Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease(Podcast)(e–Pub ahead of print)(LOE Classification)

Department of Neurology, Oregon Health & Science University, Portland, OR, USA.
Neurology (Impact Factor: 8.29). 10/2010; 75(14):1263-9. DOI: 10.1212/WNL.0b013e3181f6128c
Source: PubMed

ABSTRACT To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability.
Falling due to postural instability is a significant problem in advancing PD, and is minimally impacted by dopaminergic therapy. Anticholinergic medications increase falling in the elderly. Further, CNS cholinergic neuron loss occurs in PD. We hypothesized that acetylcholine augmentation may reduce frequent falling in subjects with PD.
We enrolled 23 subjects with PD who reported falling or nearly falling more than 2 times per week. In a randomized, placebo-controlled, crossover design, subjects were given 6 weeks of donepezil or placebo with a 3-week washout between phases. The primary outcomes were daily falls and near falls reported on postcards. Secondary outcomes included scores on the Activities of Balance Confidence Scale, Berg Balance Scale, Clinical Global Impression of Change, Folstein Mini-Mental State Examination, and the motor section of the Unified Parkinson's Disease Rating Scale.
Fall frequency per day on placebo was 0.25 ± 0.08 (SEM) compared with 0.13 ± 0.03 on donepezil (p < 0.05). The frequency of near falls was not significantly different between phases. The secondary outcomes did not differ; however, there was a trend to improvement on the subject-completed Global Impression of Change scale.
Subjects with PD fell approximately half as often during the 6 weeks on donepezil than on placebo. Larger trials of cholinergic augmentation are warranted in subjects with PD with frequent falls. Classification of evidence: This study provides Class II evidence that donepezil (maximum 10 mg per day) significantly reduced the number of falls in patients with PD (0.13 falls/day, SEM = 0.03) than when taking placebo (0.25 falls/day, SEM = 0.08, p = 0.049).

Download full-text


Available from: Fay Horak, Oct 24, 2014
34 Reads
  • Source
    • "Cognitive functions play an important role in the regulation of walking, particularly in older adults where deficits in executive functions and attention are independently associated with postural instability, impairments in daily living activities, and falls [6, 7]. In support of this idea, acetylcholinesterase inhibitors, cognitive enhancer medications for symptomatic treatment of patients with Alzheimer’s and Parkinson’s diseases, were found to reduce gait variability [8], and increase gait velocity [9, 10], in patients with Alzheimer’s disease [9, 10], and to reduce fall risks in patients with Alzheimer’s disease and in non-demented patients with Parkinson’s disease [9, 10]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Higher-level gait disorder (HLGD) in older adults is characterized by postural instability, stepping dysrhythmicity, recurrent falls and progressive immobility. Cognitive impairments are frequently associated with HLGD. The aim of this study was to compare gait and cognitive performance before and after the use of rivastigmine in patients with HLGD, free from cognitive impairment or Parkinsonism. Fifteen non-demented patients with HLGD (age 79.2 ± 5.9 years; 11 women; Mini-Mental State Examination [MMSE] 28.3 ± 1.4) received escalating doses of rivastigmine for 12 weeks in an open-label, pilot study. They were assessed before and after treatment (week 0 and week 12), and after a 4-week washout period (week 16). Assessments included the Mindstreams computerized neuropsychological battery, Activities-specific Balance Confidence Scale, State-Trait Anxiety Inventory, Geriatric Depression Scale, Timed Up and Go (TUG) test, gait speed and stride time variability. One-way multiple analysis of variance tests for repeated measures were used, and Pillai's trace test was considered as robust to investigate significant differences. The mean dose of rivastigmine during the 8-12 week period was 5.1 ± 2.3 mg/day. A positive effect was observed on the Mindstreams memory subscale and anxiety scores [Pillai's trace: F(6,724) = 0.508, p = 0.010; and F(7,792) = 0.545, p = 0.006, respectively, over the course of the study] as well as on mobility (TUG test) [Pillai's trace: F(4,863) = 0.448; p = 0.028], whereas gait speed and stride time variability did not change. The use of relatively low-dose rivastigmine did not affect gait speed and stride time variability; however, the general mobility and anxiety were improved. These preliminary results warrant a larger, randomized, placebo-controlled study.
    04/2014; 14(2). DOI:10.1007/s40268-014-0038-8
  • Source
    • "Missteps are usually more frequent than falls and may occur before a person begins to fall, enhancing the potential predictive value of missteps. Unfortunately, self-report is, to a large degree, the gold-standard method for characterizing and quantifying missteps [17-19]. Moreover, self-report of missteps is limited by the subjective nature of recall bias and the long observation period that may be required for many missteps to be reported (e.g., weeks or months) [17,19]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Falls are a leading cause of morbidity and mortality among older adults and patients with neurological disease like Parkinson's disease (PD). Self-report of missteps, also referred to as near falls, has been related to fall risk in patients with PD. We developed an objective tool for detecting missteps under real-world, daily life conditions to enhance the evaluation of fall risk and applied this new method to 3 day continuous recordings. 40 patients with PD (mean age +/- SD: 62.2 +/- 10.0 yrs, disease duration: 5.3 +/- 3.5 yrs) wore a small device that contained accelerometers and gyroscopes on the lower back while participating in a protocol designed to provoke missteps in the laboratory. Afterwards, the subjects wore the sensor for 3 days as they carried out their routine activities of daily living. An algorithm designed to automatically identify missteps was developed based on the laboratory data and was validated on the 3 days recordings. In the laboratory, we recorded 29 missteps and more than 60 hours of data. When applied to this dataset, the algorithm achieved a 93.1% hit ratio and 98.6% specificity. When we applied this algorithm to the 3 days recordings, patients who reported two falls or more in the 6 months prior to the study (i.e., fallers) were significantly more likely to have a detected misstep during the 3 day recordings (p = 0.010) compared to the non-fallers. These findings suggest that this novel approach can be applied to detect missteps during daily life among patients with PD and will likely help in the longitudinal assessment of disease progression and fall risk.
    Journal of NeuroEngineering and Rehabilitation 04/2014; 11(1):48. DOI:10.1186/1743-0003-11-48 · 2.74 Impact Factor
  • Source
    • "This demonstrated that both gait velocity and variability improved under single and dual-task conditions at follow-up [25]. Two further studies showed an improvement in stride time [26] and a reduction in falls with treatment [25,27]. A further RCT is currently underway examining these effects on a larger cohort of individuals with MCI [28]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gait impairment is common in people with Parkinson's disease. There is a lack of effective interventions to target this debilitating complication and therefore a need to identify new therapeutic options. An underlying cholinergic deficit contributes to both the gait and cognitive dysfunction seen in Parkinson's disease. The combined impact of both impairments can be assessed in gait tasks performed with concomitant cognitive tasks. The aim of this trial is to evaluate the impact of a cholinesterase inhibitor on cognitive function and gait performance in people with established Parkinson's disease.Methods/design: This is a single centre, double-blind, randomised placebo-controlled trial in 130 people with Hoehn and Yahr stage 2--3 idiopathic Parkinson's disease who have fallen in the past year. Participants will be randomised to two groups, receiving either rivastigmine capsules or identical placebo capsules for 8 months. Assessment will be undertaken at baseline and at the end of medication prescription (i.e. 8 months) with participants remaining enrolled in the trial for a further 4 months to monitor for falls and adverse events. The primary outcome is step time variability, assessed with and without the addition of concurrent cognitive tasks. Secondary outcomes will include other gait parameters, sensorimotor and balance performances, cognitive indices, falls and fall related injury, fear of falling, Parkinson's symptoms and data pertaining to possible harms. This randomised controlled trial will examine the effect of cholinesterase inhibitor therapy on gait, balance and falls in Parkinson's disease. If effective, it would offer a new therapeutic option to ameliorating gait and cognitive deficits in a population at high risk of falls.Trial registration: ISRCTN19880883, UTN U1111-1124-0244.
    BMC Neurology 12/2013; 13(1):188. DOI:10.1186/1471-2377-13-188 · 2.04 Impact Factor
Show more