Factors associated with falling in early, treated Parkinson's disease: The NET-PD LS1 cohort

Highlights

• Using the NET-PD LS-1 dataset, we examined factors associated with falling in PD.

• 728 subjects (42%) fell during the trial, including those reporting falls at baseline.

• The biggest risk factor for falls in PD remains a history of falling.

• Compared to women, men were less likely to fall until after age 70, when men and women had similar odds of falling.

• The UPDRS ADL subscale, total functional capacity and ambulatory capacity are novel risk factors needing further study.

Abstract

Background

Recognizing the factors associated with falling in Parkinson's disease (PD) would improve identification of at-risk individuals.

Objective

To examine frequency of falling and baseline characteristics associated with falling in PD using the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in PD Long-term Study-1 (NET-PD LS-1) dataset.

Methods

The LS-1 database included 1741 early treated PD subjects (median 4 year follow-up). Baseline characteristics were tested for a univariate association with post-baseline falling during the trial. Significant variables were included in a multivariable logistic regression model. A separate analysis using a negative binomial model investigated baseline factors on fall rate.

Results

728 subjects (42%) fell during the trial, including at baseline. A baseline history of falls was the factor most associated with post-baseline falling. Men had lower odds of post-baseline falling compared to women, but for men, the probability of a post-baseline fall increased with age such that after age 70, men and women had similar odds of falling. Other baseline factors associated with a post-baseline fall and increased fall rate included the Unified PD Rating Scale (UPDRS) Activities of Daily Living (ADL) score, total functional capacity (TFC), baseline ambulatory capacity score and dopamine agonist monotherapy.

Conclusion

Falls are common in early treated PD. The biggest risk factor for falls in PD remains a history of falling. Measures of functional ability (UPDRS ADL, TFC) and ambulatory capacity are novel clinical risk factors needing further study. A significant age by sex interaction may help to explain why age has been an inconsistent risk factor for falls in PD.

Introduction

Falls are common in Parkinson's disease (PD) [1], [2], [3], [4], and both falls and postural instability negatively affect health-related quality of life in PD [5], [6], [7]. Persons with PD are about 3 times as likely to sustain a fall as their peers [8], and up to 50% of falls in PD result in injury [1], [2], [3], [9], [10]. Falls and fall-related injuries remain one of the top causes of increased health services utilization and costs for those with PD [11], [12], and preventing and treating balance problems was recently identified as the top PD research priority by 1000 participants in the United Kingdom who understood the issues of living with PD [13].

The most consistently reported risk factor for falls in PD is a prior history of falls [3], [4], [6], [14]. However, a meta-analysis of six prospective studies revealed that 21% of fallers had no history of falling [3], making it difficult to consistently identify at-risk individuals. Other factors associated with falls in PD include age, disease/motor severity measures, gait/axial impairments, self-rated disability, impaired cognition, fear of falling, and poor health-related quality of life, though these have been reported inconsistently [3], [4], [6], [14], [15], [16], [17], [18]. Most research on falls in PD has been conducted in older cohorts with a longer disease duration (> 5 years) [18], when freezing and postural instability are more prominent. Existing data on falls and falls risk is limited in early PD cohorts (< 5 years disease duration). Voss et al. analyzed two randomized, clinical trials of early, untreated PD patients and found that lower PD-related quality of life, age and prior history of falls were associated with falls [6]. A recent study followed 91 newly diagnosed, falls-naïve PD patients for 3 years and found that slower gait, shorter stance time and Hoehn-Yahr score of III were the most significant predictors of a first fall [17]. A better understanding of clinical risk factors that predict falls in early PD, other than a prior history of falls, would improve identification of those at risk of falling and guide interventions to prevent further falls.

We analyzed the National Institute of Neurological Disorders and Stroke (NINDS) Exploratory Trials in Parkinson's Disease (NET-PD) Long-term Study-1 (LS-1) data set [19], a large cohort of early (within 5 years of diagnosis), treated PD subjects. Because there are limited data on factors associated with falls in an early PD population but numerous factors correlated with falls in more advanced populations, we explored many possible associations. Our main aims were to determine the frequency of falling and to examine characteristics that separate fallers from non-fallers.