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Geriatric Medicine
“Cognition and Mobility Impairment in Older People
The Collusion of Two Giants"
Manuel Montero Odasso, MD, PhD
Department of Medicine, Division of Geriatric MedicineParkwood Hospital, UWO, London ON
Lawson Health Research Institute, London ON
RGP OttawaMarch 18, 2010
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Learning objectives
1. To provide an update on current understanding of the relationship between early mobility and cognitive decline
2. To explore the value of the dual-task paradigm as a way to evaluate cognitive and mobility relationships
3. To demonstrate that gait assessment may be a complementary window to evaluate brain function
4. To explore potential/novel interventions for gait improvement in people with cognitive problems
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...If he was able to keep his body in an upright position, ...If he was able to keep his body in an upright position, to move his hands in one way and their feet in another. to move his hands in one way and their feet in another. To keep improving his brain and to use his mind as To keep improving his brain and to use his mind as best as possible, he stood a chance of success...best as possible, he stood a chance of success...””
Desmond MorrisDesmond Morris““The Naked ApeThe Naked Ape””
A ZoologistA Zoologist’’s Study of the Human Animal. 1967s Study of the Human Animal. 1967
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5 5 millionmillion yearsyears
Montero-Odasso M. [Gait Disorders in the Elderly Persons under the Scope of the Falls Syndrome] [PhD thesis]. Faculty of Medicine Library. University of Buenos Aires.2003
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• Bipedalism was a fundamental evolutionary adaptation
• It happened 1 M years before encephalization
• Necessary step for encephalization, and further creation of tools
• Bipedalism was a key feature to be the predominant species
Bipedalism and Gait
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Geriatric Medicine
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Geriatric Medicine
75 75 yearsyears
Montero-Odasso M. [Gait Disorders in the Elderly Persons under the Scope of the Falls Syndrome] [PhD thesis]. Faculty of Medicine Library. University of Buenos Aires.2003
PREDICTORS of FALLS OR (95%CI) Previous falls 3,0 (1,7-7,0)Gait and balance 2,9 (1,3-5,6)Osteoarthritis 2,4 (1.9-2,9)Medications 2,3 (1,5-3,1)Depression 2,2 (1,7-2,5)Dementia 1,8 (1,1-2,3)80 y/o and over 1,7 (1,1–2,5)
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Geriatric Medicine
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
60 65 70 75 80 85
Age in years
G
ait V
eloc
ity m
/s
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Men
Women
Both
Factors affecting Gait performanceAge-associated gait velocity decline (Data data from different series)
Bendall, EJ et al. Age Ageing 1989; 18: 327-332Bohannon RW. Age Ageing 1997;26:5-19Studenski S et al. JAGS 1998;43:324-326Alexander NB, JAGS 1996;44: 434-451
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US: 1.2 m/secCanada: 1.1 to 1.4 m/sec
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Gait and Cognition
• Gait performance and cognitive function are both key features of the human evolution
• Both deteriorate with aging yielding two geriatric syndromes: Instability and Intellectual Impairment
1.Montero-Odasso M et al J Gerontol A Biol Sci Med Sci 2005; 62:1124-11332.Petersen RC et al. Neurology 2001;56: 1133–11424 3.Montero-Odasso M et al JAGS 2006; 62:1124-1133
Instability
IntellectualImpairment
FalIs-Fractures
Dementia-Delirium
Slow GaitVelocity1,3
MCI 2
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Mild Cognitive Impairment =MCI
• MCI express early problems in “cognition” (pre-dementia state).1,2
• Difficult to characterize who will convert to dementia3
• Gait might provide a window into aspects of brain function in the preclinical onset of dementia
1. Budson AE, Price BH. Memory Dysfunction. N.Engl J Med 2005; 352:692-6992. Dubois B, Albert M. MCI or prodromal dementia? Lancet Neurol 2004; 3:246-248-11333. Petersen RC. Journal of Internal Medicine 2004; 256: 183–194
ContinuumNormal
Dementia
MCI
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• Dogma: Gait is an automatic task which is not related to the cognitive systems
• Increasing evidence of cortical control on gait
• If gait is automatic the performance of attention demanding “dual-task” during walking would not alter the gait pattern
• Instead, dual-tasking affects Gait
Gait and cognition. Is there a relationship?
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1. Ble A et al. J Am Geriatr Soc 2005; 53:410-4152. Markis M et al Arch Neurol Sci 2002; 62:1124-11333. Camicioli R et al. Neurology 1997: 48(4): 955–958.
Dual-task challenge (talking or counting while walking)interferes with gait when “brain reserve” is impaired1,2,3.
This strategy may reveal subtle brain damage
Dual-task paradigm
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Walking When Talking
• Unmonitored conversations
• Reciting names• Counting backward or
serial subtractions• Naming animals• Reaction time to auditory
or visual stimuli• Q & A• Alphabets
The Lancet 1997; 349: 617
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Mild Cognitive Impairment &
Gait Velocity (GV)
Montero-Odasso M, Bergman H, Phillips NA, Wong CH, Sourial N, Chertkow H. BMC Geriatr. 2009 Sep 1;9:41.
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MCI & Gait VelocityHypotheses
1-Gait velocity will be affected by cognitive factors2-Dual-tasking decrement will be more associated to
specific cognitive factors (executive and attention)Methods
– N=60 MCI, mean age 75.2 y– Inclusions: MCI by Peterson’s criteria, MMSE>26
MoCA<26– Exclusions: clinical gait abnormalities, depression.– Clinical assessment with an stop watch
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Gait Velocity was measured as the time taken to walk 6 meters. Subjects were instructed to perform 3 walking tasks:
10 m
6 m
Gait Assessment
1.Montero Odasso M et al. J Nutr Health Aging. 2004;8(5):340-3. 2.Montero Odasso M, Schapira M, Duque G et al. BMC Geriatrics, 2005. 5:15
Counting backwards from 100
Usual pace, participant can be promptedCounting Gait (cGV)
Naming animals
Usual pace, participant can be promptedVerbal Gait (vGV)
NoneUsual and comfortable paceUsual Gait (uGV)
Dual-TaskPaceGait Test
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cGVvGVsGV
1.25
1.00
0.75
0.50
0.25
Walking Task
Gait Velocity(m/s)
Mean (SEM): 0.66 (0.02) m/s
Mean(SEM): 0.65 (0.02) m/s
Mean (SEM) 0.87 (0.02)m/s
Figure 2. Mean gait velocity under single (sGV) and dual tasks (vGV, cGV).
Note: sGV= single gait velocity, vGV= verbal gait velocity, cGV= counting gait velocity.
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Table 2. Associations between cognitive tests and GV under single and dual-tasks (multivariate logistic regression)
Note: TMT= trail making test, MoCa= Montréal Cognitive Assessment, LNS= Letter number sequence*Statistically significant
0.03*0.09
0.060.12
0.060.18
UnadjustedFull adjusted
TMT B-A(pure executive)
0.080.10
0.150.24
0.300.61
UnadjustedFull adjusted
TMT A(attention)
0.920.77
0.540.75
0.650.37
UnadjustedFull adjusted
Delayed MoCA(memory)
0.010*0.017*
0.042*0.065
0.03*0.06
vGVp-value
0.010*0.017*
0.004*0.009*
UnadjustedFull adjustedLNS
(working memory)
0.050.06
0.1480.361
UnadjustedFull adjusted
Digit Symbol (speed)
0.01*0.04*
0.04 *0.13
UnadjustedFull adjusted
TMT B(executive)
cGVp-value
uGVp-valueAdjustmentsCognitive Tests
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• Cognitive correlates of gait are complex and NOT limited to attention.
• Association between cognition and gait varies as a function of walking condition
• Working memory was constantly associated with gait slowing
• possible shared brain networks of cognitive and motor function
Dual-tasking in MCI: Summary
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Mild Cognitive Impairment &
Gait Variability(Gva)
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Step length
Stride length
Velocity
Cadence
Cycle time
Stance time
Swing time
Double support time
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Geriatric Medicine
Gait Assessment
Stride time is a fine parameter of cortical control of gait
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1. Hausdorff JM. Gait variability: methods, modeling and meaning. J Neuroengineering.Rehabil. 2005;2:19.
2. Markis M et al Arch Neurol Sci 2002; 62:1124-11333. Camicioli R et al. Neurology 1997: 48(4): 955–958.
1- Stride time variability = Gait variability1
2- In normal controls stride time variabilityis minimal (2%)2
3- Increased gait variability in older adults has been associated with:
a) Risk of falls b) Executive dysfunctionc) Alzheimer’s disease3
d) Frontal gait disorder
Gait variability (Gva)
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1. Ble A et al. J Am Geriatr Soc 2005; 53:410-4152. Beauchet O, Dubost V, Gonthier R, Kressig RW. Gerontology 2005;51:48-52.3. HaussdorfJM et al Arch Phys Med Rehabil 2001, 82:1050-10564. Yogev G, Giladi n, PeretzC et al Eur J Neurosci 2005 812:105-109
5. Camicioli R et al. Neurology 1997: 48(4): 955–958.
Gait variability (Gva) and dual-tasking
5-12%= or ↑↓Healthy older subjects2
Unknown↑↑↓↓↓↓Older subjects with Alzheimer’s D.5
9-11%↑↑↓↓↓↓Older subjects with Parkinson’s D.4
9%↑↑↓↓↓Older subjects with falls3
2.7%=↓Healthy young subjects1
CoVGait variability
Gait Velocity
Effect of dual task challenges on gait velocity and gait variability in different populations
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MCI & Gait Variability(GVa)Hypotheses
1-Gait performance will decline as the complexity of the dual-tasks increases in people with MCI (↓GV and ↑Gva)
2-The effect on Gva will be more important that the effect on GV
Methods– N=45 MCI and 30 controls, mean age 75.2 y– Inclusions: MCI by Winblad consensus’s criteria, MMSE>26
MoCA<26– Exclusions: clinical gait abnormalities, depression.– Gaitrite assessment using different dual-tasks with increasing
complexity (naming, counting, combined)
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Table 1. Baseline demographics.
27.9 (1.6)29.7 (0.4)MMSE (mean, SD)
23.3 (2.2)27. (1.2)MoCA (mean, SD)
9%0%Stroke
11%0%Diabetes
57%29%HTA
20%14%Fear of Falling (%)
58%23%Previous falls >1 (%)
26 (4.2)25.5 (3.4)BMI (mean, SD)
51%86%Gender (% Female)
75.2 (6.2) 75.1 (4.8) Age (mean, SD)
MCI Participants (N=45)
Normal Controls (N=30)
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Gait variability in the normal and dual task conditions
Walking Condition
Normal Dual-task
Gai
t Var
iabi
lity
(CoV
ST)
0
5
10
15
20
25
Normal ControlsMCI Patients
Gait velocity in the normal and dual task conditions
Walking Condition
Normal Dual-task
Gai
t Vel
ocity
(cm
/sec
)
50
60
70
80
90
100
110
120
130
140
150
Normal ControlsMCI Patients
Gait velocity and Gait variability at single and dual-tasks
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Single task gait example
-1-1n/a-1-1-323MoCA
n-1-1-226MMSE
AbstractionNamingVisuospatial/
ExecutiveRegistrationLanguageAttention OrienRecallScore
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Dual-task gait example
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Elderly Control Elderly MCI
Figure 1. Gait variability = (stride time variability) under single and dual-task in one normal control and one participant with MCI. Note: stride=2 steps
Gait variability- Single case examples
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Gait velocity at single and dual-tasks
Mean gait velocity in MCI patients at single and dual-task conditions
Test Condition
sT dTa dT7G
ait V
eloc
ity (c
m/s
ec)
0
10
20
30
40
50
60
70
80
90
100
110
120
130
140
150
p<0.001***
p<0.01 **
Mean gait velocity in normal controls at single and dual-task conditions
Test Condition
sT dTa dT7
Gai
t Vel
ocity
(cm
/sec
)
0
102030
405060
70
8090
100110120
130140150
* p<0.05
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Stride time at single and dual-tasks
Mean stride time in MCI patients at single and dual-task conditions
Test Condition
sT dTa dT7
Stri
de T
ime
(mse
c)
0
200
400
600
800
1000
1200
1400
1600
1800
p<0.01 **p<0.001 ***
Mean stride time in normal controls at single and dual-task conditions
Test Condition
sT dTa dT7
Stri
de T
ime
(mse
c)
0
200
400
600
800
1000
1200
1400
1600
1800
* p<0.05
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Variability at single and dual-tasksMean stride time variability in MCI patients at single and dual-task conditions
Test Condition
sT dTa dT7
CoV
(ST)
0
1
2
3
4
5
6
7
8
9
10
11
12
p<0.01 **
p<0.001 *** p<0.01 **
Mean stride time variability in normal controls at single and dual-task conditions
Test Condition
sT dTa dT7
CoV
(ST)
0
1
2
3
4
5
6
7
8
9
10
11
12
Note. sT: single task,dTa: walking while naming animalsdT7: walking while serials 7.
Elderly Controls Elderly MCIs
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A 2 (Normal, MCI) x 3 (Usual, Animals, 7s) mixed model analysis of variance showeda significant main effect of test condition, F(1,40)=4.98, p<0.05, but no significant interaction according to participant type, F(1, 40)=1.91, ns.
<0.011.4810.08 (10.81)3.97 (1.43)Serial 7s
ns0.675.08 (3.28)4.21 (2.29)Animals
ns0.722.46 (1.01)2.17 (0.43)Usual
%CoV(ST)
<0.011.31595.47 (658.65)1268.07 (143.16)Serial 7s
ns1.231293.63 (243.79)1177.29 (109.48)Animals
ns1.651107.81 (76.32)1056.79 (65.82)UsualStride Time
(Sec)
ns-0.9881.3 (26.93)91.73 (16.05)Serial 7s
ns-0.2999.29 (22.79)101.91 (16.84)Animals
ns-0.68113.23 (25.71)120.09 (15.47)UsualVelocity (cm/s)
Gait Variables
<0.001-3.8523.26 (2.35)27 (2.24)MoCA
<0.01-2.7627.94 (1.67)29.71 (0.49)MMSECognitive Tests
ptMean (SD)Mean (SD)
BETWEEN-GROUP
DIFFERENCES
MCI PATIENTS(N=45)
NORMAL CONTROLS(N=30)
Table 2. Cognitive and gait variables at baseline measurement.
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0
5
10
15
20
25
30
Controls MCI AD
Walking test condition
Gai
t var
iabi
lity
(%C
oV)
Usual gaitNaming animalsSerial sevens
Figure 2. Mean gait variability in community-dwelling older adults with normal cognition (n=30), Mild Cognitive Impairment (n=45) and mild Alzheimer’s disease (n=34) while performing a usual walking task and two dual-task walking conditions.
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UGV GW CGV CB+GW NA 7s 7s+GW
01020
30
40
50
60
70
80
90
100
Coe
ffici
ent o
f var
iatio
n %
Tasks
CoV - Gait Velocity (%)
CoV - Stride Time
MCI & Gait Variability - Results
Variability of Velocity and Stride time under different dual-tasks
• In MCI, increasing the complexity of dual task affects gait
• Dual-tasks markedly impairs Gva
– In a dose response manner
– Much more than the effect seen on GV
• Results highlight the cognitive control ofgait in MCIIncreasing complexity of the tasks
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Gait Variability as a
Predictor of Dementia“The Gait and Brain Study”
Does Quantitative Gait Dysfunction Predict Dementia?
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Gait Variability as a Predictor of Dementia
40% remain stableafter 5 years
60 % will developdementia
(rate 10-15% per year)
Populationat Risk:MCI Clinical
DementiaCDR conversion
Clinical DxWill develop
demetia
SignificanceEarly prognosisEarly treatmentDelay disability
Delay placement
“The Gait and Brain Study”
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Gait Variability as a Predictor of Dementia
HypothesisGva is an early marker of conversion to dementia in people with MCI
Methods– Cohort study, n=150, follow-up 3 y.– Bi-yearly assessments: MMSE, MoCA &
GaitriteCollaborators
– Drs M. Borrie, J. Wells, and M. Speechley
“The Gait and Brain Study”
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Normal gait Abnormal gait Conditions
Higher risk of Dementia/mobility decline and falls
Mild Cognitive ImpairmentClinical
Condition
Changes on gait under dual-task
Conversion to Dementia
Lower risk of Dementia/mobility decline and falls
Proposal that gait impairment could be an early manifestation of progression to dementia and mobility decline in people with MCI.
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Background: falls are common in dementia
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Cognitive Enhancers and the Effect on Gait
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Background• Falls are very common1
– prevalent : 1/3 of older population/ per year• Falls are two-fold in people with Dementia2
– Falls are endemic in people with dementia: 2/3 per year
– People with Dementia have ↑risk of injuries falls & fractures
• Interventions / treatment – Multifactorial intervention– Single-interventions: exercises
• No intervention proved in people with dementia3
1. Tinetti ME, Speechley M, Ginter SF. Risk factors for falls among elderly persons living in the community. N Engl J Med 1988; 319:1701-1707
2. Shaw FE. Prevention of falls in older people with dementia. J Neural Transm 2007; 114:1259-1264.Petersen RC et al. Neurology 2001;56: 1133–1142
3. Oliver D, Connelly JB, Victor CR et al. Strategies to prevent falls and fractures and effect of cognitive impairment: systematic review and meta-analyses. BMJ 2007;334:82.
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Cognitive Enhancers Effect on Gait
Cognitive Enhancers:– Approved pharmacological intervention for
dementia: Donepezil, Rivastigmine, Galantamine– Modest effect on cognition but they delay
placement– The mechanism for the delay in placement is
assumed to be related to cognitive improvement– It is unknown if it is due to an effect on delaying
mobility decline or reducing falls
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Cognitive Enhancers & GaitMechanisms/Expected Action
Goal direct system:must reach the goal and avoid obstructions
Motor system:(generate the propulsive movement)1 – Basal ganglia and Bain Stem Level2 - Spinal Level: CPG=provides cadence and rhythm
Cerebral CortexCortical
Subcortical
Spinal
Basal Ganglia
Central Pattern Generator(CPG)
Gait
Postural system and peripheral limbsMuscle and JointsVestibular Ocular
Cognitive Cognitive EnhancersEnhancers
1
3
2
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Cognitive Enhancers & Gait Pilot study
Hypothesis– Cognitive enhancers reduce gait variability which is
a marker of fall risk
Methods– n= 20, >65 with new diagnosis of dementia (DSM-
IV criteria)– Open-label study for 4 months– Gait variability assessed by the GaitRite– Assessments: baseline, at month 1 and final
assessment at month 4
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Objectives
1. To determine if Donepezil may improve gait ( ↑GV and ↓Gva) in people with recent dx of dementia.
2. To assess the effect on dual-tasking in gait variability
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Effect on Gait velocity (GV)
1.Montero-Odasso M et al J Am Geriatr Soc 2009; 67:1124-1133
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1.Montero-Odasso M et al J Am Geriatr Soc 2009; 67:1124-1133
Effect on Gait variability (GVa)
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Single case example
0
20
40
60
80
100
120
140
T0 T1 T4
Time (months)
Gai
t vel
ocity
(cm
/sec
)
Usual gaitCounting Naming animals Serial sevens
Executive function:
Digit span test (forward, 0/16), 7 8
Digit span test (backward 0/14) 4 3
Trail making A test (sec) 64.7 58.9
Trail making B test (sec) 193.0 165.2
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0
500
1000
1500
2000
2500
3000
T0 T1 T4
Time (months)
Stri
de ti
me
(mse
c)
Usual gaitCounting gaitNaming animalsSerial sevens
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0
5
10
15
20
25
T0 T1 T4
Time (months)
Strid
e tim
e ga
it va
riab
ility
(%C
oV) Uusal gait
Counting Naming animals gaitSerial sevens
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Conclusions Conclusions • Donepezil treatment improved GV and reduced GVa
• More stable walking pattern in the intervention group
• Improvements were found early (1 month of intervention) and sustained during 4 months suggesting a dose-response pattern
• The effect was slightly more important during single-tasking showing that dual-tasking affects cortical control of gait.
• Our findings offer support and rationale to assess the effect ofACEIns on gait performance and risk of falling in a clinical trial
–
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Final SummaryFinal Summary• Dual tasking costs
– older adults– Subjects with neurological diseases and dementia– MCI– The effect increases with age and disease– The effect increases with cognitive decline
• Complexity of dual-tasking affects gait
• Gait variability seems to be very sensitive to dual-tasking• Gait variability may be a sensitive way to early detect MCI seniors at
higher risk of – developing dementia – risk of falling
• Enhancing attention/executive function may improve gait and fall’s risk
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AcknowledgmentsParkwood Hospital, Aging and Brain Memory Clinic
Maggie Hall Kevin HansenJanyth Mowat Dr Alvaro CasasDr Jennie Wells Dr Michael Borrie
Department of Medicine, Research OfficeDr Tom McDonald Dr Denise Goens
Department of Epidemiology and BiostatisticsDr Mark Speechley Dr. Susan Muir
Funding AgenciesLawson Health Research Institute (LHRI)The Physicians’ Services Incorporated Foundation (PSI)The Drummond FoundationCanadian Institute of Health and Research (CIHR)Schulich Clinician Scientist Award (2008-2011)
Email: [email protected]: http://dom.lhsc.on.ca/dom/divisions/geriatrics/index.html
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“It takes a child one year to acquire independent movement and ten years to acquire independent mobility.An old person can lose both in a day”
Bernard Isaacs“The Challenge of the Geriatric Medicine”