Association of Transcranial Alternating Current Stimulation with Digital Cognitive Training for Cognitive Remediation in Older Adults

BACKGROUND Cognitive decline in older adults, especially those who develop Mild Cognitive Impairment and Alzheimer's Disease, currently has limited options of pharmacological treatments, with modest efficacy.

Digital Cognitive Training (DCT) and Transcranial Alternating Current Stimulation (tACS) are two promising tools for cognitive remediation in this population. In this exploratory study, we investigate feasibility, tolerability and preliminary effects of the association of both interventions in older adults with cognitive complaints.

METHODS Older adults with cognitive complaints are being enrolled for this study, which comprises 5 daily sessions of 30 minutes of DCT using the BrainHQ platform while simultaneously receiving theta tACS (6Hz, 1.6mA) targeting the Left Dorsolateral Prefrontal Cortex.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Dysfunction; Dementia; Alzheimer Disease; Frontotemporal Degeneration; Mild Cognitive Impairment; Lewy Body Disease; Dementia, Vascular; Cognitive Decline; Beta-Amyloid; GFAP; Tau Protein
• Intervention / Treatment: Device: Transcranial Alternating Current Stimulation; Device: Digital Cognitive Training

Detailed Description

Our goals in this study are:

• To investigate the feasibility and safety of transcranial direct current stimulation (tDCS) adjunctive to cognitive training (CT) in a cohort of individuals diagnosed with mild cognitive impairment (MCI), Subjective Cognitive Decline or Alzheimer's desease in it's initial phase (CDR 1).
• To assess the efficacy of this combined intervention in modulating cognitive function, as measured by a comprehensive neuropsychological battery.
• To explore the underlying neural mechanisms of this intervention by examining changes in event-related potentials (ERPs), specifically the N200 and P300 components, which are sensitive to cognitive processes and neural plasticity.
• To identify potential peripheral biomarkers in serum that may correlate with cognitive decline and response to the intervention.
• To determine whether the combined intervention can induce lasting changes in neurophysiological markers, as assessed by repeated ERP measurements.
• To examine the relationship between the observed cognitive improvements, alterations in neurophysiological measures, and changes in serum biomarker levels, with the aim of elucidating the biological mechanisms underlying the intervention's effects.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Rogerio Panizzutti, Professor; Phone Number: +55:21-3938-5588; Email: rogerio.panizzutti@ipub.ufrj.br
• Study Contact Backup: Name: Brunno Costa, PhD student; Phone Number: +55 31996773008; Email: fc_brunno@hotmail.com

Study Locations

• Brazil
  • RJ
    • Rio De Janeiro, RJ, Brazil, 22290140
      • Recruiting
      • Clínica da Memória - IPUB / UFRJ
      • Contact: Brunno Costa, PhD student; Phone Number: +5521997790223; Email: fc_brunno@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy subjects over 50 years old, with cognitive complaints

Exclusion Criteria:

• Estimated Intelligence Quotient <80
• Dependence on psychoactive substances (DSM-V)
• Severe psychiatric or neurological disorders
• Uncorrected visual/hearing problems
• History of syncope for an unexplained reason or seizure less than a year ago
• Previous stroke
• Use of anticoagulants
• Intracranial metallic prosthesis or cardiac pacemaker
• Any contraindication to performing tACS

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tACS+DCT; 5 daily sessions of 30 minutes of DCT using the BrainHQ platform while simultaneously receiving theta tACS (6Hz, 1.6mA) targeting the Left Dorsolateral Prefrontal Cortex.	Device: Transcranial Alternating Current Stimulation; An alternate eletric current of 1.6mA in theta frequency is applied in the scalp, using two eletrodes (5x5cm). The eletrodes are located aiming for the left dorsolateral prefrontal Cortex area.; Device: Digital Cognitive Training; Using a tablet, the participant will do exercises that were designed to stimulate cognitive domains, especially attention and memory. In this case, we use the BrainHQ platform.
Sham Comparator: SHAM+DCT; 5 daily sessions of 30 minutes of DCT using the BrainHQ platform while simultaneously receiving stimulation with the device in SHAM mode (with Ramp Up, no current during the session period and Ramp down) targeting the Left Dorsolateral Prefrontal Cortex.	Device: Transcranial Alternating Current Stimulation; An alternate eletric current of 1.6mA in theta frequency is applied in the scalp, using two eletrodes (5x5cm). The eletrodes are located aiming for the left dorsolateral prefrontal Cortex area.; Device: Digital Cognitive Training; Using a tablet, the participant will do exercises that were designed to stimulate cognitive domains, especially attention and memory. In this case, we use the BrainHQ platform.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MONTREAL COGNITIVE ASSESSMENT (MOCA)	The MoCA, or Montreal Cognitive Assessment, is a screening tool designed to evaluate global cognitive function, covering domains such as memory, executive function, language, visuospatial abilities, and attention. Scores range from 0 to 30, with higher scores indicating better cognitive performance and a score below 26 often considered indicative of cognitive impairment.	1 week after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Five digits test (FDT)	The FDT assesses attention, processing speed, and executive function. Participants perform tasks involving numerical stimuli under timed conditions. Performance is evaluated based on accuracy and reaction time, with faster and more accurate responses reflecting better cognitive function.	1 week after intervention
Rey-Osterrieth complex figure (ROCF)	The ROCF evaluates visuospatial constructional abilities, visual memory, and organizational skills. Participants copy a complex figure (copy task) and later reproduce it from memory (recall task). Scores range from 0 to 36, with higher scores representing better performance and lower scores indicating impaired abilities.	1 week after intervention
Semantic and phonemic verbal fluency	These tasks measure verbal fluency and executive function by asking participants to generate as many words as possible within a category (semantic fluency) or starting with a specific letter (phonemic fluency) within a limited time. Higher scores indicate better fluency and cognitive flexibility, while lower scores suggest deficits in these areas.	1 week after intervention
The Rey Auditory Verbal Learning Test (RAVLT)	The RAVLT assesses verbal memory, including immediate recall, learning, and delayed recall, as well as susceptibility to interference. Scores vary based on the number of correctly recalled items across trials, with higher scores indicating better memory performance and lower scores reflecting poorer memory function.	1 week after intervention
Visual P300 (Event-Related Potential)	The P300 is an electrophysiological measure of cognitive processing, typically recorded using EEG during an oddball paradigm. It reflects attention and working memory processes, with shorter latencies and higher amplitudes indicating more efficient neural processing and longer latencies or reduced amplitudes suggesting impairment.	1 week after intervention
Serum GFAP Analysis	Glial fibrillary acidic protein (GFAP) is a biomarker of astrocytic activation and neuroinflammation. Higher serum GFAP levels may indicate glial activation or neurodegeneration, while lower levels are associated with normal brain health.	before intervention
Serum Beta-Amyloid Analysis	This analysis quantifies beta-amyloid peptides, key biomarkers of Alzheimer's disease pathology. Elevated beta-amyloid levels or an altered ratio of amyloid-beta 42/40 in serum may reflect early neurodegenerative processes, while normal levels are indicative of typical brain function.	before intervention
Serum Tau Protein Analysis	Serum tau protein levels reflect axonal injury or neurodegeneration. Elevated tau concentrations may indicate pathological processes such as Alzheimer's disease or other neurodegenerative disorders, while normal levels suggest no significant axonal damage.	before intervention
Prosaccade Task (Eye Tracking)	This task evaluates basic saccadic eye movement control. Participants are instructed to fixate on a peripheral target as it appears. Key metrics include reaction time, accuracy, and velocity of saccades, with faster and more accurate responses indicating better ocular motor control.	1 week after intervention
Antisaccade Task (Eye Tracking)	This task assesses inhibitory control and executive function. Participants must suppress a reflexive saccade to a peripheral target and instead look in the opposite direction. Metrics such as error rates, reaction times, and corrected errors are analyzed, with fewer errors and faster reaction times indicating better inhibitory control and executive function.	1 week after intervention
Visual Search Task (Eye Tracking):	This task evaluates visual attention and search efficiency. Participants identify a target among distractors under varying levels of complexity. Performance is measured by reaction time and accuracy, with faster and more precise responses indicating better attentional control and visual search ability.	1 week after intervention

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio de Janeiro
• Collaborators: Conselho Nacional de Desenvolvimento Científico e Tecnológico; Alzheimer's Association; Rio de Janeiro State Research Supporting Foundation (FAPERJ)
• Investigators: Principal Investigator: Rogerio Panizzutti, Professor, UFRJ

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027

Study Registration Dates

• First Submitted: December 5, 2024
• First Submitted That Met QC Criteria: December 9, 2024
• First Posted (Estimated): December 13, 2024

Study Record Updates

• Last Update Posted (Estimated): December 13, 2024
• Last Update Submitted That Met QC Criteria: December 9, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Elderly; MCI; Older Adults; Cognition; mild cognitive impairment; Cognitive enhancement; transcranial alternate current stimulation; tacs; nibs; ALzheimer
• Additional Relevant MeSH Terms: Synucleinopathies; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Leukoencephalopathies; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Cognitive Dysfunction; Alzheimer Disease; Dementia; Dementia, Vascular; Lewy Body Disease
• Other Study ID Numbers: 38114820.3.0000.5263

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All study outcomes, including primary and secondary endpoints, will be made available upon request.
• IPD Sharing Time Frame: De-identified individual participant data (IPD) collected during the study will be made available upon reasonable request. Researchers interested in accessing the data may contact the principal investigator by providing a detailed proposal outlining the purpose of the request and intended analyses. Access will be made available upon request for a period of 5 years following the publication of the study's primary results.
• IPD Sharing Access Criteria: Data will only be shared for research purposes that align with ethical guidelines and after appropriate data-sharing agreements are established.

Drug and device information, study documents

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