Nosology of Primary Progressive Aphasia and the Neuropathology of Language

Abstract

Primary progressive aphasia (PPA) is a dementia syndrome associated with several neuropathologic entities, including Alzheimer's disease (AD) and all major forms of frontotemporal lobar degeneration (FTLD). It is classified into subtypes defined by the nature of the language domain that is most impaired. The asymmetric neurodegeneration of the hemisphere dominant for language (usually left) is one consistent feature of all PPA variants. This feature offers unique opportunities for exploring mechanisms of selective vulnerability in neurodegenerative diseases and the neuroanatomy of language. This chapter reviews some of the current trends in PPA research as well as the challenges that remain to be addressed on the nosology, clinicopathologic correlations, and therapy of this syndrome.

Keywords: Alzheimer; Asymmetry; Broca; Grammar; Language; Naming; Selective vulnerability; Wernicke; Word comprehension.

Figure 1:. PPA-S versus SD-

Figure 1A shows the MRI scan of a right-handed man with symptom onset at the age of 59. On examination seven years later the clinical patterns was PPA-S and atrophy was much more prominent in the left anterior temporal lobe (ATL). At that time he had severe word comprehension impairments but no difficulty with non-verbal object recognition either in testing or in everyday life. In comparison, Figure 1B shows the MRI scan of a right-handed man with symptom onset at the age of 65. Three years later, at his initial visit, ATL atrophy was bilateral. He had prominent word comprehension and object recognition impairments. This combination led to a subsequent diagnosis of semantic dementia (SD).

Figure 2:. Asymmetry of neurodegeneration-

Post-mortem examination of a right-handed woman with symptom onset at the age of 72 and findings of agrammatic PPA with prominent word finding impairments. Death occurred 6 years later. The primary neuropathology was found to be FTLD-tau of the CBD type. The top figures show the profound asymmetry of atrophy. There is an almost cystic area of atrophy around the left inferior frontal gyrus (IFG) but no comparable atrophy of the right. The photomicrographs in the bottom, based on phospho-tau immunostaining in the same patient, show the tauopathy to be more intense in the left IFG than in the right.

Figure 3:. Correspondences of Pathology, Atrophy and Syndrome-

Quantitative MRI morphometry in 3 right-handed patients who had come to post mortem brain autopsy. Areas of significant cortical thinning compared to controls are shown in red and yellow. A- Onset of PPA-G was at the age of 65. The scan was obtained 2 years after onset. B- Onset of PP-G was at the age of 57. The scan was obtained 5 years after onset. C- Onset of PPA-S was at the age of 62. The scan was obtained 5 years after onset. Despite the differences in neuropathology and clinical syndrome, the one common denominator is the profound leftward asymmetry of atrophy.