Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia

Abstract

The logopenic variant of primary progressive aphasia is characterized by early deficits in language production and phonological short-term memory, attributed to left-lateralized temporoparietal, inferior parietal and posterior temporal neurodegeneration. Despite patients primarily complaining of language difficulties, emerging evidence points to performance deficits in non-linguistic domains. Temporoparietal cortex, and functional brain networks anchored to this region, are implicated as putative neural substrates of non-linguistic cognitive deficits in logopenic variant primary progressive aphasia, suggesting that degeneration of a shared set of brain regions may result in co-occurring linguistic and non-linguistic dysfunction early in the disease course. Here, we provide a Review aimed at broadening the understanding of logopenic variant primary progressive aphasia beyond the lens of an exclusive language disorder. By considering behavioural and neuroimaging research on non-linguistic dysfunction in logopenic variant primary progressive aphasia, we propose that a significant portion of multidimensional cognitive features can be explained by degeneration of temporal/inferior parietal cortices and connected regions. Drawing on insights from normative cognitive neuroscience, we propose that these regions underpin a combination of domain-general and domain-selective cognitive processes, whose disruption results in multifaceted cognitive deficits including aphasia. This account explains the common emergence of linguistic and non-linguistic cognitive difficulties in logopenic variant primary progressive aphasia, and predicts phenotypic diversification associated with progression of pathology in posterior neocortex.

Keywords: Alzheimer’s disease; inferior parietal lobe; language; non-linguistic functions; primary progressive aphasia; temporoparietal junction.

Figure 1

Graphical summary of the main premise of this Review. (A) Insights from cognitive neuroscience indicate that the left posterior temporal cortices (including superior/middle/inferior temporal gyrus and TPJ; together, denoted within the white square) (reprinted from Kanwisher) and left supramarginal and angular gyri (components of the IPL) (reprinted from Humphreys and Lambon Ralph) support multiple cognitive functions, possibly through deployment of domain-general and domain-selective computations. These computations support phonology and working memory, episodic and semantic memory, social and numerical cognition, visuospatial and executive abilities, as well as attention and praxis functions. (B) lvPPA targets left posterior temporal and TPJ/IPL regions (depicted here as reduced cortical thickness, i.e. warmer colours) suggesting the aforementioned cognitive functions dependent on TPJ/IPL functionality should be affected (reprinted from Leyton et al. with permission from IOS Press). (C) A recent meta-analysis of neuropsychological performance in 663 lvPPA patients (across 51 studies) found significant performance deficits across standardized neuropsychological measures of episodic memory, social and numerical cognition, executive functions, and attention in lvPPA relative to nfvPPA (‘N’ in figure) and svPPA (‘S’ in figure) groups (reprinted from Kamath et al. with permission from Cambridge University Press), showcasing the multidimensional cognitive profile of this syndrome.

Figure 2

Capturing phenotypic variations in lvPPA within a graded, multidimensional space. (A) Capturing cognitive changes to language and non-linguistic domains within a multidimensional space allows an examination of the graded, individual-level variations in patients’ profiles, as well as the underlying neural machinery that is affected in each case. STM = short-term memory; PCA = posterior cortical atrophy; AD = Alzheimer’s disease. (B) The nature of such a multidimensional graded space including the lvPPA phenotype receives support from the empirical findings of Ramanan et al. Here, principal component analysis on comprehensive neuropsychological performance data (n = 43 lvPPA) revealed multiple, independent sources of variation, captured best by two orthogonal dimensions of performance labelled ‘speech production and verbal memory’ and ‘visuospatial and executive’ (visuo-executive) performances. The finding that lvPPA patients, irrespective of the extent of their speech production and verbal memory performance, display some level of visuo-executive changes (c.f. coloured pairs) suggests individual-level variation in cognitive phenotype that necessitates the use of a multidimensional space. Here, dashed gold lines indicate lower bound of performance in healthy Controls (adapted from Ramanan et al.). (C) The adoption of a multidimensional space to account for linguistic and non-linguistic changes in lvPPA can further afford mapping of heterogeneous disease trajectories dynamically varying at the individual-level. This includes individuals showing generalized cognitive impairment that are (i) linear with disease progression (square); (ii) emerge quickly into disease onset (triangle and pentagon); or (iii) emerge slowly with disease advancement (diamond and circle). Here, numbers correspond to the clinical assessment round (1 = 1st assessment etc.). STM = short term memory.