{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T18:34:03Z","timestamp":1790620443908,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Foundation for the Study of Nanoneurosciences and Neuroregeneration"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Subjective cognitive complaints (SCCs) are common in middle-aged and older adults and may reflect early cognitive changes, alongside alterations in stress, mood, sleep, and quality of life. N-PEP-12 is a peptide-based nutritional supplement with potential neuroprotective effects, but evidence of its benefits in healthy adults with SCCs remains limited. Objective: To evaluate the effects of N-PEP-12 supplementation on attention, cognitive function, and mental wellbeing in healthy middle-aged and older adults with SCCs. Methods: In this prospective, randomized, double-blind, placebo-controlled trial, 276 participants aged 50\u201375 years with SCCs and no clinically significant cognitive impairment were randomized to placebo, N-PEP-12 45 mg, or N-PEP-12 90 mg. Assessments were performed at baseline and after 30, 90, and 180 days. Primary outcomes included Test of Attentional Performance measures. Secondary outcomes included WAIS-IV Digit Span Forward and Backward, perceived stress, mood, sleep quality, and EQ-5D-5L visual analog scale. Results: Across the three primary attention outcomes analyzed jointly in a multivariate repeated-measures model, there was a significant group-by-visit interaction (p = 0.003) and a significant effect of visit (p &lt; 0.001), without a significant main effect of treatment arm (p = 0.133), indicating a time-dependent treatment effect. This result was obtained in a sensitivity analysis population in which missing values were imputed under assumptions least favorable to the active arms. In exploratory endpoint-specific comparisons at 90 days, both N-PEP-12 groups showed greater improvements than placebo in alertness, attention omissions and memory omissions, and Digit Span Forward and Backward scores also improved. In a subsequent uncontrolled extension phase, in which all participants received active treatment, participants initially assigned to placebo showed comparable improvements after switching to N-PEP-12 90 mg. These observations are exploratory. Adverse events were infrequent and similarly distributed across groups. Conclusions: N-PEP-12 supplementation was associated with improvements in attention, working memory, and mental wellbeing in healthy middle-aged and older adults with subjective cognitive complaints. These findings support further investigation of N-PEP-12 as a nutritional intervention for early subjective cognitive changes associated with aging.<\/jats:p>","DOI":"10.3390\/nu18162739","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:37:34Z","timestamp":1787312254000},"page":"2739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Impact of N-PEP-12 Supplementation on Attentional Performance and Mental Wellbeing in Healthy Adults with Subjective Cognitive Complaints: A Randomized, Placebo-Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1589-0789","authenticated-orcid":false,"given":"Diana","family":"Chira","sequence":"first","affiliation":[{"name":"Department of Neurosciences, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Victor Babe\u0219 43, 400012 Cluj-Napoca, Romania"},{"name":"RoNeuro Institute for Neurological Research and Diagnostic, Mircea Eliade 37, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-1971-8085","authenticated-orcid":false,"given":"Nicoleta","family":"Jemna","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Victor Babe\u0219 43, 400012 Cluj-Napoca, Romania"},{"name":"RoNeuro Institute for Neurological Research and Diagnostic, Mircea Eliade 37, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0863-5002","authenticated-orcid":false,"given":"Olivia","family":"Veri\u0219ezan-Ro\u0219u","sequence":"additional","affiliation":[{"name":"RoNeuro Institute for Neurological Research and Diagnostic, Mircea Eliade 37, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Maria","family":"Buruian\u0103","sequence":"additional","affiliation":[{"name":"RoNeuro Institute for Neurological Research and Diagnostic, Mircea Eliade 37, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6112-0223","authenticated-orcid":false,"given":"\u0218tefan","family":"Strilciuc","sequence":"additional","affiliation":[{"name":"Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Gheorghe Marinescu 38, 400337 Cluj-Napoca, Romania"},{"name":"Department of Translational Neurosciences, MEDFUTURE, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Gheorghe Marinescu 38, 400337 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2954-3263","authenticated-orcid":false,"given":"Vlad-Florin","family":"Chelaru","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Victor Babe\u0219 43, 400012 Cluj-Napoca, Romania"},{"name":"RoNeuro Institute for Neurological Research and Diagnostic, Mircea Eliade 37, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"P\u00e2rvu","sequence":"additional","affiliation":[{"name":"Department of Complementary Sciences, Discipline of Hygiene and Medical Ecology, Carol Davila University of Medicine and Pharmacy, 8 Eroii Sanitari Boulevard, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dafin Fior","family":"Mure\u0219anu","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Iuliu Ha\u021bieganu University of Medicine and Pharmacy, Victor Babe\u0219 43, 400012 Cluj-Napoca, Romania"},{"name":"RoNeuro Institute for Neurological Research and Diagnostic, Mircea Eliade 37, 400354 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","unstructured":"(2026, April 07). 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