Background Dysregulation of some metabolic factors increases the risk of dementia. It remains unclear if overall metabolic dysregulation, or only certain components, contribute to cognitive aging and if these associations are sex specific. Methods Data from the 2006–2016 waves of the Health and Retirement Study (HRS) was used to analyze 7 103 participants aged 65 and older at baseline (58% women). We created a metabolic-dysregulation risk score (MDRS) composed of blood pressure/hypertension status, glycosylated hemoglobin (HbA1c)/diabetes status, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and waist circumference, and assessed cognitive trajectories from repeated measures of the HRS-Telephone Interview for Cognitive Status (HRS-TICS) over 10 years of follow-up. Linear mixed-effects models estimated associations between MDRS or individual metabolic factors (biomarkers) with mean and change in HRS-TICS scores and assessed sex-modification of these associations. Results Participants with higher MDRSs had lower mean HRS-TICS scores, but there were no statistically significant differences in rate of decline. Sex stratification showed this association was present for women only. MDRS biomarkers revealed heterogeneity in the strength and direction of associations with HRS-TICS. Lower HRS-TICS levels were associated with hypertension, higher HbA1c/diabetes, and lower HDL-C and TC, whereas faster rate of cognitive decline was associated with hypertension, higher HbA1c/diabetes, and higher TC. Participants with higher HbA1c/diabetes presented worse cognitive trajectories. Sex differences indicated that women with higher HbA1c/diabetes to have lower HRS-TICS levels, whereas hypertensive males presented better cognitive trajectory. Conclusions Our results demonstrate that metabolic dysregulation is more strongly associated with cognition in women compared with men, though sex differences vary by individual biomarker.

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代谢失调与认知衰老之间关联的性别差异：健康与退休研究

背景 一些代谢因素的失调会增加患痴呆症的风险。目前尚不清楚整体代谢失调或仅某些成分会导致认知衰老，以及这些关联是否具有性别特异性。方法 使用 2006 年至 2016 年健康与退休研究 (HRS) 的数据对 7 103 名基线年龄为 65 岁及以上的参与者（58% 为女性）进行分析。我们创建了代谢失调风险评分 (MDRS)，其中包括血压/高血压状况、糖化血红蛋白 (HbA1c)/糖尿病状况、总胆固醇 (TC)、高密度脂蛋白胆固醇 (HDL-C) 和腰围，以及通过 10 年随访中对认知状态电话访谈 (HRS-TICS) 的重复测量来评估认知轨迹。线性混合效应模型估计了 MDRS 或个体代谢因素（生物标志物）与 HRS-TICS 评分平均值和变化之间的关联，并评估了这些关联的性别改变。结果 MDRS 较高的参与者的平均 HRS-TICS 分数较低，但下降率没有统计学上的显着差异。性别分层表明这种关联仅存在于女性中。MDRS 生物标志物揭示了与 HRS-TICS 关联的强度和方向的异质性。较低的 HRS-TICS 水平与高血压、较高的 HbA1c/糖尿病以及较低的 HDL-C 和 TC 相关，而较快的认知能力下降与高血压、较高的 HbA1c/糖尿病和较高的 TC 相关。HbA1c/糖尿病较高的参与者表现出较差的认知轨迹。性别差异表明，HbA1c/糖尿病较高的女性 HRS-TICS 水平较低，而高血压男性则表现出更好的认知轨迹。结论 我们的结果表明，与男性相比，代谢失调与女性认知的相关性更强，尽管性别差异因个体生物标志物而异。