Galantamine Eases the Burden on Alzheimer’s Caregivers

Note added in proof: This article was committed to type the day before President Reagan died. We mourn his passing. RIP.
Galantamine May Make Life a Little Easier
Galantamine
Eases the Burden on Alzheimer’s Caregivers

With their own lives on the line, they deserve every break they can possibly get
By Will Block

o you ever stop and think about President Reagan? He was loved and admired by most Americans, but he had his detractors too. Even they, however, would surely not have wished such a terrible fate upon him as Alzheimer’s disease. To lose one’s mind—literally—is to become, in effect, an unperson, a mere physical shell that once housed the kind of thinking, feeling being we call human. Sad doesn’t begin to describe it.

Ronald Reagan is fortunate, though, in one regard: he has Nancy, a tower of strength whose utter devotion to her husband is legendary. Among public figures, theirs is one of the great love stories of our time. Nancy’s benevolent influence on Ronald was so profound that without her, according to their remarkably candid son Ron, he would probably never have become president, or even much of anything beyond what he already was. (Behind every great man there’s a great woman …)

We should be grateful to Nancy Reagan for inspiring and propelling her husband to greatness, and we should respect her (he is apparently beyond the ability even to recognize her) for remaining, to this day, his primary, round-the-clock caregiver (she does, however, have help, without which the task would be impossible for her to handle).

Alzheimer’s Takes a Huge Toll on Caregivers

It would be unseemly to speculate on the toll that this ordeal has taken on Mrs. Reagan, but we know from countless other cases that the burden on the caregivers of Alzheimer’s patients (as well as patients suffering from other forms of dementia) can be so overwhelming as to virtually destroy their own lives. It can become a living hell from which the only escape, short of death (of either the patient or the caregiver), is the patient’s institutionalization. That painful last resort brings with it its own set of burdens, both emotional and financial.

Whether the caregiver is a spouse, child, sibling, or friend of the patient, the responsibility is enormous and unrelenting, like that of caring for a small child. Even the problems to be dealt with are similar in many respects, although the differences are striking. The greatest difference, of course, is in the diametrically opposite outcomes that are envisioned for the subject. For the parent of a child, the vision is of joyous growth and limitless potential for a fulfilling life. For the caregiver of an Alzheimer’s patient, it is of gradual deterioration toward certain death, without even the assurance of reciprocity in the emotional bond (be it love or friendship) that once united the two parties.

Whereas the love of parents for their children comes easily and grows deeper with time, the lifelong love of a spouse or child for an Alzheimer’s patient who is no longer capable of returning that love can, tragically, be eroded with time, giving way to feelings of anger, grief, loneliness, hopelessness, depression, and resentment—and, of course, guilt. Such crushing emotional baggage can’t help but have a negative impact on one’s physical health and sense of well-being, and caregivers do, in fact, have high rates of physical and mental disorders.1 Good diet tends to go by the wayside (but not exercise, which the care provides abundantly), thus inviting chronic degenerative diseases and a shortened life expectancy. All these problems are exacerbated by sleep deprivation, which is common in such circumstances (see the sidebar).

To Sleep . . . Perchance to Dream

Sleep disorders are common in older people—and counting sheep rarely helps. One study has shown that people who have sleeping difficulties suffer from more health problems and die earlier than people who sleep well.1 Victims of Alzheimer’s disease are especially prone to sleeplessness and other sleep-related problems, such as restlessness and nightmares. These conditions tend to get worse as the disease progresses, and they take an increasing toll on the patient. They cause fatigue during the day, of course; they often exacerbate behavioral problems, such as aggression and incontinence; and they further erode the patient’s ability to function in the activities of daily living.

All of this naturally impacts the caregivers, whose own ability to get a good night’s sleep is often impaired. A sleepy, cranky caregiver is not what the doctor ordered. The myriad problems entailed in taking care of an Alzheimer’s patient, which can be overwhelming to begin with, are made that much worse by sleep deprivation—so much so that the decision to institutionalize the patient may, in sheer desperation, be accelerated. Thus the physical, emotional, and financial costs associated with sleep disorders can be great indeed.

Under such circumstances, it stands to reason that one would want to avoid anything that might aggravate the patient’s difficulties in sleeping through the night. Unfortunately, however, that very characteristic has been observed in clinical trials with one of the most widely prescribed anti-Alzheimer’s drugs, donepezil.2 On the other hand, there has been no evidence of sleep problems associated with rivastigmine, another widely prescribed drug for Alzheimer’s, or with galantamine.

American researchers recently analyzed the data from three previously published clinical trials on galantamine to determine whether sleep disturbances were more prevalent among those taking galantamine (16 or 24 mg/day) than among those taking placebo.2 The analysis took into account the effects of any additional medications the patients were taking (including those for sleep disorders) during the trial periods.

The results showed that galantamine was well tolerated in terms of sleep: it produced no more adverse events than placebo, with one exception: a higher incidence of mild nightmares at the 24-mg/day dosage (although the incidence of nightmares was very low in both groups). Overall, galantamine was judged not to be a significant problem in terms of sleep—and that’s a blessing, all things considered.

  1. Dew MA et al. Healthy older adults’ sleep predicts all-cause mortality at 4 to 19 years of follow-up. Psychosomatic Med 2003;65:63-73.
  2. Stahl SM, Markowitz JS, Papadopoulos G, Sadik K. Examination of nighttime sleep-related problems during double-blind, placebo-controlled trials of galantamine in patients with Alzheimer’s disease. Curr Res Med Opin 2004;20(4):517-24.

Alzheimer’s May Be Preventable to Some Degree, with Supplements

If you’ve read this far, you must be pretty depressed by now (sorry), and wondering if there isn’t anything positive to be said about Alzheimer’s. There is, so please read on. The first thing to know about Alzheimer’s is that it may be preventable to some degree, based on statistical correlations between this disease and other diseases that are definitely preventable—notably atherosclerosis and type 2 diabetes. Prevention of those diseases is largely a matter of good diet and regular exercise. And good diet includes the judicious use of nutritional supplements—not instead of, but in addition to, wholesome, nutritious foods.

The second thing to know about Alzheimer’s is that certain nutritional supplements may help prevent the disease, based on the results of numerous scientific studies, many of which have been discussed in detail in the pages of this magazine in recent years. Among the supplements that appear most likely to be valuable in helping to prevent Alzheimer’s disease are: antioxidants, such as vitamins E and C, lipoic acid, curcumin (from turmeric), resveratrol (from red wine), green tea polyphenols, and Ginkgo biloba extract; the B-vitamins B12 and folic acid; the mineral lithium; the acetylcholine precursor choline; the omega-3 fatty acids DHA and EPA (from fish oil); the sugar-cane extract policosanol; the cinnamon-derived compound MHCP; and the herbal alkaloid huperzine A.

Galantamine Stands Out

All these supplements have value in helping to preserve and protect memory and other cognitive functions, and thus, perhaps, to help prevent not only Alzheimer’s disease but also its usual precursor, the age-related clinical condition known as mild cognitive impairment. (See “Galantamine May Help with Mild Cognitive Impairment” in Life Enhancement, February 2003.)

But there is one supplement that stands out from the rest in this regard, because it has been shown in multiple clinical trials to be extraordinarily effective (and safe) as a treatment for mild to moderate cases—and even “advanced moderate” cases—of Alzheimer’s disease. That supplement is galantamine, a chemical compound extracted from certain flowers, notably the snowdrop, daffodil, and spider lily.*


*Galantamine has been used for many years as a nutritional supplement, and in 2001 it also became an FDA-approved prescription drug (Reminyl®) for the treatment of mild to moderate Alzheimer’s. The compound sold as a drug is the same, but it costs much more.


Galantamine Has Two Modes of Action

What sets galantamine apart from the other medications used to treat Alzheimer’s is the fact that it has two distinct modes of action in the brain, versus their one mode. It’s not so much the number of actions that counts, however, as it is their efficacy, individually and in combination, particularly when it comes to the longer term. Efficacy in this context means any of three things. In descending order of value, they are: (1) improving the patient’s condition, (2) maintaining it unchanged, and (3) slowing the rate of decline.

With the two most widely prescribed Alzheimer’s drugs, donepezil and rivastigmine, the efficacy typically manifests as the second or third of these three categories, and it lasts for about 6 months before beginning to taper off, owing to the patients’ increasing physiological resistance to the drug. That may not seem like much of a benefit, but it’s much better than nothing, especially when one considers that 6 months is an appreciable fraction of the patient’s probable life expectancy (roughly 3 years after the onset of the disease) at that point.2 Even slowing the patient’s rate of decline for 6 months, therefore, is a significant achievement.

Galantamine Works in Advanced Moderate Cases

With galantamine, by contrast, clinical trials have shown that the efficacy is often much greater—both qualitatively, in the sense that the patient’s condition may actually improve for several months, and quantitatively, in the sense that the benefits last for up to 12 months (and perhaps beyond, although hard evidence for that is still lacking).3 Furthermore, two analyses of the combined (and voluminous) data obtained in previously published, randomized, double-blind, placebo-controlled, multicenter clinical trials of galantamine’s safety and efficacy in the treatment of mild to moderate Alzheimer’s disease have shown that galantamine is both safe and effective even in those cases that can be described as “advanced moderate,” i.e., cases that are still in the moderate category but just shy of being called severe.4,5

In the first of these studies, the authors evaluated the combined data from four short-term studies of 3 to 6 months’ duration, in which the patients were given anywhere from 8 to 32 mg/day of galantamine (the commonly recommended amount is 24 mg/day).4 In the second study, the same authors (with additional ones who joined the group) evaluated the combined data from two longer-term studies of 12 months’ duration; here all the patients received 24 mg/day of galantamine.5*


*This study was the subject of an article last year ( “Galantamine Works Even Better Than Was Thought,” April 2003) in which the reader was invited to participate in a scientific “thought experiment” regarding how to solve the problem of extracting the desired information from data that did not seem amenable to yielding it.


Galantamine Works for a Year—Perhaps More

In both analyses, the authors found essentially the same results: galantamine was as effective in advanced moderate cases of Alzheimer’s as it was in mild to moderate cases, leading the authors to speculate that it may be useful even in more severe cases, for which it is currently not prescribed. Equally significant was that galantamine remained effective (and well tolerated) for the entire 12-month period of the two longer-term trials—it either improved or maintained the patients’ cognitive abilities during that period. This suggests that its efficacy might extend well beyond one year.

Furthermore, galantamine substantially improved the patients’ functional abilities (i.e., their ability to perform the routine activities of daily living, such as bathing, dressing, and eating) compared with placebo. In all the studies, it should be noted, patients on placebo declined steadily in all measures of cognitive and functional performance, so the results with galantamine on both counts were especially gratifying.

Use Your Brain to Protect Your Brain

The results described above are highly significant with respect to Alzheimer’s caregivers, because any treatment that improves, or at least stabilizes, the patient’s condition will benefit the caregiver, making his or her task less arduous and possibly more rewarding. Furthermore, it will likely reduce the economic and societal costs of Alzheimer’s by shortening the inevitable period of final decline in the patient’s life, when institutionalization may become necessary.

If there is a lesson here (and there is always a lesson), it is that prevention—to whatever degree it’s possible for Alzheimer’s—should be the Holy Grail of brain health. We should view our brains as being just as susceptible to disease as any other organ, such as the skin or heart or kidneys, and we should use our brains to help protect our brains, thereby possibly preventing a great deal of future suffering by those we love. If we believe that supplements such as galantamine can help, our brains should tell us what to do.

References

  1. Ritchie K, Lovestone S. The dementias. Lancet 2002 Nov 30;360:1759-66.
  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. Dengiz AN, Kershaw P. The clinical efficacy and safety of galantamine in the treatment of Alzheimer’s disease. CNS Spectrums 2004 May;9(5):377-92.
  4. Blesa R, Schwalen S. Galantamine significantly improves all aspects of cognition in patients with advanced-moderate Alzheimer’s disease. Brain Aging 2002;2(3):67-71.
  5. Blesa R, Davidson M, Kurz A, Reichman W, van Baelen B, Schwalen S. Galantamine provides sustained benefits in patients with “advanced moderate” Alzheimer’s disease for at least 12 months. Dement Geriatr Cogn Disord 2003;15:79-87.

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.


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

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