Nonfluent/Agrammatic PPA

FTD syndromes characterized predominantly by the gradual loss of the ability to speak, read, write and understand what others are saying fall under the category of primary progressive aphasia, or PPA. PPA is diagnosed when three criteria are met:

  1. There is a gradual impairment of language (not just speech).
  2. The language problem is initially the only impairment.
  3. The underlying cause is a neurodegenerative disease.

Experts further subdivide PPA into three clinical subtypes based on the specific language skills that are most affected.

People with the nonfluent/agrammatic variant of PPA (nfvPPA, also known as PPA-G), also called progressive nonfluent aphasia or PNFA, find it increasingly difficult to speak yet can still recall the meanings of individual words. The ability to form sounds with their lips and tongue is caused by degeneration of the parts of the brain that control certain related muscles; the muscles themselves, however, are unaffected. The technical term for such problems is apraxia of speech (AOS). As a result, their speech becomes slow and effortful and they may appear to be physically struggling to produce words. But speech problems alone are not sufficient for diagnosing PPA. When the dominant problem is speech rather than language, the diagnosis is progressive AOS rather than PPA.

The defining feature is the impairment of grammar. People with nfvPPA make many mistakes while speaking, including omitting small grammatical words, using word endings and verb tenses incorrectly, and/or mixing up the order of words in sentences. Eventually, some may develop difficulty swallowing as well as more widespread motor symptoms similar to those seen in the movement-predominant forms of FTD such as corticobasal syndrome.

Know the Signs… Know the Symptoms

Apraxia

Difficulty producing movements of lips and tongue needed for speech. This results in distorted or incorrect speech sounds with slow, labored speech, and groping movements of the face and mouth in an effort to produce the correct sound.. Effortful speech is often the first symptom. Multisyllabic words are the most difficult to produce.


Agrammatism

Omitting words in sentences, especially short connecting words (e.g., “to,” “from,” “the.” The order of words in sentences is often incorrect. Errors are made in the use of word endings, verb tenses and pronouns. Speech becomes restricted to short, simple phrases that are difficult for listener to understand because of omissions and errors.  As examples: the affected individual may use “seed” instead of “saw” or “throwed” instead of “threw.” They may say:  “Today…go lunch…ah…sister” for “today I am going to lunch with my sister.”


Impaired comprehension of complex sentences

Single-word comprehension is unaffected, but the ability to understand long or grammatically difficult sentences is reduced. Persons with PPA may find it increasingly difficult to understand what they experience as “too much” verbal information, i.e. watching television or understanding conversation in a group setting.


Mutism

The affected person does not speak at all.


Difficulty swallowing

Develops later in the progression of the disease.


Motor symptoms

Parkinson’s disease-like movement deficits can occur. The person affected may experience slow, stiff movement, lose balance or fall easily, have difficulty using an arm or leg, and experience restricted up-and-down eye movement.

Diagnosis

Doctors will consider a clinical diagnosis of nfvPPA based on this combination of symptoms:

  • Apraxia of speech
  • Agrammatism

AND at least two of the following symptoms:

  • Impaired comprehension of complex sentences
  • Single-word comprehension unaffected
  • Object knowledge unaffected

Treatment, Management, and What to Expect

As with all forms of FTD, there is no cure for PPA, and in most cases its progression cannot be slowed. No medications currently exist to treat PPA. However, some therapies may help manage it, by helping the individual affected to improve or maintain the ability to communicate.

Transcranial direct current stimulation, repetitive transcranial magnetic stimulation and speech language therapy have shown positive effects but more study is required in order to understand the relationship between amount and timing of treatment and long-term effects. Many PPA patients develop the behavioral, social and/or motor complications seen in other forms of FTD. In these patients, prognosis is obviously poorer and management more complicated. Patients who do not develop these additional symptoms are able to preserve their independence and active lifestyle for a longer period of time.

Genetics

Nonfluent/agrammatic PPA can be sporadic, familial, or hereditary. The majority of cases are not hereditary.

Pathology

According to autopsy reports, the majority of nfvPPA patients (60%) have abnormal accumulations of tau protein in the brain that are distinct from the type of tau protein that accumulates in Alzheimer’s disease. The remaining individuals with nfvPPA either have FTLD-TDP43 protein or an Alzheimer’s pathology on autopsy.


References

  • Gorno-Tempini, M.L., Hillis, A.E., Weintraub, S, et.al. Classification of primary progressive aphasia and its variants. Neurology; March, 2011.
  • Mesulam, M.M. Primary progressive aphasia and the language network. The 2013 Houston Merritt Lecture. Neurology; July,2013.
  • Tippett, D.C., Hillis, A.E., Tspakini, K.  Treatment of Primary Progressive Aphasia. Current Treatment Options Neurology; August 2015.