Causes and Diagnoses

Causes and Diagnoses of Primary Progressive Aphasia

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)
  • 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 percent of cases and by FTLD in approximately 60-70 percent 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 percent 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.

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.

A thorough evaluation of PPA includes the following:

  • Medical History
  • Neurological Examination
  • Neuropsychological Examination
  • Speech and Language Evaluation
  • Psychosocial Evaluation
  • Brain Imaging Studies
  • Psychiatric Evaluation

There are many thousands of people 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. Therefore, some people with PPA often see multiple doctors and receive many different diagnoses before receiving the diagnosis of PPA.