Assessing Mild Cognitive Impairment with Amyloid and Dopamine Terminal Molecular Imaging

We evaluated PET-based classification of neurodegenerative pathology in mild cognitive impairment (MCI). Methods: Our study was a cross-sectional and prospective evaluation of a cohort of 27 MCI subjects drawn from a university-based cognitive disorders clinic. We compared expert clinical consensus classification of MCI at entry and possible dementia at follow-up with molecular imaging-based classification using C-11-dihydotetrabenazine PET measurement of striatal dopamine terminal integrity and C-11-Pittsburgh compound B (C-11-PiB) PET measurement of cerebral amyloid burden. Results: Eleven subjects were initially classified clinically as amnestic MCI, 7 as multidomain MCI, and 9 as nonamnestic MCI. At a mean follow-up of 3 y, 18 subjects converted to dementia. PET imaging evidence of significant cerebral amyloid deposition or nigrostriatal denervation was a strong predictor of conversion to dementia. There was only moderate concordance between expert clinical classifications and PET-based classifications of dementia subtypes. Conclusion: Combined PET molecular imaging of cerebral amyloid burden and striatal dopamine terminal integrity may be useful for identifying subjects at high risk for progression to dementia and in defining neurochemically differentiated subsets of MCI subjects.