Abstract

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.

Highlights

  • Environmental, psychosocial, and behavioural factors are likely all involved in the development of Parkinson’s disease (PD) [1]

  • We examined the associations of physical fitness, body mass index (BMI), resting heart rate, blood pressure, intelligence quotient (IQ), and stress resilience measured in late adolescence with PD in a cohort of more than one million Swedish men

  • In order to evaluate the independent effect of the studied attributes, we fitted a full model where physical fitness, BMI, resting heart rate (RHR), blood pressure, IQ, and stress resilience were adjusted for one another

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Summary

Introduction

Environmental, psychosocial, and behavioural factors are likely all involved in the development of Parkinson’s disease (PD) [1]. Physical activity is a lifestyle factor associated with a reduced risk of PD [2]. The role of body mass index (BMI) on PD has been studied with inconclusive results [5], Mendelian randomization (MR) analysis supports an inverse association between BMI and PD [6]. MR analysis has the potential to investigate causal relationship between a risk factor and a disease, avoiding common methodological limitations of observational studies including reverse causation [13]. To this end, we examined the associations of physical fitness, BMI, resting heart rate, blood pressure, IQ, and stress resilience measured in late adolescence with PD in a cohort of more than one million Swedish men. We hypothesize that corroborating findings from both analyses would more likely suggest causation

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