Clinical trial NCT03430427: Brain Networks and Mobility Function: B-NET
Official title: Brain Networks and Mobility Function: B-NET
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Central Nervous System
White Matter Disease
Keywords: BNET
Brain Networks
Mobility Function
SMCCS
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-02-12
Enrollment: 192
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Extended Short Physical Performance Battery (eSPPB)
timeFrame: baseline and 6, 18, and 30 months
Secondary outcomes:
measure: Change in Cardiovascular fitness
timeFrame: baseline and 18 and 30 months
measure: Change in Digit Symbol Substitution Test (DSST)
timeFrame: baseline and 18 and 30 months
Other outcomes:
measure: Change in Gait Speed
timeFrame: baseline and 18 and 30 months
measure: Change in lower extremity muscle strength
timeFrame: baseline and 18 and 30 months
measure: Change in postural sway
timeFrame: baseline and 18 and 30 months
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Stephen Kritchevsky, PhD
role: PRINCIPAL_INVESTIGATOR
References: