Predictors of language recovery

Overview

In this chapter, we explore the distribution of language data at study entry according to key demographic factors (age, sex and living context). We then examine the relationship between key demographic factors and absolute proportion of recovery at follow-up for each language domain. Finally, we examine predictors of language recovery following aphasia after stroke; this was done by undertaking a series of meta-analyses on selected subsets of the IPD. We used a one-stage approach, simultaneously analysing all relevant IPD from the entire database, and included the individual study as a random effect in all analyses.

We examined both significance and the absolute change in raw scores. Analyses could reveal non-significant results with notable effect sizes from a clinical perspective. We therefore reported on significant as well as non-significant results, when a notable clinical effect size existed.

Language performance at study entry, stratified by age

We described language performance on each language domain for participants on study entry (baseline assessment). This time point was selected as no study intervention had yet been administered, and data were available for pre-intervention assessments across a range of time points since aphasia onset, thereby providing an indication of the distribution of language domain scores across different time points since the index stroke.

Age and overall language ability at baseline

We examined the distribution of overall language ability in RCTs (700 IPD; 19 RCTs; Figure 14a), stratified by four age groups: ≤ 55 years (209 IPD; 19 data sets), 56–65 years (204 IPD; 19 data sets), 66–75 years (149 IPD; 18 data sets) and aged 75+ years (138 IPD; 13 data sets). As time to inclusion increased, so too did baseline language ability scores across all age strata. When examining a clinically meaningful enrolment period (0–1000 days post stroke; see Figure 14c), the CIs for all age groups appeared to overlap, indicating that these differences were not significant.

FIGURE 14 Overall language ability scores by age for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

We then examined overall language ability at baseline for participants in all study types (2571 IPD; 78 data sets; see Figure 14b). Data were available for the following age groups: ≤ 55 years (845 IPD; 76 data sets), 56–65 years (708 IPD; 75 data sets), 66–75 years (605 IPD; 71 data sets) and 75 + years (413 IPD; 48 data sets). All age groups appeared to have increased overall language ability scores as time since stroke at baseline increased. We examined overall severity scores up to 1000 days after stroke onset to reflect typical trial recruitment periods after index stroke (see Figure 14c and 14d). For participants recruited within 1000 days of index stroke, the confidence limits for each age group overlapped, indicating no difference in the distributions of overall language ability scores by age in all study types.

Age and auditory comprehension at baseline

We examined the distribution of auditory comprehension scores at different baseline time points, stratified by age (633 IPD; 19 RCTs; Figure 15a). Data were available on participants aged ≤ 55 years (208 IPD; 19 RCTs), 56–65 years (201 IPD; 19 RCTs), 66–75 years (137 IPD; 18 RCTs) and > 75 years (87 IPD; 14 RCTs). The confidence limits overlapped for each age stratum, indicating that there was no evidence of a difference in distributions of auditory comprehension scores across each age group (see Figure 15a), with similar findings for the data from all study designs (2597 IPD; 67 data sets; see Figure 15b). Across all study designs, data on auditory comprehension scores at baseline were available for participants aged ≤ 55 years (939 IPD; 65 data sets), 56–65 years (721 IPD; 67 data sets), 66–75 years (626 IPD; 64 data sets) and > 75 years (311 IPD; 44 data sets). When we examined data for enrolment within 1000 days of index stroke (see Figure 15c and d), we observed similar overlaps in auditory comprehension scores across each age stratum, indicating no significant difference in the scores across different age groups.

FIGURE 15 Auditory comprehension scores by age for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Age and naming at baseline

We examined the distribution of naming scores at baseline by time since stroke and stratified by age in RCTs (748 IPD; 25 RCTs) and in all study designs (2760 IPD; 72 data sets; Figure 16a and 16b).

FIGURE 16 Naming scores by age for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Participants’ naming scores in RCTs were stratified into the following age groups: ≤ 55 years (259 IPD; 25 RCTs), 56–65 years (233 IPD; 24 RCTs), 66–75 years (168 IPD; 24 RCTs) and > 75 years (88 IPD; 16 RCTs) (see Figure 16a). RCT participants aged > 75 years appeared to suggest better naming scores as time since stroke increased at baseline; however, this could be a function of the relatively short time to baseline period for which data on this stratum were available. When examining RCT enrolment within 0–1000 days of stroke, the distribution of naming scores did not appear to differ in those aged > 75 years (see Figure 16c).

We plotted the distribution of participants’ naming scores at baseline across all study types and stratified by age (2760 IPD; 72 data sets; see Figure 16b). Data were available for participants aged ≤ 55 years (1005 IPD; 72 data sets), 56–65 years (779 IPD; 71 data sets), 66–75 years (693 IPD; 69 data sets) and > 75 years (283 IPD; 42 data sets). Once again, among participants aged > 75 years, a trend towards better naming scores was apparent when time from stroke to enrolment increased, compared with the younger participant age categories, but this difference was not significant, nor was it evident within 0–1000 days of stroke (see Figure 16b and 16d).

Age and other spoken language at baseline

We considered the distribution of other spoken-language scores at increasing time from index stroke to study entry, stratified by age, looking first at 163 IPD from two RCTs (see Report Supplementary Material 4, figure 1). Data were available for participants aged ≤ 55 years (90 IPD; 2 data sets), 56–65 years (58 IPD; 2 data sets) and 66–75 years (15 IPD; 1 data set). There were no IPD for those aged > 75 years.

Other spoken-language scores at baseline remained stable across various times since stroke for the different age groups. There appeared to be no significant differences in the distributions of other spoken-language scores by age group. We found similar distributions in the 344 participants from across seven data sets of all study designs [aged ≤ 55 years (191 IPD; 7 data sets), 56–65 years (112 IPD; 7 data sets), 66–75 years (37 IPD; 4 data sets) and > 75 years (4 IPD; 2 data sets)]. Inadequate data on study entry within 0–1000 days of stroke precluded further meaningful analyses of other spoken language (98 IPD; 2 data sets).

Age and reading comprehension at baseline

We examined the distribution of baseline reading scores at different baseline time points, stratified by age. Data were available from only one RCT and did not meet the prespecified criteria for analysis.

Participants’ reading comprehension scores across all study types at baseline (652 IPD; 9 data sets) were distributed across several age groups: ≤ 55 years (240 IPD; 8 data sets), 56–65 years (185 IPD; 9 data sets), 66–75 years (160 IPD; 8 data sets) and > 75 years (67 IPD; 6 data sets) (see Report Supplementary Material 4, figure 2). Participants aged > 75 years appeared to suggest higher reading scores with greater time since stroke at baseline when compared with participants in the other age groups, but this difference was not significant. We examined whether or not sparse data points at later time points contributed to the slopes of any of the regression lines (see Report Supplementary Material 4, figure 2) and found that reading scores at baseline did not significantly differ between different age strata for enrolment within 1000 days of index stroke.

Age and written language at baseline

We examined the distribution of writing scores among participants across all study types at baseline, stratified by age. There were insufficient data to consider RCT participants’ written language scores in isolation: data were available on 47 IPD from three RCTs. For participants across all study types (673 IPD; 11 data sets; Figure 17a), data on written language scores were available across the following age groups: ≤ 55 years (265 IPD; 11 data sets), 56–65 years (189 IPD; 11 data sets), 66–75 years (156 IPD; 8 data sets) and > 75 years (63 IPD; 5 data sets). There was no evidence of a difference in the distributions of writing scores for different age strata across the whole baseline sample, or when study entry was within 0–1000 days of index stroke.

FIGURE 17 Writing scores by age for all participants at baseline. (a) All study types; and (b) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Age and observer-rated functional communication (activity) at baseline

We examined the distribution of observer-rated functional communication (activity) in RCTs (998 IPD; 18 RCTs; Figure 18a), stratified by four age groups: ≤ 55 years (207 IPD; 18 data sets), 56–65 years (236 IPD; 17 data sets), 66–75 years (283 IPD; 18 data sets) and > 75 years (272 IPD; 15 data sets). Observer-rated activity scores overlapped across each age stratum. This pattern was also seen when examining all study types (1437 IPD; 29 data sets; see Figure 18b) and when examining a clinically meaningful enrolment period of 0–1000 days post stroke (see Figure 18c and 18d).

FIGURE 18 Observer-rated functional communication (activity) scores by age for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Observer-rated participation scores were based on the same populations, and, similarly, showed no significant differences across each age stratum, regardless of study type and within clinically meaningful enrolment periods.

Age and self-rated functional communication (activity) at baseline

Data on self-rated functional communication (activity) scores were available on only 11 IPD in one RCT, and therefore did not meet our prerequisites for analysis. For all study types, data were available on 62 IPD from three data sets across all baseline time points, and for 43 IPD from three data sets for which enrolment occurred within 1000 days of index stroke (see Report Supplementary Material 4, figure 3). We observed no significant differences in the self-rated functional communication (activity) scores across each age stratum. Data on self-rated functional communication (participation) were derived from the same data set and showed similar results (see Report Supplementary Material 4, figure 4).

Language performance at baseline, stratified by sex

Sex and overall language ability at baseline

When data were available, we considered overall language ability at baseline by sex for participants in RCTs (700 IPD; 19 RCTs; Figure 19). The confidence bands overlapped, indicating that this difference was not significant. We found similar patterns when we examined IPD across all study designs (2380 IPD; 68 data sets; see Figure 19b).

FIGURE 19 Overall language ability scores by sex for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

When we examined overall language ability scores within a more clinically relevant time point of 0–1000 days since stroke (599 IPD; 19 data sets; see Figure 19c), the data suggested that women appeared to have higher scores at later baseline time points than men, but there was no significant difference in the distributions. The findings were similar when applied to the data gathered at baseline within 1000 days of index stroke from all study designs (1665 IPD; 68 data sets; see Figure 19d).

Sex and auditory comprehension at baseline

We stratified the distribution of auditory comprehension scores at baseline time points by sex. Data were available from RCTs (622 IPD; 19 RCTs; Figure 20a) and across all study designs (2428 IPD; 60 data sets; see Figure 20b). Sex differences were not significant (see Figure 20).

FIGURE 20 Auditory comprehension scores by sex for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

We then examined whether or not the presence of a smaller number of data points at later baseline time periods influenced the slope of the regression line by plotting scores within a more clinically relevant recruitment period (1778 IPD; 59 data sets; see Figure 20c and d), but we found similar distributions and no evidence of a sex difference.

Sex and naming at baseline

We examined the available naming data at baseline for RCT data sets (745 IPD; 25 RCTs; Figure 21a) and across all study designs (2629 IPD; 65 data sets; see Figure 21b). With increasing time from stroke to study entry, naming scores declined in the RCT population. Women maintained marginally higher scores than men. However, the confidence limits overlapped, thus indicating that there was no significant sex difference between the distributions of naming scores. Overlapping confidence limits between men and women were also observed across all study designs (see Figure 21b and 21d). When examining these differences in a more clinically relevant enrolment period of 0–1000 days since stroke at baseline, we found a trend towards women having higher naming scores than men, as time to baseline assessment increased in RCTs (583 IPD; 24 RCTs; see Figure 21c) and across all data sets (1766 IPD; 64 data sets; see Figure 21d).

FIGURE 21 Naming scores by sex for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Sex and other spoken language at baseline

We considered the distribution of other spoken-language scores at baseline by time since stroke and stratified by sex for RCT data sets (163 IPD; 2 RCTs; Figure 22a) and across all study types (344 IPD; 7 data sets; Figure 22b). There did not appear to be any sex differences in the distributions of spoken-language scores at baseline assessment in RCT data sets or across all study designs.

FIGURE 22 Other spoken-language scores by sex for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Sex and reading comprehension at baseline

Data on reading comprehension in the RCT population were available for only 11 IPD in one data set and were therefore not taken forward for further analysis. When data were available, reading comprehension scores at baseline were plotted against time since stroke at baseline and stratified by sex across all study types (652 IPD; 9 data sets; Figure 23). Data suggested that women appeared to have better reading scores at baseline time points later after stroke than men at a similar stage since stroke, but this difference was non-significant.

FIGURE 23 Reading comprehension scores by sex for all participants at baseline. (a) All study types; and (b) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Sex and writing at baseline

We also examined writing scores at baseline by time since stroke and stratified by sex. In the RCT population (47 IPD; 3 RCTs; Figure 24a) and all study types (673 IPD; 11 data sets; see Figure 24b), there were no significant differences in writing scores between men and women. Examination of a more clinically relevant time point (of 0–1000 days) also revealed no significant differences between women and men (see Figure 24c and 24d).

FIGURE 24 Writing scores by sex for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Sex and observer-rated functional communication (activity) at baseline

When examining observer-rated functional communication activity measures (Figure 25), men in the RCT population (995 IPD; 18 RCTs) appeared to have better observer-rated activity scores; however, this observation was not apparent when looking at a more clinically relevant enrolment period (see Figure 25a and 25c). In all study types (1434 IPD; 29 data sets; see Figure 25b), there was no significant difference in the scores observed between men and women. Observer-rated participation scores were also based on this data set and displayed the same pattern.

FIGURE 25 Observer-rated functional communication (activity) scores by sex for all participants at baseline. (a) RCTs; (b) all study types; (c) for enrolment in RCTs within 0–1000 days of stroke; and (d) for enrolment in all study types within 0–1000 days of stroke. (Figure not reproduced here; see the original article.)

Sex and self-rated functional communication (activity) at baseline

Randomised controlled trial data were available for only 11 IPD from one data set. Therefore, these data were not carried forward to further analyses. Data for self-rated participation scores were also derived from this data set and were also not carried forward to further analyses. Data were available for 62 IPD from three data sets (see Report Supplementary Material 4, figure 5). We observed overlaps in activity scores (and participation scores; see Report Supplementary Material 4, figure 6) in men and women across all baseline time points, and across all clinically relevant enrolment time points.

Language performance by living context after stroke

Living context and overall language ability

When data permitted, we examined the distribution of overall language ability scores at baseline by time since stroke and stratified by living context, in RCTs (158 IPD; 3 RCTs; see Report Supplementary Material 4, figure 7) and across all designs (282 IPD; 8 data sets; see Report Supplementary Material 4, figure 7). There were insufficient data points to compare overall language ability scores at baseline by living context in RCTs. Using data from all study designs, it appeared that people living in formal care environments trended towards better overall language ability at baseline with greater time since stroke than those who were living alone. However, as the confidence limits overlapped, and there were sparse data points, these differences were not significant.

Living context and auditory comprehension

We examined the distribution of auditory comprehension scores at baseline across different time points after stroke and stratified by a participant’s living context, in RCT data sets (121 IPD; 3 RCTs; see Report Supplementary Material 4, figure 8). There were too few data points with the RCT data to adequately establish a relationship between living context and auditory comprehension scores over time. When we included data from all study designs (143 IPD; 5 data sets), there continued to be inadequate data at common baseline time points to enable comparison of patterns of auditory comprehension scores.

Living context and naming

We examined the baseline naming scores at time points since stroke and stratified by living context since stroke among RCT participants (163 IPD; 6 RCTs) and across all study types (176 IPD; 7 data sets; see Report Supplementary Material 4, figure 9). There were insufficient data points to adequately examine the differences in participants’ living contexts and naming.

Living context and spoken language, reading comprehension and writing

We sought data on other spoken-language scores at baseline, by time since stroke and participants’ living context after stroke, but identified only 10 IPD (from one data set), preventing further examination. Similarly, we lacked sufficient data to examine reading comprehension (10 IPD; 1 data set) or writing (10 IPD; 1 data set) at baseline.

Living context and observer-rated functional communication (activity)

Randomised controlled trial data on observer-rated functional communication (activity) were available for 280 IPD from six data sets, and for 290 IPD from seven data sets for all study types (see Report Supplementary Material 4, figure 10). There were inadequate data points at longer times to enrolment to permit reliable analyses or description after stratification by living context. Functional communication (participation) measures were also derived from this data set and showed similar results.

Living context and self-rated functional communication (activity)

Only 11 IPD from one RCT were available, which did not meet the prerequisite minimum data set for analysis. There were no further IPD available for self-rated activity or participation by living context across all study types.

Following these exploratory analyses of the data and predictive factors identified in other stroke recovery research,114–117 we identified age, sex and time since stroke as potential key variables for further examination in relation to recovery and absolute change in scores across each language domain.

Factors associated with increased proportion of change in each language domain

We examined the potential factors that were associated with a trend towards a greater absolute percentage change from baseline to first follow-up in each of the language domains using regression and adjusting for common covariates (age, sex and time since stroke), when these data were available.

After excluding participants from the natural history group (who were allocated to no SLT and were enrolled within 15 days of stroke), there were only two RCTs (22 IPD) and three data sets in all study types (34 IPD) comprising participants who received only historical SLT, and for whom data were available at the first follow-up time point following study intervention. For most of this group, participants had been permitted to receive SLT following the study intervention period and had follow-up time points that were inclusive of that usual care intervention. We were thus unable to separate out the effects of only historical SLT from study SLT in these participants. Analyses were therefore based on participants who had access to SLT in all study types to maximise available data.

Overall language ability

Regression analyses of 418 IPD (11 data sets) on age, sex, time since stroke and overall language ability recovery revealed that increasing the time between stroke onset and study enrolment by 1 month was associated with a 1% decrease in the proportion of change observed for language ability (OR 0.99, 95% CI 0.98 to 1.0; p = 0.002) (see Table 7).

Auditory comprehension

We analysed data on 508 IPD (17 data sets) on the proportion of change in auditory comprehension scores, age, sex and time since stroke. We found that an increase in time since stroke by 1 month was associated with a 1% decrease in the proportion of change in auditory comprehension scores (OR 0.99, 95% CI 0.99 to 1.0; p = 0.003; see Table 7).

Naming

Data were available on 346 IPD (14 data sets) for whom change in naming score, age, sex and time since stroke had been captured. An increase in time since stroke of 1 month was associated with a 1% decrease in the proportion of change in naming scores (see Table 7).

Other spoken language

Data were available on 155 participants from two data sets for whom change in other spoken-language scores, age, sex and time since stroke were captured. An increase in time since stroke of 1 month was associated with a 1% decrease in the proportion of change since baseline in other spoken-language scores (OR 0.99, 95% CI 0.98 to 1.00; p = 0.0006) (see Table 7).

Reading comprehension

Data were available on 11 IPD from one RCT, and therefore did not meet our prespecified criteria for analysis.

Writing

Data were available on 41 IPD (3 RCTs) for whom age, sex, time since stroke and change in writing scores since baseline were captured. Increasing time since stroke was associated with decreased proportion of change in writing score (OR 0.87, 95% CI 0.80 to 0.93; p = 0.0001) (see Table 7).

Observer-rated functional communication (activity)

Data were available on 608 IPD from 16 RCTs for whom observer-rated functional communication (activity) scores, age, sex and time since stroke were captured. An increase by 1 month in time to study entry was associated with a 2% decrease in the proportion of change since baseline in activity (see Table 7).

Observer-rated functional communication (participation)

Data were available on 608 IPD from 16 RCTs for whom observer-rated functional communication (activity) scores, age, sex and time since stroke were captured. An increase of 1 month in time to study entry was associated with a 2% decrease in the proportion of change since baseline in participation (see Table 7).

Self-rated functional communication

Data were available from only one RCT, and therefore did not meet our prespecified analysis criteria.

Factors associated with increased proportion of change using data from all study types

Overall language ability

Regression analyses of 749 IPD (19 data sets) on age, sex, time since stroke and overall language ability recovery revealed that an increase of 1 month in the time between stroke onset and study enrolment was associated with a 1% decrease in the proportion of change observed for language ability (OR 0.98, 95% CI 0.98 to 0.99; p < 0.0001) (see Table 7).

Auditory comprehension

We analysed data on 921 IPD (27 data sets) on the proportion of change in auditory comprehension scores, age, sex and time since stroke. This analysis revealed that increasing age (OR 0.98, 95% CI 0.97 to 0.99; p = 0.003) was associated with decreased proportion of change and an increase in time since stroke of 1 month was associated with a 1% decrease in the proportion of change in auditory comprehension scores.

Naming

Data were available on 636 IPD (23 data sets) for whom change in naming score, age, sex and time since stroke had been captured. An increase in time since stroke of 1 month was associated with a 1% decrease in the proportion of change in naming scores (see Table 7).

Other spoken language

Data were available on 204 participants from five data sets for whom change in other spoken-language scores, age, sex and time since stroke were captured. An increase of 1 month in time since stroke was associated with a 1% decrease in the proportion of change since baseline in other spoken-language scores (OR 0.99, 95% CI 0.98 to 1.00; p = 0.0012) (see Table 7).

Reading comprehension

Data were available on 145 IPD (3 data sets) for whom change in reading scores, age, sex and time since stroke were captured. An increase of 1 year in age was associated with a decreased proportion of change in reading comprehension (OR 0.96, 95% CI 0.94 to 0.99; p = 0.01) (see Table 7). Increasing the time since stroke to study inclusion by 1 month was associated with a 1% decrease in the proportion of change in reading scores.

Writing

Data were available on 208 IPD (7 data sets) for whom age, sex, time since stroke and change in writing scores since baseline were captured. Age, sex and time since stroke were each not associated with proportion of change in writing score (see Table 7).

Observer-rated functional communication (activity)

Data were available on 802 IPD from 22 data sets for whom observer-rated functional communication (activity) scores, age, sex and time since stroke were captured. An increase of 1 month in time to study entry was associated with a 1% decrease in the proportion of change since baseline in activity (see Table 7).

Observer-rated functional communication (participation)

Data were available on 755 IPD from 21 data sets for whom observer-rated functional communication (participation) scores, age, sex and time since stroke were captured. An increase of 1 month in time to study entry was associated with a 1% decrease in the proportion of change since baseline in activity (see Table 7).

Self-rated functional communication (activity)

Data were available on 43 IPD from two data sets for whom self-rated functional communication (activity) scores were available. Age, sex and time since stroke were not significantly associated with recovery, although the sample was very small.

Self-rated functional communication (participation)

Data were available on 43 IPD from two data sets for whom self-rated functional communication (participation) scores were available. Age, sex and time since stroke were not significantly associated with recovery, although the sample was very small.

Predictors of recovery following aphasia after stroke

We sought to examine the predictors of aphasia recovery across seven language domains in relation to participant demographics and stroke profile. Generalised linear models were used to estimate the impact of the initial severity of language impairment on subsequent recovery outcomes (defined as the absolute changes in raw scores since baseline), and this was repeated for each language domain (overall language ability, auditory comprehension, naming, other spoken language, reading comprehension, writing and functional communication).

In these analyses, we quantified the association between aphasia and eight variables (baseline score, sex, hemisphere of stroke, type, handedness, language used, age and time since stroke) using univariable and multivariable analyses. We considered language measures at baseline and first post-intervention period follow-up.

There were insufficient data on bilingualism (12 IPD available). Data on ethnicity (1475 IPD available) were also limited, but were further minimised as the variable was distributed across seven possible categories. Socioeconomic status was reported in several formats and no single composite score could be derived to describe socioeconomic status across data sets. Educational history was reported for 3125 IPD, but the variable was recorded in multiple formats, including ‘years spent in education’, ‘highest qualification’ and ‘age on leaving full-time education, making synthesis of these variables uncertain. Alternatively, analysis of years of education alone resulted in an insufficient data set. Consequently, we did not consider monolingualism/multilingualism, ethnicity, socioeconomic status or educational history in our analysis. Similarly, when a variable at each level was available only in an isolated data set, the effect of that variable on the outcome could not be distinguished from the study effect. In such cases, it was not possible to calculate estimates of the effect for non-English languages.

We first retrieved the key demographic data and identified the availability of overlapping IPD with interventions data, before excluding duplicate records, IPD that had no baseline or no follow-up data points, and non-RCT data (see Table 5). We then looked at the availability of IPD on age, sex, handedness, language used, stroke type, hemisphere, time since stroke and aphasia baseline score which would inform our planned analyses (see Appendix 8, Table 15). As prespecified, we removed variables with missing data > 20% and adjusted for initial aphasia severity. Sex, time since stroke and age are key predictive factors in recovery from stroke;114–117 although they were not always significant in this model, we included them in the analysis of population characteristics to adjust for differences between studies and changes in magnitude of effect and to inform later stages of the analyses (Table 8).

Overall language ability

Eleven RCTs (518 IPD) had data on overall language ability at study baseline, but only 482 IPD had both baseline and follow-up data of an SLT intervention and were eligible for analysis. Missing data were observed for the following variables: education (56%), handedness (44%), ethnicity (95%) and hemisphere of stroke (30%).

Demographic analysis

The outcome was absolute change in the raw score from baseline to the first follow-up after the study intervention period. A positive change indicated an improvement in overall language abilities. At univariable level, we observed statistically significant associations between baseline measures of language ability and positive change at follow-up (p < 0.0001; see Appendix 8, Table 15). Length of time since the onset of aphasia (grouped) was also a significant predictor of improvement (p = 0.017). As initial language ability scores at baseline were strongly associated with an increase in overall language abilities at follow-up, we examined an adjusted association between time since stroke and baseline language ability in a bivariable model (see Appendix 8, Table 15).

After adjusting for the effect of baseline language ability score, time since stroke was no longer associated with overall language ability scores at follow-up, whereas the language spoken by participants became significant (p = 0.021); however, as highlighted in Predictors of recovery following aphasia after stroke, this finding should be treated with caution as there were no within-data set comparisons of languages spoken and so it was not possible to distinguish a language effect from a data set effect.

The multivariable analysis revealed a similar finding, with language ability scores at baseline continuing to have a significant, positive association with language ability scores at follow-up. When handedness was included in this multivariable analysis, language ability at baseline, sex and language used were all significantly positively associated with recovery (see Appendix 8, Table 15).

We observed slightly better improvement on measures of overall language ability among women than men [female estimate mean 14.3 points (95% CI 9.01 to 19.5 points) vs. male estimate mean 12.3 points (95% CI 7.2 to 17.4 points); see Table 8]; however, this difference was not significant (p = 0.1870) (see Appendix 8, Table 15). We also observed a non-significant trend towards improvements among younger participants and those in the early stages after stroke (see Appendix 8, Table 15). For people aged < 55 years, we observed an estimate mean change of 15.4 points on the WAB-AQ, followed by an estimate mean change of 12.4 points for people aged 56–65 years (see Table 8). Similarly, for people enrolled in RCTs within 0–1 month of stroke, the estimate mean change was 19.1 points; for those enrolled within 1–3 months of stroke, the estimate mean change was 16.2 points. This could reflect the influence of spontaneous recovery in the early stages after stroke. Although the groupings by age and time since stroke were not significant at a multivariable level, the observed changes in language ability since baseline were notable and may require further study.

When analysing data from all study types, similar results were observed; time group became significantly negatively associated with improvement in overall language ability (p = 0.0098). Enrolment within 28 days of index stroke was associated with an estimate mean change of 21.0 points on the WAB-AQ, whereas enrolment within 1–3 months of stroke was associated with an estimate mean change of 16.4 points on the WAB-AQ (see Table 8).

Auditory comprehension

A total of 556 IPD from 16 RCTs had auditory comprehension data at baseline and follow-up, but only 550 IPD had both baseline and follow-up auditory comprehension analysis, relevant demographic data and a SLT intervention to support the planned analysis (see Appendix 8, Table 15).

Demographic analysis

The values in the ‘change from baseline’ variable were not normally distributed (skewed). When modelled using the baseline score as a linear function of the ‘change from baseline’, the residuals were reasonably normally distributed. Thus the ‘change from baseline’ values remained untransformed. As with measures of overall language ability, baseline auditory comprehension scores were positively associated with change at first follow-up (p < 0.0001). At univariable level, age was also inversely significantly associated with recovery (p = 0.003). This association remained strong when baseline score was controlled for. Auditory comprehension scores at baseline were significantly associated with change in scores at follow-up in multivariable analyses and age (grouped) (p = 0.002) (see Appendix 8, Table 15).

Although sex and time since stroke were not significant predictors in the model (see Appendix 8, Table 15), we included them in the analysis together with age. We considered differences between studies and changes in magnitude of effect to inform the later stages of the planned analyses. We observed little difference on measures of auditory comprehension between female and male participants [female estimate mean 3.8 points (95% CI 0.98 to 6.66 points) vs. male estimate mean 3.1 points (95% 0.35 to 5.85 points)]. We also observed greater improvements among younger participants and those in the early months after aphasia onset (p = 0.047); those aged < 55 years had an estimate mean change of 6.05 (95% CI 3.12 to 8.94) points on the TT-AAT. The inclusion of non-RCT data supported these findings (see Table 8).

Naming

We identified 13 RCT data sets involving 391 IPD with naming measures available at baseline and follow-up. Six participants who received a social support intervention were excluded; therefore, the naming analysis was based on 385 IPD (13 RCTs; see Appendix 8, Table 15).

Demographic analysis

Although the data on changes from baseline were skewed, the residuals from the model with baseline were normally distributed, and so the change value remained untransformed. Only English and Dutch languages were languages of data collection in more than one trial; although this made language of data collection a candidate for a subset analysis comparing languages, there were no within-study comparisons of language, meaning that the significant results should be interpreted with caution (see Appendix 8, Table 15). There was a trend towards a difference between age groups; because age, time since stroke and sex are typically considered in studies of stroke recovery and rehabilitation, they were included in our model to account for population differences.

An earlier time point for study enrolment (and subsequent follow-up) was associated with a higher impact on change in naming scores [estimated mean change of 11.12 points (95% CI 5.7 to 16.5 points) on the BNT] than interventions at 3–6 months after stroke, for which the mean change was non-significant (estimated mean change of 4.3 points, 95% CI –1.6 to 10.1 points) (see Table 8). Although the time group for intervention was not significant, the point estimates indicate that these trends may warrant further examination. Early intervention after stroke appeared to have the highest impact on change (with spontaneous recovery possibly contributing to recovery profile in the early phases post stroke), as did younger age, with people aged < 55 years estimated to change by 9.31 points on the BNT (95% CI 4.7 to 13.9 points), whereas older age groups had a non-significant change of 4.42 points (see Table 8).

Other spoken language

Three RCTs (182 IPD) and three non-RCT data sets (49 IPD) reported other spoken-language outcome measures. The data were transformed to the anchor measures (PICA with a scale of 0–16). There were too few comparisons using RCT data sets only, and so we report an analysis that was inclusive of all data sets (see Appendix 8, Table 15). Other spoken language scores by time and age group at baseline were significantly associated with change in scores at follow up in multivariable analyses age (group p = 0.015) and time since stroke (group p = 0.01) (see Appendix 8, Table 15).

Demographic analysis

All participants from baseline to their first follow-up after the end of treatment (when there were multiple options) were included (231 IPD; 6 data sets). As the baseline score was not a statistically significant predictor of ‘change from baseline’, we did not conduct a bivariate (baseline plus other predictive variable) analysis as we did for other domains reported in this section (see Appendix 8, Table 15).

Intervention within the first 3 months of index stroke significantly benefited spoken-language outcomes (estimated mean change of 1.9 points on the spoken-language PICA 16-point scale) compared with study enrolment > 6 months after stroke (non-significant mean change; see Table 8).

Reading comprehension

Only one RCT (11 IPD) reported reading outcomes, and so the following analyses were performed on that RCT and three non-RCT data sets (77 IPD) with reading data on participants at baseline and follow-up (see Table 8). All data (88 IDP; 4 data sets) were transformed to the CAT reading subtest (scale of 0–74).

Demographic analysis

Residuals were skewed and so the change from baseline in the following sections (see Appendix 8, Table 15) has been transformed on the log scale.

Interventions delivered earlier after stroke (between 4 weeks and 3 months since stroke) were associated with the greatest benefits of intervention on measures of reading comprehension (4.0 points on the CAT; see Table 8), possibly due, in part, to spontaneous recovery after stroke. As for other variables, younger age groups (< 55 years of age) benefited most, with a mean change of 5.5 points on the reading comprehension outcome (see Table 8).

Writing

On review of the data, we identified three RCTs (47 IPD) that reported data on writing at baseline and at a subsequent follow-up time point (see Appendix 8, Table 15). No non-RCT data sets provided writing data at these time points. All writing data were transformed to the anchor measures (the CAT with a scale of 0–76).

Demographic analysis

We analysed participants from baseline to the first follow-up after the end of treatment (when there were multiple options). Neither the data on change from baseline nor the residual values were skewed; thus, the change value remained untransformed. As the baseline writing score was not significant, we did not conduct a bivariable analysis as we did for other domains reported in this section (see Appendix 8, Table 15).

Early intervention (between 4 weeks and 3 months) was associated with a mean benefit of 7.8 points on writing domain outcomes (95% CI 2.3 to 13.4 points on the CAT writing subtest). No other significant changes were noted for other time points after stroke (see Table 8).

Functional communication

Functional communication was captured using three distinct measurement approaches: (1) tools that captured data using an observer-rated approach, (2) tools that asked participants to self-rate their functional communication abilities and (3) discourse analysis approaches that captured and quantified the presence of particular language or communicative features in a defined sample of language. Measures captured using the three different approaches could not be meta-analysed across approaches, and are thus analysed and presented separately.

Functional communication: observer-rated measures

A total of 14 RCTs (544 IPD) that reported functional communication using observational measures at baseline and at a subsequent post-intervention time point were identified. An additional five non-RCT data sets (115 IPD) provided additional functional communication data at these time points (see Table 8).

Demographic analysis

We analysed participants from baseline to the first follow-up after the end of treatment. For one measure [the Therapy Outcome Measure (TOM)], two subtests (activity or participation) were used in a single RCT capturing data on the same participants. For our purposes, either subtest could be included in the functional communication meta-analysis. Both were equally valid inclusions. We arbitrarily included the activity subtest data (see Appendix 8, Table 15) and conducted a sensitivity analysis to examine whether or not there was any change in the findings had we included the participation subtest data (reported in Appendix 9, Tables 16–17).

Using the activity subtest data from the TOMs, we found that the data on change from baseline were skewed, but the residuals from the model with baseline were reasonably normally distributed, and so the change value remained untransformed. Time since stroke was significant in univariable and multivariable analyses (see Appendix 8, Table 15). Age and sex were significant in the participant subset with complete data. All three variables were retained in the basic model.

Eleven participants did not have information on their time since stroke in a suitable format for data synthesis and were excluded from the analysis; therefore, the effective sample size from RCT data set was 533 IPD (see Table 8). Female participants had higher mean observational scores than male participants (mean 0.76, 95% CI 0.48 to 1.0, on the AAT-SSC), and the youngest participants (< 55 years of age) had higher mean scores (mean 0.75, 95% CI 0.46 to 1.0, on the AAT-SSC) than older age groups. Similarly, participants within 1 month of aphasia onset had a mean score of 1.05 on the AAT-SSC (95% CI 0.70 to 6.99), compared with participants who were > 6 months after aphasia onset (mean 0.33, 95% CI 0.00 to 0.66; see Table 8). The findings based on the non-RCT IPD supported those found above (see Table 8).

Functional communication: self-rated measures

There were insufficient data (11 IPD; 1 data set with baseline and follow-up data) to support the analysis of univariable and multivariable relationships to functional communication as rated by people with aphasia. Inclusion of the non-RCT data did not change the feasibility of the planned analysis (43 IPD; 2 data sets).

Discourse analysis

Discourse analysis data were similarly sparse (423 IPD; 5 data sets), with limited overlap in the method of data sampling and data items recorded. We were unable to synthesise these data to support the planned analysis of univariable and multivariable relationships.

Summary

Age was significantly associated with change in absolute percentage score across selected domains and time since stroke was significantly associated with absolute proportion of change since baseline across all language domains. These variables will be taken forward to be included in statistical base models in subsequent analyses, when appropriate, in Chapter 6. Across each of the multivariable analyses, baseline language domain score, age, sex and time since stroke were selectively significantly associated with absolute change in the raw language domain scores.

Further to the observations of time having a significant association with change in selected domain scores at follow-up, we observed that, across all language domains, the highest absolute change in scores from baseline were seen in those participants enrolled in a study within 1 month of index stroke and those who were aged < 55 years. Females also appeared to have a trend towards better recovery on measures of overall language ability and functional communication than males.