Introduction
Methods
Trial design
Participants
Settings and location
Intervention
Outcomes
Neuropsychological assessment
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The Rey Auditory Verbal Learning Test (RAVLT) which includes the assessment of immediate (RAVLT_I) and delayed recalls (RAVLT_D) to evaluate short-term and long-term verbal memory, respectively [34‐36]. In this study, parallel forms of RAVLT's words were used (e.g., tenda, tamburo, etc., and violino, bastone, etc.).
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The self-assessment questionnaires to investigate mood included the 2nd edition of the Beck Depression Inventory (BDI-II) [46, 47] used to assess the depressive symptoms of the participants and the State–Trait Anxiety Inventory-Form Y1 and 2 (STAI-Y1; STAI-Y2) with 40 entries [48, 49]. The STAI provides scores for two scales (20 and 20) distinguishing between a person's status and trait anxiety levels. It should be noted that parallel forms were not used for mood questionnaires.
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The Retrospective Prospective Memory Questionnaire (PRMQ) which is a self-report questionnaire that provides information for both the prospective (PRMQ-P) and retrospective (PRMQ-R) scales [50, 51]. These non-parallel tests were applied to investigate the perception of subjects in any modifications of cognitive functions [52].
Sample size
Randomization and sequence generation
Blinding
Statistical methods
Results
Participant flow
Baseline data
All (n = 44) | BR-CT first (n = 33) | Placebo first (n = 11) | |
---|---|---|---|
Age (years) | 32.7 (12.5) | 29.6 (8.1) | 33.7 (13.6) |
Women | 24 (54.55%) | 14 (42.42%) | 10 (90.90%) |
Men | 20 (45.45%) | 19 (57.57%) | 1 (9.09%) |
Body mass (kg) | 66.3 (9.0) | 60.4 (8.0) | 68.3 (8.5) |
Stature (cm) | 170 (9.2) | 163.2 (6.1) | 172 (9.0) |
BMI (kg/m2) | 22.8 (1.4) | 22.6 (1.8) | 22.9 (1.2) |
Education | |||
High school | 24 (54.55%) | 16 (48.48%) | 8 (72.73%) |
College | 17 (38.64%) | 14 (42.42%) | 3 (27.27%) |
Post-graduate | 3 (6.82%) | 3 (9.09%) | 0 (0.00%) |
Recreational sports practice | |||
Yes | 18 (40.91%) | 15 (45.45%) | 3 (27.27%) |
No | 26 (59.09%) | 18 (54.55%) | 8 (72.73%) |
Coffee consumption | |||
Yes | 34 (77.37%) | 27 (81.82%) | 7 (63.64%) |
No | 10 (22.73%) | 6 (18.18%) | 4 (36.36%) |
Outcomes and estimation
Variable | Placebo (n = 44) \(\overline{X}\) (SD) | BR-CT (n = 44) \(\overline{X}\) (SD) | Δ (SD) [95% CI] | dunb δ [95% CI] | p value | Correlation |
---|---|---|---|---|---|---|
RAVLT_D | 42.68 (7.68) | 47.95 (8.67) | 5.27 (6.52) [3.28, 7.25] | 0.632 [0.36, 0.91] | < 0.001 | 0.69 |
RAVLT_I | 8.36 (2.85) | 10.09 (2.59) | 1.72 (3.28) [0.72, 2.72] | 0.622 [0.25, 1.01] | 0.001 | 0.27 |
Digit span F | 5.56 (1.12) | 5.59 (0.97) | 0.02 (1.19) [– 0.33, 0.38] | 0.021 [– 0.31, 0.35] | 0.900 | 0.37 |
Digit span B | 3.65 (1.01) | 3.72 (0.92) | 0.06 (1.10) [– 0.26, 0.40] | 0.069 [– 0.26, 0.40] | 0.685 | 0.35 |
SDMT | 69.0 (12.01) | 64.56 (15.02) | –4.43 (15.79) [– 9.23, 0.37] | 0.320 [– 0.67, 0.02] | 0.070 | 0.33 |
FAB | 15.90 (1.42) | 16.31 (1.11) | 0.40 (1.2) [0.02, 0.79] | 0.314 [0.01, 0.61] | 0.037 | 0.53 |
COWAT/FAS | 32.52 (9.67) | 36.15 (8.00) | 3.63 (6.79) [1.57, 5.70] | 0.403 [0.16, 0.65] | 0.001 | 0.72 |
BDI | 5.79 (5.39) | 7.34 (6.19) | 1.54 (3.63) [0.44, 2.64] | 0.261 [0.07, 0.45] | 0.007 | 0.81 |
STAI Y1 | 33.95 (7.82) | 35.43 (10.52) | 1.47 (6.71) [– 0.56, 3.51] | 0.157 [– 0.05, 0.37] | 0.152 | 0.77 |
STAI Y2 | 38.59 (9.53) | 39.34 (10.32) | 0.75 (5.15) [– 0.81, 2.31] | 0.074 [– 0.07, 0.22] | 0.340 | 0.87 |
PMRQ P | 19.31 (5.27) | 19.68 (5.93) | 0.36 (3.48) [– 0.69, 1.42] | 0.064 [– 0.12, 0.24] | 0.493 | 0.81 |
PMRQ R | 18.43 (4.52) | 19.09 (4.92) | 0.65 (3.01) [– 0.25, 1.57] | 0.137 [– 0.05, 0.32] | 0.154 | 0.80 |
PMRQ TOT | 37.75 (9.31) | 39.0 (10.15) | 1.25 (6.11) [– 0.60, 3.11] | 0.126 [– 0.06, 0.31] | 0.183 | 0.81 |
Variable | Sequence AB | Sequence BA | Sequence effect | ||||||
---|---|---|---|---|---|---|---|---|---|
BR-CT (n = 33) \(\overline{X}\) (SD) | Placebo (n = 33) \(\overline{X}\) (SD) | Δ (SD) [95% CI] | dunb δ [95% CI] | Placebo (n = 11) \(\overline{X}\) (SD) | BR-CT (n = 11) \(\overline{X}\) (SD) | Δ (SD) [95% CI] | dunb δ [95% CI] | p value | |
RAVLT_D | 47.97 (8.82) | 41.84 (7.24) | – 6.12 (11.52) [– 10.2, – 2.0]* | 0.740 [1.27, 0.23] | 45.18 (8.76) | 47.90 (8.60) | 2.72 (6.66) [– 1.75, 7.20] | 0.290 [0.16, 0.78] | 0.421 |
RAVLT_I | 10.21 (2.58) | 7.69 (2.72) | – 2.51 (4.07) [– 3.95, – 1.07]* | 0.926 [1.51, 0.36] | 10.36 (2.33) | 9.72 (2.72) | – 0.63 (3.10) [– 2.72, 1.45] | 0.231 [–0.97, 0.48] | 0.095 |
Digit Span F | 5.45 (1.03) | 5.72 (0.97) | 0.27 (1.37) [– 0.21, 0.76] | 0.265 [– 0.20, 0.74] | 5.09 (1.44) | 6.0 (0.63) | 0.90 (1.04) [0.20, 1.61]* | 0.752 [0.14, 1.45] | 0.859 |
Digit Span B | 3.66 (0.95) | 3.75 (1.06) | 0.09 (1.42) [– 0.41, 0.59] | 0.088 [– 0.39, 0.57] | 3.36 (0.80) | 3.90 (0.83) | 0.54 (1.03) [– 0.15, 1.24] | 0.614 [– 0.14, 1.45] | 0.752 |
SDMT | 60.66 (13.45) | 70.96 (12.49) | 10.30 (18.51) [3.73, 16.86]* | 0.775 [0.26, 1.31] | 63.09 (8.34) | 76.27 (13.79) | 13.18 (14.00) [3.77, 22.59]* | 1.156 [0.25, 2.01] | 0.217 |
FAB | 16.36 (1.02) | 16.0 (1.29) | –0.36 (1.38) [– 0.85, 0.12] | 0.303 [– 0.72, 0.10] | 15.63 (1.80) | 16.18 (1.40) | 0.54 (0.68) [0.08, 1.00] | 0.312 [0.04, 0.62] | 0.393 |
COWAT/FAS | 37.48 (7.57) | 31.21 (9.06) | – 6.27 (11.79) [– 10.4, – 2.09]* | 0.733 [1.26, 0.23] | 36.45 (10.7) | 32.18 (8.26) | – 4.27 (5.47) [– 7.95, – 0.59] | 0.410 [0.82, 0.04] | 0.989 |
BDI | 7.30 (5.31) | 4.93 (4.39) | – 2.36 (6.54) [– 4.68, – 0.04]* | 0.473 [0.95, 0.008] | 8.36 (7.32) | 7.45 (8.62) | – 0.90 (2.02) [–2.26, 0.44] | 0.105 [0.26, 0.04] | 0.212 |
STAI Y1 | 34.45 (9.46) | 32.93 (7.48) | – 1.51 (10.97) [–5.40, 2.37] | 0.173 [–0.61, 0.26] | 37.0 (8.370) | 38.36 (13.29) | 1.36 (8.13) [– 4.10, 6.83] | 0.113 [– 0.31, 0.55] | 0.083 |
STAI Y2 | 38.51 (9.25) | 36.33 (8.76) | – 2.18 (12.29) [– 6.54, 2.17] | 0.236 [–0.71, 0.22] | 45.36 (8.82) | 41.81 (13.24) | – 3.54 (5.93) [–7.53, 0.44] | 0.291 [– 0.64, 0.03] | 0.011 † |
PMRQ P | 19.84 (6.01) | 19.27 (5.39) | – 0.57 (8.32) [– 3.52, 2.37] | 0.098 [–0.59, 0.39] | 19.45 (5.16) | 19.18 (5.92) | – 0.27 (3.03) [– 2.31, 1.76] | 0.045 [– 0.37, 0.27] | 0.863 |
PMRQ R | 19.03 (5.19) | 18.24 (4.86) | – 0.78 (7.41) [– 3.41, 1.84] | 0.153 [– 0.66, 0.34] | 19.0 (3.43) | 19.27 (4.22) | 0.27 (2.24) [– 1.23, 1.77] | 0.065 [– 0.27, 0.41] | 0.672 |
PMRQ TOT | 39.18 (10.34) | 37.51 (9.80) | – 1.66 (15.11) [– 7.02, 3.69] | 0.161 [– 0.67, 0.34] | 38.45 (8.02) | 38.45 (10.01) | 0.0 (4.47) [– 3.00, 3.00] | 0.000 [– 0.29, 0.29] | 0.965 |
Variable | Period 1 | Period 2 | Period effect | Treatment effect | ||||
---|---|---|---|---|---|---|---|---|
BR-CT (n = 33) μt (σw) | Placebo (n = 11) μt (σw) | ESt (MoEΔ) [95% CI] | BR-CT (n = 11) μt (σw) | Placebo (n = 33) μt (σw) | ESt (MoEΔ) [95% CI] | DID [95% CI] p value | p value | |
RAVLT_D | 48.28 (5.62) | 45.14 (6.12) | – 3.14 (7.56) [– 10.7, 4.42] | 48.14 (7.90) | 41.76 (4.88) | – 6.38 (9.53) [– 15.9, 3.15] | – 3.27 [– 11.3, 4.77] 0.421 | 0.032 ‡ |
RAVLT_I | 10.28 (2.24) | 10.42 (1.36) | 0.14 (1.92) [– 1.77, 2.06] | 9.85 (2.46) | 7.47 (1.20) | – 2.38 (2.96) [– 5.34, 0.57] | – 2.18 [– 4.75, 0.38] 0.095 | 0.150 |
Digit Span F | 5.61 (0.50) | 4.71 (0.98) | – 0.90 (1.17) [– 2.08, 0.27] | 6.0 (0.00) | 5.76 (0.47) | – 0.23 (0.27) [– 0.51, 0.03] | 0.09 [– 0.92, 1.10] 0.859 | 0.214 |
Digit Span B | 3.57 (0.50) | 3.28 (0.50) | – 0.28 (0.62) [– 0.91, 0.34] | 3.85 (0.83) | 3.71 (0.88) | – 0.14 (1.04) [– 1.18, 0.90] | 0.15 [– 0.79, 1.10] 0.752 | 0.343 |
SDMT | 59.09 (7.38) | 63.42 (2.66) | 4.33 (4.97) [– 0.64, 9.30] | 72.85 (6.99) | 71.19 (7.35) | – 1.66 (8.78) [– 10.4, 7.11] | – 7.72 [– 20.0, 4.63] 0.217 | 0.645 |
FAB | 16.52 (0.50) | 16.0 (1.00) | – 0.52 (1.2) [– 1.72, 0.67] | 16.42 (0.90) | 16.23 (0.79) | – 0.19 (1.11) [– 1.30, 0.92] | 0.54 [– 0.71, 1.80] 0.393 | 0.156 |
COWAT/FAS | 38.19 (4.53) | 34.57 (6.63) | – 3.61 (8.03) [– 11.6, 4.41] | 31.57 (4.47) | 32.33 (6.60) | 0.76 (6.06) [– 5.30, 6.82] | 0.06 [– 8.43, 8.55] 0.989 | 0.641 |
BDI | 7.0 (4.39) | 7.0 (5.50) | 0.00 (6.71) [– 6.71, 6.71] | 5.28 (5.55) | 4.14 (2.85) | – 1.14 (6.66) [– 7.80, 5.52] | – 3.57 [– 9.23, 2.08] 0.212 | 0.610 |
STAI Y1 | 32.42 (6.35) | 37.57 (5.77) | 5.14 (7.30) [– 2.15, 12.4] | 38.42 (11.4) | 32.14 (3.28) | – 6.28 (13.6) [– 19.9, 7.40] | – 7.97 [– 16.9, 1.04] 0.083 | 0.527 |
STAI Y2 | 38.0 (6.54) | 45.14 (5.19) | 7.14 (6.74) [0.39, 13.8]* | 42.0 (10.1) | 35.23 (6.84) | – 6.76 (12.3) [– 19.0, 5.57] | – 12.3 [– 21.7, – 2.9] 0.011† | 0.774 |
PMRQ P | 19.42 (3.84) | 19.71 (3.37) | 0.28 (4.28) [– 4.00, 4.57] | 19.42 (3.61) | 19.33 (3.91) | – 0.09 (4.56) [– 4.65, 4.46] | 0.48 [– 5.07, 6.04] 0.863 | 0.914 |
PMRQ R | 18.52 (3.38) | 19.71 (1.69) | 1.19 (2.59) [– 1.40, 3.78] | 20.0 (3.11) | 17.76 (3.48) | – 2.23 (3.94) [– 6.18, 1.70] | – 1.0 [– 5.67, 3.67] 0.672 | 0.653 |
PMRQ TOT | 38.0 (6.12) | 39.57 (5.72) | 1.47 (7.20) [– 5.73, 8.68] | 39.28 (7.10) | 37.23 (6.51) | – 2.04 (8.76) [– 10.8, 6.72] | – 0.21 [– 9.85, 9.43] 0.965 | 0.732 |