Abstract：
OBJECTIVE: The association between snoring, a very common condition that increases with age, and dementia risk is controversial. We aimed to investigate the observational and causal relationship between snoring and dementia, and to elucidate the role of body mass index (BMI).
METHODS: Using data from 451,250 participants who were dementia-free at baseline, we examined the association between self-reported snoring and incident dementia using Cox proportional-hazards models. Causal relationship between snoring and Alzheimer\'s disease (AD) was examined using bidirectional two-sample Mendelian randomization (MR) analysis.
RESULTS: During a median follow-up of 13.6 years, 8,325 individuals developed dementia. Snoring was associated with a lower risk of all-cause dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89 to 0.98) and AD (HR 0.91; 95% CI 0.84 to 0.97). The association was slightly attenuated after adjusting for BMI, and was stronger in older individuals, APOE ε4 allele carriers, and during shorter follow-up periods. MR analyses suggested no causal effect of snoring on AD, however, genetic liability to AD was associated with a lower risk of snoring. Multivariable MR indicated that the effect of AD on snoring was primarily driven by BMI.
CONCLUSIONS: The phenotypic association between snoring and lower dementia risk likely stems from reverse causation, with genetic predisposition to AD associated with reduced snoring. This may be driven by weight loss in prodromal AD. Increased attention should be paid to reduced snoring and weight loss in older adults as potential early indicators of dementia risk.
METHODS: Using data from 451,250 participants who were dementia-free at baseline, we examined the association between self-reported snoring and incident dementia using Cox proportional-hazards models. Causal relationship between snoring and Alzheimer\'s disease (AD) was examined using bidirectional two-sample Mendelian randomization (MR) analysis.
RESULTS: During a median follow-up of 13.6 years, 8,325 individuals developed dementia. Snoring was associated with a lower risk of all-cause dementia (hazard ratio [HR] 0.93; 95% confidence interval [CI] 0.89 to 0.98) and AD (HR 0.91; 95% CI 0.84 to 0.97). The association was slightly attenuated after adjusting for BMI, and was stronger in older individuals, APOE ε4 allele carriers, and during shorter follow-up periods. MR analyses suggested no causal effect of snoring on AD, however, genetic liability to AD was associated with a lower risk of snoring. Multivariable MR indicated that the effect of AD on snoring was primarily driven by BMI.
CONCLUSIONS: The phenotypic association between snoring and lower dementia risk likely stems from reverse causation, with genetic predisposition to AD associated with reduced snoring. This may be driven by weight loss in prodromal AD. Increased attention should be paid to reduced snoring and weight loss in older adults as potential early indicators of dementia risk.
摘要：
目的：打鼾之间的关联，一个非常常见的情况，随着年龄的增长，痴呆症的风险是有争议的。我们的目的是调查打鼾和痴呆之间的观察和因果关系，并阐明体重指数（BMI）的作用。
方法：使用来自基线时无痴呆的451,250名参与者的数据，我们使用Cox比例风险模型检验了自我报告的打鼾与偶发痴呆之间的关联.使用双向双样本孟德尔随机（MR）分析检查打鼾与阿尔茨海默病（AD）之间的因果关系。
结果：在13.6年的中位随访期间，8325人患上了痴呆症。打鼾与全因痴呆(风险比[HR]0.93;95%置信区间[CI]0.89至0.98)和AD(HR0.91;95%CI0.84至0.97)的风险较低相关。在调整BMI后，关联略有减弱，在老年人身上更强壮，APOEε4等位基因携带者，在较短的随访期间。MR分析表明打鼾对AD没有因果关系，然而,AD的遗传倾向与打鼾的风险较低相关.多变量MR表明AD对打鼾的影响主要由BMI驱动。
结论：打鼾和降低痴呆风险之间的表型关联可能源于反向因果关系，与AD的遗传易感性与减少打鼾有关。这可能是由前驱AD的体重减轻引起的。应更多地注意减少老年人的打鼾和体重减轻，作为痴呆风险的潜在早期指标。
方法：使用来自基线时无痴呆的451,250名参与者的数据，我们使用Cox比例风险模型检验了自我报告的打鼾与偶发痴呆之间的关联.使用双向双样本孟德尔随机（MR）分析检查打鼾与阿尔茨海默病（AD）之间的因果关系。
结果：在13.6年的中位随访期间，8325人患上了痴呆症。打鼾与全因痴呆(风险比[HR]0.93;95%置信区间[CI]0.89至0.98)和AD(HR0.91;95%CI0.84至0.97)的风险较低相关。在调整BMI后，关联略有减弱，在老年人身上更强壮，APOEε4等位基因携带者，在较短的随访期间。MR分析表明打鼾对AD没有因果关系，然而,AD的遗传倾向与打鼾的风险较低相关.多变量MR表明AD对打鼾的影响主要由BMI驱动。
结论：打鼾和降低痴呆风险之间的表型关联可能源于反向因果关系，与AD的遗传易感性与减少打鼾有关。这可能是由前驱AD的体重减轻引起的。应更多地注意减少老年人的打鼾和体重减轻，作为痴呆风险的潜在早期指标。
