Table 2.
Summary of RCTs.
| Author (Year) country | Intervention and comparator | Sample | Assessment timepoints | Results | Summary of key findings | ||||
|---|---|---|---|---|---|---|---|---|---|
| Mean (sd) for postintervention (< 2 weeks) timepoint unless otherwise stated | |||||||||
| Size, age, sex, stage of PD | Cognitive criteria | HrQoL outcomes | Wellbeing outcomes | Functional outcomes | Primary outcome | ||||
| Kalbe et al. [29] & Schmidt et al. (2021) [30] Germany |
Cognitive training (I) versus physical activity training with psychoeducation (C); Duration: 6 weeks |
N = 64 I: 67.7 years (7.2), 72.7% M C: 67.5 years (8.3), 51.6% M H & Y: 98% Stage I–III |
PD-MCI by MDS Level II criteria and subjective cognitive impairment and/or MoCA < 2 6. Excluded PDD | Baseline; postintervention; 6 months; 12 months |
PDQ39
b
I: 35.72 (22.89); C: 34.39 (21.19) Time–group interaction nonsignificant |
Not measured |
Bayer activities of daily living scale
b
I: 3.65 (4.34); C: 2.87 (1.67) Time–group interaction nonsignificant |
Executive and memory functions—effectiveness seen for executive postintervention and memory at 6 but not 12 months | No significant change in HrQoL or ADLs. Lower baseline predicted training gains except for QoL |
| Sousa et al. [31] Brazil |
Cognitive training (I) versus general rehabilitation programme (C) Duration: 4 weeks. |
N = 39 I: 60 years (7.5), 83% M, 13% H & Y Stage III, Rest I–II C: 58.5 years ACT (9.8), 87% M, 7% H & Y Stage III, Rest I–II |
PD-MCI according to MDS Level II diagnostic criteria | Baseline; postintervention |
PDQ39
b
I: 29.72 (15.29); C: 32.13 (17.74)c Change in score: I: t = 2.275, p=0.0229 C: t = 1.889, p=0.0588 |
Not measured | Not measured | Not specified | Pre–post improvement in HrQoL for intervention group. Significance of between-group changes is not reported. |
| Bernini et al. [32] Italy |
Cognitive training + physical rehabilitation (I) versus standard physical rehabilitation (C) Duration: 4 weeks. |
N = 41 I: 71.2 years (7.0), 30% M, H & Y 2.8 (0.96) C: 69.3 years (7.7), 61% M H & Y 2.9 (0.47) |
PD-MCI single or multiple domains but must include executive domain on level II criteria | Baseline; postintervention; 6 months |
PDQ-8
b at 6 months I: 39.7 (21.4); C: 39.2 (21.6) |
Not measured | Not measured | Cognition–effective. | No significant effect for HrQoL at 6 months. |
| Lawrence et al. [33] Australia |
Standard cognitive training (sCT) versus tailored cognitive training (tCT) versus sCT + tDCS versus tCT + tDCS versus tDCS alone versus control (no intervention) (C) Duration: 4 weeks |
Total n = 42; n = 21 included in this review (CT and control) sCT: 68.1 year (8.7), 57% M tCT: 65.6 years (5.2), 43% M C: 72.3 years (6.2), 43% M H & Y not reported |
PD-MCI (MDS Level II criteria); cognitive deficits that did not interfere with functional independence | Baseline; postintervention; 12 weeks | PDQ-39b sCT: 20.68 (10.76); tCT: 18.09 (5.19); C: 23.76 (14.92) Interaction∗ (F = 2.96, p=0.003): improvement in sCT (F = 7.21, p=0.001) and tCT (F = 12.48, p < 0.001) only |
Not measured |
UPDRS-II
b
sCT: 0.73 (0.74); tCT: T1 0.80 (0.40); C: 1.25 (0.94). Interaction∗ (F = 1.96, p=0.04): improvement in sCT only (F = 11.29, p < 0.001) and sCT + tDCS (F = 3.40, p=0.04) |
(Implied) Cognition and ‘practical outcomes'—cognitive training effective for cognition |
Significant improvement for HrQoL with sCT and tCT compared to other arms. Significant improvement in ADLs with sCT (with and without tDCS) compared to other arms |
| Folkerts et al. [34] The Netherlands |
Cognitive stimulation (I) versus usual care (C) Duration: 8 weeks |
N = 12 I: 76.7 years (5.6), 83% M, H & Y Stage II–III 33%, stage > III 67% C: 76.5 (8.9), 83% M H & Y Stage II–III 50%, > III 50% |
Residents of PDD-specific long-term care unit; MMSE 10–25 | Baseline; postintervention; 6 weeks. Crossover design (so no control at 6 weeks follow-up) |
EQ-5D-5L Index
a
c
I: 0.59 (0.31); C: 0.67 (0.30) EQ-5D-5L VASac I: 63.50 (11.50); C: 50.83 (26.35) QUALIDEM totalac I: 17.80 (3.21), C: 16.19 (1.67) |
Not measured |
Median
Barthel Index a c I: 12.27 (5.29); C:14.67 (4.13) |
Feasibility–Feasible. ‘Main outcomes': global cognition, neuropsychiatric symptoms, depression, ADLs, QoL, nonsignificant. |
No significant group difference for QoL or ADLs. |
|
| |||||||||
| Leroi et al. [35] UK |
Cognitive stimulation (I) versus treatment as usual (C) Duration: 12 weeks. |
N = 76.15 PD-MCI, 40 PDD, 21 DLB Median (IQR) I: 74.5 years (68–77), 79% M C: 75 years (72–81), 79% M H & Y not reported |
MDS criteria: PD-MCI: Level 1 criteria; PDD: Probable or possible; DLB: Probable or possible | Baseline; postintervention | Change from baseline, mean (sd) | Feasibility measures– feasible, acceptable and well-tolerated [36] | No significant changes for HrQoL, wellbeing or function | ||
|
PDQ-39
b
I: 38.29 (13.39); C: 29.31 (13.74) Adj mean diffd (I:C) 0.91, p=0.382 EuroQoL Indexa I: 0.57 (0.32); 0.57 (0.32) Adj mean diffd (I:C) = 0.05, p=0.241EuroQoLVASa I: 62.30 (17.94); C: 62.35 (22.22) Adj mean diffd (I:C) = 1.75, p=0.370 |
Relatives stress scale (RSS)
I: 32.48 (9.69); C: 35.20 (7.02) Adj mean diffd (I:C) −1.25, p=0.215 Brief resilience scale (BRS) I: 20.33 (4.89); C: 20.97 (5.18) Adj mean diffd (I:C) = −1.17, p=0.174 |
Pill questionnaire
b
I: 1.96 (1.30); C: 2.06 (1.01) Adj mean diffϮ (I:C) −0.05, p=0.435 |
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| Hindle et al. [37] UK |
Cognitive rehabilitation (CR) versus relaxation therapy (RT) versus treatment as usual (TAU) Duration: 8 weeks. |
N = 29 I: 75.8 years (6.6), 80% M RT: 74.9 years (6.9), 70% M TAU: 78.6 years (5.8), 89% M 90% H & Y Stage I–III; 10% Stage IV |
PDD or DLB diagnosed according to Movement Disorders Society consensus criteria and ACE-III ≤ 82 | Baseline; postintervention (T1); 6 months (T2) |
WHOQOL-BREF
a
-physical CR 12.5 (3.12); RT 12.33 (18.87); TAU 10.26 (2.69). p > 0.05 (T1 and 2) - psych CR 13.25 (8.82); RT 12.44 (2.13); TAU 10.44 (2.79), p > 0.05 (T1 and 2) - environ CR 16.13 (2.23); RT 15.33 (1.22); TAU 14.99 (2.38), p > 0.05 (T1 and 2) - social∗ CR 15.85 (2.31); RT 14.78 (3.27); TAU 14.06 (4.30) ES d (95% CI) at T1: CR versus TAU 1.11 (0.09–2.14) p=0.039, CR versus RT 1.13 (0.1–2.16) p=0.037 (T2 p > 0.05) PDQ-8b CR 29.3 (10.95) RT 31.94 (10.34) TAU 47.57 (16.3) T1: p > 0.05 [T2∗: F(1,18) = 5.2, p=0.02)] EQ5D3La(T2) -index∗ CR 0.59 (0.31); RT 0.56 (0.31); TAU 0.13 (0.26) F(1,18) = 5.23, p=0.02, ES d (95% CI) CR versus TAU 1.74 (0.59–2.9) p=0.007 -VAS CR 67.86 (17.53); RT 57.22 (18.56); TAU 46.11 (17.82) |
Generalised self-efficacy scale (GSES)
a
CR 31.5 (4.24); RT 28.22 (5.56); TAU 28.86 (2.5) ES d (95% CI): CR versus RT 1.07 (0.06–2.09) p=0.041∗ |
Modified-functional activities questionnaire (FAQ)b (T2) CR: 13.57 (7.87); RT: 13.44 (8.29); TAU: 17 (8.59). Nonsignificant |
Goal Attainment and satisfaction with goal attainment–effective | Significant improvement for QoL and self-efficacy with intervention compared to controls. For postintervention: WHOQOL-BREF social and self-efficacy significant. For 6-month follow-up: HrQoL (PDQ-8) and subjective health status (EQ-5D-3L) significant; ADLs not significant. |
|
| |||||||||
| Vlagsma et al. [38] Netherlands |
Cognitive rehabilitation with strategy training ‘ReSET' (I) versus cognitive training ‘CogniPlus' (C) Duration 7–14 weeks. |
N = 43 I: 60.2 years (10.4), 58% M, H & Y 2.4 (0.6) C: 62.6 (8.8), 68% M, H & Y 2.2 (0.4) |
Problems in executive function in everyday life: semistructured interview and/or ≥ 18 on DEX + impairment on EF tests | Baseline; 2 weeks postintervention; 3–5 months |
PDQ-39
b
I: 43.71(19.78) C: 52.06(24.16) Time–group interaction: f = 0.57 p=0.454, np2 = 0.01 |
Not measured |
Brock adaptive functioning questionnaire (BAFQ)
b [Self-score] I: 2.78 (0.48); C: 2.41 (0.52) Time–group interaction: f = 0.00, p=0.969, np2 = 0.00 |
Role Resumption list (participation in different societal domains)–no significant differences. | No significant difference in function or HrQoL |
| Reuter et al. [39] Germany |
Inpatient multimodal cognitive rehabilitation: Cognitive training + transfer training + psychomotor and endurance training (I) versus cognitive training (C1) versus cognitive training + transfer training (C2) Duration: Active rehab Phase 4 weeks; home continuation Phase 6 months |
N = 240 All: 64 years (4) I: 53% M, 89% H & Y II–III, others IV C1: 51% M, 87% H & Y II–III, others IV C2: 52% M, 87% H & Y II–III, others IV |
PD-MCI: Cognitive decline symptoms, preferably corroborated, end cognitive abnormalities which cannot be simply attributed to age but with minimal effect on daily function and no dementia | Baseline; post-inpatient intervention; at 6 months (after home training) |
6 months: PDQ-39
b
Numerical outcome data not provided. % Of participants showing improvement: 13.8% (C1), 38% (C2), 52% (I). Group difference significant (in favour of intervention) for mobility and ADL domains (p < 0.001), emotional perception, stigma and cognition (p < 0.01) and social support (p < 0.05) |
Not measured | Participants and caregivers reported improvement in ADLs in an evaluation of the intervention but no specific ADL measure reported. | ADAS-COG. All groups improved significantly, with a significant group interaction in favour of the intervention | Significant improvement in various HrQoL domains compared to active controls |
| Jung et al. [40] USA |
Physical and cognitive exercise (agility boot camp with cognitive challenge, ABC-C) (I) versus education/self-management + relaxation (C) Duration: 6 weeks |
Total n = 86; n = 28 included (MCI) Demographics of whole sample: 68.8 years (7.6); 67% M; H & Y Stage I–III 91%, H & Y Stage IV 9% |
No cognitive criteria. Secondary analysis stratified by cognition: SCOPA-COG < 27 as MCI |
Baseline; between interventions; after both intervention crossover trial | Reported as score change: Mean (standard error) | Balance-Improvement after exercise but not education | No significant improvement in ADLs or HrQoL for MCI subgroup. Note, measures taken in ‘off'-state |
||
|
PDQ39
b
I: −0.22 (1.39); C: −1.56 (0.96) β = −1.43 (CI -4.67-1.80), p=0.04 |
Not measured | MDS-UPDRS part IIb I:-0.95 (0.87); C: −0.52 (0.83) β = 0.26 (CI-2.01–2.54), p=0.8 |
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| Giguere-Rancourt et al. [41] Canada |
Goal management training (I1) versus psychoeducation with mindfulness (I2) Duration: 5 weeks. |
N = 12 I1: 71.0 years (4.0), 83% M; H & Y 1.9 (0.6) I2: 70.0 years (5.1), 83% M; H & Y 1.7 (0.8) |
PD-MCI by MDS diagnostic criteria inclusive of executive dysfunction, and MoCA 21–27. Excluded PDD | Baseline; midintervention; 1 week post; 4 weeks; 12 weeks post |
PDQ39
b
I1: 31.48 (SE 5.88); I2: 20.14 (SE 5.58)c Time–group interaction∗: F(4,36) = 5.31, p=0.002, (95%CI = 15.33–25.61), n2 = 0.066 (medium ES in favour of I2) |
Not measured | Not measured | Executive function—Improvement in both groups, group difference not significant | Significant improvement in HrQoL in psychoeducation with mindfulness group over goal management training group |
Abbreviations: C = control group, EF = executive function, ES = effect size, H & Y = Hoehn & Yahr stage, tDCS = transcranial direct current stimulation, I = intervention group, M = male.
aHigher = better, blower = better, cdata obtained from authors, dadjusted mean difference, adjusted for baseline outcome value.
∗Statistically significant at p < 0.05.