CogT BEEM Study (a tDCS Study)

NCT04099524 | Completed Results

• 2 other identifiers: STUDY00003664R21MH120734
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Co-existing neuropsychiatric symptoms (NPS) in patients with mild cognitive impairment (MCI), especially those worsening over time, are associated with more rapid cognitive and functional decline and a greater risk of Alzheimer's disease (AD). Optimal NPS management, meaning effectively managing multiple NPS simultaneously, requires a solid understanding of the shared neural mechanism across NPS. The goal of this proof-of-concept mechanistic intervention study is to validate the causal relationship between a NPS-shared neural circuit the investigators previously discovered and various NPS. The investigators will modify a key region within the NPS-shared neural circuit \[i.e. left precentral gyrus (LPG), critical for regulating visual attention\] with anodal transcranial direct current stimulation (tDCS). Our central hypothesis is that an activation of LPG and a reorganization of NPS-shared neural circuit will link to improvement in multiple NPS. Using a Stage 0 pilot randomized control trial design the investigators will recruit n = 40 older adults with informant-rated NPS that has worsened in the past 2 years, which is considered the most detrimental type of NPS in MCI. The investigators will assign participants to 4-week active anodal vs. sham LPG online tDCS group. The investigators will assess resting-state and visual attention task-related functional MRI and informant-rated NPS at baseline, and the end of week 4 and week 8, and diffusion MRI at baseline. The two primary aims are to determine the effect of tDCS on NPS-shared neural circuit (Aim 1), as well as the relationship between NPS-shared neural circuit and informant-report NPS (Aim 2). The exploratory aim will be to examine the relationship between NPS and the coherence between structural and functional aspects of the NPS-shared neural circuit. Probing the LPG via anodal tDCS provides a way to experimentally test the causal relationship between our previously discovered NPS-shared neural circuit and informant-rated NPS. The proposed research is highly innovative, while scientifically grounded, for targeting one brain region that may affect multiple NPS. Validating the hypotheses has the potential for future R01 study that directly conducts a Stage 2 trial addressing NPS in MCI, and thus ultimately improves patient's quality of life and reducing caregiving burden.

Conditions

Mild Cognitive Impairment; Neuropsychiatric Syndrome

Outcome Measures

Primary Outcomes (2)

• Change of C3 Activation (NPS-shared Neural Circuit Measure

  Change of arbitrary unit LPG activation in response to visual attention task (measured using task related fMRI). No theoretical minimum or maximum exists for this scale.

  from baseline to post-intervention (4 weeks)

• Change of C3 Connectivity (NPS-shared Neural Circuit Measure 21)

  Change of arbitrary unit of correlation between LPG and amygdala at rest (resting fMRI). No theoretical minimum or maximum exists for this scale.

  from baseline to post-intervention (4 weeks)

Secondary Outcomes (2)

• Change of Patient-report NPS

  from baseline to post-intervention (4 weeks)

• Change of Informant-rated NPS

  from baseline to post-intervention (4 weeks)

Study Arms (2)

active tDCS

EXPERIMENTAL

We will apply the stimulation for 20 minutes using current at 1.5mA with a ramp up and ramp down period of 30 seconds at the start and end of the session.

Device: tDCS

sham tDCS

SHAM COMPARATOR

tDCS will ramp up for 30 seconds with 1 mA current and then ramp off within 10 seconds. As 30 seconds is too short for tDCS to have any effects, this will be the control condition. tDCS is on for 30 seconds because that is usually the only time individuals would experience tingling and itching - a factor we aim to equate between experimental and control conditions.

Device: tDCS

Interventions

tDCS DEVICE

tDCS (LPG/C3-anode, orbitofrontal cortex/Fp2-cathode) will be administered for 4 weeks (1 session per weekday for 2 weeks, and then 2 sessions per week for 2 weeks, for a total of 14 sessions). All subjects will receive anodal tDCS stimulation for 20 minutes per session, on C3 and the cathode electrode on Fp2 using 10/20 EEG system. tDCS will be applied with a pair of 35 cm2 single-use sponges soaked in approximately 4mL of saline solution on each side (\~8mL per sponge) connected to the stimulator. During the 20-minute tDCS session, we will use online tDCS design (i.e., a subject will simultaneously work on the visual attention-oriented task.

active tDCS; sham tDCS

Eligibility Criteria

• Age: 60 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Forty subjects with MCI and comorbid NPS, which have worsened in the past 2 years (as rated by their study-partner's responses to the NPI-Q):
• In the past month, presence of \> 2 symptoms; and

You may not qualify if:

• Participants may be excluded from enrollment, or have their enrollment deferred until they are eligible, for the reasons listed below. Final decisions regarding enrollment will be determined by the PI on a case-by-case basis.
• Presence of any neurological or vascular disorders (e.g. - Multiple Sclerosis \[MS\], Traumatic Brain Injury \[TBI\], chronic heart failure \[CHF\], Parkinson's disease \[PD\]);
• Clinical diagnosis of dementia as defined by the most recent version of the DSM;
• Current enrollment in another study aimed at improving cognitive abilities and/or emotional well-being;
• MRI contraindications (e.g. - pacemaker, implantable cardioverter defibrillator \[ICD\], aneurysm clips, severe claustrophobia);
• tDCS contraindications (e.g. - scalp or skin condition, history of migraines, seizures or epilepsy, and/or strokes, TBI), metallic implants, history of adverse effects to previous tDCS or other brain stimulation techniques).

Sponsors & Collaborators

• University of Rochester: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Cabin, Ur

Rochester, New York, 14642-0001, United States

Location

Related Publications (1)

• Turnbull A, Anthony M, Tadin D, Porsteinsson AP, Heffner K, Lin FV. Effect of online tDCS to left somatomotor cortex on neuropsychiatric symptoms among older adults at risk for dementia. Cortex. 2023 Feb;159:131-141. doi: 10.1016/j.cortex.2022.10.015. Epub 2022 Dec 17.

  PMID: 36623419 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Results Point of Contact

• Title: Feng Vankee Lin, PI
• Organization: Stanford University

vankee_lin@stanford.edu

6082156005

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 19, 2019
• First Posted: September 23, 2019
• Study Start: December 6, 2019
• Primary Completion: January 19, 2022
• Study Completion: January 19, 2022
• Last Updated: November 7, 2023
• Results First Posted: November 7, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)