Comparison of Two Non-invasive Neuromodulation Techniques as Synergistic Therapy to Cognitive Stimulation in Amnestic Mild Cognitive Impairment (aMCI)
NCT Number: NCT06467253
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: NA
Conditions: Mild Cognitive Impairment
Interventions: DEVICE: 1. rTMS + CS|DEVICE: 2. rTMS Sham + CS|DEVICE: 3. tDCS + CS|DEVICE: 4. tDCS Sham + CS
Sponsor: Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: TRIPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR)|Primary Purpose: TREATMENT
Start Date: 2023-06-01
Completion Date: 2027-06-15
Locations: Instituto Nacional de Psiquiatría Ramón de la Fuente Muñiz, Mexico City, 14370, Mexico

Summary:
This is a comparative, double-blind, randomized controlled clinical trial for people with Amnestic Mild Cognitive Impairment. The investigators will compare the effects of two non-invasive neuromodulation techniques (Repetitive Transcranial Magnetic Stimulation and Transcranial Direct Current Stimulation) combined with cognitive stimulation. These non-invasive neuromodulating techniques will be applied as a treatment alternative to be able to compare non-invasive techniques with cognitive stimulation CS alone, taking into account clinical and neuropsychological evaluations in addition to: 1) the known clinical risk factors (physical activity, comorbidities treatment, etc.) that allow the investigators to characterize the participants; 2) characterize the participants with genetic biomarkers using the APOE4, CR1, COMT, TREM2 and ABCA7 genotype; 3) document the biological effects related to neurogenesis from olfactory epithelial neural progenitor cells and solubles factors of serum; 4) use hippocampal volume, cortical thickness of the medial temporal cortex and parietal cortex by means of structural magnetic resonance imaging and the default mode network by means of functional magnetic resonance imaging at rest as a biomarker of response to treatment and 5) associate the response to treatment with changes in Motor Evoked Potential (MEP) amplitude and latency in order to generate a response-to-treatment biomarker with neuromodulators in Mild Cognitive Impairment (MCI) and changes in electroencephalogram.

Primary Outcome Measures: Changes in orientation, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in language, Measured by the WAIS-IV vocabulary test. Score ranges from 1 to 19. Direct scores are converted to standardized scores. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in language, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in verbal memory, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in verbal memory, Measured by Neuropsi Attention and Memory. Score ranges from 1 to 19. Direct scores are converted to standardized scores. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in visual memory, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in visual memory, Measured by Neuropsi Attention and Memory. Score ranges from 1 to 19. Direct scores are converted to standardized scores. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in visual-constructive abilities, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in visual-constructive abilities, Measured by Neuropsi Attention and Memory. Score ranges from 10 or less to 95. Direct scores are converted to standardized scores. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in processing speed, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in processing speed, Measured by the Trail Making Test version A and B. Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in abstraction, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in verbal fluency, Measured by a verbal fluency test (semantic: animals and phonologic: F, A, S). Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in interference, Measured by the Stroop Test. Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in working memory, Measured by the Barcelona Test. Score ranges from 10 or less to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in working memory, Measured by Trail Making Test version A and B. Score ranges from 5 to 95. Direct scores are converted to percentile. Higher scores mean better outcomes., Baseline, after maintenance (15 weeks), and in follow-up phase (1 year later).|Changes in Global Cognitive Function, Measured by Montreal Cognitive Assessment. Score ranges from 0 to 30 points. Higher scores mean better outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in Global Cognitive Function, Measured by Screen for Cognitive Impairment in Psychiatry. Direct scores ranges from 37 to 115 points. Higher scores mean better outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in memory regarding situations and activities of daily life, Measure by Everyday Memory Questionnaire. Score ranges from 0 to 56. Higher scores mean worse outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later)|Changes in Global Clinical Impression, Measure by Clinical Impression Scale. Score ranges from 0 to 7. Higher scores mean worse outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in Motor Evoked Potentials, Measured by MagVenture, Transcranial Magnetic Stimulation (TMS). Evaluation of cortical excitability and synaptic plasticity using a 5 Hz-rMTS (repetitive TMS). Increased amplitude and decreased latency parameters mean better outcomes after the intervention., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in Olfactory Epithelial Neural Progenitor Cells, Measured by Neural Progenitor Cells Isolated. Quantification of the number of neural progenitor cells isolated from the olfactory epithelium. Increased number of neural progenitor cells after the intervention., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in Solubles Factors of Serum, Measured by Exosome Analysis.To find a differential content of inflammatory markers in the exosomes before and after the intervention., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in Functional Magnetic Resonance Imaging, Measured by Philips Magnetic Resonator, Ingenia 3T Equipment. The Sternberg task, which stimulates working memory and recent memory, will be used to observe changes Bold signal changes in gray matter, the hippocampus and white matter tracts., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).
Secondary Outcome Measures: Changes in Apathy symptoms, Measured by Apathy Evaluation Scale (self-report, informant report and clinician report). Score ranges from 18 to 72. Higher scores mean worse outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in Depression, Measured by Yesavage Geriatric Depression Scale. Score ranges from 0 to 30. Higher scores mean worse outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in behavioral and psychological symptoms, Measured by Cummings Neuropsychiatric Inventory. Score ranges for frequency are 1 to 4, severity score ranges from 1 to 3 and distress score ranges from 0 to 4. Higher scores mean worse outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in electroencephalogram, Measured in each frequency band (delta, theta, alfa beta y gamma) before and after the intervention with the small-worldness measure, which will be obtained in order to observe the global optimization in the transmission of brain information. Likewise, will be complemented with an analysis of the clustering coefficient, local efficiency and global efficiency, calculating these measures in the F3 and F4 regions. To find changes in the small-worldness after the intervention., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).|Changes in smell identification, Measured by the Brief Smell Identification Test. Score ranges from 0 to 12. Higher scores mean better outcomes., Baseline, after first phase (3 weeks), after maintenance (15 weeks) and in follow-up phase (1 year later).