Objective: To explore the potential role of baseline hyposmia and RBD symptoms on progression of cognitive decline at 2 years.

Background: Cognitive decline in PD patients progresses at a slow rate from the early stages of the disorder. Identification of subpopulations that experience faster decline in select cognitive domains will provide important information on the design of future clinical trials in prodromal/early PD.

Method: PPMI is an ongoing observational clinical study that enrolled 423 early PD, treatment naive subjects within 2 years of diagnosis[1]; their data were downloaded from the PPMI website in June 2017. At baseline, hyposmia is defined as having an UPSIT score ≤27 for female and ≤24 for male subjects. RBD (REM sleep behavior disorder) is defined by a baseline score of ≥6 on the RBD Questionnaire. Changes in MoCA and its subscales, SDMT (Symbol Digit Modality Test), LNS(Letter Number Sequencing), HVLT (Hopkins Verbal Learning Test) Recall and HVLT Recognition by 24 months were analysed in a Mixed Model for Repeated Measures (MMRM) model, adjusted for baseline score of the corresponding scale/subscale, as well as gender, age, disease duration, education baseline RBD or hyposmia status (where appropriate) and baseline MDS-UPDRS score.

Results: Among the 416 PD evaluable subjects, 265(64%) have hyposmia and 104(25%) have RBD at baseline. Presence of hyposmia at baseline is associated with significantly worse of performance on the MoCA Attention subscale, SDMT, Letter Number Sequencing and HVLT Recall at 2 years, while positive RBD status at baseline is linked to significantly lower scores on MoCA Visuospatial/Executive, Abstraction and Orientation subscales, as well as HVLT Recall task. [table 1] [table 2]

Conclusion: Both hyposmia and RBD are important risk factors associated with faster decline on measures of cognitive functioning in early PD patients.

References: 1. Kenneth Marek, Danna Jennings, Shirley Lasch, Andrew Siderowf, Caroline Tanner, Tanya Simuni, Chris Coffey, Karl Kieburtz, Emily Flagg, Sohini Chowdhury, Werner Poewe, Brit Mollenhauer, Paracelsus-Elena Klinik, Todd Sherer, Mark Frasier, Claire Meunier, Alice Rudolph, Cindy Casaceli, John Seibyl, Susan Mendick, Norbert Schuff, Ying Zhang, Arthur Toga, Karen Crawford, Alison Ansbach, Pasquale De Blasio, Michele Piovella, John Trojanowski, Les Shaw, Andrew Singleton, Keith Hawkins, Jamie Eberling, Deborah Brooks, David Russell, Laura Leary, Stewart Factor, Barbara Sommerfeld, Penelope Hogarth, Emily Pighetti, Karen Williams, David Standaert, Stephanie Guthrie, Robert Hauser, Holly Delgado, Joseph Jankovic, Christine Hunter, Matthew Stern, Baochan Tran, Jim Leverenz, Marne Baca, Sam Frank, Cathi-Ann Thomas, Irene Richard, Cheryl Deeley, Linda Rees, Fabienne Sprenger, Elisabeth Lang, Holly Shill, Sanja Obradov, Hubert Fernandez, Adrienna Winters, Daniela Berg, Katharina Gauss, Douglas Galasko, Deborah Fontaine, Zoltan Mari, Melissa Gerstenhaber, David Brooks, Sophie Malloy, Paolo Barone, Katia Longo, Tom Comery, Bernard Ravina, Igor Grachev, Kim Gallagher, Michelle Collins, Katherine L. Widnell, Suzanne Ostrowizki, Paulo Fontoura, Tony Ho, Johan Luthman, Marcel van der Brug, Alastair D. Reith, Peggy Taylor, The Parkinson Progression Marker Initiative (PPMI). Progress in Neurobiology, Volume 95, Issue 4, 2011, p. 629-635.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/baseline-hyposmia-and-rbd-symptoms-are-associated-with-faster-but-differential-cognitive-decline-at-2-years-in-the-ppmi-study/