Cognition and Dopamine D2 Receptor Availability in the Striatum in Older Patients with Schizophrenia

Objectives: To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D-2 receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older. Design: Open-label prospective PET [C-11]-raclopride study. Setting: A tertiary care center outpatient setting. Participants: Thirty-seven clinically stable participants with schizophrenia or schizoaffective disorder, aged 50 years or greater, and having been treated with olanzapine or risperidone monotherapy at the same dose for at least 6 months. Intervention: Gradual reduction in their olanzapine or risperidone daily dose of up to 40%. Measurements: Clinical and cognitive assessments, and [C-11]-raclopride PET to determine D-2 receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D-2 receptor availability in whole striatum. Results: Reducing the antipsychotic dose resulted in an increase in D-2 receptor availability in the whole striatum and an association between D-2 receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D-2 receptor availability and change in overall cognition. Conclusions: Our findings suggest that optimizing D-2 receptor availability by reducing antipsychotic dose allows this system to contribute more significantly to cognitive function in patients with schizophrenia. This uncovered association could be harnessed by cognitive-enhancing interventions.