Longitudinal studies of the relationship between hyperglycemia and brain health are rare and there is limited information on sex differences in associations. We investigated whether glycosylated hemoglobin (HbA1c) measured at ages of 53, 60–64 and 69 years, and cumulative glycemic index (CGI), a measure of cumulative glycemic burden, were associated with metrics of brain health in later life.

Participants were from Insight 46, a substudy of the Medical Research Council National Survey of Health and Development (NSHD) who undertook volumetric MRI, florbetapir amyloid-PET imaging and cognitive assessments at ages of 69–71. Analyses were performed using linear and logistic regression as appropriate, with adjustment for potential confounders. We observed a sex interaction between HbA1c and whole brain volume (WBV) at all 3 time points. Following stratification of our sample, we observed that HbA1c at all ages, and CGI were positively associated with lower WBV exclusively in females. HbA1c (or CGI) was not associated with amyloid status, white matter hyperintensities (WMHs), hippocampal volumes (HV) or cognitive outcomes in either sex.

Higher HbA1c in adulthood is associated with smaller WBV at 69–71 years in females but not in males. This suggests that there may be preferential target organ damage in the brain for females with hyperglycemia.

关于高血糖与大脑健康之间关系的纵向研究很少，而且有关性别差异的信息也很有限。我们研究了 53 岁、60-64 岁和 69 岁时测量的糖化血红蛋白 (HbA1c) 以及累积血糖指数 (CGI)（衡量累积血糖负荷的指标）是否与晚年大脑健康指标相关。

参与者来自 Insight 46，这是医学研究委员会国家健康与发展调查 (NSHD) 的一个子研究，他们在 69-71 岁期间进行了体积 MRI、氟贝佞淀粉样蛋白 PET 成像和认知评估。适当使用线性回归和逻辑回归进行分析，并调整潜在的混杂因素。我们在所有 3 个时间点观察到 HbA1c 与全脑体积 (WBV) 之间的性别相互作用。对样本进行分层后，我们观察到所有年龄段的 HbA1c 和 CGI​​ 均与女性的较低 WBV 呈正相关。无论性别，HbA1c（或 CGI）与淀粉样蛋白状态、白质高信号 (WMH)、海马体积 (HV) 或认知结果均无关。

对于女性来说，成年期较高的 HbA1c 与 69-71 岁时的 WBV 较小有关，但对于男性则不然。这表明，患有高血糖的女性大脑中可能存在优先的靶器官损伤。