Summary of interventions using GRADE
| Outcome characteristics and quality | Anticipated absolute effect | ||||||
| Intervention | n (primary studies) Type of primary study | GRADE | MD (95% CI)/assessment time | Cognitive assessment instrument (max score) | Cognition improvement in percentage | I2/follow-up time | |
| Non-pharmacological | Acupuncture33 | 1421 (21) RCT (+4) | ⨁⨁◯◯ Low Due to limitations in quality and publication bias | 3.14 (2.06 to 4.21)*† 2.03 (0.26 to 3.80)*‡ 5.6 (3.95 to 7.31)* | MMSE (30) MMSE (30) NCSE (12) | 10.4% (6.8–14) 6.7% (0.8–12) 46% (32–60) | I2=36% I2=72% I2=0%/4–8 weeks |
| Virtual reality8 | 97 (4)§ RCT (+4) | ⨁⨁◯◯ Low Due to imprecision and limitations in quality | 0.45 (0.05 to 0.85)*¶ End of intervention | NA | NA | I2=14.6%/no follow-up data | |
| Transcranial magnetic stimulation37 | 281 (7)† RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, inconsistency and imprecision | 3.96 (2.44 to 5.49)* End of intervention | MMSE (30) | 13% (8–18) | I2=59.8%/NA | |
| Cognitive rehabilitation; for memory training9 | 514 (13)† RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, indirectness and imprecision | 0.25 (−0.36 to 0.86)¶ 0.21 (−0.03 to 0.46)¶ End of intervention | RBMT, Wechsler Memory Scale | NA | I2=42% I2=0%/6 weeks to 5 months | |
| Cognitive rehabilitation for attention deficits32 | 223 (6) RCT (+4) | ⨁⨁◯◯ Low Due to indirectness and imprecision | 0.67 (0.35 to 0.98)*¶ End of intervention 0.53 (−0.03 to 1.08)¶ End of intervention −0.08 (−0.35 to 0.18)¶ End of intervention | Divided attention (Paced Auditory Serial Addition Test) Global attention (cognitive failures or mental slowness) Selective attention | NA | I2=NA/NA | |
| Cognitive remediation; rehabilitation for multiple domains31 | 1098 (22) RCT (+4) | ⨁⨁⨁◯ Moderate Due to limitations in quality | 0.48 (0.35 to 0.60)*¶ End of intervention | Multiple, including MMSE (30) | NA | Q=32.9 | |
| Occupational therapy16 | 33 (1) RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, indirectness and imprecision | 17.00 (−2.46 to 36.4) End of intervention | Time judgement | NA | I2=NA/3–4 weeks | |
| Chinese herbal medicine (mailuoning)38 | 62 (1)§ RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, indirectness and publication bias | 2.68 (1.82 to 3.54)* End of intervention | MoCA (30) | 9% (6–11) | I2=NA/14 days | |
| Pharmacological | Antihypertension medication withdrawal for 7 days38 | 1784 (1)§ RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, indirectness and imprecision | 1 (0.35 to 1.65)* At 90 days | MMSE (30) | 3% (1–5) | I2=NA/16 weeks |
| Selective serotonin reuptake inhibitor39 | 425 (7)† RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, inconsistency and imprecision | 0.32 (−0.23 to 0.86)¶ End of intervention | NA | NA | I2=86%/NA | |
| Antidepressant agents34 | 82 (1)† RCT (+4) | ⨁⨁◯◯ Low Due to indirectness and imprecision | −0.30 (−3.27 to 2.67) End of intervention | MMSE (30) | −1% (−10 to 9) | I2=NA/6 weeks | |
| Physical activity | Active sessions26 | 482 (12) RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, indirectness and imprecision | 0.2 (0.04 to 0.36)*‡ End of intervention (varied) | MMSE (30) FIM SIS | 1% (0.2–3) | I2=0%/1–12 months |
| Aerobics and stretching30 | 736 (14) RCT (+4) | ⨁⨁⨁◯Moderate Due to imprecision and study limitations | 0.3 (0.14 to 0.47)*¶ Immediately after intervention | MMSE (30) MoCA (30) ACE-R | 2% (1–3) | I2=15.3%/NA | |
| Aerobics27 | 394 (10)† RCT (+4) | ⨁◯◯◯ Very low Due to limitations in quality, inconsistency and imprecision | 1.30 (0.93 to 1.67)* −0.25 (−1.3 to 0.3) 0.79 (0.08 to 1.50)* 5.14 (1.16 to 9.12)* Varied time of assessment | MoCA (30) MMSE (30) P300 wave (20) ACE-R (100) | 4% (3–5) 0.8% (−4 to 1) 4% (0.4–7) 5% (1–9) | I2=NA I2=NA I2=0% I2=NA/NA | |
| Mixed activity36 | 159 (2)§** RCT (+4) | ⨁⨁◯◯ Low Due to limitations in quality and imprecision | −0.08 (−0.47 to 0.31) End of intervention | FIM cognition (35) | −0.2% (−1 to 1) | I2=18%/4–6 months | |
| Aerobics and stretching35 | 38 (1)§ RCT (+4) | ⨁⨁◯◯ Low Due to limitations in quality and imprecision | −0.83 (−2.5 to 0.87) 0.20 (−0.44 to 0.84)¶ End of intervention | MMSE (30) FIM total | −3% (−8 to 3) | I2=NA/8 weeks | |
Our certainty level of each outcome is presented using GRADE.24
*Statistically significant.
†Short-term cognition (4 weeks).
‡Long-term cognition (8 weeks).
§Subset.
¶Standardised mean difference.
**One RCT excluded due to no follow-up data.
ACE-R, Addenbrooke's Cognitive Examination-Revised; FIM, functional independence measure; GRADE, Grading of Recommendations, Assessment, Development and Evaluations; MD, mean difference; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; NA, not available; NCSE, The Neurobehavioral Cognitive Status Examination; RBMT, Rivermead Behavioural Memory Test; RCT, randomised controlled trial; SIS, six-item screener.;