title: The cognitive profile of prion disease: a prospective clinical and imaging study.
abstract: OBJECTIVE
  Prion diseases are dementing illnesses with poorly defined neuropsychological features. This is probably because the most common form, sporadic Creutzfeldt-Jakob disease, is often rapidly progressive with pervasive cognitive decline making detailed neuropsychological investigation difficult. This study, which includes patients with inherited, acquired (iatrogenic and variant) and sporadic forms of the disease, is the only large-scale neuropsychological investigation of this patient group ever undertaken and aimed to define a neuropsychological profile of human prion diseases.
  
  
  METHODS
  A tailored short cognitive examination of all of the patients (n = 81), with detailed neuropsychological testing in a subset with mild disease (n = 30) and correlation with demographic, clinical, genetic (PRNP mutation and polymorphic codon 129 genotype), and other variables (MRI brain signal change in cortex, basal ganglia or thalamus; quantitative research imaging, cerebrospinal fluid 14-3-3 protein).
  
  
  RESULTS
  Comparison with healthy controls showed patients to be impaired on all tasks. Principal components analysis showed a major axis of fronto-parietal dysfunction that accounted for approximately half of the variance observed. This correlated strongly with volume reduction in frontal and parietal gray matter on MRI. Examination of individual patients' performances confirmed early impairment on this axis, suggesting characteristic cognitive features in mild disease: prominent executive impairment, parietal dysfunction, a largely expressive dysphasia, with reduced motor speed.
  
  
  CONCLUSIONS
  Taken together with typical neurological features, these results complete a profile that should improve differential diagnosis in a clinical setting. We propose a tailored neuropsychological battery for early recognition of clinical onset of symptoms with potential for use in clinical trials involving at-risk individuals.
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; Department of Neuropsychology, NHNN, University College London Hospitals NHS Foundation Trust London, United Kingdom ; Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Diana
authors.initials: D
authors.lastname: Caine
authors.affiliation: Department of Neuropsychology, NHNN, University College London Hospitals NHS Foundation Trust London, United Kingdom.
authors.forename: Renata J
authors.initials: RJ
authors.lastname: Tinelli
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Hyare
authors.affiliation: Academic Neuroradiological Unit, Department of Brain Repair and Rehabilitation, UCL Institute of Neurology London, United Kingdom ; Lysholm Department of Neuroradiology, NHNN, University College London Hospitals NHS Foundation Trust London, United Kingdom.
authors.forename: Enrico
authors.initials: E
authors.lastname: De Vita
authors.affiliation: Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Jessica
authors.initials: J
authors.lastname: Lowe
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Ana
authors.initials: A
authors.lastname: Lukic
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Andrew
authors.initials: A
authors.lastname: Thompson
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Porter
authors.affiliation: Department of Neuropsychology, NHNN, University College London Hospitals NHS Foundation Trust London, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cipolotti
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Rudge
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: John
authors.initials: J
authors.lastname: Collinge
authors.affiliation: NHS National Prion Clinic, National Hospital for Neurology and Neurosurgery (NHNN), University College London Hospitals NHS Foundation Trust London, United Kingdom ; MRC Prion Unit, Department of Neurodegenerative Disease, UCL Institute of Neurology London, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Mead