HbA1c and brain health across the entire glycaemic spectrum

Abstract

Aims To understand the relationship between glycated haemoglobin (HbA_1c) and brain health, across the entire glycaemic spectrum. We hypothesised that individuals with increasingly higher HbA_1c would be more likely to have worse brain health outcomes in comparison to normoglycaemic individuals. Materials and methods We used data from the UK Biobank cohort, which recruited 500,000 individuals aged 40‐69 years. HbA_1c and diabetes diagnosis were used to define baseline glycaemic categories. Our outcomes included: incident all‐cause dementia, vascular dementia (VD), Alzheimer’s dementia (AD), hippocampal volume (HV), white matter hyperintensity (WMH) volume, cognitive function and decline. The reference group was normoglycaemic individuals (HbA_1c 35‐3, 80mm³, 82mm³), whereas low‐normal HbA_1c had 1% lower WMH volume and 12mm³ greater HV. Conclusion Both pre‐diabetes and known diabetes are harmful in terms of vascular dementia, cognitive decline and AD risks, as well as lower hippocampal volume. Associations appeared to be somewhat driven by antihypertensive medication, which implies that certain cardiovascular drugs may ameliorate some of the excess risk. Low‐normal HbA_1c levels, however, associate with more favourable brain health outcomes and warrant more in‐depth investigation.