Predictors of cognitive outcomes in early Parkinson disease patients: The National Institutes of Health Exploratory Trials in Parkinson Disease (NET-PD) experience

Abstract

Cognitive dysfunction is an important aspect of Parkinson disease (PD) and is increasingly being examined in various large scale PD clinical studies. However, the sensitivity of some of the cognitive measures used for detecting change in cognitive status in early PD patients is not known nor is the relationship between cognitive outcome measures and other motor and non-motor disease characteristics and various demographic parameters in early PD patients. The current analysis of the NET-PD cohort (i.e., untreated patients) was undertaken to: 1) assess which (if any) baseline demographic parameters correlate with baseline cognitive measures and any potential change in cognitive measures over the 12-18 months evaluation period; 2) assess the extent to which cognitive measures employed (i.e., Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Frontal Assessment Battery (FAB) and Letter-Number Sequencing) are sensitive to change over time; 3) examine whether initiation of symptomatic therapy is associated with change in cognitive status. At baseline, NET-PD subjects had no significant impairment on the assessments employed. Only education and age were significant predictors of cognitive score at baseline. None of the summary measures were indicative of change in cognitive status over the 12-18 months of study. These results suggest either the cognitive domains examined are not affected in the population examined or that more sensitive measures of cognition than those currently employed may need to be considered for use in a large trial setting in which an early, highly educated PD population is studied.

Figure 1

Box and whisker plots using the combined placebo data from the two NET-PD futility studies. Each plot shows the baseline cognition score, the score at the need for symptomatic therapy visit (Sx Tx Visit), and the cognition score at the first visit after the initiation of symptomatic therapy (First After, where available). The dot within the box represents the mean. The box represents the Interquartile Range (IQR). The line connects the medians across boxes. The whiskers are drawn from the edge of the box to the largest (smallest) observed value falling within the upper (lower) fence. (Fences are located 1.5×IQR above the 75th percentile and 1.5×IQR below the 25th percentile.) Outliers are identified with a circle.