Objective: To determine the anatomical basis for cognitive deficits in WD.

Background: Cognitive impairment is common in neurological presentations of Wilson’s disease (WD).¹ Various cognitive domains can be affected and subclinical deficits have been reported in hepatic presentations.² Associations with imaging abnormalities have not been systematically tested.

Method: We compared scores for 16 neuropsychological tests between patients with neurological (n=23) and hepatic (n=17) presentations and with normative data.  Associations with Unified WD Rating Scale (UWDRS) neurological examination subscores were examined. Quantitative, whole-brain, multi-modal imaging analyses were used to identify associations with neuroimaging abnormalities in chronically-treated, stable patients (n=35), as previously described.³Analyses were performed with and without including UWDRS neurological examination subscores as a covariate.

Results: Abstract reasoning, executive function, processing speed and visuospatial function scores were lower in patients with neurological presentations and correlated with UWDRS neurological examination subscores (P<0.05). Deficits in abstract reasoning and phonemic fluency were associated with lower putamen volumes even after controlling for neurological severity (region-of-interest volumetric analysis, _{FDR-corrected}P<0.05; table 1). Around half of patients with hepatic presentations had deficits in memory for faces, cognitive flexibility or associative learning. These were associated with widespread cortical atrophy (voxel-based morphometry, _{FWE-corrected}P<0.05; figure 1) and/or white matter diffusion abnormalities (tract-based spatial statistics, _{FWE-corrected}P<0.05; figure 2).

Conclusion: Subtle cognitive deficits that appear to be common in patients with hepatic presentations represent a distinct neurological phenotype associated with diffuse cortical and white matter pathology. This may precede the classical phenotype characterised by movement disorders and executive dysfunction associated with basal ganglia damage. A binary disease classification may no longer be appropriate.

References: 1. Seniów J, Bak T, Gajda J, et al. Cognitive functioning in neurologically symptomatic and asymptomatic forms of Wilson’s disease. Mov Disord 2002;17(5):1077–83.
2. Tarter RE, Switala J, Carra J, et al. Neuropsychological impairment associated with hepatolenticular degeneration (Wilson’s disease) in the absence of overt encephalopathy. Int J Neurosci 1987;37(1-2):67–71.
3. Shribman S, Bocchetta M, Sudre CH, et al. Neuroimaging correlates of brain injury in Wilson’s disease: a multimodal, whole-brain MRI study. Brain 2021. https://doi.org/10.1093/brain/awab274.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/neuroimaging-correlates-of-cognitive-deficits-in-wilsons-disease/