Rehabilitation of Cognitive Deficits Poststroke: Systematic Review and Meta-analysis of Randomized Controlled Trials

Systematic Review and Meta-Analysis of Randomized Controlled Trials

Mairead O'Donoghue, BSc; Siobhan Leahy, PhD; Pauline Boland, PhD; Rose Galvin, PhD; John McManus, MD; Sara Hayes, PhD

Disclosures

Stroke. 2022;53(5):1700-1710. 

In This Article

Results

Searches yielded a total of 66 578 studies, with 25 215 duplicates removed, resulting in 41 363 titles and abstracts screened for eligibility. Following title and abstract screening, 277 full-text studies were screened for eligibility. Out of these full texts, 64 studies met the inclusion criteria, with 42 of these studies having suitable data for meta-analysis (Figure 1). The additional 22 studies were unsuitable for meta-analysis and so descriptive data is available for these studies. Please see the Supplemental Material.

Figure 1.

PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow chart of study selection.
*The characteristics of all studies (n=64) were reported but a narrative synthesis of studies that did not provide data for the meta-analysis was not performed (n=22).

Characteristics of Included Studies

Of the 64 studies included in this review, 21 were multiple component interventions, 16 were cognitive rehabilitation interventions, 11 were physical activity interventions, 6 were NIBS protocols, 5 were occupational-based interventions, and 5 were other interventions. For the characteristics of included studies, please see the Supplemental Material.

The 64 included studies yielded a total of 4005 participants. Sample sizes ranged from nine participants to 225 participants. The mean age of participants was 62.5 years, ranging from 45 years to 76 years. The mean time since stroke onset was 20.03 months, ranging from 48 hours since stroke onset to 6.25 years poststroke.Twenty studies (31%) were conducted in the acute phase (≤3 months poststroke), 12 studies (19%) were conducted in the subacute phase (>3-6 months poststroke), 18 studies (28%) were conducted during the chronic stage (>6 months poststroke), and 14 studies (22%) had no data relating to time since stroke.

Twenty-five studies (39%) included both ischemic and hemorrhagic types of stroke, 8 studies (12.5 %) reported on ischemic stroke only, 8 studies (12.5%) reported on left-sided/right-sided stroke, and 23 studies (36%) had no data relating to type of stroke.

Twenty-four studies (38%) recruited their participants from an inpatient acute setting, 15 studies (23%) recruited from a rehabilitation setting, 18 studies (28%) recruited from an outpatient service, and 7 studies (11%) recruited from both an inpatient and outpatient setting.

Forty-one studies (64%) recruited their participants from an inpatient acute setting, 13 studies (20%) recruited from an outpatient service, whereas 4 studies (6.5%) recruited from both an inpatient and outpatient setting. Six studies (9.5%) recruited from community settings.

Risk of Bias

The risk of bias in the 64 included studies was generally mixed, with a high risk of performance bias due to incomplete blinding of participants or personnel in 22 studies, a high risk of other bias due to inadequate sample sizes or conflicts of interest in 15 studies, a high risk of detection bias due to lack of blinded outcome assessment in nine studies, a high risk of attrition bias due to incomplete outcome data in 6 studies, a high risk of reporting bias associated with selective reporting of outcomes in 2 studies, and a high risk of selection bias associated with random sequence generation in one study. For complete Cochrane Risk of Bias results, please see the Supplemental Material.

Effect of Interventions

Results of the meta-analysis are presented below according to intervention type. Data have been pooled in accordance with each intervention classification as follows: multiple component interventions, cognitive rehabilitation interventions, physical activity interventions, NIBS protocols, occupational-based interventions, and other interventions.

Multiple Component Interventions

General Cognitive Function. Three studies reported a measure of general cognitive function using the Montreal Cognitive Assessment, post multiple component intervention compared with standard control. There was a significant effect in favor of the intervention group (MD, 1.56 [95% CI, 0.69–2.43]; I2=30%; Figure 2). This effect was maintained for studies <3 months poststroke (MD, 2.38 [95% CI, 0.97–3.80]; I2=0%). For figures of these results, please see the Supplemental Material.

Figure 2.

Forest plot of general cognitive function outcomes, multiple component intervention vs standard control.

Memory

Four studies reported a measure of memory using the forward digital span test, the letter-number sequencing test, and the Digital Span test post multiple component intervention compared with a standard control. There was an effect in favor of the intervention group (SMD, 0.49 [95% CI, 0.27–0.72]; I2= 0%; Figure 3). Subgroup analysis demonstrated that studies >6 months did not show an effect in favor of the intervention group (SMD, 0.32 [95% CI, −0.03 to 0.67]; I2=0%).

Figure 3.

Forest plot of memory outcomes, multiple component intervention vs standard control.

Two studies, one between 3 and 6 months poststroke and one >6 months poststroke, reported a measure of spatial and visual memory using the forward Visual Span Test post multiple component intervention compared with a standard control. There was an effect in favor of the intervention group (MD, 0.98 [95% CI, 0.33–1.64]; I2=0%). For figures of these results, please see the Supplemental Material.

There was no evidence of an effect in favor of multiple component interventions compared with a standard control group for the cognitive domains of general cognitive function as measured by the Mini-Mental State Examination (MD, 1.20 [95% CI, −0.28 to 2.67]), attention (MD, 0.01 [95% CI, −0.08 to 0.11]), perception (SMD, 0.14 [95% CI, −0.16 to 0.45]), and on secondary outcomes of depression (SMD, −0.26 [95% CI, −0.57 to 0.06]) and quality of life (SMD, 0.19 [95% CI, −0.24 to 0.63]).There was no evidence of an effect in favor of multiple component interventions compared with an active control for the domain of neglect (MD, 4.98 [95% CI, −33.29 to 43.24]).

Secondary Outcomes. Four studies reported a measure of functional status using the Barthel Index, the modified Barthel Index, and the Functional Independence Measure post multiple component intervention compared with a standard control. An effect was found in favor of the intervention group (SMD, 0.33 [95% CI, 0.05–0.62]; I2=61%). Subgroup analysis did not show an effect for studies that were <3 months poststroke or >6 months poststroke. For figures of these results, please see the Supplemental Material.

Cognitive Rehabilitation Interventions

There was no evidence of an effect in favor of cognitive rehabilitation interventions when compared with a standard control for general cognitive function (MD, 0.37 [95% CI, −0.94 to 1.69]), memory (MD, 1.54 [95% CI, −1.90 to 4.98]), executive function (MD, 0.44 [95% CI, −1.94 to 2.82]), neglect (SMD, 0.26 [95% CI, −0.18 to 0.71]), or on secondary outcomes of quality of life (SMD, 0.17 [95% CI, −0.18 to 0.52]).

There was no evidence of an effect in favor of cognitive rehabilitation interventions when compared with an active control for general cognitive functioning (MD, 0.83 [95% CI, −1.04 to 2.71]), memory (MD, −2.27 [95% CI, −6.06 to 1.52]), executive function (MD, −53.45 [95% CI, −148.26 to 41.36]), or attention (SMD, −0.05 [95% CI, −1.02 to 0.91]).

There was no evidence of an effect in favor of cognitive rehabilitation interventions when compared with a waitlist control for the cognitive domain of memory (SMD, 0.63 [95% CI, −0.27 to 1.52]).

Physical Activity Interventions

Neglect. Two studies, both <3 months poststroke, reported a measure of neglect using the Star Cancellation Test when comparing a physical activity intervention to an active control group of sham mirror therapy. There was an effect in favor of the control group (MD, 13.99 [95% CI, 12.67–15.32]; I2=0%)(Figure 4).

Figure 4.

Forest plot of neglect outcomes, physical activity (mirror therapy) intervention vs sham mirror therapy.

Secondary Outcomes

Two studies, both >6 months poststroke, reported a measure of balance using the Berg Balance Scale when compared with an active control group (stretching group). There was an effect in favor of the intervention group (MD, 2.97 [95% CI, 0.71–5.23]; I2=0%). For figures of these results, please see the Supplemental Material.

There was no evidence of an effect of physical activity interventions when compared with an active control for the cognitive domains executive function (MD, −1.92 [95% CI, −28.68 to 24.84]).

NIBS Interventions

Neglect. Three studies reported a measure of neglect using the line bisection test when compared with an active control of sham repetitive transcranial magnetic stimulation therapy (rTMS). There was an effect in favor of the intervention group (MD, 20.79 [95% CI, 14.53–27.04]; I2=79%)(Figure 5). Subgroup analysis of studies between 3–6 months also found an effect in favor of the intervention group (MD, 18.74 [95% CI, 11.50–25.99]; I2=78%). For figures of these results, please see the Supplemental Material.

Figure 5.

Forest plot of neglect outcomes (line bisection test), repetitive transcranial magnetic stimulation (rTMS) vs sham rTMS.

Two studies, one <3 months poststroke and one between 3 and 6 months poststroke reported a measure of neglect using the Star Cancellation Test when compared with an active control of sham rTMS therapy. There was an effect in favor of the active control group (MD, −5.57 [95% CI, −8.53 to −2.61]; I2=99%; Figure 6).

Figure 6.

Forest plot of neglect outcomes (Star Cancellation Test), repetitive transcranial magnetic stimulation (rTMS) protocol vs sham rTMS protocol.

Secondary Outcomes. Two studies, one <3 months poststroke and one >6 months poststroke, reported a measure of functional status using the Modified Barthel Index and the Korean version of the Modified Barthel Index when compared with an active control of rTMS therapy. There was an effect in favor of the intervention group (MD, 14.02 [95% CI, 8.41–19.62]; I2=0%). For figures of these results, please see the Supplemental Material.

Occupational-based Interventions

There was no evidence of an effect of occupational-based interventions when compared with a standard control for general cognitive functioning (MD, 0.45 [95% CI, −1.33 to 2.23]) or the secondary outcome of functional status (SMD, 0.31 [95% CI, −0.03 to 0.65]). Subgroup analysis revealed that studies <3 months poststroke showed an effect in favor of the intervention group for general cognitive functioning (MD, 0.39 [95% CI, 0.02–0.76]; I2=0%). For figures of these results, please see the Supplemental Material.

Other Interventions

There was no evidence of an effect of other interventions, that is, prism adaptation therapy, when compared with an active control group for the cognitive domain of neglect (SMD, 0.40 [95% CI, −0.06 to 0.85]).

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