In:
PLOS ONE, Public Library of Science (PLoS), Vol. 17, No. 12 ( 2022-12-1), p. e0278412-
Abstract:
Non-invasive G amma EN trainment U sing S ensory stimulation (GENUS) at 40Hz reduces Alzheimer’s disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0278412
DOI:
10.1371/journal.pone.0278412.g001
DOI:
10.1371/journal.pone.0278412.g002
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10.1371/journal.pone.0278412.g003
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10.1371/journal.pone.0278412.g004
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10.1371/journal.pone.0278412.g005
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10.1371/journal.pone.0278412.g006
DOI:
10.1371/journal.pone.0278412.t001
DOI:
10.1371/journal.pone.0278412.t002
DOI:
10.1371/journal.pone.0278412.t003
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10.1371/journal.pone.0278412.t004
DOI:
10.1371/journal.pone.0278412.s001
DOI:
10.1371/journal.pone.0278412.s002
DOI:
10.1371/journal.pone.0278412.s003
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10.1371/journal.pone.0278412.s004
DOI:
10.1371/journal.pone.0278412.s005
DOI:
10.1371/journal.pone.0278412.s006
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10.1371/journal.pone.0278412.s007
DOI:
10.1371/journal.pone.0278412.s008
DOI:
10.1371/journal.pone.0278412.s009
DOI:
10.1371/journal.pone.0278412.s010
DOI:
10.1371/journal.pone.0278412.s011
DOI:
10.1371/journal.pone.0278412.s012
DOI:
10.1371/journal.pone.0278412.s013
DOI:
10.1371/journal.pone.0278412.s014
DOI:
10.1371/journal.pone.0278412.s015
DOI:
10.1371/journal.pone.0278412.s016
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2267670-3
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