Effects of t-DCS and Cognitive Training on Apathy in Elderly With Minor Neurocognitive Impairment (FAME3)

Effects of t-DCS Combined With Concurrent Cognitive Training on Apathy in Elderly Subjects With Minor Neurocognitive Impairment

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique using a low intensity electric current to modify cortical excitability. Apathy is a pervasive neuropsychiatric symptom characterized by a reduction in goal-directed behavior and activity that persists over time and causes identifiable functional impairment. The aim of this study is to evaluate the effects of repeated sessions of tDCS combined with simultaneous cognitive training on apathy in older people with minor neurocognitive disorders.

Study Overview

• Status: Enrolling by invitation
• Conditions: Neurocognitive Disorders; Apathy
• Intervention / Treatment: Other: tDCS; Other: SHAM tDCS

Detailed Description

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique using a low intensity electric current to modify cortical excitability. There is growing interest for tDCS for psychiatric illnesses, notably for depression.

Apathy is a pervasive neuropsychiatric symptom characterized by a reduction in goal-directed behavior and activity that persists over time and causes identifiable functional impairment. tDCS could be a promising new area for non-pharmacological treatment of apathy.

The aim of this study is to evaluate the effects of repeated sessions of tDCS combined with simultaneous cognitive training on apathy in older people with minor neurocognitive disorders. For this, 30 apathetic subjects with minor neurocognitive disorders will be included and randomized between two groups. The intervention group will follow sessions of tDCS combined with a simultaneous cognitive training on tablet. The control group will follow cognitive training with a combined sham tDCS. Intervention will last for 4-week with 3 sessions per week (12 sessions). Stimulation will be performed with Startim 20 (Neuroelectrics®) which is approved by the European Union as a Class IIa medical device and meeting European safety standards. Stimulation will last for 20 minutes and the dorsolateral prefrontal cortex (F3) will be targeted. For the intervention group, the electric current will be 2mA. Assessments will be done at baseline, just after the end of intervention and 3 months after intervention. Apathy, daily functional motor behaviors, cognitive functions and fatigue will be assessed with clinician assessment, self-administered questionnaires, ambulatory actigraphy and cognitive tests. The assessments and the intervention will be done by different people. Study will be a double-blind randomized controlled trial.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Nice, France, 06000
    • Centre Memoire Ressources et Recherche, CHU de Nice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 65 years
• Subject consulting in one of the investigating centers
• Clinical diagnosis of Minor Neurocognitive Disorder according to DSM 5 criteria (APA, 2013)
• Apathetic syndrome defined according to the Diagnostic Criteria for Apathy (Miller & al., 2021)
• Subject who can read and write French
• Subjects who are beneficiaries of a social security plan
• Signature of free and informed consent

Exclusion Criteria:

• Current clinical diagnosis of a depressive episode characterized by DSM 5 criteria (APA, 2013)
• Known diagnosis of schizophrenia, bipolar disorder, substance abuse or dependence
• Significant sensory or motor impairment
• Subject under guardianship, conservatorship, or conservatorship
• Active smoking or smoking cessation of less than one year
• Contraindications to the practice of tDCS: history of intracranial hypertension, neurosurgery, metallic implant at the cephalic level, pacemaker
• Unbalanced epilepsy
• Severe somatic disease not stabilized
• Previous use of tDCS (problem of maintaining the integrity of the blinding procedure)
• Scalp skin disease
• Concurrent participation in another drug research study or any other study that may interfere with study results

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: tDCS combined with simultaneous cognitive training	Other: tDCS; The intervention group will follow sessions of tDCS combined with a simultaneous cognitive training on tablet
Sham Comparator: cognitive training with a combined sham tDCS	Other: SHAM tDCS; The control group will follow cognitive training with a combined sham tDCS. Intervention will last for 4-week with 3 sessions per week (12 sessions).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apathy Inventory (Robert et al., 2002), clinician version	The Apathy Inventory scored from 0 (No problem) to 4 (major problem) the 3 dimensions of apathy: the emotional blunting, the loss of initiative and the loss of interest. A higher total score indicates a greater severity.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of neuropsychiatric symptoms	Clinician assess behavioral symptoms and scored the severity from 0 to 3.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of the global cognitive functioning	Mini mental state examination (MMSE): test for asses the global cognitive functioning Unit of measure: score Scored from 0 to 30. A lower score indicate lower performance in global cognitive functioning.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of cognitive functions with FAB	Frontal assessment battery (FAB): test for asses global executive functions Unit of measure: score Scored from 0 to 18. A lower score indicate lower performance in global executive functions.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of episodic memory	Grober and Bruschke test : test for asses episodic memory Unit of measure: score Scored from 0 to 48. A lower score indicate lower performance in episodic memory	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of attention and mental flexibilty	Trail Making test A_b: test for attention and mental flexibilty Unit of measure: time to realize the test A longer time indicate a lower performance in attention and mental flexibility.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of working memory	Empan de chiffres: test for asses working memory Unit of measure: score A lower score indicate a lower performance in working memory	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of verbal fluency	Fluency test: test for asses verbal fluency Unit of measure: number of words produced by the participant into 60 seconds A lower score indicate a lower performance.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of language	Test de "dénomination d'image": test for asses language Unit of measure: score A lower score indicate a lower performance.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of fatigue with Multidimensional fatigue inventory (MFI)	Multidimensional fatigue inventory (MFI): 20-item self-report questionnaire for measuring five dimensions of fatigue. Each subscale contains four items, which are scored on a five-point Likert-scale. Scores range from 4 (absence of fatigue) to 20 (maximum fatigue) for each subscale. Unit of measure: score	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of fatigue with 15-sec Sustained maximal handgrip contraction	15-sec Sustained maximal handgrip contraction: The decrease in force during the 15-s was used as the indicator of fatigability. Measure: performance for the test: The decrease in force during the 15-s was used as the indicator of fatigability. It was computed as the difference between the area under constant curve equal to the maximal grip force and the area under the force-time curve of 15-s	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of daily physical activity	Actigraphy: assessment of time physical activity of light, moderate and vigorous intensity and sedentary time in daily life in minute and % of daily activity.	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)
Assessment of tDCS adverse effects questionnaire	tDCS adverse effects questionnaire: questionnaire for asses the tDCS adverse effects. It is a 11-item scale. Each item corresponds to an adverse effect. Each item is scored from 1 (absence of the adverse effect) to 4 (severe). If the adverse effect is present (score>1) the clinician scored if this is related to tdCS from 0 (none) to 5 (definite). A higher score indicate more adverse effects. Unit of measure: score	Changes from baseline severity of apathy at 4 weeks and 18 weeks are assessed (12 weeks after the end of intervention)

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nice
• Investigators: Principal Investigator: Eric ETTORE, MD, Nice University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2022
• Primary Completion (Estimated): April 4, 2025
• Study Completion (Estimated): October 4, 2025

Study Registration Dates

• First Submitted: December 21, 2021
• First Submitted That Met QC Criteria: January 31, 2022
• First Posted (Actual): February 10, 2022

Study Record Updates

• Last Update Posted (Actual): January 30, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders
• Other Study ID Numbers: 21-PP-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No