A nationwide cohort study of 2.28 million individuals born in Sweden between 1974 and 1999 found that those diagnosed with autism spectrum disorder had a significantly higher risk of receiving a Parkinson disease diagnosis by early to mid-adulthood compared with those without autism spectrum disorder.

Investigators followed individuals from age 20 years through 2022. During the follow-up period, which spanned 33.9 million person-years, 462 first-time Parkinson disease (PD) diagnoses were identified. Among individuals with autism spectrum disorder (ASD), PD occurred at a rate of 3.9 cases per 100 000 person-years, compared with 1.3 cases per 100 000 person-years in those without ASD. After adjusting for sex, socioeconomic status, parental mental illness, depression, and psychiatric medication use, ASD was associated with a more than fourfold increased relative risk of PD (RR, 4.43; 95% CI, 2.92-6.72).

Of the 2.28 million participants, 51 954 had an ASD diagnosis. The median age at the end of follow-up was 34 years (interquartile range, 29–42 years). Although PD typically occurs later in life, the analysis focused on early-onset cases, including individuals in their 40s. The association between ASD and PD remained consistent across statistical models.

The investigators also evaluated potential contributing factors. Depression, present in 46.7% of individuals with ASD, was associated with a twofold increased risk of PD (RR, 2.01; 95% CI, 1.40-2.88), independent of ASD diagnosis. Antipsychotic exposure, present in 31.5% of individuals with ASD, was linked to a sixfold increased PD risk (RR, 6.34; 95% CI, 3.83-10.48), regardless of ASD status. However, these factors did not fully explain the elevated risk associated with ASD.

To reduce the possibility of diagnostic overlap, the analysis was repeated using only idiopathic PD cases—defined as PD without secondary or atypical causes. The association remained statistically significant and similar in magnitude (RR, 3.53; 95% CI, 1.86-6.70).

PD risk did not vary significantly by age at ASD diagnosis or gestational age at birth (preterm, full-term, or postterm), and no differences were observed between male and female participants.

Because most participants had not yet reached the typical age of PD onset, the observed cases reflect early diagnoses. Still, the increased risk was already evident. The study used national medical, birth, and prescription registers, enabling detailed tracking and adjustment for potential confounders.

All diagnoses were made by medical professionals and drawn from validated national databases. The study included rigorous adjustments for covariates and confirmed findings using multiple statistical approaches.

Although the study did not explore underlying biological mechanisms, the findings support a possible connection between early neurodevelopmental conditions and later-life neurodegeneration. Shared genetic or neurological pathways, such as dopaminergic dysfunction or variants in the PARK2 gene, may contribute to this association.

Further research is warranted to clarify the mechanisms linking ASD and PD and to better understand long-term neurologic outcomes in individuals with ASD.

Full author disclosures are available in the published study.

Source: JAMA Neurology