Front Nutr. 2026 Jan 26;13:1740494. doi: 10.3389/fnut.2026.1740494. eCollection 2026.
ABSTRACT
BACKGROUND: 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's 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.
OBJECTIVE: 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).
METHODS: In a 42-month randomized, double-blind, placebo-controlled trial, 26 participants aged 63-90 years with memory impairment were randomly assigned to receive either 30 mg/day of GLR (n = 13) or placebo (n = 12). 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.
RESULTS: 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 (p = 0.012). No significant group difference was observed in the initial 6 months, but a marginal difference in favor of GLR appeared in the later phase (30 and 42 months), including the 42-month endpoint (p = 0.079). Conversion/reversion rates were not significantly different. The GLR group demonstrated superior performance on immediate recall and delayed free recall tests (p < 0.001 and p = 0.012, respectively). MCI participants showed a greater MPI improvement with GLR (p = 0.029). No severe adverse events related to the intervention were reported.
CONCLUSION: 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.
PMID:41669080 | PMC:PMC12884063 | DOI:10.3389/fnut.2026.1740494