Cognitive impairment in liver transplanted patients with transthyretin-related hereditary amyloid polyneuropathy

Abstract

Introduction and aim: Hereditary transthyretin-related amyloidosis (ATTR-FAP) is characterized by a progressive neuropathy, cardiomyopathy, nephropathy and ocular disease. More than 90% of amyloidogenic transthyretin is produced by the liver; however, this protein is also synthesized in the choroid plexus. Although some patients have transitory neurologic events, the impact on cognition is still unknown. The aim was to study the cognitive performance of ATTR-FAP V30M patients with long disease course.Methods: A prospective observational study of a consecutive sample of patients with 10 or more years of disease duration was conducted. All patients underwent an extensive neuropsychological evaluation.Results: Sixteen patients were included, with a mean age of 53 years and mean duration of disease of 18 years. All had been submitted to liver transplantation. The functional status was not incapacitating in the majority, with 75% needing at most a stick to walk and 38% still actively working. The neuropsychological evaluation disclosed episodic memory impairments in 31% and executive dysfunction in 25% of patients.Conclusions: These novel findings suggest that cognitive dysfunction can be a delayed manifestation of hereditary transthyretin-related amyloidosis. The putative relation of cognitive dysfunction with transthyretin-amyloid deposition can provide another model to study the amyloid hypothesis of cognitive impairment.