Symptoms & Causes of PPA

• Speech is effortful and reduced in quantity.  
• Sentences become gradually shorter and words may be left out.   
• Word order may be abnormal, especially in writing or emails.  
• Words may be mispronounced or used in the reverse sense (e.g., "he" for "she" or "yes" for "no").
• Understanding single words is preserved, but sentence comprehension may suffer if the sentences are long and grammatically complex.

• The person may seem to have forgotten the names of familiar objects.
• Single words are misunderstood, even of common words. When asked to bring an orange, for example, the person may appear puzzled and may ask what an “orange” means. However, when provided with an orange, the person will know that it is something that you can eat.
• Speech is often fluent but somewhat empty of meaning. Filler words and phrases (e.g., "that thing over there") may be used more frequently.

• Individuals have difficulty recalling the names of objects and/or thinking of words in conversation, but understand what those words mean.
• Individuals may substitute a different word for the one they cannot find. They may use a simpler word or insert fillers such as "the thing that you use for it," "you know what I mean" or "whatchamacallit." 
• Speech may be fluent during causal small talk but breaks into mispronunciations and word-finding pauses when a more difficult or precise word needs to be used. 
• Individuals may have difficulty repeating phrases or sentences. 

It can be both. The word "Alzheimer’s" can be used in two different ways. The term "Alzheimer’s disease 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 to designate the accumulation of two abnormal proteins in the brain, amyloid plaques and neurofibrillary tangles. Sometimes these abnormal proteins build up in language areas (instead of memory areas) of the brain, resulting in language impairments and thus the clinical diagnosis of PPA. So, while PPA patients don’t have Alzheimer’s dementia, 30 to 40 percent may have an atypical form of Alzheimer’s disease. In this example, the individual would have a clinical diagnosis of PPA and their neuropathologic diagnosis would be Alzheimer's disease. This dual use of the word "Alzheimer’s" is confusing, even for the specialist.

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 due to AD may be referred to as an "atypical" consequence of AD.

There is no one-to-one relationship between PPA subtype and underlying pathology. However, PPA-S (semantic variant) is most commonly associated with FTLD-TDP; PPA-G (agrammatic/nonfluent variant) is most commonly FTLD-tau; and PPA-L (logopenic variant) is most commonly associated with AD. These are only probabilities. Better biomarkers are needed to determine the neuropathologic diagnosis for each individual during life.  

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 chromosome 9 open reading frame 72 (C9ORF72).

The risk factors for PPA seem to be different than that of Alzheimer's disease dementia. The biggest genetic risk factor for Alzheimer's disease dementia is ApoE4. However, research evidence indicates that ApoE4 is not a risk factor for PPA caused by AD.

Personal history or family history of learning disability in a first-degree relative, especially dyslexia, has been reported as a risk factor for PPA but not for Alzheimer's disease dementia.