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White Matter Damage in the Semantic Variant of Primary Progressive Aphasia

  • Louis-Olivier Bouchard (a1) (a2), Maximiliano A. Wilson (a2) (a3), Robert Laforce (a4) (a5) (a6) and Simon Duchesne (a1) (a2)
Abstract:

Background: The semantic variant of primary progressive aphasia (svPPA) is a form of dementia, mainly featuring language impairment, for which the extent of white matter (WM) damage is less described than its associated grey matter (GM) atrophy. Our study aimed to characterise the extent of this damage using a sensitive and unbiased approach. Methods: We conducted a between-group study comparing 10 patients with a clinical diagnosis of svPPA, recruited between 2011 and 2014 at a tertiary reference centre, with 9 cognitively healthy, age-matched controls. From diffusion tensor imaging (DTI) data, we extracted fractional anisotropy (FA) values using a tract-based spatial statistics approach. We further obtained GM volumetric data using the Freesurfer automated segmentation tool. We compared both groups using non-parametric Wilcoxon rank-sum tests, correcting for multiple comparisons. Results: Demographic data showed that patients and controls were comparable. As expected, clinical data showed lower results in svPPA than controls on cognitive screening tests. Tractography showed impaired diffusion in svPPA patients, with FA mostly decreased in the longitudinal, uncinate, cingulum and external capsule fasciculi. Volumetric data show significant atrophy in svPPA patients, mostly in the left entorhinal, amygdala, inferior temporal, middle temporal, superior temporal and temporal pole cortices, and bilateral fusiform gyri. Conclusions: This syndrome appears to be associated not only with GM but also significant WM degeneration. Thus, DTI could play a role in the differential diagnosis of atypical dementia by specifying WM damage specific to svPPA.

Des atteintes à la substance blanche du cerveau dans le cas de la variante sémantique de l’aphasie primaire progressive. Contexte: La variante dite « sémantique » de l’aphasie primaire progressive (vsAPP) constitue une forme de démence de laquelle découlent principalement des troubles du langage. À l’inverse de l’atrophie de la substance grise associée à cette démence, on a été moins portés à décrire les atteintes à la substance blanche. Notre étude entend donc cerner l’étendue de ces atteintes au moyen d’une approche à la fois sensible et neutre. Méthodes: Nous avons effectué une étude intergroupe en comparant 10 patients ayant reçu un diagnostic clinique de vsAPP à 9 témoins en santé sur le plan cognitif. À noter que ces 10 patients ont été recrutés entre 2011 et 2014 dans un centre de soins médicaux tertiaires. C’est à partir de données obtenues grâce à l’imagerie par tenseur de diffusion (diffusion tensor imaging) que nous avons extrait, au moyen d’une approche privilégiant les statistiques spatiales basées sur les voies neuronales, des valeurs d’anisotropie fractionnelle (FA). Nous avons en outre obtenu des données volumétriques concernant la substance grise en utilisant l’outil de segmentation automatisée Freesurfer. Nous avons ensuite comparé ces deux groupes à l’aide de tests des rangs signés de Wilcoxon non-paramétriques, et ce, en veillant à appliquer une correction en vue de nombreuses comparaisons. Résultats: D’entrée de jeu, précisons que nos données démographiques ont révélé que les patients et les témoins étaient comparables. Comme il fallait s’y attendre, nos données cliniques ont montré, dans le cadre de tests de dépistage cognitif, que les résultats des patients atteints de vsAPP se sont révélés inférieurs à ceux des témoins. Des examens de tractographie ont par ailleurs montré une diffusion déficiente chez ces 10 patients, les valeurs de FA ayant surtout diminué dans les faisceaux longitudinaux et uncinés, dans le cingulum et la capsule externe. Quant à nos données volumétriques, elles ont révélé une atrophie notable chez les patients atteints de vsAPP, surtout dans les régions suivantes : cortex entorhinal gauche, amygdale, temporale inférieure, mésiotemporale, temporale supérieure, cortex temporo-polaires et lobules fusiformes bilatéraux. Conclusions: Le syndrome évoqué ci-dessus semble être associé non seulement à une dégénérescence de la substance grise mais aussi à une dégénérescence importante de la substance blanche. En précisant de manière spécifique l’atteinte à la substance blanche que sous-tend la vsAPP, l’imagerie par tenseur de diffusion pourrait donc être appelée à jouer un rôle dans l’établissement de diagnostics différentiels pour des démences atypiques.

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Corresponding author
Correspondence to: Simon Duchesne, Centre de recherche CERVO, Institut universitaire en santé mentale de Québec, F-3582, 2601 de la Canardière, Québec, QC, Canada G1J 2G3. Email: simon.duchesne@fmed.ulaval.ca
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Canadian Journal of Neurological Sciences
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