Division of

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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Geriatric Medicine

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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Geriatric Medicine

...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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Geriatric Medicine

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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Geriatric Medicine

• 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

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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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Geriatric Medicine

US: 1.2 m/secCanada: 1.1 to 1.4 m/sec

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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

• 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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

Mild Cognitive Impairment &

Gait Variability(Gva)

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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

Single task gait example

-1-1n/a-1-1-323MoCA

n-1-1-226MMSE

AbstractionNamingVisuospatial/

ExecutiveRegistrationLanguageAttention OrienRecallScore

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Geriatric Medicine

Dual-task gait example

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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

Cognitive Enhancers and the Effect on Gait

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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

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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Geriatric Medicine

Effect on Gait velocity (GV)

1.Montero-Odasso M et al J Am Geriatr Soc 2009; 67:1124-1133

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Geriatric Medicine

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

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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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Geriatric Medicine

0

500

1000

1500

2000

2500

3000

T0 T1 T4

Time (months)

Stri

de ti

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c)

Usual gaitCounting gaitNaming animalsSerial sevens

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Geriatric Medicine

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5

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15

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25

T0 T1 T4

Time (months)

Strid

e tim

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it va

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ility

(%C

oV) Uusal gait

Counting Naming animals gaitSerial sevens

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Geriatric Medicine

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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Geriatric Medicine

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: mmontero@uwo.caWeb: 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”