Retrosplenial hypometabolism precedes the conversion from mild cognitive impairment to Alzheimer's disease

Abstract INTRODUCTION Not all individuals who experience mild cognitive impairment (MCI) transition through progressive stages of cognitive decline at the same rate, if at all. Previous observational studies have identified the retrosplenial cortex (RSC) as an early site of hypometabolism in MCI which seems to be predictive of later transition to Alzheimer's disease (AD). METHODS We examined N = 399 MCI subjects with baseline 18 F‐fluorodeoxyglucose positron emission tomography. Subjects were classified based on whether their diagnosis converted from MCI to AD. RESULTS Whole‐brain metabolism was decreased in converters (MCI‐AD). This effect was more prominent at the RSC, where MCI‐AD subjects showed even greater hypometabolism. Observations of RSC hypometabolism and its utility in predicting transition from MCI‐AD withstood statistical analyses in a large retrospective study. DISCUSSION These results point to the utility of incorporating RSC hypometabolism into predictive models of AD progression risk and call for further examination of mechanisms underlying this relationship. Highlights Not all individuals who develop MCI will progress to AD. Individuals with MCI who progress to AD show early whole‐brain hypometabolism. Early hypometabolism is particularly prominent at the RSC.