Brain Networks and Mobility Function: B-NET

Study Overview
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Brief Summary
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Rapidly accumulating evidence indicates that the central nervous system (CNS) plays a pivotal role in mobility function with age-associated CNS changes strongly contributing to declining mobility. Studies linking the brain to mobility have used anatomical measures like brain volume and white matter integrity, and suggest that damage to the connecting fibers of the brain (white matter) is related to mobility impairment. Unfortunately, age-related structural white matter damage appears irreversible and only indirectly indicates the functional connectivity between brain regions. It is believed that functional brain network analyses have the potential to identify individuals that may benefit from interventions prior to the development of irreversible white matter lesions. The current project will assess both physical and cognitive function and integrate these variables with measures of brain network connectivity.

Detailed Description
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Studies linking the brain to mobility have used anatomical measures like brain volume and white matter integrity, and suggest that damage to the connecting fibers of the brain (white matter) is related to mobility impairment. Unfortunately, age-related structural white matter damage appears irreversible and only indirectly indicates the functional connectivity between brain regions. The preliminary data show that directly assessed patterns of functional connectivity correlate with mobility function and can be changed by interventions that improve mobility function. It is not known how changes in CNS functional connectivity relate to changes in mobility, information critical for the design of interventions targeting CNS connectivity to improve mobility impairments. It is clear that structural connectivity underlies functional connectivity, and that structural brain lesions result in altered functional connections. B-NET will assess white matter (WM) disease burden and microstructural changes and relate these changes to functional brain network connectivity. We hypothesize that because sensory motor cortex community structure (SMC-CS) characterizes current brain organization, it will be associated with mobility function independently of anatomical damage markers. Such knowledge may permit earlier identification of persons at high risk for mobility decline and facilitate earlier and better targeted interventions.

Official Title
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Brain Networks and Mobility Function: B-NET

Conditions
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Central Nervous System, White Matter Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Community-dwelling adults aged ≥70 years Willing to provide informed consent; ability to communicate with study personnel. Exclusion Criteria: Serious or uncontrolled chronic disease such as: Cancer (stage 3 or 4) or having had radiation or chemotherapy in the past year Uncontrolled angina Heart failure (stage 3-4) Respiratory disease requiring the use of oxygen Uncontrolled endocrine/metabolic disease (fasting glucose >250mg/dL) Liver failure (AST > 40IU/L and/or ALT > 44 IU/L) Renal failure requiring dialysis Clinically diagnosed neurologic diseases: Parkinson's disease; Amyotrophic Lateral Sclerosis (ALS); Multiple Sclerosis, prior stroke with residual effects lasting longer than 24hrs Diagnosis of schizophrenia, bipolar, or other psychotic disorder Diagnosis of Alzheimer's disease or evidence of impaired cognitive function Prior traumatic brain injury with residual deficits Unwilling or unable to have an MRI brain scan (see MRI screening form). Dependent on a walker or another person to ambulate. Plans to relocate in the next 2- 3 years. Single or double amputee Musculoskeletal impairments severe enough to preclude functional testing Participating in an exercise or cognitive enhancing intervention Any other reason the PI or study physician feels the participant would not adhere to the protocol

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Community-Dwelling Older Adults<br>The group will consist of 240 community-dwelling older adults with a range of mobility function based on the short physical performance battery (SPPB). | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Extended Short Physical Performance Battery (eSPPB) | The expanded Short Physical Performance Battery (eSPPB) is a modified version of a widely used assessment of lower extremity physical function that consists of 3 standing balance tasks held for 10 seconds each (side-by-side, tandem and semi-tandem), two 4-m walk tests to assess usual gait speed, and 5 repeated chair stands. To minimize ceiling effects and maximize overall dispersion of test scores, the eSPPB increases the holding time of the semi- and full-tandem stands to 30 seconds and adds a single leg stand and a narrow walk test of balance (walking at usual pace within lines of tape spaced 20 cm apart). eSPPB scores are continuous and range from 0 to 4, with higher scores indicative of better performance. | baseline and 6, 18, and 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cardiovascular fitness | The fast-paced 400M walk protocol will be used. | baseline and 18 and 30 months | 
| Change in Digit Symbol Substitution Test (DSST) | The WAIS-III Digit Symbol Substitution Test will be used. | baseline and 18 and 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BNET, Brain Networks, Mobility Function, SMCCS