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Title: Cognitive function in cystic fibrosis and cystic fibrosis related diabetes (CFRD)
Author: Chadwick, Helen Kay
ISNI:       0000 0004 6349 8061
Awarding Body: University of Leeds
Current Institution: University of Leeds
Date of Award: 2016
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Cystic fibrosis (CF) is a complex multisystem disease caused by a gene mutation of a protein called the CF Transmembrane Conductance Regulator (CFTR). Glucose tolerance abnormalities are common in CF and the prevalence of CF related diabetes (CFRD), which shares clinical characteristics with type 1 (T1DM) and type 2 diabetes (T2DM), increases with age. Impaired glucose tolerance (IGT), T1DM and T2DM are associated with cognitive impairment relative to healthy controls. The overall aim of this thesis was to examine cognitive function in CF. Study 1 investigated the impact of CF on cognitive function, in people with CFRD (n=49), people with CF who are not diabetic (CFND, n=49) and healthy controls (n=49). Memory, attention and processing speed, and cognitive flexibility was impaired in CFRD, and to a lesser degree in CFND, relative to healthy controls. Study 2 assessed cognitive function over a 1-3 year period in people with CFRD (N=36) and found no evidence of cognitive decline despite a decline in lung function. Study 3 compared cognitive function in people with CFRD who were post transplant (CFRDTx, n=18), people with CFRD (who were not post transplant, n=18), and healthy controls (n=18). CFRD was associated with impairment in attention and processing speed, spatial working memory, cognitive flexibility and to a lesser extent verbal memory. Cognitive function did not improve post transplantation in people with CFRD. Study 4 followed up people with CFRDTx (N=8) over an 18±6 month period and found no decline in cognitive function. Taken together, the evidence presented in this thesis suggests that diabetes in CF is associated with cognitive impairment, and that maintaining glycaemic control protects against cognitive decline. The cognitive impairment observed in people with CF is of clinical significance and has implications for self care and disease management. The recent discovery that CFTR is present in the pancreas and the brain has important implications for the effects of the new CFTR potentiator and corrector therapies on cognitive function in CF.
Supervisor: Lawton, Clare L. ; Dye, Louise ; Peckham, Daniel G. ; Mansfield, Michael W. Sponsor: University of Leeds ; Medical Research Council (MRC) ; Rosetrees Trust
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available