community exercise approaches for people with huntington's

Community Exercise Approaches for People with Huntington’s Disease

Monica BusseCardiff University

What is Huntington’s Disease?

• Dominantly inherited neurodegenerative disease:

each child of affected parent has 50% risk of having

mutated HTT gene;

• Model disease;

• Incidence is on the rise;

• Age of symptom onset 35-45 years; progression

over 15-20 year period;

• HD is a life long condition: pre-manifest, early,

middle and late (full nursing care).

• Striatal spiny neurons in the direct and indirect pathways of the basal ganglia are most susceptible to damage;

• Other areas of the brain are also affected [cerebral cortex, hippocampus, purkinje cells of cerebellum; hypothalamus and thalamus];

• Triad of motor, cognitive and behavioural symptoms;

• Peripheral involvement.

Triad of symptoms

MOTOR COGNITIVE BEHAVIORAL/

EMOTIONAL

Chorea; dystonia Slowed thinking Apathy

Bradykinesia;

Akinesia

Poor reasoning and

problem solving

Depression; anxiety

Muscle weakness;

Postural instability

Difficulty sequencing

tasks

Dysregulation of

emotion and

thinking

Impaired balance

and gait

Concentration

problems/distract-

ability

Irritability

Activity limitations in HD

• Walking and balance problems: lack of confidence,

decreased endurance (fatigue), risk of falls;

• difficulty rising from sit to stand;

• decreased level of physical activity; physical de-

conditioning ;

• difficulty with activities of daily living: bathing,

dressing, eating and drinking (risk of choking);

• respiratory dysfunction.

Impaired functional skills with disease progression

• Environmental assessment;

• restorative vs. supportive;

• restorative – retraining, task practice

• supportive – adaptive equipment, adaptive

strategies

• leisure activities just as important as functional

skills;

• cognitive challenges, caregiver burden.

EHDN Physiotherapy Framework; 2008

Stage of Condition

Classification of

function

Main problems

Main goal

Management

strategy

Pre-manifest

Pathology

No signs & symptoms

Delay the onset of

mobility restriction

Preventative

Early to Early Middle

Impairments

Postural changes

Impaired Balance

Weakness of stabilizing

muscles

Dystonia

Decreased range of

motion

Choreic movements

Maintain function

Restorative

Late Middle to Late

Activity limitations &

participation

Falls

Mobility problems

Postural changes

Pain

Respiratory problems

Limit impact of

complications

Supportive

Treatment based classifications in HD

Quinn and Busse 2012

Exercise and Physical Therapies

• Important for general health and potential

symptom management including cognition;

• primary intervention or complementary to

other clinical interventions;

• encouraging evidence from environmental

enrichment and life-style studies;

• since 2007, at least 9 small scale feasibility

studies of supported exercise in people with

HD. Busse et al. Journal of Huntington’s Disease (2012)

• HD symptoms such as depression, apathy,

irritability, difficulties in organisation, planning and

adapting to new routines; Quinn et al .2010

• lack of interest, poor health, bad weather,

depression, lack of strength, fear of falling,

shortness of breath, low outcomes expectation,

transport problems, other time conflicts, social

stigma and external demands.Forkan et al. 2006

Sustaining regular exercise?

Development

Identifying evidence

Identifying theoretical components

Modelling process and outcomes

Establishing feasibility & acceptability

Establishing testing procedures;

Quantifying recruitment & retention

Determining sample size

Evaluation

Assessing effectiveness

Understanding change process

Assessing cost effectiveness

Implementation

Dissemination

Surveillance and monitoring

Long-term follow-up

Modelling real world up-take

MRC Framework for Development and

Evaluation of Complex Interventions

Craig et al 2008

Physiotherapy research in Cardiff

Move to Exercise

• Systematic controlled study of home based exercise DVD in

HD [feasibility, acceptability & benefit];

• exercises focusing on balance, flexibility, strength and

endurance; music as a form of cueing and motivation;

• significant differences between groups (n=10 intervention;

n=11 control) on the majority of outcomes (ANCOVA adjusted

scores);

• effect sizes were large (>0.8) for the majority of the

outcomes;

• follow-up multi-centre trial in set up in UK 2013-2015.

Khalil et al 2012 Physical Therapy;

Khalil et al Clinical Rehabilitation (in press)

Baseline (Mean (SD)) Follow up (Mean (SD))

Differences between groups at

follow up adjusted for baseline

measures

DomainOutcome

measure

Control group

(n=10)

Intervention

group (n=11)

Control group

(n=10)

Intervention group

(n=11)

Mean difference

(95% confidence

interval)

p

value

Effect

size

Age Age (years) 51.5 (15.8) 53.3 (11.3) NA NA NA NA NA

Disease

severityTFC 6.1 (1.7) 6.5 (2.7) NA NA NA NA NA

Disease

specific

motor scale

mMS 23.6 (6.5) 23.8 (10.5) 25.9 (7.6) 21.5 (8.7) -4.5 [-8.8, -0.2] 0.04 1.1

Gait

Gait speed

(m/s)0.88 (0.22) 0.56 (0.31) 0.87 (0.24) 0.85(0.33) 0.26 [0.07, 0.45] 0.01 1.7

Step time (s) 0.58 (0.04) 0.73 (0.2) 0.58 (0.06) 0.67 (0.26) -0.07 [-0.14, 0.01[ 0.09 1.1

Step time

(CV%)9.3 (2.4) 15.8 (9.3) 11.9 (5.2) 12.4 (8.0) -3.4 [-9.1, 2.2] 0.20 1.0

BalanceBBS 45.7 (6.9) 38.5 (12.4) 44.7 (7.5) 44.2 (10.7) 5.4 [1.0, 9.9[ 0.01 1.4

CSTS 8.8 (3.0) 5.9 (3.1) 7.7 (2.5) 8.6 (4.2) 3.4 [1.0-5.7] 0.008 1.7

Functional

activitiesPPT 14.8 (4.4) 10.0 (6.0) 14.6 (5.1) 14.7 (6.6) 4.8 [.0,7.7[ 0.002 1.8

Physical

activity

Average of

daily steps3376 (1758) 3596 (2176) 3249 (1940) 5355 (3511) 1805 [890, 2720] 0.001 1.6

TFC, Total Functional Capacity; mMS; modified Unified Huntington’s Disease Rating Scale-motor score; BBS, Berg Balance Scale;

CSTS; 30 second Chair Sit to Stand test; PPT, Physical Performance Test

Benefits of exercise

“„I think it‟s been very interesting for me to go through this experience. I just felt that this programme helped. I think it is helpful for anyone in my condition or

any other condition to do regular exercise. I think specially with my condition it would be very very good if you could get people to do this early on rather than

later as soon as they know that they potentially got it.”

“I noticed that with the neck exercises; the ones up and down she needed that to help her swallowing, to help to control it. That exercise definitely helped in controlling the food a bit more in her mouth; so say the chocking aspect was

getting better. …those exercises definitely helped her have a bit more control. You know that she has not got that much control of movement but I noticed

that she started to control her movement better.‟‟

“We have just noticed that she is not falling as many times since she has been doing the exercises. She fell a couple of times in the first couple of weeks, but probably in the last four or five weeks, she has not fallen over at all. She used to fall a couple of times a week, but like I said in the last five or six weeks she

has not fallen over at all.

Barriers to exercise

“I just think the way that she is at the moment, she finds it more difficult to cope to exercises because of her movement and her balance but in the early stages of

Huntington‟s, I think it might well benefit. I think she is quite a lot down the road. If we had done this programme 18 months ago or 2 years ago, it may benefited her

a little bit more.‟‟

“It was just difficult to get myself into it. Obviously people with HD do have the lack of motivation to start new routines. It would take me a while before I got started so

I would start later than I planned but I was always trying to find a way to get myself doing this.‟‟

“It was relatively easy to do the exercises but because of her mental status she still does have difficulty following what they are doing on the DVD. So say for example

the one way when you …. For some reason she kept doing both of them wrong and we kept correcting her. We never helped her to do the exercises from the

DVD. She was doing them and we were just prompting and explaining and that was the mental problem rather than the physical problem.‟‟

Can people with HD exercise in a gym setting?

• Systematic controlled study of 12 week long gym-based

exercise programme in HD [feasibility, acceptability &

benefit], random allocation to group;

• a weekly supervised gym session which incorporated both

aerobic and functional strength training; 2/wk unsupervised

walking programme, standard training zones

• blinded assessors: quantitative assessment on range of

outcome measures, sub-maximal exercise test;

• process evaluation: semi-structured interviews.

Assessment 2 scores (Mean ± SD) Assessment 3 scores (Mean ± SD)

Adjusted estimate, p-values & Effect sizes from

ANCOVA analysis controlling for age, gender, DBS,

physical activity

& score at assessment 2

Outcome measureControl

group

Exercise

group

Control

group

Exercise

group

Treatment Effect

estimate [95%

confidence interval]

p-value Effect size

UHDRS mMS14.6 ±7.6 11.5 ±4.9 13.2±6.9 15.4±5.1

2.41 [-0.93 to 5.75];

(n=17)0.16 0.37

UHDRS Cognitive Scores# 172.1±48.6 177.8±57.6 190.5±48.1 181.9±59.2 13.6 [-3.8, 31.0]; (n=17) 0.13 0.4

6 minute walk#389.2±99.9 386.4±78.2

405.04±98.

0393.6±81.9 27.2 [-2.8, 57.2]; (n=19) 0.08 0.44

CSST#10.8±3.9 11.3±3.3 12.2±3.4 12.8±3.9 1.28 [-1.2, 3.8]; (n=18) 0.31 0.25

Rhomberg 139.2±40.8 157.6±39.6 141.8±42.1 152.0±40.1 -8.5 [-25.6, 8.7]; (n=18) 0.32 -0.25

Heart rate at minute 9 of

exercise test # 135.1±17.9 139.4±16.3 127.10±19.3 135.11±24.3 -7.0 [-21.9, 7.8]; (n=16) 0.34 -0.25

Perceived Exertion at

minute 9 of exercise test 5.8±2.1 5.9±1.9 4.5±2.6 4.6±2.3 0.96 [-1.2, 3.1]; (n=16) 0.37 0.24

SF-36 PCS 59.8±17.4 67.7±11.4 67.1±12.2 65.8±9.8 -3.07 [-9.3, 3.2]; (n=18) 0.32 -0.24

SF-36 MCS # 50.7±9.6 45.9±7.2 43.4±7.5 50.6±5.4 7.0 [0.4, 13.7]; (n=18) 0.046 0.53

ParticiapntsAbility to attend

gym sessions

Supervision required

during gym sessions

Walking sessions;

independent/ with

somebody

Total gym

based

exercise

(minutes;

sessions

attended out

of 12)

Reasons for reduced

adherence

Average

weekly

walking

(minutes)

Average

weekly

physical

activity

(minutes)

Female, age 45.

Cognitive score 150;

UHDRS TMS 52.

Dependent on

spouse

Supervision whilst using

equipment

With partner and

independent660; 11 Holiday 322 377

Female, age 38.


UHDRS TMS 33.

Dependent on

spouse

Supervision required whilst

navigating gym environment

and using equipment

With partner 540; 9

Holiday; personal

circumstances; dental

appointment

88 133

Male age 67.


UHDRS TMS 34.

IndependentSupervision required whilst

using some of the equipmentIndependent 660; 11 Holiday 118 173

Female age 55.


UHDRS TMS 33.

Dependent on taxi

organized by

study team.

Supervision required whilst

using some of the

equipment.

Independent 720; 12 N/A 138 198

Male age 54.


UHDRS TMS 41.

Independent Independent 360; 6

Miscommunication,

staffing issues at gym;

Christmas holidays

378 408

Male age 44.


UHDRS TMS 61.

Dependent on

spouse for gym

attendance

Supervision whilst using

equipment and verbal

guidance required whilst

navigating gym environment

With partner and

independent540; 9

Fatigue; back pain;

Urinary tract infection150 195

Male age 44.


UHDRS TMS 51.

Dependent on taxi

organized by

study team.

Guidance to use some

equipmentIndependent 600; 10

Anxious participant;

could not find taxi that

was sent to home;

unable to contact for 1

further week.

175 225

Male age 64.


UHDRS TMS 41.

Dependent on

support worker for

gym attendance.

Guidance to use some

equipmentWith support worker 720; 12 N/A 363 423

Female age 71.


UHDRS TMS 4.

IndependentGuidance to use some

equipmentIndependent 420; 7

Unrelated adverse

event; christmas

holidays

43 78

Participant Target

steady

state

heart rate

(HR) for

gym

sessions

Average

steady

state

heart rate

(HR)

during

gym

sessions

Mean

rating of

perceived

exertion

(Borg

CR10)

during the

gym

sessions

Blood pressure

(BP) pre: post

Observed

falls

Frequency of

reported

fatigue;

cramps;

prolonged

aching;

weakness

related to

intervention

BMI pre;

post

Difference

in body

weight (%)

Intention to

continue

exercising

post study?

1 96-131 114 2 110/71; 116/77 0 0; 0; 0; 0 26.8; 27.1 +1.00 Yes

2 100-137 140 5 117/84; 126/71 0 1; 0; 0; 0 27.6; 27.4 -0.74 Yes

3 84-115 131 6 153/77; 125/68 0 0; 0; 1; 0 24.9; 25.0 +0.29 Yes

4 91-124 131 4 122/84; 127/82 0 0; 0; 0; 0 31.7; 29.9 -5.49 Yes

5 91-125 123 4 155/90; 136/81 0 0; 0; 0; 0 25.7; 25.0 -3.07 Yes

6 97-132 113 5 104/78; 120/84 0 1; 0; 1; 0 29.3; 29.0 -0.86 Yes

7 97-132 117 4 139/86; 132/87 0 0; 0; 0; 0 26.8; 28.3 +5.32 Yes

8 86-117 89 4 132/73; 122/68 0 0; 0; 0; 0 27.6; 28.7 +3.95 Yes

9 82-112 109 3 140/78; 113/70 0 1; 0; 0; 0 26.4;

26.90

+1.91 Yes

Facilitators

Support

•Individualised structured support

•Knowledge of HD

•Family support

Environment

•Social aspect of exercise

•Nice weather

Motivation

•Achieving /surpassing goal

•Finding activities easier to do, feeling fitter,

more energy, weight loss

•Enjoyment

Constraints

Physical

•Tiredness (after work, after gym session,

lack of sleep, fatigue)

Environment

•Poor weather (rain , snow, ice)

•Travel difficulty

•Social stigma

Other commitments

•Hospital appointments

•Domestic chores

•Caring for other family member

•Holiday

Can people with HD exercise in a gym setting?

• No adverse events; high adherence rates;

• no significant differences between groups (n=9 intervention;

n=13 control) on the majority of outcomes (ANCOVA adjusted

scores);

• significant improvement in mental component summary

scale of SF-36;

• exercise intensity was not sufficient to achieve a training

effect;

• need follow up studies that adhere to frequency, intensity,

type and time (FITT) exercise prescription principles.

Physiological exercise response in HD?

• altered heart rate (HR) response during submaximal cycling

exercise compared to a control group;

• cycling at no resistance, most individuals with HD failed to

achieve a steady state heart rate;

• fixed HR target [70-80% of estimated maximum HR, i.e. an

expected sub-anaerobic threshold], people with HD failed to

achieve steady state;

• In a subset (n=8), blood lactate and expired air analysis

revealed that some individuals with HD were working

anaerobically during unloaded cycling and at higher than

expected levels of anaerobic metabolism during the

submaximal exercise (sub-anaerobic threshold) test.

What about these people who cannot self-direct their

exercise?

• Systematic controlled study of intensive, task related and

context specific physiotherapy intervention in the home

[feasibility, acceptability & benefit],

• random allocation to group;

• 8 home visits by physiotherapist; home exercise programme

• 6 sites in UK (aiming to recruit 30 people with mid-stage HD)

• blinded assessors: quantitative assessment on range of

outcome measures;

• process evaluation: semi-structured interviews.

Enrolled / Completed 1st

assessment n=24

Final Assessment

Completed final assessment n = 2

Assessed for eligibility (n=118)Excluded (n= 89)

•Not interested

•Exclusion criteria

•Not keen on taking part in assessments

•Does not have enough time

•Too far to travel for assessments

Lost to follow-up n= 0

Discontinued Intervention n= 0

Allocated to intervention (n=11)

Lost to follow-up n= 1

Reasons: participant did not want to continue due

to finding the assessments physically difficult

Allocated to control (n= 13)

Final Assessment

Completed final assessment n = 2

Completed Final Assessment n = 4

Randomized (n=24)

Completed 2nd assessment n=8

Lost to follow-up n=0Lost to follow-up n=0

TRAIN-HD Consort Flow Diagram February 2013

Completed 2nd assessment n=9

TRAIN-HD Intervention

• Intensive therapy in patients’ homes;

• mid-stage HD, difficulty performing functional

tasks (walking, sit to stand, standing balance);

• focus on outcome of task performance, not

specific movement patterns;

• support/manual guidance: as little support as

possible to encourage patient to perform task

independently.

Walking Training GuidelinesSurface UE use

Increasing difficulty Smooth/tile ---

Carpet/uneven Carrying tray/light object

Outside Carrying heavy object/groceries

Ramps/inclines With glass of water

Stairs Pushing/pulling (e.g. Hoover)

Cueing Practice Amount

Base of support Vary distance

Arm swing Vary time

TRAIN-HD Goal setting

• therapist collaboration with each participant; minimum of 3

general goals;

• translated into 2-4 SMART goals per participant (with

research team

-2 WORSE THAN EXPECTED

-1 CURRENT

0 EXPECTED OUTCOME

+1 BETTER THAN EXPECTED

+2 MUCH BETTER THAN EXPECTED

• SMART goals reviewed and validated with participants

• 3-4 sessions to finalise goals; 11 participants allocated to

intervention to date; 9 have completed.

TRAIN-HD results so far

GAS Score Goals Percentage

-1 3 10.3%

0 8 27.6%

1 6 20.7%

2 12 41.4%

29 100.0%

TRAIN-HD Intervention fidelity

• 5 males: 6 females; mean age: 53 (min 44; max 67)

• average session duration: 58 minutes (min 30; max 61)

• time spent (minutes)

• balance: 15 (min 5; max 35)

• sit-to-stand: 11 (min 5; max 20)

• walking: 21 (min 5; max 35)

• average (range) heart rate: 99 (min 75; max 133)

• max heart rate (range) heart rate: 124 (min 82; max 191)

• adverse events: 1 fall

Exercise Experiences to date

• Individualised interventions delivered in

accordance with evidenced based practice

(task specificity, functional activities, FITT

principles);

• individual preferences;

• varied community based environments;

• importance of intervention fidelity measures

and goal attainment scaling.

Next steps

• Investigate exercise response, validate sub-maximal exercise

test to incremental exercise test;

• multi-site exercise study [16 weeks; exercise of choice;

fitness trainer supervised, gym membership or equipment in

the home];

• consolidate recommendations for outcome measures [Quinn

et al Physical Therapy (in press)] ;

• multi-site home based study (12 weeks with 6 week follow up

and social contact control);

• review of underpinning theoretical frameworks;

• focus on non-exercise physical activity spectrum.

Acknowledgments

Dr Lori Quinn, Senior Research Fellow, Cardiff UniversityEuropean Huntington’s Disease Network NISCR WalesHuntington's Disease Association of England and WalesProfessor Anne Rosser and staff at Cardiff HD centre Dr Mark Kelly South East Wales Trials UnitDr Hanan Khalil: Move to Exercise ProgrammeKaty DeBono & Karen Jones: COMMET-HD, TRAIN-HDProfessor Helen Dawes: Oxford Brookes University

community exercise approaches for people with huntington's

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