Serum levels of adipokines and insulin are associated with markers of brain atrophy and cognitive decline in the spectrum of Alzheimer's Disease

The discovery that metabolic alterations often coexist with neurodegenerative conditions has sparked interest in the examination of gastrointestinal factors as potential modulators of brain health. Here, we examined the role of adipokines (leptin, adiponectin, resistin, and IL6) and insulin on different markers of brain atrophy in participants on the spectrum of Alzheimer's Disease. We included 566 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset with 1063 follow-up time points (average follow-up: one year); and examined the association between gastrointestinal factors and volumetric MRI values, white matter hyperintensities, and measures of cognitive impairment. Higher leptin, resistin, IL6, and insulin were associated with markers of cerebral atrophy, such as lower total brain volume, or higher ventricular volume. Higher leptin and resistin were also associated with greater impairment in daily life activities. Higher adiponectin was associated with lower ventricle volume. There was no association between adipokines or insulin with white matter hyperintensities. Our findings indicate a co-occurrence between alterations in gastrointestinal factors and in brain volume along the preclinical to clinical spectrum of Alzheimer's Disease. These results suggest that strategies aimed at promoting metabolic health may positively impact brain health. ### Competing Interest Statement IGG and OD are currently employed at Clinique la Prairie