Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Selection
2.3. Study Quality Assessment
2.4. Data Extraction and Analysis
3. Results
3.1. Study Selection and Characteristics
3.2. Quality Assessment
3.3. Primary Outcome
3.4. MMSE
3.5. ADAS-Cog
3.6. NPI
3.7. Word-Recognition Task
3.8. FDS
3.9. Clock Drawing Test
3.10. Subgroup Analysis and Meta-Regression
3.11. Sensitivity Analysis and Publication Bias
3.12. Secondary Results
4. Discussion
5. Limitations
6. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Study (Time) | Sample Size | Design | Diagnosis | Gender (M/F) | Age (y) | Education (y) | Duration of Disease(y) | Outcomes for Cognition Function |
---|---|---|---|---|---|---|---|---|
Boggio et al. (2012) [51] | NE:15 NC:15 | Crossover | AD | 8/7 | 78.95 ± 8.07 | 14.42 ± 3.65 | 4.39 ± 1.88 | MMSE, VAT, ADAS-Cog, Word recall, Word recognition, Instruction remembering, VRT |
Bystad et al. (2016) [37] | NE:12 NC:13 | Parallel | AD | 7/5 7/6 | 70.0 ± 8.0 75.0 ± 8.7 | NR | NR | CVLT-II, MMSE, Clock-drawing test, TMT-A, TMT-B |
Cotelli et al. (2014) [38] | NE:12 NC:12 | Parallel | AD | 2/10 3/9 | 76.6 ± 4.6 74.7 ± 6.1 | 5.5 ± 2.4 8.9 ± 5.1 | NR | FNAT, MMSE, Tinetti balance scale, Tinetti gait scale, NPI, Picture naming task, BADA, Rivermead behavioral memory test, Rey auditory verbal learning test, TMT-A, TMT-B |
Das et al. (2019) [39] | NE:12 NC:10 | Parallel | MCI | 8/4 8/2 | 62.58 ± 8.43 63.30 ± 7.38 | 17.92 ± 3.94 16.20 ± 1.75 | NR | TOSL, DKEFS, CVLT, MMQ |
Ferrucci et al. (2008) [17] | NEa:10 NEb:10 NC:10 | Crossover | AD | 3/7 | 75.2 ± 7.3 | 10.9 ± 4.8 | NR | Word recognition task, VAT |
Gangemi(a) et al. (2021) [40] | NE:13 NC:13 | Parallel | AD | NR | 67.5 ± 2.8 69.01 ± 3.1 | 6.5 ± 2.0 6.1 ± 2.1 | NR | MMSE, MODA |
Gangemi(b) et al. (2021) [40] | NE:9 NC:9 | Parallel | AD | NR | 68.5 ± 2.8 68.7 ± 3.1 | 6.7 ± 2.0 6.2 ± 2.7 | NR | MMSE, MODA |
Gomes et al. (2019) [41] | NE:29 NC:29 | Parallel | MCI | 9/20 7/22 | 73.0 ± 9.2 71.6 ± 7.9 | NR | NR | CAMCOG, MMSE, TMT-A, TMT-B, SVF, BNT, Clock-drawing test, WLMT, WAIS, N-back, FDS, BDS |
Im et al. (2019) [42] | NE:11 NC:7 | Parallel | MCI | 1/10 2/5 | 71.9 ± 9.2 74.9 ± 5.0 | 6.3 ± 3.8 5.4 ± 5.9 | NR | MMSE, FDS, BDS, BNT, SVLT, COWAT, RCFT, Contrasting Program, Go-no go Test, Stroop Test, Clock-drawing test |
Inagawa et al. (2019) [43] | NE:7 NC:13 | Parallel | AD | 3/4 7/6 | 76.6 ± 5.7 76.2 ± 7.7 | NR | 0.9 ± 1.2 1.2 ± 1.5 | ADAS-Cog, MMSE, FAB |
Khedr et al. (2014) [44] | NEa:11 NEb:12 NC:11 | Parallel | AD | 6/5 8/4 5/6 | 68.5 ± 7.2 70.7 ± 5.4 67.3 ± 5.9 | NR | 3.0 ± 2.6 2.9 ± 1.9 3.5 ± 1.7 | MMSE, WAIS |
Khedr et al. (2019) [45] | NE:23 NC:21 | Parallel | AD | 13/10 13/8 | 64.22 ± 3.64 65.23 ± 4.52 | 1.17 ± 0.48 1.17 ± 0.39 | 4.04 ± 2.83 3.52 ± 1.96 | MMSE, Clock-drawing test, MoCA |
Lu et al. (2019) [46] | NE:69 NC:64 | Parallel | AD | 21/42 17/36 | 74.2 ± 6.7 74.5 ± 6.6 | 7.3 ± 4.8 6.5 ± 4.3 | NR | ADAS-Cog, MMSE, NPI, CVFT, FDS, BDS, TMT-A, TMT-B |
Martin et al. (2019) [47] | NE:33 NC:35 | Parallel | MCI | 13/20 10/25 | 71.8 ± 6.39 71.6 ± 6.35 | 14.5 ± 3.51 14.9 ± 3.23 | NR | CVLT-II, CANTAB, SDMT, CFQ |
Stonsaovapak et al. (2020) [48] | NE:23 NC:22 | Parallel | MCI | 2/21 2/20 | 68.39 ± 8.37 69.68 ± 7.60 | NR | NR | CANTAB |
Suemoto et al. (2014) [49] | NE:20 NC:20 | Parallel | AD | 5/15 7/13 | 79.4 ± 7.1 81.6 ± 8.0 | 5 ± 4.2 4.5 ± 3.9 | NR | NPI, ADAS-Cog, Digit cancellation task, Word list learning task, Word recognition task |
Yun et al. (2016) [50] | NE:8 NC:8 | Parallel | MCI | 3/5 2/6 | 74.75 ± 7.47 73.12 ± 4.25 | 8.06 ± 4.93 5.56 ± 2.41 | NR | MMQ |
Study (Time) | Type of Stimulation | Number of Sessions | Duration (min) | Stimulation Site | Current (mA) | Montage Size (cm2) | Stimulation Model | Adverse Effects |
---|---|---|---|---|---|---|---|---|
Boggio et al. (2012) [51] | Anode Sham | per day for 5 consecutive days | 30 | Temporal cortex bilaterally | 2 | 35 | Offline | No adverse effects were recorded after five daily tDCS sessions |
Bystad et al. (2016) [37] | Anode Sham | 6 sessions for 10 days | 30 | Left temporal lobe | 2 | 35 | Offline | No adverse effects were reported |
Cotelli et al. (2014) [38] | Anode+ICMT Sham+ICMT | 5 sessions per week for 2 weeks | 25 | Left DLPFC | 2 | 25 | Online | NR |
Das et al. (2019) [39] | Anode+SMART Sham+SMART | 8 sessions for 4 weeks | 20 | Left IFG | 2 | 15 | Offline | NR |
Ferrucci et al. (2008) [17] | Anodal Cathodal Sham | 1 session | 15 | Temporoparietal areas bilaterally | 1.5 | 25 | Offline | NR |
Gangemi(a) et al. (2021) [40] | Anode Sham | Daily, for 10 days | 20 | Left frontotemporal cortex | 2 | 0.8 | Offline | NR |
Gangemi(b) et al. (2021) [40] | Anode Sham | 10 sessions each month for 8 months | 20 | Left frontotemporal cortex | 2 | 0.8 | Offline | NR |
Gomes et al. (2019) [41] | Anode Sham | Twice per week for 5 weeks | 30 | Left DLPFC | 2 | 25 | Offline | NR |
Im et al. (2019) [42] | Anode Sham | Daily, for 6 months | 30 | Left DLPFC | 2 | 28 | Offline | NR |
Inagawa et al. (2019) [43] | Anode+CT| Sham+CT | 2 sessions per day for 5 consecutive days | 20 | Left DLPFC | 2 | 35 | Online | Neither severe adverse events nor the need for medications caused by adverse events |
Khedr et al. (2014) - [44] | Anodal Cathodal Sham | Daily, for 10 days | 25 | Left DLPFC | 2 | 24 | Offline | Two patients under active stimulation recorded itching, headache, and dizziness that were disappear after few hours |
Khedr et al. (2019) [45] | Anode Sham | 5 sessions per week for 2 consecutive weeks | 20 (each side) | Left TP lobe and right TP lobe | 2 | 35 | Offline | All the patients tolerated tDCS well without major adverse effects |
Lu et al. (2019) [46] | Anode+WMT Sham+WMT | 3 sessions per week for 4 weeks | 20 | Left LTC | 2 | 35 | Offline | three cases had skin lesions under the cathodal electrode during the repeated sessions of tDCS |
Martin et al. (2019) [47] | Anode+CT Sham+CT | 3 sessions per week for 5 weeks | 30 | Left DLPFC | 2 | 35 | Online | No adverse effects were reported |
Stonsaovapak et al. (2020) [48] | Anode Sham | 3 times per week for 4 weeks | 20 | Right DLPFC | 2 | 25 | Offline | Dizziness was found in one participant from the atDCS group. All side effects disappeared within 24 hours |
Suemoto et al. (2014) [49] | Anode Sham | 3 sessions per week for 2 weeks | 20 | Left DLPFC | 2 | 35 | Offline | TDCS was well tolerated and not associated with significant adverse effects |
Yun et al. (2016) [50] | Anode Sham | 3 sessions per week for 3 weeks | 30 | Left DLPFC | 2 | 25 | Offline | No patient reported adverse effects |
Study | Sequence Generation | Allocation Concealment | Blinding of Participants | Personnel and Outcomes Assessors | Incomplete Outcome Data | Selective Outcomes Reporting | Baseline Characteristics |
---|---|---|---|---|---|---|---|
Boggio (2012) [51] | ? | ? | ? | + | + | ? | - |
Bystad (2016) [37] | + | + | ? | ? | + | + | ? |
Cotelli (2014) [38] | ? | ? | + | + | ? | + | + |
Das (2019) [39] | + | + | + | + | ? | + | ? |
Ferrucci (2008) [17] | + | + | + | + | + | ? | ? |
Gangemi(a) (2021) [40] | ? | ? | + | + | ? | + | ? |
Gangemi(b) (2021) [40] | ? | ? | + | + | ? | + | ? |
Gomes (2019) [41] | ? | ? | ? | + | ? | + | - |
Im (2019) [42] | + | + | ? | + | + | + | + |
Inagawa (2019) [43] | + | + | ? | + | + | + | + |
Khedr (2014) [44] | + | ? | + | + | + | + | ? |
Khedr (2019) [45] | + | ? | + | + | + | + | ? |
Lu (2019) [46] | + | ? | + | + | + | + | + |
Martin (2019) [47] | + | + | ? | + | ? | + | + |
Stonsaovapak (2020) [48] | + | + | + | + | + | + | + |
Suemoto (2014) [49] | + | + | + | + | + | + | + |
Yun (2016) [50] | + | + | + | + | + | + | ? |
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Chen, J.; Wang, Z.; Chen, Q.; Fu, Y.; Zheng, K. Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Brain Sci. 2022, 12, 562. https://doi.org/10.3390/brainsci12050562
Chen J, Wang Z, Chen Q, Fu Y, Zheng K. Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Brain Sciences. 2022; 12(5):562. https://doi.org/10.3390/brainsci12050562
Chicago/Turabian StyleChen, Jiajie, Zheng Wang, Qin Chen, Yu Fu, and Kai Zheng. 2022. "Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis" Brain Sciences 12, no. 5: 562. https://doi.org/10.3390/brainsci12050562
APA StyleChen, J., Wang, Z., Chen, Q., Fu, Y., & Zheng, K. (2022). Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Brain Sciences, 12(5), 562. https://doi.org/10.3390/brainsci12050562