Patients with amnestic mild cognitive impairment (aMCI) are heterogeneous as regard to their amyloid status. As amyloid is thought to accumulate decades before first symptoms, patients who already have cognitive deficits but have no amyloid deposition raise questions regarding the origin of symptoms and offer a great opportunity to investigate the long term effect of amyloid deposition on brain and cognition. There has been no study to date assessing both cognition and brain structure and function to provide a comprehensive picture on what is similar and different between amyloid positive (Aβ+) versus amyloid negative (Aβ-) aMCI.


      Forty five aMCI patients all recruited and scanned in the same centre were dichotomized into Aβ+ and Aβ- subgroups based on cerebral Florbetapir SUVR (and a threshold based on healthy population). All patients underwent a 3T T1 structural MRI, FDG-PET scans and neuropsychological assessment. Data were compared between aMCI subgroups and to 24 matched healthy elderly Aβ- (HE). Neuroimaging data analyzes included volume and metabolism comparisons within specific AD-sensitive regions-of-interest and voxelwise analyses with SPM.


      Aβ+ and Aβ- aMCI were significantly impaired in most neuropsychological tests compared to HE. Aβ+ aMCI had lower performances in episodic memory than Aβ- aMCI, while Aβ- aMCI had worse scores than Aβ+ aMCI in executive and language functions. Aβ+ and Aβ- aMCI both showed significant (FWE p< 0.05 cluster-level corrected) hippocampal atrophy and parieto-temporal hypometabolism compared to HE, but there was no significant difference voxelwise between aMCI subgroups. Only a trend for lower hippocampal volume in the Aβ+ aMCI compared to the Aβ- aMCI (p=0.05 and 0.08 for the right and left hippocampus respectively) was found when using a ROI approach.


      These results might be interpreted in two ways. First, they suggest that the detailed neuropsychological profile is more helpful in predicting the amyloid status than the atrophy/hypometabolism pattern at the MCI stage. Second, the fact that both aMCI subgroups exhibit the same patterns of atrophy and hypometabolism suggests either that these patterns are not related with amyloid deposition or that different pathological processes conduct to the same brain alterations in aMCI.