevitably be lost.* If we mean partly reversible, however, the answer is probably yes, because even Alzheimer’s is partly reversible (but only for a period of months), and that represents a much greater therapeutic challenge.


*We look forward, optimistically, to the day when this may no longer be true. In science, the unimaginable often becomes commonplace (see, e.g., the sidebar).


Prevention is always better than cure, of course, and the best prevention for any kind of memory impairment is twofold: (1) use your brain vigorously and regularly (use it or lose it); and (2) maintain good cerebrovascular health through a good, healthy diet (including the judicious use of nutritional supplements), plenty of exercise, and, of course, no smoking. This lifestyle will also go a long way toward preventing other chronic degenerative diseases, such as heart disease, cancer, diabetes, and arthritis.

If Galantamine Treats Alzheimer’s and Other Dementias . . .

The fact that even Alzheimer’s is partly reversible, if only temporarily, is remarkable—as is the compound that accomplishes this feat: galantamine. This plant alkaloid, extracted from a variety of flowers, has long been used in folk medicine in Eastern Europe and is currently available in the USA as a nutritional supplement for the enhancement of memory and other cognitive functions. It has also been sold in the USA since 2001 as a prescription drug (Razadyne™, formerly Reminyl®) for the treatment of mild to moderate Alzheimer’s disease—the ultimate testimonial to its safety and efficacy, at least by FDA standards.†


†Galantamine is also effective against Lewy body dementia and vascular dementia, as well as the dementia associated with Parkinson’s disease. See “Galantamine’s Antidementia Action Expands—Sort Of,” “Galantamine Improves Both Alzheimer’s and Vascular Dementia,” and “Galantamine Helps in Parkinson’s Disease with Dementia” in the March 2004, July 2002, and December 2003 issues, respectively.


Galantamine acts by enhancing cholinergic function, i.e., those aspects of neural activity—including learning, memory, and other cognitive functions—that depend on the neurotransmitter acetylcholine. It accomplishes this by inhibiting the enzyme acetylcholinesterase, which degrades acetylcholine, and by enhancing the activity of certain acetylcholine receptors called nicotinic receptors.

. . . Why Not MCI?

If galantamine is effective against dementia, should it not also be effective against MCI, which is arguably just a milder form of dementia? It seems reasonable to think so, although actual clinical evidence to support this view has been frustratingly lacking—until now. Two small new studies seem to demonstrate that galantamine does help MCI patients in certain aspects of memory function. This should not surprise regular readers of Life Enhancement, who may recall the numerous articles on galantamine that have taken this position, based on reasonable assumptions. (See, e.g., “Galantamine May Help with Mild Cognitive Impairment” and “Galantamine May Help Block the Road to Alzheimer’s” in the February 2003 and September 2003 issues, respectively.)

In one randomized, double-blind, placebo-controlled study, researchers in California evaluated 19 men (average age 71) with MCI and mild impairment in global functioning.2 For 4 months, the men received either galantamine or placebo, on a dose-escalation schedule beginning with 8 mg/day and graduating to 16 mg/day after 1 month and 24 mg/day after 2 months.

The results provided by a variety of neuropsychological tests revealed significant improvements in short-term memory and global functioning; a few other areas of memory function showed some improvements that were only transitory. This study was weak, owing to its short duration and small sample size; the latter problem was compounded by the fact that 9 of the 19 men dropped out, for one reason or another, before the study was completed. Nonetheless, it’s gratifying to note that the results pointed in a positive direction.

Evidence Seems to Show that Galantamine Does Treat MCI

Similar problems characterized the other study, an open-label (no placebo control) trial involving 10 men (average age 69) with MCI, conducted by researchers in Germany.3 Here the men were treated with 4 mg of galantamine daily for 7 days and were subjected to a battery of neuropsychological tests for cognitive function. In addition, the researchers examined the men’s brains using the powerful technique of functional magnetic resonance imaging (fMRI) while they were navigating their way through computer-programmed virtual reality mazes. The objective was to observe, in particular, the effect of galantamine on the extent of neural activity in the hippocampus. This is the region of the brain most closely associated with learning and memory, as well as with spatial navigation, and it’s the first region to suffer the neurodegeneration of Alzheimer’s disease.


The fMRI images showed that
galantamine increased neural activity
(cholinergic neurotransmission) in the
hippocampus of the MCI patients.


The only cognitive improvement seen in this study was in episodic memory (memory of events, as opposed to memory of facts or concepts), as measured, in this case, by means of certain verbal tests. Episodic memory is the very aspect of memory for which the hippocampus is considered most important. Thus, this finding jibed with the additional finding, from the fMRI images, that galantamine increased neural activity (cholinergic neurotransmission) in the hippocampus of the MCI patients. In the authors’ words,

We show that an increase of cholinergic neurotransmission in subjects with MCI specifically improves hippocampal function and thus that a cholinergic deficit is functionally relevant in subjects with MCI. Malfunction of the cholinergic system may be tackled pharmacologically via the inhibition of acetylcholinesterase even when the impairment is slight.

In other words, galantamine may be an effective agent against memory impairment even in mild cases that fall well below the level of dementia. Since there is, as yet, no generally recommended therapy for MCI, it would appear that galantamine, with its strong credentials as an acetylcholinesterase inhibitor and general cholinergic function enhancer, is a good candidate.

Stay Tuned for Further Developments

Other, larger studies of the effects of galantamine on MCI are in progress or are being planned, and we eagerly await the results, which will probably support those of these small, preliminary studies. Meanwhile, whether you’re a man or a woman, it behooves you to do everything you can to preserve and protect your precious memory function—and galantamine may be one way to do that.

By the way, how could anyone forget the capital of Nebraska? As Norma Jean Baker surely knew, it’s N.

References

  1. Peterson RC. Normal aging, mild cognitive impairment, and early Alzheimer’s disease. Neurologist 1995;1:326-44.
  2. Koontz J, Baskys A. Effects of galantamine on working memory and global functioning in patients with mild cognitive impairment: a double-blind placebo-controlled study. Am J Alz Dis Other Dement 2005;20:295-302.
  3. Grön G, Brandenburg I, Wunderlich AP, Riepe MW. Inhibition of hippocampal function in mild cognitive impairment: targeting the cholinergic hypothesis. Neurobiol Aging 2006;27:78-87.

Dual-Action Galantamine

Galantamine provides a heralded dual-mode action for boosting cholinergic function: it inhibits the enzyme acetylcholinesterase, thereby boosting brain levels of acetylcholine, and it modulates the brain's nicotinic receptors so as to maintain their function. The recommended daily serving ranges from a low of 4 to 8 mg of galantamine to begin with to a maximum of 24 mg, depending on the individual's response.

For an added measure of benefit, it is a good idea to take choline, the precursor molecule to acetylcholine, as well as pantothenic acid (vitamin B5), an important cofactor for choline. Thus it is possible to cover all bases in providing the means to enhance the levels and effectiveness of your acetylcholine.

It’s also a good idea to take the following:

  • Green tea polyphenols, a class of antioxidants, operating together as a system, that can also fight amyloid-beta toxicity
  • Vitamin C and Vitamin E, which have been shown to work together to help protect your brain's hotbeds of free radical activity
  • Turmeric curcuminoids, a system of antioxidants that helps protect your neurons from damage or death caused by amyloid-beta
  • Folic acid, vitamin B6, and vitamin B12, important vitamins that help prevent damage to mitochondria (where they help repair DNA damage), cofactor the production of nitric oxide, and reduce levels of homocysteine (a neurotoxin)
  • Lithium, an important brain food that is found in the bottled waters of American and European health spas ... that also lowers the toxicity of amyloid-beta while causing an increase in neurotrophic factors that help induce neurons to repair themselves when under stress ... that helps cause an increase in gray matter and helps enhance neurogenesis of hippocampal neurons


Will Block is the publisher and editorial director of Life Enhancement magazine.

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