Monoamine Oxidase-B Inhibitors
Role in Treating Alzheimer’s Disease-Part XII of a XXVIII Part Series
As readers of this series know, there are three drugs presently approved for treatment of mild to moderate Alzheimer’s disease: tacrine (approved in 1993), donepezil (approved in 1997) and rivastigmine (approved in April 2000). Galantamine will be approved in the near future. Others in the works include the Cox-2 inhibitors, naproxen and rofecoxin as well as gamma and beta-secretase enzymes blockers. An anti-amyloid vaccine is also in the works. Estrogen appears not to work once the disease has started but may have a protective effect before cognitive decline starts. Vitamin E appears to play some part in delaying neuronal dysfunction. None of the drugs now available cures the disease. They appear to retard the progress of Alzheimer's disease in a number of the cases depending when in the process of the disease the medication regimen is started. The difficulty is in identifying the very beginning stages of Alzheimer’s disease, distinguishing between normal process of cognitive decline and process of decline associated with other dementias.
In the August 21, 2000 issue of Neurobiology of Aging (Vol. 21(2): 343-348) Thomas suggests that "stimulation of nitric oxide production by L-deprenyl could contribute to the enhancement of function in Alzheimer’s disease". L-deprenyl (Selegiline) is a monoamine oxidase-B inhibitor (MAO-B) which can elevate dopamine levels that are depleted. It is an antidepressant, inhibiting both MAO-A and MAO-B. The MAO-B inhibitors are able to set in motion protective effects on both vascular and neural tissue. See our article on Selegiline and Vitamin E in this series.
Epidemiological evidence now indicates that there are vascular risk factors associated with the cognitive impairment seen in Alzheimer’s disease. The presence of cerebrovascular disease magnifies the presence and severity of the clinical symptoms of Alzheimer’s disease. Nitric oxide preserves the integrity of vascular endothelium by enhancing an endothelium-derived relaxing factor, inhibiting vascular incidents. Nitric oxide may hook up with another signaling agent, carbon monoxide, which also exerts certain effects within and without the vascular system. Carbon monoxide is liable to self-regulation by nitric oxide. These two messenger systems interact in a varied manner, influencing each other in a synergistic or antagonistic fashion depending on conditions. Prevention of vascular incidents could reduce the incidence of cognitive decline in Alzheimer’s disease exacerbated by vascular infarctions. There may be a role for these two signaling agents in the prevention of some subtypes of Alzheimer’s disease
Alzheimer’s disease is a heterogeneous and multifactorial disorder. Its frequency increases with age, ranging from 25 to 50% in those who are over 85 years of age. The frequency rates are higher for women over 85 than for men.
Vascular risk factors appear in Alzheimer’s disease patients. This conclusion comes from autopsy reports which indicate that up to one-third of patients with Alzheimer’s disease have coexistent cerebral infarctions. Other studies have indicated additional lesions (See: Monique M. B. Breteler. Vascular Risk Factors for Alzheimer's Disease: An Epidemiologic Perspective. Neurobiology of Aging 2000; 21:153-160.) There is a need to clarify this observed relationship between vascular and neurodegenerative diseases and zero in on treatment modalities that can be effective in stopping the progress of debilitating neurodegenerative disorders such as Alzheimer’s disease. The present drugs, the acetylesterase inhibitors are a beginning step. They are all we have at the moment, with the possibility of certain complementary or alternative treatments that still need to undergo rigorous research testing
With a growing aging population, preventative measures need to be found which maximize the patients good and minimize harm. It is up to researchers to identify potential risk factors, educate individuals in preventative steps to be taken, develop interventions that target the process of the developing disease and insure that all individuals who need the treatment will have access to it.
For our other articles on Alzheimer's Disease-
See: Alzheimer's Disease
Part I-Medications for Alzheimer's.
See: Alzheimer’s Disease Part II- Selegiline and AD.
See: Alzheimer's Disease
Part III- Use of Gingko Biloba in
memory problems of Alzheimer patients.
See: Alzheimer's Disease
PartIV-Alternative Treatment.
See: Alzheimer's Disease
Part V-Possible New Drugs for Alzheimer's Disease Treatment.
See: Alzheimer's Part VI -Early Diagnosis.
See: Alzheimer's Part VII -New Medication-Metrifonate
See:Alzheimer's
Harold Rubin, MS, ABD, CRC, Guest Lecturer
July 1, 2000
http://www.therubins.com
email: hrubin12@nyc.rr.com or rubin@brainlink.com