{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T10:05:34Z","timestamp":1781085934104,"version":"3.54.1"},"reference-count":51,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T00:00:00Z","timestamp":1781049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Mild cognitive impairment (MCI) may precede dementia, and safe nutritional strategies able to support cognitive function are of clinical interest. Dietary nucleotides may contribute to membrane phospholipid synthesis, synaptic function, and neuroprotective pathways; however, clinical evidence in older adults with MCI remains limited. This randomized placebo-controlled trial evaluated the efficacy and tolerability of nucleotide-rich yeast extracts from Kluyveromyces fragilis and Saccharomyces cerevisiae. Methods: Seventy-two participants (mean age 73.5 \u00b1 7.7 years; range 60\u201385) were randomly assigned (1:1:1) to receive K. fragilis extract, S. cerevisiae extract, or placebo once daily for 180 days. Cognitive outcomes were assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) at baseline (T0), 90 days (T1), and 180 days (T2); quality of life was assessed using the SF-12 questionnaire at T0 and T2. Treatment effects were analyzed using linear mixed-effects models adjusted for age and sex. Results: After 180 days, MoCA scores increased by 4.42 points in the K. fragilis group and 3.92 points in the S. cerevisiae group, compared with 0.58 points in the placebo group (time \u00d7 treatment p &lt; 0.001; T0\u2013T2 within-group p &lt; 0.001 for both active groups and p = 0.14 for placebo). MMSE scores increased by 1.62 and 3.11 points in the K. fragilis and S. cerevisiae groups, respectively, compared with 0.25 points in the placebo group (time \u00d7 treatment p &lt; 0.001; T0\u2013T2 within-group p &lt; 0.001 for both active groups and p = 0.57 for placebo). The SF-12 mental component score increased by 7.50 and 9.16 points in the two active groups, respectively (time \u00d7 treatment p = 0.022; T0\u2013T2 p = 0.0013 and p &lt; 0.001, respectively), while physical quality-of-life scores did not change significantly (PCS time \u00d7 treatment p = 0.11). No adverse events were reported. Conclusions: Nucleotide-rich K. fragilis and S. cerevisiae yeast extracts were well tolerated and were associated with improved cognitive scores over six months in older adults with MCI. Larger multicenter trials are needed to confirm these findings.<\/jats:p>","DOI":"10.3390\/nu18121869","type":"journal-article","created":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T09:25:17Z","timestamp":1781083517000},"page":"1869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Nucleotide-Rich Kluyveromyces fragilis and Saccharomyces cerevisiae Yeast Extracts on Cognitive Function in Older Adults with Mild Cognitive Impairment: A Randomized Placebo-Controlled Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9437-676X","authenticated-orcid":false,"given":"Hammad","family":"Ullah","sequence":"first","affiliation":[{"name":"Department of Pharmacy, COMSATS University Islamabad, Abbottabad Campus, Abbottabad 22060, Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Cordara","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Milano-Bicocca, 20126 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Vittoria","family":"Morone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Piccinocchi","sequence":"additional","affiliation":[{"name":"Anaesthesia and Resuscitation A. U. O. Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza Francesca","family":"De Lellis","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Cerqua","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2877-9445","authenticated-orcid":false,"given":"Alessandra","family":"Baldi","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6199-0074","authenticated-orcid":false,"given":"Roberto","family":"Sacchi","sequence":"additional","affiliation":[{"name":"Applied Statistic Unit, Department of Earth and Environmental Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-2198","authenticated-orcid":false,"given":"Gaetano","family":"Piccinocchi","sequence":"additional","affiliation":[{"name":"Comegen S.C.S., Societ\u00e0 Cooperativa Sociale, 80125 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-9976","authenticated-orcid":false,"given":"Alessandro","family":"Di Minno","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy"},{"name":"CEINGE-Biotecnologie Avanzate, 80145 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaia","family":"Spadarella","sequence":"additional","affiliation":[{"name":"Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-7713","authenticated-orcid":false,"given":"Maria","family":"Daglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Napoli Federico II, 80131 Naples, Italy"},{"name":"International Research Center for Food Nutrition and Safety, Jiangsu University, Zhenjiang 212013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.ncl.2024.05.005","article-title":"Dementia: Common syndromes and modifiable risk and protective factors","volume":"42","author":"Jean","year":"2024","journal-title":"Neurol. 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