Establishing two principal dimensions of cognitive variation in logopenic progressive aphasia

Logopenic Progressive Aphasia is a neurodegenerative syndrome characterised by sentence repetition and naming difficulties arising from left-lateralised temporoparietal brain atrophy. Mapping of the clinical phenomenology of this syndrome has largely concentrated on its language deficits. Accumulating evidence, however, points to the presence of cognitive deficits, even on cognitive tasks with minimal language demands. Traditionally, non-linguistic cognitive deficits in Logopenic Progressive Aphasia have been thought to scale with advancing disease severity. When grouped according to the severity of language dysfunction, however, subgroups of Logopenic Progressive Aphasia frequently display overlapping cognitive profiles, suggesting individual-level systematic variation in non-linguistic cognitive performance that may be independent of primary language dysfunction. To address this issue, we used principal component analysis to decompose variation in cognitive performance at an individual level, in a large, well-characterised cohort of Logopenic Progressive Aphasia patients (N = 43). Patients underwent detailed, standardised neuropsychological assessments of language, memory, executive and visuospatial functioning, in addition to structural neuroimaging. The principal component analysis solution revealed the presence of two, statistically independent factors, providing stable and clinically intuitive explanations for the majority of variance in cognitive performance in the syndrome. Factor 1 reflected ‘speech production and verbal memory’ deficits which typify Logopenic Progressive Aphasia. Systematic variations were also confirmed on a second, orthogonal factor mainly comprising visuospatial and executive processes – domains previously thought to be affected later in the disease stage. Adopting a case-comparison approach, we further demonstrate that pairs of patients with comparable speech production and verbal memory factor scores, regardless of their severity, diverge considerably on visuo-executive test performance, underscoring the inherent inter-individual variability in cognitive profiles in comparably ‘logopenic’ patients. Whole-brain voxel-based morphometry analyses revealed that speech production and verbal memory factor scores correlated with left middle frontal gyrus, while visuospatial and executive factor scores were associated with grey matter intensity of right-lateralised temporoparietal, middle frontal regions and their underlying white matter connectivity. Importantly, Logopenic Progressive Aphasia patients with poorer visuospatial and executive factor scores demonstrated greater right-lateralised temporoparietal and frontal atrophy. Our findings demonstrate the inherent variation in general cognitive performance at an individual- and group-level in Logopenic Progressive Aphasia, suggesting the presence of a genuine co-occurring global cognitive impairment, spanning multiple domains, that is independent of language function and disease severity. This variation reflects distinct underlying patterns of neural atrophy, suggests caution in conceptualising Logopenic Progressive Aphasia as exclusively a disorder of language.