Blood Amyloid-β Reduction Following Chongnoi-tang Treatment in Alzheimer's Spectrum Conditions: A Retrospective Pilot...

Anti-amyloid immunotherapies reduce amyloid-β (Aβ) plaques but carry a 15-35% risk of amyloid-related imaging abnormalities (ARIA), particularly in APOE ε4/ε4 carriers. This preliminary observational study evaluated blood Aβ oligomer changes following treatment with the multi-component herbal formula Chongnoi-tang (CNT) and contextualized these findings against natural disease trajectories in National Alzheimer's Coordinating Center (NACC) and Alzheimer's Disease Neuroimaging Initiative (ADNI) reference cohorts.

This retrospective pilot cohort included 16 patients with Alzheimer's spectrum conditions treated with CNT. Blood Aβ oligomers were measured using the AlzOn Plus immunoassay. Primary analysis (n = 13) excluded cases with a ceiling-level baseline value, an intercurrent potentially confounding condition, or no true baseline measurement.

Mean blood Aβ oligomer levels decreased by 15.8% ± 13.4% at 6 months (median -20.6%; 95% CI -23.9% to -7.8%; Wilcoxon signed-rank test, p < 0.001; paired Cohen's dz = 1.07). At each participant's final available follow-up, all 13 primary-analysis patients had values below baseline. High-risk patients (n = 4) showed a mean 25.7% reduction. Baseline Aβ level and 6-month percent biomarker change exhibited an exploratory, non-significant inverse trend in the Pearson correlation (r = -0.489, p = 0.090) that was weaker and non-significant in the Spearman sensitivity analysis (ρ = -0.300, p = 0.320), consistent with regression to the mean and mathematical coupling as plausible contributors. Importantly, all four APOE ε4/ε4 homozygotes showed Aβ reductions without ARIA-like clinical events. Mini-Mental State Examination (MMSE) worsening occurred in 37.5% (3/8) of CNT-treated patients versus 42.9% (15/35) in propensity-matched NACC controls (p = 0.89); given the small sample, this comparison is inconclusive.

In this small, uncontrolled pilot study, CNT was associated with blood Aβ reductions, which should be interpreted as a statistical association rather than confirmed evidence of a treatment effect; no treatment discontinuations due to adverse effects were documented in this small cohort, including among APOE ε4/ε4 carriers. These hypothesis-generating findings warrant further confirmation in prospective randomized controlled trials.