A language-based sum score for the course and therapeutic intervention in primary progressive aphasia

Elisa Semler,Johannes Prudlo,Matthias L Schroeter,Martin Lauer,Holger Jahn,Beate Einsiedler,Johannes Kornhuber,Ingo Uttner,Rainer Muche,Anja Schneider,Albert C Ludolph,Adrian Danek,Klaus Faßbender ,Hans‐Jürgen Huppertz ,G Bernhard Landwehrmeyer ,Sarah Anderl‐Straub ,Janine Diehl‐Schmid ,Klaus Fließbach ,Markus Otto

doi:10.1186/s13195-018-0345-3

Abstract

BackgroundWith upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions.MethodsWe assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials.ResultsSignificant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures.ConclusionOur findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies.

Highlights

With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects
Primary progressive aphasia (PPA) comprises a group of neurodegenerative disorders in which language problems are the principal cause of impaired daily living activities, whereas other neurobehavioral or cognitive deficits are rare during the initial stages of the illness [1]
Post-hoc tests revealed earlier symptom onset (p =0.011) and longer disease duration (p =0.008) in Semantic variant primary progressive aphasia (svPPA) compared to Nonfluent variant primary progressive aphasia (nfvPPA)

Summary

Introduction

With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. Rogalski et al [9] examined the longitudinal course of PPA over a 2-year period in 10 nfvPPA, 8 svPPA, and 8 lvPPA patients. They concluded that analyzing a focal cortical language network is a more sensitive clinical outcome measure than whole brain or ventricular volume measures. None of these studies provided a clinical tool that can be used for comprehensive language assessment and for sample size calculation of a clinical trial. This is, prerequisite for any upcoming trials, e.g., using tau protein immunization strategies [10]

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