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Title: Type 2 diabetes mellitus and cognitive impairment : assessment of brain and cardiac function using magnetic resonance imaging
Author: Hunt, Leanne
ISNI:       0000 0004 7651 8092
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
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Aims: The risk of developing mild cognitive impairment (MCI) increases with Type 2 diabetes (T2DM). Brain morphometric alterations such as cerebral atrophy and Cerebral Blood Flow (CBF) changes have been associated with T2DM but not with people with T2DM and MCI. It is also known that T2DM patients develop cardiac systolic and diastolic dysfunction. The main aim of this study is not only to relate T2DM cerebral brain status on imaging to cognition but also to investigate them in relation to T2DM patients with MCI. The secondary aim of the study is to investigate whether cardiac output has any relation to any demonstrated cerebral findings. Methods: Seventy-six age and gender matched subjects [30, T2DM+normal cognition (T2DM); 17, T2DM+MCI (T2DM/MCI) and 29, healthy volunteers (HV)] were recruited. All subjects underwent clinical and questionnaire (Addenbrooke's Cognitive Assessment [ACE-R]) assessments and high-resolution, cardiac and cerebral Magnetic Resonance Imaging (MRI) at 3T. Cerebral and Cardiac images were analysed visually and quantitatively (VBM, FSL, Oxford; SIENAX FSL, Oxford; Freesurfer MGH, Harvard; Nordic Ice, Nordic Neuro Lab, Bergen, Norway; MEDIS suite, Medis medical imaging systems, Leiden, The Netherlands). Results: Demographic data revealed aged-matched participants between all three groups (mean age 69.3-71.5 years, ANOVA, p = 0.164). T2DM/MCI ACE-R score (mean+SD; 83 4) was significantly lower compared to other groups (HV=96 2, T2DM=94 3; ANOVA, p<0.001). T2DM/MCI group had significantly lower regional cross-sectional grey matter volumes compared to HV in the left (p<0.0005) and right hippocampi (p<0.05), left putamen (p<0.05), caudate (p<0.05) and amygdala (p<0.05). There was significantly lower CBF in T2DM/MCI compared to T2DM and HV in the medial temporal lobes (CBF 76.8 ml/100g/min, ANOVA p<0.05), insula (CBF 67.5 ml/100g/min ANOVA p<0.005), and frontal lobes (CBF 71.8 ml/100g/min, ANOVA p<0.005). Pearson's correlation revealed significant correlations between ACE-R score and regional CBF measurements in the medial temporal lobes, (p<0.05, r=0.25) thalamus (p<0.05, r=0.23) and the insula (p<0.05, r=0.29). The cardiac data revealed significant reductions in SV/BSA (ANOVA, p<0.05) and ED/BSA (ANOVA, p<0.05) in the T2DM/MCI group compared to the HV and T2DM Groups. Conclusion: This study demonstrates significantly lower cortical volumes and CBF in areas that have been associated with cognition in patients with T2DM and cognitive impairment. The cardiac data revealed mild abnormalities in diastolic dysfunction but this was not statistically relatable to the cerebral changes or cognitive changes seen. This may be essential to help our understanding of the pathological mechanisms that occur behind the increased risk of developing cognitive impairment in people with T2DM. Further investigation of both anatomical and functional cerebral involvement is required to examine the pathological mechanisms underlying the increased cognitive impairment risk associated with T2DM.
Supervisor: Wilkinson, I. D. ; Selvarajah, D. Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available