Motor impairment is present in up to 50% of adults by age 85 and associated with adverse health outcomes. Understanding its neuropathology is essential for efforts to meet this growing public health challenge. The overall goal of Brain and Spinal Cord Microvascular Pathology and Late-Life Motor Impairment is to test the hypothesis that microvascular pathology in the brain and spinal cord contributes to late-life motor impairment. Brain imaging studies suggest that microvascular pathology, as inferred by white matter hyperintensities, is an important factor in late-life motor impairment. We propose to directly investigate specific microvascular pathologies including, arteriolosclerosis, microscopic infarcts and cerebral amyloid angiopathy. These pathologies are not visible via brain imaging and can only be directly studied using histopathologic techniques. Furthermore, to understand late-life motor impairment it is essential to examine both the brain and spinal cord, since damage to either or both can cause motor deficits. Indeed, though microvascular pathology in the spinal cord has been documented, its contribution to late-life motor impairment has not been studied. Furthermore, although microvascular pathology in the brain is recognized as a possible cause of motor impairment, systematic studies of microvascular pathology from motor-related regions of the brain and the spinal cord from the same individuals with clinical data proximate to death are lacking. Compelling preliminary data from post-mortem indices collected in the cognitive-brain regions show that even among older adults without evidence of macroscopic infarcts, microvascular pathology is present in more than 35% of brains and common in the spinal cord. Further, more severe microvascular pathology in the brain is associated with a lower level and more rapid motor decline. Building on these data, we propose to directly examine microvascular pathology in the motor system by taking advantage of the Memory and Aging Project (R01AG17911). This study will donate the clinical and post-mortem specimens they have already collected for the proposed collection of microvascular pathology from the brain and spinal cord from the same individuals. Establishing that microvascular pathology in the brain and spinal cord contributes to progressive late-life motor impairment would fill important gaps in our scientific knowledge and is essential for interventions to alleviate this growing public health challenge.

Public Health Relevance

Motor impairment is present in up to half of all adults by age 85. Demonstrating that microvascular pathology in the brain and spinal cords may underlie late-life motor impairment is essential for efforts to alleviate this growing public health challenge an would greatly expand the role of cerebrovascular pathologies as an important barrier in need of treatment to maintain independence in old age.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
4R01AG043379-05
Application #
9084469
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
St Hillaire-Clarke, Coryse
Project Start
2012-09-30
Project End
2017-05-31
Budget Start
2016-06-01
Budget End
2017-05-31
Support Year
5
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Neurosciences
Type
Schools of Medicine
DUNS #
068610245
City
Chicago
State
IL
Country
United States
Zip Code
60612
Lim, Andrew S P; Gaiteri, Chris; Yu, Lei et al. (2018) Seasonal plasticity of cognition and related biological measures in adults with and without Alzheimer disease: Analysis of multiple cohorts. PLoS Med 15:e1002647
Lamar, Melissa; Yu, Lei; Rubin, Leah H et al. (2018) APOE genotypes as a risk factor for age-dependent accumulation of cerebrovascular disease in older adults. Alzheimers Dement :
Buchman, Aron S; Leurgans, Sue E; VanderHorst, Veronique G J M et al. (2018) Spinal motor neurons and motor function in older adults. J Neurol :
Kapasi, Alifiya; Leurgans, Sue E; James, Bryan D et al. (2018) Watershed microinfarct pathology and cognition in older persons. Neurobiol Aging 70:10-17
Jansen, Willemijn J; Wilson, Robert S; Visser, Pieter Jelle et al. (2018) Age and the association of dementia-related pathology with trajectories of cognitive decline. Neurobiol Aging 61:138-145
Buchman, Aron S; Dawe, Robert J; Yu, Lei et al. (2018) Brain pathology is related to total daily physical activity in older adults. Neurology 90:e1911-e1919
Sohail, Shahmir; Yu, Lei; Schneider, Julie A et al. (2017) Sleep fragmentation and Parkinson's disease pathology in older adults without Parkinson's disease. Mov Disord 32:1729-1737
Buchman, Aron S; Leurgans, Sue E; Nag, Sukriti et al. (2017) Spinal Arteriolosclerosis Is Common in Older Adults and Associated With Parkinsonism. Stroke 48:2792-2798
Buchman, Noa M; Leurgans, Sue E; Shah, Raj J et al. (2017) Urinary Incontinence, Incident Parkinsonism, and Parkinson's Disease Pathology in Older Adults. J Gerontol A Biol Sci Med Sci 72:1295-1301
Arvanitakis, Zoe; Capuano, Ana W; Leurgans, Sue E et al. (2017) The Relationship of Cerebral Vessel Pathology to Brain Microinfarcts. Brain Pathol 27:77-85

Showing the most recent 10 out of 29 publications