AUTHOR=Martini Douglas N. , Morris Rosie , Kelly Valerie E. , Hiller Amie , Chung Kathryn A. , Hu Shu-Ching , Zabetian Cyrus P. , Oakley John , Poston Kathleen , Mata Ignacio F. , Edwards Karen L. , Lapidus Jodi A. , Grabowski Thomas J. , Montine Thomas J. , Quinn Joseph F. , Horak Fay 

TITLE=Sensorimotor Inhibition and Mobility in Genetic Subgroups of Parkinson's Disease

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00893

DOI=10.3389/fneur.2020.00893

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> Mobility and sensorimotor inhibition impairments are heterogeneous in Parkinson's disease (PD). Genetics may contribute to this heterogeneity since the apolipoprotein (<italic>APOE</italic>) ε4 allele and glucocerebrosidase (<italic>GBA</italic>) gene variants have been related to mobility impairments in otherwise healthy older adult (OA) and PD cohorts. The purpose of this study is to determine if <italic>APOE</italic> or <italic>GBA</italic> genetic status affects sensorimotor inhibition and whether the relationship between sensorimotor inhibition and mobility differs in genetic sub-groups of PD.</p><p><bold>Methods:</bold> Ninety-three participants with idiopathic PD (53 non-carriers; 23 ε4 carriers; 17 <italic>GBA</italic> variants) and 72 OA (45 non-carriers; 27 ε4 carriers) had sensorimotor inhibition characterized by short-latency afferent inhibition. Mobility was assessed in four gait domains (pace/turning, rhythm, trunk, variability) and two postural sway domains (area/jerkiness and velocity) using inertial sensors.</p><p><bold>Results:</bold> Sensorimotor inhibition was worse in the PD than OA group, with no effect of genetic status. Gait pace/turning was slower and variability was higher (<italic>p</italic> &lt; 0.01) in PD compared to OA. Postural sway area/jerkiness (<italic>p</italic> &lt; 0.01) and velocity (<italic>p</italic> &lt; 0.01) were also worse in the PD than OA group. Genetic status was not significantly related to any gait or postural sway domain. Sensorimotor inhibition was significantly correlated with gait variability (<italic>r</italic> = 0.27; <italic>p</italic> = 0.02) and trunk movement (<italic>r</italic> = 0.23; <italic>p</italic> = 0.045) in the PD group. In PD non-carriers, sensorimotor inhibition related to variability (<italic>r</italic> = 0.35; <italic>p</italic> = 0.010) and trunk movement (<italic>r</italic> = 0.31; <italic>p</italic> = 0.025). In the PD ε4 group, sensorimotor inhibition only related to rhythm (<italic>r</italic> = 0.47; <italic>p</italic> = 0.024), while sensorimotor inhibition related to pace/turning (<italic>r</italic> = −0.49; <italic>p</italic> = 0.046) and rhythm (<italic>r</italic> = 0.59; <italic>p</italic> = 0.013) in the PD <italic>GBA</italic> group. Sensorimotor inhibition was significantly correlated with gait pace/turning (<italic>r</italic> = −0.27; <italic>p</italic> = 0.04) in the OA group. There was no relationship between sensorimotor inhibition and postural sway.</p><p><bold>Conclusion:</bold> ε4 and <italic>GBA</italic> genetic status did not affect sensorimotor inhibition or mobility impairments in this PD cohort. However, worse sensorimotor inhibition was associated with gait variability in PD non-carriers, but with gait rhythm in PD ε4 carriers and with gait rhythm and pace in PD with <italic>GBA</italic> variants. Impaired sensorimotor inhibition had a larger effect on mobility in people with PD than OA and affected different domains of mobility depending on genetic status.</p>