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

To assess the impact of reducing the dose of antipsychotics on cognition and dopaminergic D₂ receptor availability in the whole striatum, and identify their relationship in patients with schizophrenia aged 50 years or older.

Open-label prospective PET [¹¹C]-raclopride study.

A tertiary care center outpatient setting.

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.

Gradual reduction in their olanzapine or risperidone daily dose of up to 40%.

Clinical and cognitive assessments, and [¹¹C]-raclopride PET to determine D₂ receptor availability at baseline and after the dose reduction. Main outcome measures were overall cognition and D₂ receptor availability in whole striatum.

Reducing the antipsychotic dose resulted in an increase in D₂ receptor availability in the whole striatum and an association between D₂ receptor availability and overall cognition despite lack of change in the latter. There was also an association between change in D₂ receptor availability and change in overall cognition.

Our findings suggest that optimizing D₂ 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.