In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies. The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI. A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data. A total of 25.8% of subjects (95% confidence interval [CI] 23.5-28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6-15.3), followed by visuospatial (11.0%; 9.4-13.0) and attention/executive ability impairment (10.1%; 8.6-11.9). Regarding cognitive profiles, 11.3% (9.7-13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0-9.9) as amnestic single-domain, 4.8% (3.8-6.1) as amnestic multiple-domain, and 1.3% (0.9-2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage. MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.

Objective: Using resting-state (RS) fMRI, we investigated the functional integrity of the default-mode network (DMN) in cognitively unimpaired patients with Parkinson disease (PD). Methods: RS fMRI at 3 T was collected in 16 cognitively unimpaired patients with PD and 16 age- and gender-matched healthy controls. Single-subject and group-level independent component analysis was used to investigate differences in functional connectivity within the DMN in patients with PD and healthy controls. Statistical analysis was performed using BrainVoyager QX. In addition, we used voxel-based morphometry to test whether between-group differences in RS functional connectivity were related to structural abnormalities. Results: Patients with PD compared with controls showed a decreased functional connectivity of the right medial temporal lobe and bilateral inferior parietal cortex within the DMN. Although patients with PD were cognitively unimpaired, the decreased DMN connectivity significantly correlated with cognitive parameters but not with disease duration, motor impairment, or levodopa therapy. The analysis of regional volume differences did not reveal any differences in local gray matter between patients and controls. Conclusions: Our findings revealed a functional disruption of the DMN in cognitively unimpaired patients with PD, in the absence of significant structural differences between patients and controls. We hypothesize that a dysfunction of the DMN connectivity may have a role in the development of cognitive decline in PD.

The variability in the clinical phenotype of Parkinson’s disease seems to suggest the existence of several subtypes of the disease. To test this hypothesis we performed a cluster analysis using data assessing both motor and non-motor symptoms in a large cohort of newly diagnosed untreated PD patients. We collected data on demographic, motor, and the whole complex of non-motor symptoms from 100 consecutive newly diagnosed untreated outpatients. Statistical cluster analysis allowed the identification of different subgroups, which have been subsequently explored. The data driven approach identified four distinct groups of patients, we have labeled: 1) Benign Pure Motor; 2) Benign mixed Motor-Non-Motor; 3) Non-Motor Dominant; and 4) Motor Dominant. Our results confirmed the existence of different subgroups of early PD patients. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms. Identification of such subtypes may have important implications for generating pathogenetic hypotheses and therapeutic strategies.