Which Gait Tasks Produce Reliable Outcome Measures of Freezing of Gait in Parkinson's Disease?

Background: Measurement of freezing of gait (FOG) relies on the sensitivity and reliability of tasks to provoke FOG. It is currently unclear which tasks provide the best outcomes and how medication state plays into this. Objective: To establish the sensitivity and test-retest reliability of various FOG-provoking tasks for presence and severity of FOG, with (ON) and without (OFF) dopaminergic medication. Methods: FOG-presence and percentage time frozen (% TF) were derived from video annotations of a home-based FOG-provoking protocol performed in OFF and ON. This included: the four meter walk (4MW), Timed Up and Go (TUG) single (ST) and dual task (DT), 360° turns in ST and DT, a doorway condition, and a personalized condition. Sensitivity was tested at baseline in 63 definite freezers. Test-retest reliability was evaluated over 5 weeks in 26 freezers. Results: Sensitivity and test-retest reliability were highest for 360° turns and higher in OFF than ON. Test-retest intra-class correlation coefficients of % TF varied between 0.63-0.90 in OFF and 0.18-0.87 in ON, and minimal detectable changes (MDCs) were high. The optimal protocol included TUG ST, 360° turns ST, 360° turns DT and a doorway condition, provoking FOG in all freezers in OFF and 91.9% in ON and this could be done reliably in 95.8% (OFF) and 84.0% (ON) of the sample. Combining OFF and ON further improved outcomes. Conclusions: The highest sensitivity and reliability was achieved with a multi-trigger protocol performed in OFF + ON. However, the high MDCs for % TF underscore the need for further optimization of FOG measurement.

Freezing of gait is a very burdensome and episodic symptom in Parkinson's disease that is difficult to measure. Measurement of freezing is needed to determine whether someone has freezing and how severe this is, and relies on observation during a freezing-triggering protocol. However, it is unclear what protocol is sufficiently sensitive to trigger freezing in many freezers, and whether freezing can be triggered reliably at different timepoints. Here, we investigated 1) which tasks can trigger freezing-presence and freezing-severity sensitively and reliably, 2) how medication state influences this, and 3) what task combination was most reliable. Sixty-three patients with daily freezing performed several freezing-triggering tasks in their homes, both with (ON) and without (OFF) anti-Parkinsonian medication. In twenty-six patients, the measurement was repeated 5 weeks later to determine test-retest reliability. First, we found that performing 360° turns in place with a cognitive dual task was the most sensitive and reliable task to trigger FOG. Second, sensitivity and reliability were better in OFF than in ON. Third, the most reliable protocol included: the Timed-Up and Go, 360° turns in place with and without the dual task, and a doorway condition. This protocol triggered freezing in all patients in OFF and 91.9% in ON and did so reliably in 95.8% (OFF) and 84.0% (ON) of the sample. We recommend to measure freezing with this protocol in OFF + ON, which further improved reliability. However, the measurement error for freezing-severity was high, even for this optimal protocol, underscoring the need for further optimization of freezing measurement.

On-Demand Cueing for Freezing of Gait in Parkinson's Disease: A Randomized Controlled Trial.

BACKGROUND: Cueing can alleviate freezing of gait (FOG) in people with Parkinson's disease (PD), but using the same cues continuously in daily life may compromise effectiveness. Therefore, we developed the DeFOG-system to deliver personalized auditory cues on detection of a FOG episode. OBJECTIVES: We aimed to evaluate the effects of DeFOG during a FOG-provoking protocol: (1) after 4 weeks of DeFOG-use in daily life against an active control group; (2) after immediate DeFOG-use (within-group) in different medication states. METHOD: In this randomized controlled trial, 63 people with PD and daily FOG were allocated to the DeFOG or active control group. Both groups received feedback on their daily living step counts using the device, but the DeFOG group also received on-demand cueing. Video-rated FOG severity was compared pre- and post-intervention through a FOG-provoking protocol administered at home off and on-medication, but without using DeFOG. Within-group effects were tested by comparing FOG during the protocol with and without DeFOG. RESULTS: DeFOG-use during the 4 weeks was similar between groups, but we found no between-group differences in FOG-severity. However, the within-group analysis showed that FOG was alleviated by DeFOG (effect size d = 0.57), regardless of medication state. Combining DeFOG and medication yielded an effect size of d = 0.67. CONCLUSIONS: DeFOG reduced FOG considerably in a population of severe freezers both off and on medication. Nonetheless, 4 weeks of DeFOG-use in daily life did not ameliorate FOG during the protocol unless DeFOG was worn. These findings suggest that on-demand cueing is only effective when used, similar to other walking aids. © 2024 International Parkinson and Movement Disorder Society.

Protocol for the DeFOG trial: A randomized controlled trial on the effects of smartphone-based, on-demand cueing for freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait (FOG) is a highly incapacitating symptom that affects many people with Parkinson's disease (PD). Cueing triggered upon real-time FOG detection (on-demand cueing) shows promise for FOG treatment. Yet, the feasibility of implementation and efficacy in daily life is still unknown. Therefore, this study aims to investigate the effectiveness of DeFOG: a smartphone and sensor-based on-demand cueing solution for FOG. METHODS: Sixty-two PD patients with FOG will be recruited for this single-blind, multi-center, randomized controlled phase II trial. Patients will be randomized into either the intervention group or the active control group. For four weeks, both groups will receive feedback about their physical activity using the wearable DeFOG system in daily life. In addition, the intervention group will also receive on-demand auditory cueing and instructions. Before and after the intervention, home-based assessments will be performed to evaluate the primary outcome, i.e., "percentage time frozen" during a FOG-provoking protocol. Secondary outcomes include the training effects on physical activity monitored over 7 days and the user-friendliness of the technology. DISCUSSION: The DeFOG trial will investigate the effectiveness of personalized on-demand cueing in a controlled design, delivered for 4 weeks in the patient's home environment. We anticipate that DeFOG will reduce FOG to a greater degree than in the control group and we will explore the impact of the intervention on physical activity levels. We expect to gain in-depth insight into whether and how patients control FOG using cueing methods in their daily lives. TRIAL REGISTRATION: Clinicaltrials.gov NCT03978507.

Combining transcranial direct current stimulation with a motor-cognitive task: the impact on dual-task walking costs in older adults.

BACKGROUND: The performance of a secondary task while walking increases motor-cognitive interference and exacerbates fall risk in older adults. Previous studies have demonstrated that transcranial direct current stimulation (tDCS) may improve certain types of dual-task performance, and, that tDCS delivered during the performance of a task may augment the benefits of stimulation, potentially reducing motor-cognitive interference. However, it is not yet known if combining multi-target tDCS with the simultaneous performance of a task related to the tDCS targets reduces or increases dual-task walking costs among older adults. The objectives of the present work were (1) To examine whether tDCS applied during the performance of a task that putatively utilizes the brain networks targeted by the neuro-stimulation reduces dual-task costs, and (2) to compare the immediate after-effects of tDCS applied during walking, during seated-rest, and during sham stimulation while walking, on dual-task walking costs in older adults. We also explored the impact on postural sway and other measures of cognitive function. METHODS: A double-blind, 'within-subject' cross-over pilot study evaluated the effects of 20 min of anodal tDCS targeting both the primary motor cortex (M1) and the left dorsolateral prefrontal cortex (lDLPFC) in 25 healthy older adults (73.9 ± 5.2 years). Three stimulation conditions were assessed in three separate sessions: (1) tDCS while walking in a complex environment (tDCS + walking), (2) tDCS while seated (tDCS + seated), and (3) walking in a complex environment with sham tDCS (sham + walking). The complex walking condition utilized virtual reality to tax motor and cognitive abilities. During each session, usual-walking, dual-task walking, quiet standing sway, and cognitive function (e.g., Stroop test) were assessed before and immediately after stimulation. Dual-task costs to gait speed and other measures were computed. RESULTS: The dual-task cost to gait speed was reduced after tDCS + walking (p = 0.004) as compared to baseline values. Neither tDCS + seated (p = 0.173) nor sham + walking (p = 0.826) influenced this outcome. Similar results were seen for other gait measures and for Stroop performance. Sway was not affected by tDCS. CONCLUSIONS: tDCS delivered during the performance of challenging walking decreased the dual-task cost to walking in older adults when they were tested just after stimulation. These results support the existence of a state-dependent impact of neuro-modulation that may set the stage for a more optimal neuro-rehabilitation. TRIAL REGISTRATION: Clinical Trials Gov Registrations Number: NCT02954328.

Treadmill walking reduces pre-frontal activation in patients with Parkinson's disease.

BACKGROUND: Among patients with Parkinson's disease (PD), gait is typically disturbed and less automatic. These gait changes are associated with impaired rhythmicity and increased prefrontal activation, presumably in an attempt to compensate for reduced automaticity. RESEARCH QUESTION: We investigated whether during treadmill walking, when the pace is determined and fixed, prefrontal activation in patients with PD is lower, as compared to over-ground walking. METHODS: Twenty patients with PD (age: 69.8 ±â€¯6.5 yrs.; MoCA: 26.9 ±â€¯2.4; disease duration: 7.9 ±â€¯4.2 yrs) walked at a self-selected walking speed over-ground and on a treadmill. A wireless functional near infrared spectroscopy (fNIRS) system measured prefrontal lobe activation, i.e., oxygenated hemoglobin (Hb02) in the pre-frontal area. Gait was evaluated using 3D-accelerometers attached to the lower back and ankles (Opal™, APDM). Dynamic gait stability was assessed using the maximum Lyapunov exponent to investigate automaticity of the walking pattern. RESULTS: Hb02 was lower during treadmill walking than during over-ground walking (p = 0.001). Gait stability was greater on the treadmill, compared to over-ground walking, in both the anteroposterior and medio-lateral axes (p < 0.001). SIGNIFICANCE: These findings support the notion that when gait is externally paced, prefrontal lobe activation is reduced in patients with PD, perhaps reflecting a reduced need for compensatory cognitive mechanisms.