Actigraphy Detects Greater Intra-Individual Variability During Gait in Non-Manifesting LRRK2 Mutation Carriers

Article type: Research Article

Authors: van den Heuvel, Lieneke^{a; 1; *} | Lim, Andrew S.^b | Visanji, Naomi P.^a | Huang, Jana^a | Ghate, Taneera^a | Mestre, Tiago A.^c | AlDakheel, Amaal^a | Connolly, Barbara S.^a | Gasca-Salas, Carmen^{a; 2} | Kern, Drew S.^d | Jain, Jennifer^a | Slow, Elizabeth J.^a | Pondal, Margarita^a | Faust-Socher, Achinoam^a | Rogaeva, Ekaterina^e | Tomlinson, George^f | Lang, Anthony E.^a | Marras, Connie^a

Affiliations: [a] Toronto Western Hospital Morton and Gloria Shulman Movement Disorders Centre and the Edmond J. Safra Program in Parkinson’s Disease, University of Toronto, Toronto, ON, Canada | [b] Department of Medicine, Division of Neurology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada | [c] Department of Medicine, Parkinson’s disease and Movement disorders Centre, Division of Neurology, The Ottawa Hospital Research Institute, Ottawa Brain and Mind Research Institute, Ottawa, Canada | [d] Department of Neurology, Movement Disorders Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA | [e] Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada | [f] Department of Medicine, University Health Network/Mt Sinai Hospital, University of Toronto, Toronto, ON,  Canada

Correspondence: [*] Correspondence to: Lieneke van den Heuvel, Department of Neurology, Radboud University Medical Centre, Reinier Postlaan 4, Postbus 9101, 6500 HB Nijmegen, The Netherlands. Tel.: +31 24 36166 00; E-mail: [email protected].

Note: [1] Current address: Radboud University Medical Centre, Nijmegen, The Netherlands

Note: [2] Current address: CINAC, HM Puerta del Sur, Hospitales de Madrid, Móstoles, Madrid, Spain

Abstract: Background:With recent advances in the search for disease-modifying therapies for Parkinson’s disease (PD) the importance of identifying prodromal markers becomes greater. Non-manifesting LRRK2 mutation carriers (NMC) are at risk for developing PD, and provide a population in which to identify possible markers. Objective:The aim of this study was to test the hypothesis that NMC have differences in daily activity, fragmentation of sleep, arm swing asymmetry, and movement variability during walking, detectable by actigraphy, as compared to matched control subjects. Methods:Eleven NMC, fourteen PD patients (4 LRRK2-PD, 10 idiopathic PD (iPD)), and twenty-nine controls wore wristbands containing an accelerometer for seven days, and performed a daily walking task. Outcome measures included daily activity, fragmentation of activity, fragmentation of sleep, arm swing asymmetry during walking, and intra-individual variability. Results:Compared to healthy controls, both NMC and LRRK2/iPD showed higher intra-individual variability in activity during walking compared to healthy controls. Individuals with LRRK2-PD/iPD, but not NMC, tend to have lower activity levels, more arm swing asymmetry and less increase of arm swing with transition from slow to faster walking speed compared to healthy controls. Conclusion:Higher intra-individual variability of gait-associated movements might be a useful biomarker of prodromal PD. These results encourage replication in a larger sample and longitudinal analysis is warranted.

Keywords: Actigraphy, high risk Parkinson, LRRK2 mutation, non-manifestingLRRK2 carrier, Parkinson’s disease, variability of gait

DOI: 10.3233/JPD-171151

Journal: Journal of Parkinson's Disease, vol. 8, no. 1, pp. 131-139, 2018