Gait and cognitive abnormalities are associated with regional cerebellar atrophy in elderly fallers - A pilot study.

OBJECTIVES: To investigate cerebellar lobule atrophy patterns in elderly fallers (EFs) and their association with gait and cognitive performance. BACKGROUND: Cognitive impairments, gait, and balance deficits are major risk factors for falls in older adults, however, their neural fingerprints remain poorly understood. Recent evidence from neuroimaging studies highlight the role of the cerebellum in both sensorimotor and cognitive networks, suggesting that it may contribute to fall risk. METHODS: Fourteen EFs (mean age ± SD = 78 ± 1.5 yrs.) and 20 healthy controls (HCs) (mean age ± SD = 69.6 ± 1.3 yrs.) underwent a 3 T MRI scan obtaining 3D T1-weighted images, cognitive, and gait assessments. Cerebellar lobule segmentation was performed, and the obtained cerebellar lobules volumes were adjusted for intracranial volume (ICV). The relationship between lobules volumes, gait, and cognitive performance scores was assessed using hierarchical multiple linear regression adjusted for age and gender. RESULTS: EFs exhibited lower cerebellar volumes in the posterior cerebellum, lobules V, VI, VIIB, VIIIA, VIIIB, and Crus II, and significantly higher volumes in the anterior cerebellum and lobule IV (p = 0.018 and p = 0.046) compared to HCs. In EFs, lobule V, VI, VIIB, VIIIA, VIIIB, and anterior cerebellum volumes were found to be independent predictors of usual walking (UW) gait speed, dual-task (DT) gait speed, mini Best, MOCA, CTTa, and CTTb (p < 0.05). CONCLUSIONS: The observed patterns of cerebellar lobule atrophy and their associations with motor and cognitive performance scores suggest that cerebellar atrophy contributes to the pathophysiology of fall risk in EFs.

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.

Gait.

Gait is one of the keys to functional independence. For a long-time, walking was considered an automatic process involving minimal higher-level cognitive input. Indeed, walking does not take place without muscles that move the limbs and the "lower-level" control that regulates the timely activation of the muscles. However, a growing body of literature suggests that walking can be viewed as a cognitive process that requires "higher-level" cognitive control, especially during challenging walking conditions that require executive function and attention. Two main locomotor pathways have been identified involving multiple brain areas for the control of posture and gait: the dorsal pathway of cognitive locomotor control and the ventral pathway for emotional locomotor control. These pathways may be distinctly affected in different pathologies that have important implications for rehabilitation and therapy. The clinical assessment of gait should be a focused, simple, and cost-effective process that provides both quantifiable and qualitative information on performance. In the last two decades, gait analysis has gradually shifted from analysis of a few steps in a restricted space to long-term monitoring of gait using body fixed sensors, capturing real-life and routine behavior in the home and community environment. The chapter also describes this evolution and its implications.

Subcortical Volumes Differ in Parkinson's Disease Motor Subtypes: New Insights into the Pathophysiology of Disparate Symptoms.

OBJECTIVES: Patients with Parkinson's disease (PD) can be classified, based on their motor symptoms into the Postural Instability Gait Difficulty (PIGD) subtype or the Tremor Dominant (TD) subtype. Gray matter changes between the subtypes have been reported using whole brain Voxel-Based Morphometry (VBM), however, the evaluation of subcortical gray matter volumetric differences between these subtypes using automated volumetric analysis has only been studied in relatively small sample sizes and needs further study to confirm that the negative findings were not due to the sample size. Therefore, we aimed to evaluate volumetric changes in subcortical regions and their association with PD motor subtypes. METHODS: Automated volumetric magnetic resonance imaging (MRI) analysis quantified the subcortical gray matter volumes of patients with PD in the PIGD subtype (n = 30), in the TD subtype (n = 30), and in 28 healthy controls (HCs). RESULTS: Significantly lower amygdala and globus pallidus gray matter volume was detected in the PIGD, as compared to the TD subtype, with a trend for an association between globus pallidus degeneration and higher (worse) PIGD scores. Furthermore, among all the patients with PD, higher hippocampal volumes were correlated with a higher (better) dual tasking gait speed (r = 0.30, p < 0.002) and with a higher global cognitive score (r = 0.36, p < 0.0001). Lower putamen volume was correlated with a higher (worse) freezing of gait score (r = -0.28, p < 0.004), an episodic symptom which is common among the PIGD subtype. As expected, differences detected between HCs and patients in the PD subgroups included regions within the amygdala and the dorsal striatum but not the ventral striatum, a brain region that is generally considered to be more preserved in PD. CONCLUSIONS: The disparate patterns of subcortical degeneration can explain some of the differences in symptoms between the PD subtypes such as gait disturbances and cognitive functions. These findings may, in the future, help to inform a personalized therapeutic approach.

The Role of the Frontal Lobe in Complex Walking Among Patients With Parkinson's Disease and Healthy Older Adults: An fNIRS Study.

BACKGROUND: Gait is influenced by higher order cognitive and cortical control mechanisms. Functional near infrared spectroscopy (fNIRS) has been used to examine frontal activation during walking in healthy older adults, reporting increased oxygenated hemoglobin (HbO2) levels during dual task walking (DT), compared with usual walking. OBJECTIVE: To investigate the role of the frontal lobe during DT and obstacle negotiation, in healthy older adults and patients with Parkinson's disease (PD). METHODS: Thirty-eight healthy older adults (mean age 70.4 ± 0.9 years) and 68 patients with PD (mean age 71.7 ± 1.1 years,) performed 3 walking tasks: (a) usual walking, (b) DT walking, and (c) obstacles negotiation, with fNIRS and accelerometers. Linear-mix models were used to detect changes between groups and within tasks. RESULTS: Patients with PD had higher activation during usual walking (P < .030). During DT, HbO2 increased only in healthy older adults (P < .001). During obstacle negotiation, HbO2 increased in patients with PD (P = .001) and tended to increase in healthy older adults (P = .053). Higher DT and obstacle cost (P < .003) and worse cognitive performance were observed in patients with PD (P = .001). CONCLUSIONS: A different pattern of frontal activation during walking was observed between groups. The higher activation during usual walking in patients with PD suggests that the prefrontal cortex plays an important role already during simple walking. However, higher activation relative to baseline during obstacle negotiation and not during DT in the patients with PD demonstrates that prefrontal activation depends on the nature of the task. These findings may have important implications for rehabilitation of gait in patients with PD.

Technology in Parkinson's disease: Challenges and opportunities.

The miniaturization, sophistication, proliferation, and accessibility of technologies are enabling the capture of more and previously inaccessible phenomena in Parkinson's disease (PD). However, more information has not translated into a greater understanding of disease complexity to satisfy diagnostic and therapeutic needs. Challenges include noncompatible technology platforms, the need for wide-scale and long-term deployment of sensor technology (among vulnerable elderly patients in particular), and the gap between the "big data" acquired with sensitive measurement technologies and their limited clinical application. Major opportunities could be realized if new technologies are developed as part of open-source and/or open-hardware platforms that enable multichannel data capture sensitive to the broad range of motor and nonmotor problems that characterize PD and are adaptable into self-adjusting, individualized treatment delivery systems. The International Parkinson and Movement Disorders Society Task Force on Technology is entrusted to convene engineers, clinicians, researchers, and patients to promote the development of integrated measurement and closed-loop therapeutic systems with high patient adherence that also serve to (1) encourage the adoption of clinico-pathophysiologic phenotyping and early detection of critical disease milestones, (2) enhance the tailoring of symptomatic therapy, (3) improve subgroup targeting of patients for future testing of disease-modifying treatments, and (4) identify objective biomarkers to improve the longitudinal tracking of impairments in clinical care and research. This article summarizes the work carried out by the task force toward identifying challenges and opportunities in the development of technologies with potential for improving the clinical management and the quality of life of individuals with PD. © 2016 International Parkinson and Movement Disorder Society.

Aging, the Central Nervous System, and Mobility in Older Adults: Neural Mechanisms of Mobility Impairment.

BACKGROUND: Mobility is crucial for successful aging and is impaired in many older adults. We know very little about the subtle, subclinical age-related changes in the central nervous system (CNS) that mediate mobility impairment. METHODS: A conference series focused on aging, the CNS, and mobility was launched. The second conference addressed major age-associated mechanisms of CNS-mediated mobility impairment. Speakers and conference attendees recommended key areas for future research, identified barriers to progress, and proposed strategies to overcome them. RESULTS: Priorities identified for future research include (a) studying interactions among different mechanisms; (b) examining effects of interventions targeting these mechanisms; (c) evaluating the effect of genetic polymorphisms on risks and course of age-related mobility impairment; and (d) examining the effect of age on CNS repair processes, neuroplasticity, and neuronal compensatory mechanisms. Key strategies to promote research include (a) establish standard measures of mobility across species; (b) evaluate the effect of aging in the absence of disease on CNS and mobility; and (c) use advanced computational methods to better evaluate the interactions between CNS and other systems involved in mobility. CONCLUSIONS: CNS is a major player in the process, leading to mobility decline with aging. Future research in this area has the potential to prolong independence in older persons. Better interactions among disciplines and shared research paradigms are needed to make progress. Research priorities include the development of innovative approaches to integrate research on aging, cognition, and movement with attention to neurovascular function, neuroplasticity, and neurophysiological reserve.

Changes in oxygenated hemoglobin link freezing of gait to frontal activation in patients with Parkinson disease: an fNIRS study of transient motor-cognitive failures.

Recent studies have suggested that deficits in executive function contribute to freezing of gait (FOG), an episodic disturbance common among patients with Parkinson's disease (PD). To date, most findings provide only indirect evidence of this relationship. Here, we evaluated a more direct link between FOG and frontal lobe dysfunction. Functional, near infrared spectroscopy measured frontal activation, i.e., oxygenated hemoglobin (HbO2) levels in Brodmann area 10 before and during FOG. Eleven patients with PD and eleven healthy older adults were studied. Changes in frontal lobe activation before and during FOG that occurred during turns were determined. Altogether, 49 FOG episodes were observed-28 occurred during turns that were anticipated (i.e., the patient knew in advance that the turn was coming), 21 during unanticipated turns that were performed "abruptly", according to the examiner's request. During anticipated turns, HbO2 increased by 0.22 ± 0.08 µM (p = 0.004) before FOG and by an additional 0.19 ± 0.13 µM (p = 0.072) during FOG. In contrast, during unanticipated turns, HbO2 did not increase before or during FOG. HbO2 decreased by 0.32 ± 0.08 µM (p = 0.004) during turns without FOG; in healthy controls HbO2 did not change during turns. These findings support the existence of an association between FOG episodes and changes in frontal lobe HbO2. Increased activation in Brodmann area 10 before FOG, specifically during anticipated turns, highlights the connections between motor planning, information processing, and FOG. These results support the idea that alterations in executive control play a role in this debilitating motor disturbance.

Effects of walking speed on asymmetry and bilateral coordination of gait.

The mechanisms regulating the bilateral coordination of gait in humans are largely unknown. Our objective was to study how bilateral coordination changes as a result of gait speed modifications during over ground walking. 15 young adults wore force sensitive insoles that measured vertical forces used to determine the timing of the gait cycle events under three walking conditions (i.e., usual-walking, fast and slow). Ground reaction force impact (GRFI) associated with heel-strikes was also quantified, representing the potential contribution of sensory feedback to the regulation of gait. Gait asymmetry (GA) was quantified based on the differences between right and left swing times and the bilateral coordination of gait was assessed using the phase coordination index (PCI), a metric that quantifies the consistency and accuracy of the anti-phase stepping pattern. GA was preserved in the three different gait speeds. PCI was higher (reduced coordination) in the slow gait condition, compared to usual-walking (3.51% vs. 2.47%, respectively, p=0.002), but was not significantly affected in the fast condition. GRFI values were lower in the slow walking as compared to usual-walking and higher in the fast walking condition (p<0.001). Stepwise regression revealed that slow gait related changes in PCI were not associated with the slow gait related changes in GRFI. The present findings suggest that left-right anti-phase stepping is similar in normal and fast walking, but altered during slow walking. This behavior might reflect a relative increase in attention resources required to regulate a slow gait speed, consistent with the possibility that cortical function and supraspinal input influences the bilateral coordination of gait.

Evidence for a relationship between bilateral coordination during complex gait tasks and freezing of gait in Parkinson's disease.

BACKGROUND: Freezing of gait is a debilitating and common gait disturbance observed in individuals with Parkinson's disease (PD). Although the underlying mechanisms of freezing remain unclear, bilateral coordination of steps, measured as a phase coordination index, has been suggested to be related to freezing. Phase coordination index has not, however, been measured during tasks associated with freezing such as turning and backward walking. Understanding how bilateral coordination changes during tasks associated with freezing may improve our understanding of the causes of freezing. METHODS: Twelve individuals with PD who freeze (freezers), 19 individuals with PD who do not freeze (non-freezers), and 10 healthy, age-matched older adults participated. General motor disease severity and freezing severity were assessed. Phase coordination index was calculated for all subjects during forward walking, backward walking, continuous turning in small radius circles, and turning in large radius circles. RESULTS: Freezers and non-freezers had similar disease duration and general motor severity. Stepping coordination (measured as phase coordination index) was significantly worse in freezers compared to non-freezers and controls. Turning and backward walking, tasks related to freezing, resulted in worse coordination with respect to forward walking. Coordination was associated with severity of freezing scores such that worse coordination was correlated with more severe freezing. CONCLUSIONS: These results provide evidence that stepping coordination is related to freezing in people with PD. Identifying variables associated with freezing may provide insights into factors underlying this symptom, and may inform rehabilitative interventions to reduce its occurrence in PD.

Postural instability and fall risk in Parkinson's disease: impaired dual tasking, pacing, and bilateral coordination of gait during the "ON" medication state.

The interplay between gait and specific cognitive faculties, in particular executive function (EF) and dual tasking abilities, has been described in healthy adults and in patients with Parkinson's disease (PD). There is, however, little direct evidence on the relationship between cognitive function, gait, and fall risk in PD, especially in the "ON" state (i.e., under the influence of the anti-parkinsonian medications). To address this issue, we evaluated cognitive function and gait under usual walking and dual-task conditions in 30 patients with PD in the ON state of the medication cycle. Subjects were classified as fallers or non-fallers based on their history. A computerized battery quantified cognitive function. Gait was assessed under three conditions: (1) Usual walking, (2) While subtracting serial 3 s, and (3) While subtracting serial 7 s. The EF and attention scores were lower in the fallers, compared to non-fallers (P ≤ 0.037), but general measures of cognition, e.g., memory, (P = 0.341) were not. Gait speed, variability, and the bilateral coordination of gait were worse in the fallers in all conditions. The DT effects on gait variability and bilateral coordination were larger in the fallers (P = 0.044, P = 0.061, respectively). These results suggest that patients with PD who have a high risk of falling are more sensitive to DT effects, perhaps as a result of relatively poor EF. These cognitive and motor deficits may increase the likelihood of loss of balance during everyday attention-demanding tasks among patients with PD.