An interventional study of Active rTMS (Bilateral DLPFC) and Active rTMS (Bilateral LPC) in Mild Cognitive Impairment, Mild Neurocognitive Disorder and Cognitive Decline, sponsored by Palo Alto Veterans Institute for Research. Completed at 1 site in United States. Open to participants aged 55 Years to 90 Years. Per ClinicalTrials.gov, last updated 2025-09-03.
Sponsored by Palo Alto Veterans Institute for Research · Not applicable, Interventional, and Treatment
Among 1,419 studies in Cognitive Dysfunction with a site in United States — 329 open to participants now, 433 under way, 13 of them phase 3. Cognitive Dysfunction · United States.
Among the 1,419 studies in Cognitive Dysfunction with a site in United States, this one is the 502nd largest by enrollment of the 1,144 interventional ones that give a count, is one of 84 that started in 2018, is one of 713 with no phase, and was the 512th registered.
3,875 studies on the registry are indexed under Cognitive Dysfunction; 1,121 are open to participants now.
Browse Cognitive Dysfunction studies →329 of the 1,419 studies in Cognitive Dysfunction with a site in United States are open now. Recruiting first, the newest first:
National Institute of Mental Health (NIMH) · Sites in United States
Ages 50–100 · Healthy volunteers
Prevention Research Consortium Corp. · Sites in United States
Ages 55+ · Healthy volunteers
University of California, San Francisco · Sites in United States
Ages 65+
University of Pittsburgh · Sites in United States
Ages 65+
The University of Texas Medical Branch, Galveston · Sites in United States
Ages 50–100 · Healthy volunteers
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 751 Cognitive Dysfunction studies recruiting now, 363 (48%) set no upper age limit and 143 (19%) stop at 75 or younger; 46 take children under 18; 259 take healthy volunteers.
This study: 55 Years to 90 Years · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
1,419 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 126 · Phase 2 234 · Phase 3 54 · Phase 4 58
First in 1993; this study’s year is marked. 84 started in 2018.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 69 is close to the median of 64 across 2,796 interventional studies indexed under Cognitive Dysfunction.
Median enrollment 59 across the 1,144 interventional studies, 150 across the 270 observational. Of the 885 that completed or were terminated, 377 (43%) have results posted.
This tab as a report to print or save as PDF → With an account.
209 of 1,419 have an industry lead sponsor. The 10 most frequent:
Palo Alto Veterans Institute for Research is the lead sponsor of 53 studies on the registry; 10 are open to participants now.
Palo Alto Veterans Institute for Research has 3 studies filed under Cognitive Dysfunction — fewer than ten, so there is no comparison to draw.
176 of the studies in Cognitive Dysfunction with a site in United States that are under way reach primary completion within a year, 4 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03860857Phase 3University of California, IrvineBiomarker Exploration in Aging, Cognition and Neurodegeneration | 2026-12-22 |
| NCT03887455Phase 3Eisai Inc.A Study to Confirm Safety and Efficacy of Lecanemab in Participants With Early Alzheimer's Disease | 2026-12-31 |
| NCT06191965Phase 3Mclean HospitalMitoQ for Early-phase Schizophrenia-spectrum Disorder and Mitochondrial Dysfunction | 2027-01-31 |
| NCT06950190Phase 3Ellis MedicineEvaluating Cognitive Changes on Patients in Chemotherapy (ECCPC) | 2027-02-20 |
| NCT03560960Boston UniversityMulti-Center Development of a Novel Diagnostic Test for Alzheimer's Disease | 2026-11 |
Add all 176 to your calendar (.ics) → With an account.
Among the 1,419 studies in Cognitive Dysfunction with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
This study aims to test the efficacy of a non-pharmacological treatment for MCI that involves noninvasive brain stimulation (NIBS). Early studies in Alzheimer's disease (AD) dementia patients have found that repetitive transcranial magnetic stimulation (rTMS, a form of NIBS) improved global cognitive function and activities of daily living. Given that in AD, neuronal loss and synaptic dysfunction progress along brain networks, the results of these early studies of brain stimulation suggest there is sufficient neuroplasticity in AD for efficacious effects of brain stimulation. Of the very few rTMS studies in MCI that have been published, the effect size appears to be moderately large. However, it is not clear whether the dorsolateral prefrontal cortex (DLPFC), the stimulation site used in the most of the prior MCI/AD rTMS trials, is the optimal site for achieving the most efficacious effects including effects on episodic memory. Importantly, when other investigators used rTMS to stimulate a lateral parietal cortical (LPC) site in healthy young adults, significant effects of rTMS on memory were measureable weeks later. Moreover, functional connectivity of brain regions was selectively increased, including the posterior cingulate cortex (PCC), a "hub" of brain networks that is affected in amnestic MCI.
Because stimulation of the DLPFC and the LPC may each have distinct effects, we designed this pilot trial to have two active rTMS treatment groups: DLPFC and LPC. A third group will receive inactive (placebo) rTMS to achieve a controlled, randomized, double-blind trial. For each of the three groups, stimulation will be bilateral, based on effects achieved in the AD studies. The primary hypothesis is that active rTMS (to either site of stimulation) will be superior to inactive (placebo) rTMS in improving memory. Measures of change in functional connectivity will be computed to examine whether there is evidence that rTMS changes connectivity of the PCC with other regions of the brain. In addition to looking at effects of rTMS on functional connectivity and cognition in relation to the cortical site stimulated, genetic markers will be collected toward addressing heterogeneity of response. To track the durability of rTMS effects on memory, participants will be followed longer than in any prior study (up to 6 months after the intervention). If this study finds rTMS improves memory in older adults with MCI, further clinical development of this non-pharmacological treatment could ultimately improve the lives of millions of older adults who have MCI and are at an increased risk of developing dementia.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Inclusion Criteria:
Exclusion Criteria:
History of a medical condition or current use/abuse of medications and substances that increase the risk of a seizure, specifically:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
One-third of participants will receive active rTMS to the right and left dorsolateral prefrontal cortex (DLPFC).
Device: Active rTMS (Bilateral DLPFC)
One-third of participants will receive active rTMS to the right and left lateral parietal cortex (LPC).
Device: Active rTMS (Bilateral LPC)
One-third of participants will receive placebo/inactive rTMS, either to the DLPFC or the LPC. Those receiving placebo rTMS will serve as the control group.
Device: Placebo rTMS (Inactive)
TMS Stimulation Parameters for the active DLPFC rTMS intervention group will be: 10 Hz, 4-second train duration and 11-second inter-train interval. During each session, 2,000 pulses will be applied for each hemisphere (for a total of 4,000 pulses per session). Participants will receive 20 sessions (1 or 2 sessions per day, M-F).
TMS Stimulation Parameters for the active LPC rTMS intervention group will be: 10 Hz, 4-second train duration and 11-second inter-train interval. During each session, 2,000 pulses will be applied for each hemisphere (for a total of 4,000 pulses per session). Participants will receive 20 sessions (1 or 2 sessions per day, M-F).
For the Placebo rTMS (Inactive) group, the participant will wear scalp electrodes through which a low voltage, low electric current (2-20mA at no more than 100V) is passed to mimic the sensation of receiving actual rTMS. Participants will receive 20 sessions (1 or 2 sessions per day, M-F).
Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 1 Week After Intervention and Adjusted for Baseline Performance
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Total Number of Words Correctly Recalled, List Learning, California Verbal Learning Test-II, Assessed 3 Months After Intervention and Adjusted for Baseline Performance
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.
Time frame: 3 months after completing the 20-session intervention (acceptable window for assessment: 76-104 days after the final intervention session)
California Verbal Learning Test-II (CVLT-II) Semantic Clustering Score, 1 Week After Intervention and Adjusted for Baseline Performance
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of 16 semantically related words and remember the list after a delay interval. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. A measure of semantic clustering is calculated by a computer program. It is a measure of the participant's tendency to recall words in semantically organized clusters (e.g. the participant recalled "apple" and "orange" even though the two fruit words were not presented sequentially). The computer algorithm includes words recalled on Trials 1-5 and adjusts for the possibility that a semantic cluster occurred by chance. The range of CVLT-II Semantic Clustering Scores is -3 to 9. Higher values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
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
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. After 5 learning trials and a subsequent 20-minute delay filled with unrelated tests, the participant was asked to recall the 16-word target list of the CVLT-II again. The total number of words correctly recalled was computed (range = 0 to 16). Higher values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention
Depressive Symptoms, as Measured by the Geriatric Depression Scale (GDS), Assessed 1 Week After Intervention and Adjusted for Baseline Performance
The 15-item Geriatric Depression Scale (GDS) was also used as an outcome measure. Five of the GDS items are oriented toward the absence of depressive symptoms (e.g., Do you feel full of energy?) and 10 are oriented toward current depressive symptoms (e.g., Do you often feel helpless?). The participant is asked to answer "yes" or "no" on the basis of how they have been feeling over the past week. The GDS total score ranges from 0 to 15. Lower values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Everyday Functional Outcomes, as Measured by the Everyday Cognition (ECog) Questionnaire (Participant Version) Completed 1 Week After Intervention
The Everyday Cognition (ECog) questionnaire is comprised of 39 items about the ability to perform everyday tasks. Each item relates to memory, language, visual-spatial, or executive function. Each item is rated on a scale from 1 to 4 (1 = better or no change…4 = consistently much worse compared to 10 years ago). For the Participant version of the ECog, the participant is asked to "Please rate your ability to perform certain everyday tasks now, as compared to your ability to do these same tasks 10 years ago." Total score range: 39-156. Higher values represent a worse outcome. The outcome score was adjusted for baseline.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention
Everyday Functional Outcomes, as Measured by the Everyday Cognition Questionnaire (Informant /Study Partner Version) Completed 1 Week After Intervention
The Everyday Cognition (ECog) questionnaire is comprised of 39 items about the ability to perform everyday tasks. Each item relates to memory, language, visual-spatial, or executive function. Each item is rated on a scale from 1 to 4 (1 = better or no change…4 = consistently much worse compared to 10 years ago). For the Informant version of the ECog, the participant's study partner was asked to "Please rate the participant's ability to perform certain everyday tasks NOW, as compared to his/her ability to do these same tasks 10 years ago." Total score range: 39-156. Higher values represent a worse outcome. The outcome score was adjusted for baseline.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention
Instrumental Activities of Daily Living (IADLs), as Measured by the Functional Assessment Questionnaire, Completed 1 Week After Intervention
Functional Assessment Questionnaire, completed by the study partner at end of treatment (1 week after intervention, adjusted for baseline). Each 10 item is rated on a scale from 0 to 3 (0 = Normal; 1 = Has difficulty, but does by self; 2 = Requires assistance; 3 = Dependent. Total score range: 0-30 (sum of 10 items). Interpretation: A total score of 9 (dependent in 3 or more activities) is the recommended cut-point for an indication of impaired function. Higher values represent a worse outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Global Cognitive Function, as Measured by the Montreal Cognitive Assessment (MoCA), Assessed 1 Week After Intervention and Adjusted for Baseline
The Montreal Cognitive Assessment (MoCA) is a brief measure of global cognitive function. The total score has a range of 0 to 30; higher values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention
Visuospatial Memory, as Measured by the Brief Visuospatial Memory Test-Revised (BVMT-R), assessed1 Week After Intervention and Adjusted for Baseline Performance
Brief Visuospatial Memory Test-Revised (BVMT-R) Trials 1-3 total recall raw score at end of treatment (1 week after intervention, adjusted for baseline); range: 0-36; higher values represent a better outcome
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Language Function, as Measured by Category Fluency (CF), Assessed 1 Week After Intervention and Adjusted for Baseline Performance
Category Fluency is a measure of verbal fluency in which the participant is asked to generate different exemplars from a semantic category specified by the examiner. For example, if the examiner says, 'articles of clothing,' correct responses include exemplars such as, 'shirt,' 'tie,' or 'hat.' The participant is given one minute to say all the responses they can think of. The values reported reflect the total number of correct, unique responses produced. Higher values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Language Function, as Measured by 42-item Boston Naming Test (BNT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance
The Boston Naming Test (BNT) assesses the ability to verbally name pictured objects. The subject is shown a series of line drawings and asked to name the object. The test items become progressively more difficult. (The 42 items are presented in order of decreasing frequency of the target word). The total number of correct responses can range from 0 to 42. Higher values represent a better outcome.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Visuoconstructional Function, as Measured by the Rey-Osterrieth Complex Figure (ROCF) Copy Score, assessed1 Week After Intervention and Adjusted for Baseline Performance.
Rey-Osterrieth Complex Figure (ROCF) Copy score at end of treatment (1 week after intervention, adjusted for baseline); range: 0-36; higher values represent a better outcome
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Speed of Processing and Executive Function, as Measured by Trail Making Part B, Assessed 1 Week After Intervention and Adjusted for Baseline Performance
In the Trail Making Part B test, the response form has a series of 25 circles; each circle contains a number or a letter. The participant is asked to connect the circles in order by alternating between the numbers and letters. The maximum time allowed is 300 seconds. Trails B is thought to require executive skills as well as processing speed. The Trail Making B seconds-to-complete scores were log transformed because the distribution of scores was positively skewed. We also reverse scored the log scores so that higher values would indicate a better outcome. To reverse the log scores, we used the formula: reverse score = max(x) + 1 - x, where max(x) is the natural log of 300 or 5.70378. For example, if a participant's time-to-complete score was 74 seconds, the natural log transformed score was 4.304. Reverse scoring yields a value of 2.4 (2.4 = 5.70378 + 1 - 4.304). The reverse-scaled, log transformed seconds-to-complete scores were used in all statistical analyses.
Time frame: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Attention, as Measured by the Attentional Network Task (ANT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance
Attentional Network Task(ANT) correct reaction time, as measured by the ANT computerized test
Time frame: planned: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Change From Baseline in Brain Functional Connectivity
Change from Baseline in Functional connectivity metrics (derived from the pre- and the post-intervention functional magnetic resonance imaging (fMRI) scans rs-fMRI scans) will be computed with respect to: connectivity within the Default Mode Network (DMN), and connectivity between the DMN and the Central Executive Network (CEN).
Time frame: planned: 1 week after completing the 20-session intervention, which was typically 4 weeks after starting the intervention.
Pre-post Change in Peripheral Levels of Brain-derived Neurotrophic Factor (BDNF)
Brain-derived Neurotrophic Factor (BDNF) plasma levels were measured from blood samples that were collected during the first session and the last session of TMS intervention, after a minimum of 4 hours of fasting. Higher change scores represent a better outcome.
Time frame: First Intervention session to Last Intervention session. The average time frame from the first to the 20th and last session is 18 days.
Participants were enrolled at the Stanford/VA Aging Clinical Research Center over a 4-year period, which included a 13-month hiatus during the Coronavirus disease (COVID-19) pandemic. The study was open for recruitment on 05/16/2018. The first participant was enrolled and randomized on 06/15/2018; the last participant was enrolled and randomized on 11/22/2022.
| Milestone | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Started | 14 | 13 | 13 |
| Completed | 14 | 12 | 11 |
| Not completed | 0 | 1 | 2 |
| Withdrew: Pandemic disruption | 0 | 1 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 |
| Milestone | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Started | 14 | 12 | 11 |
| Completed | 12 | 11 | 9 |
| Not completed | 2 | 1 | 2 |
| Withdrew: Adverse event | 1 | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 |
| Withdrew: Withdrawal by subject | 1 | 0 | 0 |
| Withdrew: Termination of funding | 0 | 1 | 0 |
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.
| total number of words correctly recalled | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| 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 ± 11.0 | 48.8 ± 8.7 | 37.0 ± 11.4 |
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. The total number of words correctly recalled on the 5 list-learning trials was computed (range = 0 to 80). Higher values represent a better outcome.
| total number of words correctly recalled | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| 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 ± 10.3 | 53.0 ± 14.3 | 41.3 ± 6.9 |
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of 16 semantically related words and remember the list after a delay interval. There are 5 orally presented learning trials; each is followed by immediate recall of the words in any order. A measure of semantic clustering is calculated by a computer program. It is a measure of the participant's tendency to recall words in semantically organized clusters (e.g. the participant recalled "apple" and "orange" even though the two fruit words were not presented sequentially). The computer algorithm includes words recalled on Trials 1-5 and adjusts for the possibility that a semantic cluster occurred by chance. The range of CVLT-II Semantic Clustering Scores is -3 to 9. Higher values represent a better outcome.
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| California Verbal Learning Test-II (CVLT-II) Semantic Clustering Score, 1 Week After Intervention and Adjusted for Baseline Performance | 0.5 ± 1.0 | 0.5 ± 1.2 | 0.1 ± 0.6 |
The California Verbal Learning Test, Second edition (CVLT-II) is a memory task that yields several indices of the ability to learn a list of semantically related words and remember the list after a delay interval. The target list ("List A") of the CVLT-II contains 16 words. After 5 learning trials and a subsequent 20-minute delay filled with unrelated tests, the participant was asked to recall the 16-word target list of the CVLT-II again. The total number of words correctly recalled was computed (range = 0 to 16). Higher values represent a better outcome.
| total number of words correctly recalled | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| 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 ± 4.2 | 10.3 ± 3.6 | 6.2 ± 3.5 |
The 15-item Geriatric Depression Scale (GDS) was also used as an outcome measure. Five of the GDS items are oriented toward the absence of depressive symptoms (e.g., Do you feel full of energy?) and 10 are oriented toward current depressive symptoms (e.g., Do you often feel helpless?). The participant is asked to answer "yes" or "no" on the basis of how they have been feeling over the past week. The GDS total score ranges from 0 to 15. Lower values represent a better outcome.
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Depressive Symptoms, as Measured by the Geriatric Depression Scale (GDS), Assessed 1 Week After Intervention and Adjusted for Baseline Performance | 3.2 ± 2.3 | 1.9 ± 1.2 | 2.9 ± 2.3 |
The Everyday Cognition (ECog) questionnaire is comprised of 39 items about the ability to perform everyday tasks. Each item relates to memory, language, visual-spatial, or executive function. Each item is rated on a scale from 1 to 4 (1 = better or no change…4 = consistently much worse compared to 10 years ago). For the Participant version of the ECog, the participant is asked to "Please rate your ability to perform certain everyday tasks now, as compared to your ability to do these same tasks 10 years ago." Total score range: 39-156. Higher values represent a worse outcome. The outcome score was adjusted for baseline.
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Everyday Functional Outcomes, as Measured by the Everyday Cognition (ECog) Questionnaire (Participant Version) Completed 1 Week After Intervention | 84.8 ± 21.0 | 66.1 ± 12.7 | 72.3 ± 16.1 |
The Everyday Cognition (ECog) questionnaire is comprised of 39 items about the ability to perform everyday tasks. Each item relates to memory, language, visual-spatial, or executive function. Each item is rated on a scale from 1 to 4 (1 = better or no change…4 = consistently much worse compared to 10 years ago). For the Informant version of the ECog, the participant's study partner was asked to "Please rate the participant's ability to perform certain everyday tasks NOW, as compared to his/her ability to do these same tasks 10 years ago." Total score range: 39-156. Higher values represent a worse outcome. The outcome score was adjusted for baseline.
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Everyday Functional Outcomes, as Measured by the Everyday Cognition Questionnaire (Informant /Study Partner Version) Completed 1 Week After Intervention | 73.2 ± 30.9 | 61.1 ± 17.4 | 61.5 ± 29.2 |
Functional Assessment Questionnaire, completed by the study partner at end of treatment (1 week after intervention, adjusted for baseline). Each 10 item is rated on a scale from 0 to 3 (0 = Normal; 1 = Has difficulty, but does by self; 2 = Requires assistance; 3 = Dependent. Total score range: 0-30 (sum of 10 items). Interpretation: A total score of 9 (dependent in 3 or more activities) is the recommended cut-point for an indication of impaired function. Higher values represent a worse outcome.
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Instrumental Activities of Daily Living (IADLs), as Measured by the Functional Assessment Questionnaire, Completed 1 Week After Intervention | 3.29 ± 4.41 | 1.00 ± 1.32 | 1.33 ± 3.27 |
The Montreal Cognitive Assessment (MoCA) is a brief measure of global cognitive function. The total score has a range of 0 to 30; higher values represent a better outcome.
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Global Cognitive Function, as Measured by the Montreal Cognitive Assessment (MoCA), Assessed 1 Week After Intervention and Adjusted for Baseline | 23.0 ± 4.5 | 23.8 ± 2.8 | 23.6 ± 2.2 |
Brief Visuospatial Memory Test-Revised (BVMT-R) Trials 1-3 total recall raw score at end of treatment (1 week after intervention, adjusted for baseline); range: 0-36; higher values represent a better outcome
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Visuospatial Memory, as Measured by the Brief Visuospatial Memory Test-Revised (BVMT-R), assessed1 Week After Intervention and Adjusted for Baseline Performance | 17.8 ± 8.5 | 18.5 ± 6.2 | 21.6 ± 6.5 |
Category Fluency is a measure of verbal fluency in which the participant is asked to generate different exemplars from a semantic category specified by the examiner. For example, if the examiner says, 'articles of clothing,' correct responses include exemplars such as, 'shirt,' 'tie,' or 'hat.' The participant is given one minute to say all the responses they can think of. The values reported reflect the total number of correct, unique responses produced. Higher values represent a better outcome.
| correct, unique responses | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Language Function, as Measured by Category Fluency (CF), Assessed 1 Week After Intervention and Adjusted for Baseline Performance | 16.7 ± 3.8 | 19.8 ± 4.8 | 19.4 ± 6.0 |
The Boston Naming Test (BNT) assesses the ability to verbally name pictured objects. The subject is shown a series of line drawings and asked to name the object. The test items become progressively more difficult. (The 42 items are presented in order of decreasing frequency of the target word). The total number of correct responses can range from 0 to 42. Higher values represent a better outcome.
| correct responses | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Language Function, as Measured by 42-item Boston Naming Test (BNT), Assessed 1 Week After Intervention and Adjusted for Baseline Performance | 36.3 ± 3.9 | 38.4 ± 3.8 | 35.9 ± 4.8 |
Rey-Osterrieth Complex Figure (ROCF) Copy score at end of treatment (1 week after intervention, adjusted for baseline); range: 0-36; higher values represent a better outcome
| score on a scale | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Visuoconstructional Function, as Measured by the Rey-Osterrieth Complex Figure (ROCF) Copy Score, assessed1 Week After Intervention and Adjusted for Baseline Performance. | 33.8 ± 4.1 | 32.7 ± 3.8 | 34.9 ± 1.8 |
In the Trail Making Part B test, the response form has a series of 25 circles; each circle contains a number or a letter. The participant is asked to connect the circles in order by alternating between the numbers and letters. The maximum time allowed is 300 seconds. Trails B is thought to require executive skills as well as processing speed. The Trail Making B seconds-to-complete scores were log transformed because the distribution of scores was positively skewed. We also reverse scored the log scores so that higher values would indicate a better outcome. To reverse the log scores, we used the formula: reverse score = max(x) + 1 - x, where max(x) is the natural log of 300 or 5.70378. For example, if a participant's time-to-complete score was 74 seconds, the natural log transformed score was 4.304. Reverse scoring yields a value of 2.4 (2.4 = 5.70378 + 1 - 4.304). The reverse-scaled, log transformed seconds-to-complete scores were used in all statistical analyses.
| reverse scaled, log transformed scores | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| 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 ± 0.64 | 2.42 ± 0.32 | 2.42 ± 0.33 |
Attentional Network Task(ANT) correct reaction time, as measured by the ANT computerized test
No measurements were reported for this outcome.
Change from Baseline in Functional connectivity metrics (derived from the pre- and the post-intervention functional magnetic resonance imaging (fMRI) scans rs-fMRI scans) will be computed with respect to: connectivity within the Default Mode Network (DMN), and connectivity between the DMN and the Central Executive Network (CEN).
No measurements were reported for this outcome.
Brain-derived Neurotrophic Factor (BDNF) plasma levels were measured from blood samples that were collected during the first session and the last session of TMS intervention, after a minimum of 4 hours of fasting. Higher change scores represent a better outcome.
| pg/mL | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Pre-post Change in Peripheral Levels of Brain-derived Neurotrophic Factor (BDNF) | 394.83 ± 1773.65 | 1188.85 ± 3513.12 | 687.17 ± 2145.18 |
Collected over Adverse event data were collected from over a period of 6 to 12 months. The reporting timeframe for All-Cause Mortality and Serious Adverse Events is from enrollment and randomization until 6 months after completion of the 20-session device intervention, typically 7 months. The reporting timeframe for other adverse events is from enrollment and randomization until 1 week after completion of the 20-session device intervention, typically 1 month.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active rTMS (Bilateral DLPFC) | 0/14 (0%) | 1/14 (7.1%) | 5/14 (35.7%) |
| Active rTMS (Bilateral LPC) | 0/13 (0%) | 0/13 (0%) | 5/13 (38.5%) |
| Placebo rTMS (Inactive) | 0/13 (0%) | 2/13 (15.4%) | 3/13 (23.1%) |
| Event | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| pancreatic cancerNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 0/14 | 0/13 | 1/13 |
| rotator cuff (surgerical repair)Musculoskeletal and connective tissue disorders | 0/14 | 0/13 | 1/13 |
| hip fractureMusculoskeletal and connective tissue disorders | 1/14 | 0/13 | 0/13 |
| Event | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) |
|---|---|---|---|
| Site discomfortGeneral disorders | 3/14 | 2/13 | 0/13 |
| HeadacheNervous system disorders | 0/14 | 2/13 | 0/13 |
| Muscle twitchingMusculoskeletal and connective tissue disorders | 0/14 | 1/13 | 0/13 |
| Site painGeneral disorders | 0/14 | 1/13 | 0/13 |
| PneumoniaRespiratory, thoracic and mediastinal disorders | 0/14 | 1/13 | 0/13 |
| Low back painMusculoskeletal and connective tissue disorders | 0/14 | 0/13 | 1/13 |
| Upper respiratory infectionRespiratory, thoracic and mediastinal disorders | 0/14 | 0/13 | 1/13 |
| Urinary incontinenceRenal and urinary disorders | 0/14 | 0/13 | 1/13 |
| Toothache/TMJ painGastrointestinal disorders | 1/14 | 0/13 | 0/13 |
| FatiguePsychiatric disorders | 1/14 | 0/13 | 0/13 |
The population analyzed included all participants who received at least 1 session of the intervention and who provided primary outcome data post-baseline.
| Age, Continuous(years) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| Mean | 73.6 ± 5.8 | 75.7 ± 7.5 | 74.0 ± 5.3 | 74.4 ± 6.1 |
| Sex: Female, Male(Participants) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| Female | 5 | 6 | 5 | 16 |
| Male | 9 | 6 | 6 | 21 |
| Ethnicity (NIH/OMB)(Participants) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| Hispanic or Latino | 1 | 1 | 0 | 2 |
| Not Hispanic or Latino | 12 | 10 | 11 | 33 |
| Unknown or Not Reported | 1 | 1 | 0 | 2 |
| Race (NIH/OMB)(Participants) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 1 | 0 | 0 | 1 |
| Asian | 2 | 1 | 1 | 4 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 1 | 0 | 2 |
| White | 10 | 8 | 9 | 27 |
| More than one race | 0 | 1 | 1 | 2 |
| Unknown or Not Reported | 0 | 1 | 0 | 1 |
| Region of Enrollment(participants) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| United States | 14 | 12 | 11 | 37 |
| Education(years) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| Mean | 17.0 ± 2.7 | 16.9 ± 2.2 | 17.1 ± 2.5 | 17.0 ± 2.4 |
| Mild Cognitive Impairment Stage(Participants) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| Early | 6 | 7 | 5 | 18 |
| Late | 8 | 5 | 6 | 19 |
| Clinical Dementia Rating Scale Sum of Boxes Score(units on a scale) | Active rTMS (Bilateral DLPFC) | Active rTMS (Bilateral LPC) | Placebo rTMS (Inactive) | Total |
|---|---|---|---|---|
| Mean | 1.3 ± 0.7 | 1.0 ± 0.5 | 1.1 ± 0.6 | 1.1 ± 0.6 |
4 further baseline measures are reported on the registry.
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Jun 2018 to primary completion in Dec 2022, 54 months.
Results were first posted in Sep 2025, 2 years 8 months after primary completion.
Of 1,445 non-industry interventional studies with no phase under Cognitive Dysfunction, half reached primary completion within 27 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 51. This study's 54 months is above that.
Counting every sponsor, half of 1,514 studies reached it within 27 months; a quarter within 12 and three quarters within 50.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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Palo Alto Veterans Institute for Research