All 68 patients with MS completed the SDMT. The oral version was administered to four patients who scored ≥ 2 points on the pyramidal or cerebellar functional scales involving the dominant hand. The BVMT-R results were missing for two patients. The BDI was administered to 55 (81%) patients.
The main characteristics of the study population are outlined in Table 1. The mean age of the MS group was 39.2 ± 9.9. The mean age of the HC group was 38.5 ± 9.9. In the HC group, 84% were employed, whereas in the MS group, 57% were employed. Forty-nine HC participants and Fifty MS participants had ≥ 15 y of education. The proportion of patients with ≤ 14 y of education was slightly higher in the control group (28 % vs. 26%).
The MS group comprised 52 patients (78.8%) with relapsing-remitting MS (RRMS), 12 with secondary progressive MS (SPMS), and 4 with primary progressive MS (PPMS). The mean disease duration in patients was 7.0 ± 5.7 y. Forty-nine percent of patients had a ≤ 5-y history of MS. Ten percent of patients had newly diagnosed MS. The mean BDI score was 12 ± 9.0 points. Clinically significant moderate to severe depression (≥ 19 points) was identified in 14 patients (25 %).
Table 1
Characteristics of the study population
| patients | controls |
Number of participants n | 68 | 68 |
Age (y), mean ± SD | 39.2 (± 9.9) | 38.5 (± 9.9) |
Women n (%) | 48 (71%) | 46 (68%) |
Men n (%) | 20 (29) | 22 (32%) |
Education (y), mean ± SD | 14.3 ± 2.1 | 14.5 ± 1.9 |
Education ≥ 15 y, n (%) | 50 (74%) | 49 (72%) |
Education ≤ 14 y, n (%) | 18 (26%) | 19 (28%) |
Employed n (%) | 39 (57%) | 57 (84%) |
Unemployed n (%) | 29 (43%) | 11 (16%) |
Disease duration (y), mean ± SD | 7.0 ± 5.7 | - |
EDSS score, mean ± SD | 3.3 ± 1.6 | - |
MS subtype | | |
RRMS n (%) | 52 (76%) | - |
SPMS n (%) | 12 (18%) | - |
PPMS n (%) | 4 (6%) | - |
EDSS, expanded disability status scale; RRMS, relapsing-remitting MS; SPMS, secondary progressive MS; PPMS, primary progressive MS |
As shown in Table 2, the test-retest reliability coefficient was adequate to good for all three tests. The SDMT showed the highest reliability.
Table 2
BICAMS test-retest reliability
| Test | Retest | r | p |
SDMT/MS | 35.5 ± 12.7 | 37.5 ± 10.0 | 0.87 | < 0.001 |
CVLT-II/MS | 51.0 ± 11.2 | 58.0 ± 8.5 | 0.83 | < 0.001 |
BVMT-R/MS | 22.0 ± 8.0 | 25.1 ± 3.6 | 0.80 | < 0.001 |
SDMT/HC | 46.0 ± 11.8 | 48.1 ± 11.2 | 0.78 | < 0.001 |
CVLT-II/HC | 58.5 ± 8.2 | 62.9 ± 8.1 | 0.75 | < 0.001 |
BVMT-R/HC | 25.6 ± 6.8 | 32.6 ± 3.9 | 0.70 | < 0.001 |
Scores are mean ± SD; SDMT, Symbol Digit Modality Test; CVLT-II, California Verbal Learning Test 2nd edition; BVMT-R, Brief Visual Memory Test-Revised
The mean scores on all cognitive tests were lower in the patient group. The greatest discrepancy between the MS and HC groups was seen on the SDMT (Table 3).
Table 3
Comparison of mean ± SD test scores between patients with MS and healthy controls (HC)
| MS group | HC group | p | Cohen’s d |
n | 68 | 68 | | |
SDMT | 35.5 ± 12.7 | 46.0 ± 11.8 | < 0.001 | 0.86 |
CVLT-II | 51.0 ± 11.8 | 58.5 ± 8.2 | < 0.001 | 0.74 |
BVMT-R | 22.0 ± 8.0 | 25.6 ± 6.8 | < 0.001 | 0.48 |
Age was negatively correlated with all test scores in the HC group (Table 4). Such a correlation was observed with only the SDMT scores in the patient group (Table 5). In the HC group, we found a significant positive correlation between years of education and scores on all three tests. In the patient group, an analogous correlation was identified for the BVMT-R and SDMT, but not for the CVLT-II. Among 18 patients with fewer than 14 y of education, CI was identified in 14 (78%). In contrast, among 19 HCs with fewer than 14 y of education, CI was identified in only 2 (10.5%).
Table 4
Correlations of BICAMS scores with age and education in the HC group
| Age | Education |
| r | p | r | p |
SDMT | -0.457 | < 0.001 | 0.523 | < 0.001 |
CVLT-II | -0.368 | < 0.001 | 0.439 | 0.002 |
BVMT-R | -0.506 | < 0.001 | 0.348 | 0.04 |
Table 5
Correlations of BICAMS scores in patients with MS
| Age | Education | Duration | EDSS | BDI |
| r | p | r | p | r | p | r | p | r | p |
SDMT | -0.400 | 0.001 | 0.243 | 0.04 | -0.177 | 0.1 | − 0.582 | < 0.001 | -0.288 | 0.02 |
CVLT-II | -0.112 | 0.4 | 0.207 | 0.09 | -0.106 | 0.4 | -0.403 | < 0.001 | -0.152 | 0.7 |
BVMT-R | -0.192 | 0.07 | 0.297 | 0.01 | 0.125 | 0.3 | -0.342 | < 0.001 | -0.06 | 0.7 |
Education, years of education; Duration, disease duration; EDSS, expanded disability status scale; BDI, Beck Depression Inventory |
Table 6 shows comparisons of patients with shorter and longer disease duration. The mean scores on the BICAMS tests were higher in patients with shorter (≤ 10 y) disease durations, i.e., 31.0 ± 12.6 vs. 37.3 ± 11.8 for the SDMT, 47.6 ± 10.5 vs. 52.2 ± 11.1 for the CVLT-II and 21.8 ± 8.4 vs. 22.4 ± 7.5 for the BVMT-R. The mean age was higher in patients with longer disease durations (41.0 ± 8.0 vs. 38.4 ± 10.0). On the other hand, the proportion of individuals with fewer than 14 y of education was higher in patients with a disease duration ≤ 10 y (31.5% vs. 14.3%).
The overall prevalence of CI in our MS sample was 43%. Cognitive dysfunction was found in 67% of patients with SPMS and in 75% of patients with PPMS. In the RRMS subgroup, CI prevalence was 34%. Cognitive decline was identified in 19 patients (28%) by the SDMT, in 22 patients (32%) by the CVLT-II, and in 13 patients (19%) by the BVMT-R. Among patients with MS who had CI, 31% performed below the cutoff score (i.e., showed CI) on all three tests, 24% showed CI on two of the tests, and 41% showed CI on one test.
Table 6
Comparison of patients with shorter and longer disease duration
| ≤ 10 y disease duration | ≥ 11 y disease duration |
Number of participants n | 54 | 14 |
Age (y), mean ± SD | 38.4 (± 10.0) | 41.0 (± 8.3) |
Women n (%) | 38 (70.4%) | 11 (76.6%) |
Men n (%) | 16 (29.6%) | 3 (21.4%) |
Education (y), mean ± SD | 14.1 ± 2.2 | 14.9 ± 1.2 |
Education ≥ 15 y, n (%) | 37 (68.5%) | 12 (85.7%) |
Education ≤ 14 y, n (%) | 17 (31.5%) | 2 (14.3%) |
EDSS score, mean ± SD | 3.0 ± 1.3 | 3.8 ± 2.3 |
MS subtype | | |
RRMS n (%) | 44 (81.5%) | 8 (57.1%) |
SPMS n (%) | 8 (14.8 %) | 4 (28.6%) |
PPMS n (%) | 2 (3.7 %) | 2 (14.3 %) |
SDMT | 37.3 ± 11.8 | 31.0 ± 12.6 |
CVLT-II | 52.2 ± 11.1 | 47.6 ± 10.5 |
BVMT-R | 22.4 ± 7.5 | 21.8 ± 8.4 |
SDMT, Symbol Digit Modality Test; CVLT-II, California Verbal Learning Test 2nd edition; BVMT-R, Brief Visual Memory Test-Revised |