Some of the most usable results are found in …
Real Life Galantamine
Home data may be more meaningful
By Will Block
here are studies and there are studies. When researchers investigate animals taken out of their environments, the results are often quite different. As a budding field, animal studies has been characterized as the study of animals in a variety of cross-disciplinary ways. Scholars have chimed in from widely diverse fields. These include art history, anthropology, biology, film studies, geography, history, psychology, literary studies, philosophy, and sociology. Not to mention—believe it or not!—various “theoretical” perspectives, including: feminism, Marxist theory, and queer theory.* What, you may ask, is going on here?
Altogether, animal studies—which grew out of the animal liberation movement and was grounded in “ethical” questions about co-existence with other species—is purportedly geared to understand both human-animal relations now and in the past, and to understand animals as beings-in-themselves separate from our knowledge of them. Whatever the validity of this “unrestrained discipline” (that’s a contradiction, if ever there was one), scholars and others (non-scholars such as scientists, you might suppose) are exercising the “freedom” to define their own criteria and structure for the field. Is this science or reality television? It certainly would appear to have little to do with animal testing—which is where we should have started—and it isn’t science.
The human testing aspects of
human studies may differ in
their results depending on whether
a particular study is administrated in
a real life situation.
But there is some insight that can be borrowed from this illusory field. Namely, in parallel with animal differences outside of their natural environment, the human testing aspects of human studies may differ in their results depending on whether a particular study is administrated in a real life situation. In such circumstances, where surveillance of the participants is less tight, compared to that of a controlled setting, where some important considerations may be lost, the results may differ.
Welcome to Real Reality
Alzheimer’s disease (AD) is the most common form of dementia occurring in the elderly. Within this population, acetylcholinesterase inhibitors (AChEIs)—including donepezil, rivastigamine, and galantamine—are clinically used for symptomatic treatment of AD. They have shown both short- and long-term benefits in regard to behavioral and cognitive measurements. In fact, they are the only drugs (the first two) and herbal nutrient (galantamine) recommended for treatment of mild to moderate AD. Controlled randomized trials and meta-analyses have documented a consistent, albeit sometimes modest effect, on cognition, behavioral symptoms and activities of daily living (ADLs). Although minor adverse effects are commonly reported with AChEIs, the products are generally well tolerated and have a favorable safety profile.
New research from Brussels, Belgium reports on the “real life” appreciation of elderly patients, their caregivers, and physicians for a once daily formulation of prolonged-release galantamine in the treatment of mild to moderate AD. Prior controlled randomized trials and meta-analyses have shown a consistent, although “modest” effect on cognition, behavioral symptoms, and ADLs, a measure used in healthcare referring to daily self-care activities that take place within an individual’s home, in outdoor environments, or both. A modest effect may make a big difference, especially when it’s a loved one’s mind or even your own.
Physicians and other health professionals normally refer to the ability or inability to perform ADLs as a measurement of an individual’s functional status, especially in the elderly and in those with disabilities. ADLs are things that we normally do to take care of ourselves, such as eating, washing, dressing, grooming, work, managing money, and homemaking. ADLs also include leisure activities. While a number of national surveys collect data on ADL status of the population, ADLs vary from person to person. As an example, self-esteem may not be an equally-valued ADL, but it can represent the sum total of the quality of life that you enjoy.
Agreement among Patients, Caretakers, and Physicians
In the Brussels’ study, a prospective, multicenter, observational protocol was employed. In total, 128 elderly subjects diagnosed with mild to moderate AD were treated for 6 months with galantamine,* donepezil or rivastigmine—all of these are AChEIs, but only galantamine is also a natural material and a nutritional supplement. Most subjects were given galantamine, and 82 of the initial 97 (84.5%) recipients lasted the full 6 months of the study. These patients reported their condition as improved (49%), unchanged (47%), and worsened (4%). Their caregivers rated global evaluation as 37% better, 41% unchanged, and 22% worse. At the same time, their physicians rated global clinical impression of change as 46% better, 34% unchanged, and 20% worse. Measurements of cognition and behavior remained stable.
Of the patients treated with
galantamine, all those who finished
the study chose to continue
their treatment at the end of
the trial, a major vote of
confidence in galantamine.
It was significant that the appreciation of physicians and caregivers corresponded quite well. Plus, the incidence of serious side-effects possibly related to galantamine was 9.3%, which was not different from those using the other AChEIs. At the end of the study, the researchers found that in a real life setting, galantamine is safe and is favorably appreciated by patients, their caregivers, and physicians. Of the patients treated with galantamine, all those who finished the study chose to continue their treatment at the end of the trial, a major vote of confidence in galantamine.
Long-Term Galantamine Stabilizes Cognition
One of the principal shortfalls with galantamine/AD research, especially in the elderly, has been the lack of long-term benefit evaluation. Two very recent studies have delved into this, and arrived at some interesting and valuable conclusions. In the first study—conducted at the Nobel Prize famed Karolinska Institute in Stockholm, Sweden—the effects of galantamine treatment on the brain functional activities of blood flow and glucose metabolism were examined in 18 subjects with mild AD in relation to brain acetylcholinesterase (AChE) activity, nicotinic receptors, and cognitive function. The amount of galantamine given ranged from 16 to 24 mg/day.
A modest effect may make
a big difference, especially
when it’s your mind.
In the initial phase of this study, the subjects were double blinded for the short term of three months. This was followed by an open-label stage that lasted nine additional months, constituting the long term. As the study proceeded, the AD patients were examined with positron emission tomography (PET), a nuclear medicine imaging technique that produces a three-dimensional image or picture of functional processes in the body through the use of tracers.
Importantly, these regional changes
associated with galantamine
correlated positively with a
stabilization of cognition.
In this study, PET images of regional cerebral blood flow were taken at baseline, 3 weeks, and after 3 and 12 months of treatment. Also, images that measured regional cerebral metabolic rate for glucose were taken at baseline and at the end of the study, at 12 months. Other neuropsychological assessments were performed to follow changes in cognition during the treatment period.
Throughout the study, the data showed that there were differences in regional cortical blood flow attributed to the use of galantamine. These differences correlated positively with AChE activity, nicotinic receptor activity, and cognition—and were viewed as positive changes. Also, the regional cerebral metabolic rate for glucose increased in the frontal brain region and stabilized in other cortical areas at 12 months of galantamine use.
Significantly, these regional changes associated with galantamine correlated positively with a stabilization of cognition. In due course, the results suggest that treatment with galantamine has a long-term positive effect on brain perfusion and glucose distribution, benefits associated with stabilized cognition.
Who is Likely to Benefit from Galantamine
Over the Long Run?
The second long-term study investigated the operational, clinically relevant responses achieved through the use of galantamine in mild to moderate AD clinical trials of 5–6 month’s duration as a means to determine who would be apt to benefit most from long-term galantamine therapy.
AD subjects who demonstrated
improvement, stability, or limited
cognitive decline 2–5 months after
reaching maintenance doses of
galantamine are more likely to
experience continued benefit from
long-term galantamine therapy.
There were two groups of trials that were analyzed. The first group was comprised of 6 placebo-controlled trials of no more than 6 months’ duration. The subjects in these trials received maintenance doses of galantamine in the range of 16–24 mg/day. In the second group were 12 open-label extension trials using galantamine at 24 mg/day maintenance levels. Extension trials are those that continue beyond the endpoint of prior trials that are complete in themselves based on their initial design.
Galantamine Enhances Neuroprotective
Benefits of Curcumin
At Panjab University in Chandigarh, India, a new study investigating the role of brain senescence in cognitive dysfunction and neurodegenerative disorders has found a valuable role for curcumin, one of the active compounds in turmeric. The researchers reported it to have a beneficial effect against several neurodegenerative disorders including Alzheimer’s disease. First, the scientists induced cognitive dysfunction, oxidative damage, and mitochondrial dysfunction in mice through the use of the chronic administration of D-galactose for 6 weeks (as measured by both the Morris water maze and the elevated plus maze).
Then, after the researchers gave galantamine (5 mg/kg), along with curcumin (15 and 30 mg/kg), for 6 weeks, significant improvement across all fronts was found: cognitive tasks, locomotor activity, oxidative defense, and restored mitochondrial enzyme complex activity. Galantamine and curcumin together significantly decreased D-galactose-induced acetylcholinesterase activity. This indicates that the effects of galantamine and curcumin are at least additive and possibly synergistic.
- Kumar A, Prakash A, Dogra S. Protective effect of curcumin (Curcuma longa) against d-galactose-induced senescence in mice. J Asian Nat Prod Res 2011 Jan;13(1):42-55.
Using the AD Assessment Scale-Cognitive subscale (ADAS-Cog 11), the researchers examined changes from baseline in the 11-item scale. ADAS-Cog 11 tests for a variety of cognitive functions, such as memory, attention, learning, language, reasoning ability, and the ability to visualize spatial relationships.
When the pooled data in the 5–6 month trials was analyzed at the endpoint (determined by reaching maintenance doses), the results were revealing. There were 1,173 galantamine-treated subjects versus 801 placebo-treated subjects. Among galantamine users, according to the criteria, 45.8% were “improved,” 59.5% were “stable,” and 87.6% were in “non-rapid decline.” Among placebo takers, the results were 27.2%, 37.1%, and 69.7%, respectively. These differences were significant.
Improvement and Stability Cue for
Long Term Benefits
At the same time, changes in ADAS-Cog 11 scores versus baseline were –4.9, –4.7, and –2.9 points, respectively (indicating reductions in cognitive decline) for “improved,” “stable,” and “non-rapid decline” galantamine-treated patients (–1.5 points for galantamine recipients overall).
“Improved” or “stable” galantamine-treated patients displayed mean improvement in ADAS-Cog 11 scores over baseline until 18 months after starting treatment, with lessened deterioration thereafter. “Non-rapid decline” galantamine-treated patients exhibiting mean ADAS-Cog 11 scores returned to baseline after approximately 12 months.
In the final analysis, AD subjects who demonstrated improvement, stability, or limited cognitive decline 2–5 months after reaching maintenance doses of galantamine are more likely to experience continued benefit from long-term galantamine therapy.
- Sakurai H, Hanyu H, Kanetaka H et al. Prevalence of coexisting diseases in patients with Alzheimer’s disease. Geriatr Gerontol Int 2010;10:216–7.
- Van Puyvelde K, Mets T. Galantamine (Reminyl) once daily outcome and satisfaction survey (RODOS) in mild to moderate Alzheimer’s disease: A study in a real life population. Geriatr Gerontol Int 2011 Jan 4. doi: 10.1111/j.1447-0594.2010.00674.x. [Epub ahead of print]
- Keller C, Kadir A, Forsberg A, Porras O, Nordberg A. Long-term effects of galantamine treatment on brain functional activities as measured by PET in Alzheimer’s disease patients. J Alzheimers Dis 2010 Dec 14. [Epub ahead of print]
- Kavanagh S, Howe I, Brashear HR, Wang D, Baelen BV, Todd M, Schwalen S. Long-term response to galantamine in relation to short-term efficacy data: pooled analysis in patients with mild to moderate Alzheimer’s disease. Curr Alzheimer Res 2011 Jan 11. [Epub ahead of print]
Will Block is the publisher and editorial director of Life Enhancement magazine.