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）浓度与中老年女性痴呆风险的关联仍未明确。本研究依托大型人群队列研究英国生物银行（UK Biobank），探讨中老年女性血清SHBG水平与全因痴呆及其亚型发病风险的关联。方法：采用免疫分析法检测血清总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水平最低四分位数组的受试者相比，SHBG水平最高四分位数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% CI 1.07~1.62）及其他类型痴呆（HR 1.44；95% CI 1.21~1.70）发病风险均更高。然而，该关联在血管性痴呆中未达到统计学显著性（HR 1.16；95% 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发病风险升高存在独立关联，但与血管性痴呆无显著关联。