Stroke is one of the leading cause of disability and functional impairments in the United States (Mozaffarian et al., 2015). In addition, stroke survivors have a considerably higher rate of subsequent cardiovascular events, resulting in high mortality. There is an increasing evidence that physical exercise improves quality of life and daily functioning in stroke survivors (Legg & Langhorne, 2004). However, evidence supporting effectivity of physical exercise is limited which could be attributed to the heterogeneity of interventions administered and differential diagnostic performance of various tools used to assess outcome measures. Additionally, epidemiological studies exploring the role of physical exercise as interventions suffer from several inherent biases including inability to conceal allocation, and blinding the investigators assessing the study outcome.

In the present proposal, a stratified randomized controlled, parallel-group single-blind trial, with a twelve-week follow-up, investigating the effect of three different walking interventions or arms (n=45 each), namely three sessions of 20 minutes/week, three sessions of 30 minutes/week, and three sessions of 60 minutes/week, respectively on Standardised Mini-Mental State Examination (SMMSE)  scale for cognition, Neuropsychiatric Inventory (NPI) scale for anxiety,  and Cornell Scale for Depression in Dementia (CSDD) scale for depression, is planned. A control arm of standard care will also be employed (n=45).

A stratified randomized controlled (RCT), parallel-group single-blind trial comparing the role of different intensities of physical exercise intervention will be conducted. ….Stroke will be diagnosed by a primary care physician on the basis of relevant medical history and CT/MRI scans. The classification of sub-acute stroke will be based on a minimum Barthel Index (BI) of 30. Inclusion criteria: (1) Patients above 50 years of age, (2) Patients had a single sub-acute stroke during last three months. (3) Patient with adequate cognitive status with a mini mental status examination (MMSE) score>22. Additionally, fitness test will be conducted based on the performance on cycle ergometer with minimum ability to pedal at 60 rpm and raise hear rate to atleast 60% of its maximum capacity. Exclusion criteria: (1) Patients have other co-existing neurological conditions, (2) Patients diagnosed with unable cardiovascular disease preventing them from undergoing physical activity sessions. The study will be conducted according to the Helsinki Declaration for human experiments.

A written informed consent will be obtained from all the study participants.

Sampling

Three rehabilitation centres will be randomly selected from. However, prior to the randomization of treatment, stratified random sampling will be used within this study to account for heterogeneity in study participants recruited from various rehabilitation centers (Suresh, 2011)

Randomization

The treatment will be randomized among four groups or four arms, named arms A, B, C and D. Arm A will comprise a control group who will not receive any RT treatment except for standard care. The arms B, C, and D will be assigned walking interventions of three sessions of 20 minutes/week, three sessions of 30 minutes/week, and three sessions of 60 minutes/week, respectively.

Study outcomes

Cognition, anxiety and depression will be assessed using the Standardized Mini-Mental State Exam (SMMSE), Neuropsychiatric Inventory Questions (NPI), and Cornell Scale for Depression in Dementia (CSDD) respectively.

Blinding

The patients will be instructed not to inform the assessors about the treatment they received.

The differences between categorical variables will be tested using Chi-square or Fisher exact test. The distribution of normally distributed variables will be compared between various study arms using a t-test or analysis of variance test (ANOVA), as required. Similarly, the distribution of non-normally distributed variables will be compared between various study arms using a Mann-Whitney U test or the Kruskal-Wallis test, as appropriate (du Prel et al., 2010). Confidence intervals (CI) of effect-sizes will be computed at the 95% significance level, and A p-value below 0.05 will be considered statistically significant. to compare several outcomes in a single statistical test, the researcher will perform a One-Way Repeated Measures (RM) MANOVA test to determine if there are significant differences between the control group and any of the intervention arms (RT groups) according to pre-and post-intervention measures of cognition, depression, and anxiety. The test conducts significance testing for differences in the mean changes from pre- to post-test in two or more outcomes between treatment groups. On the contrary, if our data do not meet the assumptions for MANOVA (i.e., Adequate sample size, normality of distribution, outliers, linearity, multicollinearity and singularity, and homogeneity of variance-covariance matrices), we will use analogous distance components (DISCO) methodology, as a nonparametric extension of MANOVA (Rizzo & Székely, 2010).

References

du Prel, J. B., Röhrig, B., Hommel, G., & Blettner, M. (2010). Choosing statistical tests: part 12 of a series on evaluation of scientific publications. Dtsch Arztebl Int, 107(19), 343-348. https://doi.org/10.3238/arztebl.2010.0343

Legg, L., & Langhorne, P. (2004). Rehabilitation therapy services for stroke patients living at home: systematic review of randomised trials. Lancet, 363(9406), 352-356. https://doi.org/10.1016/s0140-6736(04)15434-2

Mozaffarian, D., Benjamin, E. J., Go, A. S., Arnett, D. K., Blaha, M. J., Cushman, M., de Ferranti, S., Després, J. P., Fullerton, H. J., Howard, V. J., Huffman, M. D., Judd, S. E., Kissela, B. M., Lackland, D. T., Lichtman, J. H., Lisabeth, L. D., Liu, S., Mackey, R. H., Matchar, D. B., McGuire, D. K., Mohler, E. R., 3rd, Moy, C. S., Muntner, P., Mussolino, M. E., Nasir, K., Neumar, R. W., Nichol, G., Palaniappan, L., Pandey, D. K., Reeves, M. J., Rodriguez, C. J., Sorlie, P. D., Stein, J., Towfighi, A., Turan, T. N., Virani, S. S., Willey, J. Z., Woo, D., Yeh, R. W., & Turner, M. B. (2015). Heart disease and stroke statistics–2015 update: a report from the American Heart Association. Circulation, 131(4), e29-322. https://doi.org/10.1161/cir.0000000000000152

Rizzo, M. L., & Székely, G. J. (2010). DISCO ANALYSIS: A NONPARAMETRIC EXTENSION OF ANALYSIS OF VARIANCE. The Annals of Applied Statistics, 4(2), 1034-1055. https://doi.org/10.2307/29765541