Table 2.
Summary of non-pharmacological interventions against AD.
| Methods | Targeted Region | Protocol | Subjects | Status | Summary | [Ref] |
|---|---|---|---|---|---|---|
| 1. Deep-brain stimulation | ||||||
| DBS | Fornix | Forneceal DBS | Mild AD | Phase II | Slight cognitive benefit in the elderly | [103,104] |
| Mild AD | Phase III | Ongoing | [105] | |||
| NBM | NBM-DBS | Mild to moderate AD | Phase I | Cognitive stabilization and improvement, response rate 67% | [106] | |
| 2. Vagus nerve stimulation | ||||||
| VNS | Tenth cranial nerve | Invasive VNS | Probable AD | Phase I | Cognitive stabilization and improvement, response rate 70% | [107,108] |
| Tenth cranial nerve | Non-invasive VNS | MCI | Not Applicable | Ongoing | [109] | |
| 3. Transcranial magnetic stimulation | ||||||
| High-frequency rTMS | Left DLPFC | 10 Hz/120% MT/3000 pulses per session/10 sessions/2 weeks * | MCI | Phase IV | Executive functional improvement | [110] |
| 10 Hz/120% MT/2000 pulses per session/20 sessions/4 weeks * | MCI | Not Applicable | Ongoing | [111] | ||
| 20 Hz/100% MT/2000 pulses per session/20 sessions/4 weeks * | Moderate AD | Not Applicable | Improved language performance | [112] | ||
| 20 Hz/80% MT/1200 pulses per session/20 sessions/4 weeks * | AD patients with BPSD | Not Applicable | Cognitive and functional improvement | [113] | ||
| 20 Hz/100% MT/2000 pulses per session/20 sessions/4 weeks * | Mild to moderate AD | Not Applicable | Improvement in trained associative memory, add-on effect | [114] | ||
| 20 Hz/80–100% MT/1000 pulses per session/20 sessions/4 weeks * | Mild to moderate AD | Not Applicable | Cognitive and functional improvement, add-on effect | [115] | ||
| 5 Hz/100% MT/1500 pulses per session/15 sessions/3 weeks * | Probable AD | Not Applicable | Cognitive and functional improvement | [116] | ||
| Bilateral DLPFCs | 20 Hz/90% MT/2000 pulses per session/5 sessions/5 days * | Mild to severe AD | Not Applicable | Cognitive and functional improvement in mild to moderate AD | [117] | |
| 20 Hz/90–100% MT/2000 pulses per session/13 sessions/4 weeks * | Mild to moderate AD | Not Applicable | Cognitive improvement | [118] | ||
| Right IFG | 10 Hz/90% MT/2250 pulses per session/single session * | MCI | Not Applicable | Improvement in attention and psychomotor speed | [119] | |
| 10 Hz/90% MT/2250 pulses per session/single session * | MCI to moderate AD | Not Applicable | Cognitive improvement | [120] | ||
| Right STG | 10 Hz/90% MT/2250 pulses per session/single session * | MCI to moderate AD | Not Applicable | Cognitive improvement | [120] | |
| Left parietal lobe | 20 Hz/100% MT/1600 pulses per session/10 sessions/1 week * | Early AD | Not Applicable | Improvement in episodic memory | [121] | |
| Bilateral parietal lobes | 20 Hz/Unavailable MT/1 h per session/30 sessions/6 weeks * | Mild to moderate AD | Not Applicable | Better performance in memory and language in mild AD | [122] | |
| Low-frequency rTMS | Bilateral DLPFCs | 1 Hz/90% MT/600 pulses per session/2 sessions/1 day * | Healthy individuals-MCI | Not Applicable | Improvement in recognition memory | [123] |
| 1 Hz/100% MT/2000 pulses per session/5 sessions/5 days * | Mild to severe AD | Not Applicable | Less cognitive efficacy than high-frequency rTMS | [117] | ||
| 4. Transcranial electrical stimulation | ||||||
| Transcranial direct current stimulation | Left DLPFC | 2 mA/30 min per session/single session ** | Mild to moderate AD | Not Applicable | Improved recognition memory | [124] |
| 2 mA/25 min per session/10 sessions/2 weeks ** | Mild to moderate AD | Not Applicable | Cognitive improvement | [125] | ||
| 2 mA/20 min per session/6 sessions/2 weeks ** | Moderate AD | Phase II | No cognitive or behavioral improvement, no change in apathy symptoms Requirement of more than 6 sessions |
[126] | ||
| 2 mA/30 min per session/daily session/6 months ** | Early AD | Not Applicable | Cognitive and functional improvement, rescue of executive function | [127] | ||
| 1.5 mA/15 min per session/single session ** | MCI | Not Applicable | Enhanced free recall and recognition of memory | [128] | ||
| 2 mA/30 min per session/1-5 sessions ** | MCI | Not Applicable | Improvement in selective attention, processing speed, and planning ability tasks Optimal frequency of 3 sessions/week |
[129] | ||
| Left parietal lobe | 2 mA/30 min per session/single session ** | Mild to moderate AD | Not Applicable | Improvement in recognition memory | [124] | |
| 2 mA/30 min per session/6 sessions/10 days ** | Mild to moderate AD | Not Applicable | No improved verbal memory function | [130] | ||
| Bilateral temporoparietal lobe | 1.5 mA/15 min per minute/2 sessions (anodal and cathodal) ** | Mild AD | Not Applicable | Improved word recognition in anodal group, cognitive worsening in cathodal group | [131] | |
| 2 mA/30 min per session/5 sessions/1 week ** | Mild to moderate AD | Not Applicable | Improvement in visual recognition memory | [132] | ||
| 2 mA/20 min per session/10 sessions/2 weeks ** | Early AD | Not Applicable | Improved cognitive performance | [133] | ||
| Left temporoparietal lobe | 2 mA/20 min per session/10 sessions/2 weeks ** | Advanced AD | Not Applicable | Stabilized neuropsychological performance, long-term protective effect | [134] | |
| Transcranial alternating current stimulation | Left DLPFC | 40 Hz/1.5 mA/30 min per session/40 sessions/4 weeks *** | MCI to moderate AD | Not Applicable | Improved cognitive performance | [135] |
| Superior parietal cortex | 40 Hz/3 mA/30 min per session/single session *** | AD patients | Not Applicable | Completed, no published data | [136] | |
| Left angular gyrus | 40 Hz/unavailable intensity/20 min per session/3 sessions *** | Healthy individuals to mild AD | Not Applicable | Ongoing | [137] | |
NBM—nucleus basalis of Meynert, DLPFC—dorsolateral prefrontal cortex, MT—motor threshold. * Protocol of rTMS: Frequency/Intensity/Number of pulses per session/Total number of sessions/Duration. ** Protocol of tDCS: Current intensity/Stimulation duration/Total number of sessions/Duration. *** Protocol of tACS: Frequency/Intensity/Stimulation duration/Total number of sessions/Duration.