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

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.Electronic supplementary materialThe online version of this article (10.1186/s13195-018-0345-3) contains supplementary material, which is available to authorized users.

Clinical and cortical decline in the aphasic variant of Alzheimer's disease

“…Thus, cortical ROI measures such as the PSTC R may be useful for future clinical trials and may allow for smaller sample sizes to detect a significant effect. Intriguing summary scores of language performance are emerging [10] and may be useful to detect change as they are optimized. Understanding consistency of these measures at the individual level over the disease course is important before they can be reliably introduced as clinical trial outcome metrics.…”

“…Determinants of the pace of decline in PPA are incompletely understood, especially whether the presence of AD versus non-AD pathology influences the rate of deterioration. This is in part because of a dearth of prospective longitudinal investigations [8][9][10][11][12][13][14] relative to crosssectional investigations and the historic lack of in vivo neuropathologic biomarkers. Disease duration estimates for individuals with PPA range from 3 to 20 years, highlighting the individual variability in progression rates.…”

Quantifying progression in primary progressive aphasia with structural neuroimaging

“…A total of n = 106 subjects and their volumetric data of up to three timepoints (V1 to V3) was finally included in this study. Data were collected between 2011 and 2018 from 10 German sites (Bonn, Erlangen, Göttingen, Hamburg, Homburg/Saar, Leipzig, Munich, Rostock, Ulm, Würzburg); data subsets have been used previously 29,30 …”

“…Each study visit included a neurological and an extensive neuropsychological protocol (for details see Semler et al 29 29 indicated each patient's language abilities.…”

“…Each study visit included a neurological and an extensive neuropsychological protocol (for details see Semler et al 29 ) The balanced PPA sum score 29 indicated each patient's language abilities. Trained raters conducted the Frontotemporal-specific Clinical Dementia Rating Scale (FTLD-CDR) 31 at each visit.…”