Methods for Quantifying the Role of Attention and Executive ...

Methods for Quantifying the Role of Mood and Cognitive Function in Gait Jeffrey M. Hausdorff, PhD Laboratory for Gait & Neurodynamics, Tel-Aviv Sourasky Medical Center Department of Physical Therapy, Sackler School of Medicine Department of Medicine, Harvard Medical School Bethesda, Maryland September 2007 Do these studies tell us about causal relationships among Triad Members? POINTS TO BE DISCUSSED How to study mobility as a function of mood and cognitive function? Whats automaticity?

Is gait automatic? Dual tasking Plasticity of the motor-cognitive competition Why are certain gait changes predictive of dementia? ?Whats automaticity Automatic movements are executed without attention being clearly directed towards the details of the movement. Automaticity is common, especially for movements that require low levels of precision or for movements that are frequently

made. (Bernstein 1967, from Wu and Hallet 2005) Gait / Mobility Assessment Wearable systems Footswitches, insoles Accelerometers Gyroscopes Goniometers Actigraphs Gait Mats Camera-based systems USB STATUS LED


START/STOP SWITCH Which parameters of gait to measure in order to test automaticity? Gait Speed / Stride Length (pace) Cadence / Stride Time (rhythm) Swing / Stance / Double Support time (dynamic balance) Stride-to-Stride Fluctuations (variability) Stride width, asymmetry, toe clearance All of these inter-related (just like cognitive domains inter-related, but there is unique behavior as well) J Verghese et al. JNNP 2007

Gait Variability How does one stride differ from the other in ?time A closer look reveals Stride-to-Stride Fluctuations Increased Gait Variability in Fallers Time (min)

Time (min) Hausdorff et al., Arch Phys Med Rehabil, 1997 Studies that Have Found Increased Gait Variability in Fallers Elderly fallers Maki; Barak et al.; Springer et al.; Menz et al.; Auvinet et al. Peripheral neuropathy Richardson et al.; DeMott et al. Parkinsons disease Schaafsma et al. Alzheimers disease

Sheirdan et al.; Nakamura et al.. Higher level gait disorders Herman et al. Arguments in favor of Automaticity Decerebrate cats can walk Infants can generate locomotor pattern Adults can walk, talk, chew gum etc. Imaging studies PET and SPECT studies found no evidence for activity in areas associated with cognitive function during bipedal movements (bicycling) and paced walking (Christensen et al 2000, Fukuyama et al 1997) Findings supporting the idea that gait is not automatic

Dual Tasking Simultaneous performance of two tasks A common paradigm for studying the attentional demand of a given task Requires dividing attention, an executive function ability Dual tasking 500 493 486 479 472 465 458 451 444 437 430 423 Commonly Used Dual Tasks Talking while walking Arithmetic

Backwards counting, subtractions Phoneme monitoring Alphabet recital (backwards, forward, skipping) Memorization Verbal fluency GoNoGo tests Motor tasks Effects of Dual Tasking on Gait Variability in Alzheimers Disease Routine Walking Dual Task Walking Sheridan et al., 2003 Cognitive Challenge Increases

Gait Variability in Parkinsons disease USUAL Dual Tasking Hausdorff et al., J Ger Psyc Neurol, 2003 DT Increases Gait Variability in PD, but not in Controls Yogev et al, Eur J Neurosci. 2005 Effect of Dual Tasking on Variabilit PD Swing Time CV (%)

Swing Time Variability: Increased Only in PD, not in Controls Group Effect 4.5 4 P=0.005 PD 3.5 Loading Effect 3

P < 0.001 2.5 CONTROLS 2 1.5 none easy moderate Cognitive load

difficult Only in PD Group x Load P<0.001 Yogev et al, EJN, 2005 G a it S p e e d ( m /s e c ) :Gait Speed Similar Effects in PD & CONTROLS 1.4 CONTROLS

1.3 1.2 1.1 PD 1.0 0.9 0.8 none easy moderate Cognitive load

difficult Since 1993-2007, at least 40 studies have examined DT effects on gait (and many more on balance): healthy young and older adults frail, fallers Parkinsons disease

Alzheimers disease CVA, head injuries Negative effects on gait (i.e., speed, gait variability, stride length, etc) What predicts gait variability during dual ?tasking Age? Usual walking abilities?

Disease severity? Memory? Executive function? All of the above? What predicts gait variability during dual ?tasking Depends on: Population Dual task Instructions Specific measure Correlations between Gait Variability and Executive Function in PD

Cognitive Load Level Correlation )P Value( Usual Walking Easy Dual Task Difficult Dual Task 0.34P=.18 *0.52P = .034

*0.64P=.005 Dual task Effects in Healthy Older Adults (n=228) Gait Speed (m/s) 1.3 1.2 1.1 1.0 PM

Serial 3's Serial 7's (%)Swing Time Variability No DT 3.5 3.0 2.5 2.0 No DT

Looking for a home, 2008?? PM Serial 3's Serial 7's Correlations between the dual task decrements and cognitive function, mobility and affect Gait Speed Swing Variability Outcome Measure

Cognitive Function Performancebased measures of Mobility and Balance PM Serial 7's PM Serial 7's

Executive function index -0.07 (0.283) -0.05 (0.516) -0.22 (0.0008) -0.20 (0.003) Attention index

-0.09 (0.202) -0.05 (0.463) -0.17 (0.009) -0.25 (0.0002) Memory index -0.05 (0.450)

0.04 (0.531) -0.14 (0.044) -0.10 (0.151) Visual-spatial function index -0.05 (0.494) 0.02 (0.726)

-0.06 (0.390) -0.06 (0.385) Dynamic Gait Index 0.031 (0.655) 0.08 (0.261) -0.26 (0.0001)

-0.19 (0.005) Berg Balance Score -0.03 (0.716) -0.01 (0.913) -0.19 (0.005) -0.19 (0.006)

Timed Up and Go -0.06 (0.406) -0.08 (0.282) 0.19 (0.005) 0.20 (0.003) 0.07 (0.312)

0.05 (0.492) -0.04 (0.527) -0.07 (0.304) Geriatric Depression Scale 0.08 (0.256) 0.09

(0.219) 0.07 (0.309) 0.14 (0.050) Trait Anxiety Inventory 0.06 (0.397) 0.08 (0.299)

0.18 (0.011) 0.12 (0.095) State Anxiety Inventory 0.12 (0.107) 0.08 (0.273) 0.15 (0.029)

0.07 (0.299) ABC Balance Confidence Scale Affect Brixton scores of EF P=0.05 NonFreezers N=52

Freezers N=63 UPDRS III motor scores Do Freezers have Poorer ?Executive Function P=0.46 NonFreezers N=52 Freezers N=63 Freezing of gait in Parkinsons disease:

why do some patients freeze? Starts Freezing when Subtracting (SFWS) Task Specificity: Are the observed ?properties specific to gait Effects of Dual Tasking on Pedaling No Dual Task Dual Task ?Freezing of Pedaling in PD TWO MODELS OF GAIT

? Automatic, Rhythmic, Repetitive, Little Cognitive Input ? Decision making and real-time control Let your fingers do the walking Assessment of tapping and catching Computerized cognitive assessment system Catch Game Neurotrax Corp, NJ

Table 1:correlation between walking and tapping and between walking and catching Tapping Catching Average tapping interval Average gait speed NS walking Average

Stride time stride time variability NS NS Variability of tapping interval NS NS NS Time to first move

NS NS 0.43 (0.004) Number of direction changes NS NS 0.43 (0.005)

Accuracy 0.38 (0.013) NS -0.42 (0.006) NS NS 0.44 (0.004)

Degree of errors Hausdorff et al., 2005 Association between walking and Stroop test To tease out effects, Make Gait more Difficult Correlation between executive function and walking speed in older persons InChianti study, Ble et al 2005 Subjects with worse EF walk slower in a challenging

environment The effects of mood on gait / Spatiotemporal gait patterns during over ground locomotion in major depression compared with healthy controls Lemke et al, J Psychiatric Research, 2000 Gait unsteadiness and fall risk in two affective disorders Hausdorff et al 2004 Effects of pharmacologic therapy

Paleacu et al 2007 Fear of falling Correlation between Fear of Falling and Gait Variability in patients with HLGD r=0.74 p<0.01 Herman et al., 2005 The Effects of Support (reducing FOF) on Gait Speed in Patients with HLGD 1.2 Hand Holding

Other 1.0 Gait Speed (m/sec) improved speed .8 .6 interventions did not

P < .002 .4 Normal Balash et al., 2007 Walker Guarding Hand 8weeks of Tai Chi for FOF in almost Frail Elderly Tai Chi reduced FOF Compared to control group NO significant effect on GAIT SPEED JG Zhang et al. 2006

Intervention Studies Can they tell us anything about the triad? Common cause or random? A gold standard for studying motor- cognitive associations: RCT, double-blinded, in young & old Measure gait & neuro-imaging response to single and dual task Controlled intervention / DT training Compare change in performance across groups Change in cortical activation (predefined ROIs) Correlation of the two TrainingInduced Functional Activation Changes

in Dual-Task Processing: An fMRI Study Erickson et al. 2007 Training of visual RT as single & dual tasks Most regions involved in dual task processing before training showed reductions in activation after training. Many of the decreases in activation were correlated with improved performance on the task.

An area in the dorsolateral prefrotal cortex (DLPFC) showed an increase in activation for the training group for the dual task condition. SP- single pure SM- single mixed DM- dual mixed Effects of dual task training on postural sway Pellecchia GL 2005 Training of balance under single and dual task conditions in older adults with balance impairment Silsupadol, Shumway- Cook, Woollacott 2006 3 patients were trained for 4 weeks, 3 times a week, 1

hour each session Patient 1- single tasks Patient 2- training of DT, instructed to share attention between tasks Patient 3 training of dual task, instructed to prioritize each time another task Effects of Dual Task Training on Gait Effects of training and detraining on the static and dynamic balance in elderly fallers and nonfallers: a pilot study Toulotte et al 2006 16 older adults fallers and non- fallers trained for 3 month, twice a week, 1 hour each session Training included: Strengthening exercise

Balance exercise Flexibility exercise Walking with and without dual task exercises Non-Fallers 3 months before 2 days before 2 days after 3 months after Fallers 3 months before 2 days before 2 days after 3 months after Effects of Methylphenidate

(aka MPH, aka Ritalin) Attention enhancer affects gait? Effects of MPH in Children with ADHD Gait variability while 2.7 performing cognitive task 2.6 2.5 2.4 2.3 2.2 2.1 2 Without ritalin

placebo With ritalin Leitner et al. 2007 Executive scores 104 103 102 101 100 99 98 97

96 1 Pre ritalin Post ritalin MPH Effects in Patients with PD 2.2 2.1 Stride time CV 2 1.9

1.8 1.7 1 Pre ritalin Post ritalin 12.5 12 TUG time (SEC) 11.5 11 10.5 10

9.5 1 Pre ritalin Post ritalin Auriel et al. 2006 Devos et al., JNNP 2006 Swing Time Variability (%) Effects of Single Dose of MPH on Swing Time Variability in Elderly 8

6 4 2 Pre Placebo Ritalin Usual Walking Pre Placebo Ritalin Serial 3 Subtractions Placebo effects were NS P=0.039 Pre vs. Ritalin for Usual Walking P=0.012 Pre vs. Ritalin for Serial 3s Ben-Itzhak et al., Neurology, 2007 (abstract)

1) If gait utilizes EF, Gait Predict Vascular Dementia: is this Changes a case of use it or lose it? 2) If gait utilizes EF,Six Years in Advance More than subtle changes in gait reflect subtle changes in EF?

Verghese et al, NEJM, 2002 POINTS TO CONSIDER Different aspects of gait / mobility mood cognitive function (not necessarily sensitive to same inputs) To study these relationships: Cross sectional (compare cognitive to mobility; across different populations with known deficits) Neuro-Imaging (but difficult with gait) Manipulate the complexity of the gait task Intervene / change cognitive function Change / manipulate instruction set Compare across tasks Suggestions Be more specific (not sufficient to say gait is not

automatic) Need to better understand discrepant studies Need to quantify cognitive loading; distinguish among different DTs Need to develop clinically relevant, quantifiable tests Because of triad, need to consider, mood, CF and mobility - not in isolation CALL FOR PAPERS Special issue of the Journal of Gerontology Medical Sciences The Role of Cortical Function in Age-associated Changes in Balance and Gait II February 22-24,2008 Amsterdam A Lesson from Shrek

Shrek: Ogres are like onions. Donkey: They stink? Shrek: Yes. No. Donkey: Oh, they make you cry. Shrek: No. Donkey: Oh, you leave em out in the sun, they get all brown, start sproutin' little white hairs. Shrek: NO. Layers. Onions have layers. Ogres have layers. Onions have layers. You get it? We both have layers. Substitute: gait and cognitive function for Onions and Ogres. Gait Thank you Mood

Cognitive Function

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