Risk of Parkinson Disease in Individuals With Autism Spectrum Disorder

Importance: Recent research suggests a plausible biological link between autism spectrum disorder (ASD) and Parkinson disease (PD). Nonetheless, large longitudinal studies examining the risk of PD following ASD are lacking. Objective: To examine the association between ASD and future PD risk. Design, Setting, and Participants: A nationwide population-based prospective cohort study was performed using data from Swedish national registers. All individuals born in Sweden from 1974 to 1999 with follow-up from age 20 years until December 31, 2022, and with complete covariate data were included. The analysis was completed in August 2024. Exposures: Diagnoses of ASD as a time-varying exposure obtained from the National Patient Register. Main Outcomes and Measures: Diagnoses of PD were obtained from the National Patient Register through 2022. The relative risk (RR) of PD was quantified using incidence rate ratios with 95% CIs from Poisson regression. Preterm birth, depression, antidepressant use, and antipsychotic exposure over time were potentially modifying life events. Results: The study included 2 278 565 individuals (median IQR age at exit, 34 29-42 years; 1 106 772 female 48.6%), contributing 33 858 476 person-years. PD occurred in 438 of 2 226 611 individuals without ASD (0.02%; 1.3 cases/100 000 person-years) and 24 of 51 954 individuals with ASD (0.05%; 3.9 cases/100 000 person-years) (RR, 4.43 95% CI, 2.92-6.72). The risk estimates were similar after adjusting for sex, socioeconomic status, family history of mental illness, family history of PD, and age at ASD diagnosis. Preterm or early-term birth was not associated with and did not modify the PD risk. Depression and antidepressant use (present in 24 257 individuals with ASD 46.7%) were associated with increased risk of PD (RR, 2.01 95% CI, 1.40-2.88), independent of ASD. Antipsychotic exposure (present in 16 387 individuals with ASD 31.5%) reduced but did not fully attenuate the association (RR, 2.00 95% CI, 1.27-3.14) and showed no interaction with ASD on PD risk. Conclusions and Relevance: ASD was associated with increased risk of PD, even after adjusting for depression or antidepressant use and antipsychotic exposure. These findings suggest a potential shared etiology between neurodevelopmental disorders and PD, and a heightened awareness of long-term neurological conditions in individuals with ASD may be warranted.