Distinct alterations of adiponectin, FGF-21 and IGFBP-2 link dysmetabolism with cognitive decline across the Alzheimer’s disease spectrum
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Introduction
Metabolic disorders are risk factors for Alzheimer’s disease (AD), although underlying mechanisms remain unclear. We investigated the relationship between peripheral metabolic markers – adiponectin, FGF-21 and IGFBP-2 – and AD.
Methods
Participants 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.
Results
Metabolic 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.
Discussion
These 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.
