“Extreme Caregiving” for Someone with Behavioral Changes

This article on extreme caregiving appeared in a summer issue of Neurology Now magazine.  “Extreme caregiving” refers to caregiving for someone with behavioral changes.

The article mentions these two books on caregiving that sound worthwhile:

* “Elder Rage, or Take My Father Please! How to Survive Caring for Aging Parents,” Jacqueline Marcell, 2001.  (I suggest you check out Jacqueline Marcell’s website elderrage.com.)

* “The Emotional Survival Guide for Caregivers,” Barry J. Jacobs, Psy. D., 2006

The article includes a section called “Your Coping Toolbox.”  It is a handy list of things you should do to help your loved one and help yourself (caregiver).

Also, I liked the “MITIGATING AGITATION” section of this article.

There’s a short summary on the use of antipsychotics in treating dementia.

Definitely worth reading…




Who’s There?: When stroke or Alzheimer’s changes a person’s behavior, caregiving can become extreme. Here, experienced caregivers, patients, and experts share their stories and advice.
Neurology Now, Volume 5(4), July/August 2009, p 26-29
by Stephanie Stephens

Hands gripping her throat, Jacqueline Marcell’s elderly father, Jake, raged at his caregiver daughter for switching on a television movie channel he didn’t remember ordering. She finally broke free and frantically dialed 911.

After the incident, police took Jake to a psychiatric hospital, where he morphed back into a teddy bear. Eventually he returned to his chaotic, homebound life, struggling but failing to care for his elderly wife, Mariel. And Marcell was left once again to pick up the pieces for a father whose behavior was frequently and intensely out of control.

Both her parents had been diagnosed with Alzheimer’s disease, says Marcell, though not soon enough. She’s since become a passionate and refreshingly humorous advocate for caregivers, through speaking engagements and as the author of Elder Rage, or Take My Father Please! How to Survive Caring for Aging Parents (Impressive Press, 2nd edition, 2001). She’s on a mission to assure caregivers they have company-plenty of it-and counsels them to take care of themselves lest stress take its toll.

I was undergoing the most incredible stress of my life and catching every cold and sore throat possible. I felt like my immune system wasn’t working as well as it should. Later, I was diagnosed with invasive breast cancer and underwent six surgeries. Was the fact that I wasn’t taking care of myself directly related to my breast cancer? It’s my opinion that it was. (Studies done over the past 30 years of the relationship between psychological factors, including stress, and cancer risk have produced conflicting results. Stronger relationships have been found between psychological factors and cancer growth and spread than between psychological factors and cancer development.)

Your life and theirs comes apart, she says. You can’t trust them, a child in an adult’s body, and often they don’t trust you either.

Her father called her every name you can imagine. She wept consistently for a year. Still, Marcell reviewed her list of gratitudes daily-things for which she was grateful-and staunchly bore her emotional shield when confronting the worst moments. Her own struggle may be more extreme than what many of us will experience, but the wisdom she’s gained is universally applicable.

Every person who has ever lived has undergone the heartache of those who came before us getting old, getting sick, and passing away, she says. We understand it intellectually, but when it happens to our loved ones, no words can prepare us. We somehow think we’re the only one who’s ever experienced it.

Wendy Sessler understands, for she and her mother Mary Morgan have also walked this lonely but well-traveled road. Morgan, age 69, of Kill Devil Hills, NC, exhibited no apparent risk factors when she suffered a massive stroke in 1996. A clot in her brain stem affected everything, she says, resulting in behavioral changes.

It was like an alien had overtaken my body, says Morgan, who also cathartically authored her story, the book Like a Bolt (LAF Publishing, 2004). Lacking feeling on her left side, she uses a power wheelchair and walks maybe 10 feet if I hold on to something. I can’t keep my balance.

Unwelcome psychological changes have been no picnic. It’s pretty horrible, she asserts. She’s chronically depressed and knows why.

You wake up and half of your body’s turned to JELL-O.

Her devoted daughter, then 32 and happily married with three children, selflessly returned to help her irritable, frustrated, and frightened mother. She remembers Morgan needing things done right now! and using few words to say so, because it was easier.

When she made me upset, I reasoned that it wasn’t really ‘her.’ Taking care of her was just what I had to do, Sessler says.

A struck-down and fragmented Morgan says she didn’t mean to shout.

There was so much anger, yet I was in the background ‘listening’ with a detached feeling: mouth running, brain just going on, thinking I’d lost control of everything. A statement would come out of my mouth, and I’d think: ‘Where did that come from?’

Reacquainted with her pre-stroke identity eight years ago, she says, It was the first time I referred to myself as ‘Mary.’ I still look like her, have a lot of her parts, but I’m not her. Morgan knows many caregivers also struggle to identify their survivor as the person they once knew.

This condition is as new to the affected as it is to you. Understand their difficulties and know that loving them is something that you can’t overdo, Morgan says.

Cognitive dysfunctional changes in behavior are distressing and can be dangerous, whether caused by stroke or the progression of Alzheimer’s. Ignore them and they won’t go away.

If you don’t understand how to cope, you’ll flounder, Marcell says. Seek out the right doctors and the right medications for your loved one. Take it on like a project.

Remember too that the resulting behavioral changes are due to the disease or brain injury rather than the personality. Don’t take the changes personally, counsels Barry J. Jacobs, Psy. D., clinical psychologist, family therapist, and author of The Emotional Survival Guide for Caregivers (The Guilford Press, 2006). Caregivers can learn to stay cool when patients react to feeling threatened, misinterpret what’s happening, or become confused or agitated.

Still, managing paranoia, increased aggression, or psychosis can perplex and overwhelm even the most seasoned caregivers, including professionals. With Alzheimer’s, it’s essential to understand the progressive stages of the disease, says Dr. Jacobs. Healthcare professionals usually describe three broad categories (sometimes broken down into seven more detailed categories); ask yours to explain how they apply to the person you’re caring for.

In the early stages, the person comes to grips with the diagnosis and exhibits recent memory loss, often with depression or apathy. Caregiver supervision, including necessary reminders, may sustain precious patient independence.

Moderate/middle stage patients may be very frightened, agitated, confused with misperceptions, exhibit rambling speech, and get lost in familiar settings. Obvious emotional and behavioral problems are worsened by stress or change. Caregivers will want to provide orientation with predictable, secure routines that avoid over-stimulation.

In severe/late stages, the patient abandons self-care, is generally incapacitated with delirium or hallucinations, and becomes confused about past or present.

Then even the most devoted caregiver has a very hard time day in and day out, says Dr. Jacobs.

To lighten the load, he advocates locating resources like home health aides, support groups, and government services-locally or online-and emphasizes that knowledge is power when it comes to brain injuries such as stroke. Neurologists can delineate the stroke’s severity and location in the brain, along with how both factors affect memory, reasoning, vision, motor skills, and behavior. Neuropsychological testing can paint a clearer picture of current and future cognitive strengths and deficits.

You’ll have a pretty good idea of where they’re likely to be over time and what kind of compensatory strategy everyone must adopt, says Dr. Jacobs.

Temper flares are common, Dr. Jacobs says, but not every survivor becomes a brute. Instead, a patient may react slowly to stimuli, manifest little emotional expression, be seemingly unresponsive, or go from laughter to tears in seconds.

Marriages and partnerships may also be at risk, Dr. Jacobs notes. In fact, many simply don’t survive the tumult caused by stroke or other major neurological problems. In June 2009, The Journal of Clinical Nursing reported that after a stroke, sexual relationships were significantly affected, gender roles became blurred, and feelings like anger and frustration were confounded by a lack of independence and ongoing fatigue.

Agitation is a common behavior in people with dementia, and it can have a broad range of meanings, says Jason Karlawish, M.D., of the University of Pennsylvania Health System, Division of Geriatric Medicine, where he is Director of the Alzheimer’s Disease Center’s Education and Information Transfer Core and Associate Director of The Penn Memory Center. The patient wants to tell us something.

Often caused by fear, fatigue, or something bothersome in the environment, agitation may also be spurred by an unmet need. Medication might be required to quell it. In the event that the person manifests psychosis-loss of contact with reality-an antipsychotic may be prescribed. Antidepressants might be prescribed for depression or anxiety, and disinhibition-the inability to control impulses-may require mood stabilizers. (See box, Antipsychotics in Dementia Treatment.)

Beyond medication, though, caregivers can help reassure an agitated person and redirect or channel behavior in a new direction without flippantly minimizing the person’s suffering, says Dr. Karlawish.

Example: Don’t say, ‘Oh Mom, my memory’s not that good either.’ Acknowledge that it’s frightening and say, ‘I’m here for you even if you do have a memory problem. You still have a great smile and a sense of humor.’ Then move to another topic.

A physiological complaint may also prompt agitation, Dr. Karlawish says.

A parent who understands a child’s cry knows when it’s not a good one, and astute caregivers develop similar radar. Unmet medical needs can include infection, bowel impaction, or simply acute pain. Therefore, it’s critical to know when something’s different.

Unfulfilled psychosocial requirements such as boredom from sitting all day may be remedied by attendance at adult day care. However, a change in regular patient activities should still respect what’s already in place.

I always try to establish a predictable routine for patients-getting up and dressed, bathing, eating meals, says Martha Lentz, owner of Personal Health Care Solutions in Charlotte, NC. Lentz, a geriatric care manager, supervises clients with neurological conditions. Like others in this tight-knit caregiver community, she freely shares successful strategies.

When confusion or agitation set in, she calmly redirects client attention without being challenging. For instance, Lentz was falsely accused of being the girlfriend of a female client’s husband. The gerontologist reiterated that she was in fact a cousin and shifted gears by inquiring where the client had been lately. The response led to pleasant discussion of the client vacationing in Florida as a child with her parents, thus diffusing potential conflict.

An 18-year caregiver, Andrea Allen, also of Charlotte, avoids making strict demands of clients. Instead, she treads softly and makes suggestions.

Talk to them as though they’re a real person instead of someone with problems, she says. Don’t be so quick and definitely don’t force.

Marcell’s parents would ask certain questions over and over again. To deal with it, she wrote answers to these common questions on file cards. Then, she would ask her mom and dad the question before they did. It became a kind of cognitive exercise, a game that they actually enjoyed.

Since people with dementia may have difficulty determining the date and time, Marcell suggests that caregivers go with the flow and live in the reality of the loved one’s moment. When asking their age, know that they may be many ages in a day. Remove mirrors and instead surround them with photos of their past years.

Mary Morgan implores caregivers: Please don’t assume you know what the stroke survivor is thinking. Listen and pay attention. If the survivor says ‘that hurts,’ believe it.

She also advises keeping noise and distraction at a minimum, both of which put the survivor’s brain in the ‘blender mode’ and prevent focus on one task. Offer meals without too many confusing choices and present options singly: Do you want beef? Do you want chicken?

Watch for inklings of possible survivor self-harm. When you’re vibrant, the life of the party, and suddenly you don’t go to the party any more, it’s bad, Morgan says. You were once respected for your intelligence, and now nobody thinks you have any. Reassure the survivor that ‘You’re important to me’. I want you to be around.

Of course, for caregivers to still be around, they have to take care of themselves first, Marcell insists: If you go down, you can’t help, so be Number One. Take a walk or a hot bath. Get a massage. Know that if your loved one were totally cognizant, he or she wouldn’t want the child to have this much stress.”

Most important, touch and hug the survivor. It’s amazing how the whole body just lights up, Morgan says.

Stephanie Stephens’ mother is entering late-stage Alzheimer’s.

Antipsychotics in Dementia Treatment

* An increased risk of death has been reported in patients with dementia receiving antipsychotics. A three-year study led by Clive Ballard, M.D., of the Wolfson Center for Age-Related Diseases at Kings College in London, showed that only 30 percent of demented patients on antipsychotics were still alive at the end of 12 months, compared to 59 percent of those who took a placebo. Researchers found that the risk increases substantially after more than a year on the medications.

* The British study is not the first to recommend judicious use of antipsychotics among patients with dementia.

* Antipsychotics do have benefits for the psychotic patient who cannot be redirected, comments Dr. Karlawish. The decision to use them has to be based upon very careful understanding of whether known risks are worth the potential benefits of treatment. A clear, measurable goal should be set regarding benefits and if that goal is not achievable, the medication should be stopped.

* For Jacqueline Marcell, the risks were worth it. If doctors had not utilized these medications, she says, I could not possibly have controlled my father. If medication use shortens life, it is my opinion that the patient could also shorten others’ lives if not correctly managed.

* Dr. Karlawish cites FDA black box warnings noting increased risk of death and contra-indicating use of the drugs for control of agitation with Alzheimer’s dementia. Other potential problems, he says, include difficulty with walking, exacerbated risk of falls, increased risk of developing diabetes, and increased risk of death from cardiovascular disease.

Your Coping Toolbox

* Believe it when that person says, It hurts.
* Redirect and diffuse aggression.
* Offer single choices of meals or other options. Don’t force.
* Explore the healing power of touch.
* Minimize noise and distraction.
* Tune into signs of possible patient self-harm or suicide.
* Understand the condition, treatment (including medications), and recovery prognosis.
* Be creative: ask questions, play games, decorate with photos.
* Utilize adult daycare and social worker or volunteer visits.
* If behavior changes become unmanageable, seek professional help.

* Don’t take it personally.
* Walk, exercise, meditate, pet your pet, get a massage, do yoga.
* If your mood, thoughts, or behavior nosedive, seek professional help.

Vietnam Vets, Agent Orange, and PD

An article in yesterday’s New York Times might be of interest to Vietnam
War vets with neurodegenerative disorders… .


October 13, 2009
Door Opens to Health Claims Tied to Agent Orange
By James Dao
New York Times

Under rules to be proposed this week, the Department of Veterans
Affairs plans to add Parkinson’s disease, ischemic heart disease and
hairy-cell leukemia to the growing list of illnesses presumed to have
been caused by Agent Orange, the toxic defoliant used widely in Vietnam.

The proposal will make it substantially easier for thousands of
veterans to claim that those ailments were the direct result of their
service in Vietnam, thereby smoothing the way for them to receive
monthly disability checks and health care services from the department.

The new policy will apply to some 2.1 million veterans who set foot
in Vietnam during the war, including those who came after the
military stopped using Agent Orange in 1970. It will not apply to
sailors on deep-water ships, though the department plans to study the
effects of Agent Orange on the Navy.

The shift underscores efforts by the secretary of veterans affairs,
Eric Shinseki, a retired Army chief of staff and a Vietnam veteran
himself, to reduce obstacles to sick or disabled veterans’ receiving
benefits. The department has come under sharp criticism from Congress
and veterans groups for long delays in processing disability claims.

“Since my confirmation as secretary, I’ve often asked why, 40 years
after Agent Orange was last used in Vietnam, we’re still trying to
determine the health consequences to our veterans who served in the
combat theater,” Mr. Shinseki said in a statement. “Veterans who
endure a host of health problems deserve timely decisions.”

The veterans department already recognizes more than a dozen
conditions as being presumptively connected to Agent Orange exposure
in Vietnam, including Hodgkin’s disease, prostate cancer and Type 2 diabetes.

But for diseases not on that list, veterans are required to provide
evidence directly relating their service in Vietnam to their illness,
a requirement that often leads to application rejections and prolonged appeals.

Veterans department officials estimate that about 200,000 veterans
might seek benefits under the proposed change in policy. But they
said they could not estimate the cost of the change until the policy
underwent public review and was published in final form, which could
take several months.

Mr. Shinseki’s decision is a victory for groups like Vietnam Veterans
of America, which has been pushing the department to add Parkinson’s
disease, ischemic heart conditions and hypertension to the list of
diseases presumptively linked to Agent Orange.

But the new policy is also likely to prompt debate over how much
responsibility the federal government should take in compensating and
caring for aging veterans who are exhibiting a growing list of
physical and psychological problems.

The most common of the three illnesses, ischemic heart disease,
restricts blood flow to the heart, causing irregular heartbeats and
deterioration of the heart muscle.

Parkinson’s disease is associated with a loss of cells that secrete
dopamine, a brain chemical essential for normal movement. Patients
develop tremors, rigid posture, impaired balance and an inability to
initiate movement.

Hairy-cell leukemia, a rarer condition, is a slow-growing cancer in
which the bone marrow produces too many infection-fighting cells,
lymphocytes, that crowd out healthy white blood cells, red blood
cells and platelets.

Agent Orange, named after the color-coded band on storage drums, was
the most common herbicide used in Vietnam to clear jungle canopy and
destroy crops. It contained one of the most toxic forms of dioxin,
which has since been linked to some cancers.

Aides said Mr. Shinseki’s decision was influenced by a report
released in July from the Institute of Medicine that found “limited
or suggestive evidence” of an association between exposure to
herbicides and an increased chance of Parkinson’s disease and
ischemic heart disease in Vietnam veterans. The report also found
“sufficient evidence,” a stronger category, of an association between
herbicides and hairy-cell leukemia.

The report, written by a 14-member panel appointed by the institute,
was based on a review of scientific literature. The institute is
required by Congress to monitor the health effects of herbicides used
in Vietnam and produce updates every two years.

In its report, the panel warned that there was a paucity of
epidemiological data about Vietnam veterans. As a result, the panel
said, its findings did not represent “a firm conclusion” about
herbicides and Parkinson’s and herbicides and ischemic heart disease.
It said it could not estimate the chances of veterans’ developing
either disease.

Despite those caveats, the Institute of Medicine report has been
cited by veterans advocates as providing sufficient evidence to
justify a rule change. Under laws governing Agent Orange policies for
veterans, the department cannot make benefits decisions based on
cost, only on the scientific evidence. Aides to Mr. Shinseki said the
Institute of Medicine report provided that evidence.

Some doctors and researchers say the expansion of Agent Orange
benefits has been based on weak or inconclusive science, given the
lack of studies on Vietnam veterans. Those skeptics argue that
diseases like prostate cancer or Type-2 diabetes are just as likely
the result of aging, lifestyle or genetic predisposition as exposure
to Agent Orange.

“Clinical outcomes” paper – full paper available

Earlier in the year we posted about the O’Sullivan “Clinical outcomes” paper on PSP and MSA.  This is one of the most important papers published to date on these two disorders.

The UK researchers analyze the clinical records (to determine clinical milestones and survival time) of 110 pathologically-confirmed PSP cases and 83 path-confirmed MSA cases (all from Queen Square Brain Bank).

This paper is now available online for free.  I’ve noticed that articles don’t always remain free, so if you want a copy I suggest you save it to your hard drive now.

Here’s a link to the article:

Brain. 2008 Apr 2
Clinical outcomes of progressive supranuclear palsy and multiple system atrophy.
O’Sullivan SS, Massey LA, Williams DR, Silveira-Moriyama L, Kempster PA, Holton JL, Revesz T, Lees AJ.

http://brain.oxfordjournals.org/cgi/content/full/131/5/1362 –> HTML version

http://brain.oxfordjournals.org/cgi/reprint/131/5/1362 –>
PDF version

Update:  local support group member Ted has explained some of the statistics in this paper.  See our post here about the key statistics.


Dr. Hermanowicz (10/8) on PSP – Webinar Notes

Here’s my soapbox message today… I’m finding lots of things tedious about these CurePSP webinars. Two hours is too long, and the repeated info from Janet Edmunson and Kathy Speca is unnecessary. My “control panel” showed the attendee count varied between 160 and 190. Can’t CurePSP determine if a majority of these are repeat visitors, and skip the duplicate stuff? The Parkinson’s Disease Foundation had a great webinar last week that was one-hour long; that was perfect. The other thing that is a total waste of time is that the questions are read verbatim and with all the introductory comments. Can’t CurePSP skip this, and consolidate the questions?

And here are my comments about Dr. Hermanowicz’s presentation… I liked the fact that his message to spouse caregivers was so strong: spouse caregivers should not be caregiving 7×24. This is not a good situation for the caregiver. And I thought the format he used to describe PSP, CBD, and MSA was very effective. He seemed to be very up on the O’Sullivan and Williams research but I thought it was unfortunate that he didn’t take the opportunity to explain that there are two common forms of PSP — one with dementia and one without. Those dealing with the non-dementia form of PSP don’t appreciate hearing that a primary symptom of PSP is dementia.

Enough of my layperson opinions. What follows are the PSP-related and general notes I took from the webinar.


Background Info on Presenter – Dr. Neal Hermanowicz

He’s a Board certified neurologist with fellowship training in Movement Disorders at the Univ of Michigan. His mentors there were Drs. Anne Young, Sid Gilman, and the late Jack Penney.

Since 1999, he’s been at the University of California Irvine to establish a clinical program in Movement Disorders (in the Institute for Memory Impairments and Neurological Disorders). Clinical trials in treatment development for PD, dystonia, Huntington’s Disease and, soon, MSA.

Since 1999, he’s been the Medical Director for the Traub Center for Movement Disorders at the Eisenhower Medical Center in Rancho Mirage, CA.

He just attended the UCI atypical parkinsonism support group meeting on 10/7..

Presentation by Dr. Neal Hermanowicz
Topic: Fundamentals & Diagnosis of PSP, CBD, MSA, and Related Disorders

Three Disorders

These three disorders have common features — slowness and stiffness of movement (Parkinsonism)
Similar ages of onset
Progressive (and gradual)
Unknown cause (which is not unusual in neurology)
Uncommon (so it’s hard for clinicians to make a diagnosis)
No specific treatment for the diseases

The diagnoses of these three disorders is established by clinical assessment, ie, history and physical examination.
No tests confirm the diagnosis.
There is always some level of uncertainty, even among experienced clinicians.


Patient #1 – PSP
68 year old man referred for possible PD. He has been falling recurrently and without warning for the past year and a half. Gravelly voice (noticed by wife). He coughs when eating and drinking. He is losing weight. He complains of vision problems. He acknowledges that he is slower in his movement and his neck feels stiff.

History of PSP: Dr. Richardson, in Toronto, saw a patient in 1955. He called the disease by the name “progressive supranuclear palsy.” Steele, Richardson, and Olszewski published on PSP in 1964. This 1964 included brain pathology. Seemed reminiscent of post-encephalitic parkinsonism.

PSP Background:
Prevalence is 1 to 6 in 100,000
Jankovic: of 100 PD patients he sees in his clinic, actually 5 have PSP [Robin’s note: not sure I got that right] Symptom onset average age 63.5
Diagnosis average age 66.5
More men than women affected at a ratio of around 2:1. (We don’t know why. This is similar to PD.)
Rarely runs in families

PSP Initial Symptoms:
Unsteady gait or falls: unpredictable falls
Speech difficulty
Cognitive/behavioral change
Vision problems
Swallowing difficulty

[Robin’s note: the initial symptoms for Richardson’s Syndrome are very different from PSP-Parkinsonism. This is well-explained in the O’Sullivan et al 2008 paper and several Williams papers.]

PSP Diagnosis: consolidated several criteria here, including the SPSP-NINDS criteria
Onset 40 or older, and gradually progressive
Impaired balance and falls in the first year
Eye movement abnormalities (difficulty looking downward or side to side is characteristic of PSP)
Early speech and swallowing difficulty
Symmetric (both right and left side of body) slowness and stiffness
Cognitive impairment (different from the type we see in Alzheimer’s)

Difficulty looking upward is very common, even in normal aging

PD is asymmetric

PSP Pathology: described by Richardson; brain cell loss in characteristic areas; neurofibrillary tangles within brain cells (tau); locations correlate to symptoms and exam

PSP Cause:
The cause is unknown. Research on environmental and genetic factors is currently underway, enrolling at 10 sites within the US. This is not a treatment study but a gathering-of-information study.

PSP Prognosis: (according to O’Sullivan et al 2008)
Measure of time from onset to milestones:
* Frequent falls: 3.9 +/- 2.5 years
* Wheelchair: 6.4 +/- 2.7 years
* Severe swallowing difficulties: 6.4 +/- 2.4 years
* Disease duration: 8.0 +/- 4.1 years
These are averages, statistics. More severely impaired people may be seen at these centers that were part of the study.
Progression rate is variable from one person to another.

[Robin’s note: The O’Sullivan et al 2008 article is titled “Clinical outcomes of progressive supranuclear palsy and multiple system atrophy.” This article is available for free online here
http://brain.oxfordjournals.org/cgi/con … 131/5/1362 ]

PSP Treatment: (from Burn & Warren 2005)
Nothing specific for the disease process itself
Involuntary eyelid closure (blepharospasm or apraxia of eyelid opening) can be treated with botulinum toxin injections
Double vision can be treated with prisms in eyeglass lenses
Dry eyes can be treated with artificial tears
Speech and swallow problems should be evaluated by a speech pathologist
Excessive saliva can be treated with atropine drops or botulinum toxin injections into salivary glands

PSP Treatment:
Cognitive symptoms treatment is under investigation. Mixed reports on Aricept (donepezil). Exelon (rivastigmine) is being looked at and is potentially beneficial. He tends not to use Alzheimer’s medications.
Mobility/fall risk reduction through physical therapy.
PD medications such as levodopa and amantadine are reasonable to try in PSP. These medications have the potential for unpleasant side effects.
Brain surgery: not yet beneficial; under investigation
Support: support groups and websites give people a feeling of empowerment

Other related brain disorders include:
Frontotemporal Dementia
Dementia with Lewy Bodies
Parkinson’s Disease

Questions and Answers: (All answers were given Dr. Hermanowicz, unless indicated otherwise.)

Three Disorders (note: though some of the questions are specific to a disorder, the answers are more general)

Q: Is there anything new on stem cell therapy?

A: Stem cell therapy presents great hope to lots of people. Transplantation is further away. Another way stem cell therapy can be helpful is to model the disease. UCI is doing this in Huntington’s Disease.

Stem cell treatment is being tried in MSA-C (“the ataxia type”) in South Korea. These stem cells are being injected into veins, not the brain. But the stem cells find their way to the brain.

Q: What is the relationship between alpha-synuclein and tau, and the effect on them by hsp70?

A: Alpha-synuclein is causing abnormal clumps in MSA while tau is causing abnormal clumps in PSP and CBD. hsp70 is a protein that might help reduce this clumping. It has been looked at in the lab. This may perhaps open up a new avenue of treatment, or something like hsp70. Not yet in clinical trials.

[Robin’s note: You can read the research findings on Hsp70 here:
Personally, I think this research will only be of interest to those dealing with PSP and CBD, as the discovery is about tau. And the research was in mice, so we are years away from any clinical trials.]

Q: My wife, with PSP, had an MRI that was inconclusive. What part do MRIs play in diagnosing PSP?

A: A brain MRI is not helpful in diagnosing any of these three disorders. No imaging study is helpful. There are sometimes hints or clues. I would never make a conclusive diagnosis from an imaging study.

Q: My husband, with PSP, fell and fractured his hip. With his impulsivity, how can we help him to understand the safety precautions he must now take to prevent further falls?

A: No medication can help with impulsivity. This requires ongoing discussion and reinforcement with the person with PSP. In some cases, a caregiver is needed 24×7. It doesn’t always need to be the spouse. Perhaps it can be a hired caregiver.

The risk of a fracture or subdural hematoma is always present with falls.

Q: My mother, with PSP, lives in Montana and has never seen a movement disorder specialist. Should we travel to see the leading experts in the US?

A: One does want to be certain about the diagnosis. These disorders are uncommon. If an MD or NP has never seen one of these disorders before, it’s hard to recognize them. I hate to encourage people to travel great distances but it might be at least worth at least one visit with someone in the western US with movement disorder training. Try Boise, ID, or Seattle, WA. This is a problem. It can be gratifying for people to get a diagnosis but it can be frustrating as there’s very little for treatment. Telemedicine is being developed as a technology for diagnosis. I think this could be diagnosed remotely via a camera.

Q: What medicine is the best to treat muscle stiffness?

A: Levodopa is a reasonable medication to try. Baclofen is another possible choice. If it’s localized, injection with botulinum toxin might be helpful.

Q: My wife, with PSP, has a problem with bed wetting. She is in diapers, doesn’t drink liquid after 7pm, and takes medication. What else can I do?

A: Elevating the head of the bed by 30 degrees can reduce urinary urgency. She should be seen by gynecologist or urologist so it’s clear what is causing the problem, though it’s probably related to PSP. Be sure she doesn’t have a UTI. Void the bladder before going to bed. Sometimes incontinence briefs are the best resolution. Consider a bed-side commode or bed-side urinal (for men).

Q: My relative has PSP. Does CoQ10 help? What is it used for?

A: CoQ10 tries to encourage brain cells to get more energy for their operation. UC Irvine is participating in a couple of CoQ10 trials in PD and Huntington’s Disease. But the jury is still out on CoQ10. It’s not known to be effective but it’s not known to be harmful either. I don’t discourage people from taking it.

Q: Is lithium an effective treatment?

A: Lithium is being studied, but it hasn’t been proven to be effective. This medication has potential toxicities. It can have neurological side effects. It has to be monitored closely and used with caution. It is primarily for mood disorders, bipolar disorders.

[Robin’s note: The NIH-funded trial into the safety of lithium in PSP and CBD has ended. Many patients reported unacceptable side effects. To my knowledge, lithium has not been studied in MSA.]

Q: I have been diagnosed with PSP. Can I remain at home (my preference) or must I have to an assisted living facility. Money is not an issue.

A: For many people, money is an issue. Insurance doesn’t cover facility-based care. If you can financially sustain it, the best care is at home. But I discourage the spouse to be the 7×24 caregiver. There is burnout associated with that.

Q: My husband has early-stage PSP, with his full mental capacities. We’ve been discussing the pros and cons of a feeding tube. He insists he doesn’t want one. I and my children would like him to have one. What should we do?

A: His wishes are clear. I do not encourage him to get a feeding tube.

Q: My MD first said I had CBD. Then the diagnosis changed to “slow moving PD.” What is this?

A: I don’t know. This is not a conventional term.

Q: My husband has MSA. There is some 1990 research on the effect of the iron binding protein ferritin. Is there any current info on this?

A: Iron deposits have been associated with neurodegenerative diseases. There’s lots of interest in this topic though nothing has panned out.

Q: I’m a Korean war vet. Would toxin exposure have caused PSP?

Carbon monoxide and manganese exposure can lead to PD. But the great majority of PD, PSP, and MSA cases have no toxin identified yet.

Q: Should levodopa be taken 1 hour before or 2 hours after a meal rather than with meals? If a PSP sufferer is not responsive to levodopa, should the dosage be increased to 2000mg/day?

A: I hate to have people orchestrating medication in relationship with their meals because it’s upsetting to people’s lives.

I don’t usually take people up to 2000mg/day. That’s a huge dose. I might take people up to 600mg/day, perhaps 800mg/day.

Q: My husband has been told by different neurologists that he has MSA or PD. Do I really have to wait for an autopsy report to find out what he has?

A: Yes. Even PD, a far more common disorder, can be hard to diagnose.

If it’s Parkinson’s-like, we use PD medications — whether it’s MSA or PD. No definitive test or clinical exam during life is available.

Q: My mom has one of these disorders and has a problem accepting it. What can I do to make my mother accept her condition?

A: Denial isn’t necessarily a bad thing. There’s nothing specific that can be done to force someone to accept her condition. Perhaps this will change over time.


Q: I have had PSP since December 2008. I have impaired voice and minor walking difficulty. How long do you guess that I have to live?

A: I don’t know. People ask me this. The data says 8 years +/- 4.1 years, but the data may be biased towards severe cases.

Q: My relative has PSP. Why is there such a difference in survival time for different people?

A: According to one study, the average is 8 years, though there is some variability. We don’t know why there is such variability. Perhaps it is connected to why people get the disease in the first place.

Q: What progress has there been in finding out the causes of PSP?

A: This is the thrust of the national study being organized by Dr. Irene Litvan. One of the participating sites is UCLA. This study is underway presently. In terms of progress, there hasn’t been enough. In terms of research, it’s ongoing.

Q: Is there any progress in finding a treatment for PSP?

A: There has been some but not enough. There are studies underway to identify the cause and brain mechanisms involved in PSP. This will lead to better understanding and better treatments.

Q: My husband, with PSP, is currently taking Sinemet, Namenda, and nortriptyline. Are there any new medications effective for treating PSP?

A: Nothing new has been proven to be effective.

Q: My mother died of PSP. What is the incidence of heredity in PSP?

A: I’m guessing that it’s less than 5% of all cases. It’s rare. In some families there is PSP showing up from generation to generation.

Q: My mother passed away due to PSP. My brother has multiple sclerosis. Is there a connection between PSP and MS?

A: Not that we know of. MS is an autoimmune disorder. PSP is not an autoimmune disorder, though there is an immune system component.

Q: My mother has PSP. She cannot walk with assistance. How does the disease progress in later stages?

A: More advanced stages of PSP is “more of the same.” More impairment of speech, more problems walking, more swallowing problems, more cognitive problems. Aspiration can occur with swallowing problems.

Q: I am a urologist (John B in Houston). One of my patients has PSP. What are the urinary problems in PSP?

A: The overwhelming majority of people with PSP have urinary problems (urgency, frequency or incontinence).

Q: I’ve been diagnosed with cerebellar ataxia but it sounds a lot like PSP. What’s the difference?

A: Cerebellar ataxia = sense of incoordination; feeling like you are drunk; irregular speech; poor coordination of walking, arms, and legs

PSP = stiffness of trunk and neck; problems with balance and falling; not the same type of incoordination

They look different.


Q: Can I get a copy of today’s webinar?

Answer by Larry Schenker: A summary will be posted to forum.psp.org. Get a copy of the presentation by emailing Kate DeSantis, [email protected].

Q: What is the latest clinical research that is being done for PSP?

A: Dr. Yvette Bordelon is doing a future webinar on PSP, CBD, and MSA research. I will defer to her.

Future webinars:
10/22 – Robert Hutchman – Interventions
11/5 – Yvette Bordelon – Latest Research
11/19 – Lawrence Golbe – Research for Dummies
12/3 – Jerome Lisk and a panel of movement disorder specialists

Research findings: clearing tau in mice by targeting Hsp70

This is a report on some basic research involving the protein tau and an update of sorts of the tau-busting drug Rember.

This University of South Florida press release was posted earlier this week to EurekAlert! Byrd Alzheimer’s Institute neuroscientist Chad Dickey studies how the protein tau can be removed from the brain through drugs or gene therapy. Tau is the protein involved in Alzheimer’s Disease, PSP, CBD, and some other disorders.

A study in mice (genetically modified to develop tau tangles) revealed that inhibiting the protein Hsp70 rapidly reduced the level of tau in the brains. “Hsp70 is a one of several ‘chaperone’ proteins that supervises the activity of tau inside nerve cells. The normal function of tau is to support the structure of nerve cells, much like the skeleton provides a scaffold to support the body. Tau is inside nerve cells, while another hallmark protein associated with Alzheimer’s, beta amyloid, is outside the neurons.”

Several compounds were tested in cell models and genetically modified mice to see if they had any effect on Hsp70. According to the abstract of the journal article about this research, this is the first time that Hsp70 has been targeted and the first time a “newly developed high-throughput screening system” was utiilized.

“One of the more effective Hsp70-inhibitor drugs the researchers discovered was a derivative of methylthioninium chloride, or Rember™, the first experimental medication reported to directly attack the tau tangles in patients with Alzheimer’s disease. Rember™ was heralded as a major development in the fight against Alzheimer’s when results in early clinical trials were announced last year at the International Conference on Alzheimer’s disease. But Rember™ and its derivatives do have some inherent problems; they’re not very potent so effective therapy would require fairly high doses, Dickey said.”

“The drug does help prevent the protein (tau) from clumping together, but that in itself doesn’t mean it’s actively getting rid of the toxic tau,” he said. “Now that we know Hsp70 is a target of Rember™, we can develop similarly-acting drugs that will more specifically target this chaperone protein in affected areas of the brain, resulting in fewer side effects.”

I’ve copied the USF Health press release below. This research was supported by a Pollin CBD research grant from CurePSP. (Abe Pollin has a clinical diagnosis of CBD.) Too bad that the press person at USF couldn’t get the acronym for the disorder spelled correctly (“CDB”) or the disorders CBD and PSP put into the article. (I guess money doesn’t buy accurate publicity.)

I’ve also copied the abstract of the Journal of Neuroscience article.


http://www.eurekalert.org/pub_releases/ … 092809.php

University of South Florida Health Press Release

Protein inhibitor helps rid brain of toxic tau protein
Laboratory study shows drug targets chaperone Hsp70 to reduce Alzheimer’s protein

Tampa, FL (September 30, 2009) — Inhibiting the protein Hsp70 rapidly reduces brain levels of tau, a protein associated with Alzheimer’s disease when it builds up abnormally inside nerve cells affecting memory, neuroscientists at the University of South Florida found. The study is reported online today in the Journal of Neuroscience.

“Now that we’ve discovered that targeting the chaperone protein Hsp70 can clear tau, it could be helpful in finding more effective drugs for Alzheimer’s disease,” said the study’s senior author Chad Dickey, PhD, assistant professor of molecular medicine who works out of the Byrd Alzheimer’s Institute at USF Health “The therapeutic strategy may also be applicable to other neurodegenerative diseases involving Hsp70, such as Huntington disease, amyotrophic lateral sclerosis (ALS), and some cancers.”

Hsp70 is a one of several “chaperone” proteins that supervises the activity of tau inside nerve cells. The normal function of tau is to support the structure of nerve cells, much like the skeleton provides a scaffold to support the body. Tau is inside nerve cells, while another hallmark protein associated with Alzheimer’s, beta amyloid, is outside the neurons.

Working with researchers at the University of Michigan, the USF team tested the effects of several compounds on Hsp70 in cell models and brain tissue from mice genetically modified to develop the memory-choking tau tangles. Some compounds activated Hsp70, and others were Hsp70-inhibitors.

One of the more effective Hsp70-inhibitor drugs the researchers discovered was a derivative of methylthioninium chloride, or Rember™, the first experimental medication reported to directly attack the tau tangles in patients with Alzheimer’s disease. Rember™ was heralded as a major development in the fight against Alzheimer’s when results in early clinical trials were announced last year at the International Conference on Alzheimer’s disease.

But Rember™ and its derivatives do have some inherent problems; they’re not very potent so effective therapy would require fairly high doses, Dickey said.

“The drug does help prevent the protein (tau) from clumping together, but that in itself doesn’t mean it’s actively getting rid of the toxic tau,” he said. “Now that we know Hsp70 is a target of Rember™, we can develop similarly-acting drugs that will more specifically target this chaperone protein in affected areas of the brain, resulting in fewer side effects.”

The USF researchers originally thought activating Hsp70 would direct the chaperone protein to decrease the tau gone bad — preventing tau from stacking up into tangles inside cells involved in memory and destroying them. But instead of restoring tau to its normal supportive function, activating Hsp70 actually led to tau’s preservation and even more accumulation, Dickey said. “Basically we think the chaperone binds to the tau, and somehow in the process of trying to fix things decides to keep holding onto tau when it shouldn’t. So, activating Hsp70 is not necessarily what we want to do; we ultimately want to inhibit Hsp70 to promote the release or clearance of tau …to kill the bad tau.”

Dr. Dickey emphasizes that problems with Hsp70 alone do not cause Alzheimer’s. It likely develops from a convergence of various factors in the brain, he said, including deposits of the other featured Alzheimer’s protein beta amyloid, or a genetic defect; disruption of cell signaling; a breakdown in the neuron’s support structure, and then accumulation of tau into the memory-choking tangles.

Dr. Dickey’s team at USF focuses on how to manipulate with drugs or gene therapy the chaperone proteins that regulate tau’s fate ­ determining whether it’s preserved or cleared from the brain. The University of Michigan team works on identifying and developing compounds that may be effective against Alzheimer’s disease and other tauopathies.


The study was supported by the national Alzheimer’s Association, the National Institute on Aging, the Abe and Irene Pollin Fund for CDB from the Society for Progressive Supranuclear Palsy (CurePSP), and the National Institute of Neurological Disorders and Stroke.

The study’s other authors were Umesh Jinwal (lead author), Yoshinari Miyata, John Koren III, Jeffrey Jones, Justin Trotter, Lyra Chang, John O’Leary, David Morgan, Daniel Lee, Cody Shults, Aikaterini Rousaki, Edwin Weeber, Erik Zuiderweg, and Jason Gestwicki.

USF Health is dedicated to creating a model of health care based on understanding the full spectrum of health. It includes the University of South Florida’s colleges of medicine, nursing, and public health; the schools of biomedical sciences as well as physical therapy & rehabilitation sciences; and the USF Physicians Group. With more than $380.4 million in research grants and contracts last year, USF is one of the nation’s top 63 public research universities and one of 39 community-engaged, four-year public universities designated by the Carnegie Foundation for the Advancement of Teaching. For more information, visit www.health.usf.edu

Here’s the abstract of the recently-published research article:

Journal of Neuroscience. 2009 Sep 30;29(39):12079-88.

Chemical manipulation of hsp70 ATPase activity regulates tau stability.

Jinwal UK, Miyata Y, Koren J 3rd, Jones JR, Trotter JH, Chang L, O’Leary J, Morgan D, Lee DC, Shults CL, Rousaki A, Weeber EJ, Zuiderweg ER, Gestwicki JE, Dickey CA.
Departments of Molecular Medicine, USF Health Byrd Alzheimer’s Institute, University of South Florida, Tampa, Florida.

Alzheimer’s disease and other tauopathies have recently been clustered with a group of nervous system disorders termed protein misfolding diseases. The common element established between these disorders is their requirement for processing by the chaperone complex. It is now clear that the individual components of the chaperone system, such as Hsp70 and Hsp90, exist in an intricate signaling network that exerts pleiotropic effects on a host of substrates. Therefore, we have endeavored to identify new compounds that can specifically regulate individual components of the chaperone family.

Here, we hypothesized that chemical manipulation of Hsp70 ATPase activity, a target that has not previously been pursued, could illuminate a new pathway toward chaperone-based therapies. Using a newly developed high-throughput screening system, we identified inhibitors and activators of Hsp70 enzymatic activity.

Inhibitors led to rapid proteasome-dependent tau degradation in a cell-based model. Conversely, Hsp70 activators preserved tau levels in the same system. Hsp70 inhibition did not result in general protein degradation, nor did it induce a heat shock response.

We also found that inhibiting Hsp70 ATPase activity after increasing its expression levels facilitated tau degradation at lower doses, suggesting that we can combine genetic and pharmacologic manipulation of Hsp70 to control the fate of bound substrates.

Disease relevance of this strategy was further established when tau levels were rapidly and substantially reduced in brain tissue from tau transgenic mice. These findings reveal an entirely novel path toward therapeutic intervention of tauopathies by inhibition of the previously untargeted ATPase activity of Hsp70.

PubMed ID#: 19793966 (see pubmed.gov for this abstract, available for free)