Galantamine may help to . . .

Enhance Your Cognitive Visual Skills
New evidence indicates that galantamine, a natural
cholinergic agonist, can improve certain aspects of vision
By Will Block

The eye sees only what the mind is prepared to comprehend.
—Henri Bergson

n 1906, Alois Alzheimer—the German psychiatrist and neuropathologist for whom Alzheimer’s disease is named—first observed the unusual behavioral symptoms that would thereafter characterize “his” disease in a woman at a Frankfurt asylum. Upon the patient’s death, Dr. Alzheimer sent her records and brain to a Munich laboratory, where he was also employed. There, using staining techniques, the two most important physical characteristics of the disease—still considered so to this date—were identified: amyloid plaques and neurofibrillary tangles. The symptoms Alzheimer had observed in his patient included, among others, a loss of short-term memory and diminished visual perception.

Visual Perception Decline Linked to Cognitive Dysfunction

Since the early 20th Century, studies have shown that visual perception is altered in Alzheimer’s disease (AD) patients, and that visual problems are linked to diminished cognitive function.1 Other evidence has shown that auditory perception affects cognition,2 and that perception is altered in AD and mild cognitive impairment (MCI).3,4 The first author of the last two studies cited, Arun L.W. Bokde, PhD, a principal investigator at Trinity College Institute of Neuroscience in Dublin, is currently the research deputy of the team put together by Harald Hampel, MD, MSc, Professor and Chair of Psychiatry at the Trinity School of Medicine. It is the work of this team, specializing in neuroimaging research with a strong focus on neurodegeneration—particularly Alzheimer’s disease—that we will discuss.


Since the early 20th Century,
studies have shown that visual
perception is altered in Alzheimer’s
disease (AD) patients, and that visual
problems are linked to diminished
cognitive function.


MCI Increases the Risk of Developing AD

In their paper on the alteration of perception in MCI,4 Bokde et al. confirm that those with MCI have a higher risk of developing AD than healthy controls. In one recent study, 25% of those with MCI and high cytochrome c levels, a measure of apoptosis, converted to AD within 11 months.5 Overall, according to Michael Ewers, a senior scientist with Hampel’s team, only 15% of people with mild cognitive impairment will develop full-blown AD, while 20% revert to normal.6 However, if there is sensory impairment, cognitive impairment is likely to be more severe, and the conversion rates are likely to he higher.

Bokde et al. measured activation changes in the visual systems of two groups, one comprised of 16 MCI subjects and another with 19 control subjects. All subjects were given two tasks, one involving face matching and the other location matching. When brain activation was calculated using functional magnetic resonance imaging (fMRI) [see sidebar], the researchers found no differences in task performance. While the control group selectively activated the ventral pathway during the face-matching tasks and the dorsal pathway during the location-matching tasks, the MCI group did not. However, the MCI group had greater activation than the control group in the left frontal lobe during the location matching task.

Better Than X-Ray Vision

Magnetic resonance imaging (MRI) is a noninvasive technique that has greatly improved medical diagnostic practice by providing amazingly detailed images of virtually all the internal organs of the body. It is especially useful for looking inside structures that are surrounded by bone, notably the brain and spinal cord. Functional MRI (fMRI) goes standard MRI one better by revealing vital information about metabolism, i.e., how a particular organ or part of an organ is functioning while the scan is being conducted.

Unknown to most patients is that “magnetic resonance imaging” is a euphemism coined for the benefit of those who are easily (and irrationally) frightened by the word nuclear. Based on Nobel Prize-winning discoveries by nuclear physicists in the 1940s, the technique was originally called nuclear magnetic resonance (NMR), a name that better reflects its actual scientific roots. It is still called NMR by chemists and physicists, who have been using it for half a century in the laboratory to study the structures and interactions of molecules.

What does fMRI measure?

  1. In response to a sensory stimulus or a cognitive process, neurons fire and a sequence of events increases local cerebral metabolism.

  2. An increase in neural activity (and metabolism) causes an increased demand for oxygen for which the vascular system increases the amount of oxygenated haemoglobin relative to deoxygenated haemoglobin.

  3. fMRI measures changes in the Blood Oxygen Level Dependent (BOLD) signal due to changing in neural activity.

Three advantages of MRI over computerized tomography (CT) are: (1) MRI uses diagnostic radiation that is harmless (a radio-frequency field coupled with a strong magnetic field) rather than x-rays, which can damage the tissues they penetrate; (2) MRI can “see” soft tissues more clearly than CT can; and (3) MRI can distinguish between healthy and diseased tissues better than CT can. Nonetheless, CT is still a valuable imaging technique, as are various others, each of which has special strengths.

A useful variant of CT is electron beam computed tomography (EBCT), in which, yes, electron beams are used instead of x-rays. (For an example of the use of EBCT in heart disease, see “Is There Too Much Calcium in Your Arteries?” in the November 2004 issue.)

Another powerful modern imaging technique is positron emission tomography (PET), in which a radioactive compound with an affinity for a particular part of the body—usually the brain or heart—is injected into the bloodstream. As the radioactive atoms in the compound decay, they emit subatomic particles called positrons (positively charged electrons), whose interactions with other particles release gamma radiation. This radiation is recorded to build up an image of the part of the body in question.

A landmark in neurological research is the recent development of a radioactive imaging compound (a type of dye) that will selectively attach itself to the gunky, proteinaceous deposits called amyloid plaques in the brains of Alzheimer’s victims.1 This makes the plaques visible via a PET scan of the living patient, whereas previously the only way to see the plaques was at autopsy.

When the new technique, which is still in the research stage, enters clinical practice several years from now (assuming that all goes well in the necessary clinical trials and the regulatory maze), it will enable doctors, for the first time, to obtain hard evidence of this type of brain damage in Alzheimer’s disease relatively early in the game and to monitor the efficacy of whatever treatment is prescribed. Stay tuned.

Reference

  1. Klunk WE, Engler H, Nordberg A, et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound-B. Ann Neurol 2004;55:306-19.

There were no areas of increased activation in the control group compared with the MCI group. The MCI group, as a compensatory mechanism, activated both visual pathways and increased activation in the left frontal lobe during the location matching task compared with the healthy controls. To the researchers’ knowledge, this is the first study examining visual processing in MCI. Conclusion: visual perception is altered in MCI.

Can Galantamine Enhance Visual Perception?

Over the last 10 years, we have written extensively about galantamine in the pages of this publication (81 articles to date), and to the best of our knowledge, the benefits of galantamine on visual perception have not previously been shown, except in one small study on its use in schizophrenia,7 but not for AD or MCI.

A new study conducted by Bokde et al. has sought to examine whether the active cholinergic agent galantamine can help that aspect of cognitive dysfunction which involves vision.8 Up until now, galantamine has been found to improve cognition in mild to moderate and even severe AD. Starting with 8 subjects with mild AD, analysis was performed on 5 subjects who were given open-label treatment with galantamine for 3 months. All subjects began with an fMRI scanning session a few days before start of treatment. The treatment was 4 mg twice a day for the first month, 8 mg twice a day for the second month, and 12 mg twice a day for the last month. At the end of the 3 months, the patients had a second fMRI imaging session. The goal was to examine changes in brain activation owing to treatment.


Visual perception is altered in MCI.


There were two tests of visual perception. The first test was a face-matching task, a measure of activation along the ventral visual pathway. The second test was a location-matching task, a measure of neuronal function along the dorsal pathway. For each of these tests functional magnetic resonance imaging was used to determine brain activation.

There were no differences in the Consortium to Establish a Registry for Alzheimer’s Disease battery—the object of which is to track task performance and cognitive scores—before or after treatment. While there were no differences in activation for the face-matching task after treatment, in the location-matching task, there was a statistically significant decrease in activation along the dorsal visual pathway attributable to galantamine treatment.


There was a statistically significant
decrease in activation along the
dorsal visual pathway attributable to
galantamine treatment.


In a previous study, AD patients had higher activation along the same pathway in the location-matching task compared with healthy controls. Thus, the data in the current study indicate that galantamine treatment leads to more efficient visual stimuli processing, or results in compensatory mechanism changes in mild AD. Bokde et al.8 may have found a specific effect of galantamine on the dorsal visual pathway during the location-matching task, because the effects of galantamine were situated in areas where there are differences between mild AD patients and controls.


Galantamine treatment leads to more
efficient visual stimuli processing, or
results in compensatory mechanism
changes in mild AD.


The Story of the Empty Room

Have you ever found yourself in a room, not knowing (having forgotten) why you went there? It’s a common experience for most of us as we get on in years, and it becomes even more so with age-related memory/cognitive decline or MCI. Once again, visual perception is altered in MCI and visual perception decline is linked to cognitive dysfunction. While the current study shows that galantamine enhances visual stimuli processing in mild AD, it remains to be seen what it can do for mild cognitive impairment (MCI) in this regards. Keep your eyes wide open and remember that “The eye[s] sees only what the mind is prepared to comprehend.”

References

  1. Cronin-Golomb A, Corkin S, Growdon JH. Visual dysfunction predicts cognitive deficits in Alzheimer’s disease. Optom Vis Sci 1995;72:168-76.
  2. Uhlmann RF, Larson EB, Rees TS, et al. Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. JAMA 1989;261:1916-9.
  3. Bokde ALW, Lopez-Bayo P, Born C, et al. Functional abnormalities in the ventral and dorsal visual pathways in Alzheimer’s disease patients: an fMRI Study. 2007. In press.
  4. Bokde AL, Lopez-Bayo P, Born C, Dong W, Meindl T, Leinsinger G, Teipel SJ, Faltraco F, Reiser M, Möller HJ, Hampel H. Functional abnormalities of the visual processing system in subjects with mild cognitive impairment: an fMRI study. Psychiatry Res 2008 Aug 30;163(3):248-59. Epub 2008 Jul 30.
  5. Papaliagkas VT, Anogianakis G, Tsolaki MN, Koliakos G, Kimiskidis VK. Prediction of conversion from mild cognitive impairment to Alzheimer’s disease by CSF cytochrome c levels and N200 latency. Curr Alzheimer Res 2009 Jun;6(3):279-84.
  6. Mulvihill M. Harald Hampel and his team zero in on the disease's biomarkers. http://www.the-scientist.com/2008/07/01/s70/1.
  7. Lee SW, Lee JG, Lee BJ, Kim YH. A 12-week, double-blind, placebo-controlled trial of galantamine adjunctive treatment to conventional antipsychotics for the cognitive impairments in chronic schizophrenia. Int Clin Psychopharmacol 2007 Mar;22(2):63-8.
  8. Bokde AL, Karmann M, Teipel SJ, Born C, Lieb M, Reiser MF, Möller HJ, Hampel H. Decreased activation along the dorsal visual pathway after a 3-month treatment with galantamine in mild Alzheimer disease: a functional magnetic resonance imaging study. J Clin Psychopharmacol 2009 Apr;29(2):147-56.

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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