Physical activity post-stroke to prevent cognitive impairment
emotional function in stroke survivors. In addition, this
study explored the association between adherence to
the intervention and the outcome variables.
METHODS
LAST is a prospective, randomized, single-blinded, multicentre,
2-arm parallel group clinical trial. Between October 2011 and
January 2016, patients were recruited 3 months post-stroke
from 2 Norwegian hospitals; Trondheim University Hospital
and Bærum Hospital with intervention and follow-up for 18
months in the primary healthcare services in the municipalities
of Trondheim, Asker and Bærum (NCT01467206) (10). The
current study analysed secondary outcomes.
Participants
Inclusion criteria were: patients aged over 18 years, with first-
ever or recurrent stroke due to infarction and intracerebral
haemorrhage, community-dwelling with modified Rankin Scale
(mRS) score < 5. Exclusion criteria were serious medical co-
morbidity with short life-expectancy, cognitive deficits, as eva-
luated by Mini Mental State Examination (MMSE) < 21 points
(or < 17 points for patients with aphasia) and contraindication
to participate in motor training (10). Neurological impairment
was measured by the National Institute of Health Stroke Scale
(NIHSS), which ranges from zero to 42. The patients were trea-
ted in the acute and subacute phase according to international
and national guidelines from 2011 (11). Risk assessment and
individualized secondary prevention was initiated at discharge
from hospital after the index stroke, with recommendation for
long-term risk factor control as part of usual care.
Randomization
Participants were stratified according to functional level post-
stroke (mRS > 2 points), age ≥ 80 years and recruitment site, and
randomized by a web-based randomization system developed
and administered by the Unit of Applied Clinical Research,
Faculty of Medicine and Health Sciences, Norwegian Univer-
sity of Science and Technology, Trondheim, Norway. Patients
randomized to the control group received usual care.
Intervention
In addition to usual care, the intervention group received regular
individualized coaching performed by physiotherapists, aiming to
achieve physical activity 30 min daily, and 45–60 min physical
exercise including 2–3 bouts of vigorous activity every week. The
intervention did not include supervised or observed training. The
physiotherapists carried out home visits to provide education and
tailored training programmes, based on the patient’s preferences
and goals. The patients were encouraged to report their activi-
ties in standardized training diaries. The patients had a monthly
meeting with their coach, going through training diaries, with
reassessment according to needs. These meetings were face-to-
face in the first 6 months. For the next 6 months, every second
meeting could take place as a phone meeting. During the final 6
months, 4 of the 6 meetings could take place as a phone meeting.
Outcomes
Cognitive function was measured using standardized neuropsy-
chological tests assessing for global function, processing speed
647
and executive function (normal scores); MMSE (minimum
score 0 to maximum score 30), Trail Making A and B (TMT A
(< 60 s considered a normal score) and B (< 180 s considered a
normal score) (12, 13) at inclusion 3 months post-stroke and at
18 months follow-up. Symptoms of anxiety and depression were
assessed by Hospital Anxiety and Depression Scale (HADS A
and D) (14). Each domain consists of 7 questions with scores
ranging from 0 (no symptoms) to 3 points. The outcomes were
changes in cognitive and emotional measures from baseline to
18 months follow-up.
Adherence to the intervention was measured using self-
reported activity through the diaries and evaluation by the
physiotherapists, defined as the number of weeks patients in
the intervention group completed at least 210 min of physical
activity (minimum 30 min every day) and 45 min of exercise
(in total per week). Despite considerable variation, it has been
shown that the participants established and maintained mode-
rate-to-good adherence to the intervention (15).
Statistical analyses
Sample size was calculated according to the primary outcome
(Motor Assessment Scale) in the main study (9). Descriptive
statistics are given as mean (SD), median (interquartile range),
or frequency (percentage), where relevant. According to the
CONSORT instructions, all outcomes underwent intention-to-
treat (ITT) analysis (16). Linear regression analyses were used,
with TMT A and B, MMSE and HADS A and D, respectively,
as dependent variables, and intervention group, age, sex, stroke
severity (measured by mRS), hospital site, treatment group, and
cognitive or emotional status at inclusion as covariates.
For patients in the treatment arm, linear regression analyses
were carried out with the cognitive and emotional outcome
measures, TMT A, TMT B, MMSE, HADS A, and HADS D,
at 18-month follow-up from baseline, as dependent variables,
one at a time, with adherence to physical activity and exercise
as primary covariate. These regression analyses were carried
out both unadjusted and adjusted for the following covariates,
one at a time and simultaneously: age, sex, mRS, MMSE, if
appropriate, and the corresponding outcome variable score, all
measured at baseline 3 months post-stroke.
On HADS and MMSE, the subjects with less than 50% missing
values on a scale, the missing values were imputed singly using
the expectation–maximization algorithm on that scale. Thereafter,
multiple imputation was used to impute missing scale sums and
other missing values, with m = 100 imputation, as recommended
by van Buuren (17). Patients who died during follow-up were ex-
cluded from the analyses. The normality of residuals was checked
by visual inspection of QQ plots. Two-sided p-values < 0.05 were
considered statistically significant, and 95% confidence intervals
(95% CI) are reported where relevant.
Ethics
The study was approved by the Regional Committee of Medical
and Health Research Ethics (REK no 2011/1427) and registered
with ClinicalTrias.gov, number NCT01467206. All participants
provided informed consent.
RESULTS
In total, 380 patients were recruited and randomized in
the main study (the trial profile is reported elsewhere;
J Rehabil Med 51, 2019