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Mild cognitive impairment (MCI) has been identified as an early phase of Alzheimer's disease (AD), a neurodegenerative disorder expected to affect 13.9 million Americans by 2060. AD causes a progressive cognitive decline, including problems related to learning and memory, that adversely affects life quality. Treatment intervention at the MCI stage of the disease could potentially slow down the rate at which people may convert from MCI to AD. Increasing evidence suggests that abnormal activity in frontal regions of the brain is associated with cognitive deficits observed in AD. Furthermore, previous research has shown that neurofeedback (NFB) training targeting these regions can improve memory, making it a potential treatment for AD. NFB is a technique where an individual learns to change his/her brain function in a particular direction, once that function has been made accessible through a visual or auditory metaphor. We are proposing a novel, computer-based brain-training program to enhance frontal gamma oscillatory activity in individuals with MCI. Results from this study will build the scientific foundation necessary for larger clinical trials dedicated to improving treatment options and outcomes for patients with MCI.
This is a randomized, double-blind, clinical trial to test the efficacy of gamma-neurofeedback (G-NFB) compared to a placebo (P-NFB) in individuals with MCI. 112 consented participants will be randomized to receive G-NFB (n=56) or placebo-NFB (n=56) during 30-45 minute sessions twice per week for 12 weeks (24 total sessions). Memory and other cognitive domains will be measured using paper and pencil and computerized tests every 4 weeks during the study and at 4 weeks post completion of study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active Treatment | Experimental | Subjects will be given a choice of videos consisting of still images set to music. Whether the video progresses and music continues to play will depend on the subject's ability to maintain frontal gamma oscillatory activity within a prespecified range. Over successive weeks, the parameters for positive feedback (music and video progression) will become incrementally more difficult. |
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| Placebo | Sham Comparator | Video and music progression will be random and will not depend on brain activity. Any progression will be by random chance alone. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neurofeedback | Behavioral | Neurofeedback is a technique where brain functions are made accessible to the subject in the form of a metaphor. For instance, frontal brain activity may be shown as an airplane flying. Once the activity is made accessible, the subject can modulate it in a pre-specified direction. The parameters used to achieve successful feedback are made difficult over time and hence the brain is taught or conditioned to improve performance. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Working Memory accuracy | Change in the computerized test, N-back will be used to measure working memory. | From baseline to 12 weeks of treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Durability of Change in Working Memory accuracy | Change in the computerized test, N-back will be used to measure working memory. | From baseline to 4weeks post end of study |
| Change in Gamma Band Response |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California at San Diego | La Jolla | California | 92093 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23020641 | Background | Diamond A. Executive functions. Annu Rev Psychol. 2013;64:135-68. doi: 10.1146/annurev-psych-113011-143750. Epub 2012 Sep 27. | |
| 17915264 | Background | Dohnel K, Sommer M, Ibach B, Rothmayr C, Meinhardt J, Hajak G. Neural correlates of emotional working memory in patients with mild cognitive impairment. Neuropsychologia. 2008 Jan 15;46(1):37-48. doi: 10.1016/j.neuropsychologia.2007.08.012. Epub 2007 Aug 23. |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Oct 2, 2024 | Jun 4, 2025 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D058765 | Neurofeedback |
| ID | Term |
|---|---|
| D001676 | Biofeedback, Psychology |
| D026441 | Mind-Body Therapies |
| D000529 | Complementary Therapies |
| D013812 | Therapeutics |
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MCI subjects will be assigned to active intervention or placebo.
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Double-blind, randomized.
|
| Placebo | Other | Subjects in this arm will undergo all of the same testing as active treatment. Music and video progression will not depend on brain activity. Instead feedback will be random. |
|
Change in Gamma oscillations will be measured while the subject performs the n-back task.
| From baseline to 12 weeks of treatment |
| Durability of Gamma Band Response | Change in Gamma oscillations will be measured while the subject performs the n-back task. | From baseline to 4weeks post end of study |
| 1422803 | Background | Leuchter AF, Newton TF, Cook IA, Walter DO, Rosenberg-Thompson S, Lachenbruch PA. Changes in brain functional connectivity in Alzheimer-type and multi-infarct dementia. Brain. 1992 Oct;115 ( Pt 5):1543-61. doi: 10.1093/brain/115.5.1543. |
| 17015233 | Background | Uhlhaas PJ, Singer W. Neural synchrony in brain disorders: relevance for cognitive dysfunctions and pathophysiology. Neuron. 2006 Oct 5;52(1):155-68. doi: 10.1016/j.neuron.2006.09.020. |
| 12488788 | Background | Stam CJ, van Cappellen van Walsum AM, Pijnenburg YA, Berendse HW, de Munck JC, Scheltens P, van Dijk BW. Generalized synchronization of MEG recordings in Alzheimer's Disease: evidence for involvement of the gamma band. J Clin Neurophysiol. 2002 Dec;19(6):562-74. doi: 10.1097/00004691-200212000-00010. |
| D001521 |
| Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
| D030141 | Feedback, Psychological |