Table 2.
Characteristics of the primary studies included in the meta-analysis.
| Study | Diagnostic criteria for PD | RBD assessment | Participants (n men) | Age (years) | PD duration (years) | Edu | UPDRS-III | H&Y stage | LEDD (mg) | Analyzed cognitive tests |
|---|---|---|---|---|---|---|---|---|---|---|
| CONFIRMED-RBD | ||||||||||
| Arnaldi et al. (54) | Clinical criteria Gelb et al. (43) | PSG + clinical evaluation (ICSD-2) | 24 RBD+ (16) | 69.4 ± 6.0 | NM | 10.3 ± 4.6 | 14.1 ± 5.7 | NM | 0 | MMSE |
| 16 RBD– (8) | 67.2 ± 7.2 | NM | 11.8 ± 5.0 | 9.5 ± 3.5 | NM | 0 | ||||
| Gagnon et al. (57) | NM | PSG | 7 RBD+ (6) | 68.4 ± 7.5 | 5.4 ± 6.0 | NM | NM | 1.8 ± 0.8 | 313.6 ± 184.8 | MMSE |
| 8 RBD– (3) | 61.0 ± 7.3 | 5.5 ± 2.9 | NM | NM | 1.8 ± 0.7 | 277.3 ± 148.0 | ||||
| Gagnon et al. (82) | PDSBB | PSG (ICSD-2) | 22 RBD+ 18 RBD– |
66.4 ± 8.5 65.2 ± 8.9 |
4.9 ± 3.5 5.8 ± 3.2 |
14.7 ± 3.9 15.4 ± 2.1 |
18.6 ± 7.7 17.3 ± 11.0 |
2.0 ± 0.8 2.1 ± 0.8 |
392.6 ± 363.6 353.6 ± 324.4 |
RAVLT, delayed recall; RAVLT, recognition; SVF; DSB; TMT: B; Stroop errors; ROCF, copy |
| Gaudreault et al. (58) | PDSBB | PSG (ICSD-2) | 16 RBD+ (11) | 64.7 ± 8.0 | 5.4 ± 3.5 | 14.8 ± 4.1 | 18.1 ± 8.6 | 2.1 ± 0.8 | 506.1 ± 383.3 | MMSE |
| 15 RBD– (9) | 63.1 ± 6.0 | 5.4 ± 3.8 | 14.5 ± 3.3 | 20.7 ± 9.7 | 2.2 ± 0.8 | 398.4 ± 273.7 | ||||
| Huang et al. (60) | PDSBB | PSG + clinical evaluation (ICSD-3) | 92 RBD+ (68) | 65.1 ± 5.8 | 3.0 (1.0–5.0)b | 8.4 ± 3.5 | 24.3 ± 10.0 | 2.0 (1.5–2.5)b | 300.0 (100.0–450.0)b | MOCA |
| 82 RBD– (45) | 64.0 ± 9.3 | 3.0 (1.0–5.0)b | 8.8 ± 3.2 | 23.7 ± 11.5 | 2.0 (1.5–2.5)b | 300.0 (100.0–450.0)b | ||||
| Jozwiak et al. (5) | NM | PSG (ICSD-2) | 53 RBD+ (40) 40 RBD– (21) |
68.0 ± 8.4 63.2 ± 8.5 |
6.1 ± 4.5 6.1 ± 4.3 |
14.5 ± 3.9 15.1 ± 3.0 |
23.1 ± 9.5 20.3 ± 9.8 |
2.5 ± 0.8 2.2 ± 0.9 |
492.2 ± 402.3 383.7 ± 283.3 |
MMSE; vocabulary; RAVLT, delayed recall; RAVLT, recognition; ROCF, delayed recall; SVF; TMT: B; Stroop errors; TMT: A; ROCF, Copy |
| Kamble et al. (61) | PDSBB | MSQ + RBDSQ + PSG |
25 RBD+ | 60.4 ± 8.2 | 6.8 ± 4.6 | NM | 27.4 ± 11.1 | NM | 535 ± 178.9 | MOCA; story recall (delayed); CBTT; FAB; DSB; SVF; DSF |
| 25 RBD– | 57.3 ± 6.6 | 7.5 ± 3.5 | NM | 32.7 ± 8.22 | NM | 754 ± 349.7 | ||||
| Kim et al. (63) | PDSBB | PSG + RBDSQ-K | 9 RBD+ (0) | 70.1 ± 6.8 | 1.9 ± 1.5 | 2.4 ± 2.5 | NM | NM | NM | K-MMSE |
| 22 RBD– (10) | 67.7 ± 8.4 | 1.9 ± 1.4 | 8.5 ± 4.8 | NM | NM | NM | ||||
| Marques et al. (66) | Clinical criteria Gelb et al. (43) |
PSG | 10 RBD+ (3) 10 RBD– (3) |
64 ± 2.9 59 ± 2.6 |
7.6 ± 1.7 8.1 ± 3.7 |
10 ± 0.6 10 ± 0.9 |
NM NM |
NM NM |
703 ± 157 435 ± 133 |
MMSE; Number of words correctly encoded; DSB; LNS; Stroop color-word; SVF; SDMT; DSF |
| Nardone et al. (67) | NM | PSG + clinical evaluation (ICSD-2) | 10 RBD+ (8) | 65.9 ± 6.5 | 5.0 ± 2.3 | 10.1 ± 3.8 | 17.5 ± 4.3 | NM | 578 ± 2.9 | MMSE |
| 13 RBD– (9) | 63.7 ± 6.4 | 6.0 ± 2.8 | 10.5 ± 3.7 | 18.3 ± 4.3 | NM | 627 ± 341 | ||||
| Nomura et al. (15) | NM | PSG + interview | 18 RBD+ (5) | 71.3 ± 8.3 | 9.0 ± 4.7 | NM | NM | 3.0 ± 0.9 | 408 ± 214 | MMSE |
| 23 RBD– (10) | 71.5 ± 7.2 | 5.3 ± 4.8 | NM | NM | 2.7 ± 0.9 | 347 ± 199 | ||||
| Nomura et al. (68) | PDSBB | PSG + interview | 27 RBD+ (14) | 76.5 ± 5.9 | 8.8 ± 5.2 | NM | NM | 3.0 ± 0.8 | 455 ± 230 | MMSE |
| 32 RBD– (14) | 74.5 ± 8.1 | 7.0 ± 8.2 | NM | NM | 2.5 ± 0.6 | 233 ± 150 | ||||
| Nomura et al. (70) | PDSBB | PSG + clinical evaluation (ICSD-3) | 47 RBD+ (26) | 73.1 ± 7.3 | 9.0 ± 6.0 | NM | NM | 3.0 ± 0.8 | 437 ± 250 | MMSE |
| 89 RBD– (35) | 71.1 ± 7.8 | 5.7 ± 6.8 | NM | NM | 2.5 ± 0.7 | 250 ± 199 | ||||
| Plomhause et al. (71) | Clinical criteria Gibb and Lees (45) |
PSG + clinical evaluation (ICSD-2) | 17 RBD+ (8) | 65 ± 8 | 11 ± 4c | NM | 14 ± 8 | NM | 0 | MDRS |
| 40 RBD– (27) | 60 ± 12 | 15 ± 12c | NM | 15 ± 6 | NM | 0 | ||||
| Plomhause et al. (72) | Clinical criteria Gelb et al. (43) |
PSG + clinical evaluation (ICSD-2) | 15 RBD+ (14) | 63.2 ± 7.7 | 7.0 ± 3.7 | 11.8 ± 3.9 | 18.8 ± 8.6 | NM | 435.1 ± 171.1 | MDRS; Lexis denomination task |
| 15 RBD– (11) | 61.4 ± 7.5 | 4.1 ± 3.2 | 10.5 ± 1.7 | 19.8 ± 6.5 | NM | 633.0 ± 342.3 | ||||
| Postuma et al. (73) | PDSBB | PSG + clinical evaluation (ICSD-2) | 27 RBD+ (23) | 70.5 ± 7.4 | 9.7 ± 4.3 | NM | 34.1 ± 16.5 | NM | NM | MOCA |
| 15 RBD– (11) | 67.5 ± 10.5 | 9.5 ± 4.8 | NM | 26.2 ± 16.2 | NM | NM | ||||
| Sixel-Doring et al. (16) | PDSBB | PSG | 210 RBD+ (62) | 69 ± 8 | 8.7 ± 4.4 | 5.2 ± 4.6 | 30 ± 14 | 3.2 ± 1.1 | 500.6 ± 375.3 | MMSE |
| 247 RBD– (64) | 66 ± 11 | 7.3 ± 5.6 | 4.2 ± 3.6 | 28 ± 15 | 2.9 ± 0.9 | 422.9 ± 330.4 | ||||
| Vendette et al. (35) | PDSBB | PSG + clinical evaluation (ICSD-2) | 18 RBD+ 16 RBD– |
65.61 ± 7.73 65.13 ± 7.69 |
5.2 ± 2.3 6.0 ± 3.2 |
15.0 ± 3.7 15.8 ± 1.9 |
17.3 ± 7.7Δ 15.6 ± 10.7Δ |
2.06 ± 0.78 2.22 ± 0.77 |
417.2 ± 425.6 399.8 ± 315.0 |
MMSE; RAVLT, delayed recall; RAVLT, recognition; SVF; TMT: B; Stroop errors; TMT: A; ROCF, Copy |
| PROBABLE-RBD | ||||||||||
| Ba et al. (75) | Clinical criteriaa + DAT imaging deficit | RBDSQ (>5) | 136 RBD+ (92) 214 RBD– (137) |
61.2 ± 9.4 60.4 ± 9.9 |
7.51 ± 6.69c 7.35 ± 6.29c |
15.6 ± 2.9 15.6 ± 3.0 |
21.6 ± 9.4 19.6 ± 8.4 |
1.6 ± 0.5 1.5 ± 0.5 |
0 0 |
MOCA; HVLT, total recall; HVLT, Recognition; SVF; SDMT; LNS; BJLOT |
| Boucetta et al. (76) | Clinical criteriaa | RBDSQ (≥5) + positive response to item 5, 6.3 or 6.4 |
69 RBD+ (52) 240 RBD– (149) |
60.9 ± 9.2 61.6 ± 9.8 |
6.3 ± 6.6c 6.9 ± 6.7c |
15.9 ± 2.3 15.6 ± 2.9 |
22.5 ± 9.5 |
NM NM |
0 0 |
MOCA; SVF; SDMT; BJLOT |
| Chahine et al. (31) | Clinical criteriaa + DAT imaging deficit | RBDSQ (≥6) | 108 RBD+ (79) 315 RBD– (198) |
61.9 ± 9.9 61.7 ± 9.7 |
0.25 (0.17–0.59)b 0.34 (0.25–0.67)b |
15.3 ± 2.9 15.6 ± 3.0 |
22.0 ± 8.8 20.5 ± 8.9 |
NM NM |
0 0 |
MOCA; HVLT-R, delayed free recall; HVLT-R, recognition; SVF; SDMT; LNS; BJLOT |
| Duarte Folle et al. (55) | NM | Interview | 160 RBD+ (122) | 70.0 ± 9.6 | 3.5 ± 3.1 | 14.3 ± 3.7 | 23.4 ± 2.5 | ≥3, N = 25 | 459 ± 349 | MMSE |
| 616 RBD– (371) | 70.6 ± 10.4 | 3 ± 2.5 | 13.6 ± 4.7 | 22.6 ± 2.4 | ≥3, N = 99 | 388 ± 332 | ||||
| Ford et al. (56) | PDSBB | MSQ | 46 RBD+ (36) | 66.4 ± 9.9 | 6.5 ± 5.1c | 13.0 ± 3.6 | 26.3 ± 10.0 | 2.2 ± 0.7 | 179.2 ± 144.7 | MMSE |
| 78 RBD– (48) | 65.8 ± 10.9 | 6.0 ± 4.4c | 13.0 ± 4.1 | 27.3 ± 11.9 | 1.9 ± 0.6 | 172.6 ± 128.2 | ||||
| Gjerstad et al. (59) | Clinical criteria (93) |
SSQ | 34 RBD+ (25) | 71.6 ± 7.9 | 11.1 ± 6.2 | NM | 29.5 ± 15.8 | 3.0 ± 1.1 | 626 ± 312 | MMSE |
| 197 RBD– (89) | 73.7 ± 8.5 | 8.6 ± 5.5 | NM | 28.2 ± 15.9 | 2.8 ± 1.0 | 452 ± 236 | ||||
| Kim et al. (62) | PDSBB | ICSD-R | 578 RBD+ (266) | 64.6 ± 8.8 | 7.66 ± 4.66 | NM | NM | 2.25b | 795.3 ± 406.2 | MMSE; FAB |
| 366 RBD– (182) | 62.2 ± 10.0 | 6.21 ± 3.91 | NM | NM | 2.03b | 693.0 ± 421.6 | ||||
| Kotagal et al. (77) | PDSBB + DTBZ PET imaging | MSQ | 27 RBD+ (25) | 63.4 ± 6.7 | 6.4 ± 3.7 | NM | 27.6 ± 10.9 | 2.3 ± 0.4 | NM | MOCA |
| 53 RBD– (35) | 65.3 ± 7.1 | 5.8 ± 4.0 | NM | 25.1 ± 11.2 | 2.3 ± 0.5 | NM | ||||
| Lavault et al. (28) | PDSBB | Interview | 39 RBD+ (26) | 66.6 ± 7.9 | 7.5 ± 5.1 | NM | 22.0 ± 12.4 | NM | 576 ± 353 | MMSE; FAB |
| 22 RBD– (13) | 60.3 ± 11.1 | 5.8 ± 3.9 | NM | 13.5 ± 6.5 | NM | 649 ± 403 | ||||
| Lee et al. (8) | PDSBB | ICSD-R | 164 RBD+ (79) | 65.1 ± 8.4 | 7.28 ± 5.18 | NM | 20.3 ± 10.4 | 2.2 ± 0.7 | 527 ± 292 | MMSE |
| 283 RBD– (128) | 63.1 ± 9.6 | 5.47 ± 4.16 | NM | 18.2 ± 11.2 | 2.1 ± 0.6 | 485 ± 285 | ||||
| Lim et al. (64) | PDSBB | RBDSQ + PSG (partial confirmation) |
24 RBD+ (12) | 69.8 ± 6.4 | 6.2 ± 2.9 | NM | 12.4 ± 2.5 | 1.9 ± 0.4 | NM | MMSE |
| 14 RBD– (8) | 69.7 ± 7.2 | 4.4 ± 3.7 | NM | 22.4 ± 10.6 | 1.6 ± 0.5 | NM | ||||
| Liu et al. (78) | PDSBB | RBDSQ (≥5) | 31 RBD+ (14) | 60.4 ± 10.8 | 2.71 ± 3.52 | 9.2 ± 3.8 | 21.3 ± 9.0 | 1.9 ± 0.5 | 0 | MOCA |
| 127 RBD– (61) | 58.3 ± 10.4 | 1.90 ± 1.72 | 10.3 ± 3.9 | 20.1 ± 10.9 | 2.0 ± 0.4 | 0 | ||||
| Mahale et al. (65) | Queen Square Brain Bank criteria | RBDSQ | 10 RBD+ (0) | 62.5 ± 10.3 | 4.1 ± 2.8 | NM | 27.5 ± 9.9 | 2.4b | 675.0 ± 521.5 | MMSE |
| 27 RBD– (0) | 51.2 ± 10.7 | 5.3 ± 4.9 | NM | 31.0 ± 9.7 | 2.3b | 588.5 ± 313.5 | ||||
| Meral et al. (81) | PDSBB | Interview (ICSD) | 36 RBD+ (24) 43 RBD– (26) |
66.5 ± 8.79 67.6 ± 8.5 |
7.27 ± 3.59 5.60 ± 3.65 |
NM NM |
23.3 ± 11.5 17.5 ± 11.0 |
NA NA |
423.2 ± 198.8 339.0 ± 245.9 |
STMS; WMS, delayed recall; SBST, recognition; SBST, delayed recall; SVF; stroop error; WCST, category; BJLOT |
| Naismith et al. (34) | PDSBB | RBDSQ (≥5) | 51 RBD+ 47 RBD– |
65.5 ± 7.2 65.0 ± 9.7 |
6.8 ± 5.7 4.6 ± 4.4 |
13.3 ± 2.9 14.2 ± 3.3 |
NM NM |
2.2 ± 0.7 2.2 ± 0.7 |
773.3 ± 577.7 512.9 ± 551.1 |
MMSE; Logical memory, encoding; DSB; TMT: B-A |
| Nomura et al. (69) | PDSBB | RBDSQ-J (≥6) | 27 RBD+ (15) | 68.8 ± 8.6 | 9.1 ± 7.7 | NM | NM | 2.8 ± 0.7 | 500 ± 351 | MOCA |
| 43 RBD– (16) | 69.4 ± 8.6 | 6.4 ± 5.2 | NM | NM | 2.5 ± 0.9 | 322 ± 243 | ||||
| Pagano et al. (79) | Clinical criteriaa + DAT imaging deficit | RBDSQ (≥5) | 158 RBD+ (109) 263 RBD– (166) |
61.8 ± 9.7 61.5 ± 9.8 |
6.5 ± 6.5c 6.7 ± 6.6c |
15.6 ± 2.9 15.5 ± 3.0 |
20.9 ± 8.8 20.4 ± 8.8 |
1.54 ± 0.50 1.58 ± 0.51 |
0 |
MOCA; HVLT, immediate recall; HVLT, delayed recognition; SVF; LNS; SDMT; BJLOT |
| Rahmani et al. (80) | Clinical criteriaa | RBDSQ | 10 RBD+ (8) | 61 ± 8.15 | NM | 15.8 ± 3.1 | 18.9 ± 10.8 | NM | NM | MOCA |
| 7 RBD– (6) | 64 ± 6.6 | NM | 14.4 ± 3.4 | 24.5 ± 6.9 | NM | NM | ||||
| Rolinski et al. (33) | PDSBB | RBDSQ | 224 RBD+ (148) | 67.5 ± 9.4 | 1.6 ± 1.0 | NM | 26.8 ± 10.6 | 1.9 ± 0.5 | 345.2 ± 189.6 | MOCA; SVF |
| 251 RBD– (144) | 67.9 ± 9.5 | 1.4 ± 1.0 | NM | 26.9 ± 11.2 | 1.9 ± 0.5 | 322.9 ± 196.7 | ||||
| Sinforiani et al. (19) | PDSBB | Clinical evaluation (ICSD) | 79 RBD+ (46) 31 RBD– (19) |
68.0 ± 8.4 63.0 ± 8.2 |
10.3 ± 4.9 9.5 ± 4.5 |
NM NM |
47.7 ± 12.6 35.2 ± 10.3 |
3.5b 3b |
1087.9 ± 442.3 1114.5 ± 270.4 |
MMSE; CBTT; DSF; Logical memory test; FAB |
| Zhang et al. (74) | PDSBB | MSQ + RBDSQ + PSG (partial confirmation) | 32 RBD+ (23) 42 RBD– (20) |
64.9 ± 5.2 62.2 ± 8.3 |
4.0 ± 2.5 4.2 ± 2.7 |
9.5 ± 2.3 9.8 ± 2.6 |
19.8 ± 12.0 20.0 ± 9.6 |
2.0 (1.5–2.5)b 2.0 (1.5–2.5)b |
292.3 ± 210.2 298.2 ± 237.2 |
MOCA; SVF; RAVLT, delayed recall; RAVLT, recognition; ROCF, recall; DSB; TMT: B, time; Stroop time; DSF; TMT: A; SDMT; ROCF, Copy |
Data are shown as the mean ± SD unless otherwise noted.
PD, Parkinson's disease; RBD, REM sleep behavior disorder; Edu, education; UPDRS III, Unified Parkinson's Disease Rating Scale, part 3; H&Y stage, Hoehn and Yahr stage; LEDD, levodopa equivalent daily dose; PSG, polysomnography; ICSD-2, second edition of the International Classification of Sleep Disorders; NM, not mentioned; MMSE, Mini-Mental State Examination; PDSBB, U.K. Parkinson's Disease Society Brain Bank criteria; RAVLT, Rey auditory–verbal learning test; SVF, semantic/category verbal fluency test; DSB, digit span backward; TMT: B, trail making test: part B; ROCF, Rey–Osterrieth complex figure test; ICSD-3, third edition of the International Classification of Sleep Disorders; MOCA, Montreal Cognitive Assessment; TMT: A, trail making test: part A; MSQ, Mayo Sleep Questionnaire; RBDSQ, REM Sleep Behavior Disorder Screening Questionnaire; CBTT, Corsi's block tapping test; FAB, frontal assessment battery; DSF, digit span forward; RBDSQ-K, Korean version of REM Sleep Behavior Disorder Screening Questionnaire; K-MMSE, Korean version of the Mini-Mental State Examination; LNS, letter–number sequencing; SDMT, symbol digit modalities test; MDRS, Mattis Dementia Rating Scale; DAT, dopamine transporter; HVLT, Hopkins Verbal Learning Test; BJLOT, Benton judgment of line orientation test; HVLT-R, Hopkins Verbal Learning Test—Revised; SSQ, Stavanger Sleepiness Questionnaire; ICSD-R, International Classification of Sleep Disorders—Revised; DTBZ, dopaminergic denervation on [11C]dihydrotetrabenazine; STMS, Short Test of Mental Status; WMS, Wechsler Memory Scale; SBST, sözel bellek surecleri testi; WCST, Wisconsin Card Sorting Test; TMT: B-A, trail making test: part B–part A; RBDSQ-J, Japanese version of REM Sleep Behavior Disorder Screening Questionnaire.
a
All clinical data were extracted from the PPMI database. Further information is described in detail at http://www.ppmi-info.org.
b
Median (IQR).
c
Months.