Decreasing Fall Risk: Intensive Cognitive Training and Blood Pressure Control

Falls increase the probability of mortality, disability, and hospitalization in older adults.1 To alleviate this public health burden, it is imperative first to elucidate and then to minimize or remediate factors associated with risk of falling. Cognitive impairment in elderly adults increases the probability of falling and associated negative consequences. Two-thirds of older adults with dementia fall each year, double the incidence of cognitively normal older adults,2 and individuals with dementia are more likely to be injured and require hospitalization and long-term care as a result of falling.3 These findings underscore the point that walking is a complex behavior that integrates sensorimotor and cognitive (e.g., attention, planning) processes.4 Thus, even mild cognitive weaknesses on tests that measure sustained attention, processing speed (PS), and executive functioning (EF) increase fall risk in older adults without dementia.5 Cognitive impairment is not the only condition that predicts falls in elderly adults. Declines in physical mobility (e.g., walking speed and balance) and depression also increase the probability of falling.2, 6 Simultaneous investigation of multiple risk factors is necessary to inform appropriate interventions to reduce falls. In this issue of the Journal of the American Geriatrics Society, Davis and colleagues address this point by investigating the predictive value of baseline measures of cognition, physical mobility, and psychological well-being in determining subsequent falls in a large community-dwelling sample of older adults with mild cognitive problems and a history of falls in the year before.7 They found that a composite PS-EF score was the strongest predictor of different types of falls (e.g., injurious, indoor), followed by measures of walking speed, balance, depression, and emotional well-being. These results provide further evidence of the interconnection between PS-EF, depression, and mobility and generate an important discussion on treatments that target shared etiological abnormalities. At least two factors tie PS-EF to depression and mobility. Most obvious is anatomic proximity of cortical structures influencing these three functions. Numerous studies indicate that processing within the prefrontal and frontal cortex heavily influences affective status and PS-EF. The prefrontal and frontal cortex is adjacent to the medial supplementary motor and motor cortex, which controls important aspects of lower motor function and gait. These cortical structures connect to deeper structures and the other hemisphere through ascending, descending, and crossing white matter connections of the anterior corona radiata and corpus callosum. The white matter pathways traverse the vicinity of the frontal horns, further concentrating their proximity to each other. It is likely that anterior periventricular white matter is a frequent location for disruption of these pathways and the functions they support. For example, disease processes within (e.g., hydrocephalus) and adjacent to (e.g., multiple sclerosis) the ventricles commonly result in elements of frontal lobe dysfunction, namely impairments in PS-EF, reduced mobility, and affective disturbance. Evidence of brain microvascular disease is observed on fluid-attenuated inversion recovery magnetic resonance imaging as a large volume of white matter hyperintensities (WMHs) in approximately two-thirds of individuals aged 75 and older.8 The accrual of WMHs in older persons is progressive, almost doubling in volume over 4 years.9 WMHs are most often in the most-posterior and -anterior periventricular regions but also involve the adjacent corona radiata10 and sometimes more-superficial white matter. Accrual of WMHs occurs by expansion of the lesions,11 with recent evidence suggesting ischemia in the surrounding white matter.12 These regions support diverse cognitive, sensorimotor, and emotional functions, and a large body of evidence shows that longitudinal progression of WMHs is associated with declines in PS-EF, worsening depression, and decreases in mobility in older adults.9, 11, 13 Moreover, severe WMH burden has been prospectively linked to greater risk of falls (relative risk = 1.63, 95% confidence interval = 1.11–2.40), and this association remains after accounting for PS-EF and physical mobility performance.14 Together these findings suggest that interventions to reduce fall risk in older adults should include slowing of the accrual of WMH. Davis and colleagues note the intriguing possibility of using cognitive training to reduce fall risk. Cognitive training is a behavioral intervention that uses time-intensive and repetitive learning events to improve cognition and other clinical outcomes. Randomized clinical trials suggest the benefit of cognitive training in aging populations. The remediation of PS-EF in healthy older adults leads to less decline in PS-EF and reported activities of daily living over 10 years than in control subjects.15 Cognitive training also improves PS-EF and reduces depression in elderly adults, even in treatment-resistant individuals who do not respond to standard care with antidepressants.16 The exact mechanism of action in cognitive training is unclear. Evidence from animal and human models suggests that cognitive training enacts neuroplasticity (new formation and reorganization of synaptic connections), including increases in activity in the dopaminergic prefrontal-striatal-limbic circuitry17 involved in the modulation of PS-EF, mood, and gait control. Cognitive training to reduce fall risk would ostensibly enhance the executive control processes inherent to successful walking, engender plasticity in brain regions important to PS-EF and mobility, or both. In support of this theory, Verghese and colleagues18 reported preliminary findings showing that cognitive training resulted in faster walking speed in a small sample of older adults than in a wait-list control group. Although Verghese and colleagues’18 results are thought provoking, cognitive training appears to work only where these is potential for growth, meaning that training can change the behavior of neural systems that are dysfunctional but not destroyed. Thus, even low levels of microvascular disease in older adults may interfere with the efficacy of cognitive training.19 Targeting cardiovascular risk factors may decrease the probability of falling and improve functional outcomes. Two groups of older adults were compared based upon 24-hour ambulatory systolic blood pressure (SBP). Findings indicated that those with high 24-hour ambulatory SBP (143 mmHg) had more WMHs and walked more slowly than those with low 24-hour SBP (122 mmHg). Moreover, walking speed in the higher ambulatory SBP group decreased 0.15 m/s more than in the low SBP group.8 Although small in magnitude, this difference represents a between-group change after only 2 years of observation. These findings suggested that an intervention using intensive BP control (goal 24-hour ambulatory SBP ≤130 mmHg) could reduce progression of microvascular disease in elderly adults more than standard control (goal 24-hour systolic BP ≤145 mmHg) and thus favorably affect function. A clinical trial testing this hypothesis (Intensive versus Standard Ambulatory Blood Pressure Lowering to Prevent Functional Decline in the Elderly)20 is nearing completion, which will enable clarification of the role of BP control in the progression of microvascular disease and its effects on cognition and physical mobility in individuals aged 75 and older. Appropriate BP control may reduce the progression of microvascular disease although it cannot reverse damage already present. Thus, treatment geared toward optimizing existing function, as presented in the study by Davis and colleagues, provides a complementary approach to diminishing the risk of falls. The best approaches to treatment may prove to be a combination of these strategies, and future investigators should consider interventions that slow the accrual of WMHs (e.g., BP control) and optimize neural functioning (e.g., cognitive training, exercise). In summary, the study by Davis and colleagues provides clinically relevant information for the care of older adults and provides an underpinning on which continued research can explore treatment interventions targeting mobility and underlying neuroabnormalities. This article is timely and critical considering the public health burden of falls in our aging population, as well as advances in the treatment of cardiovascular risk factors21 and cognitive remediation. Conflict of Interest: None. Financial Disclosure: Dr. Wolfson is supported by R01 AG022092 from the National Institute on Aging. Author Contributions: Manning, Wolfson: Editorial concept and design, preparation of manuscript. Sponsor's Role: The National Institute on Aging had no role in the preparation, review, or approval of the manuscript or the decision to submit the manuscript for publication.