The impact of light therapy on emotional enhancement in APOE-ε4 carrying and biomarker-positive high-risk populations for Alzheimer's disease (SCD/aMCI) and analysis of associated risk factors

This randomized controlled trial assessed the intervention effect of a 4‑week morning blue‑green light therapy (500 nm) on mood in Alzheimer’s disease (AD) high‑risk individuals (subjective cognitive decline/amnestic mild cognitive impairment, SCD/aMCI) who are APOE‑ε4 carriers and/or exhibit positive AD fluid biomarkers and explored its clinical value as a non‑pharmacological intervention. 120 eligible participants (all with baseline HAMD‑17 ≥ 8) were randomized to two groups: the intervention group received 50 min/day of blue‑green light, while the control group was exposed to standard indoor lighting and wore a sham device. The primary outcome was clinically significant mood improvement (≥ 20% reduction in HAMD‑17 score from baseline). Baseline cognitive function was evaluated via MMSE to analyze its correlation with treatment response. All participants underwent 3T structural MRI and plasma Aβ42, Aβ40, and p‑tau181 measurements. Morning blue‑green light therapy (500 nm, 506 lx, 50 min/day for 4 weeks) resulted in significant mood improvement in high‑risk AD patients (SCD/aMCI), with 66.67% achieving clinically meaningful mood improvement (≥ 20% reduction in HAMD-17 scores; p < .001 compared to 22.64% in controls). When using the conventional 50% reduction criterion, response rates were 38.33% vs. 9.43%. Notably, baseline MMSE scores were predictive of treatment efficacy: each 1‑point increase was associated with a 2.08‑fold elevated risk of treatment failure (OR = 2.082, 95% CI 1.241–3.493; p = 0.005). Furthermore, an MMSE threshold > 28 predicted non‑response with moderate diagnostic accuracy (AUC = 0.741, sensitivity 80.0%, specificity 62.5%), suggesting that preserved cognitive function may attenuate therapeutic benefits. Morning blue-green light exposure effectively enhances mood in approximately two-thirds of biomarker-confirmed AD high-risk patients, while baseline MMSE scores may serve as a clinical predictor for treatment stratification. Trial registration: [Chinese Clinical Trial Registry] [ChiCTR2500104069] (2025-06-10). Retrospectively registered.