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 #
3R01AG041785-05S1
Application #
9515178
Study Section
Program Officer
St Hillaire-Clarke, Coryse
Project Start
2013-09-15
Project End
2019-05-31
Budget Start
2017-09-01
Budget End
2019-05-31
Support Year
5
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Hebrew Rehabilitation Center for Aged
Department
Type
DUNS #
030832075
City
Boston
State
MA
Country
United States
Zip Code
02131
Zhou, Junhong; Lo, On-Yee; Lipsitz, Lewis A et al. (2018) Transcranial direct current stimulation enhances foot sole somatosensation when standing in older adults. Exp Brain Res 236:795-802
Lipsitz, Lewis A; Manor, Brad; Habtemariam, Daniel et al. (2018) The pace and prognosis of peripheral sensory loss in advanced age: association with gait speed and falls. BMC Geriatr 18:274
Poole, Victoria N; Wooten, Thomas; Iloputaife, Ikechukwu et al. (2018) Compromised prefrontal structure and function are associated with slower walking in older adults. Neuroimage Clin 20:620-626
Chung, Chen-Chih; Pimentel Maldonado, Daniela A; Jor'dan, Azizah J et al. (2018) Lower cerebral vasoreactivity as a predictor of gait speed decline in type 2 diabetes mellitus. J Neurol 265:2267-2276
Manor, Brad; Zhou, Junhong; Harrison, Rachel et al. (2018) Transcranial Direct Current Stimulation May Improve Cognitive-Motor Function in Functionally Limited Older Adults. Neurorehabil Neural Repair 32:788-798
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
Veronese, Nicola; Cereda, Emanuele; Stubbs, Brendon et al. (2017) Risk of cardiovascular disease morbidity and mortality in frail and pre-frail older adults: Results from a meta-analysis and exploratory meta-regression analysis. Ageing Res Rev 35:63-73
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
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

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