Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies
Non-invasive Gamma ENtrainment Using Sensory 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2022-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714926/?tool=EBI |
| _version_ | 1811297838602125312 |
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| author | Diane Chan Ho-Jun Suk Brennan L. Jackson Noah P. Milman Danielle Stark Elizabeth B. Klerman Erin Kitchener Vanesa S. Fernandez Avalos Gabrielle de Weck Arit Banerjee Sara D. Beach Joel Blanchard Colton Stearns Aaron D. Boes Brandt Uitermarkt Phillip Gander Matthew Howard Eliezer J. Sternberg Alfonso Nieto-Castanon Sheeba Anteraper Susan Whitfield-Gabrieli Emery N. Brown Edward S. Boyden Bradford C. Dickerson Li-Huei Tsai |
| author_facet | Diane Chan Ho-Jun Suk Brennan L. Jackson Noah P. Milman Danielle Stark Elizabeth B. Klerman Erin Kitchener Vanesa S. Fernandez Avalos Gabrielle de Weck Arit Banerjee Sara D. Beach Joel Blanchard Colton Stearns Aaron D. Boes Brandt Uitermarkt Phillip Gander Matthew Howard Eliezer J. Sternberg Alfonso Nieto-Castanon Sheeba Anteraper Susan Whitfield-Gabrieli Emery N. Brown Edward S. Boyden Bradford C. Dickerson Li-Huei Tsai |
| author_sort | Diane Chan |
| collection | DOAJ |
| description | Non-invasive Gamma ENtrainment Using Sensory 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. |
| first_indexed | 2024-04-13T06:10:09Z |
| format | Article |
| id | doaj.art-c43eb432021f40a58ded16cd9e8cf551 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T06:10:09Z |
| publishDate | 2022-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-c43eb432021f40a58ded16cd9e8cf5512022-12-22T02:59:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032022-01-011712Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studiesDiane ChanHo-Jun SukBrennan L. JacksonNoah P. MilmanDanielle StarkElizabeth B. KlermanErin KitchenerVanesa S. Fernandez AvalosGabrielle de WeckArit BanerjeeSara D. BeachJoel BlanchardColton StearnsAaron D. BoesBrandt UitermarktPhillip GanderMatthew HowardEliezer J. SternbergAlfonso Nieto-CastanonSheeba AnteraperSusan Whitfield-GabrieliEmery N. BrownEdward S. BoydenBradford C. DickersonLi-Huei TsaiNon-invasive Gamma ENtrainment Using Sensory 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.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714926/?tool=EBI |
| spellingShingle | Diane Chan Ho-Jun Suk Brennan L. Jackson Noah P. Milman Danielle Stark Elizabeth B. Klerman Erin Kitchener Vanesa S. Fernandez Avalos Gabrielle de Weck Arit Banerjee Sara D. Beach Joel Blanchard Colton Stearns Aaron D. Boes Brandt Uitermarkt Phillip Gander Matthew Howard Eliezer J. Sternberg Alfonso Nieto-Castanon Sheeba Anteraper Susan Whitfield-Gabrieli Emery N. Brown Edward S. Boyden Bradford C. Dickerson Li-Huei Tsai Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies PLoS ONE |
| title | Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies |
| title_full | Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies |
| title_fullStr | Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies |
| title_full_unstemmed | Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies |
| title_short | Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies |
| title_sort | gamma frequency sensory stimulation in mild probable alzheimer s dementia patients results of feasibility and pilot studies |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714926/?tool=EBI |
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