Tau aggregation, 12/08 research (Japan)

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Here’s the most interesting part of this new abstract on research into tau aggregation: “It is believed that aberrant modifications of tau, including phosphorylation, truncation, and conformational changes, induce filamentous aggregation. However, the mechanism underlying the conversion of tau protein from a soluble state to one of insoluble aggregates still remains elusive. ”

Current Alzheimer Research. 2008 Dec;5(6):591-8.

Tau oligomerization: a role for tau aggregation intermediates linked to neurodegeneration.

Sahara N, Maeda S, Takashima A.
Laboratory for Alzheimer’s Disease, RIKEN Brain Science Institute, Wako-shi, Saitama, Japan.

Intracellular accumulation of filamentous tau proteins is a defining feature of neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, corticobasal degeneration, Pick’s disease, and frontotemporal dementia with Parkinsonism linked to chromosome 17, all known collectively as tauopathies. Tau protein is a member of microtubule (MT)-associated proteins. Tau is a highly soluble and natively unfolded protein dominated by a random coil structure in solution. It is believed that aberrant modifications of tau, including phosphorylation, truncation, and conformational changes, induce filamentous aggregation. However, the mechanism underlying the conversion of tau protein from a soluble state to one of insoluble aggregates still remains elusive. The importance of tau aggregation intermediates (e.g. tau dimer, tau multimer, and granular tau oligomer) in disease pathogenesis was suggested by recent studies. Here, we review the latest developments in tracking the structural changes of tau protein and discuss the utility improving our understanding of tau aggregation pathway leading to human tauopathies.

PubMed ID#: 19075586 (see pubmed.gov for abstract only)

POLST, DNR, Advance Health Care Directive, etc.

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A few of us braved the rain Sunday night to attend the support group meeting.  I thought I would pass on one of the short discussions some of us had, and give you some related links to forms and info available online.

Cheri said that several people told her she could get a DNR (do not resuscitate) form from her doctor.  Well, she asked two doctors and neither had such a form.  She said that she had been advised to get such a form for her husband and sign it because if you don’t have such a form emergency medical personnel can go down a path the patient and family don’t want to go down.  However, Cheri pointed out that even if you have a signed DNR, the healthcare POA (power of attorney) can always say “we want resuscitation efforts to be made.”  Having a signed DNR gives the healthcare POA some flexibility.  Not having a signed DNR puts all the responsibility on the POA and gives him/her no flexibility. (I hope I’ve adequately described the point.)

Ted and I talked about our preference for the POLST form to a simple DNR form.  POLST stands for Physician Orders for Life-Sustaining Treatment.  It is signed by an MD, and serves as an MD’s instructions for what sorts of treatment anyone has determined he/she wants to have.  Paramedics, RNs, and MDs will accept and take instructions from the POLST.*  The POLST goes through a few more scenarios than just the person-is-not-breathing-and-has-no-pulse scenario.  For example, it asks what level of treatment should a person have — full treatment, limited treatment, or comfort measures only.  It asks if antibiotics are to be included in comfort measures.  It asks if intubation is to be included with full treatment.  It does NOT have as many scenarios, however, as “Five Wishes.”  And, in contrast with “Five Wishes,” the POLST is signed by an MD so these are “doctors’ orders.”

You can find general info on POLST at polst.org; this is a national effort that started at Oregon Health & Science University.  The POLST has recently become usable in California. State-licensed facilities are now being required to have a POLST form on all residents.  [Editor’s note:  you can now find California’s form at capolst.org.]

The POLST is a great form of anyone with a neurodegenerative condition or terminal illness to have completed and signed by his/her MD.

For the non-neurodegenerated, there’s the Advance Health Care Directive.  In our state, the California Medical Association has an Advance Health Care Directive Kit.  The cost is $5.  I have a few more free copies left; let me know at the next support group meeting if you want to get a copy from me.

This question-and-answer from the California Medical Association website may be of interest:

#18 Q:  I have reached a point in my life that I don’t want the paramedics to give me CPR. Will this Advance Health Care Directive keep this from happening?

#18 A:  If the paramedics are made aware of your Advance Health Care Directive before they start resuscitative efforts, and the Advance Health Care Directive clearly instructs them not to start these efforts, your wishes should be respected. You may also want to complete the “Prehospital Do Not Resuscitate (DNR)” form and obtain a “Do Not Resuscitate– EMS” medallion approved by California’s Emergency Medical Services Authority. You may order copies of the DNR form (which includes instructions on ordering the medallion) from CMA publications.

If someone signs a DNR form, it means that they do not want CPR used.  The DNR form for use in California can be ordered from the California Medical Association.  The cost is $2.  The CMA has a two-page brochure on the effectiveness and risks of CPR.

As for the Five Wishes document….  As far back as 2005, one of our founding group members, Storme, discusses it at most support group meetings she attends.  She has completed the form herself, and worked with her mother to complete the form.  Hearing Storme, many other group members have completed the form, including me. More recently, I heard Dr. Melanie Brandabur, a neurologist at The Parkinson’s Institute in Sunnyvale, recommend it.

Five Wishes is useful to fill out, and review with your healthcare POA.  This presents many scenarios, describing in detail things you may and may not want.  It addresses your medical, personal, emotional and spiritual wishes.  It is an invaluable resource for your healthcare POA, if you are unable to communicate your wishes.  The cost is $5.

Beneath my name, I’ve provided all the links you’ll need.  Here’s where you can get general info, find the POLST form for CA, learn about Five Wishes, order the CMA AHCD Kit, order the DNR form, and all the stuff described above.

Happy planning!
Robin

* Paramedics and RNs cannot take instructions based on a Living Will and they may not take instructions from any other Advance Directive you may have.  In the absence of a DNR or POLST, paramedics may be required to perform CPR if they have no MD’s orders to the contrary.

—————————

POLST:
polst.org

Patients and Families FAQ on POLST:
www.ohsu.edu/ethics/polst/patients-families/faqs.htm

POLST form for CA:
[Editor’s note:  the form is now at capolst.org]

Five Wishes from Aging with Dignity:  (cost is $5)
www.fivewishes.org/

Info on the CMA Advance Health Care Directive Kit:
www.cmanet.org/publicdoc.cfm?docid=7&parentid=4

View a “Sample” Copy of the CMA AHCD Kit:  (unfortunately you can’t print a usable copy)
www.cmanet.org/upload/AdvDir2003Finalwatermarked.pdf

Order the CMA AHCD Kit:  (cost is $5)
www.cmanet.org/bookstore/product.cfm?catid=12&productid=154

Order the Pre-Hospital Do Not Resuscitate (DNR) form:  (cost is $2)
www.cmanet.org/bookstore/product.cfm?catid=12&productid=59

View the CMA’s brochure on CPR:
www.cmanet.org/upload/cma_cpr_brochure.pdf

Family Caregiver Alliance Fact Sheet on end-of-life decision making:
www.caregiver.org/caregiver/jsp/content_node.jsp?nodeid=401

Researchers Identify An Underlying Cause Of Pneumonia in PD

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This news about the underlying cause of pneumonia in those with PD may be of interest to some. Presumably these findings apply to the atypical parkinsonism world as well. This press release from mid-September ’08 is from the University of Pittsburgh Medical Center.

http://www.upmc.com/MediaRelations/News … nsons.aspx

Pitt Researchers Identify An Underlying Cause Of Pneumonia Common In Parkinson’s Disease Patients

PITTSBURGH, September 17, 2008 — Impaired coordination between breathing and swallowing may be the underlying cause of aspiration pneumonia in patients with Parkinson’s disease, report researchers from the University of Pittsburgh School of Medicine in a recent issue of the journal Dysphagia.

At least half of all Parkinson’s patients report having difficulty swallowing, and a higher percentage show swallowing abnormalities on X-ray tests. Aspiration pneumonia, a leading cause of death for individuals with Parkinson’s, often develops as a complication of mealtime swallowing problems, leading to the inhalation of food and drink. The high prevalence of swallowing problems and risk of aspiration pneumonia in these patients may be largely due to flawed breathing and swallowing patterns, according to the researchers.

The findings, marking a significant step toward preventing aspiration pneumonia in patients with Parkinson’s, indicate that swallowing problems may be respiratory-based as well as neuromuscular-based, helping to explain why Parkinson’s medications do not consistently help to improve swallowing function.

“Most Parkinson’s patients don’t know they have swallowing problems ­ even though aspiration pneumonia often is a severe complication of the disease ­ and Parkinson’s drugs most often do not improve these patients’ swallowing function,” said Roxann Diez Gross, Ph.D., principal investigator and assistant professor in the Department of Otolaryngology at the University of Pittsburgh School of Medicine. “Now that we know the respiratory system may play an important role in swallowing problems in patients with Parkinson’s disease, we can develop therapies to help these patients re-coordinate breathing and swallowing patterns to improve swallowing function and possibly avoid aspiration pneumonia,” said Dr. Gross, who also is a speech language pathologist and director of the Swallowing Disorders Center at the University of Pittsburgh Medical Center’s (UPMC) Department of Otolaryngology.

Dr. Gross, an expert in swallowing and its disorders, has begun to incorporate this and other research into therapies for Parkinson’s patients at the UPMC Swallowing Disorders Center, which is under the medical direction of the UPMC Department of Otolaryngology’s Ricardo Carrau, M.D., Bridget Hathaway, M.D., and Libby Smith, D.O. Dr. Gross currently sees Parkinson’s patients with swallowing disorders, and thus far, she has been able to stop aspiration instantly in some patients, after quickly teaching them how to re-coordinate their breathing and swallowing patterns.

While the underlying cause of swallowing problems in Parkinson’s has not been well understood, prior research has found that healthy adults swallow most often during exhalation and that exhalation regularly follows the swallow, even when a swallow occurs during inhalation. Dr. Gross’s study looked at 25 Parkinson’s patients and a control group of healthy adults, all between ages 51 and 84, as they swallowed standardized portions of pudding and cookies. While participants from both groups spontaneously ate, researchers measured their nasal airflow and respiratory movement to determine where swallowing took place in the respiratory cycle. This data was then blinded and analyzed, and results found the Parkinson’s patients inhale during and after swallowing significantly more often than the healthy adults. Also, the Parkinson’s patients swallowed at low lung volumes more often than the healthy adults.

This research was performed at the University Drive location of the VA Pittsburgh Healthcare System and was funded by the Department of Veteran’s Affairs Research and Rehabilitation Merit Review Program. Additional authors include Sheryl B. Ross, M.A., UPMC Department of Otolaryngology; Charles W. Atwood, Jr., M.D., UPMC Department of Pulmonary, Allergy and Critical Care Medicine and VA Pittsburgh Healthcare System; Kimberly A. Eichhorn, M.S., and Patrick J. Doyle, Ph.D., VA Pittsburgh Healthcare System; and Joan W. Olszewski, M.A., Henry Ford Hospital, Detroit.

Ask the Doctor – diseases mistaken for PSP

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Here’s the “Ask the Doctor” section of the Fall ’08 CurePSP Magazine, which I received in the mail on 12/1/08: (not yet available on psp.org)

Ask the Doctor
Lawrence I. Golbe, MD
Director of Research and Clinical Affairs, CurePSP
CurePSP Magazine, Fall ’08

Q: I’ve heard that some people with a diagnosis of PSP actually have corticobasal degeneration. Should I worry about that and get another opinion on my diagnosis?

A: No. PSP and corticobasal degeneration (CBD) are very similar and some experts think they’re even two versions of the same basic disease. They are treated similarly, start at the same average age, have the same long-term prognosis and even share a specific genetic variant as a contributing factor. The difference is that in CBD, there is less falling than in PSP but more difficulty in using the limbs for fine movement. CBD also tends to develop minor jerking movements and abnormal postures of the limbs. The limb problems of CBD are typically highly asymmetric — that is, far worse on one side than the other. All of the symptoms of both PSP and CBD are treated “palliatively,” which means that if the symptom appears, the doctor treats it as a symptom. Some day, if we are able to cure or slow the progression of one but not the other, or if the cures for the two disorders are different, then it will be important to differentiate between the two diagnostically.

Q: OK, so are there any diseases that have cures or very useful treatments that can be mistaken for PSP?

Parkinson’s disease (PD) is sometimes mistaken for PSP when it fails to respond to levodopa, a drug that replaces insufficient brain dopamine. Often, this is simply the result of insufficient dosing. Very often patients with PD have difficulty looking in the upward direction. The combination of this with a much greater-then-average need for levodopa can fool an inexperienced physician into diagnosing PD as PSP. But PD would not display difficulty looking down, the cardinal feature of PSP, and differs in most other respects as well.

Another condition that can be mistaken for PSP and requires special treatment is multiple small strokes. Aggressive management of lipids and blood pressure, administration of blood thinners, repair of narrowed arteries feeding the brain and treatment of heart problems can all reduce the risk of future strokes.

Finally, a very rare brain infection called Whipple’s disease can superficially mimic PSP. However, it usually has rhythmic movements of the eyes and jaw that are absent in PSP. It is diagnosed via MRI with contrast and a spinal tap and treated with antibiotics. In 20 years as a PSP specialist, I have never seen a case.

Brigadier Michael Koe writes a book about his wife Sara Koe who had PSP

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My online friend Joe Blanc posted this to the Society for PSP’s Forum recently. It’s about Brigadier Michael Koe writing a book about his wife Sara, who had progressive supranuclear palsy (PSP). The Koes established the PSP Association in the UK, which is a wonderful organization.

Here’s an excerpt from the newspaper article:

“Mr Koe…said one of the reasons he decided to write the book was to help him deal with the experience of watching a loved one deteriorate from a condition which robs people of their balance, movement, speech, eyesight and ability to swallow. He said: ‘It’s also difficult in that the symptoms can make it seem like the sufferer has been drinking. Friends of Sara’s became less friendly. It was a pretty traumatic time and a pretty bad experience and I think writing it down has helped.'”

Robin

Book tells of tragic death of wife 

Brigadier Michael Koe with the book Charity begins at Home, which wrote after the death of his wife

Published Date: 01 December 2008
By Nick Spoors
A former soldier who set up a leading charity after losing his wife to a little-known brain disease has published an account to raise awareness.

Brigadier Michael Koe and his wife Sara started the progressive supranuclear palsy (PSP) association in 1994 after she was diagnosed with the condition. However, just eight months later she died from complications arising from the illness.

Mr Koe, of Wappenham, near Towcester, said one of the reasons he decided to write the book was to help him deal with the experience of watching a loved one deteriorate from a condition which robs people of their balance, movement, speech, eyesight and ability to swallow.

He said: “It’s also difficult in that the symptoms can make it seem like the sufferer has been drinking. Friends of Sara’s became less friendly.

“It was a pretty traumatic time and a pretty bad experience and I think writing it down has helped.”

The couple set up the PSP Association because they were frustrated at the lack of knowledge about PSP, even among medical professionals.

Since then, the charity has grown to a position where it now employs 21 people with nine volunteers, has helped 3,000 people and invested more then £2 million in research.

Mr Koe was awarded an OBE for his charity work.

Charity Begins At Home can be purchased from the PSP Association for £20 plus £3.50 postage and packaging with proceeds after costs going to the charity.

Cheques can be sent to PSP House, 167 Watling Street West, Towcester, Northamptonshire, NN12 6BX.

The charity can also be contacted via www.pspeur.org, by email on [email protected] or on 01327 3224110.