Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies
<jats:p>Non-invasive <jats:underline>G</jats:underline>amma <jats:underline>EN</jats:underline>trainment <jats:underline>U</jats:underline>sing <jats:underline>S</jats:underline>ensory stimulation (GENUS) at 40Hz reduces Alzheimer’s disease (AD)...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2022
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| Online Access: | https://hdl.handle.net/1721.1/146911 |
| _version_ | 1826205279088279552 |
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| author | Chan, Diane Suk, Ho-Jun Jackson, Brennan L Milman, Noah P Stark, Danielle Klerman, Elizabeth B Kitchener, Erin Fernandez Avalos, Vanesa S de Weck, Gabrielle Banerjee, Arit Beach, Sara D Blanchard, Joel Stearns, Colton Boes, Aaron D Uitermarkt, Brandt Gander, Phillip Howard, Matthew Sternberg, Eliezer J Nieto-Castanon, Alfonso Anteraper, Sheeba Whitfield-Gabrieli, Susan Brown, Emery N Boyden, Edward S Dickerson, Bradford C Tsai, Li-Huei |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Chan, Diane Suk, Ho-Jun Jackson, Brennan L Milman, Noah P Stark, Danielle Klerman, Elizabeth B Kitchener, Erin Fernandez Avalos, Vanesa S de Weck, Gabrielle Banerjee, Arit Beach, Sara D Blanchard, Joel Stearns, Colton Boes, Aaron D Uitermarkt, Brandt Gander, Phillip Howard, Matthew Sternberg, Eliezer J Nieto-Castanon, Alfonso Anteraper, Sheeba Whitfield-Gabrieli, Susan Brown, Emery N Boyden, Edward S Dickerson, Bradford C Tsai, Li-Huei |
| author_sort | Chan, Diane |
| collection | MIT |
| description | <jats:p>Non-invasive <jats:underline>G</jats:underline>amma <jats:underline>EN</jats:underline>trainment <jats:underline>U</jats:underline>sing <jats:underline>S</jats:underline>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.</jats:p> |
| first_indexed | 2024-09-23T13:10:12Z |
| format | Article |
| id | mit-1721.1/146911 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T13:10:12Z |
| publishDate | 2022 |
| publisher | Public Library of Science (PLoS) |
| record_format | dspace |
| spelling | mit-1721.1/1469112022-12-20T03:22:38Z Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies Chan, Diane Suk, Ho-Jun Jackson, Brennan L Milman, Noah P Stark, Danielle Klerman, Elizabeth B Kitchener, Erin Fernandez Avalos, Vanesa S de Weck, Gabrielle Banerjee, Arit Beach, Sara D Blanchard, Joel Stearns, Colton Boes, Aaron D Uitermarkt, Brandt Gander, Phillip Howard, Matthew Sternberg, Eliezer J Nieto-Castanon, Alfonso Anteraper, Sheeba Whitfield-Gabrieli, Susan Brown, Emery N Boyden, Edward S Dickerson, Bradford C Tsai, Li-Huei Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Harvard University--MIT Division of Health Sciences and Technology <jats:p>Non-invasive <jats:underline>G</jats:underline>amma <jats:underline>EN</jats:underline>trainment <jats:underline>U</jats:underline>sing <jats:underline>S</jats:underline>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.</jats:p> 2022-12-19T14:28:37Z 2022-12-19T14:28:37Z 2022 2022-12-19T13:55:19Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146911 Chan, Diane, Suk, Ho-Jun, Jackson, Brennan L, Milman, Noah P, Stark, Danielle et al. 2022. "Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies." PLOS ONE, 17 (12). en 10.1371/journal.pone.0278412 PLOS ONE Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science (PLoS) PLoS |
| spellingShingle | Chan, Diane Suk, Ho-Jun Jackson, Brennan L Milman, Noah P Stark, Danielle Klerman, Elizabeth B Kitchener, Erin Fernandez Avalos, Vanesa S de Weck, Gabrielle Banerjee, Arit Beach, Sara D Blanchard, Joel Stearns, Colton Boes, Aaron D Uitermarkt, Brandt Gander, Phillip Howard, Matthew Sternberg, Eliezer J Nieto-Castanon, Alfonso Anteraper, Sheeba Whitfield-Gabrieli, Susan Brown, Emery N Boyden, Edward S Dickerson, Bradford C Tsai, Li-Huei Gamma frequency sensory stimulation in mild probable Alzheimer’s dementia patients: Results of feasibility and pilot studies |
| 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://hdl.handle.net/1721.1/146911 |
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