Transcranial Alternating Current Stimulation for the Improvement of Episodic Memory in Healthy Older Adults
- Conditions
- Healthy Older Adults
- Interventions
- Device: Sham tACS over the precuneusDevice: Gamma tACS (40 Hz) over the precuneus
- Registration Number
- NCT06284720
- Lead Sponsor
- Universidade Católica Portuguesa
- Brief Summary
Memory complaints are a common symptom among Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer disease. Indeed, episodic memory and Alzheimer disease are highly sensitive to aging. Many brain areas become active when we remember an event from the past. The precuneus, part of the posterior system of default mode network, has been identified as a central node of episodic memory retrieval and a central node in various psychiatric and neurological disorders, such as Alzheimer disease. Age-related changes have been consistently found in the default mode network connectivity, occurring within its posterior areas and with the reduction of connectivity between anterior and posterior subnetwork. It has also been found that aging is associated with decreased functional connectivity in the precuneus and posterior cingulate of the default mode network. Furthermore, γ-Aminobutyric acid (GABA), which plays an essential role in regulating brain activity and modulating the default mode network, shows a decrease throughout the normal course of aging, in Mild Cognitive Impairment and Alzheimer disease. It was also verified a link between cognitive decline and the dysfunction of the inhibitory activity of GABAergic interneurons, particularly parvalbumin-positive interneurons, that play a role in control local circuitry, brain networks and memory processing. Parvalbumin interneurons are the fast-spiking interneurons that generate and maintain gamma frequency. Gamma band has been associated with the encoding and retrieval of episodic memory. Impairments of gamma oscillations have been observed in healthy aging, Mild Cognitive Impairment and Alzheimer disease.
By identifying these functional connectivity changes, non-invasive neuromodulation techniques may offer a new strategy for improving cognitive functions. Transcranial Alternating Current Stimulation (tACS) is a form of non-invasive brain stimulation that modulates cortical activity by applying weak, oscillating electrical currents to the cortex via two or more scalp electrodes. By using alternating currents, it is possible to simulate the rhythmic pattern of electrophysiological activity of the brain. tACS can interact with neural firing at behaviorally relevant frequencies linked to memory.
In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether stimulation with gamma tACS on the precuneus can improve episodic memory in healthy older adults.
- Detailed Description
Memory complaints are a common symptom among Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer disease. Indeed, episodic memory and Alzheimer disease are highly sensitive to aging. Many brain areas become active when we remember an event from the past. The precuneus, part of the posterior system of default mode network, has been identified as a central node of episodic memory retrieval and a central node in various psychiatric and neurological disorders, such as Alzheimer disease. Age-related changes have been consistently found in the default mode network connectivity, occurring within its posterior areas and with the reduction of connectivity between anterior and posterior subnetwork. It has also been found that aging is associated with decreased functional connectivity in the precuneus and posterior cingulate of the default mode network. Furthermore, γ-Aminobutyric acid (GABA), which plays an essential role in regulating brain activity and modulating the default mode network, shows a decrease throughout the normal course of aging, in Mild Cognitive Impairment and Alzheimer disease. It was also verified a link between cognitive decline and the dysfunction of the inhibitory activity of GABAergic interneurons, particularly parvalbumin-positive interneurons, that play a role in control local circuitry, brain networks and memory processing. Parvalbumin interneurons are the fast-spiking interneurons that generate and maintain gamma frequency. Gamma band has been associated with the encoding and retrieval of episodic memory. Impairments of gamma oscillations have been observed in healthy aging, Mild Cognitive Impairment and Alzheimer disease.
By identifying these functional connectivity changes, non-invasive neuromodulation techniques may offer a new strategy for improving cognitive functions. Transcranial Alternating Current Stimulation (tACS) is a form of non-invasive brain stimulation that modulates cortical activity by applying weak, oscillating electrical currents to the cortex via two or more scalp electrodes. By using alternating currents, it is possible to simulate the rhythmic pattern of electrophysiological activity of the brain. tACS can interact with neural firing at behaviorally relevant frequencies linked to memory.
In this randomized, double-blind, sham-controlled, cross-over study, the investigators will evaluate whether stimulation with gamma tACS on the precuneus can improve episodic memory in healthy older adults.
Participants will be randomized into two groups in a 1:1 ratio, and the order of administration of either intervention (i.e., gamma-tACS or sham) will be counterbalanced across all participants. Stimulation will be inverted (crossover phase) after 1 week (wash-out). Participants will be evaluated with neuropsychological tests (AVLT and FNMT) and neurophysiological measures of functional connectivity (rs EEG).
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 16
- Older adults aged 65 or over;
- Normal general cognition: score within the normative values for the Portuguese population in the Addenbrooke's Cognitive Examination
- Neurological disorders (stroke, tumours, significant head trauma, and epilepsy), psychiatric conditions (such as autism, schizophrenia, depression), or uncontrolled medical illness (hypertension, metabolic, endocrine, toxic, and infectious diseases) able to interfere with cognition;
- Sensory deficits likely to interfere with neuropsychological assessment;
- Impairment in activities of daily living;
- Chronic alcohol or drug abuse;
- Non-native Portuguese speakers;
- Metal implants on the head or implanted electronic devices.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Comparator: sham tACS Sham tACS over the precuneus 5 sessions of sham over the Precuneus Experimental: real tACS Gamma tACS (40 Hz) over the precuneus 5 sessions of gamma tACS (40 Hz) at 2 mA over the Precuneus
- Primary Outcome Measures
Name Time Method Changes in immediate free recall and delayed recognition Face-Name Memory Test scores During the first session/day 1 of intervention of gamma tACS/sham and during the first session on the crossover-phase/day12 Face-Name Memory Test requires learning 20 unfamiliar face-name pairs and include a training, initial learning phase (learning 1 and 2), immediate recall and after 30 minutes a delayed recall, facial recognition, and a multiple-choice recognition trial. During learning phase (1 and 2) participants will underwent two exposures to all 20 face and name. It is shown a face on a grey background with a fictional first name printed in black underneath the face, forming a face-name pair; the participants must say whether the photograph they see is of a man or a woman, read the name below out loud and try to learn each face-name pair. Following each exposure, they were asked for name associated with each face. After a 30-minute delay they were asked to identify the previously learned face from three pictures, asked for name associated with each face, and asked to select the name associated with the face among four proper names
Changes in immediate and delayed free recall Auditory Verbal Learning Test scores Baseline (immediately before the stimulation protocol/on the first session/day 1) and post stimulation (after 5 sessions of 5 consecutive days of gamma tACS/sham/day 5). After one week, measures will be repeated in the crossover phase day 12 and 17. Auditory Verbal Learning Test is a list-learning paradigm, and consists of five consecutive immediate free recall trials, a delayed free recall trial (after 30 minutes of the fifth immediate free recall trial), and a delayed recognition trial. Different lists will be used during pre- and post-stimulation to avoid learning effects.
- Secondary Outcome Measures
Name Time Method Change in functional connectivity Baseline (immediately before the stimulation protocol/on the first session/day 1) and post stimulation (after 5 sessions of 5 consecutive days of gamma tACS/sham/day 5). After one week, measures will be repeated in the crossover phase day 12 and 17. By using resting state electroencephalogram the investigators will evaluate the effects of gamma tACS in functional connectivity between precuneus and hippocampus
Trial Locations
- Locations (1)
Filipa Ribeiro
🇵🇹Lisbon, Portugal