0688 Post-illumination Pupillary Response (PIPR) Is Attenuated in Patients with REM-sleep Behaviour Disorder

Abstract Introduction Circadian disruptions are conspicuous in patients with Parkinson’s disease (PD). Previous study showed that melanopsin-mediated post-illumination pupillary response (PIPR) was attenuated in patients with PD. iRBD is often regarded as a prodromal phase of PD, but it remains unclear whether there is an early emergence of changes in PIPR in patients with iRBD. Methods This case-control study compared the PIPR, sleep and circadian parameters among controls and patients with iRBD. PIPR was measured by DP-2000 pupillometer (NeurOptics, Irvine, CA, USA). Post-stimulus continuous pupil size recording for 60s was conducted after a 1-second blue stimulus (467nm, 2.0log lux) and a 1-second red light stimulus (632nm, 2.0 log lux), respectively, with 2 minutes of dark adaptation in between. The PIPR was defined as the pupil size at 6s post-stimulus, normalized to the baseline pupil diameter. Net-PIPR is calculated by subtracting PIPR-red from PIPR-blue. One-week actigraphy, sleep diary data and an overnight urinary 6-sulfatoxymelatonin (aMT6s) sample (except those on exogenous melatonin) were also collected. Group difference was compared by Chi Square test or t-test where appropriate. Linear regression analyses were conducted to examine the relationship between PIPR and other circadian parameters. Results At present, 50 controls (Age, mean±standard deviation: 62.9±7.1 years) and 37 patients with iRBD (64.4±5.4 years) were recruited. The Net-PIPR was significantly attenuated in the iRBD group (19%±0.11 vs 26%±0.11, p=0.003). Net-PIPR has significant association with aMT6s (B=0.13, 95% Confidence interval (CI)=0.05-0.21, p=0.001), actigraphic M10 (B=2.6, CI:0.8,4.4, p=0.005), mesor (B=1.5, CI: 0.48-2.51, p=0.005), and amplitude (B=1.1, CI:0.2 - 2.1, p=0.02), while controlled for age, gender, photoperiod, time since awake, use of medication. A higher PIPR was associated with a lower odds for iRBD (Odd ratio=0.03, CI:0,89,0.99,p=0.014), adjusted for age, gender, photoperiod, and MOCA score. Conclusion Our results showed that PIPR is attenuated in patients with iRBD and is associated with other markers of circadian disruptions. The study supported the early emergence of circadian disruptions in iRBD patients and PIPR is a potential convenient non-invasive circadian marker. Further longitudinal study is needed on whether PIPR would predict circadian disruption and future neurodegeneration. Support (if any) Direct grant of The Chinese University of Hong Kong (Ref. 2021.054)