Different Scales of Cortical Organization are Selectively Targeted in the Progression to Alzheimer's Disease

Previous studies have shown that the topological organization of the cerebral cortex is altered in Alzheimer's disease (AD). However, it remains unknown whether different levels of the cortical hierarchy are homogeneously affected during disease progression, and which of these levels are mostly involved in the breakdown of metabolic (functional) connectivity. To fulfill these goals, we acquired structural magnetic resonance images (MRI) and positron emission tomography (PET) with the radiotracer 18F-fludeoxyglucose (FDG) in 29 healthy old (HO) adults, 29 amnestic mild cognitive impairment (aMCI) and 29 mild AD patients. Structural and metabolic connections were obtained from inter- regional correlations of cortical thickness and glucose consumption, respectively. Results showed that AD and HO groups differed at all levels of cortical organization (i.e. whole cortex, hemisphere, lobe and node), whereas differences among the three groups were only evident at the lobe and node levels. The correlation between structural and metabolic connectivity (F-S coupling) was also disturbed during AD progression, affecting to different connectivity scales: it decreased at the local level, revealing a progressive increase of metabolic connections in those local communities with fewer structural connections; whereas it increased at the global level, likely due to a parallel reduction of cortical thickness and glucose consumption between long-distance cortical regions. Collectively, these results reveal that different levels of cortical organization are selectively affected during the transition from normal aging to dementia, which could be helpful to track cortical dysfunctions in the progression to AD.