Primary Progressive Aphasia

Excerpt

Primary Progressive Aphasia Overview

Aphasia is a language disorder arising from damage to a specific brain area controlling language comprehension, formulation, and expression. Primary progressive aphasia (PPA) refers to a group of neurodegenerative diseases in which gradual speech and language impairment are the primary presenting symptoms, unaccompanied by marked cognitive, physical, or behavioral changes. Classic aphasia occurring after conditions such as stroke develops abruptly, but PPA has a gradual onset.

PPA characterization and differentiation based on linguistic and nonlinguistic profiles are now easier to accomplish due to extensive research. Advanced neuroimaging techniques like diffusion-weighted imaging (DWI) and resting-state functional magnetic resonance imaging (fMRI) allow healthcare providers to go beyond distinct focal gray matter atrophy patterns to a deeper understanding of PPA's effects on structural and functional connectivity changes. However, despite significant diagnostic advances, a clear consensus on its pathology remains elusive. Nevertheless, improved PPA characterization may positively impact patient management.

Fluent aphasia refers to deficits related to comprehension and is usually associated with Wernicke brain area pathologies. In contrast, nonfluent aphasias produce a failure in written or verbal language expression and are often associated with Broca brain area lesions. The general concept of a primary progressive language impairment disease process without cognitive effects was first described in the 1890s by Pick and Serieux. However, Mesulam is presently credited for exploring "slowly progressive aphasia" and coining its name in the 1980s. "Slowly progressive aphasia" was later renamed in the literature as "primary progressive aphasia."

PPA is closely related to Alzheimer and Pick diseases. Thus, PPA classification and diagnosis can sometimes be controversial. PPA's 3 main variants are nonfluent/agrammatic (nfvPPA), semantic (svPPA), and logopenic (lvPPA). PPA presents similarly to primary progressive apraxia, a gradual, degenerative disorder affecting the planning, programming, and execution of sensorimotor commands required for speech production. Pathologically, nfvPPA is grouped under the frontotemporal dementia (FTD) syndromes. In contrast, the logopenic variant is frequently classified as an atypical Alzheimer disease form.

Anatomical Considerations for PPA

In PPA, neuroanatomical changes primarily affect brain regions associated with language processing. The specific areas vary depending on the PPA subtype, but commonly involved brain regions affect left-hemisphere language functions. The Broca area within the left inferior frontal gyrus' posterior portion is responsible for language production and grammar. The Wernicke area within the left superior temporal gyrus' posterior aspect is involved in language comprehension. The angular gyrus at the parietal, temporal, and occipital lobe junction is implicated in semantic processing and reading. The left temporal lobe is crucial in language processing, including semantic memory and word retrieval. Damage to these areas can lead to word-finding and semantic knowledge deficits.

The frontal lobes, especially the left inferior frontal gyrus, are involved in language production, grammar, and articulation. Injury to these areas results in nonfluent or agrammatic speech. The parietal lobes, including the angular gyrus, contribute to language processing, particularly in reading and semantic comprehension. Damage to these regions can impair reading comprehension and semantic processing. Some PPA cases may also affect posterior language areas beyond the traditional language cortex. These areas include regions involved in visual processing and multisensory integration, impacting reading and comprehension abilities. Understanding PPA's neuroanatomical basis is crucial for accurate diagnosis, prognosis estimation, and developing targeted interventions tailored to individual patients' specific language deficits and affected brain regions.