Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson's Disease

Jennifer R Mammen; Jamie L Adams; Rikki Mangrum; Yuge Xiao; William Barbosa; Mirinda Tyo; Christopher Redmond; Cheryl Carter; Kelly Cifelli; Robert Cifelli; Hope Maruzo; Jim Meeker; Gerry Shultz; Colbren Thomas; Claire Bale; Evan Davies; Catherine M Kopil; Connie Marras; Tiago Mestre; Thomas Morel; Tanya Simuni; Glenn T Stebbins; Daniel Weintraub; Diane Stephenson

doi:10.1038/s41531-025-00907-2

Systematic review and consensus conceptual model of meaningful symptoms and functional impacts in early Parkinson's Disease

NPJ Parkinsons Dis. 2025 Apr 3;11(1):65. doi: 10.1038/s41531-025-00907-2.

Authors

Jennifer R Mammen^#¹, Jamie L Adams^#^{2

3}, Rikki Mangrum⁴, Yuge Xiao⁵, William Barbosa^{3

6}, Mirinda Tyo⁷, Christopher Redmond⁶, Cheryl Carter⁶, Kelly Cifelli⁶, Robert Cifelli⁶, Hope Maruzo⁶, Jim Meeker⁶, Gerry Shultz⁶, Colbren Thomas⁶, Claire Bale⁸, Evan Davies⁹, Catherine M Kopil⁵, Connie Marras¹⁰, Tiago Mestre¹¹, Thomas Morel¹², Tanya Simuni¹³, Glenn T Stebbins¹⁴, Daniel Weintraub¹⁵, Diane Stephenson¹⁶

Affiliations

¹ University of Massachusetts, Dartmouth, College of Nursing and Health Sciences, Dartmouth, MA, USA. jmammen@umassd.edu.
² Center for Health + Technology, University of Rochester Medical Center, Rochester, NY, USA.
³ Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
⁴ Vector Psychometric Group, LLC, Chapel Hill, NC, USA.
⁵ The Michael J Fox Foundation for Parkinson's Research, New York City, NY, USA.
⁶ People affected by Parkinson's - patient and family advisory panel, New York City, NY, USA.
⁷ University of Massachusetts, Dartmouth, College of Nursing and Health Sciences, Dartmouth, MA, USA.
⁸ Parkinson's UK, London, UK.
⁹ Roche, Basel, Switzerland.
¹⁰ University of Toronto, Toronto, Canada.
¹¹ Parkinson's disease and Movement Disorders Center, Division of Neurology, Department of Medicine, The Ottawa Hospital Research Institute, The University of Ottawa Brain and Research Institute, Ottawa, ON, Canada.
¹² UCB, Department of Patient Centred Outcomes Research, Bulle, Switzerland.
¹³ Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁴ Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.
¹⁵ University of Pennsylvania, School of Medicine, Department of Psychiatry, Philadelphia, PA, USA.
¹⁶ Critical Path Institute, Tucson, AZ, USA.

^# Contributed equally.

Abstract

A comprehensive, patient-centered conceptual model of early Parkinson's is lacking and is greatly needed. A systematic review and meta-synthesis of qualitative and quantitative research was conducted by a multi-stakeholder taskforce using JBI Mixed Methods Review criteria and GRADE-CERQual standards for assessment of evidence. Over 340 symptoms and impacts were identified across ten symptom domains (Movement, Cognitive, Psychiatric, Sleep, Sensory, Speech, Digestive, Urinary, Sexual, Autonomic) and two impact domains (Physical and Psychosocial functioning). A wide range of motor and non-motor symptoms were present in early disease, with strongest support for tremor, dexterity, gait, stiffness, slow movements, cognitive, mood, and sleep alterations, urinary dysfunction, constipation, pain, and fatigue. These affected mobility, self-concept, coping, effort of living, interactions and important activities, with evidence of many understudied concepts. This model offers the most comprehensive catalogue of symptoms and impacts in Parkinson's to date and will support clinical practice and endpoint selection for therapeutic trials.