To analyze nonmotor features documented before Parkinson disease diagnosis and their association with subsequent diagnosis.
Approach:
Study Design: Retrospective matched case-control study using the National Institutes of Health All of Us Research Program Registered Tier dataset.
Participants: Included 2,673 patients aged 40 years or older with at least 2 distinct PD diagnosis dates and 10,692 matched controls.
Nonmotor Features Examined: Nine features were analyzed: REM sleep behavior disorder, mild cognitive impairment, orthostatic hypotension, constipation, urinary dysfunction, depression, anxiety, insomnia, and erectile dysfunction.
Key Findings:
REM sleep behavior disorder showed the strongest association with PD, documented in 2.7% of PD patients vs 0.2% of controls, associated with nearly 10-fold higher odds.
Mild cognitive impairment was documented in 4.8% of PD cases vs 0.9% of controls, associated with approximately 4-fold higher odds.
Orthostatic hypotension was documented in 5.6% of PD cases vs 2.2% of controls, associated with 83% higher primary conditional odds and 88% higher age- and sex-adjusted unconditional odds.
Depression and anxiety were less consistently associated with PD.
Interpretation:
Associations for REM sleep behavior disorder, mild cognitive impairment, and orthostatic hypotension remained stable across various analyses, while depression and anxiety showed less secure associations.
Limitations:
Electronic health record documentation may not reflect true biological onset.
The overall model had modest discrimination with an area under the curve of 0.585.
Conclusion:
Electronic health record–documented nonmotor features were informative at the group level but insufficient for individual PD prediction.
Autopsy-confirmed findings linked diagnostic errors, co-pathology, and genetic variation to distinct pathologic patterns across more than 3,300 donors with Parkinsonian disorders.
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