Primary progressive aphasia: conceptual evolution and challenges

Abstract

Since the modern description of primary progressive aphasia (PPA) more than 30 years ago, the interest in neurodegenerative conditions that selectively target the language network has grown exponentially. Fueled by advances in neuroimaging and biomarkers, progress in the field has brought new insights into clinical categorization, neural correlates of language, and pathological mechanisms of progression in PPA. Of relevance, the inception of logopenic progressive aphasia as an atypical presentation of Alzheimer's disease and the formalization of the international diagnostic criteria and classification of PPA represent milestones in the field. Paradoxically, those advances have also brought controversy and challenges. The application of the current classification in cases with mixed or very mild language deficits is still challenging, while the accurate pathological prediction at the individual level remains elusive. In addition, it is more evident now that nonlanguage deficits, including other cognitive and motor deficits, can appear early on and potentially assist in the differential diagnosis. From a historical perspective, this review addresses the conceptual evolution of PPA and the contribution that clinical refine - ments, cognitive neuropsychology, and pathology have made to the field.