STUDY PROTOCOL article
Front. Nutr.
Sec. Nutrition, Psychology and Brain Health
Volume 12 - 2025 | doi: 10.3389/fnut.2025.1686381
Taxifolin for prevention of COGnitive impairment (T-COG trial): a study protocol for a randomized, double-blind, placebo-controlled trial
Provisionally accepted
Tetsuya Chiba
Yorito Hattori*
Koko Asakura
Yuka Sano
Satoshi SaitoManabu Minami
Haruko Yamamoto
Masafumi Ihara- National Cerebral and Cardiovascular Center (Japan), Suita, Japan
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Background: In 2023 and 2024, the novel anti-β-amyloid antibodies lecanemab and donanemab have been approved for treatment of mild cognitive impairment and mild dementia in several countries, including Japan and the United States. Although they successfully eliminate accumulated β-amyloid, they merely delay cognitive deterioration and do not improve cognitive function. This suggests that β-amyloid elimination is insufficient for cognitive improvement. Therefore, novel treatments with pleiotropic neuroprotective effects are warranted. Taxifolin, a bioactive flavonoid, shows pleiotropic effects, such as inhibition of amyloid-β aggregation and oligomerization and hippocampal neuroinflammation, as well as stimulation of brain lymphatic vessel formation in our previous experimental studies. Furthermore, our preliminary observational study showed that oral administration of taxifolin was associated with cognitive improvement in patients with mild cognitive impairment or mild dementia. Methods: This is a randomized, double-blind, placebo-controlled, crossover trial involving 60 patients with mild cognitive impairment or mild dementia. All participants will take 100-mg taxifolin or placebo capsules orally once daily for 12 weeks. The washout period will be 6 weeks. The primary objective is to determine the effect of taxifolin on cognitive impairment using the Montreal Cognitive Assessment. The main secondary objectives are to evaluate the impact of taxifolin on (i) prevention further cognitive decline, as evaluated by changes in the scores for total Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 and trail making test and (ii) changes in white matter hyperintensity volume and number of cerebral microbleeds on brain magnetic resonance imaging. Discussion: This T-COG trial may provide valuable insights into new therapeutic approaches, considering that taxifolin has multitarget neuroprotection, which could prevent further cognitive decline, along with its highly safe profile and inexpensive cost. Clinical trial registration: The T-COG trial was prospectively registered in the Japan Registry of Clinical Trials (registration number: jRCTs051250004, https://jrct.mhlw.go.jp) on April 7, 2025.
Keywords: Taxifolin, Alzheimer's disease, Mild Cognitive Impairment, randomized controltrial, double-blind, placebo
Received: 15 Aug 2025; Accepted: 30 Sep 2025.
Copyright: © 2025 Chiba, Hattori, Asakura, Sano, Saito, Minami, Yamamoto and Ihara. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yorito Hattori, yoh2019@ncvc.go.jp
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.