Treatment of Alzheimer's Disease-Selegiline and AD-Part II

(11/22//06)-This month marks the 100th anniversary of Alois Alzheimer's report on his senile patient, Auguste D. Her brain had stringy tangles inside neurons and "senile plaques" around them.

(2001)- This web site is always on the lookout for information on the treatment of Alzheimer's disease (AD) since the number of people in the US with Alzheimer's disease will increase to 5 million by the year 2000. As life span increases, more and more people will suffer from Alzheimer's and related neurovascular disorders. Treatment regimens are sorely needed.

In the article below we mentioned the MAO-B inhibitor selegiline as a possible treatment in Alzheimer disease. We cited the Sano study, which used a combination of selegiline and vitamin E as treatment for memory symptoms associated with Alzheimer disease. A study* from the Czech group under Vaclav Filip did a long-term randomized placebo-control trial of selegiline. It found it "has a long-term beneficial effect on Alzheimer’s disease on memory modalities that reflect the function of the prefrontal areas of the brain, which are rich in dopamine receptors. The delayed appearance of difference between selegiline and placebo support the notion that mechanism of action is through neuronal rescue or neuroprotection". The long-term treatment improved cognitive and behavioral functions in those diagnosed with mild to moderate Alzheimer disease. Object and spatial memory showed pronounced improvement. The brain area responsible for these functions is the prefrontal lobe, which is also rich in dopamine receptors, which might be where selegiline is acting.

Adverse effects noted with the administration of selegiline include an increase in irritability, restlessness and occurrences of uncooperativeness. The authors indicate that decreasing the dose of selegiline can control this.

*The reference for this study is Journal of Psychiatry and Neuroscience 1999; 24(3): 234-243.

We recently came across a study being done by members of the Alzheimer's Disease Cooperative Study group under Dr. M. Sano (N. Eng. J. Med. 1997. April 24; 336:1216-22.) entitled "A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's Disease." The goal was to compare the effectiveness of selegiline, alpha-tocopherol or a combination of both with placebo in slowing the clinical progression of AD. Included were 341 patients (mean age 73 years, 65% women) with probable AD of moderately severity, who were free of other central nervous system diseases, were not taking psychoactive medications and were living at home or in a supervised setting without skilled nursing attendants. The dose of selegiline was 5 mg BID and Vitamin E 1000IU BID.

The outcome measurements they used to evaluate the effects of this drug regimen were the time to the occurrence of any one of the following: death, institutionalization, and loss of ability to perform 2 of the three basic activities of living or severe dementia. Secondary outcome measures include cognition, ADL, behavior and presence or absence of EPS.

They concluded that selegiline or alpha-tocopherol slowed the progression of AD in patients with moderate impairment.

This study adds to evidence that neuronal loss in AD is mediated by inflammation (involving free radicals) and that anti-inflammatory drugs may delay the onset and progression of AD.

Other Studies

Estrogen may play a neuroprotective role in women. However, concern about the efficacy, safety and compliance problems of these agents currently preclude their prescription in Alzheimer's Disease according to experts in this field.

There is a need for robust evidence that a relatively inexpensive, non-prescriptive antioxidant slows progression of AD.

(See: Perry, WJ, Perry, P, Slahelen, HB. The relationship between antioxidants and memory performance in the old and very old. J Am Geriatric Soc. 1997; 45:718-24)

Another "player" in the field

A new drug that is near completion of the testing process is Metrifonate, a long lasting inhibitor of acetylcholinesterase, the enzyme responsible for breaking down acetylcholine, which many researchers believe plays a role in memory loss.

Ian Hinmarch, Ph. D., professor of human psychopharmacology at the University of Surrey noted: "Alzheimer's disease is typically characterized by a syndrome of dementia, including loss of intellectual functions including memory, judgment and reason; a lowering of general mood; a disturbance, sometimes violent, of personality and a progressive worsening of the capacity to perform the general activities of everyday living…(metrifonate) will be a great benefit since the drug has the ability to delay or ameliorate the rate of decline of the patient." (Medical Herald, December 1997). The FDA to date has not approved this drug.

We repeat this caveat: No drug has been found to reverse the progress of the syndrome of Alzheimer's Disease. Some of the drugs may prolong the decline process in some individuals who have the 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: Part IV-Alternative Treatments for AD
See: Part V-Possible New Drugs for Alzheimer's Disease
See: Part VI-Early Diagnosis
See: Part VII-Metrifonate
See: Part VIII-Implications of a Longer Life Expectancy
See: Alzheimer's Part IX-Ethical Care Principles
See: Alzheimer's Disease-Part X-Estrogen and Alzheimer's Disease
See: Alzheimer's Disease Part XI-Pocket Smell Test (PST)
See: Alzheimer's Disease Part XII-MAO-B
See: Alzheimer's Disease Part XIII -Critical Flicker Fusion Threshold Test
See: Alzheimer's Disease Part XIV-Donepezil
See: Alzheimer's Disease Part XV-Cerebrolysin
See: Alzheimer's Disease Part XVI-MCI
See: Alzheimer's Disease Part XVII-Summary
See: Alzheimer's Disease Part XVIII-NO Releasing NSAIDs
See: Alzheimer's Disease Part XIX-Vitamin E
See: Alzheimer's Disease-Part XX-Clinical Trials
See: Alzheimer's Disease-Part XXI- AD and the Brain
See: Alzhemer's Disease-Part XXII-Lewy Bodies Disease
See: Alzheimer's Disease-Part XXIII-HMG
See: Alzheimer's Disease-Part XXIV-A Prequel
See: Alzheimer's Disease-Part XXV- Plus Psychosis
See: Alzheimer's Disease-Part XXVII- AD and Diabetes
See: Alzhemeir's Disease-Part XXVIII - Insulin and AD



By Harold Rubin, MS, ABD, CRC, Guest Lecturer
updated November 22, 2006

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