Category Archives: Uncategorized

Medicine cabinet research

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On November 3 of this year I posted on some work with a zebrafish model of tauopathy showing that a class of drug called carbonic anhydrase inhibitors could slow disease progression. Those drugs are commonly prescribed for glaucoma and other conditions. One insightful commenter has asked if it might be possible to use an existing patient database to search for a correlation between CAIs and PSP risk.

There has been one such attempt, but it included too few patients to answer this question. Earlier this year, Jay Iyer and colleagues (including me) at multiple institutions used a database of 305 patients with PSP observed over a 12-month period to look for any relationship between concomitant drug use and rate of progression on the PSP Rating Scale. It found that benzodiazepines were associated with more rapid progression. Here’s the paper. The table’s “F value,” as the caption indicates, measures the “interaction between change in PSPRS scores and time.” That’s a sophisticated version of the rate of progression.

Iyer con medsDownload

But CAIs are too rarely prescribed to show up in that type of analysis. In fact, the statistics considered only those drugs used by at least 10% of the patients, as lower frequencies would not have produced statistically significant results.

This approach, seeking a relationship between the risk factor (medication use) and an outcome (disease severity) is only one way to approach this problem. Another is to compare people with PSP to people without it with regard to the risk factor. Another is to compare people with the risk factor to people without it with regard to the frequency of the disease. For a disease as rare as PSP and a risk factor as rare as CAIs, one would need a huge database, like those maintained by national health care systems. Unfortunately, no such analysis of PSP and CAI use has been attempted to date, but in theory, it can be done despite PSP’s misdiagnosis rate in the general population outside of dedicated movement disorder centers.

A new game in town

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I want to draw your attention to a new PSP-related blog, started by CurePSP on October 22. In keeping with CurePSP’s overall mission, the blog concerns not only PSP, but also corticobasal syndrome (CBS) and multiple system atrophy (MSA), which can be difficult to distinguish from PSP, especially in early stages. 

The one post so far is an excellent discussion of speech-assistive devices and voice banking by CurePSP staffers Courtney Malberg and Oscar Sullivan.  Although I’m CurePSP’s Chief Clinical Officer, I’ve provided no advice nor content for the blog to date and haven’t been asked to. That’s the way it should be — I’ve got my own blog, completely independent of CurePSP.

The single blog post so far is mixed in with news items related to CurePSP’s activities.  Each item is labeled “News” or “Blog” (in the small pink ovals at the bottom).  Of course, both should be of interest to the same readers.   

Here’s a screen shot of the page. The first blog post is the second from the left.

So, why zebrafish?

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In response to a commenter’s question on how zebrafish became an experimental model: Zebrafish have been systematically used in research since the 1950s, starting with studies of the causes of birth defects. The original reasons for choosing that species were that it takes only four days from fertilization to hatching and that the eggs develop outside the mother’s body. The latter makes it easy to expose the developing embryos to experimental toxins by simply adding them to the water. Even after only a week post-hatching, young zebrafish half a centimeter long display most of the physiological and behavioral features of adults 6-8 times that size. Juvenile zebrafish are transparent, allowing many experimental outcomes to be easily observed without harming the animal or further interfering in its function. Besides, they’re easy to clone as a genetically uniform colony and react to toxins in ways very similar to mammals. Much of the earliest research in developing zebrafish as a genetic model was performed in the 1960s to 80s by George Streisinger, a Holocaust survivor working at the University of Oregon. Here’s a great biosketch.

More fishy news

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My post from two weeks ago, entitled, “A big little fish,” was about zebrafish as an experimental model for PSP.  This creature, once the normal human tau gene has been added to its genome, is uniquely suited for efficiently screening long lists of drugs as treatment for tauopathies.  I specifically cited a publication screening 147 currently available drugs modulating the attachment of phosphate groups or other regulators of tau production. It yielded two reasonable candidates for further research in other animal models or in people with PSP.

This week, there’s another important finding in zebrafish, except that it concerns not tau production, but tau disposal.

A research group at the University of Cambridge led by Drs. Ana Lopez, Angeleen Fleming and David Rubinsztein used zebrafish with the normal human tau gene to screen 1,437 compounds for use against tauopathies.  All had been either FDA-approved for medical use or found in clinical trials to be safe, even if ineffective for whatever they were being tested for. 

Next, they tested those 1,437 for the ability to improve the survival of a set of cells in the fishes’ eyes (the rods) that normally produce the tau protein.  Of the 71 passing that test, the researchers chose the 16 that seemed easiest to study further.  Of those, the most effective at rescuing cells from degenerating was the drug methocarbamol, which is available by prescription for muscle spasms under the brand name “Robaxin.”  One of the several actions of methocarbamol unrelated to muscle relaxation is inhibition of an enzyme called carbonic anhydrase, which regulates the acid-base balance of cells. 

Drugs that specifically inhibit carbonic anhydrase are available for use in glaucoma and in a variety of neurological disorders.  Three of the most popular anhydrase inhibitors are acetazolamide (brand name Diamox), methazolamide (Neptazane) and dorzolamide (Trusopt). To determine if carbonic anhydrase inhibition explains the benefit of methocarbamol in the zebrafish, the researchers gave those three drugs to a different colony of zebrafish with a human tau gene, but in this case the human gene carried a mutation called P301L, which causes a rare, hereditary, PSP-like illness. 

To the Cambridge team’s delight and ours, all three carbonic anhydrase inhibitors provided major protection against the damage caused by that tau gene mutation.  A further set of experiments showed that the mechanism of protection was that the drugs work by improving the export of tau from the cells by the lysosomes.  Those are organelles that perform part of our cells’ complicated garbage disposal mechanism.

I’ll let the researchers’ own words describe the overall results:

Together, our results suggest that CA [carbonic anhydrase] inhibition ultimately regulates lysosomal acidification and cellular distribution, promoting lysosomal exocytosis and tau secretion. This mechanism lowers tau levels within neurons, which, in turn, have lower levels of hyperphosphorylated and aggregated toxic tau forms, accounting for an improvement in phenotypic, neuronal loss and behavioral defects in vivo in zebrafish and mouse models. This raises the possibility of rapid repurposing of CA inhibitors for tauopathies, as our studies were performed in mice at human-like plasma concentrations. Furthermore, our data suggest that stimulation of unconventional secretion may also be a potent therapeutic approach for other neurodegenerative diseases caused by toxic, aggregate-prone intracellular proteins.

So, the “elevator explanation” is that carbonic anhydrase inhibitors make the fluid in lysosomes more acidic, enhancing their ability to load up on abnormal tau protein and dump it out of the brain cell.

This finding could lead to repurposing existing, off-patent carbonic anhydrase inhibitor drugs not only for PSP but potentially also for the many other neurodegenerative diseases that rely on the lysosomes to dispose of abnormal, misfolded proteins.  Let’s hope that other animal models confirm this and that a clinical trial follows. 

All the carbonic anhydrase inhibitors available are off patent, which means that their manufacturers would not be interested in investing the many millions of dollars needed to test them for a new use.  But drug companies have been known to reformulate old drugs into longer-acting or better-absorbed versions, or to make inconsequential but patentable tweaks to old drugs’ chemical structure. Or maybe a deep-pocketed, non-commercial funder such as the NIH could fund a clinical trial of an existing carbonic anhydrase inhibitor. 

So, that’s what should happen . . . and here’s what should not happen: For you to doctor-shop until you find one willing to prescribe a carbonic anhydrase inhibitor.  For one thing, those drugs come with a long list of possible side effects and drug interactions. For another, it would be difficult to know if it’s working to slow the rate progression in you as an individual.  If you go on a potentially neuroprotective drug and develop some moderate side effect, the decision to continue or discontinue the drug would depend on its benefit in you specifically, not on its effect in zebrafish or even in other people with PSP averaged together. That’s why drug trials observe each participant for a whole year and involve hundreds of participants randomized to experimental drug or placebo.  We need faster and cheaper ways to do such trials and a lot of work is addressing that problem right now. 

Meanwhile, don’t give up hope — or give in to the temptation of unproven, unmeasurable treatment.

Latest wonder drug: home safety

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A support group leader in Florida just sent me his notes from a presentation by an occupational therapist.  She made some sensible safety recommendations that I had not heard before, so I’m passing them along to you:

  1. Increase the lumens of light bulbs around the house, especially in the bathroom, kitchen and stairways, three frequent locations for falls.
  2. Despite the need for better light, glare from overhead lighting or a window can impair visual performance.  So, use window treatments to diffuse direct sunlight, use shades on bare bulbs and consider multiple task lighting units in strategic locations instead of a single, bright fixture.
  3. Use night lights controlled by a motion sensor.  These are available with battery power, so that they can be placed anywhere.
  4. If you don’t have carpet on your stairway, attach a tread with a reflective strip on each step and different-appearing ones on the top and bottom landings. 
  5. Some walkers are available with floor lighting.
  6. To ease the task of locating food on the plate, use plates that contrast with that specific meal’s food.
  7. Remove loose rugs from bathroom floors.  To avoid slipping on wet spots, try stiff, rubber mats that stick to the floor.
  8. Grab bars in and around the shower/tub and toilet are an obvious thing, but make sure they’re installed into studs. 
  9. Use grab bars with suction cups in temporary situations such as travel. 
  10. Toilet safety rails that rest on the floor allow safer landings onto the seat and easier liftoffs, especially if paired with a seat riser.
  11. A bidet is a good idea if you have trouble wiping.  Many models can be installed in a few minutes (according to the manufacturer) by someone with no plumbing skills.

Keep in mind that this is not a complete list – just a few things that I had not seen or written about before.  Www.curepsp.org has lots more advice on optimizing daily activities, including pamphlets and videos.

I also hasten to add that no list of tips is a substitute for a consultation with an occupational therapist with follow-ups as your symptoms evolve over time.  If you can’t find one and your doctor doesn’t know one, just call the OT department in your nearest good hospital for recommendations.

Four reasons to hope

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It’s high time I updated you on currently – or imminently – recruiting PSP clinical trials.

Here are the four in chronological order. All these are for “neuroprotection,” meaning slowing of the underlying disease process. They don’t attempt to improve the existing symptoms, however. That’s called “symptomatic” treatment and I’ll get around to that soon.

More details:

Sodium selenate provides supplemental selenium, which is critical for the function of 25 human enzymes with a wide range of functions. Two are relevant to PSP: glutathione peroxidase 4 and protein phosphatase 2A. The first regulates one type of programmed cell death and the second removes phosphate groups abnormally attached to the tau protein. The trial is happening only in Australia. See here for details, including contact information.

FNP-223 inhibits an enzyme called 0-GlcNAcase (pronounced “oh-GLIK-nuh-kaze”), which removes an unusual sugar molecule from its attachment to tau. The sugar is called N-acetyl-glucosamine and it prevents abnormal tau from attaching at the same spots on the tau molecule. It’s an oral tablet and the trial, which has just started, will be in both Europe and North America. Click here for details and contact info.

AMX-0035 is a mixture of two drugs in an oral solution. Both are currently marketed for conditions unrelated to neurodegeneration. The PSP trial has started in North America and will do so in Europe and probably Japan in the next few months. One of the two drugs, called sodium phenylbutyrate (marked as Buphenyl), addresses the brain cells’ management of abnormal proteins. The other, taurursodeoxycholic acid, marketed as TUDCA, helps maintain the mitochondria. Click here for details and contact info.

Finally, GV-1001 is an enzyme with anti-inflammatory action in the brain. But it’s not like a steroid or non-steroidal anti-inflammatory drug. It acts by an mechanism that the drug company is keeping close to its chest and has something to do with DNA transcription into proteins. The drug has to be injected subcutaneously every day, like insulin. A small trial is in progress in South Korea and in you live there, here’s enrollment info. There are plans to start a trial in the US in 2025, but that could depend on the current trial’s outcome.

Soon, I’ll post something on neuroprotection trials in which the double-blind recruitment is over but the results are pending. After that will be symptomatic trials.

With all these trials in progress, CurePSP’s “Hope Matters” tagline is truer than ever.

A big little fish

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I’ve not posted much in a while.  Lots of other commitments, but unlike this blog, they had deadlines, you see.  So, I have lots to catch you up on, starting with a cool study in zebrafish. This cute, 1-2-inch fishy is a popular aquarium pet. As it turns out, it also makes a great animal model for PSP. 

The model is created by injecting a normal human tau gene into a fertilized fish ovum.  Human tau comes in six different versions, called isoforms. The tau gene used here encodes only the single isoform that accumulates in the neurofibrillary tangles of typical, non-hereditary PSP, called 0N4R tau. The resulting adult fish not only swims poorly — its eyes don’t move very well, either.  It can then be bred to form an ongoing colony. Compared with mice, the leading PSP model until now, zebrafish are cheaper and easier to maintain and provide a much more efficient way to screen dozens of drugs quickly.

The figures below are from a new publication from the University of Pittsburgh led by senior author Dr. Edward A. Burton with first author Dr. Qing Bai. 

Panel A shows still images from a video of a zebrafish as seen from above.  The large, dark ovals are eyes and the smudge toward the bottom is the body.  Panel B shows the movements of the eyes when shown a moving array of black-and-white stripes.  The blue tracing is from a fish without the added human tau gene.  Its eyes move crisply from one stripe to the next, but the red tracing, from a fish with the human tau gene, shows a weak response.  This is identical to the response in people with PSP who are asked by a neurologist to count the stripes on a strip of cloth moved across their field of vision.  It’s called “opticokinetic nystagmus” and is a good way to detect the earliest, asymptomatic involvement of the eye movements of PSP or some other disorders. 

If you go to the link provided above and scroll down to the link for “Supplementary movie 1,” you’ll see a video of the eye movements and the stimulus stripes.

Armed with this experimental set-up and another to trace traced the fish’s spontaneous swimming in a circular dish, Drs. Bai and colleagues then screened a panel of 147 chemical compounds for any ability to correct the problems.  The 147 were chosen because of their ability to modulate the attachment of small molecules to genes, one type of “epigenetic” alteration that we know occurs in PSP. Large drug screens in vertebrates are much more easily performed in zebrafish than in mice. 

The graph below shows the results. Each circle is one drug and the vertical axis is the improvement or worsening it produces in the zebrafish.  The “whiskers” on each circle indicate the variation among the 12 fish tested on that drug.  The drugs’ results are displayed left-to-right in descending order of benefit, which means that the drugs on the right, below the “0” line, were actually deleterious.  The black square labeled “sibling” indicates a littermate fish without the human tau against which the drugs’ effects are compared.  The red square labeled “tau” shows another kind of comparators — the fish with human tau that were left untreated.  The dotted, horizontal lines are placed at a point three standard deviations (σ) from the average (μ) of the 147 drugs’ degree of benefit (upper line) or worsening (lower line). That’s the researchers’ threshold of significant interest for the drugs.

The best-performing drug was something with the weird name, (+)-JQ1.  It’s a member of a group called “bromodomain inhibitors,” which have nothing to do with the element bromine.  A bromodomain is a string of 110 amino acids that forms part of many proteins involved in regulating the transcription of certain genes into their own proteins.  Other inhibitors of bromodomain-containing proteins are being tested as treatment for various cancers.  My clinicaltrial.gov search on “bromodomain inhibitor” produced 52 such trials, though none so far for (+)-JQ1 itself.  The second-best bromotomain inhibitor emerging from the zebrafish screen is trichostatin-A, a non-FDA-approved, anti-fungal antibiotic with potential anti-cancer properties and 137 listings in clinicaltrials.gov.  Third is 2,4-OPD, on which I found no information anywhere.

Bonus fact for the real science nerds: The graph shows a green data point for (-)-JQ1. That’s the “enantiomer” of (+)-JQ1. Enantiomers are pairs of molecules with identical sets of atoms in mirror-image configurations. Some such pairs have identical properties but many don’t. A good example of the latter is levodopa, the (-) version of dihydroxyphenylalanine. It helps Parkinson’s dramatically and PSP modestly, but the (+) version, which would be called “dextrodopa,” does neither. The “dextro-” and “levo-” prefixes refer to the clockwise or counterclockwise rotation that a solution of the compound imparts to the plane of polarized light.

So, let’s await experiments of (+)-JQ1 and trichostatin-A in other models such as tau knock-in mice, stem cells and organoids.  Let’s also await screens of other classes of drugs in the cute little zebrafish that provide a great new, efficient test bed for PSP treatments.

Less is more

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Have you ever heard of the PSP Quality of Life Scale (PSP-QoL)?  It’s widely accepted among researchers, but with 45 questions, each rated on a 0-4 scale plus one question rated on a 0-100 scale, the 30 minutes it takes to administer is just too long.  Still, the PSP-QoL is used in most clinical treatment trials, just not as the primary outcome measure.  Of its 45 items, 22 are motor (including eye movements) and 23 are cognitive and behavioral.  The total score correlates with the PSP Rating Scale (the usual primary outcome measure in clinical trials) to a high degree, with a correlation coefficient of 0.65, where 1.00 is perfect correlation and 0 indicates a random relationship.  That’s considered very good, because you don’t want the secondary measure to correlate perfectly with the primary – you want it to provide additional information.

Now, a group of German neurologists has figured out how to streamline the PSP-QoL down to 12 items:  7 motor and 5 cognitive/behavioral.  They call it the “PSP-ShoQoL.”

The correlation with the PSP Rating Scale is 0.51 (still a good figure) and the correlation with the original PSP-QoL is 0.93.  That means that the short version can be used in place of the original for most purposes.  The PSP-ShoQoL progresses over time just as the original does, which means that it can be used to help decide if a treatment slows the progression of PSP over a period such as a year.

Here are the items in the short version, each rated 0: no problem, 1: slight problem, 2: moderate problem, 3: marked problem, or 4: extreme problem.

MOTOR DIFFICULTY: Do you have difficulty . . .

Grooming, washing or dressing yourself?

Doing things around the house such as housework or do-it-yourself projects?

Using public transport?

Enjoying active leisure activities including gardening or walking?

Climbing stairs?

Using the toilet independently?

Walking?

COGNITIVE AND BEHAVIORAL DIFFICULTY: Have you . . .

Found your thinking is muddled?

Felt not motivated to do things?

Felt confused?

Felt anxious?

Felt your relationships with family members has changed?

I doubt that you will be designing a formal clinical trial any time soon, so why am I telling you about this scale?  So that in preparation for each visit with your neurologist, you can consider completing it on your own or with help (it’s designed for either).  Your neurologist could then get a nice, concise picture of the quality of your life and hopefully integrate that information into their recommendations.  It saves time for questions, emotional support and other critical things that are hard to fit into a 20- or 30-minute visit.

Sing, o muse!

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You’ll recall from my 7/4/24 post that Rep. Jennifer Wexton of Virginia announced last year that she has PSP.  Below is a new press release from her office.  My point relates to its final paragraph.

Wexton Marks Disability Pride Month on House Floor Using New AI Voice Model

Washington, July 25, 2024

Washington, DC — Today, Congresswoman Jennifer Wexton (D-VA) delivered a speech on the floor of the House of Representatives to recognize Disability Pride Month, celebrated each July. Wexton utilized her new AI voice model for the first time on the House floor to share how she has fought throughout her career for disability rights and accessibility issues, and how that has now become a personal fight for her since her Progressive Supranuclear Palsy (PSP) diagnosis last year.

“I hope that when people see me continuing to do all I can to keep living my life and doing this job I love as best I can, they understand and appreciate the courage, resilience, and spirit that so many Americans of differing abilities demonstrate each and every day. I hope I can be a voice — even an AI voice — for Americans facing accessibility challenges and other disabilities, because too often people only see us for that disability. And in truth we are so much more,” said Wexton.

The AI voice model was created through ElevenLabs, a software company that specializes in developing natural-sounding speech synthesis software using deep learning. The model was generated consensually using a collection of previous public speeches from Rep. Wexton provided by her team. Any additional questions about the ElevenLabs technology can be directed to press@elevenlabs.io.

More than the nominal topic of Disability Pride Month, the text mentions that she used an AI-based speech aid to deliver a speech on the floor of the House.  It used audio recordings of her public speeches before PSP’s dysarthria set in to train the AI software to translate a written text into speech in her own voice, not the electronic, synthetic voice we all recognize as “computer speech.”  This is important because the distinctive timbre of one’s speech provides an important emotional identifier. 

This technique, relying as it does on a prepared, written text, is not suitable for ordinary two-way conversations unless you can type extremely fast. Few people with PSP can do that, even with the help of word-completion software.  Besides, hardly anyone has a collection of old audio clips on which to “train” the AI software that Rep. Wexton used.  An audio bank deliberately created for this purpose in an early stage of illness is one potential solution.

I wanted to review the latest on this topic, mostly to help me advise CurePSP about what sort of programs or research it might support going forward.  So, I consulted my newest muse, ChatGPT.  Here’s what it had to say about voice banking and other solutions for severe dysarthria:

You can bank your own voice for future use in a speech generation app in case you become disabled. Voice banking involves recording a variety of phrases and sentences while your voice is still healthy. These recordings can later be used to create a synthetic version of your voice, allowing speech generation apps to produce speech that sounds like you.

Here are the general steps to bank your voice:

    Choose a Voice Banking Service: Select a service that offers voice banking. Some popular options include VocaliD, Acapela, and ModelTalker.

    Record Phrases: Follow the service’s instructions to record a set of phrases and sentences. The more you record, the better the quality of the synthesized voice.

    Submit Recordings: Upload your recordings to the voice banking service.

    Voice Synthesis: The service will process your recordings and create a synthetic version of your voice.

    Integration with Speech Generation App: Once your synthetic voice is ready, it can be integrated into a speech generation app. This allows you to communicate using your own voice even if you lose the ability to speak naturally.

Voice banking is a proactive step that can significantly improve the quality of life for individuals facing conditions that may affect their ability to speak.

Alternatives to voice banking?

If voice banking is not a suitable option for you, there are several alternatives that can help with communication if you become disabled. Here are a few options:

1. Voice Cloning

Voice cloning uses advanced AI to create a synthetic version of your voice with fewer recordings. Services like Respeecher and Descript can create high-quality voice models from a limited amount of audio data.

2. Text-to-Speech (TTS) with Customization

Text-to-speech technology can be customized with different voices, accents, and tones. Some TTS systems allow you to adjust parameters to make the voice sound closer to your own. Popular TTS engines include:

    Amazon Polly

    Google Text-to-Speech

    Microsoft Azure Speech Service

3. Pre-Recorded Messages

You can record common phrases and sentences that you might need. These recordings can be played back as needed. Devices like the GoTalk series or AAC (Augmentative and Alternative Communication) devices often support this feature.

4. Alternative and Augmentative Communication (AAC) Devices

AAC devices and apps provide various ways to communicate through symbols, text, and synthetic speech. Examples include:

    Tobii Dynavox

    Proloquo2Go

    TouchChat

5. Predictive Text Apps

Predictive text apps can assist in quicker communication by predicting the words and phrases you are likely to use. These apps learn from your typing habits to offer more accurate suggestions. Notable apps include:

    SwiftKey

    Gboard

6. Communication Boards and Books

Low-tech options such as communication boards or books with pictures, symbols, or letters can be very effective, especially in environments where technology might not be available.

7. Eye-Tracking Technology

For individuals with severe physical disabilities, eye-tracking technology allows communication through eye movements. Devices like the Tobii Eye Tracker can be used to control computers and AAC software.

8. Sign Language and Gestures

If you retain some physical ability, learning sign language or using a system of personalized gestures can be an effective way to communicate.

Each of these alternatives offers different advantages depending on your specific needs and circumstances. Exploring these options can help you find the most effective means of communication in the event of disability.

Now back to human me. 

It goes without saying that these solutions have to be tailored to the individual – no easy task considering that the disease itself worsens with time.  Another complication is that many of the techniques require manual dexterity or eye movement control beyond the abilities of many people with PSP.  (It also goes without saying that anything from ChatGPT can be incomplete or even wrong.)

Medicare pays most of the cost of some of these things if there’s a doctor’s prescription. Discuss with a speech pathologist, which you should be doing anyway for general PSP-related speech and swallowing issues.

If you consider me your PSP muse, whose mine? Now I know.

Quantifying love

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This audience does not have to be told that caring for a loved one with PSP can be a major burden.  Two CurePSP Centers of Care have now quantified this using the Zarit Caregiver Burden Scale completed from 2014 to 2022 by 139 caregivers of 131 persons with atypical Parkinsonian disorders.  The results are published in Clinical Parkinsonism & Related Disorders.  Here’s the scale:

Ninety (65%) of the caregivers were women.  Of the 131 patients they were caring for, 59% had PSP, 28% MSA and 13% CBS.  The patients were on average about 4.5 years into their illnesses.  (All three disorders have about the same average rate of progression and survival duration.)  Here are the salient statistically significant results, adjusted for potential confounders as necessary:

  • The average (i.e., mean) total score was 28.8 of a possible 88.
  • Of the four disorders, PSP, CBS and MSA-cerebellar gave similar average scores, but scores for MSA-Parkinson were milder by a margin of about 8 points.
  • Female patients regardless of diagnosis involved a greater caregiver burden than males, regardless of the caregiver gender.
  • Female caregivers reported greater burden than males regardless of the patient’s gender or diagnosis.

The authors list several weaknesses of the analysis and propose a prospective study to avoid these.  They include the absence of consideration of:

  • the relationship between patient and caregiver
  • age and any chronic illness of the caregivers
  • changes in the score over time
  • measures of the patient’s disability, especially falling frequency

The authors’ subjective opinion is that the patient’s cognitive and behavioral deficits are perhaps the most important determinant of the caregiver’s burden.  A future study should examine this hypothesis in a formal way.

Adding these variables to the analysis would require a larger number of patient/caregiver pairs.  This might be best accomplished in the context of a large treatment trial, where “secondary” and “exploratory” measures always accompany the “primary” measure of the drug’s efficacy.  Alternatively, all 36 CurePSP Centers of Care could undertake such a project outside of any treatment trial, assuming adequate funding is available.

The first author of the new paper is Jessica Shurer, a medical social worker who serves as CurePSP’s Director of Clinical Affairs and Advocacy.  The two senior authors are neurologists Alexander Pantelyat and Miriam Sklerov, directors of the Centers of Care at Johns Hopkins and the University of North Caroline at Chapel Hill, respectively, The three are credited with having conceptualized the study along with the second-named author, Margaret Ivancic, a medical social worker at UNC.