The phenotypical core of Alzheimer's disease-related and nonrelated variants of the corticobasal syndrome: A systematic clinical, neuropsychological, imaging, and biomarker study

Francesca Di Stefano; Aurélie Kas; Marie-Odile Habert; Pierre Decazes; Foudil Lamari; Simone Lista; Harald Hampel; Marc Teichmann

doi:10.1016/j.jalz.2016.02.005

The phenotypical core of Alzheimer's disease-related and nonrelated variants of the corticobasal syndrome: A systematic clinical, neuropsychological, imaging, and biomarker study

Alzheimers Dement. 2016 Jul;12(7):786-95. doi: 10.1016/j.jalz.2016.02.005. Epub 2016 Mar 15.

Authors

Francesca Di Stefano¹, Aurélie Kas², Marie-Odile Habert², Pierre Decazes³, Foudil Lamari⁴, Simone Lista⁵, Harald Hampel⁶, Marc Teichmann⁷

Affiliations

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: [email protected].

PMID: 26988428
DOI: 10.1016/j.jalz.2016.02.005

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.

Keywords: Alzheimer's disease; Aphasia; CSF biomarkers; Corticobasal syndrome; Neuroimaging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease / classification
Alzheimer Disease / diagnosis*
Alzheimer Disease / diagnostic imaging
Alzheimer Disease / pathology
Biomarkers / cerebrospinal fluid*
Humans
Language Tests / statistics & numerical data
Neurodegenerative Diseases / diagnosis*
Neurodegenerative Diseases / diagnostic imaging
Neurodegenerative Diseases / pathology
Neuropsychological Tests / statistics & numerical data
Phenotype

Substances

Biomarkers