The role of dopaminergic imaging in patients with symptoms of dopaminergic system neurodegeneration

Diagnosis of neurological and psychiatric conditions associated with disturbances of dopaminergic functioning can be challenging, especially in the early stages, and may be assisted with biomarkers such as dopamine system imaging. Distinguishing between Alzheimer's disease and dementia with Lewy bodies is a major diagnostic challenge. Clinical diagnosis of Parkinson's disease is straightforward with classic presentation, but accurate distinction among Parkinsonian variants may be difficult; non-Parkinson's disease conditions are commonly misdiagnosed as Parkinson's disease, and ∼20% of patients with Parkinson's disease are not clinically diagnosed despite coming to medical attention. Early and accurate diagnosis is desirable to improve management. Imaging of the dopamine transporter using single-photon emission computed tomography may be of particular utility in this regard. Abnormal imaging indicates underlying nigrostriatal neurodegeneration, supportive of a diagnosis of Parkinson's disease, atypical parkinsonism or dementia with Lewy bodies, and identifies patient groups in whom dopaminergic therapy may be beneficial. Normal imaging supports diagnosis of a condition not involving nigrostriatal neurodegeneration such as Alzheimer's disease, essential tremor or drug-induced parkinsonism and hence a different therapeutic approach. In patients in whom there was diagnostic uncertainty between degenerative parkinsonism and non-degenerative tremor disorders, baseline imaging with the dopamine transporter ligand [123I]ioflupane (DaTscan™) has shown 78% sensitivity and 97% specificity with reference to clinical diagnosis at 3 years, versus 93% and 46%, respectively, for baseline clinical diagnosis. In a Phase III trial of [123I]ioflupane in patients with initial clinical diagnosis of probable or possible dementia with Lewy bodies or non-Lewy body dementia, mean specificity for excluding non-Lewy body dementia (predominantly Alzheimer's disease) was 90.4%. Using clinical diagnosis as a reference against which to assess sensitivity and specificity of dopamine transporter imaging is a limitation, but definitive diagnosis via pathological confirmation is generally not feasible. In a series of patients with post-mortem brain examination, imaging using [123I]ioflupane has demonstrated higher sensitivity (88%) and specificity (100%) for differentiating dementia with Lewy bodies from non-Lewy body dementia than clinical diagnosis (75% and 42%, respectively). Dopaminergic system imaging may be particularly valuable in patients with clinically inconclusive parkinsonism or a clinical diagnosis of possible dementia with Lewy bodies; it is not helpful in differentiating between Parkinson's disease and atypical parkinsonism, although postsynaptic dopaminergic imaging may be of utility. Other potential uses of dopamine transporter imaging include identification of patients with premotor Parkinson's disease, monitoring disease progression in testing novel therapeutics, and as an inclusion criterion for entry into clinical trials.