scholarly journals 124 Correlating structure and function to better identify surrogate end points for clinical trial design: a longitudinal clinical and imaging study of primary progressive aphasia

2019 ◽  
Vol 90 (e7) ◽  
pp. A40.2-A40
Author(s):  
Colin Mahoney
Keyword(s):  
White Matter ◽  
Trial Design ◽  
Primary Progressive Aphasia ◽  
Longitudinal Change ◽  
Imaging Biomarkers ◽  
Therapeutic Trial ◽  
End Points ◽  
White Matter Tracts ◽  
Progressive Aphasia ◽  
Primary Progressive

IntroductionMeasuring longitudinal change in white matter tracts offers a highly sensitive way of monitoring the course of a range of neurodegenerative conditions. However, it remains unclear how structural changes correlate with symptom progression. Clinically meaningful outcomes remain a key requirement in therapeutic trial design so imaging biomarkers need to accurately predict these outcomes. Identifying surrogate clinical end points is of particular importance in neurodegenerative conditions where clinical change evolves slowly. To address this the current study aims to identify potential surrogate end points by assessing correlations between clinical and neuroimaging measures.Methods30 patients meeting consensus criteria for a diagnosis of primary progressive aphasia underwent longitudinal imaging and neuropsychological assessments at baseline and one year. A mixed effects model was designed to test for significant interactions over time between changes in neuropsychological performance and Fractional Anisotropy (FA) in key white matter tracts.ResultsDeclining single word comprehension correlated with reducing FA within bilateral inferior longitudinal fasciculus (ILF), bilateral superior longitudinal fasciculus (SLF) and the genu of the corpus callosum; declining naming ability correlated with reducing FA in the left ILF, right uncinate fasciculus and right SLF; declining word repetition correlated with reducing FA within the left ILF.ConclusionsDeclining neuropsychological scores correlated with longitudinal decline in FA in a number of white matter tracts across an anatomically distributed language network. Correlations between function and structure provide evidence that monitoring structural white matter changes in the tracks identified may have value as a surrogate end point for future clinical trials.

scholarly journals Frontal White Matter Tracts Sustaining Speech Production in Primary Progressive Aphasia

2014 ◽  
Vol 34 (29) ◽  
pp. 9754-9767 ◽  
Author(s):  
M. L. Mandelli ◽  
E. Caverzasi ◽  
R. J. Binney ◽  
M. L. Henry ◽  
I. Lobach ◽  
...  
Keyword(s):  
White Matter ◽  
Speech Production ◽  
Primary Progressive Aphasia ◽  
White Matter Tracts ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Frontal White Matter

scholarly journals Infratentorial pathology in frontotemporal dementia: cerebellar grey and white matter alterations in FTD phenotypes

2021 ◽  
Author(s):  
Mary Clare McKenna ◽  
Rangariroyashe H. Chipika ◽  
Stacey Li Hi Shing ◽  
Foteini Christidi ◽  
Jasmin Lope ◽  
...  
Keyword(s):  
White Matter ◽  
Fractional Anisotropy ◽  
Cortical Thickness ◽  
Cerebellar Atrophy ◽  
Primary Progressive Aphasia ◽  
Radial Diffusivity ◽  
Axial Diffusivity ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Crus I

AbstractThe contribution of cerebellar pathology to cognitive and behavioural manifestations is increasingly recognised, but the cerebellar profiles of FTD phenotypes are relatively poorly characterised. A prospective, single-centre imaging study has been undertaken with a high-resolution structural and diffusion tensor protocol to systematically evaluate cerebellar grey and white matter alterations in behavioural-variant FTD(bvFTD), non-fluent variant primary progressive aphasia(nfvPPA), semantic-variant primary progressive aphasia(svPPA), C9orf72-positive ALS-FTD(C9 + ALSFTD) and C9orf72-negative ALS-FTD(C9-ALSFTD). Cerebellar cortical thickness and complementary morphometric analyses were carried out to appraise atrophy patterns controlling for demographic variables. White matter integrity was assessed in a study-specific white matter skeleton, evaluating three diffusivity metrics: fractional anisotropy (FA), axial diffusivity (AD) and radial diffusivity (RD). Significant cortical thickness reductions were identified in: lobule VII and crus I in bvFTD; lobule VI VII, crus I and II in nfvPPA; and lobule VII, crus I and II in svPPA; lobule IV, VI, VII and Crus I and II in C9 + ALSFTD. Morphometry revealed volume reductions in lobule V in all groups; in addition to lobule VIII in C9 + ALSFTD; lobule VI, VIII and vermis in C9-ALSFTD; lobule V, VII and vermis in bvFTD; and lobule V, VI, VIII and vermis in nfvPPA. Widespread white matter alterations were demonstrated by significant fractional anisotropy, axial diffusivity and radial diffusivity changes in each FTD phenotype that were more focal in those with C9 + ALSFTD and svPPA. Our findings indicate that FTD subtypes are associated with phenotype-specific cerebellar signatures with the selective involvement of specific lobules instead of global cerebellar atrophy.

PROMINENT MICROGLIAL ACTIVATION IN CORTICAL WHITE MATTER IS SELECTIVELY ASSOCIATED WITH CORTICAL ATROPHY IN PRIMARY PROGRESSIVE APHASIA

2017 ◽  
Vol 13 (7) ◽  
pp. P1499
Author(s):  
Daniel T. Ohm ◽  
Garam Kim ◽  
Tamar Gefen ◽  
Alfred Rademaker ◽  
Sandra Weintraub ◽  
...  
Keyword(s):  
White Matter ◽  
Microglial Activation ◽  
Primary Progressive Aphasia ◽  
Cortical Atrophy ◽  
Progressive Aphasia ◽  
Primary Progressive

scholarly journals Whole-brain white matter disruption in semantic and nonfluent variants of primary progressive aphasia

2011 ◽  
Vol 34 (4) ◽  
pp. 973-984 ◽  
Author(s):  
Graeme C. Schwindt ◽  
Naida L. Graham ◽  
Elizabeth Rochon ◽  
David F. Tang-Wai ◽  
Nancy J. Lobaugh ◽  
...  
Keyword(s):  
White Matter ◽  
Primary Progressive Aphasia ◽  
Whole Brain ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Brain White Matter

scholarly journals White Matter Hyperintensities Contribute to Language Deficits in Primary Progressive Aphasia

2020 ◽  
Vol 33 (3) ◽  
pp. 179-191
Author(s):  
Erin L. Meier ◽  
Bonnie L. Breining ◽  
Shannon M. Sheppard ◽  
Emily B. Goldberg ◽  
Donna C. Tippett ◽  
...  
Keyword(s):  
White Matter ◽  
White Matter Hyperintensities ◽  
Primary Progressive Aphasia ◽  
Language Deficits ◽  
Progressive Aphasia ◽  
Primary Progressive

scholarly journals Emotion detection deficits and changes in personality traits linked to loss of white matter integrity in primary progressive aphasia

2017 ◽  
Vol 16 ◽  
pp. 447-454 ◽  
Author(s):  
Namita Multani ◽  
Sebastiano Galantucci ◽  
Stephen M. Wilson ◽  
Tal Shany-Ur ◽  
Pardis Poorzand ◽  
...  
Keyword(s):  
White Matter ◽  
Personality Traits ◽  
Primary Progressive Aphasia ◽  
White Matter Integrity ◽  
Emotion Detection ◽  
Progressive Aphasia ◽  
Primary Progressive

scholarly journals Divergent Longitudinal Propagation of White Matter Degradation in Logopenic and Semantic Variants of Primary Progressive Aphasia

2015 ◽  
Vol 49 (3) ◽  
pp. 853-861 ◽  
Author(s):  
Sicong Tu ◽  
Cristian E. Leyton ◽  
John R. Hodges ◽  
Olivier Piguet ◽  
Michael Hornberger
Keyword(s):  
White Matter ◽  
Primary Progressive Aphasia ◽  
Progressive Aphasia ◽  
Primary Progressive

User-Independent Analyses of White Matter Tractography in Primary Progressive Aphasia (P03.091)

Neurology ◽  
2012 ◽  
Vol 78 (Meeting Abstracts 1) ◽  
pp. P03.091-P03.091 ◽  
Author(s):  
C. Brun ◽  
C. McMillan ◽  
P. Yushkevich ◽  
J. Gee ◽  
M. Grossman
Keyword(s):  
White Matter ◽  
Primary Progressive Aphasia ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
White Matter Tractography

scholarly journals White Matter Integrity Predicts Electrical Stimulation (tDCS) and Language Therapy Effects in Primary Progressive Aphasia

2020 ◽  
Vol 35 (1) ◽  
pp. 44-57
Author(s):  
Yi Zhao ◽  
Bronte Ficek ◽  
Kimberly Webster ◽  
Constantine Frangakis ◽  
Brian Caffo ◽  
...  
Keyword(s):  
White Matter ◽  
Diffusion Tensor ◽  
Inferior Frontal Gyrus ◽  
Mean Diffusivity ◽  
Primary Progressive Aphasia ◽  
White Matter Integrity ◽  
Language Therapy ◽  
Progressive Aphasia ◽  
Primary Progressive ◽  
Language Pathways

Background Transcranial direct current stimulation (tDCS), in conjunction with language therapy, improves language therapy outcomes in primary progressive aphasia (PPA). However, no studies show whether white matter integrity predicts language therapy or tDCS effects in PPA. Objective We aimed to determine whether white matter integrity, measured by diffusion tensor imaging (DTI), predicts written naming/spelling language therapy effects (letter accuracy on trained and untrained words) with and without tDCS over the left inferior frontal gyrus (IFG) in PPA. Methods Thirty-nine participants with PPA were randomly assigned to tDCS or sham condition, coupled with language therapy for 15 daily sessions. White matter integrity was measured by mean diffusivity (MD) and fractional anisotropy (FA) in DTI scans before therapy. Written naming outcomes were evaluated before, immediately after, 2 weeks, and 2 months posttherapy. To assess tDCS treatment effect, we used a mixed-effects model with treatment evaluation and time interaction. We considered a forward model selection approach to identify brain regions/fasciculi of which white matter integrity can predict improvement in performance of word naming. Results Both sham and tDCS groups significantly improved in trained items immediately after and at 2 months posttherapy. Improvement in the tDCS group was greater and generalized to untrained words. White matter integrity of ventral language pathways predicted tDCS effects in trained items whereas white matter integrity of dorsal language pathways predicted tDCS effects in untrained items. Conclusions White matter integrity influences both language therapy and tDCS effects. Thus, it holds promise as a biomarker for deciding which patients will benefit from language therapy and tDCS.

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