Affiliations: [a] St. Hedwig-Hospital, Clinic for Sleep- & Chronomedicine, Berlin, Germany | [b] Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Physiology, Sleep Research & Clinical Chronobiology, Berlin, Germany
Correspondence to: Jan de Zeeuw, Charité-Universitätsmedizin Berlin, Institute of Physiology, Sleep Research & Clinical Chronobiology, c/o St. Hedwig-Krankenhaus, Grosse Hamburger Strasse 5-11, 10115 Berlin, Germany. E-mail: [email protected].
Note:  These authors contributed equally to this work.
Abstract: Neurodegenerative processes in the brain are reflected by structural retinal changes. As a possible biomarker of cognitive state in prodromal α-synucleinopathies, we compared melanopsin-mediated post-illumination pupil response (PIPR) with cognition (CERAD-plus) in 69 patients with isolated REM-sleep behavior disorder. PIPR was significantly correlated with cognitive domains, especially executive functioning (r = 0.417, p < 0.001), which was more pronounced in patients with lower dopamine-transporter density, suggesting advanced neurodegenerative state (n = 26; r = 0.575, p = 0.002). Patients with mild neurocognitive disorder (n = 10) had significantly reduced PIPR (smaller melanopsin-mediated response) compared to those without (p = 0.001). Thus, PIPR may be a functional—possibly monitoring—marker for impaired cognitive state in (prodromal) α-synucleinopathies.