Veterinary Medicine - July 2008 - (Page V5)

A roundtable discussion and mood disturbances are common with dementia and we often treat both in the elderly. About two dozen FDA-approved antidepressants and as many sedatives are on the market. A lot of new ones have come out in the past few years that help people sleep but are less habit-forming. We can alleviate depression and anxiety in elderly patients much better than we could before. On the other hand, there is always concern about side e ects because the elderly are much more vulnerable to them. We always have to start with a low dose and increase it gradually. Landsberg: Veterinarians may use uoxetine to try to re-establish more normal sleep cycles and a benzodiazepine as a sleep agent in older pets. Are there similarities in how you use these in people? Mischoulon: It is very similar to what we would do. of action of SAMe in the treatment of depression or dementia since many pathways could be involved. Landsberg: Many products used to slow or treat cognitive dysfunction in older pets have antioxidant mechanisms. Does SAMe play an antioxidant role? Bottiglieri: Yes. SAMe is a precursor molecule to the transulfuration pathway that leads to the synthesis of glutathione. Preclinical and clinical studies have shown that after administration of SAMe there is an increase in glutathione in the blood and liver. Other studies have shown that SAMe can modulate glutathione levels and markers for lipid peroxidation in brain tissue.6-8 Landsberg: With aging, is there a change in endogenous SAMe production? Bottiglieri: There is experimental evidence to show that tissue levels of SAMe are signi cantly decreased in 30-month old rats compared to younger rats. The decline in SAMe concentration was evident in most organs, including the brain. Studies in people have also shown that there is an age-related e ect in the concentration of SAMe in cerebrospinal uid (CSF). In the rst year of life SAMe concentrations are relatively high and begin to decline thereafter. Interestingly this decline with age follows the concentration of folate levels in CSF. There have not been any studies, which have looked at SAMe concentrations in blood or CSF from elderly subjects. However, folate levels tend to decline and homocysteine levels tend to increase with advancing age.9-12 Landsberg: In veterinary medicine, we have used SAMe for years in cases of liver disease. We are less familiar with its use as a supplement for the brain. Dr. Mischoulon, tell us about using SAMe and its use for cognition in elderly people. Mischoulon: In people, SAMe has been studied primarily as an antidepressant. There are at least 45 published clinical Table 1. Most common clinical signs of cognitive dysfunction at baseline Increased total amount of sleep during a 24-hour period Decreased attention to surroundings, disinterest, apathy Decreased purposeful activity Loss of formerly acquired knowledge (including elimination behaviors) Intermittent anxiety (apprehension, panting, moaning, shivering) trials examining di erent forms of SAMe. It is generally accepted in the psychiatric eld that SAMe is e ective for depression. Currently, it is one of the more popular over-the-counter agents that people use if they want to selfmedicate for depression. One of the appealing qualities of SAMe, as opposed to some other natural products, is that it doesn’t appear to have any adverse interactions with other medications. My group has focused on using SAMe as an adjunctive agent. We have found that by giving SAMe in addition to another antidepressant, we get a more robust antidepressant response in the patient. We have published a study demonstrating this, and have other such studies in progress. SAMe helps with the whole spectrum of depressive symptoms, including di culties with cognition, memory, and concentration, as well as mood enhancement. SAMe has few adverse e ects and is well tolerated. It is not hepatoxic and is, in fact, bene cial to the liver. In many ways, it is the ideal medication for an elderly person. Not much clinical data on SAMe’s e ect on dementia exist. We know that SAMe de ciencies are associated with increases in compounds that are toxic to the brain. We know that SAMe administration in animals can reverse or attenuate some of the adverse e ects. Landsberg: In clinical practice, we do see some senior pets that appear to be depressed, but in veterinary medicine, we don’t use the term depression except when talking about 83.3% 77.8% 75.0% 72.2% 61.1% A new therapeutic tool: SAMe Landsberg: We now have a new therapeutic tool available for cognitive dysfunction in dogs— S-adenosylmethionine, commonly known as SAMe. Dr. Bottiglieri, please tell us about the molecule itself. Bottiglieri: S-adenosylmethionine (SAMe) is produced naturally in the body and every cell has the ability to synthesize it. In fact de-novo synthesis of SAMe is required because dietary sources do not provide su cient amounts. It is one of the most versatile molecules involved in a myriad of biochemical reactions, second only to adenosine triphosphate (ATP) as a pivotal molecule in biochemistry and cellular function. It is formed when methionine and ATP combine. The function of SAMe is to donate a methyl group to small molecules such as the neurotransmitters dopamine and epinephrine and to macromolecules, such as DNA, proteins, and lipids. The effects of methylation are as varied as the molecules that are methylated, so it is difficult to know the exact mechanism 5

Table of Contents Feed for the Digital Edition of Veterinary Medicine - July 2008

Veterinary Medicine - July 2008 Contents Leading Off Practical Matters Idea Exchange Clarification Dental Corner The Diagnostic Approach to Hematuria Guidelines for Evaluating Hypercalcemic Cats CE Form Advertiser Index Marketplace/Classifieds Mind Over Miller

Veterinary Medicine - July 2008

For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.