Deep brain stimulation (DBS) is associated with significant improvement of motor complications in patients with severe Parkinson's disease after some 6-12 months of treatment. Long-term results in a large number of patients have been reported only from a single study centre. We report 69 Parkinson's disease patients treated with bilateral DBS of the subthalamic nucleus (STN, n = 49) or globus pallidus internus (GPi, n = 20) included in a multicentre study. Patients were assessed preoperatively and at 1 year and 3-4 years after surgery. The primary outcome measure was the change in the 'off' medication score of the Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) at 3-4 years. Stimulation of the STN or GPi induced a significant improvement (50 and 39%; P < 0.0001) of the 'off' medication UPDRS-III score at 3-4 years with respect to baseline. Stimulation improved cardinal features and activities of daily living (ADL) (P < 0.0001 and P < 0.02 for STN and GPi, respectively) and prolonged the 'on' time spent with good mobility without dyskinesias (P < 0.00001). Daily dosage of levodopa was significantly reduced (35%) in the STN-treated group only (P < 0.001). Comparison of the improvement induced by stimulation at 1 year with 3-4 years showed a significant worsening in the 'on' medication motor states of the UPDRS-III, ADL and gait in both STN and GPi groups, and speech and postural stability in the STN-treated group. Adverse events (AEs) included cognitive decline, speech difficulty, instability, gait disorders and depression. These were more common in patients treated with DBS of the STN. No patient abandoned treatment as a result of these side effects. This experience, which represents the first multicentre study assessing the long-term efficacy of either STN or GPi stimulation, shows a significant and substantial clinically important therapeutic benefit for at least 3-4 years in a large cohort of patients with severe Parkinson's disease.

Cognitive defects associated with cortical pathology may be a marker of dementia in Parkinson's disease (PD). There is a need to improve the diagnostic criteria of PD dementia (PDD) and to clarify the cognitive impairment patterns associated with PD. Current neuropsychological batteries designed for PD are focused on fronto-subcortical deficits but are not sensitive for cortical dysfunction. We developed a new scale, the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), that was designed to cover the full spectrum of cognitive defects associated with PD. We prospectively studied 92 PD patients [30 cognitively intact (CogInt), 30 mild cognitive impairment (MCI), 32 PDD] and 61 matched controls who completed the PD-CRS and neuropsychological tests assessing the cognitive domains included in the PD-CRS. Acceptability, construct validity, reliability, and the discriminative properties of the PD-CRS were examined. The PD-CRS included items assessing fronto-subcortical defects and items assessing cortical dysfunction. Construct validity, test-retest and inter-rater reliability of PD-CRS total scores showed an intraclass correlation coefficient >0.70. The PD-CRS showed an excellent test accuracy to diagnose PDD (sensitivity 94%, specificity 94%). The PD-CRS total scores and confrontation naming item scores-assessing "cortical" dysfunction-independently differentiated PDD from non-demented PD. Alternating verbal fluency and delayed verbal memory independently differentiated the MCI group from both controls and CogInt. The PD-CRS appeared to be a reliable and valid PD-specific battery that accurately diagnosed PDD and detected subtle fronto-subcortical deficits. Performance on the PD-CRS showed that PDD is characterized by the addition of cortical dysfunction upon a predominant and progressive fronto-subcortical impairment.

In this first study to prospectively analyze the frequency of minor hallucinatory phenomena in incident, untreated PD patients, hallucinations appeared as a frequent early non-motor symptom that may even predate the onset of parkinsonism.