Distinct alterations of adiponectin, FGF-21 and IGFBP-2 link dysmetabolism with cognitive decline across the Alzheimer's disease spectrum

STRUCTURED ABSTRACTO_ST_ABSIntroductionC_ST_ABSMetabolic disorders are risk factors for Alzheimers disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers - adiponectin, FGF-21 and IGFBP-2 - and AD. MethodsParticipants with subjective cognitive decline (SCD), mild cognitive impairment (MCI), AD and cognitively healthy controls (CH) were from the CIMA-Q cohort (n=287). Serum adiponectin, FGF-21, and IGFBP-2 concentrations were measured, compared between groups, and assessed for associations with clinical, cognitive, biochemical and MRI data. ResultsMetabolic dysfunction was linked to lower adiponectin and IGFBP-2, but higher FGF-21. Both FGF-21 and IGFBP-2 increased with age and were inversely associated with cognitive performance. IGFBP-2 was elevated at SCD stage and correlated with plasma pTau181 and amygdala atrophy. Adiponectin was unrelated to cognition. DiscussionThese findings suggest that IGFBP-2, and FGF-21 to a lesser extent, may serve as early biomarkers of cognitive impairment, reflecting intricate links between peripheral dysmetabolism and AD.