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Cognitive Function in Cystic Fibrosis and CFTR Modulator Therapy

Background: Cystic fibrosis is not typically associated with cognitive dysfunction that is easily discernible. Whether having a CFTR mutation has a direct effect on the CNS function is yet to be elucidated, despite widespread expression of the CFTR protein throughout the human nervous system. 
Methods: We aimed to study the effects of CFTR modulators ivacaftor and lumacaftor/ivacaftor on cognition in two separate CF cohorts. These were ivacaftor, in CF patients with at least one copy of the G551D mutation, and lumacaftor/ivacaftor in homozygous F508del subjects. Using a panel of cognitive testing tools (MOCA, TMT, Cogstate™) targeting various domains that included executive function, memory and attention.
Results: The two cohorts improved significantly on CFTR modulator treatment when measured by the MOCA, TMT and by a combined cognitive score. Most prominently, these represent improvements in executive function. 
Conclusion: Suggested CNS effect of CFTR mutation in CF and the impact of CFTR modulators on this.