The olfactory-glymphatic syndrome: linking smell dysfunction, cognitive impairment and sleep disturbances in neuropathological disorders.

Olfactory dysfunction is a common feature of several neuropathological disorders - including Alzheimer's and Parkinson's diseases - whose shared profile often includes glymphatic dysfunction, cognitive impairment, and sleep disturbances. Importantly, smell loss frequently precedes cognitive or motor symptoms by years, highlighting its potential as an early clinical marker. This article reviews mechanisms that may link olfactory dysfunction to disease development in a wide range of neuropathological diseases and advances a research-based hypothesis for a shared etiologic pathway underlying these overlapping symptoms. In particular, it examines metabolic syndrome as a possible upstream driver that promotes nasal turbinate vasodilation, disrupts nasal lymphatic drainage, and culminates in an olfactory-glymphatic syndrome. Integrating glymphatic imaging or assessment with olfactory testing, cognitive evaluation, and metabolic risk profiling - hypertension, diabetes mellitus, hyperlipidemia, and elevated body mass index - may enable earlier detection and open new avenues for prevention and novel therapeutic opportunities for neuropathological disorders.