Diabetes and the Metabolic Syndrome as Drivers of Neurodegeneration: Convergent Mechanisms Linking Peripheral Neuropathy and Dementia.

The metabolic syndrome, a state of progressive metabolic dysfunction, injures the peripheral and central nervous systems, promoting peripheral neuropathy (PN) and cognitive impairment (CI), respectively. We posit PN and CI are connected in the metabolic syndrome framework, built on the premise that neurons, whether in the peripheral or central nervous systems, are susceptible to similar injury from shared metabolic risk factors and pathophysiological processes. We highlight future studies for determining the relative evolution of PN and CI in metabolic syndrome, and propose revising the "stocking-glove" description of PN to "stocking-glove-hat" encompassing CI, concluding with research, therapeutic, and clinical implications. ANN NEUROL 2026;100:458-476.