N/A N=40 Randomized Quadruple-blind Treatment

Noninvasive Brain Stimulation for Mild Cognitive Impairment

Mild Cognitive Impairment · Mild Neurocognitive Disorder · Cognitive Decline · Mental Deterioration · Cognitive Dysfunction

Bottom Line

View on ClinicalTrials.gov: NCT03331796 ↗

Enrolled (actual)

Serious AEs

7.5%

Results posted

Sep 2025

Primary outcome: Primary: Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 1 Week After Intervention and Adjusted for Baseline Performance — 36.1; 48.8; 37.0 total number of words correctly recalled — p=0.63

Study Design & Population

Study type: Interventional
Phase: N/A
Interventions: Active rTMS (Bilateral DLPFC) (Device); Active rTMS (Bilateral LPC) (Device); Placebo rTMS (Inactive) (Device)
Age: Adult, Older Adult · 55+ yrs
Sex: All
Sponsor: Palo Alto Veterans Institute for Research
Primary completion: Dec 2022

Outcome Measures

Outcome	Result	p-value
PRIMARY Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 1 Week After Intervention and Adjusted for Baseline Performance	36.1; 48.8; 37.0	0.63
SECONDARY Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 3 Months After Intervention and Adjusted for Baseline Performance	38.4; 53.0; 41.3	0.45
SECONDARY California Verbal Learning Test-II (CVLT-II) Semantic Clustering Score, 1 Week After Intervention and Adjusted for Baseline Performance	0.5; 0.5; 0.1	0.29
SECONDARY Total Number of Words Correctly Recalled During the "Long Delay Free Recall" Component of the California Verbal Learning Test-II (CVLT-II), Assessed 1 Week After Intervention and Adjusted for Baseline Performance	6.2; 10.3; 6.2	.33
SECONDARY Depressive Symptoms, as Measured by the Geriatric Depression Scale (GDS), Assessed 1 Week After Intervention and Adjusted for Baseline Performance	3.2; 1.9; 2.9	0.58
SECONDARY Everyday Functional Outcomes, as Measured by the Everyday Cognition (ECog) Questionnaire (Participant Version) Completed 1 Week After Intervention	84.8; 66.1; 72.3	0.30
SECONDARY Everyday Functional Outcomes, as Measured by the Everyday Cognition Questionnaire (Informant /Study Partner Version) Completed 1 Week After Intervention	73.2; 61.1; 61.5	0.996
SECONDARY Instrumental Activities of Daily Living (IADLs), as Measured by the Functional Assessment Questionnaire, Completed 1 Week After Intervention	3.29; 1.00; 1.33	0.97
SECONDARY Global Cognitive Function, as Measured by the Montreal Cognitive Assessment (MoCA), Assessed 1 Week After Intervention and Adjusted for Baseline	23.0; 23.8; 23.6	0.84
SECONDARY Visuospatial Memory, as Measured by the Brief Visuospatial Memory Test-Revised (BVMT-R), assessed1 Week After Intervention and Adjusted for Baseline Performance	17.8; 18.5; 21.6	0.48
SECONDARY Language Function, as Measured by Category Fluency (CF), Assessed 1 Week After Intervention and Adjusted for Baseline Performance	16.7; 19.8; 19.4	0.075
SECONDARY Language Function, as Measured by 42-item Boston Naming Test (BNT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance	36.3; 38.4; 35.9	0.28
SECONDARY Visuoconstructional Function, as Measured by the Rey-Osterrieth Complex Figure (ROCF) Copy Score, assessed1 Week After Intervention and Adjusted for Baseline Performance.	33.8; 32.7; 34.9	0.66
SECONDARY Speed of Processing and Executive Function, as Measured by Trail Making Part B, Assessed 1 Week After Intervention and Adjusted for Baseline Performance	2.11; 2.42; 2.42	0.59
SECONDARY Attention, as Measured by the Attentional Network Task (ANT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance	—	—
SECONDARY Change From Baseline in Brain Functional Connectivity	—	—
SECONDARY Pre-post Change in Peripheral Levels of Brain-derived Neurotrophic Factor (BDNF)	394.83; 1188.85; 687.17	0.768

Summary

The goal of this study is to test the efficacy of repetitive Transcranial Magnetic Stimulation (rTMS) as a treatment for Mild Cognitive Impairment (MCI). Participants will be randomly assigned to one of three treatment groups: Group 1: Active Dorsolateral Prefrontal Cortex (DLPFC) rTMS; Group 2: Active Lateral Parietal Cortex (LPC) rTMS; and Group 3: Inactive rTMS (Placebo) control (evenly split between each coil location). Participation in the study takes approximately 7 ½ months-including a 2-to 4-week treatment phase (20 rTMS sessions) and a 6-month follow-up phase.

Eligibility Criteria

Both Veterans and Non-Veterans may enroll if they meet the following criteria **

Inclusion Criteria

Diagnosed with amnestic Mild Cognitive Impairment (aMCI);
Stable medications (including any dementia-related meds) for at least 4 weeks prior to Baseline;
Geriatric Depression Scale score less than 6;
Ability to obtain a motor threshold, determined during the screening process;
Study partner available; living situation enables attendance at clinic visits;
Visual and auditory acuity adequate for neuropsychological testing;
Good general health with no diseases expected to interfere with the study;
Participant is not pregnant or of childbearing potential (i.e. women must be 2 years post-menopausal or surgically sterile);
Modified Hachinski Ischemic score less than or equal to 4;
Agree to DNA extraction for single nucleotide polymorphism (SNP) genotyping;
Able to understand study procedures and comply with them for the entire length of the study.

Exclusion Criteria

Prior exposure to rTMS within the past 12 months;
Magnetic field safety concern such as a cardiac pacemaker, cochlear implant, implanted device in the brain (deep brain stimulation), or metal fragments or foreign objects in the eyes, skin or body;
Any significant neurological disease other than suspected incipient Alzheimer's disease;
Unstable cardiac disease or recent (< 3 months previous) myocardial infarction. Any significant systemic illness or unstable medical condition that could lead to difficulty with protocol adherence;
History of epilepsy or repetitive seizures, as determined by patient report or chart review;
History of a medical condition or current use/abuse of medications and substances that increase the risk of a seizure, specifically:
Traumatic brain injury within 2 months that would increase the risk for seizure;
Unable to safely withdraw, at least 4 weeks prior to Baseline, from medications that substantially increase the risk of having seizures (for example: theophylline, clozapine, and methylphenidate).
Current or past history of a mass lesion, cerebral infarct, or other noncognitive active neurological disease that would increase the risk for seizure.
Stimulant abuse within the previous 90 days. Cocaine and abuse of amphetamine and methylphenidate are associated with an increased risk of seizures;
Major depression or bipolar disorder (DSM-IV) within the past 1 year, or psychotic features within the last 3 months that could lead to difficulty with protocol adherence;
Taking sedative hypnotics or medications with anti-cholinergic properties and unable to withdraw at least 4 weeks prior to Baseline;
Current alcohol or substance abuse (not including caffeine or nicotine) within the past 1 year, as determined by chart review, participant or study partner report, or greater than "moderate" alcohol use defined by the Quantity-Frequency-Variability Index (Cahalan, Cisin, & Crossley, 1969);
Any contraindications for magnetic resonance imaging (MRI) studies, e.g. severe claustrophobia, weight above 350 lb maximum allowed by MRI scanner, pregnancy;
Participation in another concurrent clinical trial;
Inability or unwillingness of individual or legal representative to give written informed consent.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT03331796). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.