Namenda (memantine) and PSP

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A group member with progressive supranuclear palsy asked me recently what I knew about two Alzheimer’s drugs — Aricept and Namenda — in treating PSP. I posted a few days ago about Aricept, which is an acetylcholinesterase inhibitor.

Here is a link to that post:

https://www.brainsupportnetwork.org/aricept-and-psp-2001-study

This post is about Namenda, which is a chemical receptor agonist that appears to work by regulating the activity of glutamate, a messenger chemical in the brain. Glutamate plays an essential role in learning and memory.

I found an interesting fact sheet on Namenda from the Alzheimer’s Association:

http://search.alz.org/Resources/FactSheets/FSmemantine.pdf

According to this Alzheimer’s Association publication, Namenda is approved for moderate to severe AD, which is defined as initial scores ranging from 3 to 14 on the Mini-Mental State Exam or MMSE. The FDA’s approval was based on the evidence provided by two drug-company studies. In one study, those taking Namenda showed a small but statistically significant benefit in a test of their ability to perform daily activities and on the Severe Impairment Battery when compared to those taking a placebo. In another study of people who had previously taken Aricept for 6 months, those taking Namenda showed a statistical benefit in performing daily activities and on the Severe Impairment Battery when compared to those taking a placebo and Aricept.

From this publication I learned that Namenda is NOT approved for mild Alzheimer’s. I will take this information to my father’s neurologist next month. My dad has mild to moderate dementia, I would say, yet he’s been on Namenda for 2 years.

Robin

“Health Challenges & Recommendations for the Older Adult”

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Stanford University (stanford.edu) sponsored a 3-part series on geriatric health in May. The first evening, May 11, 2006, included this lecture:

“Health Challenges & Recommendations for the Older Adult”
Speaker: Peter Pompei, MD, Assoc Prof of Geriatric Medicine, Stanford Univ

Local support group member Karen D. gave me her notes on the lecture. This post attempts to summarize some of the key points in that lecture.

Robin
——————

Karen’s Notes from

“Health Challenges & Recommendations for the Older Adult”
Speaker: Peter Pompei, MD, Assoc Prof of Geriatric Medicine, Stanford University
May 11, 2006

Dr. Pompei distributed a document on “Aging parents: Five warning signs of health problems.” You can find a copy of this online at:

mayoclinic.com/health/aging-parents/HA00082

The five warning signs are:
* unintended weight loss
* difficulties maintaining their home (so that the home becomes unsafe)
* failure to keep up with daily routines and personal appearance
* poor mood (down or depressed)
* difficulty getting around (which means that they have difficulty caring for themselves)

Dr. Pompei introduced the concept of homeostenosis. When we were young, we could adapt to stressful environments. But when we’re older, we can’t bounce back.

Dr. Pompei also distributed an article in the April 2006 issue of Geriatrics magazine, titled “Health promotion in older adults: Promoting successful aging in primary care settings.” You can find a copy of this online at:

www.geri.com/geriatrics/data/articlestandard/geriatrics/152006/318873/article.pdf

The article states that:

“Although achieving and maintaining health is influenced by many factors,
one of those is within the grasp of almost everyone: Making wise health
choices… (These) choices…can be summarized by an easy to remember
phrase: eat right, eat less, and exercise more.”

(That particular issue of Geriatrics magazine has a number of interesting articles, including one on exercises for the frail and home bound:
www.geri.com/geriatrics/data/articlestandard/geriatrics/202006/327139/article.pdf.)

Dr. Pompei recommended two websites with health information:

American Geriatrics Association
www.healthandage.com

Merck Foundation
www.merckmedicus.com

The lead article on the American Geriatrics Association website is how
physical fitness can fight off dementia.

During the Q&A period, someone asked how a patient should be told he/she is losing it. Dr. Pompei’s answer was: be forthright but show that the patient may not understand.

“Foiling Chemical Event May Combat Brain Breakdown”

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This post is about an interesting article on preventing misfolded protein accumulations (which occurs in AD, PD, and many related diseases), protecting an enzyme (called called protein disulphide isomerase), and stopping a chemical (nitric oxide) from wreaking havoc in the brain.

The Bloomberg News article talks about a study just published in the journal Nature. The aarticle notes:

“While previous studies showed that nitric oxide can be involved in the degeneration of brain cells through a variety of mechanisms, the new study shows a previously unrecognized relationship between the chemical and protein misfolding.”

Here’s a link to the article:

www.bloomberg.com/apps/news?pid=10000082&sid=avdCh4_MT55U

Foiling Chemical Event May Combat Brain Breakdown, Study Says
Bloomberg.com
May 24, 2006

Aricept and PSP (2001 study)

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A group member with progressive supranuclear palsy (PSP) asked me recently what I knew about two Alzheimer’s drugs — Aricept and Namenda — in treating PSP.

I’ve done a little bit of digging on the subject today and found a randomized, double-blind, placebo-controlled study funded by NIH done in 2001. The abstract follows.

Bottom line — these MDs do not recommend that those with PSP take Aricept (donepezil) because although the “Double Memory Test” scores will improve, status of activities of daily living (ADL) and mobility scores will worsen significantly.

I will search a bit on Namenda over the next few days. Since Namenda is NOT an acetylcholinesterase inhibit (Aricept is), this study will not apply.

Robin

———————–
www.neurology.org/cgi/content/abstract/57/3/467
Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy

I. Litvan, MD; M. Phipps, BA;, V. L. Pharr, MA; M. Hallett, MD; J. Grafman, PhD; and A. Salazar, MD

From the Cognitive Neuropharmacology Unit (Dr. Litvan, M. Phipps, and V.L. Pharr) and the Defense and Veteran Head Injury Program (Dr. Salazar), Henry M. Jackson Foundation; and the Medical Neurology Branch (Dr. Hallett) and the Cognitive Neuroscience Section (Dr. Grafman), National Institute of Neurological Disorders and Stroke, National Institutes of Health. (Robin’s note: Dr. I. Litvan is now at the University of Louisville in KY.)

Objective:­ There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age ± SD; 65.7 ± 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial.

Methods:­ Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status.

Results:­ Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened.

Conclusion:­ The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population.

“A Surprising Clue to Parkinson’s” (MIT Technology Review)

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I saw an article in the May/June ’06 issue of Technology Review, an MIT publication, related to protein aggregations in those with PD and other diseases. What I found interesting was the fact that there is not scientific agreement over whether abnormal protein aggregations in the brain are a bad thing. The author says that the MIT biotechnology study demonstrates “that increased protein aggregation can improve the health of cells modeling neurodegenerative disease.”

That led to a related article published on the Technology Review’s website on 3/7/06. Excerpts from that March article:

“It’s easy to distinguish a healthy person from a person with advanced Parkinson’s: the Parkinson’s sufferer has large clumps of proteins in his or her brain cells. Scientists disagree, however, about the nature of these clumps. Some contend that they lead to the massive neuronal cell death and resulting movement disorders in Parkinson’s, others that the clumps are merely a byproduct of the disease — and some scientists contend that the clumps are actually protective, sequestering toxic proteins so they can’t hurt the cell. Mounting evidence points to the last possibility.”

“Existing research already suggests that the biggest clumps, known as inclusions, are helpful. Cells that form clumps of the mutant Huntington protein, for example, survive longer than clump-free cells. Now MIT scientists have discovered a compound that increases clumps in cell models of Huntington’s and Parkinson’s disease and makes the cells healthier. Scientists aren’t sure how the compound works, but they think it might be helping cells get rid of toxic forms of the proteins floating around in the cell by isolating them into clumps.”

Here’s a link to the older article:

www.technologyreview.com/read_article.aspx?id=16517&ch=biotech

A Surprising Clue to Parkinson’s
Drugs that boost the protein clumping that occurs during neurodegenerative disease could provide a new route to treatment.
Technology Review (MIT)
By Emily Singer
March 7, 2006

And a link to the newer article:

www.technologyreview.com/read_article.aspx?ch=biotech&sc=&id=16825&pg=2

A Curious Clue to Parkinson’s
Drugs that boost protein aggregation could provide a new route to treatment
Technology Review (MIT)
May/June 2006