This proposal leverages and extends the MOBILIZE Boston Study (MBS), which previously demonstrated significant relationships between abnormal cerebral blood flow (CBF) regulation, slow gait speed, and the development of falls in a representative population of elderly people living in the Boston metropolitan area. Our findings have led to the hypothesis that alterations in CBF regulation are associated with microvascular damage to periventricular and subcortical white matter in the brain, which ultimately results in slowing of gait, executive dysfunction, and falls. We also hypothesize that those individuals who can redistribute blood flow to healthy cortical networks during cognitive or motor tasks can prevent slowing of gait and falls, despite the presence of white matter damage. The current proposal will add rigorous transcranial Doppler and neuroimaging (structural, diffusion tensor, and functional MRI) measures to the third assessment of 250 MBS participants to determine whether: 1) reduced CBF in response to a cognitive or motor task (neurovascular coupling), is longitudinally associated with the slowing of gait speed, executive dysfunction, functional decline, and recurrent falls over 2 years of followup;2) abnormalities in CBF regulation, including CO2 vasoreactivity and neurovascular coupling, are associated with loss of white and gray matter microstructural integrity on MRI and diffusion tensor imaging (DTI);3) these structural changes in the brain are associated with slowing of gait, executive dysfunction, functional decline, and recurrent falls over 2 years;and 4) the brain's ability to increase blood flow to healthy regions during cognitive or motor tasks can attenuate the adverse effects of white or gray matter microstructural damage on functional decline and falls. The study is unique in focusing on alterations in CBF as a pathological mechanism of falls, developing cutting-edge MR imaging techniques to detect early microstructural markers of brain damage that can predict falls, and identifying a compensatory mechanism that protects some people from the effects of this damage on falls - all in a large representative elderly cohort. Our successful 7-year retentio and followup of the MBS cohort and collaboration with the Boston VA Neuroimaging Center will help assure we achieve our goals. Relevance: 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 prevent future falls.

Public Health Relevance

This study explores alterations in cerebral blood flow as a pathological mechanism of falls, develops cutting-edge magnetic resonance imaging techniques to detect early microstructural markers of brain damage that can predict falls, and identifies a compensatory mechanism that protects some people from the effects of this damage on falls - all in a large representative elderly cohort of the MOBILIZE Boston Study. The study will provide new information necessary for the early diagnosis and ultimate prevention of cerebrovascular causes of falls and mobility impairments in elderly people.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG041785-02
Application #
8733119
Study Section
Neurological, Aging and Musculoskeletal Epidemiology Study Section (NAME)
Program Officer
Chen, Wen G
Project Start
2013-09-15
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
2
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Hebrew Rehabilitation Center for Aged
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02131
Jor'dan, Azizah J; Poole, Victoria N; Iloputaife, Ikechukwu et al. (2017) Executive Network Activation is Linked to Walking Speed in Older Adults: Functional MRI and TCD Ultrasound Evidence From the MOBILIZE Boston Study. J Gerontol A Biol Sci Med Sci 72:1669-1675
Lo, Justine; Lo, On-Yee; Olson, Erin A et al. (2017) Functional implications of muscle co-contraction during gait in advanced age. Gait Posture 53:110-114
Tchalla, Achille E; Wellenius, Gregory A; Sorond, Farzaneh A et al. (2017) Elevated Soluble Vascular Cell Adhesion Molecule-1 Is Associated With Cerebrovascular Resistance and Cognitive Function. J Gerontol A Biol Sci Med Sci 72:560-566
Zhou, Junhong; Habtemariam, Daniel; Iloputaife, Ikechukwu et al. (2017) The Complexity of Standing Postural Sway Associates with Future Falls in Community-Dwelling Older Adults: The MOBILIZE Boston Study. Sci Rep 7:2924
Gow, Brian J; Hausdorff, Jeffrey M; Manor, Brad et al. (2017) Can Tai Chi training impact fractal stride time dynamics, an index of gait health, in older adults? Cross-sectional and randomized trial studies. PLoS One 12:e0186212
Lo, On-Yee; Halko, Mark A; Zhou, Junhong et al. (2017) Gait Speed and Gait Variability Are Associated with Different Functional Brain Networks. Front Aging Neurosci 9:390
Varma, Vijay R; Hausdorff, Jeffrey M; Studenski, Stephanie A et al. (2016) Aging, the Central Nervous System, and Mobility in Older Adults: Interventions. J Gerontol A Biol Sci Med Sci 71:1451-1458
Zhou, Junhong; Lipsitz, Lewis; Habtemariam, Daniel et al. (2016) Sub-sensory vibratory noise augments the physiologic complexity of postural control in older adults. J Neuroeng Rehabil 13:44
Sri-on, Jiraporn; Tirrell, Gregory Philip; Lipsitz, Lewis A et al. (2016) Is there such a thing as a mechanical fall? Am J Emerg Med 34:582-5
Berry, Sarah D; Placide, Sebastian G; Mostofsky, Elizabeth et al. (2016) Antipsychotic and Benzodiazepine Drug Changes Affect Acute Falls Risk Differently in the Nursing Home. J Gerontol A Biol Sci Med Sci 71:273-8

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