Table 3.
Ultrasound stimulation in Alzheimer's disease.
| Refs. | Experimental animals | Brain targets | Protocol of ultrasound stimulation | Efficacy |
|---|---|---|---|---|
| Animal Research | ||||
| Jordão et al. (131) | Male and female TgCRND8 mice (132–137 days) | The right hemisphere | FF: 0.558 MHz PRF: 1 Hz TBD:10 ms SD:120 s | With the help of microbubbles, ultrasound stimulation locally increases the permeability of the blood brain barrier (BBB). |
| Jordão et al. (132) | Male and female TgCRND8 mice (4 months) | The right cortex | FF: 0.558 MHz PRF: 1 Hz TBD:10 ms SD:120 s | (1) With the help of microbubbles, ultrasound stimulation locally increases the permeability of the blood brain barrier (BBB). (2) Plaque burden is reduced in cortical brain regions targeted with focused ultrasound stimulation. (3) MRIgFUS-dependent BBB opening allows endogenous immunoglobulin to enter the brain. |
| Burgess et al. (133) | TgCRND8 mice (7 months) | Hippocampus | FF: 1.68 MHz PRF: 1 Hz TBD: 10 ms SD: 120 s | (1) BBB blood-brain barrier was opened. (2) Ultrasound stimulation improved cognition. (3) Ultrasound stimulation reduced plaque load and increased neuronal plasticity. |
| Shen et al. (134) | Female 3 × Tg-AD mice (8 months) | Hippocampus | FF: 0.996 MHz PRF: 1 Hz TBD: 10 ms SD: 60 s A peak-rarefactional pressure amplitude of 0.64 MPa | (1) Ultrasound stimulation improved cognition. (2) Ultrasound stimulation ameliorated Aβ deposits and mitigated tau pathology in the hippocampus. |
| Eguchi et al. (135) | Male 5XFAD mice (14–16 weeks) | Whole brain | FF: 1.875 MH PRF: 6.0 kHz TBD: 17 us SD: 20 min Ispta: 90 mW/cm2 Isppa: 99 mW/cm2 the number of cycles: 32 The width of the ultrasound beam at each depth of brain tissue ranged from 3.6 to 4.0 mm | Ultrasound stimulation ameliorated cognitive impairments associated with improved cerebral blood flow (CBF). |
| Bobola et al. (136) | Male 5XFAD mice (6 months) | Hippocampus | FF: 2.0 MHz PRF: 40 Hz TBD: 400 ms Isppa: 190 W/cm2 SD: 1 h Chronic: 1 h per day for 5days | (1) Acute ultrasound stimulation can increase the number of microglia around Aβ plaque. (2) Acute ultrasound stimulation reduced Aβ plaque burden. |
| Lee et al. (137) | 5XFAD mice | Hemisphere | FF: 715 kHz PRF: 1 Hz DC: 2 % TBD: 20 ms SD: 60 s | (1) Ultrasound stimulation improved cognition. (2) Ultrasound stimulation enhanced solute Aβ clearance from the brain, but not plaques, to cerebrospinal fluid (CSF) space. |
| Poon et al. (138) | male and female TgCRND8 mice (7 months) | Hippocampus | FF: 1.1 MH PRF: 1 Hz TBD: 10 ms SD: 120 s The situ pressures of 0.4–0.8 MPa once every other week, for a total of 10 weeks | Ultrasound stimulation reduces the size of existing β-amyloid plaques. |
| Leinenga et al. (139) | Male APP23 mice (median age, 12.8 months) | Whole brain | FF: 1 MHz PRF: 10 Hz DC: 10 % TBD: 6 s Peak rarefactional pressure is 0.7MPa. The focal zone of the array was an ellipse of about 1.5 mm × 1.5 mm × 12 mm | (1) Ultrasound stimulation engages microglia and promotes the internalization of Ab into microglial lysosomes. (2) Ultrasound stimulation reduces Ab and plaque load. |
| Leinenga et al. (140) | APP23 mice (21–22 months) | Whole brain | FF: 1 MHz PRF: 10 Hz DC: 10 % TBD: 6 s Peak rarefactional pressure is 0.7 MPa. The focal zone of the array was an ellipse of about 1.5 mm × 1.5 mm × 12 mm 4 times for 8 weeks | (1) SUS treatment increases the number of plaque-associated microglia. (2) SUS Treatment does not reduce the total plaque area but reduces the fraction of larger plaques. (3) SUS treatment reduces fibrillar amyloid. (4) There was no tissue damage. |
| Clinical research | ||||
| Lipsman et al. (144) | Patients with early to moderate Alzheimer's disease | Presumed non-eloquent cortex in the right frontal lobe, namely the superior frontal gyrus white matter of the dorsolateral prefrontal cortex (DLPFC) | FF: 220 kHz TBD: 2 ms SD: 300 ms DC: 0.74 % ISI: 2.7 s | Open the BBB in human patients |
| D'Haese et al. (148) | Patients aged between 50 and 85 years with early AD | Hippocampus and EC | FF: 220 kHz SD: 90 s DC: 50–60% sonication using a range of power of 4–11.5 W | (1) FUS BBB opening is feasible and safe (2) induce a reduction in β-amyloid plaque burden |
| Nicodemus et al. (149) | Alzheimer's disease patients with age from 40 to 95 | The mesial temporal lobe | FF: 2 MHz 520 mW/cm2 Eight consecutive, weekly, 1-h | 62.5% of patients demonstrated clinically significant improvement on at least one cognitive measure |
| Beisteiner R | Alzheimer's disease patients | Dorsolateral prefrontal cortex | PRF: 1–5 Hz TBD: 3 us Ispta: 0.1 W/cm2 Maximum number of pulses per treatment: 6,000 Maximum peak pressure 25 MPa Every ROI was stimulated twice per session and most patients were stimulated for 4 weeks | (1) No major side effects (2) Neuropsychological scores improve significantly after TPS treatment and improvement lasts up to 3 months and correlates with an upregulation of the memory network (fMRI data) |