Primary Progressive Aphasia- Notes from Weintraub Talk

There was a conference call today for support group leaders put on by the Association for Frontotemporal Dementias. (PSP and CBS/CBD fall into the “movement disorders” type of FTDs, which is how/why I’m invited to attend.) The topic of the call was Primary Progressive Aphasia, and the speaker was Sandy Weintraub, PhD, of Northwestern, one of the centers in the US studying PPA (and all FTDs).

My notes are below.


FYI – PPA has been addressed briefly in two webinars this year:

Boeve Webinar: Dr. Weintraub’s presentation is an expansion of the PPA topic within Dr. Brad Boeve’s recent webinar on cognitive and behavioral aspects in FTDs. Dr. Boeve said taht 60% of those with a clinical diagnosis of PPA end up being diagnosed with a tauopathy (such as PSP, CBD, or AD) upon brain autopsy.

I posted my notes on Dr. Boeve’s webinar back in April 2010:

Litvan Webinar: As we learned in Dr. Irene Litvan’s presentation, one of the three clinical presentations of CBS is PPA. In my notes on Dr. Litvan’s presentation, I had complained that she hadn’t covered the “progressive aphasia” presentation at all. Well, today’s conference call certainly supplied the missing pieces.

I posted my notes on Dr. Litvan’s webinar back in October 2010:

FTD Support Group Leaders’ Conference Call
Organizer: Association for Frontotemporal Dementias (

Topic: Primary Progressive Aphasia: Understanding language presentations and approaches to care

Speaker: Sandra Weintraub, PhD
Northwestern University’s CNADC (Cognitive Neurology and Alzheimer’s Disease Center)
Chicago, IL

The FTD class of disorders is ever-widening.

Three main types of FTD disorders, depending on early symptoms:
* change in behavior, personality, and emotions: bvFTD
* decline in language (speaking, understanding, reading, writing): PPA
* change in motor function and movement: PSP, CBS, MND

“Early” = first 2 years. These years are critical for families. And critical for clinicians to understand the underlying pathology.

PSP, CBS, and MND often have cognitive symptoms associated with them as they progress.

All FTD disorders are progressive.

What is aphasia?
1. A disorder of language: inability to link words to thoughts for communication
2. Caused by brain damage: usually associated with a sudden loss of language function, caused by a stroke but in PPA is slowly progressive because the cause is neurodegenerative disease
3. Affects all aspects of language usage, not just speech output. A disorder of speech alone without language
impairment is “dysarthria” and it does not prevent the individual from communicating their thoughts since they can
still write normally. Asking the patient to write is one way to distinguish aphasia and dysarthria.

Early Symptoms of PPA (Primary Progressive Aphasia)
1. Gradual loss of language (aphasia): word-finding, speaking in full sentences, understanding conversation and/or written words, writing.

Subtypes include: Agrammatic, Logopenic, Semantic. Subtype depends on what the language disorder is.
Agrammatic: They say “water” rather than “I want water now.”
Logopenic: Slow output and groping for words.
Semantic: What is “salt”? Single-word comprehension deficit. (Called “Semantic Dementia”.)

2. Other cognitive functions are normal or relatively so. Hard to test someone’s memory if they can’t speak.

3. Daily living activities are affected mostly by aphasia in early stages. This is because short term memory and personality are intact.

4. Aware of symptoms and can become depressed due to this awareness.

5. Symptoms progress over time and other problems develop.

Boston Naming Test is used in diagnosis.

Example – Pictures of objects. The patient is asked to name the object.

Example – Test of single word comprehension – nouns and verbs. “Show me the picture where someone is laughing.” Someone with Semantic subtype cannot do.

Example – Color name comprehension. “Show me the color blue.”

Example – Body part name comprehension. “Show me the nose.”

“My sister like to have wheat bread. She will puts the mayo, cheese, turkey and lettuce. She will take a knife to cut the sandwich. The sandwich will put on the plate, My sister will have milk in a glass.”

–> This is agrammatic

“Get whatever type of bread you would like. Then add cheese, with different types. Then add liquid on the bread. Then leados, vegitables, chicken or turkey or other different ones. Then you have a good one!”

–> Fewer nouns here. The patient is having difficulty coming up with the right words. Could be agrammatic, logopenic or semantic! Lots of overlap! She thinks it is a logopenic patient. (I think “leados” is “lettuce.”)

MRI scan on the left. (Taken as if you were standing above the patient’s head.) PET scan on the right. The left side of the images are the right side of the brain.

Later Symptoms:
1. Mutism. Usually this is a late symptom. In rare cases, someone can be mute for 3-4 years.
2. Severe difficulty understanding what others are saying even though hearing is normal
3. Personality changes
4. Memory loss
5. Daily living activities severely limited

Early PPA vs. bvFTD:
PPA patients have aphasia but no other symptoms.
bvFTD patients have personality change, concentration problem, and social-interpersonal problems.
Motor symptoms may be present in both.

Late PPA vs. bvFTD:
PPA patients have aphasia and concentration problem. They may or may not have memory loss, visual disorder, personality change, and social-interpersonal.
bvFTD patients have personality change, concentration problem, and social-interpersonal problems. They may or may not have aphasia, memory loss, and visual disorder.
Motor symptoms may be present in both.

Visual disorder = your brain can’t see.

bvFTD and PPA
* Psychosocial and treatment strategies differ vastly from memory loss dementia.
* Need specialized education, support services, community resources.

Northwestern’s PPA/FTD Program
* website:
* semi-annual newsletters to NWU patients and families
* monthly caregiver support groups. They’ve been asked to split these into two — PPA and bvFTD.
* one conference per year (caregivers and patients)

In the new FTD booklet, there’s a section on PPA:

Strategies for families in managing symptoms of aphasia:
* Speak in simple sentences to patients — simpler words and simple forms of construction. Don’t use the word “or”!
* Construct a communication notebook for patients. Have a page devoted to “my favorite grocery items.” Take pictures and label them with words. iPhone application says words aloud.
* Devise a strategy for emergency situations bypassing the need to use the telephone
* Seek treatment from a speech-language pathologist
* Provide patient with identifying information, Example – MedicAlert bracelets.
* These are from: Weintraub S, Morhardt DJ: Treatment, education and resources for non Alzheimer dementia: One size does not fit all. Alzheimer’s Care Quarterly, July/September: 201-214, 2005. They are summarized in one of the handouts we received.

Question & Answer:

Q: What about the patient who lives alone?

A: Though some of these patients can’t speak, they may still be highly functional. Need to assess how this person can react to an emergency.

Q: What about depression?

A: This can be a serious problem. Medications can be very helpful. Families should be on the look-out for this.

Talking therapy is not always the best thing!

Comment by audience member: There can be profound loneliness in PPA.

Q: Any learnings from your patient support group?

A: Keep gatherings small. More like one-on-one or two-on-one. Any more people gets confusing for the patient.

Q: How does your patient support group work?

A: The patients demanded their own support group. Over time, the amount of talking has declined. Group leaders now insert activities when there isn’t much talking.

Q: What percentage of PPA patients end up having personality involvement?

A: We don’t know. All of the research has been with small series of patients.

Some studies show that the Semantic patients end up with more emotional/behavioral disturbances. This may be due to frontal lobe involvement.

Q: Is Namenda helpful in PPA?

A: Namenda didn’t help with PPA in a trial they did (3-6 months). There was no short-term benefit. So they assumed there was no long-term benefit.

Comment by audience member: Namenda helped his wife for several years.

Q: What portion of FTDs are PPA?

A: We don’t know. Northwestern sees a huge number of PPA patients.

Q: What do we know about genetic patterns with PPA?

A: There are only two PPA families we know of where it seems to be inherited.

In families, where someone has PPA, other family members (first degree relatives) may have early learning disorders (eg, dyslexia).

We haven’t followed those with early learning/language disorders to find out if they develop neurodegenerative diseases later.

Q: What are the pathological diagnoses for PPA?

A: We do have data on this:

60% of all PPA have some form of FTLD pathology (whether it’s tauopathy, FTDP43, CBD, PSP, etc).

40% have Alzheimer’s pathology.

If you have the logopenic form of PPA, you are more likely to have the Alzheimer’s form.

If you have the grammar form of PPA, you are more likely to have a tauopathy.

Cortical atrophy differentiates RS from PSP-P

These Australian researchers looked at the brains of 24 pathologically confirmed PSP cases. 17 cases had PSP-Richardson’s Syndrome and 7 cases had PSP-Parkinsonism — the two most common forms of PSP.

They found:

* “Cortical atrophy was more severe in PSP-RS than PSP-P and affected more frontal lobe regions.”

* “Additionally, atrophy of the internal globus pallidus, amygdala, and thalamus was more severe in PSP-RS.”

* “As expected, more severe frontal lobe tau pathology differentiated PSP-RS from PSP-P.”

And, most interestingly, they found:

* “No correlations were found between the degree of atrophy and severity of tau pathology in any region assessed…”

* No correlations “between the severity of atrophy or tau pathology and the presence or absence of cardinal PSP symptoms.”

* “Our study shows that thalamocortical atrophy is a defining feature of PSP-RS, but this atrophy does not correlate with the presence of any specific cardinal clinical feature.”


Movement Disorders. 2010 Dec 13. [Epub ahead of print]

Cortical atrophy differentiates Richardson’s syndrome from the parkinsonian form of progressive supranuclear palsy.

Schofield EC, Hodges JR, Macdonald V, Cordato NJ, Kril JJ, Halliday GM.
Neuroscience Research Australia and the University of New South Wales, Sydney, New South Wales, Australia.

To determine whether brain atrophy differs between the two subtypes of progressive supranuclear palsy (PSP), Richardson’s syndrome (PSP-RS), and PSP parkinsonism (PSP-P), and whether such atrophy directly relates to clinical deficits and the severity of tau deposition.

We compared 24 pathologically confirmed PSP cases (17 PSP-RS and 7 PSP-P) with 22 controls from a Sydney brain donor program.

Volume loss was analyzed in 29 anatomically discrete brain regions using a validated point-counting technique, and tau-immunoreactive neurons, astrocytes and oligodendrocytes/threads semiquantified.

Correlations between the two pathological measures and the presence or absence of cardinal PSP symptoms were investigated.

Cortical atrophy was more severe in PSP-RS than PSP-P and affected more frontal lobe regions (frontal pole, inferior frontal gyrus). The supramarginal gyrus was atrophic in both subtypes. Additionally, atrophy of the internal globus pallidus, amygdala, and thalamus was more severe in PSP-RS.

As expected, more severe frontal lobe tau pathology differentiated PSP-RS from PSP-P. No correlations were found between the degree of atrophy and severity of tau pathology in any region assessed, or between the severity of atrophy or tau pathology and the presence or absence of cardinal PSP symptoms.

Our study shows that thalamocortical atrophy is a defining feature of PSP-RS, but this atrophy does not correlate with the presence of any specific cardinal clinical feature.

Interestingly, there is a disassociation between tau pathology and atrophy in the brain regions affected in PSP-RS that requires further investigation.

© 2010 Movement Disorder Society.

PubMed ID#: 21154980 (see for this abstract only)

Tests Detect Alzheimer’s Risks, Should Patients Be Told?

This article is about whether people should be given tests that address their risk of getting Alzheimer’s, and whether they should be told the results of the tests. And it’s about physicians’ views on the same topics.

There was a related discussion about a year ago on the local PBS radio station. The interviewee was Dave Iverson, who has Parkinson’s Disease. His father had PD and his brother has PD. He was asked if he wanted to know whether he carried a genetic mutation associated with PD. He said he did not. He was willing to participate in research studies of his genetic profile but told researchers not to pass the results to him. I believe he also said that after he died, researchers could provide the info to his daughter, if she wanted to know.

There are obviously many viewpoints on these topics. Presumably medical ethicists will need to advise medical centers on how to proceed.


Tests Detect Alzheimer’s Risks, but Should Patients Be Told?
By Gina Kolata
New York Times
December 17, 2010

MRI brainstem studies – 2 main PSP types and PD

The two main types of PSP — Richardson’s syndrome and PSP-parkinsonism — are very different. I remember being in support group meetings early on, when the evidence of these two types wasn’t yet published, and wondering if the person sitting next to me was dealing with PSP at all! (“How can your parent not have cognitive impairment?”)

It’s great to have studies now that look in detail at the pathologic, radiologic, and clinical differences in these two main types. RS is easier to diagnose because it’s very different from Parkinson’s Disease or Alzheimer’s Disease; it is called “classic PSP.” PSP-P is much harder to diagnose accurately because it looks so much like Parkinson’s Disease or Multiple System Atrophy.

An Italian study was published this week that looks at MRI measurements of brainstem structures in RS (10 patients), PSP-P (10 patients), and Parkinson’s Disease (25 patients). Using certain measurements, MRIs could be used to differentiate RS from PD but the accuracy of differentiating PSP-P from PD was not as high. The authors say that the such MRI measurements “can, at least partially, contribute to the identification of patients with PSPP versus those with PD.”

The search continues for something to differentiate PSP-Parkinsonism from Parkinson’s Disease and MSA….

I’ve copied the abstract below.


Movement Disorders. 2010 Dec 15. [Epub ahead of print]

MRI measurements of brainstem structures in patients with Richardson’s syndrome, progressive supranuclear palsy-parkinsonism, and Parkinson’s disease.

Longoni G, Agosta F, Kostic VS, Stojkovic T, Pagani E, Stošic-Opincal T, Filippi M.
Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Ospedale San Raffaele, Milan, Italy.

We investigated the diagnostic accuracy of brainstem MRI measurements in patients with different progressive supranuclear palsy (PSP) syndromes and Parkinson’s disease (PD).

Using 3D T1-weighted images, midbrain, and pons areas, as well as superior (SCP) and middle cerebellar peduncle (MCP) widths were measured in 10 patients with Richardson’s syndrome (PSP-RS), 10 patients with PSP-parkinsonism (PSP-P), 25 patients with PD, and 24 healthy controls.

The ratio between pons and midbrain areas (pons/midbrain), that between MCP and SCP widths (MCP/SCP), and the MR parkinsonism index ([pons/midbrain]*[MCP/SCP]) were calculated.

The pons/midbrain and the MR parkinsonism index allowed to differentiate PSP-RS from PD with high sensitivity (90%, 100%), specificity (96%, 92%), and accuracy (94%, 97%).

Only the pons/midbrain was found to distinguish PSP-P from PD, but with a lower diagnostic accuracy (sensitivity = 60%, specificity = 96%, accuracy = 86%).

Compared to PSP-RS, PSP-P experience a relatively less severe involvement of infratentorial brain.

The pons/midbrain looks as a promising measure in the differentiation of individual PSP-P from PD patients.

© 2010 Movement Disorder Society.

PubMed ID#: 21162106 (see for this abstract only)

Can patient be expected to remain at home?

I received these questions via email:

Based on what you understand about PSP, have most of the patients (whose caregivers want them to) been able to remain at home for the duration of the condition — i.e. is it possible for a PSP patient to remain in the home throughout the disease process — whether via home help, hospice and the like? I guess I’m trying to figure out for my mom — unless there is some crazy complication — it seems to me that she could remain in the home for the rest of her life — and any medical equipment that we may need down the line (oxygen, respirator?) could be equipment that we could provide in the home. (she has an excellent medical plan, so cost here is not likely an issue.)

Offhand, I can’t think of any equipment that couldn’t be provided in the home. Does this sound right to you?

(Of course, if she needed surgery, a transfusion, or chemo, or something like that, she would need to go into a medical facility….) But on the whole, from what i understand with PSP, she could, theoretically, remain in the home.

Do you hear the same?


The key in determining whether someone can stay at home or not is whether the patient is safe at home and whether the caregiver is safe in providing care. Sometimes it’s not possible to keep people at home. Common reasons for facility placement in PSP are:

* the patient weighs lots more than the caregiver, and the patient cannot assist with transfers;
* the patient requires 7×24 care (or monitoring), and the caregiver cannot provide this; (perhaps the patient is a fall-risk and must be monitored 7×24 for falls)
* the patient is incontinent, and the caregiver cannot deal with this situation; (perhaps because the patient wants to get up multiple times during the night)
* the patient is yelling and verbally abusive, and the caregiver cannot tolerate this;
* the patient has insomnia and often wakes up the caregiver; and
* the caregiver’s mental and physical health are compromised by providing daily care.

In our local support group, probably half of all PSP patients are in facilities receiving some level of care (assisted, skilled) or are at home receiving some level of care.