2.3.2. TMT

TMT assesses attention, processing speed, sequencing, mental flexibility, and visualmotor skills [12]. TMT contains two parts: In part A, numbers are required to be connected as fast as possible in numerical order. Part B is similar, but now the subject is required to alternate between numbers and letters, adding a component of executive functioning. The primary outcome variable is completion time. By calculating the difference between the completion time of TMT B and TMT A, a measure of cognitive flexibility is produced [20]. TMT has been proven to be sensitive to neurological impairment [12].

#### 2.3.3. MPAI-4

MPAI-4 consists of 30 questions aimed at assessing commonly occurring difficulties after brain injury. The score ranges from 0 to 111, where a lower score indicates better recovery. The instrument consists of three subscales: ability index, adjustment index, and participation index. The ability index measures sensory, motor, and cognitive abilities; the adjustment index measures mood and interpersonal interaction; and the participation index measures social contacts, initiation, work/school, and money management. Previous studies have demonstrated good person reliability (0.92) and item reliability (0.94) [11]. MPAI-4 is linked to the International Classification of Functioning, Disability, and Health and is an established tool for investigating long-term functional outcome after TBI [21]. The instrument covers areas of physical, cognitive, emotional, behavioral, and social problems

that persons with brain injury can encounter and furthermore contains assessments of areas where problems commonly arise when patients are reintegrated in society [11].

#### 2.3.4. CRASH Model

In order to control for acute injury severity, the acute injury composite (corticosteroid randomization after significant head injury, CRASH) was used, representing a % risk of unfavorable outcome at 6 months, as calculated and used in previously published studies on the Probrain material [22]. The crash composite score includes data collected within the first 24 h regarding GCS, pupillary reaction, presence of major extracranial injury, age, country, and five CT-brain features [23]. A higher score indicates a greater risk of unfavorable outcome.

#### 2.3.5. GOSE

GOSE score spans from 1 (dead) to 8 (upper good recovery). Traditionally, a score in the range of 1–4 is considered an unfavorable outcome, and a score in the range of 5–8 is considered a favorable outcome. The GOSE has good interrater reliability and validity and is an established measure of global outcome after traumatic brain injury [24]. GOSE was included as a descriptive variable in order to more fully depict the patient group.

#### *2.4. Analysis*

Statistical analyses were computed using the Jamovi statistical software [25]. A significance level of 0.05 was used for all statistical tests. Differences in demographic characteristics between groups were analyzed with Student's *t*-test for parametric data and a Mann–Whitney and χ2 test for nonparametric data. For measures of effect size, Cohen's *d* was used, where 0.2 is considered a small effect size, 0.5 medium, and 0.8 large. In order to analyze the relationship between results on neuropsychological screening and outcome according to MPAI-4, correlation analysis with Spearman's rho was used. To investigate the effect of the controlling variables on the relationship between results on neuropsychological tests and outcome, linear regression was used. Since the MPAI-4 subscales are not independent of each other, linear regression on the total score was not used. Three linear regressions were computed for BNIS and cognitive flexibility separately, one for each MPAI-4 subscale score, which was used as the dependent variable, in total six models. CRASH and educational level were added as independent variables to adjust for age, injury severity, and cognitive reserve. Age is included in the CRASH model and, therefore, not entered separately in the linear regression model.

#### *2.5. Ethics*

The study was approved by the Regional Ethics Committee of Stockholm (numbers 2009/1644/31/3 and 2016/1465-31/4). The patient gave written informed consent in cases where he or she had the capacity to do so. In the majority of cases, the patient lacked capacity, and the patient's nearest relative gave consent.

#### **3. Results**

#### *3.1. Demographics*

At 3 months, 74 patients were able to complete BNIS, and out of these, 41 patients also completed MPAI-4 at the long-term follow-up (Figure 1). Of these 41 patients, 38 had data on educational level, and 33 of them also had TMT data. MPAI-4 was completed by the patients themselves in 22 cases and in 13 cases by rehabilitation personnel. For 6 patients, MPAI-4 was completed both by rehabilitation personnel and the patients themselves. In these cases, the differences between scores were usually small (median = 2 points).

Descriptive statistics of demographic variables, neuropsychological screening scores, MPAI-4, and GOSE for the included patients are presented in Table 1. The high education group was significantly younger than the low education group. No other significant

CRASH

differences were found between educational groups, although according to Cohen's *d*, there was a large effect size of educational level on BNIS and TMT scores.


**Table 1.** Descriptive statistics for all participants, separated by educational level.

Note: Values are displayed as median and interquartile range (IQR) for nonparametric data and mean and standard deviation for parametric data (age). TMT missing data are 2 in the low education group and 6 in the high education group. Mann–Whitney was used for examining differences between the groups, except for age, where a Student's *t*-test was used. \* value at 3 months' follow-up. \*\* value at 5–8 years' follow-up.

#### *3.2. Screening Instruments and MPAI-4 in Relation to Demographic Variables*

Significant correlations between demographic variables and BNIS score, Cognitive Flexibility(TMTB-TMTA), and MPAI-4 can be seen in Table 2. There were no significant gender differences on any of the measures. In the high education group, seven patients (28%) were above the cut-off value of 47, indicating no cognitive dysfunction, compared to one patient (8%) in the low education group.


with CT <sup>−</sup>0.007 0.11 <sup>−</sup>0.38 \* <sup>−</sup>0.36 \* <sup>−</sup>0.44 \*\* <sup>−</sup>0.26

**Table 2.** Correlation for neuropsychological tests and MPAI-4 with age and injury-related variables.

\* = *p* < 0.05, \*\* = *p* < 0.01.
