Brain Networks and Mobility Function: B-NET (B-NET)

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.

Study Overview

• Status: Completed
• Conditions: Central Nervous System; White Matter Disease

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 192

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Community-dwelling adults reflecting the gender/race composition of Forsyth County in the target age-range will be identified. The 70 and up age-span was chosen because epidemiologic data shows accelerating functional decline and increased prevalence of white matter abnormalities across this age-range.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Community-Dwelling Older Adults; 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?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Gait Speed	This will be assessed over 4 meters 3 times at usual pace and 3 times at fast pace using an instrumented mat (GAITRite System), which provides data on average step and stride length, initial and terminal double support time, as well as the variability in these measures	baseline and 18 and 30 months
Change in lower extremity muscle strength	Maximal isokinetic knee extension and flexion strength will be measured using an isokinetic dynamometer	baseline and 18 and 30 months
Change in postural sway	Postural sway during quiet stance will be assessed from Center-of-Pressure (COP) trajectory data collected at 100 Hz using an Advanced Mechanical Technology Incorporated (AMTI) AccuSway biomechanics force platform.	baseline and 18 and 30 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Stephen Kritchevsky, PhD, Wake Forest University Health Sciences

Publications and helpful links

Helpful Links

• Effects of a Motor Imagery Task on Functional Brain Network Community Structure in Older Adults: Data from the Brain Networks and Mobility Function (B-NET) Study
• Corrigendum: Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study
• Examining the intersection of cognitive and physical function measures: Results from the brain networks and mobility (B-NET) study
• Associations of physical function and body mass index with functional brain networks in community-dwelling older adults

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2018
• Primary Completion (Actual): July 12, 2023
• Study Completion (Actual): July 12, 2023

Study Registration Dates

• First Submitted: January 26, 2018
• First Submitted That Met QC Criteria: February 5, 2018
• First Posted (Actual): February 12, 2018

Study Record Updates

• Last Update Posted (Actual): August 18, 2023
• Last Update Submitted That Met QC Criteria: August 14, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: BNET; Brain Networks; Mobility Function; SMCCS
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Leukoencephalopathies
• Other Study ID Numbers: IRB00046460; 1R01AG052419-01A1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No