{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:54:02Z","timestamp":1785405242400,"version":"3.56.0"},"reference-count":25,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014383","name":"Italfarmaco","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100014383","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/05xsppr58","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Subthreshold depression is a prevalent condition among the elderly and often remains untreated due to the limited efficacy and poor tolerability of standard antidepressants. Choline alfoscerate, a cholinergic precursor, is indicated for the treatment of a condition, pseudodepression in the elderly, that is currently clinically classified as subthreshold depression in older adults. Also, choline alfoscerate has shown neuroprotective and antidepressant-like effects. Objective: This pilot study aims to evaluate the efficacy and safety of choline alfoscerate in elderly patients with subthreshold depressive symptoms, using contemporary diagnostic criteria and standardized outcome measures. Methods: Seventeen patients aged \u226565 years were enrolled in an open-label, single-arm study and received 1200 mg\/day of choline alfoscerate for 8 weeks. Clinical and neuropsychological assessments were performed at baseline, after 4 weeks, and at the study\u2019s end. Results: A statistically significant improvement was observed in depressive symptoms, as reflected by reductions in HAMD-17 (p &lt; 0.001) and GDS-15 scores (p &lt; 0.05), as well as in overall clinical severity assessed by the Clinical Global Impression\u2013Severity scale (CGI-S, p &lt; 0.05). No significant changes were noted in cognitive performance (MOCA) or apathy (AES-I). The treatment was well tolerated. Conclusions: Choline alfoscerate may represent a potentially safe and promising therapeutic option for subthreshold depression in older adults. However, given the exploratory nature of this open-label pilot study, these findings should be considered preliminary and hypothesis-generating and require confirmation in randomized controlled trials.<\/jats:p>","DOI":"10.3390\/jcm15114037","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T16:06:08Z","timestamp":1779465968000},"page":"4037","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Choline Alfoscerate in the Treatment of Subthreshold Depression in the Elderly: A Pilot Study (CARTESIO)"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1538-6025","authenticated-orcid":false,"given":"Filippo","family":"Fleishhacker","sequence":"first","affiliation":[{"name":"Dipartimento di Salute Mentale e Dipendenze, ASST Lodi, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Bonfanti","sequence":"additional","affiliation":[{"name":"Dipartimento di Salute Mentale e Dipendenze, ASST Lodi, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicol\u00f2","family":"Granata","sequence":"additional","affiliation":[{"name":"Dipartimento di Salute Mentale e Dipendenze, ASST Lodi, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Mencacci","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Mentali e Neuroscienze, ASST Fatebenefratelli, 20157 Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7153-9191","authenticated-orcid":false,"given":"Mario","family":"Mangrella","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Italfarmaco S.p.a., 20216 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5556-3590","authenticated-orcid":false,"given":"Roberto","family":"Piazza","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Italfarmaco S.p.a., 20216 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6631-3634","authenticated-orcid":false,"given":"Ilaria","family":"Coco","sequence":"additional","affiliation":[{"name":"Medical Affairs Department, Italfarmaco S.p.a., 20216 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3247-7300","authenticated-orcid":false,"given":"Giancarlo","family":"Cerveri","sequence":"additional","affiliation":[{"name":"Dipartimento di Salute Mentale e Dipendenze, ASST Lodi, 26900 Lodi, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1080\/13651501.2022.2087530","article-title":"Subthreshold depression\u2014concept, operationalisation and epidemiological data. 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