Aphasia is a disorder of language, and there are several variants of primary progressive aphasia (PPA) where language declines slowly and in a manner that affects a particular aspect of language. 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.”
In the semantic variant of PPA, also known as semantic dementia, individuals have key difficulty in their ability to name and understand objects. It is thought that this is due to a disorder in the representation of object concepts in the brain. Because of difficulty with the names of objects, speech in these individuals often can seem empty of content. Likewise, there is often difficulty understanding what others are saying. Because this is a disorder of the entire concept, individuals with the semantic variant of PPA also can have difficulty recognizing and using objects properly.
Other features can be seen in the semantic variant of PPA. For example, some individuals have difficulty reading site vocabulary words. This deficit with concepts can extend to difficulty recognizing people, including famous faces.
In some individuals who present with the semantic variant of Primary Propgressive Aphasia, a disorder of behavioral comportment and social cognition can emerge over time. This can involve rigidity and elaborate rituals that can become religious in nature. There can also be explosive anger without provocation. Conversely, individuals who present with a social disorder can develop the semantic variant of PPA over time.
The syndrome of the semantic variant of PPA is associated with a characteristic MRI finding, namely, atrophy in the portion of the temporal lobe that sits behind the eye and deep to the ear. The semantic variant of PPA most often begins with disease in the left temporal lobe. As the disease spreads further back in the temporal lobe over time, there is increasing difficulty with comprehension and naming. The disease also can involve portions of the right temporal lobe. In parallel with atrophy involving more of the right temporal lobe, the individual may begin to demonstrate increasingly unusual behaviors.
The brains of individuals with the semantic variant of PPA has been studied at autopsy by researchers at thePenn Frontotemporal Degeneration Center. The most common cause of the semantic variant of PPA is the accumulation of a protein found in he nucleus of brain cells known as 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. Less commonly, aggregations of the microtubule-associated protein tau or combinations of tau tangles and Aβ plaues consistent with Alzheimer’s disease pathology, are found as the underlying disorder for this syndrome.
There are currently no clinical trials targeting TDP-43. Treatment of the semantic variant of PPA thus is largely symptomatic. Individuals with the semantic variant of PPA can take advantage of behavioral and speech therapies and improve their own naming and comprehension skills through practice in normal conversations. Some individuals benefit from a picture dictionary. Communication efficacy is enhanced when conversing in a familiar environment at a slow speech rate, supplemented by gestures. Computer devices can hold prerecorded phrases and sentences that the individual can use to assist communication.
In addition to performing detailed studies to characterize individuals with the semantic variant of PPA, scientists at the Penn FTD Center have developed techniques to study the CSF, perform detailed analyses of MRI scans, and to relate language, MRI and CSF characteristics together to provide an accurate diagnosis of patients with PPA so that the most effective treatments can be applied.