Chinese herbal medicine formulas for Alzheimer's disease: Evidence, mechanisms, and translational standards

Alzheimer's disease (AD) is defined biologically by amyloid and tau pathology. The emergence of biomarker-based diagnostic criteria, blood-based assays, and anti-amyloid therapeutic trials has substantially raised the evidentiary standard for all candidate AD interventions, including Chinese herbal medicine (CHM) formulas. However, CHM formula evidence for AD lacks critical appraisal and methodological standards. Thus, this review aims to: (1) critically evaluate the clinical, mechanistic, and translational evidence for oral or topical CHM formulas used in AD, specifically those selected according to Traditional Chinese Medicine (TCM) diagnostic; and (2) assess the methodological requirements necessary for credible development of such formulas in AD research. Preclinical studies suggest plausible effects of CHM formulas on amyloid-related pathways, tau phosphorylation, neuroinflammation, oxidative stress, and energy metabolism, but these findings remain hypothesis-generating rather than clinically validated. Most included studies relied on clinical diagnoses, likely encompassing mixed pathologies (e.g., vascular dementia, dementia with Lewy bodies, or depression-related cognitive impairment), rendering their results preliminary rather than confirmatory for biologically defined AD. Current evidence does not support CHM formulas as established therapies for AD. Future studies will require biomarker-confirmed diagnosis, rigorous formula quality control, prespecified TCM pattern stratification, clinically meaningful cognitive and functional endpoints, mechanistic target-engagement measures, and prospective safety and herb-drug interaction monitoring.