TY - JOUR
T1 - Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease
AU - Chung, Kathryn A.
AU - Lobb, Brenna M.
AU - Nutt, John G.
AU - Horak, Fay B.
N1 - Funding Information:
Study funding: This was an investigator-initiated project funded with an unrestricted grant from Pfizer Inc., who did not design or monitor the study or receive the data or influence the writing of the manuscript. Supported by a Veterans Administration Career Development Award, US Public Health Service Grant (ULIRR024140-02) , and the NIH (R01-NS21062 and NIA AG006457) . Pfizer Inc. provided drug and matched placebo.
Funding Information:
Dr. Chung has received research support from a VA Career Development Award. B.M. Lobb receives support from the Department of Veterans Affairs. Dr. Nutt has received funding for travel from Novartis and Teva Pharmaceutical Industries Ltd.; has received speaker honoraria from Novartis; has served as a consultant for XenoPort Inc., IMPAX Laboratories, Inc., Neurogen Inc., Synosia Therapeutics, and NeuroDerm, Ltd.; and has received research support from Schering-Plough Corp, the NIH (NINDS R01 NS 21062 [PI] and UL1-RR024140 [PI]), the Veterans Administration (PADRECC [Co-PI]), and the National Parkinson Foundation. Dr. Horak serves on scientific advisory boards for the Movement Disorders Society, Novartis, and the MS Society; serves as an Associate Editor for Cerebellum and on the editorial boards of Gait and Posture and the Journal of Biomechanics; holds/has filed patents re: Device for conditioning balance and motor coordination and instrumented mobility system to objectively measure balance and gait; serves as Chief Scientific Officer and member of the board of APDM, Inc.; and receives research support from the NIH (NIDCD R01 DC004082-07 [PI], NIA R37 AG006457 [PI], and RC1 NS068678 [PI]), the National MS Society, Parkinson's Alliance, and the Kinetics Foundation.
PY - 2010/10/5
Y1 - 2010/10/5
N2 - Objective: To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability. Background: 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. Methods: 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. Results: 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. Conclusions: 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.
AB - Objective: To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability. Background: 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. Methods: 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. Results: 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. Conclusions: 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.
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U2 - 10.1212/WNL.0b013e3181f6128c
DO - 10.1212/WNL.0b013e3181f6128c
M3 - Article
C2 - 20810998
AN - SCOPUS:77958190022
SN - 0028-3878
VL - 75
SP - 1263
EP - 1269
JO - Neurology
JF - Neurology
IS - 14
ER -