Galantamine May Help with Mild Cognitive Impairment

Galantamine’s Usefulness May Begin Early

Galantamine May Help with Mild Cognitive Impairment
Catching MCI early is the key to avoiding more serious consequences later
By Will Block

ild is nice, usually. Mild weather, a mild-mannered person, a mild mustard—all nice. Even our ailments aren’t so bad when they can be described as mild: a mild cold, e.g., or a mild case of the blues. With time and a little TLC, they usually go away, and we’re as good as new. We don’t worry about things that are mild. There are so many severe things to worry about, like terrorists and termites and taxes and . . . uh . . . there was one more thing I wanted to add here, but I can’t remember what it was. I must be having a mild memory lapse.

Uh-oh. What if . . . nah, I’m too young for that kind of thing. Couldn’t happen to me. Besides, even if it were happening, I’d surely know about it early on, isn’t it?

Um, sorry, those words didn’t come out quite right. But with time and a little TLC, they usually go away, and . . . oh, wait, I said that already—about something else, I think.

Enough already! It’s not as though I’m cognitively impaired or anything, I’m just having a mild episode of . . . something.

MCI Is a Major Risk Factor for Dementia

OK, that was silly and a bit exaggerated, but here’s the point: mild cognitive impairment (MCI) is something that can sneak up on anyone, even middle-aged people who are seemingly in good health. (See the sidebar, “What Is MCI, Exactly?”) Worse yet, it can slip quietly into your brain and take up residence without your even knowing it. And it usually doesn’t go away—it just goes from mild to worse, if you don’t fight back. In the worst-case scenario, it can eventually lead to dementia—most likely Alzheimer’s disease or vascular dementia—and that’s no laughing matter.

What Is MCI, Exactly?

The term mild cognitive impairment does not necessarily mean the same thing as a variety of similar terms that have commonly been used to describe disorders of this kind. Other terms, such as age-related cognitive decline (ARCD) and age-related memory impairment (ARMI), have different meanings that are important to neurologists. What all these disorders have in common, however, is obvious: a slowing down of mental function beyond that of normal aging. Where they differ is in the exact nature of the condition, the degree of impairment, the likely implications for its progression, and the best therapeutic approach.

The problem is that even the neurologists don’t all agree on how to define MCI. One group, e.g., says, “. . . the term MCI may, and often does, involve other cognitive domains besides memory, including deficits in language, attention, motivation, affect, and executive function.”1

The definitive word, however, is probably that of the Quality Standards Subcommittee of the American Academy of Neurology, which defines MCI more narrowly as “the clinical state of individuals who are memory-impaired but are otherwise functioning well and do not meet clinical criteria for dementia.”2 Specifically, they characterize MCI patients as having memory complaints (preferably corroborated by another party) and objective memory impairment, but with normal general cognitive function, intact activities of daily living, and no evidence of dementia.

Actually, that definition is too restrictive in terms of the potential benefits of a substance such as galantamine, which, in Alzheimer’s patients, provides improvements not just in memory function but also in global ratings of overall function as well as in cognitive tests, assessments of the activities of daily living, and behavior.3 For our purposes, therefore, we can interpret MCI to mean the general decline in memory and other cognitive functions that accompany the aging process but that appear to exceed what would be considered normal in this regard.

  1. Meyer JS, Li Y, Xu G, Thornby J, Chowdhury M, Quach M. Feasibility of treating mild cognitive impairment with cholinesterase inhibitors. Int J Geriatr Psychiatry 2002;17:586-8.
  2. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133-42.
  3. Olin J, Schneider L. Galantamine for Alzheimer’s disease (Cochrane review). In The Cochrane Library, Issue 2, 2001. Oxford: Update Software.

That MCI is a major risk factor for both Alzheimer’s disease and vascular dementia is beyond question, but it is not clear whether it will inevitably lead to either of these diseases. (See the sidebar, “Does MCI Beget Dementia?”) In any case, mild cognitive impairment can be thought of as a transitional phase between normal aging and early (mild) dementia.* Whereas normal aging takes the mental clarity of youth and merely fogs it up somewhat, MCI will probably, eventually, drag it down into the black hole of dementia. Researchers believe that if MCI could be nipped in the bud, millions of people might be spared the irreversible loss of memory and other cognitive functions that come with Alzheimer’s disease and vascular dementia.


*Scientists who are concerned with the cognitive decline associated with normal aging lament the fact that they can’t define the parameters clearly. They continue, however, to refine their methods of qualitative and quantitative analysis of this amorphous condition. Meanwhile, as with many other phenomena that do not lend themselves readily to clear definition, clinical experience has taught the experts to “know it when they see it.”


Does MCI Beget Dementia?

If dementia is a form of severe cognitive impairment, then it must have started as mild cognitive impairment, right? One would think so, because severe disorders don’t just appear full-blown out of nowhere. The question is vexing, though, because many people are diagnosed with dementia without previously having been diagnosed with MCI—the symptoms of impairment may not have been obvious enough to anyone to lead to that conclusion before the disorder had progressed sufficiently to qualify as dementia. Furthermore, not all cases of MCI that are recognized lead to dementia, even after many years.

All people are different, after all, and the course of the disorder can follow many different paths, in terms of how fast it develops, what functions are impaired, and how those impairments become manifest in the person’s behavior and daily activities. It’s likely that, among the many millions of known cases, whether of MCI or dementia, no two are exactly alike.

In any case, there is no doubt that people with MCI are at high risk for Alzheimer’s disease or vascular dementia.1 Even though neither of those dreadful outcomes is assured, it would be foolish to ignore the possibility. Some experts believe that MCI patients “convert” to Alzheimer’s at the rate of about 10 to 15% per year, which means that at least half of them will have the disease within five years (the editorial in last month’s issue of Life Enhancement was in error on this point).2 Other experts think the rate is lower, or higher—anywhere from 6 to 25% per year.1

Whatever the actual rate is, it’s likely that all individuals who do develop Alzheimer’s disease or vascular dementia (which together constitute 80% of all cases of dementia) had some form of MCI previously, whether or not they or anyone else knew it. And for all practical purposes, it’s reasonable to assume that most people who have MCI will be afflicted with some form of dementia within a few years.

  1. Petersen RC, Stevens JC, Ganguli M, Tangalos EG, Cummings JL, DeKosky ST. Practice parameter: early detection of dementia: mild cognitive impairment (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2001;56:1133-42.
  2. Wysocki B, Jr. As details slip, one man battles a loss of memory. The Wall Street Journal, Dec. 3, 2002, p A1.

MCI Can Steal Your Mental Faculties

Nipping MCI in the bud implies, for starters, that you know, or at least suspect, that it’s there—and therein lies a major problem. The word insidious may have been invented to describe MCI, a thief so subtle and sly that it often steals away the very faculties that would enable you to recognize it in the first place.

Not that you—all of us—don’t become aware from time to time, as we grow older, of a certain tendency to forgetfulness and perhaps a little dulling of the gleaming razor that once shaved the fuzz off our thoughts. That’s normal, and nothing to worry about—as long as our thoughts don’t become so fuzzy that they start resembling those of Winnie-the-Pooh, whose brain, as we know, was made of fluff. As endearing as Pooh was, he was, well, not the brightest creature in the Hundred Acre Wood.


MCI can slip quietly into your 
brain and take up residence 
without your even knowing it.
And it usually doesn’t go away—
it just goes from mild to worse,
if you don’t fight back.


But how do you know if you’re getting sort of fuzzy in the brain? How do you know if those episodes of forgetfulness are not a benign accompaniment to growing older, but rather symptoms of something more sinister? How do you know, in short, if you’re becoming the victim of mild cognitive impairment?

Early Detection of MCI Is Invaluable

The answer is, you may not know, unless it becomes so obvious that someone near and dear to you screws up the courage to tell you (in which case you may not believe it anyway) or you get yourself tested by experts in this field. As with most disorders, early detection is invaluable. Using certain tests—primarily involving measures of short-term recall (a weakness in which is the leading indicator of MCI)—they can tell the difference, more or less, between MCI and the normal effects of getting older. It’s “more or less” because this is far from an exact science, and the criteria for deciding among alternative diagnoses are themselves rather fuzzy.1


In our rapidly aging society, the 
problem of MCI and dementia is so 
great that combating them has 
become a major public health issue.


The experts do the best they can, however. Their goal is threefold: (1) finding ways of diagnosing MCI more accurately; (2) finding ways of slowing or halting its progress; and (3) most importantly, figuring out how to prevent it to begin with. In our rapidly aging society, the problem of MCI and dementia is so great that combating them has become a major public health issue and a high priority for scientists at universities, drug companies, and government research laboratories. At least 4 million Americans already have Alzheimer’s, and experts estimate that another 8 million have MCI, mostly undiagnosed. Those numbers are expected to increase dramatically in the coming years unless we can find effective interventions.

Galantamine for Dementia: Proven Long-Term Benefits

An intervention that appears particularly promising is galantamine, a compound extracted from various flowers, such as the snowdrop, daffodil, and spider lily. Galantamine has a long history of use in Europe as a natural herbal remedy for a variety of ailments. During the past decade, modern science has discovered overwhelming evidence of its efficacy and safety in the treatment of mild to moderate cases of Alzheimer’s disease, and it is also effective against the other major form of dementia, vascular dementia.2,3,4*


*Life Enhancement has published 17 prior articles on galantamine, starting in October 2000. Comprehensive reviews of the results described in the first 15 of them can be found in the last two: Remember Galantamine? (How Could You Forget?) and Galantamine Combats Alzheimer’s and Vascular Dementia, which can be found in the September 2002 and November 2002 issues, respectively.


Because of its unique dual mode of action, galantamine appears to be superior to the most widely prescribed anti-Alzheimer’s drugs, donepezil and rivastigmine.* It has been found that galantamine (usually at dosages of 24 or 32 mg/day) provides substantially longer-term benefits than donepezil and rivastigmine and that, unlike those drugs, it can not only slow the progression of Alzheimer’s but halt it altogether (not always, but sometimes), and it can sometimes even bring about modest improvements in the patients’ condition.5,6 It is not, however, a cure for Alzheimer’s—there is no cure.


*Galantamine itself became an FDA-approved “drug” in 2001, although the agency did not have the right to take that action: galantamine was grandfathered under the Dietary Supplement Health and Education Act of 1994, having been sold as a dietary supplement before October 15, 1994. It is still legally sold as such.


Research Is Underway on Galantamine for MCI

It’s tempting to think that an agent that can alleviate the symptoms of dementia could do just as well, if not better, against the less severe symptoms associated with mild cognitive impairment, thus perhaps halting or reversing that condition and preventing it from progressing to the stage of full-blown dementia. Indeed, it seems highly likely that galantamine could do that, because it is, beyond any doubt, effective in combating mild to moderate cases of Alzheimer’s disease and vascular dementia. There is no substitute for actual clinical evidence, however, and a major international study to investigate the MCI question is currently underway. The results will be reported in this magazine as soon as they are published.


Galantamine might alleviate the
less severe symptoms of MCI
just as well as, if not better than,
those of dementia, thus
perhaps preventing MCI from
progressing to dementia.


Galantamine Could Be the Best Thing Yet

It’s still not clear whether MCI is really just early-stage dementia or a distinct disorder that often develops into dementia for whatever reason. From a scientific point of view, it’s important to find out, but from a practical point of view, does it matter? Not any more than understanding gravitational theory matters if you want to avoid falling off a cliff. All that matters is doing whatever you can to prevent MCI, or combat it if you already have it. The earlier it’s detected, the better your chances of dealing with it effectively.

Will leading an exemplary life—good diet, plenty of exercise, no smoking, etc.—guarantee immunity from MCI? Sadly no, although it will almost certainly improve the odds. So lead an exemplary life! (Giving advice is so easy—I should do it more often.) Happily, a further improvement of the odds may be achievable with nature’s own galantamine, which could turn out to be the best weapon in the fight against mild cognitive impairment.

References

  1. Ritchie K, Touchon J. Mild cognitive impairment: conceptual basis and current nosological status. Lancet 2000;355:225-8.
  2. Olin J, Schneider L. Galantamine for Alzheimer’s disease (Cochrane review). In The Cochrane Library, Issue 2, 2001. Oxford: Update Software.
  3. Lilienfeld S, Kurz A. Broad therapeutic benefits in patients with probable vascular dementia or Alzheimer’s disease with cerebrovascular disease treated with galantamine. Ann NY Acad Sci 2002;977:487-92.
  4. Meyer JS, Xu G, Thornby J, Chowdhury MH, Quach M. Is mild cognitive impairment prodromal for vascular dementia like Alzheimer’s disease? Stroke 2002;33:1981-5.
  5. Tariot PN. Maintaining cognitive function in Alzheimer disease: how effective are current treatments? Alzheimer Dis Assoc Disord 2001;15 Suppl 1:S26-33.
  6. Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV. Efficacy of galantamine in probable vascular dementia and Alzheimer’s disease combined with cerebrovascular disease: a randomised trial. Lancet 2002 Apr 13;359:1283-90.

 

Galantamine for Autism?

It’s rare for a disease of infancy to have much in common with a disease of aging. Curiously, though, at least one kind of autism, called Heller’s dementia, is clinically similar to Alzheimer’s disease. This has piqued researchers’ interest in the possible use of galantamine, which is effective in mild to moderate cases of Alzheimer’s.

Autism is a disorder that begins early—the symptoms always appear before the age of 3, and they usually persist throughout the patient’s life. Autistic children behave in compulsive and ritualistic ways and fail to develop normal social relationships and communications skills; most have subnormal intelligence. Characteristically, they prefer to be alone, they won’t cuddle, they avoid eye contact, they resist change and are easily irritated, and they become excessively attached to familiar objects. It is a tragedy for them and their families.

The cause of autism is unknown, but it is not poor parenting, as some have suspected. Various brain abnormalities can sometimes be seen in autistic children or adults, using noninvasive imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI). No drugs seem to improve autism significantly. Some provide limited, temporary alleviation of certain symptoms, but they also have possible severe side effects.

Naturally, researchers keep looking for something new that will help, especially if it’s well tolerated. In a study on 20 autistic boys (average age 7.4, with an average IQ of 68), they found recently that galantamine provided a slight improvement in the boys’ irritability, compared with placebo.1 None of the boys seemed to have headaches or stomachaches, although their ability to communicate such information was limited, so it’s hard to be sure. The authors concluded, in any case, that galantamine might be moderately effective in the short-term treatment of irritability in autistic children.

  1. Niederhofer H, Staffen W, Mair A. Galantamine may be effective in treating autistic disorder (Letters). Brit Med J 2002;325:1422.

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.



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

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