{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T16:27:58Z","timestamp":1787243278005,"version":"build-2736575974"},"reference-count":46,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer's Disease Reports"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>Ketamine's ability to lift mood and spur new synapse growth has put glutamate biology at the center of modern neurotherapeutics. Yet the drug's intravenous route, monitoring requirements, and dissociative effects make it a poor candidate for long-term prevention of Alzheimer's disease (AD). This hypothesis article proposes a low-cost oral glutamatergic regimen that targets early synaptic and glutamatergic dysfunction in AD pathogenesis. Here we advance a testable hypothesis: an all-oral \u201csynaptogenic stack\u201d could mimic ketamine's downstream benefits\u2014namely, the rise in brain-derived neurotrophic factor and the activation of mechanistic target of rapamycin (mTOR)\u2014while avoiding its toxicities. The stack combines three inexpensive agents that have decades of human use. First, dextromethorphan, kept in circulation with a small dose of a CYP2D6 inhibitor, provides gentle NMDA antagonism. Second, piracetam acts as a positive modulator of AMPA receptors, boosting fast excitatory transmission. Third, oral L-glutamine replenishes presynaptic glutamate stores and buffers against excitotoxic spill-over. Working in concert, these drugs should reduce extrasynaptic NMDA stress, enhance AMPA throughput, and preserve dendritic spine density in the aging brain. If this mechanism proves sound, the regimen offers a low-cost, scalable way to delay the clinical onset of AD, particularly in people who already show prodromal biomarkers or genetic risk. Prospective trials are needed to evaluate safety, target engagement, and long-term cognitive outcomes.<\/jats:p>","DOI":"10.1177\/25424823261433953","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T05:44:21Z","timestamp":1773467061000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["The Cheung Glutamatergic Regimen as a candidate for primary and secondary prevention of Alzheimer's disease onset"],"prefix":"10.1177","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3481-893X","authenticated-orcid":false,"given":"Ngo","family":"Cheung","sequence":"first","affiliation":[{"name":"Cheung Ngo Medical Limited, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,3,13]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2013.08.013"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-160763"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507313103"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.10.035"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-170879"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2303878120"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04687-y"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02057.x"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","unstructured":"Cheung N. Clinical experience and optimisation of the Cheung glutamatergic regimen for refractory psychiatric diseases. Preprints 2025. DOI:10.20944\/preprints202511.2246.v1.","DOI":"10.20944\/preprints202511.2246.v1"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","unstructured":"Cheung N. DXM CYP2D6-inhibiting antidepressants piracetam and glutamine: proposing a ketamine-class antidepressant regimen with existing drugs. Preprints 2025. DOI:10.20944\/preprints202511.1815.v1.","DOI":"10.20944\/preprints202511.1815.v1"},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","unstructured":"Cheung N. Ultra-low-dose paroxetine as CYP2D6 inhibitor enables safe OTC glutamatergic augmentation in a depressive patient on lisdexamfetamine. Preprints 2025. 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Glutamine: biochemistry, physiology, and clinical applications. Boca Raton: CRC Press, 2017."},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2018.00561"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.6.737"},{"key":"e_1_3_3_28_2","first-page":"2794","article-title":"Glutamine supplementation preserves glutamatergic activity in an Alzheimer mouse model","volume":"15","author":"Son H","year":"2023","unstructured":"Son H, Baek JH, Kang H, et al. Glutamine supplementation preserves glutamatergic activity in an Alzheimer mouse model. 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