There are several forms of aphasia, or a disorder of language, that can gradually worsen over time. These are not due to head trauma, stroke, cancer or other observable secondary changes in the brain, and hence appear to be intrinsic disorders of brain functioning – as such, we refer to this class of conditions as “primary.”
Several features characterize the nonfluent/agrammatic variant of primary progressive aphasia (PPA), also known as Progressive Nonfluent Aphasia (PNFA). The most salient characteristic is a slowing of speech production. Healthy adults typically speak at a rate of about 140 words per minute, but individuals with the nonfluent/agrammatic variant of PPA speak on average at a rate of about 40 words per minute, or less than a word per second. This slowed speech rate is not due primarily to a motor disorder. Nor does this appear to be due to difficulty with general cognitive planning and organization. Instead, there appears to be a specific disorder of integrating words together into a sentence.
We refer to the integration of words into a sentence as grammar, or the uniquely human ability to build sentences creatively with novel word sequences. Grammar is the set of rules that interrelate words in a sentence, even if they are not adjacent to each other. It appears that individuals with the nonfluent/agrammatic variant of PPA have difficulty using these grammatical rules to construct sentences, and thus have profoundly slowed speech.
Over time, individuals with the nonfluent/agrammatic variant of PPA can become virtually mute. This grammatical deficit also can affect sentence comprehension, particularly sentences that are lengthy and depend on grammar for their meaning. Similar grammatical difficulties are seen in reading and writing, although these may emerge later than difficulties in oral speech. This is because the rate of language use is under the control of readers and writers, but oral speech and comprehension is more difficult to control.
Individuals with the nonfluent/agrammatic variant of PPA can have other difficulties as well. These individuals can have many speech sound errors in their speech. This includes substituting one sound for another in a word, exchanging speech sounds between words, or omitting sounds from a word.
Individuals with the nonfluent/agrammatic variant of PPA also can develop other neurological difficulties. Some individuals can develop an extrapyramidal disorder such as progressive supranuclear palsy or corticobasal syndrome. These are characterized by involuntary movements such as tremor (a rhythmic involuntary movement of a limb or the head), myoclonus (a sharp, non-rhythmic, jumping movement of a limb or the body), or dystonia (a cramping, involuntary clenching or extending posture of a limb that lasts for seconds). Some individuals can develop stiffness or rigidity of a limb or the body. There can also be difficulty with walking and postural stability.
Other individuals with the nonfluent/agrammatic variant of PPA can develop motor weakness or loss of force in the limbs or body. Small muscles can be seen to quiver underneath the skin and there can be loss of muscle bulk. This condition is known as amyotrophic lateral sclerosis. Physicians at the Penn FTD Center carefully examine individuals with the nonfluent/agrammatic variant of PPA to look for early signs of these conditions and initiate treatments.
Inspection of the brain at autopsy reveals that the most common cause of the nonfluent/agrammatic variant of PPA is the accumulation of misfolded tau protein in neurons of the brain’s gray matter and in the deep white matter of the brain. These changes are seen in about 70% of individuals with the nonfluent/agrammatic variant of PPA.
During life, it is possible to identify the cause of the nonfluent/agrammatic variant of PPA by inspection of the cerebrospinal fluid (CSF). This is the fluid that bathes the brain and spinal cord, and thus contains some of the proteins that are found in the brain. Rather than performing a brain biopsy to study the brain during life, a lumbar puncture (also known as a spinal tap) can be performed. Researchers at the Penn FTD Center have developed techniques for measuring tau protein in the CSF that is suggestive of the nonfluent/agrammatic variant of PPA.
In other individuals with the nonfluent/agrammatic variant of PPA, there can be an accumulation of TDP-43. Researchers at the Penn FTD Center discovered this protein in 2006. TDP-43 is important for correcting errors during a cell’s production of RNA from DNA, and helps protect brain cells from inflammation associated with a wide variety of brain processes. TDP-43 also accumulates in the brains of many individuals with amyotrophic lateral sclerosis.
It can be difficult to diagnose the nonfluent/agrammatic variant of PPA solely on the basis of inspecting the CSF. To improve diagnostic accuracy, researchers at the Penn FTD Center have developed novel imaging techniques to study the gray matter and the white matter of the brain. MRI scans of individuals with the nonfluent/agrammatic variant of PPA often show atrophy in the region of the left frontal lobe, the area of the brain behind the eye. LINK When measures of these areas of atrophy are combined with studies of the CSF, an accurate diagnosis can be achieved in most cases.
It is important to achieve an accurate diagnosis because treatment trials are beginning to emerge that can help block the accumulation of misfolded tau in the brain. Researchers at the Penn FTD Center are actively engaged in developing treatments for nonfluent/agrammatic primary progressive aphasia and other conditions caused by misfolded tau, and our collaborators are continuing to develop new treatments.
While there are currently no treatments available by prescription, it is possible to borrow medications that are available for other neurodegenerative conditions to help with the symptomatic management of the speech and language difficulties of individuals with the nonfluent/agrammatic variant of PPA.
Speech therapies can be implemented that help with grammatical comprehension. Communication efficacy is enhanced when conversing in a familiar environment at a slow speech rate, supplemented by gestures. Computer devices are very helpful for individuals with the nonfluent/agrammatic variant of PPA since these can hold prerecorded phrases and sentences that the individual can use to assist communication.
Some medications are also available to help manage some of the non-speech neurological aspects of the nonfluent/agrammatic variant of PPA.