Promoting Adaptive Neuroplasticity in Mild Cognitive Impairment

The aging US population threatens to overwhelm our healthcare infrastructure, especially since the rate of Alzheimer's disease (AD) alone is expected to triple in the coming decades. Memory cause functional impairment, reduced quality of life, increased caregiver burnout, and eventual institutionalization. The diagnosis of mild cognitive impairment (MCI) identifies those with memory deficits but who remain relatively independent in everyday life. MCI provides a window for interventions that target memory functioning. The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from different types of memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. This first-of-its-kind study has the potential to meaningfully translate more "basic" science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment; Alzheimer's Disease
• Intervention / Treatment: Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit

Detailed Description

Enrollment and interactions/interventions are temporarily paused due to COVID-19 and are expected to resume in the future. This is not a suspension of IRB approval.

The proposed study focuses specifically on a groundbreaking combination of mnemonic rehabilitation and non-invasive brain stimulation. The main idea is that brain stimulation can enhance functioning in the specific brain regions/networks, thereby increasing the patients' ability to benefit from memory rehabilitation. This will be a randomized, double-blind study (active vs. fake brain stimulation), that provides multiple treatment session. Outcome will be examined using both laboratory-based and real-world memory testing as well as brain imaging. This first-of-its-kind study has the potential to meaningfully translate more "basic" science findings into neuroanatomically targeted and functionally meaningful treatments for our aging population.

The general purpose of this study is to examine the effects of two types of treatments for memory impairment in those with mild cognitive impairment (MCI). One form of treatment is cognitive rehabilitation, which involves teaching new ways to learn and remember information. The second form of treatment uses a type of electrical brain stimulation called transcranial direct current stimulation (tDCS) to increase activity in certain brain areas that may be involved with memory. We will use brain imaging to see whether these treatments changed how individuals learn and remember information. We will also use cognitive tests and questionnaires to examine whether memory (and related abilities) changed because of treatment.

Values were updated in February 2023 after discovering coding errors in the original database. An exploratory outcome variable (effect of brain volumes) was removed at that time since the electrical field analyses are fundamentally dependent on brain volumes - the EF outcome measure remained but was modified to remove the two sham conditions since, by design, they did not receive any electric field (i.e., sham) and the statistical corrections could not be performed.

• Study Type: Interventional
• Enrollment (Actual): 107
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48105
      • VA Ann Arbor Healthcare System, Ann Arbor, MI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

General inclusion criteria (all patients):

• All medications stable for approximately 2-3 months;
• No history of severe mental illness;
• No current untreated alcohol or substance abuse/dependence;
• English as native and preferred language;
• MRI-compatible if taking part in fMRI studies
• Able to give informed consent.

MCI Inclusion Criteria:

- Diagnosis of amnestic MCI based on criteria set forth by Petersen (2004). Additionally, other potential causes of cognitive deficit ruled out by the referring physician

Exclusion Criteria:

• History of neurological disease or injury
• History of severe mental illness
• Current untreated alcohol or substance abuse
• Other conditions may exclude; please discuss with contact

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active tDCS + mnemonic strategy training; Group receives active brain stimulation plus memory rehabilitation	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Active brain stimulation; Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Sham (placebo)
Active Comparator: sham tDCS + mnemonic strategy training; Group receives sham brain stimulation plus memory rehabilitation	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Active brain stimulation; Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Sham (placebo)
Active Comparator: active tDCS + autobiographical memory recall; Group receives active brain stimulation plus reminiscence training	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Active brain stimulation; Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Sham (placebo)
Active Comparator: sham tDCS + autobiographical memory recall; Group receives sham brain stimulation plus reminiscence training	Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Active brain stimulation; Device: Transcranial direct current stimulation (tDCS) Soterix Medical Inc. tDCS unit; Sham (placebo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Face-name Memory Test Performance	Raw number of face-name pairs correctly recalled with a maximum of 15 points; higher values are better at each time point. Change at post-session 5 (day 5 after baseline)) calculated relative to baseline performance (positive differences indicate improvement; negative values indicate decline). Data coding errors were identified and accurate values were reported 2/6/2023.	change from baseline to post session 5 (day 5 after baseline)
Object Location Association Memory Test Performance - Recognition Condition	Performance measured using number of correctly identified locations (3 locations per stimulus; 15 total stimuli). Higher values indicate better performance. Change at post-session 5 (day 5 after baseline) calculated relative to baseline performance (positive differences indicate improvement; negative values indicate decline). Data coding errors were identified and accurate data were updated 2/6/2023.	change from baseline to post session 5 (day 5 after baseline)
fMRI Betaweight Change	Changes in task related blood oxygen dependent signal (BOLD) activation for the face-name (novel post > novel pre) contrast in the left inferior frontal gyrus (pars triangularis, pars orbitalis, pars opercularis). Data are preliminary betaweights for the above noted contrast. Positive values reflect increased BOLD signal while negative values represent reduced BOLD signal. Not all participants were able to complete fMRI, which explains sample size discrepancies with other outcome measures. Data coding errors were discovered and accurate, updated data reported on 2/6/2023	change from baseline to post session 5 (day 5 after baseline)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MMQ - Strategy Subscale	Changes on the Multifactorial Memory Questionnaire - strategy subscale. Raw points where higher values reflect better performance at each time point (0-76 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline.	change from baseline to post session 5 (day 5 after baseline)
Prose Memory	Performance on the Ecological Memory Simulations- Medical Instructions subtest. Raw points where higher values reflect better performance at each time point (0-15 possible points at each time point). Reported values reflect change from baseline (i.e., post-session day 5 vs. baseline) where positive values represent improvement and negative values represent decline. Corrected values are now included (2/23) that account for age, sex, and baseline neuropsychological abilities.	change from baseline to post Session 5 (day 5 after baseline)
Spatial Navigation	Performance on Ecological Memory Simulations routes subtest (serial order). Higher values indicate better performance at each time point (0-9 possible points at each time point). Change from baseline is reported (post-session day 5 vs. baseline) so higher values indicate better recall while negative values indicate decline. Corrected data are now reported (2/23) accounting for age, sex, and baseline neuropsychological abilities.	change from baseline to post session 5 (day 5 after baseline)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Planned (Tertiary) Analyses of Patient-specific Characteristics That Affect Treatment Outcome	Planned analyses to examine patient specific characteristics that affect treatment efficacy and would be vital for clinical translation at the individual patient level. Data analyzed using a composite "recognition" score that combined the face-name and object-location task recognition scores (total on a 0-30 point scale; values below are change from baseline; higher values are "better" and reflect improved memory test performance). Patient-level factors of age, sex, race, RBANS Delayed Memory Index, MoCA, Emory version of the Wisconsin Card Sorting Test (total sorts) were included as covariates.	change from baseline post treatment (within ~ 96 hours of session 5)
Change in Beta-weights Controlling for Electric Field (EF)	Outcome measure is the change in betaweight (as a percent signal change: post session 5 minus baseline) during the face-name and object-location tasks (same metric as Primary Outcome measure 3) while controlling for the electric field (EF). Finite element model based measurement of electric field in the targeted brain regions (Values range from 0 to no theoretical upper limit with higher values reflecting more electrical current; most values will be under 0.5 V/m). The EF was calculated using the baseline MRI T1 scan for each individual. EF values were then included in the linear mixed model analysis of fMRI Beta-weight change (post training vs. baseline) since EF values at the targeted brain region varied across participants. Note, EF values only apply to active HD-tDCS groups, so sham groups have no data to report and were removed accordingly (updated 2/23).	Betaweight change: Post session 5 (day 5) minus baseline

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Benjamin M. Hampstead, PhD, VA Ann Arbor Healthcare System, Ann Arbor, MI

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): February 28, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: May 29, 2014
• First Submitted That Met QC Criteria: June 2, 2014
• First Posted (Estimated): June 4, 2014

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 8, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: transcranial direct current stimulation; Imaging; Aging; Magnetic Resonance Imaging (MRI); Neurology; Cognitive Disorders; Alzheimer's Disease/Dementia; Physical Medicine & Rehabilitation
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: N1534-R

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No