Open AccessThe cognitive profile of prion disease: a prospective clinical and imaging study
Author(s) -
Caine Diana,
Tinelli Renata J.,
Hyare Harpreet,
De Vita Enrico,
Lowe Jessica,
Lukic Ana,
Thompson Andrew,
Porter MarieClaire,
Cipolotti Lisa,
Rudge Peter,
Collinge John,
Mead Simon
Publication year - 2015
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.195
Subject(s) - neuropsychology , medicine , prnp , disease , executive dysfunction , executive functions , cognition , dementia , neuroscience , neuropsychological assessment , white matter , pathology , audiology , pediatrics , psychiatry , magnetic resonance imaging , radiology , psychology , prion protein
Abstract Objectives 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. Interpretation 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.