Objective:

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.

Sources:

• npj Parkinson’s Disease