Literature
Clinical Pearls & Morning Reports
Published January 11, 2017
What underlying pathologic processes are associated with primary progressive aphasia?
The anterior temporal lobe is an area of the brain that is critically involved in object naming and word comprehension. Multiple lines of evidence suggest that the left anterior temporal lobe is specialized for word comprehension (recognition), whereas the right anterior temporal lobe may serve a similar function for objects and faces. A new Original Article explains.
Clinical Pearls
Q: What underlying pathologic processes are associated with primary progressive aphasia?
A: In patients with primary progressive aphasia, the underlying pathologic process is usually caused by frontotemporal lobar degeneration or Alzheimer’s disease. Approximately 60% of cases of primary progressive aphasia are associated with frontotemporal lobar degeneration, and 40% are associated with Alzheimer’s disease.
Q: How does primary progressive aphasia differ from typical dementia?
A: In contrast to typical dementias that occur in late life, primary progressive aphasia most commonly starts before 65 years of age and is not associated with memory loss. There are three variants of primary progressive aphasia: agrammatic, logopenic, and semantic.
Morning Report Questions
Q: Describe some of the features of the three variants of primary progressive aphasia.
A: The agrammatic variant is characterized by the construction of grammatically incorrect sentences and a loss of fluency in the setting of preserved word comprehension. The logopenic variant is characterized by impairment of word finding, poor language repetition, and fluctuating fluency in the setting of preserved grammar and word comprehension. The semantic variant is characterized by impairment of object naming and word comprehension in the setting of preserved fluency, repetition, and grammar. Pauses for word finding and impaired object naming can occur in each of the variants. Each variant of primary progressive aphasia is associated with a different anatomical site of peak atrophy in the left-hemisphere language network: the inferior frontal gyrus (Broca’s area) in the agrammatic variant, the temporoparietal junction (Wernicke’s area) in the logopenic variant, and the anterior temporal lobe in the semantic variant.
Figure 1. (10.1056/NEJMcpc1613459/F1) Variants of Primary Progressive Aphasia.
Q: What type of neuronal deposits are associated with the semantic variant of primary progressive aphasia caused by frontotemporal lobar degeneration?
A: There is a strong correlation between the semantic variant of primary progressive aphasia and a type of frontotemporal lobar degeneration that is linked to the presence of abnormal deposits of trans-activation response element (TAR) DNA-binding protein 43 (TDP-43), an RNA-binding protein with a wide range of targets. TDP-associated frontotemporal lobar degeneration is further classified into subgroups defined according to the pattern of inclusions: type A is associated with the presence of many neuronal cytoplasmic inclusions and short dystrophic neurites, type B with the presence of some neuronal cytoplasmic inclusions and rare dystrophic neurites, and type C with the presence of rare neuronal cytoplasmic inclusions and long dystrophic neurites. Although the clinicopathological correlations are not exact, type C lesions often occur with the semantic variant of primary progressive aphasia, semantic dementia, or the behavioral variant of frontotemporal lobar degeneration.