Enhancing diagnosis of mild cognitive impairment through brain-heart-gut metabolic networks in whole-body PET imaging

Mild cognitive impairment (MCI) is the prodromal stage of dementia involving complex interactions between the brain and peripheral organs. Emerging evidence indicates that heart dysfunction and gut microbiota dysbiosis contribute to MCI pathogenesis. Here, we present a framework integrating brain-heart-gut interactions using whole-body positron emission tomography (PET) to enhance brain-only diagnostic performance. Our brain-only model achieves diagnostic performance comparable to that of whole-body PET and shows promising generalizability across four datasets comprising 1,543 whole-body PET and 1,721 brain PET images. We identify key brain regions involving the limbic, parietal, frontal, and temporal cortices that engage the default mode, central autonomic, and sensorimotor networks. These regions, along with specific myocardium and distal colon, constitute an integrated brain-heart-gut metabolic network, underscoring multi-organ crosstalk mediated by neural, biochemical, and mechanical pathways. Overall, our generalizable framework not only shows great potential for clinical translation in MCI diagnosis but also provides broad applicability to other systemic diseases beyond MCI.