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

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 4year 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.

Keywords: Falls; NET-PD; Parkinson's disease.

Figure 1

Percentage of Falls Over Follow-up Time

Figure 2. Adjusted Odds Ratio of A Post-baseline Fall with 95% Confidence Intervals, multiple logistic model

The model is logit(probability of ever falling)=0.931 + 0.7487*UPDRSFalling -2.3748*Male + 0.0317*Male*Age + 0.1259*AmbulCapacity + 0.0582*UPDRSADL-0.1365*TFC - 0.3876*DAA (N=1730, 683 subjects ever fall). The adjusted odds ratios and confidence intervals are OR=2.11, 95% CI [1.36,3.28] for patients reporting baseline UPDRS item 13 > 0 (UPDRS Falling); OR=0.09, 95% CI [0.04,0.24] for Males versus Females; OR=1.17, 95% CI [1.09,1.26] per 5 year increase in age for males; OR=1.13, 95% CI [1.04,1.24] per 1-unit increase in ambulatory capacity; OR=1.34, 95% CI [1.13,1.58] per 5-unit increase in UPDRS ADL score (UPDRSADL); OR=0.87, 95% CI [0.80,0.95] per 1-unit increase in baseline TFC; OR=0.68, 95% CI [0.55,0.84] if on dopamine agonist alone at baseline (DAA); all else held constant. For TFC higher scores represent “better” clinical status at baseline. For all else, higher scores are “worse”.

Figure 3. Adjusted Fall Rate Ratio (RR) and 95% Confidence Intervals, negative binomial model

Adjusted Odds Ratios estimated from negative binomial regression model of the rate of post-baseline falls (N=1730). Adjusted rate ratios are RR=1.75, 95% CI [1.37, 2.24] for patients reporting baseline UPDRS item 13 > 0 (versus those who did not); RR=0.68, 95% CI [0.59, 0.79] for males; RR=1.10, 95% CI [1.05, 1.14] per 5-year increase in age; RR=1.10, 95% CI [1.04,1.16] per 1-point increase in ambulatory capacity; RR=1.37, 95% CI [1.23,1.53] per 5-point increase in UPDRS ADL; RR=0.88, 95% CI [0.83,0.93] per 1-point increase in TFC; RR=0.71, 95% CI [0.60, 0.83] for use of dopamine agonist alone at baseline; all else being held constant. For TFC higher scores represent “better” clinical status at baseline. For all else, higher scores are “worse”.