Bioscience and Biomedical Engineering Thrust, Systems Hub, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou, Guangdong, China.
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong, SAR, China.
BMC Med. 2023 Mar 29;21(1):114. doi: 10.1186/s12916-023-02816-8.
Emerging data suggests the neuroprotective and anti-neuroinflammatory effects of glucosamine. We aimed to examine the association between regular glucosamine use and risk of incident dementia, including dementia subtypes.
We conducted large-scale observational and two-sample Mendelian randomization (MR) analyses. Participants in UK Biobank having accessible data for dementia incidence and who did not have dementia at baseline were included in the prospective cohort. Through the Cox proportional hazard model, we examined the risks of incident all-cause dementia, Alzheimer's disease (AD), and vascular dementia among glucosamine users and non-users. To further test the causal association between glucosamine use and dementia, we conducted a 2-sample MR utilizing summary statistics from genome-wide association studies (GWAS). The GWAS data were obtained from observational cohort participants of mostly European ancestry.
During a median follow-up of 8.9 years, there were 2458 cases of all-cause dementia, 924 cases of AD, and 491 cases of vascular dementia. In multivariable analysis, the hazard ratios (HR) of glucosamine users for all-cause dementia, AD, and vascular dementia were 0.84 (95% CI 0.75-0.93), 0.83 (95% CI 0.71-0.98), and 0.74 (95% CI 0.58-0.95), respectively. The inverse associations between glucosamine use and AD appeared to be stronger among participants aged below 60 years than those aged above 60 years (p = 0.04 for interaction). The APOE genotype did not modify this association (p > 0.05 for interaction). Single-variable MR suggested a causal relationship between glucosamine use and lower dementia risk. Multivariable MR showed that taking glucosamine continued to protect against dementia after controlling for vitamin, chondroitin supplement use and osteoarthritis (all-cause dementia HR 0.88, 95% CI 0.81-0.95; AD HR 0.78, 95% CI 0.72-0.85; vascular dementia HR 0.73, 95% CI 0.57-0.94). Single and multivariable inverse variance weighted (MV-IVW) and MR-Egger sensitivity analyses produced similar results for these estimations.
The findings of this large-scale cohort and MR analysis provide evidence for potential causal associations between the glucosamine use and lower risk for dementia. These findings require further validation through randomized controlled trials.
新出现的数据表明氨基葡萄糖具有神经保护和抗炎作用。我们旨在研究定期使用氨基葡萄糖与痴呆症发病风险的关系，包括痴呆症的亚型。
我们进行了大规模的观察性和双样本孟德尔随机化（MR）分析。在 UK Biobank 中，参与者如果有可获取的数据来评估痴呆症的发病情况，且在基线时没有痴呆症，则被纳入前瞻性队列。通过 Cox 比例风险模型，我们检测了氨基葡萄糖使用者和非使用者发生全因性痴呆症、阿尔茨海默病（AD）和血管性痴呆症的风险。为了进一步验证氨基葡萄糖使用与痴呆症之间的因果关系，我们利用全基因组关联研究（GWAS）的汇总统计数据进行了双样本 MR。GWAS 数据来自主要为欧洲血统的观察性队列参与者。
在中位随访 8.9 年期间，共有 2458 例全因性痴呆症、924 例 AD 和 491 例血管性痴呆症。在多变量分析中，氨基葡萄糖使用者的全因性痴呆症、AD 和血管性痴呆症的风险比（HR）分别为 0.84（95% CI 0.75-0.93）、0.83（95% CI 0.71-0.98）和 0.74（95% CI 0.58-0.95）。在年龄小于 60 岁的参与者中，氨基葡萄糖使用与 AD 之间的反比关系似乎强于年龄大于 60 岁的参与者（交互作用 p=0.04）。APOE 基因型未改变这种关联（交互作用 p>0.05）。单变量 MR 表明氨基葡萄糖的使用与较低的痴呆风险之间存在因果关系。多变量 MR 表明，在控制维生素、软骨素补充剂使用和骨关节炎后，服用氨基葡萄糖继续预防痴呆症（全因性痴呆症 HR 0.88，95% CI 0.81-0.95；AD HR 0.78，95% CI 0.72-0.85；血管性痴呆症 HR 0.73，95% CI 0.57-0.94）。单变量和多变量逆方差加权（MV-IVW）和 MR-Egger 敏感性分析对这些估计产生了类似的结果。
这项大规模队列和 MR 分析的结果为氨基葡萄糖的使用与痴呆症风险降低之间存在潜在的因果关系提供了证据。这些发现需要通过随机对照试验进一步验证。
