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Is glycaemia associated with poorer brain health and risk of dementia? Cross sectional and follow-up analysis of the UK Biobank

By Victoria Garfield, Aliki-Eleni Farmaki, Sophie V Eastwood, Rohini Mathur, Christopher T Rentsch, Krishnan Bhaskaran, Liam Smeeth, Nish Chaturvedi

Posted 20 Feb 2020
medRxiv DOI: 10.1101/2020.02.18.20024471

ObjectiveTo understand the relationship across the glycaemic spectrum with incident dementia, brain structure, and cognitive decline. Research Design and MethodsUK Biobank participants, aged 40-69 at recruitment. HbA1c and diabetes diagnosis define baseline glycaemic categories. Outcomes included incident vascular dementia (VD), Alzheimers dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. All results are in reference to normoglycaemic individuals (HbA1c 35-<42 mmol/mol). Results210433 (47%), 15246 (3%), 3280 (0.7%), 20793 (5%) individuals had low HbA1c, pre-diabetes, undiagnosed diabetes, and known diabetes, respectively. Pre- and known diabetes markedly increased incident VD, (hazard ratios (HR) 1.51, 95%CI=1.01;2.25 and 1.96, 95%CI=1.49;2.58, respectively), less so AD (1.18, 0.92;1.52 and 1.13 0.95,1.33), adjusting for demographic and socioeconomic variables. For VD, multivariate adjustment, driven by antihypertensives, attenuated associations, HR 1.27, 0.84;1.91 and 1.45,1.07;1.97. Pre- and known diabetes conferred elevated risks of cognitive decline (odds ratio OR 1.53, 1.02;2.29 and 1.49, 1.02;2.18, respectively). People with pre-diabetes, undiagnosed and known diabetes had higher WMH volumes (4%, 30%, 3%, respectively), and lower HV (34.51 mm3, 11.73 mm3 and 61.13 mm3 respectively). People with low-normal HbA1c (<35 mmol/mol) had 5% lower WMH volume and 13.6 mm3 greater HV than normoglycaemic individuals. ConclusionsPre and known diabetes increase VD risks, less so AD. Excess VD risks were largely accounted for by treated hypertension. Hyperglycaemic states were associated with adverse, whereas low normal HbA1c was associated with favourable brain structure compared to normoglycaemic individuals. Our findings have implications for cardiovascular medication in hyperglycaemia for brain health.

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