Clinical trial NCT03224988: Bilateral Brain Dynamics in Cognition and Aging
Official title: Bilateral Brain Dynamics Supporting Cognition in Normal Aging and Dementia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Alzheimer Disease
Aging
MCI
Keywords: Alzheimer's Disease
AD
MCI-AD
MCI
Memory
TMS
Transcranial Magnetic Stimulation
Neuropsychological evaluation
MRI
DTI
EEG
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
name: National Institutes of Health (NIH)
First posted: 2017-07-21
Enrollment: 30
Sex: ALL
Minimum age (years): 60
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.


Eligibility criteria: Inclusion Criteria:

1. Willing to provide informed consent
2. English speaking
3. Signed HIPAA authorization
4. Use of effective method of birth control for women of childbearing capacity

Exclusion Criteria:

1. Current or recent (within the past 6 months) of substance abuse or dependence, excluding nicotine and caffeine (urine test).
2. Current serious medical illness (self report).
3. 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); \[TMS Adult Safety Screening (TASS) form\].
4. Subjects are unable or unwilling to give informed consent.
5. Diagnosed any Axis I DSM-IV disorder (MINI, DSM-IV)
6. Subjects with a clinically defined neurological disorder including, but not limited to:

   1. Any condition likely to be associated with increased intracranial pressure
   2. Space occupying brain lesion.
   3. History of stroke.
   4. Transient ischemic attack within two years.
   5. Cerebral aneurysm.
   6. Dementia.
   7. Mini Mental Status Exam (MMSE) score of \<24.
   8. Parkinson's disease.
   9. Huntington's disease.

   i. Multiple sclerosis.
7. Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold.
8. Subjects not willing to tolerate the confinement associated with being in the MRI scanner.
9. Women who are pregnant or breast-feeding (urine test).
10. Blindness.
11. Inability to read or understand English.
12. Intracranial implants, such as:

    1. Cochlear implants;
    2. Aneurysms clips;
    3. Shunts;
    4. Stimulators;
    5. Electrodes;
    6. Cardiac pacemakers;
    7. Vagus Nerve stimulation devices.

Primary outcomes:
measure: Establish the structural basis for bilateral brain interactions in healthy older adults.
timeFrame: 2 years
measure: Establish the structural basis for bilateral brain interactions in MCI-AD older adults.
timeFrame: 2 years
Secondary outcomes:
measure: Establish the temporal dynamics of cross-hemispheric communication in normal aging using unilateral TMS
timeFrame: 3 years
measure: Establish the temporal dynamics of cross-hemispheric communication in normal aging using bilateral TMS
timeFrame: 3 years
measure: Establish the temporal dynamics of cross-hemispheric communication in normal aging using EEG
timeFrame: 3 years
measure: Establish the temporal dynamics of cross-hemispheric communication in MCI-AD using unilateral TMS
timeFrame: 3 years
measure: Establish the temporal dynamics of cross-hemispheric communication in MCI-AD using bilateral TMS
timeFrame: 3 years
measure: Establish the temporal dynamics of cross-hemispheric communication in MCI-AD using EEG
timeFrame: 3 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
Study officials:
affiliation: Duke University
name: Simon Davis, PhD
role: PRINCIPAL_INVESTIGATOR
References: