{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:57:11Z","timestamp":1790575031396,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Memory and cognitive impairments remain disabling, with few effective treatments. Low-intensity transcranial ultrasound (TUS) is a non-invasive neuromodulation approach with a favorable safety profile and preliminary evidence of cognitive benefit, with one hypothesized but unproven mechanism involving microtubule resonance and reassembly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This open-label pilot study evaluated the safety and preliminary efficacy of the US Pro2000 unfocused ultrasound device in adults with memory or cognitive difficulties, a sample spanning subjective cognitive decline among self-administering participants to diagnosed dementia among caregiver-rated recipients, and described self-reported symptom trajectories.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a within-participant design, adults with self-reported cognitive impairment, or their caregivers, applied the device at the right temporal window for 5 min three times daily (target 15 min\/day), in cycles of 3 weeks on and 1 week off. Outcomes (GAD-7, CESD-5, Inoue battery, and caregiver-rated MDS 3.0) and adverse events were collected online. Mixed-effects models with age and device-use covariates assessed change over time, with False Discovery Rate correction within aim.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Twenty-seven participants enrolled and 26 initiated treatment. Across 2,174 daily assessments, no serious or unanticipated adverse events occurred; only headache (15.4%) and transient jaw clenching (3.8%) were possibly related, and none caused discontinuation. Among self-administered participants, depression (CESD-5) declined significantly (\n                      <jats:italic>p<\/jats:italic>\n                      _FDR = 0.016) and five of eight monthly self-report symptoms improved, including memory, word-finding, and problem-solving (all\n                      <jats:italic>p<\/jats:italic>\n                      _FDR \u2264 0.040); anxiety trended downward, and the objective cognitive battery, near ceiling at baseline, did not change. Caregiver-rated outcomes were stable. Device use showed no dose response, and sensitivity analyses were consistent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Home-based self-administered low-intensity TUS was well tolerated, with only mild transient events, although adverse-event ascertainment relied on unblinded self-report and relatedness judgments were made by unblinded investigators. Efficacy signals were confined to self-report, while objective cognition and caregiver ratings were unchanged. The uncontrolled design, small subgroups, and reliance on self-report preclude causal inference. These findings support the safety and feasibility of TUS and justify an adequately powered, double-blind, sham-controlled trial.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1937897","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T05:44:24Z","timestamp":1790574264000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Home-administered unfocused transcranial ultrasound in subjective cognitive decline and dementia: an open-label, uncontrolled feasibility pilot study"],"prefix":"10.3389","volume":"18","author":[{"given":"Helan\u00e9","family":"Wahbeh","sequence":"first","affiliation":[{"name":"Research Department, Institute of Noetic Sciences","place":["Novato, CA, United States"]},{"name":"Department of Neurology, Oregon Health and Science University","place":["Portland, OR, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sterling","family":"Cooley","sequence":"additional","affiliation":[{"name":"Ultra DAO","place":["Berkeley, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven Russell","family":"Chamberlin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Oregon Health and Science University","place":["Portland, OR, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Brophy","sequence":"additional","affiliation":[{"name":"Research Department, Institute of Noetic Sciences","place":["Novato, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Hameroff","sequence":"additional","affiliation":[{"name":"Quantum Life Technologies Inc.","place":["San Francisco, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1186\/s12885-021-08722-7","article-title":"Exposure to low intensity ultrasound removes paclitaxel cytotoxicity in breast and ovarian cancer cells.","volume":"21","author":"Amaya","year":"2021","journal-title":"BMC Cancer"},{"key":"B2","doi-asserted-by":"publisher","first-page":"8979","DOI":"10.1021\/jm301079z","article-title":"Microtubule stabilizing agents as potential treatment for Alzheimer\u2019s disease and related neurodegenerative tauopathies.","volume":"55","author":"Ballatore","year":"2012","journal-title":"J. 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