risks of developing Alzheimer’s disease (AD). The objective of the present study was to identify which condition in cognitively normal (CN) individuals is the most associated with an AD-like pattern of neurodegeneration. Methods: For this purpose, we compared structural-MRI and FDG-PET data in i) a group of 15 CN individuals with SCD recruited from a memory clinic to 45 matched controls without SCD recruited from the general population, and ii) a group of 10 CN individuals with amyloidpositive (Ab+) Florbetapir-PET scan to 29 matched controls with amyloid-negative scan. SCD and Ab+ individuals were matched for age, education, sex and MMSE. Results: Regarding structural-MRI, highly significant gray matter atrophy in the hippocampal region was found in the SCD compared to the controls with no SCD, and this atrophy correlated with episodic memory decline. Note that this result was not related to amyloid deposition since both groups did not differ in the proportion of amyloid positive individuals. By contrast, the Ab+ individuals did not show any sign of brain atrophy relative to the amyloid-negative controls. Regarding FDG-PET, no significant hypometabolism was found either in the SCD or in the Ab+ groups. Conclusions: Our findings showed that only CN individuals with SCD who refer to a memory clinic, but not CN individuals with amyloid deposition in the brain, have greater episodic memory-related hippocampal atrophy. Hippocampal atrophy is a key hallmark of neurodegeneration in AD and the closest biomarker of its first clinical manifestation. Thus, even if they are still asymptomatic, the short-term prognosis in individuals with SCD could be worse than that of individuals having amyloid deposition in the brain. These results emphasize the critical interest for SCD in preclinical AD.