Cerebrovascular Mechanisms of Slow Gait and Falls
Principal Investigator: Lewis A. Lipsitz, MD
Falls and mobility problems are common causes of disability and death in elderly people, yet their causes are poorly understood. Slowing of gait is a prominent feature of human aging, even in the absence of specific diseases, and it is strongly associated with falls (1), dementia (2), and mortality (3). Recent studies by our group, supported by an NIA-funded program project grant called the MOBILIZE Boston Study (an acronym for the Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly of Boston) have demonstrated significant relationships between abnormal blood flow to the brain, slow gait speed, and falls in elderly subjects. By measuring cerebral blood flow velocity (CBF) with transcranial Doppler ultrasonography (TCD) in a representative population-based cohort of 419 seniors living in the Boston metropolitan area, we have shown that:
- Low cerebral vasoreactivity (i.e., changes in brain blood flow in response to changes in carbon dioxide (CO2) in the air we breathe) is associated with slow gait speed and falls (4).
- Impairment in the ability to increase brain blood flow during cognitive tasks is associated with slow gait speed (5).
- Damage to white matter on Magnetic Resonance Images of the brain (MRI) is associated with slow gait speed (5).
These observations have led us to the overall hypothesis that alterations in the control of brain blood flow associated with aging and cardiovascular risk factors are associated with white matter damage to the brain, which ultimately results in slowing of gait, cognitive impairment, and their functional consequences such as falls.
This study will explore this hypothesis by performing TCD measurements of brain blood flow and MRI measurements of brain structures and functions in 100 elderly participants in the MOBILIZE Boston study (MBS). Our specific aims are:
- To determine whether abnormalities in blood flow to the brain are associated with slowing of gait speed, cognitive dysfunction, functional decline, and recurrent falls in the MBS cohort, and
- To determine whether abnormalities in blood flow to the brain are associated with damage to white matter on brain MRIs that can explain the onset of slow gait and falls in older age.
These aims will be accomplished by recruiting 50 subjects with the lowest brain blood flow and 50 subjects with the highest brain blood flow when it was measured at the beginning of the MBS 6-8 years ago. We will invite these subjects to come to the IFAR Clinical Research Laboratory for repeat blood flow measurements, then obtain brain MRI studies at the Boston VA hospital. All of the proposed tests have been performed safely without complications in very elderly subjects previously participating in the MOBILIZE Boston Study and have been approved in the past by the IRB. MRIs for MOBILIZE Boston participants are already approved by the VA IRB and are being performed as part of Dr. Leveille's MOBILIZE Boston project that examines the effect of pain on falls. The current project will increase the number of MRI studies in the MOBILIZE Boston database, making it more valuable for these two projects, as well as future ancillary studies.
This study will provide novel information necessary for the early detection and ultimate prevention of cerebrovascular causes of falls and mobility impairments in elderly people. If abnormal brain blood flow is discovered to be a cause of falls, currently available interventions to increase brain blood flow, prevent cerebrovascular damage, grow new blood vessels, or build new neural pathways may be tested to prevent future falls.
Tai Chi training and physiologic complexity in older adults, PI: Lewis Lipsitz, PhD
With funding from the National Institute on Aging and the National Center for Complementary and Alternative Medicine, we are conducting two separate randomized controlled trials to examine the effects of long-term Tai Chi training on physical, cognitive and cardiovascular outcomes in 1) healthy, community-dwelling older adults aged 50-79, and 2) at-risk older adults aged 70 and over living within supportive housing facilities. Our hypothesis is that across multiple physiological systems, the multifaceted stimulus of Tai Chi training will increase the dynamic complexity (i.e., information-rich structure correlated over multiple temporal and/or spatial scales) and enhance the ability to adapt to physical and cognitive stressors.
Clinical Trial Registration:
Nonlinear Dynamics of Frailty, PI: Lewis Lipsitz
The Aims of this NIA-funded project are 1) To determine cross-sectionally in a representative population of elderly people aged 70 years and over, whether there is a relationship between “frailty” and loss of complexity in the dynamics of multiple physiologic systems. 2) To determine whether a loss of complexity in cardiovascular, cerebrovascular, and/or balance dynamics, is associated with an impaired ability to adapt to common physiologic stresses imposed on these systems. 3) To determine longitudinally over a two-year follow-up period in the same population, whether reduced complexity in the dynamics of these physiologic systems at baseline, or loss of complexity in these systems over time, is predictive of the subsequent development of frailty, its component symptoms, and/or other measures of physical and cognitive functional decline
Evaluation of stochastic resonance insoles to Improve Mobility in Healthy Older Adults, PI: Lewis Lipsitz, MD
Age-related loss of somatosensory function (tactile and proprioceptive senses) has been shown to be strongly predictive of a propensity to fall. It has been demonstrated in several biological systems, ranging from ion channels to sensory neurons to human psychophysics, that the presence of a particular sub-threshold level of noise can be used to enhance signal recognition and detection. This phenomenon is known as stochastic resonance (SR). Previous studies indicate that SR is potentially a viable technology to improve balance and gait if used in a therapeutic medical device. Noise-based devices, such as shoe insoles, may therefore enhance the control of dynamic balance activities and thus, enable those with reduced function to overcome mobility impairments caused by aging.
The purpose of this research study is to evaluate how applying small, sub-threshold vibrations to the bottom of the feet via shoe insoles affects balance and gait. The study also aims to determine if different levels of vibrations have different effects on functional outcomes, and if the level at which an individual can feel the vibrations changes throughout the day. The information collected from this study will be used to develop shoe insoles which may enhance balance and walking in older adults.
Mobility enhancement via noninvasive brain stimulation, PI: Brad Manor, PhD
Mobility, defined as the ability to independently navigate one’s environment in order to complete activities of daily living, is not only dependent upon the peripheral neuromuscular, skeletal and cardiorespiratory systems, but also upon numerous brain networks and a host of cognitive functions. Transcranial direct current stimulation (tDCS) is a noninvasive, safe and inexpensive means of modulating brain tissue excitability. In healthy young adults, 20min of 2mA tDCS targeting the left prefrontal cortex (PFC)—a region involved in both cognitive and motor function—acutely increases attention, working memory and executive function, as well as cerebral perfusion and functional connectivity within known cognitive brain networks. Through collaboration with the Academy for Advanced Interdisciplinary Studies at Peking University, and funding from the National Natural Science Foundation of China, we are conducting a trial to identify the acute and chronic effects of tDCS on mobility and brain function in older adults
Identification of locomotor brain networks using fMRI, PI: Brad Manor, PhD
Foot sole somatosensation is an important source of feedback for the control of gait and balance. The goal of this project is to enable investigation into the brain networks involved in processing and utilizing this source of afferent feedback, and how they are affected with aging and disease. To do so, we have developed an MRI-compatible stimulation system capable of applying controlled pressures to the entire foot sole that closely mimic those experienced when walking. Our effects to date have demonstrated that the application of walking-related foot sole pressure elicits a characteristic pattern of brain activation in healthy adults. Through several ongoing studies in collaboration with Peking University in Beijing, China, we are now examining 1) the effects of performing a simultaneous cognitive distraction task on the brain’s response to walking-related foot sole pressures, 2) the effects of age- and disease-related somatosensory impairments on the brain’s response to applied foot sole pressure, and 3) the capacity of noninvasive brain stimulation to augment the brain’s response to applied foot sole pressures.
Monitoring falls within the nursing home setting, PI: Lewis Lipsitz, MD
Falls comprise the leading cause of injury-related morbidity and mortality among adults over the age of 65. Currently, an automated method for accurately recording falls is not available. The Philips Lifeline with AutoAlert fall detection technology is a newly marketed technology for older adults living alone for use in case of a fall where the patient cannot reach a phone to request outside assistance. This system is worn as a pendant and uses both a traditional patient-activated button as well as technology capable of detecting falls and automatically reporting them to the response center. In this way, the Philips system allows patients to prolong autonomy in their own home without the need for supervision.
From a scientific perspective, this technology may dramatically improve the quality of data recorded in an objective manner in a community or institutional setting where trained health care professionals are not available for documenting falls. In addition, data collection is not dependent upon patient reporting, recall or response rate, a significant limitation to previous methods of measurement. The primary objective of this exploratory study is to assess the validity of Philips Lifeline with AutoAlert for detecting falls, as compared to falls reported by nursing staff, in a nursing home setting.
Prediction of Activity of Daily Living Disability in Older Adults, PI: Dae Kim, MD
This research is to develop and validate a practical clinical prediction model for activity of daily living disability in community-dwelling older adults, using data from the Cardiovascular Health Study and Established Populations for Epidemiologic Studies of the Elderly. The prediction model will compare self-reported health information, objective tests of cognitive and physical performance, and laboratory and non-invasive test results in their ability to predict activity of daily living disability. It is funded by the Charles A. King Trust Foundation Postdoctoral Fellowship Award.
Functional outcomes of older patients with severe aortic stenosis, PI: Dae Kim, MD
This prospective cohort study is a collaborative project between gerontology and interventional cardiology at Beth Israel Deaconess Medical Center. The objective is to examine the change in cognitive and physical function and activity of daily living disability in older patients with symptomatic severe aortic stenosis. Functional status and disability are assessed via repeated telephone interviews for 12 months. These outcomes will be compared between patients who are treated with transcatheter or surgical aortic valve replacement and patients who are treated conservatively. This research will also test a novel approach to combine functional outcomes with traditional outcomes of hospitalizations and mortality in testing the effectiveness of aortic valve replacement.