Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Box 210, 171 77, Stockholm, Sweden.
Eur J Epidemiol. 2021 Oct;36(10):1055-1064. doi: 10.1007/s10654-021-00730-y. Epub 2021 Mar 6.
To investigate whether physical and cognitive fitness measured in late adolescence was associated with future risk of Parkinson's disease (PD). The cohort included 1,259,485 Swedish men with physical fitness, body mass index (BMI), resting heart rate (RHR), blood pressure, intelligence quotient (IQ), and stress resilience measured at the age of 17-20 in relation to conscription. Incident cases of PD were ascertained from the Swedish Patient Register. Hazard ratios were estimated from Cox models, after controlling for multiple confounders. We further performed Mendelian randomization (MR) analyses to assess the causality of the associations, using GWAS summary statistics with > 800,000 individuals. During follow-up, we identified 1,034 cases of PD (mean age at diagnosis = 53). Men with an RHR > 100 beats per minute had a higher risk of PD compared to men with an RHR of 60-100 beats per minute (HR = 1.47; 95% CI = 1.08-1.99). Men with IQ above the highest tertile had a higher risk of PD compared to men with an IQ below the lowest tertile (HR = 1.46; 95% CI = 1.19-1.79). We found no association for physical fitness, BMI, blood pressure, or stress resilience. A causal relationship was suggested by the MR analysis between IQ and PD, but not between RHR and PD. RHR and IQ in late adolescence were associated with a higher risk of PD diagnosed at relatively young age. The association of IQ with PD is likely causal, whereas the association of RHR with PD suggests that altered cardiac autonomic function might start before 20 years of age in PD.
探究青少年晚期时的身体和认知健康状况与日后帕金森病（PD）发病风险之间的相关性。方法：该队列研究纳入了 1259485 名瑞典男性，他们在 17-20 岁兵役体检时接受了身体机能、体重指数（BMI）、静息心率（RHR）、血压、智商（IQ）和抗压能力的检测。PD 发病情况通过瑞典患者注册库确定。采用 Cox 模型调整多重混杂因素后，计算了风险比（HR）。为了评估关联的因果关系，我们还进行了孟德尔随机化（MR）分析，该分析使用了超过 80 万名个体的 GWAS 汇总统计数据。在随访期间，共发现 1034 例 PD（诊断时的平均年龄为 53 岁）。与 RHR 为 60-100 次/分的男性相比，RHR＞100 次/分的男性 PD 发病风险更高（HR=1.47；95%CI=1.08-1.99）。与 IQ 最低三分位的男性相比，最高三分位的男性 PD 发病风险更高（HR=1.46；95%CI=1.19-1.79）。我们未发现身体机能、BMI、血压或抗压能力与 PD 发病风险之间存在相关性。MR 分析提示 IQ 与 PD 之间存在因果关系，而 RHR 与 PD 之间则无因果关系。青少年晚期的 RHR 和 IQ 与相对年轻发病的 PD 风险增加相关。IQ 与 PD 之间的关联可能具有因果关系，而 RHR 与 PD 之间的关联则表明 PD 患者的心脏自主神经功能可能在 20 岁之前就已经发生改变。
