Neuroimaging biomarkers, namely hippocampal volume loss, temporoparietal hypometabolism, and neocortical ␤-amyloid (A␤) deposition, are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our aim was to characterize the cognitive and brain profiles of elders classified as positive or negative for each biomarker to further our understanding of their use in the preclinical diagnosis of AD. Fifty-four cognitively normal individuals (age ϭ 65.8 Ϯ 8.3 years) underwent neuropsychological tests (structural MRI, FDG-PET, and Florbetapir-PET) and were dichotomized into positive or negative independently for each neuroimaging biomarker. Demographic, neuropsychological, and neuroimaging data were compared between positive and negative subgroups. The MRI-positive subgroup had lower executive performances and mixed patterns of lower volume and metabolism in AD-characteristic regions and in the prefrontal cortex. The FDG-positive subgroup showed only hypometabolism, predominantly in AD-sensitive areas extending to the whole neocortex, compared with the FDG-negative subgroup. The amyloid-positive subgroup was older and included more APOE 4 carriers compared with the amyloidnegative subgroup. When considering MRI and/or FDG biomarkers together (i.e., the neurodegeneration-positive), there was a trend for an inverse relationship with A␤ deposition such that those with neurodegeneration tended to show less A␤ deposition and the reverse was true as well. Our findings suggest that: (1) MRI and FDG biomarkers provide complementary rather than redundant information and (2) relatively young cognitively normal elders tend to have either neurodegeneration or A␤ deposition, but not both, suggesting additive rather than sequential/causative links between AD neuroimaging biomarkers at this age. Key words: Alzheimer's disease; amyloid; biomarkers; FDG; MRI; PET Significance StatementNeuroimaging biomarkers are included in the recent research criteria for preclinical Alzheimer's disease (AD). However, how to use these biomarkers is still being debated, especially regarding their sequence. Our findings suggest that MRI and FDG-PET biomarkers should be used in combination, offering an additive contribution instead of reflecting the same process of neurodegeneration. Moreover, the present study also challenges the hierarchical use of the neuroimaging biomarkers in preclinical AD because it suggests that the neurodegeneration observed in this population is not due to ␤-amyloid deposition. Rather, our results suggest that ␤-amyloid-and tau-related pathological processes may interact but not necessarily appear in a systematic sequence.

Cortical and subcortical gray matter abnormalities are associated with cognitive status in patients with RBD, with more extensive patterns in patients with MCI. Our results highlight the importance of distinguishing between subgroups of patients with RBD according to cognitive status in order to better understand the neurodegenerative process in this population.