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

<jats:title>ABSTRACT</jats:title><jats:sec><jats:title>INTRODUCTION</jats:title><jats:p>To understand the relationship across the glycaemic spectrum, with brain health.</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>UK Biobank participants. HbA<jats:sub>1c</jats:sub> and diabetes diagnosis define baseline glycaemic categories. Outcomes: incident vascular dementia (VD), Alzheimer’s dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. Reference group: normoglycaemic individuals (HbA<jats:sub>1c</jats:sub> 35-&lt;42 mmol/mol).</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>Pre- and known diabetes increased incident VD, (HR 1.54, 95%CI=1.04;2.28 and 2.97, 95%CI=2.26;3.90). Known diabetes increased AD risk (HR 1.84, 95%CI=1.44;2.36). Pre- and known diabetes elevated risks of cognitive decline (OR 1.42, 1.48;2.96 and 1.39, 1.04;1.75). Pre-diabetes, undiagnosed and known diabetes conferred higher WMH volumes (4%, 26%, 5%,) and lower HV (22.4mm<jats:sup>3</jats:sup>, 15.2mm<jats:sup>3</jats:sup>, 62.2mm<jats:sup>3</jats:sup>). Low-normal HbA<jats:sub>1c</jats:sub> had 2% lower WMH volume and 13.6mm<jats:sup>3</jats:sup> greater HV.</jats:p></jats:sec><jats:sec><jats:title>DISCUSSION</jats:title><jats:p>Pre and known diabetes increase VD risks; known diabetes increases AD risk. Low-normal HbA<jats:sub>1c</jats:sub> associates with favourable neuroimaging outcomes. Our findings may have implications for cardiovascular medication in hyperglycaemia for brain health.</jats:p></jats:sec>