Cognitive impairment in Wilson's disease

Abstract

Wilson's disease (WD) or hepatolenticular degeneration is a rare, genetic and systemic disease, caused by a deficit in the metabolism of copper, leading to its accumulation in different organs, mainly the liver, followed by the central nervous system, especially the basal ganglia. When symptoms begin between the second and third decades of life, approximately 50% of the patients show neurological symptoms. Although dystonia and dysarthria are the most common neurological signs, cognitive changes have been reported since the first cases were described in 1912. Memory change is one of the most common impairments, but other cognitive changes have been reported, including dementia in untreated cases. In this article we review the cognitive changes in WD patients and the occurrence of dementia.

Psychiatric manifestations in Wilson’s disease: possibilities and difficulties for treatment

“… 1 , 12 Clinical symptoms are often nonspecific, causing difficulties in diagnosis, including misdiagnoses (isolated obsessive-compulsive disorder or anorexia nervosa, for example). 28 , 29 It is common to observe classic psychiatric syndromes in later early adulthood, including behavioral and personality changes, 30 anxiety, depression, 31 manic and hypomanic syndrome, 10 , 32 – 34 cognitive deficits, 35 – 39 sleep problems (dyssomnias) 30 , 40 and sexual dysfunctions including excessive sexual drive. 41 Some patients also have substance abuse problems, 42 , 43 and the presence of a harmful use or dependence syndrome could further complicate the clinical presentation and lead to a delay in the diagnosis of WD.…”

“… 10 The cognitive domains affected include attention, visuospatial perception and reasoning, learning and memory, and verbal and abstract reasoning. 35 – 39 Generally, cognitive deficits are mild and potentially reversible at disease onset, but can deteriorate during the progression of the disease, and some patients may eventually receive the diagnosis of mild cognitive disorder or even dementia. 35 We note that separate diagnostic categories exist in ICD-10 classification for other BG diseases, such as dementia in PD and dementia in HD.…”

“…In contrast to neurodegenerative dementias, intellectual deficits presenting in WD patients are secondary to metabolic changes, similarly to those occurring in hepatic encephalopathy or manganism, and are potentially reversible with anti-copper treatment. 35 , 38 The most frequent deficits are found in the executive domain, while verbal intelligence and episodic memory are preserved. 39 WD patients may also have a slow processing speed and mild impairment in all cognitive domains, particularly in working memory, attention and abstract thinking.…”

Cognitive impairment and magnetic resonance imaging correlations in Wilson's disease

“…Despite being present in the first patients described by Wilson in 1912, cognitive impairment has been little studied and is still a matter of controversy until today . Patients with neurological involvement present impaired performance on scales of intelligence evaluation and global cognitive performance , as well as in memory and divided attention tests .…”

Which factors are associated with global cognitive impairment in Wilson's disease?

“…The cognitive symptoms present in the first recorded patients were not studied in depth for some time. 2 The first studies assessing cognitive performance described changes in memory and executive functions in patients with neurological symptoms of WD, 3 , 4 raising doubts as to whether the motor symptoms were in fact responsible for the cognitive impairment. 3 Patients with only hepatic symptoms did not exhibit cognitive abnormalities.…”