Bilateral Brain Dynamics in Cognition and Aging

NCT03224988 | Completed FDA Device

• 1 other identifier: Pro00085432
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This project is focused on the gap in understanding of bilateral brain interactions and their role in helping normative and clinical elderly populations maintain cognitive health. The investigator will focus on investigating this neural mechanism of these interactions and promoting them with a precise application of TMS, in order to test the hypothesis that excitatory interactions between the hemispheres can provide positive outcomes for patients with pre-clinical AD (amnestic Mild Cognitive Impairment or MCI-AD). In Session 1, the investigator will establish the spatial specificity of bilateral brain mechanisms with combination of behavior, TMS, and structural neuroimaging in cortical sites known to be active during memory encoding. In Session 2, the investigator will establish the underlying dynamics of interhemispheric communication using a novel combination of TMS and electroencephalography (EEG) to establish the coordinated activity between the hemispheres; Lastly, in Session 3, the investigator will use the TMS entraining parameters delineated in Aim 2 to promote specific cross-hemispheric communication, applied to participants performing a Picture Encoding task, a general task of memory performance. The outcome of these studies will allow our group to evaluate the strength of this brain stimulation protocol in alleviating age-related and dementia-related cognitive decline, and enable development of novel treatment protocols for dementia in elderly cohorts.

Conditions

Alzheimer Disease; Aging; MCI

Keywords

Alzheimer's Disease; AD; MCI-AD; MCI; Memory; TMS; Transcranial Magnetic Stimulation; Neuropsychological evaluation; MRI; DTI; EEG

Outcome Measures

Primary Outcomes (2)

• Establish the structural basis for bilateral brain interactions in healthy older adults.

  This will be examined using a Picture Encoding (PE) task in healthy older adults, which will allow identification of spatial brain targets based on the structural pathways connecting left and right DLPFC, ultimately relating the integrity of these pathways based on PE task performance. This Primary Outcome measure will therefore be performance scores (% correct) on this PE task.

  2 years

• Establish the structural basis for bilateral brain interactions in MCI-AD older adults.

  This will be examined using a Picture Encoding (PE) task in MCI-AD participants, which will allow identification of spatial brain targets based on the structural pathways connecting left and right DLPFC, ultimately relating the integrity of these pathways based on PE task performance. This Primary Outcome measure will therefore be performance scores (% correct) on this PE task.

  2 years

Secondary Outcomes (6)

• Establish the temporal dynamics of cross-hemispheric communication in normal aging using unilateral TMS

  3 years

• Establish the temporal dynamics of cross-hemispheric communication in normal aging using bilateral TMS

  3 years

• Establish the temporal dynamics of cross-hemispheric communication in normal aging using EEG

  3 years

• Establish the temporal dynamics of cross-hemispheric communication in MCI-AD using unilateral TMS

  3 years

• Establish the temporal dynamics of cross-hemispheric communication in MCI-AD using bilateral TMS

  3 years

Study Arms (2)

Normal Adults

Device: TMS

MCI Adults

Device: TMS

Interventions

TMS DEVICE

A multimodal approach consisting of single pulse TMS, dual-coil TMS, and EEG will be used to examine whether synchronous hemispheric interactions associated with TMS will be present in weighted phase-lag coherence (WPLI), if these measures will be enhanced by in-phase TMS and reduced by counter-phase TMS, and if WPLI will be greater for normal controls than MCI-ADs.

MCI Adults; Normal Adults

Eligibility Criteria

• Age: 60 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Participants will be recruited from the Duke Bryan Alzheimer's Disease Research Center Alzheimer's Disease Prevention Registry (ADRC ADPR). Thirty healthy volunteers and thirty MCI-ADs will be recruited.

You may qualify if:

• Willing to provide informed consent
• English speaking
• Signed HIPAA authorization
• Use of effective method of birth control for women of childbearing capacity

You may not qualify if:

• Current or recent (within the past 6 months) of substance abuse or dependence, excluding nicotine and caffeine (urine test).
• Current serious medical illness (self report).
• History of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, head injury, cranial metal implants, known structural brain lesion, devices that may be affected by TMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator); \[TMS Adult Safety Screening (TASS) form\].
• Subjects are unable or unwilling to give informed consent.
• Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV)
• Subjects with a clinically defined neurological disorder including, but not limited to:
• Any condition likely to be associated with increased intracranial pressure
• Space occupying brain lesion.
• History of stroke.
• Transient ischemic attack within two years.
• Cerebral aneurysm.
• Dementia.
• Mini Mental Status Exam (MMSE) score of \<24.
• Parkinson's disease.
• Huntington's disease.

Sponsors & Collaborators

• Duke University: lead
• National Institute on Aging (NIA): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Saliva samples were collected on a subset of participants who consented to this additional study component.

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Simon Davis, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 10, 2017
• First Posted: July 21, 2017
• Study Start: March 20, 2018
• Primary Completion: January 20, 2022
• Study Completion: January 20, 2022
• Last Updated: March 3, 2022

Record last verified: 2022-02

Locations

US (1)