FDG-PET markers of heterogeneity and different risk of progression in amnestic MCI

INTRODUCTIONAmnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition. METHODSWe looked at a cohort of N = 207 aMCI subjects, with baseline fluorodeoxyglucose positron emission tomography (FDG-PET), T1 magnetic resonance imaging, cerebrospinal fluid (CSF), apolipoprotein E (APOE), and neuropsychological assessment. An algorithm based on FDG-PET hypometabolism classified each subject into subtypes, then compared biomarker measures and clinical progression. RESULTSThree subtypes emerged: hippocampal sparing-cortical hypometabolism, associated with younger age and the highest level of Alzheimer's disease (AD)-CSF pathology; hippocampal/cortical hypometabolism, associated with a high percentage of APOE & epsilon;3/& epsilon;4 or & epsilon;4/& epsilon;4 carriers; medial-temporal hypometabolism, characterized by older age, the lowest AD-CSF pathology, the most severe hippocampal atrophy, and a benign course. Within the whole cohort, the severity of temporo-parietal hypometabolism, correlated with AD-CSF pathology and marked the rate of progression of cognitive decline. DISCUSSIONFDG-PET can distinguish clinically comparable aMCI at single-subject level with different risk of progression to AD dementia or stability. The obtained results can be useful for the optimization of pharmacological trials and automated-classification models. HighlightsAlgorithm based on FDG-PET hypometabolism demonstrates distinct subtypes across aMCI;Three different subtypes show heterogeneous biological profiles and risk of progression;The cortical hypometabolism is associated with AD pathology and cognitive decline;MTL hypometabolism is associated with the lowest conversion rate and CSF-AD pathology.