From Physiological Spaces to Cognitive Health: A New Perspective on Combined Acupuncture and Chinese Herbal Medicine for Alzheimer's Disease.

Alzheimer's disease (AD) is an escalating global health challenge. Although the target-centric paradigm focusing on targets such as β-amyloid (Aβ) deposition, tau hyperphosphorylation, and neuroinflammation has advanced our understanding of AD, translated therapies remain limited in reversing disease progression. Viewing the brain through the lens of physiological spaces offers an alternative framework for re-evaluating AD pathogenesis. Under this theoretical model, the body comprises both physical structures ("entities") and fluid-filled interstitial networks ("spaces"), with the latter facilitating metabolic transport, waste clearance, and intercellular signaling. Cerebral perivascular spaces, the extracellular space, and the glymphatic pathway represent specialized cranial interstitial networks. Fluid dynamic impairment within these spatial domains may serve as an upstream trigger for downstream Aβ aggregation, tau pathology, and neuroinflammatory cascades. Combining acupuncture with Chinese herbal medicine may restore fluid homeostasis and spatial patency across these networks. In a preliminary exploration study of 11 patients with mild-to-moderate AD, combined intervention showed encouraging trends toward improving cognitive performance and modulating relevant fluid biomarkers. This spatial perspective provides a complementary target for future AD disease-modifying strategies.