Differentiating Alzheimer's disease from dementia with Lewy bodies and Parkinson's disease with (+)-[11C]dihydrotetrabenazine positron emission tomography

Abstract

Background: Several progressive neurologic disorders begin with cognitive decline or parkinsonism, notably Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). We used positron emission tomography (PET) in attempts to differentiate these disorders.

Methods: We performed PET with (+)-[11C]dihydrotetrabenazine ([11C]DTBZ) to examine blood-to-brain ligand transport (K(1)) and striatal monoaminergic presynaptic binding (distribution volume [DV]) in 25 DLB, 30 PD, and 25 AD patients and 57 elderly controls (NC).

Results: [11C]DTBZ DV was decreased significantly in caudate nucleus, anterior putamen, and posterior putamen in DLB and PD compared with AD and NC. DLB and PD groups showed an anterior-to-posterior gradient of binding loss relative to NC, least in caudate nucleus and largest in posterior putamen. The gradient was significantly steeper in PD than DLB. Both PD and DLB showed significantly greater interhemispheric striatal binding asymmetry than NC, and PD had greater asymmetry than DLB. Cerebral cortical [11C]DTBZ K(1) was decreased diffusely by 4% to 8% in PD. Larger K(1) deficits occurred in AD and DLB temporoparietal and prefrontal association cortices and posterior cingulate cortex. Greater reduction of K(1) occurred in occipital cortex in DLB than AD. Receiver operating characteristic curve analyses distinguished DLB from AD more effectively on the basis of striatal DV than occipital K(1) and distinguished DLB from PD more effectively on the basis of cerebral cortical K(1) than striatal DV patterns. Overall, 90% of cases were properly classified by combining these measures.

Conclusions: PET with [11C]DTBZ can differentiate DLB from both PD and AD in a single neuroimaging study.