Are Cholinesterase Inhibitors Effective in Improving Balance in Parkinson’s Disease?

Abstract

BackgroundMost falls in Parkinson's disease (PD) appear to be due to a primary balance dysfunction rather than an environmental factor [1]. Accumulating evidence suggests that balance dysfunction cannot only be attributed to changes in the dopaminergic system that seems to be responsible for most of the other motor symptoms in PD [1]. The interventions often helpful in improving other PD symptoms, dopaminergic medications and deep brain stimulation, do not consistently improve balance and falls [2,3]. Degeneration in other brain areas, such as cholinergic cortex, the adrenergic locus coeruleus or the cholinergic/glutaminergic pedunculopontine nucleus may be the origin of the balance problems associated with PD [4].Cholinesterase inhibitors have a positive impact on global assessments, cognitive function, behavioral disturbances, and activities of daily living in persons with PD with Dementia, Lewy Body Dementia, and PD with Cognitive impairment but without dementia (CIND) [5]. A pooled estimate of therapeutic benefit of cholinesterase inhibitors on cognitive function was found with a standard mean difference (SMD) of -0.34 (95% CI -0.46 to -0.23, p<0.00001) versus placebo. A study enrolling 23 subjects in a cross-over design, showed a reduction in falls in persons with PD without dementia when taking donepezil for six weeks. Fall frequency per day decreased from 0.25 ± 0.08 on placebo to 0.13 ± 0.03 on donepezil (p<0.05) [6].It is not clear the exact role cholinergic function plays in gait, balance, and falls. It is clear that functional walking without falls requires executive function, such as the ability to switch attention quickly [7]. The relationship between cholinergic function and falls has been demonstrated with PET imaging [8]. The cholinergic system, specifically the pendunculopontine nucleus (PPN), may have direct effects on gait and balance. Loss of PPN cells is correlated with balance performance and may affect attention [9][10][11]. There are also extensive cholinergic projections to the cerebral cortex with the nucleus basalis of Meyert that suplies the marjority of input to the frontoparietal attention Abstract Background: Cholinesterase inhibitors have been reported to reduce falls in a double blind pilot study. The mechanism by which cholinesterase inhibitors reduce falls is unknown.