Northwestern University Feinberg School of Medicine

Northwestern University Feinberg School of Medicine

About Dementia

Symptoms & Causes

Symptoms

People with PPA can experience many different types of language symptoms.

In many instances, the person with PPA may be the first to note that something is wrong and the complaints may initially be attributed to stress or anxiety. People with PPA initially experience one or more of the following symptoms:

People with PPA tend to have similar clusters of symptoms. Researchers who specialize in PPA currently recognize three subtypes: agrammatic, logopenic and semantic.

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-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. 

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 very few nouns and is therefore somewhat empty of meaning.  However, it sounds perfectly fluent because of the liberal use of fillers.  The person may seem to have forgotten the names of familiar objects.

Causes

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 contrast, PPA is a very rare manifestation of AD.  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.

This can be confusing because 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.

In the vast majority of individuals, PPA is not genetic.  However, in a small number of families, PPA can be caused by hereditary forms of FTLD.  The most common gene implicated in these families is the progranulin gene (GRN). Other, less common genes implicated in FTLD include the microtubule associated protein tau (MAPT) and a newly discovered gene, chromosome 9 open reading frame 72 (C9ORF72).

Even in families with genetic mutations, one family member may have PPA while others may have behavioral variant frontotemporal degeneration (bvFTD) or movement disorders, including corticobasal degeneration (CBD) or progressive supranuclear palsy (PSP).  In the presence of a genetic mutation, up to 50% of all family members will have FTLD.  Therefore, genetic testing is not usually recommended unless several family members have clinical patterns characteristic of PPA, bvFTD, CBD or PSP. Before proceeding with genetic testing, it’s 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.

Progression

Because PPA is progressive, decline in language ability continues. Additionally, some non-language abilities (memory, attention, judgment or changes in behavior and personality) can be affected.  Disinhibited, inappropriate behaviors (also seen in behavioral variant frontotemporal degeneration) 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.  The rate of decline is variable from person to person and unfolds over many years. It is unclear why some people progress more rapidly than others.

This page last updated Jun 18, 2012

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