DOI: 10.1002/alz.13385 ISSN: 1552-5260

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

Silvia Paola Caminiti, Silvia De Francesco, Giacomo Tondo, Alice Galli, Alberto Redolfi, Daniela Perani, ,
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Amnestic mild cognitive impairment (aMCI) is emerging as a heterogeneous condition.


We 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.


Three 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 ε3/ε4 or ε4/ε4 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.


FDG‐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.


Algorithm 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.

More from our Archive