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The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomisation Study in the UK Biobank

Garfield, V; Farmaki, A-E; Fatemifar, G; Eastwood, SV; Mathur, R; Rentsch, CT; Denaxas, S; ... Chaturvedi, N; + view all (2021) The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomisation Study in the UK Biobank. Diabetes 10.2337/db20-0895. (In press). Green open access

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Abstract

We investigated the relationship between glycaemia and cognitive function, brain structure and incident dementia using bidirectional Mendelian randomisation (MR). Data were from UK Biobank (n∼500,000). Our exposures were genetic instruments for type-2 diabetes (157 variants) and HbA1c (51 variants) and our outcomes were reaction time (RT), visual memory, hippocampal and white matter hyperintensity volumes, Alzheimer’s dementia (AD). We also investigated associations between genetic variants for RT (43 variants) and, diabetes and HbA1c. We used conventional inverse-variance weighted (IVW) MR, alongside MR sensitivity analyses. Using IVW, genetic liability to type-2 diabetes was not associated with reaction time (exponentiated ß=1.00, 95%CI=1.00; 1.00), visual memory (expß=1.00, 95%CI=0.99; 1.00), white matter hyperintensity volume (WMHV) (expß=0.99, 95%CI=0.97; 1.01), hippocampal volume (HV) (ß coefficient mm3=4.56, 95%CI=-3.98; 13.09) or AD (OR 0.89, 95%CI=0.78; 1.01). HbA1c was not associated with RT (expß=1.01, 95%CI=1.00; 1.01), WMHV (expß=0.94, 95%CI=0.81; 1.08), HV (ß=7.21, 95%CI=-54.06; 68.48), or risk of AD (OR 0.94, 95%CI=0.47; 1.86), but HbA1c was associated with visual memory (expß=1.06, 95%CI=1.05; 1.07) using a weighted median. IVW showed that reaction time was not associated with diabetes risk (OR 0.96, 95%CI=0.63; 1.46) or with HbA1c (ß coefficient mmol/mol=-0.08, 95%CI=-0.57; 0.42). Overall, we observed little evidence of causal association between genetic instruments for T2D or peripheral glycaemia and some measures of cognition and brain structure in midlife.

Type: Article
Title: The Relationship Between Glycaemia, Cognitive Function, Structural Brain Outcomes and Dementia: A Mendelian Randomisation Study in the UK Biobank
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.2337/db20-0895
Publisher version: https://doi.org/10.2337/db20-0895
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Population Science and Experimental Medicine > MRC Unit for Lifelong Hlth and Ageing
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Health Informatics > Clinical Epidemiology
URI: https://discovery.ucl.ac.uk/id/eprint/10123767
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