Primary Progressive Aphasia (PPA) is a clinically diverse neurological syndrome most commonly associated with Alzheimer’s Disease or frontotemporal dementia. It can also rarely occur in Parkinson's-plus disorders. PPA typically begins with gradual, subtle language deficits that progresses to a nearly complete inability to speak.
The age of onset is 50s to early 60s. It affects males and females equally. In terms of incidence within diagnosed dementias, frontotemporal dementia represents approximately 15% of all dementia cases, and PPA accounts for between 20 to 40% of the these patients.
The progression of PPA begins with asymptomatic changes in the language centres, followed by early signs of symptoms of mild cognitive impairment. The progression of non-amnestic MCI continues, until prominent aphasia is observed.[1] The disease further progresses into mutism for most cases. Loss of independence occurs 7 years into the diagnosis in about 50% of cases. The average survival time is 7 to 10 years. After the diagnosis of PPA, patients will typically be diagnosed with a secondary syndrome (e.g. - frontotemporal dementia, progressive supranculear palsy, or corticobasal degeneration).[2]
Developmental disability is a risk factor for PPA.[3]
There are three variants of PPA:
Name | Rater | Description | Download |
---|---|---|---|
Progressive Aphasia Symptom Severity (PASS) | Clinician | The PASS is a clinical instrument used to rate presence and severity of impairment in specific domains of speech and language, as opposed to making a single global language rating. The clinician make ratings on a 5 point scale from “normal” (0) to “questionable/very mild” (0.5), “mild” (1.0), “moderate” (2.0), or “severe” (3.0) impairment.[4] | Download |
The 2011 Criteria proposed by Gorno-Tempini et al are:[5]
For any PPA subtype, there is all
of:
In the semantic subtype (also known as semantic dementia or PPA-S), individuals will have receptive dysfunction and loss of word meaning. There can be prosopagnosia and remote memory loss as well. Speech remains fluent.
Both of:
At least 3
of 4:
The logopenic variant (PPA-L or lvPPA) is characterized by impairment in word retrieval with phonological deficits, and impaired repetition.
Both of:
At least 3
of 4:
The Non-fluent subtype (also know as progressive non-fluent aphasia, PNFA, or also called agrammatic variant, PPA-G) is characterized by distortion of word and sentence construction. This includes abnormal order of words (i.e. - syntax), distortion of word endings, misuse of pronouns, and a lack of grammatical words such as articles (words that define a noun as specific or unspecific, e.g. - a, an, the) and prepositions (these are words show the relationship between the noun and pronoun in a sentence, e.g. - at, for, in, off, on, over, under, into, upon, onto, out of, from within)
At least 1
of 2:
At least 2
of 3:
Depression, anxiety, and dysphoria are the most common symptoms across all subtypes of PPA.[8] Commonly, patients have also have apathy. Changes in eating behaviors are more evident in PPA patients, including hyperorality. Psychotic symptoms in PPA are rare. Disinhibition in patients should make the clinician think of an underlying FTD pathology rather than Alzheimer's pathology for the PPA.
Subtype | Semantic (PPA-S) | Logopenic (PPA-L) | Agrammatic (PPA-G) |
---|---|---|---|
Other abbreviations or names | • Semantic dementia (SD) • Semantic variant PPA (svPPA) | • Logopenic variant PPA (lvPPA) | • Non-fluent variant PPA (nfvPPA) • Progressive non-fluent aphasia (PNFA) |
Grammar | N | N | Imp |
Repetition | N | Imp | Imp |
Single word comprehension | Imp | N | N |
Naming | Imp (due to impaired word-retrieval and comprehension) | Imp (due to impaired word-retrieval and anomia) | N or Imp |
Speech and Fluency | Speech is vague but remains fluent, with circumlocutions and semantic paraphasias | May appear normal during small talk. Word retrieval pauses leads to some degree of loss of fluency. Circumlocution and phonemic paraphasias are common. | Effortful and apraxic, word-finding hesitations. Abnormal order of words, distortion of word endings, misuse of pronouns, and a lack of grammatical words such as (e.g. - a, the), or prepositions (e.g. - at, for, on, into) |
Sample speech | Saying “clock” instead of “watch” when asked to name a wristwatch | Saying “baby flitter” instead of “baby sitter” | Syntax and speech is abnormal, with poor use of tense and modifiers |
Neuroimaging | Atrophy in the anterior temporal lobe | Atrophy in posterior temporoparietal part of language network | Atrophy in left inferior frontal gyrus |
Common Pathology | FTD with TDP-43 type C (80-90% cases) | Alzheimer's | FTD with tauopathy (60% of cases) |
Rarer Pathology | Alzheimer's | • FTD with TDP-43 type A • FTD with tau | • FTD with TDP-43 type A • Alzheimer's |
Clinical progression | Cases may progress into symptoms characteristic of behavioural-variant frontotemporal dementia | There is typically a mix of aphasia, and memory difficulties, characteristic of the predominant Alzhemier's pathology. | Parkinsonism most commonly occurs in the non-fluent subtype, with a corticobasal or progressive supranuclear palsy (PSP) etiology being the most likely. In both cases, the underlying pathology is a tauopathy.[9] |
The vast majority of PPA cases are sporadic. Of the genes that have been identified, there is variability in transmission of these genes. Risk factor genes include GRN (granulin), MAPT (tau), C9ORF72 (protein C9orf72), and PSEN1 (presenilin1).
Since PPA is a syndromic diagnosis, its' pathophysiological etiology can be divided into one of two underlying pathophysiological processes:[10]
For each PPA subtype, the most common neuropathologies are:[11]
Since PPA has disproportionate language impairment compared to other dementias, cognitive testing scores (especially on language-sensitive tests such as the Montreal Cognitive Assessment) can appear significantly worse compared to the patient's actual functional ability and stage of dementia.
All current medications for PPA are off-label treatments. There are no treatments that can stop or alter the course of disease.
Treatment of behavioural and psychological symptoms for PPA (due to bvFTD) include: