Alteration of cholesterol homeostasis in the Huntington's ...
Community Exercise Approaches for People with Huntington's
Transcript of 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.
Cognitive score 196;
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.
Cognitive score 178;
UHDRS TMS 34.
IndependentSupervision required whilst
using some of the equipmentIndependent 660; 11 Holiday 118 173
Female age 55.
Cognitive score 202;
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.
Cognitive score 165;
UHDRS TMS 41.
Independent Independent 360; 6
Miscommunication,
staffing issues at gym;
Christmas holidays
378 408
Male age 44.
Cognitive score 101;
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.
Cognitive score 124;
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.
Cognitive score 163;
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.
Cognitive score 234;
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