1Reta Lila Weston Institute, UCL Queen Square Institute of Neurology, London.
2Dementia Research Centre, UCL Queen Square Institute of Neurology, London, United Kingdom.
3MRC Unit for Lifelong Health and Ageing, University College London, London, United Kingdom.
4Centre for Medical Image Computing, University College London, London, United Kingdom.
5Biomedical Engineering & Imaging Sciences, King's College London, London, United Kingdom.
6Tenoke Ltd, Cambridge, United Kingdom.
7Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, London, United Kingdom.
8Wellcome Centre for Human Neuroimaging, UCL Queen Square Institute of Neurology, London, United Kingdom.
9Department of Clinical Chemistry, Northern General Hospital, Sheffield, United Kingdom.
10UCL Institute of Liver and Digestive Health and Royal Free Hospital, London, United Kingdom.
11Sheffield Institute of Translational Neuroscience, Sheffield, United Kingdom.
Background: Cognitive impairment is common in neurological presentations of Wilson's disease (WD). Various domains can be affected, and subclinical deficits have been reported in patients with hepatic presentations. Associations with imaging abnormalities have not been systematically tested.
Objective: The aim was to determine the neuroanatomical basis for cognitive deficits in WD.
Methods: We performed a 16-item neuropsychological test battery and magnetic resonance brain imaging in 40 patients with WD. The scores for each test were compared between patients with neurological and hepatic presentations and with normative data. Associations with Unified Wilson's Disease Rating Scale neurological examination subscores were examined. Quantitative, whole-brain, multimodal imaging analyses were used to identify associations with neuroimaging abnormalities in chronically treated stable patients.
Results: Abstract reasoning, executive function, processing speed, calculation, and visuospatial function scores were lower in patients with neurological presentations than in those with hepatic presentations and correlated with neurological examination subscores. Deficits in abstract reasoning and phonemic fluency were associated with lower putamen volumes even after controlling for neurological severity. About half of patients with hepatic presentations had poor performance in memory for faces, cognitive flexibility, or associative learning relative to normative data. These deficits were associated with widespread cortical atrophy and/or white matter diffusion abnormalities.