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enthusiasm dramatically outpaces science FDA Category 2 classifications for peptides like Semax reflect absence of FDA-standard evidence, not documented harmsRussian clinical experience suggests reasonable safety, but long-term effects by Western standards remain uncharacterized Established interventionsexercise, Mediterranean diet, sleep optimization, cardiovascular risk management, cognitive engagementhave far more consistent evidence than any peptide for dementia risk reduction For Research Prioritization Compounds meriting continued investigation: GLP-1 Agonists: Prevention trials in preclinical/presymptomatic populations, testing compounds with better brain penetration (dulaglutide, lixisenatide) SS-31/Elamipretide: Cognitive outcomes in mitochondrial disease populations, potential expansion to brain aging indications P21: Phase I human trials to establish safety, pharmacokinetics, and proof-of-mechanism for CNTF-pathway neurogenesis Klotho: Watch for Phase 1 results from Jocasta Neuroscience (expected 2027-2028)

doi: 10.3389/fpsyt.2020.00172 Received 25 December 2019 Accepted 21 February 2020 Published 18 March 2020 Volume 11 - 2020 Edited by Guillaume Gourcerol, Universit de Rouen, France Reviewed by Juntaro Matsuzaki, University of California, San Francisco, United States

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