Predictors of time to requiring dopaminergic treatment in 2 Parkinson's disease cohorts

Abstract

The rate of progression of Parkinson's disease (PD) is highly variable. Knowledge of factors associated with disease milestones and commonly used research outcome measures helps with patient counseling and guides the design and interpretation of clinical studies. The objective of the study was to identify prognostic factors for time to acquiring disability requiring dopaminergic therapy that are reproducible within 2 large prospectively followed cohorts. Potential prognostic factors were identified using data from the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism (DATATOP) trial, and their reproducibility was examined using data from the Parkinson Research Examination of CEP-1347 trial (PRECEPT). In multivariable analyses of the DATATOP cohort, higher baseline Unified Parkinson's Disease Rating Scale (UPDRS) scores, full-time employment, a lesser smoking history, and onset on the left side were associated with a shorter time to disability requiring dopaminergic therapy. PRECEPT data confirmed the associations of higher baseline UPDRS scores and full-time employment with shorter time to requiring treatment. Any clinical trial using the end point of time to disability requiring dopaminergic therapy should ensure that groups are well balanced with respect to baseline UPDRS scores and the proportion of subjects employed full time and should consider including these variables as covariates in the statistical model for primary analysis of treatment effects. We suspect that individuals employed full time may have a lower threshold for requiring dopaminergic therapy because of occupational demands.

Quitting smoking: An early non-motor feature of Parkinson's disease?

“…This is possibly due to the reduced sample size and to the lack of longitudinal motor data, not allowing clearly assessing the efficacy of smoking on motor symptoms [7]. However, it has been suggested that smoking possibly does not have a neuroprotective effect in patients already diagnosed with PD [30].…”

“…Apparently, this association is dosedependent with reduced PD risk in relation to intensity and duration of smoking [4e6]. Furthermore, a positive effect of smoking on motor features has been reported with a delayed time to disability requiring dopaminergic therapy [7], and on non-motor symptoms (NMS), with an improvement of smell in PD [8].…”

Measuring Disease Progression in Early Parkinson Disease

“…Other important predictors include higher level of education, 6 full time employment, lesser smoking history, and left-sided onset. 17, 18 …”

“…Using the time between baseline and the need for symptomatic therapy as an end-point has been a common characteristic of many studies in early PD, particularly clinical trials of agents with disease modifying potential. 4, 5, 13, 18 Our analysis now identifies the measures that are most likely to reflect the progression of impairment and disability that leads to the decision to treat.…”

The six gaps in the search of neuroprotection for Parkinson’s disease

“…A great deal of attention has been focused on the latter, lower-hanging fruit. The 'delayed start' design [1] appears to be theoretically superior than the 'time to levodopa' [2] and 'withdrawal' designs [3] previously used, and currently may be the most rigorous methodology for assessing neuroprotection. Delayed-start clinical trials, however, require patients to stay untreated for 6-9 months, which may not be long enough to modify biological processes related to abnormal neuronal aging.…”