Supplementary Material for: Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-aged to older Women: Results from the UK Biobank Cohort Study

Introduction: The association of serum sex hormone-binding globulin (SHBG) concentrations with dementia risk remains uncertain in middle-aged to older women. We examined associations of serum SHBG levels with incidence of all-cause dementia and its subtypes in middle-aged to older women from the large population-based UK Biobank cohort study. Methods: Serum total SHBG levels were measured by immunoassay. The incidence of all-cause dementia and its subtypes was recorded. Cox proportional hazards models were used to calculate hazard ratios (HR) for main outcomes. Results: Among 171,482 community-dwelling women (mean (SD) age was 59.9 (5.4) years, median follow-up of 11.8 years), 2,368 developed dementia, including 1,088 from Alzheimer's disease (AD), 451 from vascular dementia (VAD), and 1,609 from other dementia. After multivariable adjustments, higher serum SHBG levels were significantly associated with higher risks of all-cause dementia, AD and other dementia (All P<0.05). Compared to those in the lowest quartile of SHBG levels, participants in the highest quartile of SHBG levels had a higher risk of all-cause dementia (HR 1.34; 95% confidence interval [CI] 1.16-1.53), AD (HR 1.32; 95% CI 1.07-1.62), and other dementia (HR 1.44; 95% CI 1.21-1.70). However, this relationship was not significant for VAD (HR 1.16; 95% CI 0.86-1.56). Conclusion: These findings indicated that higher serum SHBG concentrations were independently associated with higher risks of incident all-cause dementia, as well as AD and other dementia among middle-aged to older women. No association was found for VAD.

引言：血清性激素结合球蛋白（sex hormone-binding globulin, SHBG）浓度与痴呆风险的关联在中老年女性群体中仍不明确。本研究依托大型人群队列研究英国生物银行（UK Biobank），针对中老年女性群体，探讨血清SHBG水平与全因痴呆及其亚型发病风险的关联。
方法：采用免疫法测定血清总SHBG水平，记录全因痴呆及其亚型的发病情况，使用Cox比例风险模型（Cox proportional hazards models）计算主要结局的风险比（hazard ratio, HR）。
结果：本研究纳入171482名社区居住女性，平均（标准差）年龄为59.9（5.4）岁，中位随访时长11.8年，其中2368名受试者发生痴呆，包括1088例阿尔茨海默病（Alzheimer's disease, AD）、451例血管性痴呆（vascular dementia, VAD）以及1609例其他类型痴呆。经多变量校正后，较高的血清SHBG水平与全因痴呆、阿尔茨海默病及其他类型痴呆的发病风险升高显著相关（所有P<0.05）。与SHBG水平最低四分位组的受试者相比，最高四分位组受试者的全因痴呆（HR 1.34；95%置信区间（confidence interval, CI）1.16~1.53）、阿尔茨海默病（HR 1.32；95%置信区间（confidence interval, CI）1.07~1.62）及其他类型痴呆（HR 1.44；95%置信区间（confidence interval, CI）1.21~1.70）发病风险均显著升高。但上述关联在血管性痴呆中未显示统计学显著性（HR 1.16；95%置信区间（confidence interval, CI）0.86~1.56）。
结论：本研究结果表明，在中老年女性群体中，较高的血清SHBG浓度与全因痴呆、阿尔茨海默病及其他类型痴呆的新发风险呈独立正相关，未发现其与血管性痴呆存在关联。