Cognitive dysfunction and white matter hyperintensities in Fabry disease

J Inherit Metab Dis. 2022 Jan 7. doi: 10.1002/jimd.12472.

PMID: 34994980

P Murphy, F Williams, I Davagnanam

Highlights: Neuropsychological assessment and rehabilitation should be routinely offered to patients with Fabry Disease.

Abstract

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder that affects multiple systems, including cerebrovascular disease. Patients with FD have a higher risk of ischaemic stroke and transient ischemic attack (TIA). Although white matter hyperintensities are prevalent, their clinical significance in terms of cognition is unknown. Previous research into the neuropsychological profile of FD has been unsatisfactory, owing in part to methodological flaws such as small sample sizes.

Objective and methods: In a case-control research, we compared 26 patients with Fabry disease who had mild to moderate disease symptoms to 18 healthy controls who were matched for age and premorbid intellectual level. On the severity of white matter alterations, we gathered extensive neuropsychological and MRI neuroimaging data. Mood was taken into account as a potential confounder.

Results: The FD group's executive functioning and information processing speed were significantly compromised, according to our findings. The compromise of executive functions could not be totally explained by slowed information processing speed, according to error analyses. In the FD group, we found a significant correlation between cognitive impairment and the overall volume of white matter hyperintensities.

Conclusion: Even in the absence of stroke or mood problems, our findings hint to severe cognitive impairment in FD. This suggests that neuropsychological assessment and rehabilitation should be routinely offered to patients with FD.

Keywords: Fabry disease, cognition, neuropsychological testing, white matter hyperintensity