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


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).

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Available from: Fay Horak, Oct 24, 2014
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    • "Weekly postcards. [18] "
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    ABSTRACT: Background: There is increasing evidence to suggest a tight relationship between cognitive impairment and falls in Parkinson's disease (PD). Here, we draw attention to a potentially significant flaw in the existent falls-related research, namely the apparent exclusion of patients with cognitive impairment or dementia. Objective: Our objective was to review all published, ongoing or scheduled fall-related intervention studies, in order to investigate the extent to which cognitively impaired individuals with PD were included in these studies. Methods: We analyzed published controlled trials regarding falls and PD in commonly used databases, as well as relevant ongoing clinical trials registered within the World Health Organization database, and the European Clinical Trials Database. Results: Fourteen of the fifteen published studies included had explicit cognitive exclusion criteria as part of their study protocol. Most of the 54 ongoing PD fall-related studies excluded patients with cognitive impairment. Conclusions: This suggests that individuals with cognitive impairment or dementia are excluded from fall-related research studies. We strongly recommend that future work in this area should include a representative sample of patients with PD, including subjects with cognitive decline.
    Full-text · Article · Sep 2015 · Journal of Parkinson's Disease
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    • "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]. "
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    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.
    Full-text · Article · Apr 2014
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    • "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]. "
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    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.
    Full-text · Article · Apr 2014 · Journal of NeuroEngineering and Rehabilitation
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