Francesca Di Stefano1, Aurélie Kas2, Marie-Odile Habert2, Pierre Decazes3, Foudil Lamari4, Simone Lista5, Harald Hampel6, Marc Teichmann7. 1. Department of Neurology, Institut de la mémoire et de la maladie d'Alzheimer, Centre de Référence 'Démences Rares', Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; Department of Neurology, University of Cagliari, Cagliari, Italy. 2. Service de Médecine Nucléaire, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; Université Pierre et Marie Curie-Paris 6, INSERM, UMR-S 678, Paris, France. 3. Service de Médecine Nucléaire, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France. 4. Department of Metabolic Biochemistry, Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France. 5. AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie, Paris, France; Institut du Cerveau et de la Moelle Epinière (ICM), ICM-INSERM 1127, FrontLab, Paris, France. 6. Department of Neurology, Institut de la mémoire et de la maladie d'Alzheimer, Centre de Référence 'Démences Rares', Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; AXA Research Fund & UPMC Chair, Sorbonne Universités, Université Pierre et Marie Curie, Paris, France; Institut du Cerveau et de la Moelle Epinière (ICM), ICM-INSERM 1127, FrontLab, Paris, France. 7. Department of Neurology, Institut de la mémoire et de la maladie d'Alzheimer, Centre de Référence 'Démences Rares', Hôpital de la Pitié-Salpêtrière, AP-HP, Paris, France; Institut du Cerveau et de la Moelle Epinière (ICM), ICM-INSERM 1127, FrontLab, Paris, France. Electronic address: marc.teichmann@psl.aphp.fr.
Abstract
INTRODUCTION: The corticobasal syndrome (CBS) constitutes a neurodegenerative disease spectrum with substantial phenotypical or biological heterogeneity, requiring large or multimodal studies to identify its clinico-biological signature while disentangling Alzheimer's disease (AD)-related from non-AD-related CBS. METHODS: We analyzed a large (N = 45) monocenter expert-clinic CBS cohort, recruited in motor and/or cognitive units to avoid recruitment biases, assessed with standardized motor and/or cognitive-language tests, brain perfusion imaging, and cerebrospinal fluid biomarkers. RESULTS: CBS mainly manifests as a motor and/or language disorder incorporating a "mixed progressive aphasia" phenotype, consistent with left-lateralized damage to frontal-parietal-temporal cortices. Biomarker expression indicates in 18% underlying AD causing predominant parietal-temporal damage and Gerstmann syndrome (sensitivity 75%; specificity 75%), whereas non-AD-CBS presented with predominant prefrontal and lexical-semantic impairment. DISCUSSION: CBS is primarily a "motor-plus-aphasia" disease unfolding into AD-related and non-AD-related variants with distinctive cognitive-anatomic patterns. CBS, and notably its "Gerstmann variant", should be included in the new AD "lexicon" and categorized in the evolving diagnostic spectrum of "atypical AD"d.
INTRODUCTION: The corticobasal syndrome (CBS) constitutes a neurodegenerative disease spectrum with substantial phenotypical or biological heterogeneity, requiring large or multimodal studies to identify its clinico-biological signature while disentangling Alzheimer's disease (AD)-related from non-AD-related CBS. METHODS: We analyzed a large (N = 45) monocenter expert-clinic CBS cohort, recruited in motor and/or cognitive units to avoid recruitment biases, assessed with standardized motor and/or cognitive-language tests, brain perfusion imaging, and cerebrospinal fluid biomarkers. RESULTS: CBS mainly manifests as a motor and/or language disorder incorporating a "mixed progressive aphasia" phenotype, consistent with left-lateralized damage to frontal-parietal-temporal cortices. Biomarker expression indicates in 18% underlying AD causing predominant parietal-temporal damage and Gerstmann syndrome (sensitivity 75%; specificity 75%), whereas non-AD-CBS presented with predominant prefrontal and lexical-semantic impairment. DISCUSSION: CBS is primarily a "motor-plus-aphasia" disease unfolding into AD-related and non-AD-related variants with distinctive cognitive-anatomic patterns. CBS, and notably its "Gerstmann variant", should be included in the new AD "lexicon" and categorized in the evolving diagnostic spectrum of "atypical AD"d.
Authors: Jonathan Graff-Radford; Keir X X Yong; Liana G Apostolova; Femke H Bouwman; Maria Carrillo; Bradford C Dickerson; Gil D Rabinovici; Jonathan M Schott; David T Jones; Melissa E Murray Journal: Lancet Neurol Date: 2021-03 Impact factor: 44.182
Authors: Nobutaka Sakae; Keith A Josephs; Irene Litvan; Melissa E Murray; Ranjan Duara; Ryan J Uitti; Zbigniew K Wszolek; Jay van Gerpen; Neil R Graff-Radford; Dennis W Dickson Journal: Alzheimers Dement Date: 2019-08-06 Impact factor: 16.655
Authors: Daniel W Sirkis; Luke W Bonham; Taylor P Johnson; Renaud La Joie; Jennifer S Yokoyama Journal: Mol Psychiatry Date: 2022-04-07 Impact factor: 13.437