Frequently Asked Questions about Primary Progressive Aphasia:
Diagnosis, causes, genetics and treatments
What is Primary Progressive Aphasia (PPA)?
PPA is a progressive impairment of language function.
Language is a uniquely human faculty that allows us to communicate with each other through the use of words. A language impairment caused by a brain disease is known as an "aphasia." Progressive language difficulties in word-finding, word usage, word order, word comprehension or word spelling lead to a diagnosis of PPA. Each individual with PPA has a different pattern of impairment, leading to the classification of PPA into subtypes. Memory for recent events and the location of personal objects, spatial orientation, recognizing faces and the essential features of personality are initially preserved. In the beginning, all limitations of professional, social and recreational activities can largely be blamed on the language impairment. Aphasias caused by head trauma, stroke or brain tumor do not qualify for a PPA diagnosis. PPA is diagnosed only if the underlying cause is a "neurodegenerative" disease that progresses over many years.
What are some initial features of PPA?
This varies from one person to another.
In many instances, the patient may be the first to note that something is wrong and the complaints may initially be attributed to stress or anxiety. One or more of the following can emerge as the initial symptom:
- Slowed or halting speech
- Word-finding hesitations
- Sentences with abnormal word-order in speech or e-mails
- Substitution of words (e.g., "table" instead of "chair)
- Using words that are mispronounced or incomprehensible
- Difficulty understanding conversation despite normal hearing
- Sudden lapse in understanding simple words
- Forgetting the names of familiar objects
- Inability to think of names of people, even though the person is recognized
- New impairments in spelling
What are the subtypes of PPA?
Researchers currently recognize three subtypes of PPA: agrammatic, semantic and logopenic.
Researchers currently recognize three subtypes of PPA: agrammatic, semantic and logopenic.
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PPA-G (Agrammatic/Nonfluent Subtype): A problem with word-order and word-production. Speech is effortful and reduced in quantity. Sentences become gradually shorter and word-finding hesitations become more frequent, occasionally giving the impression of stammering or stuttering. Pronouns, conjunctions and articles are lost first. Word-order may be abnormal, especially in writing or e-mails. Words may be mispronounced or used in the reverse sense (e.g., "he" for "she" or "yes" for "no"). Word understanding is preserved but sentence comprehension may suffer if the sentences are long and grammatically complex. PPA-S (Semantic Subtype): A problem with word-understanding. The principal feature is a loss of word meaning, even of common words. When asked to bring an orange, for example, the person may appear puzzled and may ask what an "orange" means. Speech has less nouns and is therefore somewhat empty of meaning. However, it sounds perfectly fluent because of liberal use of fillers. The person may seem to have forgotten the names of familiar objects. This is the one subtype where changes of personality and behavior are frequent. There may be agitation, display of excessive friendliness to strings, change of dietary habits, etc. PPA-L (Logopenic Subtype): A problem with word-finding. In contrast to PPA-G, speech is fluent during causal small talk but breaks into mispronunciations and word-finding pauses when a more difficult or precise word needs to be used. Some people with PPA-L are very good at going around the word they cannot find. They learn to use a less apt or simpler word as well as to insert fillers such as "the thing that you use for it," "you know what I mean," or "whatchamacallit." Spelling errors are common. The naming of objects becomes impaired. Understanding long and complex sentences can become challenging but the comprehension of single words is preserved. Specialized testing also shows impairment in the ability to repeat phrases and sentences. |
Patterns of brain degeneration in subtypes of PPA. From: Mesulam M et al. Arch. Neurol. 2009;66(12):1545-51 |
What causes PPA?
PPA can be caused by Alzheimer's disease (AD) or Frontotemporal Lobar Degeneration (FTLD).
PPA arises when nerve cells in language-related parts of the brain malfunction. The underlying diseases are called "degenerative" because they cause gradually progressive nerve cell death that cannot be attributed to other causes such as head trauma, infection, stroke or cancer. There are several types of neurodegeneration that can cause PPA. The two most commonly encountered types are frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Both FTLD and AD can lead to many different patterns of clinical impairments, depending on the region of the brain that bears the brunt of the nerve cell loss. When AD or FTLD attacks the language areas (usually on the left side of the brain), PPA results. PPA is caused by AD in approximately 30-40% of cases and by FTLD in approximately 60-70% of cases. In the vast majority of patients with AD, the most prominent clinical symptom is a memory loss for recent events (amnesia) rather than an impairment of language (aphasia). PPA is therefore said to be an "atypical" consequence of AD. The logopenic type of PPA has a particularly high probability of being caused by AD. Specialized positron emission tomography (PET) scans and examination of the spinal fluid may help to resolve the distinction between the two underlying diseases. Whether or not PPA is caused by AD or FTLD can be determined definitively only at autopsy through examination of brain tissue with a microscope.
(right) Microscopic examination of the brain after death determines the underlying pathological disease in PPA.
Is it PPA or is it Alzheimer's?
It can be both.
For reasons outlined in the previous paragraph, the word "Alzheimer's" can be used in two different ways. The term Alzheimer's dementia (or Dementia of the Alzheimer-Type) is used to designate a progressive loss of memory leading to a more generalized loss of all cognitive functions. The term Alzheimer's disease (as opposed to Alzheimer's dementia) is used in a different way to designate a precise pattern of microscopic abnormalities in the brain. Sometimes these abnormalities become concentrated in language areas (instead of memory areas) of the brain and become the cause of PPA. So, while PPA patients don't have Alzheimer's dementia, 30-40% may have an atypical form of Alzheimer's disease. This dual use of the word "Alzheimer's" is confusing, even for the specialist, but is a feature of medical nomenclature that is here to stay.
How is PPA different than behavioral-variant frontotemporal dementia (bvFTD)?
bvFTD is a change in personality and behavior while PPA is an impairment in language function.
Behavioral-variant frontotemporal disease (bvFTD) is a diagnosis given when changes in personality and behavior (rather than memory or language) are the most prominent symptoms during the initial few years of a neurodegenerative condition. It is most often caused by FTLD, and on rare occasion by "atypical" Alzheimer's disease. Often, people with bvFTD develop language problems as their illness progresses but this does not change the diagnosis to PPA since language is not the initial and most prominent problem. Conversely, people with PPA, especially those with PPA-S, may develop features characteristic of bvFTD as the disease progresses.
What is the relationship of PPA to Corticobasal Degeneration (CBD) and Progressive Supranuclear Palsy (PSP)?
CBD and PSP are two additional disorders caused by FTLD. They are characterized by impairments of hand movements, eye movements and gait. Some people with PPA, especially those with PPA-G, may experience the additional impairments of movement and mobility as the disease progresses. So, in some people, PPA may blend into PSP and CBD. In other instances, the autopsy in a PPA patient may reveal CBD-type or PSP-type changes in the brain even if there were no major movement problems during life. In such cases, the patient is said to have had a PPA syndrome with underlying CBD (or PSP) neuropathology. For more information about CBD and PSP, visit www.curepsp.org.
Why have I never heard of PPA? Why has my doctor not heard of PPA?
Because PPA is relatively rare.
There are many thousands of patients with PPA. Nonetheless, compared to the millions of patients with Alzheimer-type amnestic dementias, PPA is rare. Furthermore, it can start in a person's 40s and 50s, an age range that physicians do not usually associate with neurodegenerative diseases.
How does PPA progress?
PPA progresses with different rates and trajectories.
The progression is variable and unfolds over many years. Word-finding and word-understanding become more impaired over time. Additional problems eventually arise in behavior, problem solving, memory and dexterity. Disinhibited, inappropriate behaviors (also seen in bvFTD) are more common with PPA-S while impairments in problem solving, multi-tasking, movement and mobility (of the type seen in CBD and PSP) are more common in PPA-G.
Brain degeneration in the left hemisphere at baseline (green) and two years later (green and blue).
From: Rogalski et al. Neurology 2011;76(21):1804-10
From: Rogalski et al. Neurology 2011;76(21):1804-10
Is PPA automatically diagnosed in every person with a progressive language impairment?
No. Aphasia can be a symptom in other forms of dementia.
PPA is diagnosed only if the language disorder arises in isolation and becomes the most prominent impairment during an initial period of approximately two years. There are many patients with typical amnestic Alzheimer-type dementias or with bvFTD who eventually also develop word usage and understanding problems. These individuals do not qualify for the PPA diagnosis because the language impairment is secondary in importance or late in appearance.
Is there treatment for PPA?
There are no pills yet for PPA. However, there are life-enriching interventions and speech therapies that help.
- Because of the 30-40% probability of AD, some physicians will prescribe AD drugs such as Exelon (rivastigmine), Razadyne (galantamine), Aricept (donepezil) or Namenda (memantine). None have been shown to improve PPA.
- Speech therapy may offer benefits in the early stages by teaching more effective communication strategies and ways to compensate for language difficulties.
- Quality of life enrichment and caregiver support programs offer individuals and families ways of coping with a diagnosis of PPA. Education and training can lead to interventions to maximize strengths and circumvent weaknesses for as long as possible. The effectiveness of such life enrichment programs is demonstrated by the growing interest in caregiver conferences held at specialized medical centers.
- Patients may be understandably depressed and frustrated. The depression may not be expressed verbally because of the aphasia. An appointment with a psychiatrist familiar with PPA and dementia may be necessary. Treatment with antidepressants may be indicated where appropriate.
Does the diagnosis of PPA mean the end of an active life?
Absolutely not.
Absolutely not.
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People with PPA usually have to make major adjustments at work since almost all professions are heavily dependent on verbal communication. However, many people with PPA remain independent for many years, participate in social and civic activities, travel widely and take up novel hobbies ranging from gardening to square dancing, painting, carpentry, photography, etc. We encourage people with PPA to remain physically and mentally as active as possible. |
Artwork by Linda, diagnosed with PPA at age 56. |
Is PPA hereditary?
PPA is hereditary in a small number of patients.
In some families, there is an increased incidence of dyslexia and this may be a risk factor. In the vast majority of diagnosed individuals, PPA is not genetic. In a small number of people, PPA can be caused by hereditary forms of FTLD. The most common gene implicated in these families is the progranulin gene (GRN). Even in families with GRN mutations, one family member may have PPA while others may have bvFTD. In the presence of GRN mutations, up to 50% of all family members will have FTLD. We therefore do not usually recommend genetic testing unless several family members have clinical patterns characteristic of PPA, bvFTD, PSP or CBD. Before proceeding with genetic testing, it is necessary to meet with a genetic counselor to review the implications of the results. The immediate purpose of genetic testing is to determine whether the person has a mutation that is responsible for the disease. However, the results have profound implications for family members who are healthy, especially those of child-bearing age. Do family members want to know the presence of a genetic disease for which there is no treatment? Do they realize that a negative result does not rule out the presence of a mutation in another gene not covered by the testing? Genetic testing for clinical purposes is a serious step that should not be initiated lightly.
A schematic of the GRN gene.
From: Gass J et al. Hum. Mol. Genet. 2006;15:2988-3001
From: Gass J et al. Hum. Mol. Genet. 2006;15:2988-3001
Why should I participate in research?
It may sound trite to say that research is the only hope for finding answers to PPA, but, it is true. Patients, families and health-care professionals are all on the same team, working towards the same goal. Participation in brain-imaging studies, clinical trials, longitudinal cognitive testing, contributing blood and spinal fluid and agreeing to brain donation are key elements of a comprehensive research program. An individual with PPA may agree to participate in some aspects of the research program but not in all. All participation is obviously entirely voluntary and consent to participate may be withdrawn at any point. The information obtained through research will allow us to understand the genetic and molecular causes of PPA, to find more accurate ways to predict whether the underlying disease in an individual is AD or FTLD, and to develop effective treatment programs.
Where can I go for more information?
Go to the links page on this website.