Cognitive impairment and the brain dopaminergic system in Parkinson disease - [F-18]fluorodopa positron emission tomographic study

Objective: To investigate the role of the brain dopaminergic system in cogn itive impairment in patients with Parkinson disease (PD). Design: We studied 28 patients with PD and 16 age-matched healthy control s ubjects using [F-18]fluorodopa (fluorodopa F 18) positron emission tomograp hy. Patients with PD showed a variable degree of cognitive impairment, whic h was assessed using the Mini-Mental State Examination and detailed neurops ychologic assessment, including tests sensitive for frontal lobe function. Results: [F-18]Fluorodopa uptake was reduced in the putamen ito 36% of the control mean: P < .001), the caudate nucleus (to 61% of the control mean: P < .001), and the frontal cortex (to 45% of the control mean: P < .001) in patients with PD compared with controls. There was no significant associati on between the degree of overall cognitive impairment of patients and [F-18 ] fluorodopa uptake values. The influx constant (K-l(occ)) in the caudate n ucleus had a negative association with performance in the attention-demandi ng Stroop interference task, especially with the interference time. The K-l (occ) in the frontal cortex had a positive correlation with performance in the digit span (backwards) verbal fluency, and verbal immediate recall test s. Thus, the better the patient performed in tasks demanding immediate and working memory and executive strategies, the better the [F-18]fluorodopa up take in the frontalcortfs. In the putamen, no significant correlation was s een between the k(l)(occ) value and any of the cognitive tests. The severit y of the motor symptoms of PD and [F-18]fluorodopa uptake show ed a negativ e correlation in the putamen (r = -0.38; P = .04), and in the caudate nucle us a similar trend was seen (r = -0.36; P = .06), Conclusions: Reduced [F-18]fluorodopa uptake in PD in the caudate nucleus ( and frontal cortex) is related to impairment in neuropsychologic tests meas uring verbal fluency, working memory, and attentional functioning reflectin g frontal lobe function. This indicates that dysfunction of the dopamine sy stem has an impact on the cognitive impairment of patients with PD. However , our results do not exclude the possibility of more generalized cognitive impairment in PD, the pathophysiology of which is probably different and mo re generalized.