D-2 Receptor Blockade by Attention Deficits in Risperidone Correlates With Late-Life Schizophrenia

The negative impact of antipsychotic drugs on attention is expected to be greater in late-life schizophrenia because of the age-related changes in the dopamine receptor reserve. The objective of this study was to examine the relationship between dopamine D-2 receptor blockade by risperidone and the cognitive function in late-life schizophrenia. Subjects with schizophrenia or schizoaffective disorder aged 50 or older who were receiving risperidone completed a [C-11]raclopride positron emission tomography scan to measure D-2-binding potential in the striatum. The D-2 receptor blockade by risperidone was calculated using age-corrected measures from healthy individuals and region of interest analysis of dynamic positron emission tomography data coregistered to the subjects' magnetic resonance imaging scans. Cognitive function was assessed using a battery of neuropsychological tests that included the Dementia Rating Scale-2 (DRS). Eleven subjects (mean +/- SD age, 64 +/- 8 years) participated in this study. The mean +/- SD D-2 receptor blockade was 69% +/- 14% (range, 34%-80%). The age-corrected score on the attention subscale in the DRS was negatively correlated with the D-2 receptor blockade. The DRS attention subscale score was lower in the subjects who experienced 74.9% or higher D-2. blockade (median value, corresponding to a daily risperidone dose of >3.0 mg) than in those who did not. Although a causal attribution cannot be made in light of the cross-sectional nature of this study, the results suggest the critical importance of identifying the lowest effective dose of antipsychotic drugs in older patients with schizophrenia.