Subclinical dopaminergic dysfunction in asymptomatic Parkinson's disease patients' relatives with a decreased sense of smell

By the time a clinical diagnosis of Parkinson's disease (PD) is made, a sig nificant loss of dopaminergic neurons has already occurred. Identifying pat ients in the period between the presumed onset of dopaminergic cell loss an d the appearance of clinical parkinsonism may be of major importance in the development of effective neuroprotective treatment strategies. In an effor t to develop a feasible strategy to detect preclinical PD, a combination of olfactory processing tasks, including odor detection, odor identification, and odor discrimination was used to select groups of hyposmic and normosmi c individuals from a total of 250 relatives (parents, siblings, or children ) of subjects with PD, Single photon emission computed tomography (SPECT) w ith [I-123]beta -CIT as a dopamine transporter ligand was used to assess ni grostriatal dopaminergic function in 25 hyposmic and 23 normosmic relatives of PD patients, An abnormal reduction in striatal dopamine transporter bin ding was found in 4 out of 25 hyposmic relatives of PD patients, two of who m subsequently developed clinical parkinsonism, and in none of the 23 normo smic relatives. These observations demonstrate that subclinical reductions in dopamine transporter binding can be detected in asymptomatic relatives o f sporadic PD patients by means of [I-123]beta -CIT and SPECT. The results further indicate that olfactory deficits may precede clinical motor signs i n PD.