{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:24:15Z","timestamp":1789986255608,"version":"4.0.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T00:00:00Z","timestamp":1769385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates cellular defense mechanisms and has been proposed as a therapeutic target for Alzheimer\u2019s disease (AD). Preclinical studies suggest that long-term oral administration of glucoraphanin (GLR), a natural Nrf2 activator, mitigates age-related cognitive decline in animal models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study evaluated the long-term efficacy of GLR supplementation on cognitive function in older adults at an elevated risk for AD, including those with mild cognitive impairment (MCI).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63\u201390\u202fyears with memory impairment were randomly assigned to receive either 30\u202fmg\/day of GLR (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f13) or placebo (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f12). The primary outcome was the change in Memory Performance Index (MPI) scores from the MCI Screen. Secondary outcomes included conversion\/reversion rates between normal cognition and MCI.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Ten participants in the GLR group and nine participants in the placebo group completed the trial. Analysis using a Linear Mixed Model (LMM) across the entire study period revealed a significant group by time-point interaction for MPI scores, with the GLR group showing a significantly greater improvement in MPI scores compared to the placebo (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.012). No significant group difference was observed in the initial 6\u202fmonths, but a marginal difference in favor of GLR appeared in the later phase (30 and 42\u202fmonths), including the 42-month endpoint (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.079). Conversion\/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f&amp;lt;\u202f0.001 and\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.012, respectively). MCI participants showed a greater MPI improvement with GLR (\n                      <jats:italic>p<\/jats:italic>\n                      \u202f=\u202f0.029). No severe adverse events related to the intervention were reported.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Long-term GLR supplementation may help preserve cognitive function in individuals at elevated risk for AD, particularly those with MCI. Larger trials are warranted to confirm efficacy and clarify underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnut.2026.1740494","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T09:43:31Z","timestamp":1769420611000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of 42-month oral administration of glucoraphanin in preventing cognitive decline in individuals at elevated risk of dementia, including those with mild cognitive impairment: a randomized, double-blind, placebo-controlled pilot study"],"prefix":"10.3389","volume":"13","author":[{"given":"Sunao","family":"Shimizu","sequence":"first","affiliation":[{"name":"Diet & Well-being Research Institute, KAGOME Co., Ltd.","place":["Nasushiobara, Japan"]},{"name":"Department of Vegetable Life Science, Hirosaki University Graduate School of Medicine","place":["Hirosaki, 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Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Suganuma","sequence":"additional","affiliation":[{"name":"Diet & Well-being Research Institute, KAGOME Co., Ltd.","place":["Nasushiobara, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigenori","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Diet & Well-being Research Institute, KAGOME Co., Ltd.","place":["Nasushiobara, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Murashita","sequence":"additional","affiliation":[{"name":"Research Institute of Health Innovation, Hirosaki University","place":["Hiroaki, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeyuki","family":"Nakaji","sequence":"additional","affiliation":[{"name":"Department of Preemptive Medicine, Innovation Center for Health Promotion, Hirosaki University Graduate School of Medicine","place":["Hirosaki, 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