Primary progressive aphasia and the evolving neurology of the language network

Abstract

Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke’s area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

Aphasic variant of Alzheimer disease

“…The peak atrophy pattern for the group (figure 2) showed a distribution similar to previous reports of atrophy and hypoperfusion in PPA participants with autopsy or biomarker evidence of AD. 25,27 The concentration of atrophy in the temporoparietal junction and adjacent superior temporal gyrus mirrors atrophy patterns of PPA-L 13 and is in keeping with the greater representation of logopenic participants in the group atrophy map shown in figure 2. The asymmetrical atrophy distribution in our PPA cohort differs from typical amnestic forms of AD, 29 which tends to be symmetric.…”

“…The 2011 classification guidelines for PPA-S, PPA-G, and PPA-L were followed with a few modifications. 2,13 None of the 19 fit the PPA-S criteria. The differentiation of PPA-L from PPA-G is arguably the most challenging aspect of PPA classification.…”

“…The differentiation of PPA-L from PPA-G is arguably the most challenging aspect of PPA classification. 13,14 In this study, the diagnosis of PPA-G was made when 2 criteria were met: (1) noncanonical sentence production scores of #80% on the NAT-NAVS; and (2) presence of agrammatic sentences in recorded narrative or writing samples. The cutoff at 80% performance on the NAT-NAVS test was empirically chosen based on a prior investigation of PPA subtyping at mild impairment stages.…”

Neuroanatomical foundations of naming impairments across different neurologic conditions

“…26,27 Their difficulty resides in accessing the mental representations to name objects they know. The pathology underlying this variant of PPA is similar to findings typical of AD, 12,13 which can also present with word retrieval difficulties. Likewise, naming impairment in patients with AD is thought to result from degeneration of temporal and parietal circuitry.…”

“…10,11 Patients with progressive neurodegeneration of these areas exhibit marked impairment in naming and single word comprehension, producing relatively fluent speech, albeit filled with semantic paraphasias and circumlocutions. 12 A prime example of this condition is the semantic variant of primary progressive aphasia (PPA-S), which is usually associated with frontotemporal lobar degeneration (FTLD)-TDP pathology. 13 Impaired naming and semantic errors are also characteristic of patients with damage to the left posterior temporal cortex, especially in the superior gyrus (figure 2, area 4), most frequently as a result of stroke.…”