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The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS

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Abstract

Fragile X–associated tremor/ataxia syndrome (FXTAS) is a genetic neurodegenerative disorder characterized by cerebellar ataxia, tremor, and cognitive dysfunction. We examined the impact of dual-task (DT) cognitive-motor interference and fast-paced (FP) gait on gait and turning in FXTAS. Thirty participants with FXTAS and 35 age-matched controls underwent gait analysis using an inertial sensor–based 2-min walk test under three conditions: (1) self-selected pace (ST), (2) FP, and (3) DT with a concurrent verbal fluency task. Linear regression analyses were performed to assess the association between FXTAS diagnosis and gait and turn outcomes. Correlations between gait variables and fall frequency were also calculated. FXTAS participants had reduced stride length and velocity, swing time, and peak turn velocity and greater double limb support time and number of steps to turn compared to controls under all three conditions. There was greater dual task cost of the verbal fluency task on peak turn velocity in men with FXTAS compared to controls. Additionally, stride length variability was increased and cadence was reduced in FXTAS participants in the FP condition. Stride velocity variability under FP gait was significantly associated with the number of self-reported falls in the last year. Greater motor control requirements for turning likely made men with FXTAS more susceptible to the negative effects of DT cognitive interference. FP gait exacerbated gait deficits in the domains of rhythm and variability, and increased gait variability with FP was associated with increased falls. These data may inform the design of rehabilitation strategies in FXTAS.

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Acknowledgments

The authors would like to thank the patients and volunteers who participated in this study, as well as the Movement Disorders staff for assistance with study recruitment. We also thank Andrew McAsey, Colleen Huml, Alexandra Bery, Timothy Young, Lili Zhou, and Jonathon Jackson for assistance with the data collection.

Funding

This work was supported by the NIH (K01 HD088762) (JAO), Rush University Cohn Fellowship Award 2014 (JAO), Rush Translational Science Award 2015 (JAO), Rush Dean’s Fellowship Award 2018 (JG), National Fragile X Foundation 2015 Summer Fellowship Award (ER), and FRAXA Foundation grant (EBK).

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  1. Department of Cell & Molecular Medicine, Rush University Medical Center, Chicago, IL, 60612, USA

    Joan A. O’Keefe, Erin Robertson, Alexandras Biskis, Jessica Joyce, Danielle Carnes & Nicollette Purcell

  2. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, 60612, USA

    Joan A. O’Keefe, Bichun Ouyang, Yuanqing Liu, Elizabeth Berry-Kravis & Deborah A. Hall

  3. Rush Medical College, Rush University Medical Center, Chicago, IL, USA

    Joseph Guan

  4. Departments of Pediatrics and Biochemistry, Rush University Medical Center, Chicago, IL, USA

    Elizabeth Berry-Kravis

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  1. Joan A. O’Keefe
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Correspondence to Joan A. O’Keefe.

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Joan A. O’Keefe receives research support from the NIH (K01 HD088762); she reports no disclosures or conflicts of interests related to this manuscript. Joseph Guan reports no disclosures or conflicts of interests related to this manuscript. Erin Robertson reports no disclosures or conflicts of interests related to this manuscript. Alexandras Biskis reports no disclosures or conflicts of interests related to this manuscript. Jessica Joyce reports no disclosures or conflicts of interests related to this manuscript. Bichun Ouyang no disclosures or conflicts of interests related to this manuscript. Yuanqing Liu reports no disclosures or conflicts of interests related to this manuscript. Danielle Carnes reports no disclosures or conflicts of interests related to this manuscript. Nicollette Purcell reports no disclosures or conflicts of interests related to this manuscript. EBK has received funding from Seaside Therapeutics, Novartis, Roche, Alcobra, Neuren, Cydan, Fulcrum, GW, Neurotrope, Marinus, Zynerba, BioMarin, Ovid, Acadia, Yamo, Ionis, Ultragenyx, Lumos, GeneTx Pharmaceuticals to consult on trial design or development strategies and/or conduct clinical trials in FXS or other NDDs or neurodegenerative disorders, from Vtesse/Sucampo/Mallinkcrodt to conduct clinical trials in NP-C, and from Asuragen Inc. to develop testing standards for FMR1 testing as well as research support from NICHD, NINDS, NIMH, CDC, NCATS and the John Merck Fund. All funding to EBK is directed to Rush University Medical Center to support rare disease programs. EBK receives no personal funds. She reports no conflicts of interests related to this manuscript. Deborah A. Hall receives research support from the NIH, the Parkinson’s Foundation, Abbvie, Biogen, Biohaven, Neurocrine, Fujifilm, and Pfizer; she reports no conflicts of interests related to this manuscript.

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O’Keefe, J.A., Guan, J., Robertson, E. et al. The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS. Cerebellum 20, 212–221 (2021). https://doi.org/10.1007/s12311-020-01199-3

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