Primary progressive aphasia: a clinical approach

Abstract

The primary progressive aphasias are a heterogeneous group of focal 'language-led' dementias that pose substantial challenges for diagnosis and management. Here we present a clinical approach to the progressive aphasias, based on our experience of these disorders and directed at non-specialists. We first outline a framework for assessing language, tailored to the common presentations of progressive aphasia. We then consider the defining features of the canonical progressive nonfluent, semantic and logopenic aphasic syndromes, including 'clinical pearls' that we have found diagnostically useful and neuroanatomical and other key associations of each syndrome. We review potential diagnostic pitfalls and problematic presentations not well captured by conventional classifications and propose a diagnostic 'roadmap'. After outlining principles of management, we conclude with a prospect for future progress in these diseases, emphasising generic information processing deficits and novel pathophysiological biomarkers.

Keywords: Alzheimer’s disease; Frontotemporal dementia; Logopenic aphasia; Primary progressive aphasia; Semantic dementia.

Fig. 1

Neuroanatomical and cognitive profiles of the canonical syndromes of progressive aphasia. The top panels present coronal T1-weighted brain MRI sections (in radiological convention, with the left hemisphere on the right) of patients with typical syndromes of nonfluent–agrammatic variant primary progressive aphasia (nfvPPA), showing asymmetric (predominantly left sided) inferior frontal, insular and anterior–superior temporal gyrus atrophy; semantic variant primary progressive aphasia (svPPA), showing asymmetric (predominantly left sided) anterior inferior and mesial temporal lobe atrophy; and logopenic variant primary progressive aphasia (lvPPA), showing atrophy predominantly involving left temporo-parietal junction (posterior–superior temporal and inferior parietal cortices). The cut-away brain schematic (right) indicates the distributed cerebral networks involved in each syndrome; the left cerebral hemisphere is projected forward and major neuroanatomical associations are in bold italics: a, amygdala; ATL, anterior temporal lobe; BG, basal ganglia; h, hippocampus; IFG, inferior frontal gyrus/frontal operculum; ins, insula; OFC, orbitofrontal cortex; PMC, posterior medial cortex (posterior cingulate, precuneus); STG, superior temporal gyrus; TPJ, temporo-parietal junction. The ‘target diagrams’ below show typical profiles of neuropsychological test performance for each syndrome; concentric circles indicate the percentile scores relative to a healthy age-matched population and the distance along the radial dimension represents the level of functioning in the following cognitive domains: ex, executive skills; l, literacy skills; n, naming; nm, nonverbal memory; pr, phrase repetition; s, sentence processing; v, visuo-spatial; vm, verbal memory; wm, word meaning; wr, word repetition

Fig. 2

Example of a picture that can be used to elicit conversational speech (reproduced with permission of Professor EK Warrington). A scene of this kind can be used to assess naming and also to probe aspects of language comprehension, at the level of single words (using questions such as, ‘Where is the sandcastle?’) and grammatical relations embodied in sentences (using instructions such as, ‘Point to the thing that the boy is holding above the boat’)

Fig. 3

A clinical ‘roadmap’ for diagnosis of canonical primary progressive aphasia syndromes, synthesising key features on history and examination. The ‘forks’ comprising the middle section of the map indicate major decision points, for corroboration using the more detailed framework presented in Table 2. Neuropsychological assessment (where available) is used both to support and quantify the clinical impression and to reveal additional cognitive deficits that may not be emphasised in the clinic but define the overall syndrome (see Fig. 1). Brain imaging (wherever feasible, MRI) is essential to rule out brain tumours and other non-degenerative pathologies that can occasionally present with progressive aphasia; it also has an important ‘positive’ role in corroborating the neuroanatomical diagnosis (see Fig. 1). Ancillary investigations such as CSF examination are used to stratify pathologies within particular syndromes (e.g., lvPPA), with a view to prognosis and treatment. A significant minority of cases will not be diagnosed by this algorithm, falling into the still poorly defined category of ‘atypical’ progressive aphasias (see text and Table 1). lvPPA, logopenic variant primary progressive aphasia; nfvPPA, nonfluent–agrammatic variant primary progressive aphasia; svPPA, semantic variant primary progressive aphasia