Dementia And Physical Activity (DAPA) trial of moderate to high intensity exercise training for people with dementia: randomised controlled trial
the bmj | BMJ 2018;361:k1675 | doi: XXXXXXXXXX
mj.k1675 1
RESEARCH
Dementia And Physical Activity (DAPA) trial of moderate to high
intensity exercise training for people with dementia: randomised
controlled trial
Sarah E Lamb,1,2 Bart Sheehan,3 Nicky Atherton,3 Vivien Nichols,2 Helen Collins,4
Dipesh Mistry,2 Sukhdeep Dosanjh,2 Anne Marie Slowther,5 Iftekhar Khan,2 Stavros Petrou,2
Ranjit Lall,2 on behalf of the DAPA Trial Investigators
ABSTRACT
OBJECTIVE
To estimate the effect of a moderate to high intensity
aerobic and strength exercise training programme on
cognitive impairment and other outcomes in people
with mild to moderate dementia.
DESIGN
Multicentre, pragmatic, investigator masked,
andomised controlled trial.
SETTING
National Health Service primary care, community and
memory services, dementia research registers, and
voluntary sector providers in 15 English regions.
PARTICIPANTS
494 people with dementia: 329 were assigned to an
aerobic and strength exercise programme and 165
were assigned to usual care. Random allocation was
2:1 in favour of the exercise arm.
INTERVENTIONS
Usual care plus four months of supervised exercise
and support for ongoing physical activity, or usual
care only. Interventions were delivered in community
gym facilities and NHS premises.
MAIN OUTCOME MEASURES
The primary outcome was score on the Alzheimer’s
disease assessment scale-cognitive subscale (ADAS-
cog) at 12 months. Secondary outcomes included
activities of daily living, neuropsychiatric symptoms,
health related quality of life, and carer quality of life
and burden. Physical fitness (including the six minute
walk test) was measured in the exercise arm during
the intervention.
RESULTS
The average age of participants was 77 (SD 7.9) years
and 301/494 (61%) were men. By 12 months the
mean ADAS-cog score had increased to 25.2 (SD 12.3)
in the exercise arm and 23.8 (SD 10.4) in the usual
care arm (adjusted between group difference −1.4,
95% confidence interval −2.6 to −0.2, P=0.03). This
indicates greater cognitive impairment in the exercise
group, although the average difference is small and
clinical relevance uncertain. No differences were
found in secondary outcomes or preplanned subgroup
analyses by dementia type (Alzheimer’s disease or
other), severity of cognitive impairment, sex, and
mobility. Compliance with exercise was good. Over
65% of participants (214/329) attended more than
three quarters of scheduled sessions. Six minute
walking distance improved over six weeks (mean
change 18.1 m, 95% confidence interval 11.6 m
to 24.6 m).
CONCLUSION
A moderate to high intensity aerobic and strength
exercise training programme does not slow cognitive
impairment in people with mild to moderate
dementia. The exercise training programme improved
physical fitness, but there were no noticeable
improvements in other clinical outcomes.
TRIAL REGISTRATION
Cu
ent Controlled Trials ISRCTN XXXXXXXXXX.
Introduction
Nearly 47.5 million people worldwide have dementia.1
The challenge to families and health and social
services is substantial.1 The hypothesis that aerobic
and strengthening exercise might slow cognitive
impairment in dementia has gained widespread
popularity. Many studies describe plausible
mechanisms using mammalian models, but there are
fewer studies using human participants.2 3
The results of recent systematic reviews of trials
of exercise training in people with dementia have
conflicted. One review concluded that exercise can
improve physical but not cognitive impairment,
neuropsychiatric symptoms, or health related quality
of life.4 Another suggested that aerobic exercise has
a positive effect on cognitive impairment, regardless
of the type of dementia or dose of intervention.5 All
eviews confirm the multiplicity of small studies
of low methodological quality, limited duration of
follow-up, and high unexplained heterogeneity in
findings. In 2012, the UK government launched a
prime minister’s challenge in which research to seek
a cure for, or alleviation of, dementia symptoms was
set as a national priority. The National Institute for
1Centre for Rehabilitation
Research and Centre for
Statistics in Medicine,
Nuffield Department of
Orthopaedics Rheumatology
& Musculoskeletal Sciences,
Botnar Research Centre,
University of Oxford, Oxford
OX3 7LD, UK
2Warwick Clinical Trials
Unit, University of Warwick,
Coventry, UK
3Coventry and Warwickshire
Partnership Trust, Coventry, UK
4Oxford University Hospitals
NHS Foundation Trust, John
Radcliffe Hospital, Oxford, UK
5Division of Health Sciences,
University of Warwick,
Coventry, UK
Co
espondence to: S E Lamb
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Cite this as: BMJ 2018;361:k1675
http:
dx.doi.org/10.1136
mj.k1675
Accepted: 28 March 2018
WhAT IS AlReAdy knoWn on ThIS TopIC
The role of exercise in slowing cognitive decline in people with dementia is
uncertain
There is a paucity of randomised controlled trials of sufficient size and
methodological quality to inform practice
WhAT ThIS STudy AddS
People with mild to moderate dementia can engage and comply with moderate to
high intensity aerobic and strengthening exercise and improve physical fitness
These benefits do not, however, translate into improvements in cognitive
impairment, activities in daily living, behaviour, or health related quality of life
The exercise programme might possibly have worsened cognitive impairment
on 13 F
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RESEARCH
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mj.k1675 | BMJ 2018;361:k1675 | the bmj
Health Research (NIHR) commissioned the Dementia
And Physical Activity (DAPA) trial to inform the debate
about the potential benefit of exercise on cognitive
impairment in people with dementia.
We compared the effect on cognitive impairment
at 12 months of a combination of a moderate to
high intensity aerobic and strength exercise training
programme in addition to usual care compared with
usual care alone in people with mild to moderate
dementia. We designed and tested an intervention
that targeted known mechanistic pathways in vascular
and Alzheimer’s type dementia and which, if found
effective, could be scaled for use within the UK
National Health Service.
Methods
Study design
A full protocol has been published previously.6 This
was a multicentre, pragmatic, investigator masked,
andomised controlled trial. Random allocation was
2:1 in favour of the exercise arm. Participants were
ecruited from memory services in university and
district general hospitals, NIHR dementia research
egisters and networks, and from primary care practices
and community dementia services in 15 regions across
England. Interventions were delivered in community
gym facilities and occasionally in NHS facilities.
We recruited people with mild to moderate
dementia and, when available, their primary carer.
We asked carers to provide data about their relative
or close friend with dementia for measures that
specified the primary respondent should be the carer.
For people with dementia, we determined capacity
to consent in accordance with the principles of the
Mental Capacity Act XXXXXXXXXXusing research nurses
and physiotherapists who received specific training.
The assessment of capacity was based on a subjective
opinion developed during the preliminary phases of
enrolment. The nurses or physiotherapists made an
assessment, using gentle questioning, to determine
how much information was understood and
processed. When people with dementia were assessed
as having capacity, we obtained their informed
consent. If people with dementia were assessed
as lacking capacity, we asked the primary carer or
personal consultee about the participant’s past and
present wishes and feelings about taking part in
esearch studies and we asked the primary carer or
personal consultee to provide consent. If people with
dementia were unable to give informed consent, and
there was no carer or personal consultee, we sought
nominated consultees who were well placed and
prepared to act on behalf of potential participants (for
example, a health professional independent of the
study). We excluded people who lacked capacity and
had no personal or nominated consultee. Carers gave
their written informed consent to provide data about
the person with dementia. We checked agreement for
continued participation at each visit.
As a separate analysis, we asked carers to provide
data on their own quality of life and caring experience.
Carers provided separate written informed consent for
the carer element of the study.
Participants
People with dementia were eligible if they had
a clinically confirmed diagnosis of dementia in
accordance with the Diagnostic and Statistical Manual
of Mental Disorders, fourth edition (DSM-IV)7 and a
standardised mini mental state examination score
(sMMSE)8 of greater than 10, were able to sit on a chair
and walk 10 feet (3.05 m) without assistance, and
lived in the community either alone or with others.
We excluded people with acute, unstable physical or
terminal illness that would make participation in the
exercise programme unsafe.
Study treatments
The interventions and rationale are described in detail
elsewhere.9 Physiotherapists and exercise assistants
prescribed and delivered interventions in the exercise
arm. People with dementia attended an individual
assessment where the prescription of aerobic and
strength exercises was tailored to their fitness and
health status. The assessment included a review of
health conditions that required modifications of the
exercise prescription (eg, diabetes, cardiovascular
conditions, musculoskeletal conditions), and drugs
that might be needed during sessions (eg. glyceryl
trinitrate sprays, inhalers). Thereafter, people with
dementia attended group sessions in a gym twice a
week for four months; each session lasted 60 to 90
minutes. We also asked the participants to do home
exercises for one additional hour each week during
this period. The supervised programme lasted four
months, after which we prescribed a more frequent
home based programme with a target of unsupervised
physical activity or exercise of 150 minutes each week
(total). We used behavioural strategies (described
elsewhere9) to promote adherence throughout, and
up to three telephone motivational interviews were
administered after the supervised programme. The
ehavioural strategies included guiding participants
to choose home exercises or activities that matched
their preferences for venue, personal situation, and
ease of completion.
During the supervised period, people with dementia
were overseen in groups of six to eight participants to
minimise costs. In each group session, aerobic exercise
consisted of static cycling with a five minute warm-up
period followed by up to 25 minutes of