Specific molecular and neurochemical changes mark each dementia, and, in a revolutionary fashion, neuroimaging can identify such changes through use of specific ligands. In the research sphere, the use of Aβ-binding agents has provided the means to visualize early evidence of plaques in the living brain. The first agent to be widely used, the carbon 11–radiolabeled agent BTA or Pittsburgh Compound B, has been handicapped by the need for a cyclotron near the PET imaging center, but fluorine 18–radiolabeled agents, including florbetapir (AV-45), florbetaben (BAY-949172 or AV-1), and flutemetamol, have now achieved wide use in research studies. The Alzheimer's Disease Neuroimaging Initiative studies, funded through a partnership between the National Institutes of Health and industry, have shown the ability, even in different centers using different imaging instruments, to reliably detect amyloid binding. A very high percentage of cases of clinical AD, and essentially 100% of cases of pathologically proven AD, show amyloid binding through PET imaging techniques using these agents. Similarly, persons with MCI who progress to AD generally show evidence of amyloid deposition by amyloid PET imaging. However, amyloid binding seen on PET scans also occurs in a moderate percentage (20%-40%) of persons with normal cognition, depending on age.14,15 The favored implication of this finding is that persons with such ligand binding are at the beginning, asymptomatic, stage of AD, which might become manifest at some later age. Imaging findings have now been incorporated into the new clinical criteria for AD, MCI, and presymptomatic AD.3- 6 Because clinical drug trials are aimed at interrupting AD at the earliest stage, these trials may increasingly demand evidence of amyloid binding by PET as an eligibility criteria to increase the homogeneity and accuracy of diagnosis. In one recent European trial16 that did not use amyloid binding as an eligibility factor, nearly 20% of subjects entering the trial with clinically probable AD had no significant amyloid binding, which suggests a likely erroneous diagnosis of AD in those cases. Similar evidence for imperfect clinical diagnosis is present in the observational Alzheimer's Disease Neuroimaging Initiative study as well as in neuropathological series. Ligand imaging may assist in diagnosis but is also potentially useful in monitoring treatment. Drug trials with an intravenously administered antibody specific for Aβ42 (ie, bapineuzumab) have shown in vivo reduction of brain amyloid levels in human research subjects.16 Nuclear medicine imaging techniques using PET or SPECT can also detect changes in nigrostriatal function seen in Parkinson disease and Lewy body dementia. Positron emission tomographic imaging with fluorine 18–radiolabeled fluorodopa can reveal presynaptic dopaminergic insufficiency. Likewise, PET imaging using the investigational agent 18F-AV-133, or SPECT imaging using radiolabeled tropanes (eg, 123I-ioflupane [DaTscan], which was recently approved in the United States) that are taken up by the vesicular monoamine transporters, can confirm clinically suspected dopaminergic deficits in Parkinson disease or Lewy body dementia.