Imaging of the dopaminergic system in differential diagnosis of dementia

Neurodegenerative dementia is an increasingly common disorder with Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) accounting for most cases. Due to the overlap in clinical symptoms, their differential diagnosis may be challenging. As clinical classification is not completely satisfying, there is a need to improve the diagnostic accuracy by complementary methods such as functional single-photon emission computed tomography (SPECT) and positron emission tomography (PET) imaging. The latter may be helpful to address one distinct biological difference between DLB and AD, the severe nigrostriatal degeneration which occurs in DLB, but not to any significant extent in AD. Based on this principle, autoradiographic studies targeting presynaptic dopaminergic functions have consistently demonstrated the ability to distinguish DLB from AD in postmortem series. At the same time, several single-site and one multicentre study have independently confirmed-no matter what technique was used (SPECT or PET) and which presynaptic function was addressed (dopamine turnover, dopamine transporter, vesicular monoamine transporter)-significantly compromised scan results in DLB subjects, whereas AD patients maintained almost normal findings. Even more important, in vivo findings of presynaptic dopaminergic imaging correlated well with neuropathological findings at autopsy, suggesting a remarkable sensitivity of 88% and a specificity of 100% for the imaging procedure to distinguish between DLB and AD. Taken together, imaging of presynaptic dopaminergic terminal functions with SPECT and PET has currently the greatest evidence base to support its use, and therefore, may be highly recommended to help in the discrimination between DLB and AD. Compared to presynaptic functions, corresponding data targeting postsynaptic dopamine receptors are comparatively rare, less conclusive and suggest a very limited role for this purpose. This review discusses the findings of studies specifically dealing with imaging of the dopaminergic system in the differential diagnosis of dementia.