{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:04:19Z","timestamp":1791497059067,"version":"4.3.4"},"reference-count":49,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T00:00:00Z","timestamp":1761350400000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010302","name":"Robert A. and Renee E. Belfer Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010302","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n We evaluated the long\u2010term effects of daily 40\u00a0Hz (gamma frequency) audiovisual stimulation on cognition and biomarkers in five patients with mild Alzheimer's disease (AD).<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n Over 2 years, patients received 1\u2010h daily stimulation. Electroencephalography (EEG) was used to assess neural entrainment; magnetic resonance imaging (MRI) measured brain volumes; actigraphy monitored activity patterns; neuropsychological tests evaluated cognition; and S\u2010PLEX assay measured plasma pTau217.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n No adverse events occurred over the study period. Three female patients with late\u2010onset AD (LOAD) retained strong EEG entrainment and showed less decline in Mini\u2010Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and Functional Assessment Scale (FAS) scores compared to matched controls from National Alzheimer's Coordinating Center (NACC), Alzheimer's Disease Neuroimaging Initiative (ADNI), and Longitudinal Early\u2010Onset Alzheimer's Disease Study (LEADS). Plasma samples were available for only two of five participants \u2013 both with LOAD \u2013 and both showed pTau217 reductions of 47% and 19%.<\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n These findings suggest that long\u2010term 40\u00a0Hz audiovisual stimulation is safe, feasible, and may offer cognitive and biomarker benefits in some individuals with mild AD, supporting further investigation.<\/jats:p>\n <\/jats:sec>\n \n CLINICAL TRIAL REGISTRATION INFORMATION<\/jats:title>\n \n ClinicalTrials.gov<\/jats:ext-link>\n (NCT04055376).\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n Five mild Alzheimer's disease (AD) patients safely used daily 40\u00a0Hz audiovisual stimulation for 2 years.<\/jats:p>\n <\/jats:list-item>\n \n Late\u2010onset AD (LOAD) patients showed increased 40\u00a0Hz electroencephalography (EEG) power and improved cognitive scores.<\/jats:p>\n <\/jats:list-item>\n \n National Alzheimer's Coordinating Center (NACC) data enhanced early\u2010phase analysis and support precision medicine in AD studies.<\/jats:p>\n <\/jats:list-item>\n \n Plasma pTau217 declined in 2 LOAD patients after 2 years of daily use.<\/jats:p>\n <\/jats:list-item>\n \n This small pilot is the first to link long\u2010term 40\u00a0Hz therapy to AD biomarker change.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70792","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T10:10:01Z","timestamp":1761387001000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Gamma sensory stimulation in mild Alzheimer's dementia: An open\u2010label extension study"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-190X","authenticated-orcid":false,"given":"Diane","family":"Chan","sequence":"first","affiliation":[{"name":"Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA"},{"name":"Department of Neurology Massachusetts General Hospital Boston Massachusetts USA"},{"name":"Department of Neurology Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"de Weck","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brennan L.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA"},{"name":"Health Sciences and Technology Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ho\u2010Jun","family":"Suk","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah P.","family":"Milman","sequence":"additional","affiliation":[{"name":"Department of Behavioral and Systems Neuroscience Oregon Health and Sciences University Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Kitchener","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA"},{"name":"Brenner Center for Psychological Assessment and Consultation William James College Newton Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa S. Fernandez","family":"Avalos","sequence":"additional","affiliation":[{"name":"Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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