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posted on 2021-07-12, 22:05authored byVictoria Garfield, Aliki-Eleni Farmaki, Ghazaleh Fatemifar, Sophie V. Eastwood, Rohini Mathur, Christopher T. Rentsch, Spiros Denaxas, Krishnan Bhaskaran, Liam Smeeth, Nish Chaturvedi
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.
Funding
This work was jointly funded by Diabetes UK and British Heart Foundation grant 15/0005250. KB holds a Sir Henry Dale Fellowship funded by Wellcome and the Royal Society (grant number 107731/Z/15/Z).