Donepezil and the Risk of Falls in Seniors With Cognitive Impairment

Older adults with cognitive problems have a higher risk of falls, with annual incidence of around 60-80%; at least twice that of cognitively normal older adults. The consequences of falls in this population can be quite serious; fallers with cognitive problems are approximately five times more likely to be admitted to institutional care than people with cognitive issues who do not fall. They are also at risk of major fall-related injuries such as fractures and head injuries leading to increased mortality. Although the reasons for the increased fall risk in cognitively impaired people are not completely understood, what is known is that these impaired cognitive abilities that can limit their attentional resource allocation while walking. As well, since executive function is also an important cognitive resource for normal walking performance, impairments in this domain are also associated with both dementia and risk of falls. Falls is a major cause of disability and dependence in older Ontarians, especially for those experiencing cognitive problems, and through their associated costs relating to hospital admissions, provision of treatments, and nursing home placements, forms a definite burden for the provincial health care system.

One approach that can be used to understand the risk of falls in people with memory problems is to target them in the early stages of cognitive decline. Mild Cognitive Impairment (MCI) is an entity that is conceived as a transitional state between benign age-related cognitive change and early dementia. Specific diagnostic criteria have been developed and validated to diagnose MCI, with the prevalence of the diagnosis being estimated at 19% among older adults, increasing to 29% in those over age 85. People with MCI have been found to have a 10 to 15 times higher risk of developing Alzheimer's disease (AD), as well as a higher risk of falling compared with age-matched controls.

Although walking has long been considered as primarily an automatic motor task, emerging evidence suggests that this view may be overly simplistic. Cognitive function may play a key role in the regulation of even routine walking, particularly in older adults. Attention is a necessary cognitive resource for maintaining normal walking and there is evidence that cognitive and attentional deficits are independently associated with postural instability, impairment in performing daily living activities, and future falls. The role of cognition in walking is even more marked in people with cognitive dysfunction, whose gait performance is affected by any extra cognitive load. A sensitive way to quantify gait performance is by assessing the gait variability. Gait variability is defined as the stride-to-stride variation in time, and quantifies the automaticity of gait, with greater variability indicating less rhythmicity and a more unstable gait pattern. Evaluating gait variability offers an accurate methodology to identify subtle changes on walking because of pathological conditions or disease. For instance, cognitively normal older adults have low gait variability; however, high gait variability has been described in Parkinson's disease, Alzheimer disease, and has been associated with high risk of future falls and mobility decline. Additionally, previous studies have demonstrated that gait variability may serve as a clinically relevant parameter in the evaluation of mobility, and may be a responsive measure for different interventions in fall prevention.

Cholinesterase inhibitors have been tried in MCI individuals with the goal to delay the progression to dementia. A recent RCT demonstrated that cognitive enhancers, specifically donepezil, might improve cognition in this population; however, the effect was weak and had questionable clinical significance. Currently, there is no indication to use cognitive enhancers to treat people with MCI with the goal of delaying or preventing further functional or mobility decline.

Recently, it has been suggested that ChEI may improve gait performance through an improvement in attentional resource allocation due to the fact that ChEI are known to improve attention and executive function. We will expect as a result of our intervention with donepezil during a 6 month period, a reduction of gait variability, an important marker of fall risk, through an improvement on cognition, namely attention an executive function