Sachiko Koyama, Linh Pham, Yuka Murakawa, Yoko Ogawa, 寺内加奈子, Keith Davis
Dementia, including Alzheimer's disease (AD), represents one of the most pressing public health challenges of the 21st century, affecting more than 55 million individuals worldwide, with projections reaching 139 million by 2050. Current pharmacological treatments offer limited efficacy and significant side effects, driving intense interest in plant-derived natural products as both preventive and therapeutic agents. This review synthesizes preclinical and clinical evidence for key phytochemical classes, including polyphenols, phenolic acids, flavonoids, terpenoids, and alkaloids, in the context of dementia and age-related cognitive decline. Molecular mechanisms are examined in detail, including effects on antioxidant defense and redox homeostasis, suppression of neuroinflammation, and enhancement of synaptic plasticity and neurotransmission. Despite promising preclinical and epidemiological evidence, most clinical trials remain limited in scale and duration and provide mixed results on the efficacy of using phytochemicals for cognitive health. Among the compounds with the most consistent clinical support are the ginkgo diterpene extract EGb 761, saffron carotenoids, curcumin, and rosmarinic acid. A dedicated section addresses the emerging evidence for aromatherapy as a non-pharmacological intervention for behavioral and cognitive symptoms of dementia. Future directions include strategies to improve bioavailability of phytochemicals, the utilization of aromatherapy together with oral supplements, and the need for larger randomized controlled trials using well-characterized and reproducibly manufactured formulations and purified active compounds. Priority areas for future investigation include resolving pharmacokinetic barriers to central nervous system (CNS) delivery, standardizing herbal product composition, and conducting adequately designed clinical trials in well-defined patient populations.