We propose an in vivo method for use with positron emission tomography (PET) that results in a quantitative characterization of neuroleptic binding sites using radiolabeled spiperone. The data are analyzed using a mathematical model that describes transport, nonspecific binding, and specific binding in the brain. The model demonstrates that the receptor quantities Bmax (i.e., the number of binding sites) and KD-1 (i.e., the binding affinity) are not separably ascertainable with tracer methodology in human subjects. We have, therefore, introduced a new term, the binding potential, equivalent to the product BmaxKD-1, which reflects the capacity of a given tissue, or region of a tissue, for ligand-binding site interaction. The procedure for obtaining these measurements is illustrated with data from sequential PET scans of baboons after intravenous injection of carrier-added [18F]spiperone. From these data we estimate the brain tissue nonspecific binding of spiperone to be in the range of 94.2 to 95.3%, and the regional brain spiperone permeability (measured as the permeability-surface area product) to be in the range of 0.025 to 0.036 cm3/(s X ml). The binding potential of the striatum ranged from 17.4 to 21.6; these in vivo estimates compare favorably to in vitro values in the literature. To our knowledge this represents the first direct evidence that PET can be used to characterize quantitatively, locally and in vivo, drug binding sites in brain. The ability to make such measurements with PET should permit the detailed investigation of diseases thought to result from disorders of receptor function.

Parkinson's disease seems to occur more commonly in men than women based primarily on studies of death rates and prevalence. In recent years, several population based incidence studies of Parkinson's disease that included sex data have been conducted in a variety of populations around the world. To investigate whether these incidence studies suggest an increased risk of Parkinson's disease in men, a meta-analysis was performed of the differences in incidence of Parkinson's disease between men and women reported in seven studies that met the inclusion criteria. A significantly higher incidence rate of Parkinson's disease was found among men with the relative risk being 1.5 times greater in men than women. Possible reasons for this increased risk of Parkinson's disease in men are toxicant exposure, head trauma, neuroprotection by oestrogen, mitochondrial dysfunction, or X linkage of genetic risk factors. Whether there is a sex difference in risk for Parkinson's disease (PD) is controversial.1 PD seems to occur more commonly in men than women based primarily on studies of death rates and prevalence. 1 2 Death rates, however, do not accurately reflect the incidence of PD 3 because of inaccurate diagnoses on death certificates. Likewise, prevalence data are problematic. Prevalence studies are subject to potential sex differences in survival, access to health care, access to the system whereby cases were ascertained for inclusion in the study, and sex differences in the underlying population. 1Because incidence of PD represents the number of new cases developed or diagnosed during a specific time interval within a predefined population at risk, incidence measurements are more direct and unambiguous epidemiological estimates of risk for developing PD than are death rates or prevalence. Incidence data from well defined populations obviate a number of concerns with prevalence data, such as differential mortality between men and women.In recent years, several population based incidence studies of PD that included sex data have been conducted in a variety of populations around the world. To determine whether these incidence studies suggest an increased risk of PD in men, we performed a meta-analysis of the differences in incidence of PD between men and women reported in these studies. METHODSThe Medline database was searched for population based ascertainment studies of PD average annual incidence rates adjusted for sex and age. The studies included in our metaanalysis met six criteria: (1) The study must have been published after 1980. Inclusion of studies published before 1980 would lead to the inclusion of neurodegenerative disorders that would be recognised now as not being PD (for example, progressive supranuclear palsy, multiple system atrophy, etc). Also, older studies are more likely to be contaminated with cases of post-encephalitic parkinsonism than studies published after 1980; (2) studies must have excluded secondary and/or drug induced parkinsonism; (3) studies must have ascertained at least 50 cases of PD; (4...

This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations.

Basal ganglia structures comprise a portion of the neural circuitry that is hypothesized to coordinate the selection and suppression of competing responses. Parkinson’s disease (PD) may produce a dysfunction in these structures that alters this capacity, making it difficult for patients with PD to suppress interference arising from the automatic activation of salient or overlearned responses. Empirical observations thus far have confirmed this assumption in some studies, but not in others, due presumably to considerable inter-individual variability among PD patients. In an attempt to help resolve this controversy, we measured the performance of 50 PD patients and 25 healthy controls on an arrow version of the Eriksen flanker task in which participants were required to select a response based on the direction of a target arrow that was flanked by arrows pointing in the same (congruent) or opposite (incongruent) direction. Consistent with previous findings, reaction time (RT) increased with incongruent flankers compared to congruent or neutral flankers, and this cost of incongruence was greater among PD patients. Two novel findings are reported. First, distributional analyses, guided by dual-process models of conflict effects and the activation-suppression hypothesis, revealed that PD patients are less efficient at suppressing the activation of conflicting responses, even when matched to healthy controls on RT in a neutral condition. Second, this reduced efficiency was apparent in half of the PD patients, whereas the remaining patients were as efficient as healthy controls. These findings suggest that although poor suppression of conflicting responses is an important feature of PD, it is not evident in all medicated patients.