Mental Strategy Training in Mild Cognitive Impairment

Reducing Hippocampal Hyperactivity in Patients With Mild Cognitive Impairment

This study aims to reduce hippocampal activity in people at high risk of developing Alzheimer's disease (AD) and aims to examine whether this improves their episodic memory performance. We apply mental strategy trainings with strategies extracted from our previous study that applied real-time fMRI neurofeedback to reduce hippocampal activity. Participants take part in mental strategy trainings 2, 4, or 6 times. At baseline and after each 2 trainings, we assess their hippocampal activity as well as their episodic memory performance using an fMRI pattern separation task. In addition, we will gather blood samples to obtain Apolipoprotein E gene status (ApoE, only once) as well as plasma pTau (pTau217; 4 time-points). ApoE will be included as a covariate in our statistical models. For pTau217, we will calculate the change between each assessment to examine whether the mental strategy training will change the accumulation of pTau217.

Study Overview

• Status: Completed
• Conditions: Mild Cognitive Impairment; Mild Cognitive Impairment (MCI) Amnestic
• Intervention / Treatment: Other: Mental Strategy Training

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3000
      • Universitäre Psychiatrische Dienste Bern

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• diagnosis of Mild Cognitive Impairment
• between 60 - 80 years of age
• fluent in German
• normal or corrected-to-normal vision
• normal or corrected-to-normal hearing

Exclusion Criteria:

• any history of seizures
• current psychotropic medication
• other severe neurological or psychiatric disease
• current or lifetime drug or alcohol abuse
• severe brain damage other than atrophy in the hippocampus or the medial temporal lobe
• claustrophobia
• magnetisable implants (e.g., cardiac pacemakers, brain stimulator)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A: 15 participants will be assigned to group A; Group A will attend 6 mental strategy trainings and will start the training after the first assessment. The training content is identical for all groups. The groups differ only in the number of training sessions and in the timing of the intervention onset (i.e., after the first assessment or after three assessment time points).	Other: Mental Strategy Training; Trainings will be done in groups of up to five people. During training, participants will be presented with an implicit pattern separation task (i.e., for which no response is necessary). At the same time, they will apply mental strategies that were beneficial for hippocampal activity reduction in our previous study. We will use four different mental strategies ("Imagination", "Bodily Perception", "Active Thinking" and "Visual Perception") during each of the training sessions. During imagination participants will need to vividly imagine a scene that exerts a calming effect on them. During "bodily perception" participants will be instruced to focus on their feet or hands while slowly contracting and relaxing them. During active thinking they will perform cognitive tasks such as reciting the alphabet or counting. During visual perception they will focus on a specific part of the presented image. The order of the mental strategies is similar for all participants and all trainings.
Experimental: Group B: 15 participants will be assigned to group B; Group B will attend 4 mental strategy trainings and will start with the training after the first assessment. The training content is identical for all groups. The groups differ only in the number of training sessions and in the timing of the intervention onset (i.e., after the first assessment or after three assessment time points).	Other: Mental Strategy Training; Trainings will be done in groups of up to five people. During training, participants will be presented with an implicit pattern separation task (i.e., for which no response is necessary). At the same time, they will apply mental strategies that were beneficial for hippocampal activity reduction in our previous study. We will use four different mental strategies ("Imagination", "Bodily Perception", "Active Thinking" and "Visual Perception") during each of the training sessions. During imagination participants will need to vividly imagine a scene that exerts a calming effect on them. During "bodily perception" participants will be instruced to focus on their feet or hands while slowly contracting and relaxing them. During active thinking they will perform cognitive tasks such as reciting the alphabet or counting. During visual perception they will focus on a specific part of the presented image. The order of the mental strategies is similar for all participants and all trainings.
Experimental: Group C: 15 participants will be assigned to group C; Group C will attend 2 mental strategy trainings and will start with the training after the first assessment. The training content is identical for all groups. The groups differ only in the number of training sessions and in the timing of the intervention onset (i.e., after the first assessment or after three assessment time points).	Other: Mental Strategy Training; Trainings will be done in groups of up to five people. During training, participants will be presented with an implicit pattern separation task (i.e., for which no response is necessary). At the same time, they will apply mental strategies that were beneficial for hippocampal activity reduction in our previous study. We will use four different mental strategies ("Imagination", "Bodily Perception", "Active Thinking" and "Visual Perception") during each of the training sessions. During imagination participants will need to vividly imagine a scene that exerts a calming effect on them. During "bodily perception" participants will be instruced to focus on their feet or hands while slowly contracting and relaxing them. During active thinking they will perform cognitive tasks such as reciting the alphabet or counting. During visual perception they will focus on a specific part of the presented image. The order of the mental strategies is similar for all participants and all trainings.
Active Comparator: Group D: 10 participants will be assigned to group D; Group D will attend 2 mental strategy trainings and will start with the training after the third assessment. The training content is identical for all groups. The groups differ only in the number of training sessions and in the timing of the intervention onset (i.e., after the first assessment or after three assessment time points).	Other: Mental Strategy Training; Trainings will be done in groups of up to five people. During training, participants will be presented with an implicit pattern separation task (i.e., for which no response is necessary). At the same time, they will apply mental strategies that were beneficial for hippocampal activity reduction in our previous study. We will use four different mental strategies ("Imagination", "Bodily Perception", "Active Thinking" and "Visual Perception") during each of the training sessions. During imagination participants will need to vividly imagine a scene that exerts a calming effect on them. During "bodily perception" participants will be instruced to focus on their feet or hands while slowly contracting and relaxing them. During active thinking they will perform cognitive tasks such as reciting the alphabet or counting. During visual perception they will focus on a specific part of the presented image. The order of the mental strategies is similar for all participants and all trainings.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hippocampal activity during the pattern separation task	In each 4 fMRI sessions, we apply a pattern separation task (i.e., the mnemonic similarity test, MST). Participants need to answer to specific trial types. These are stimuli of everyday objects and the participants have to identify if a stimulus is "new" (they have not seen it before), "old" (exactly the same stimulus has been presented already) or "similar" (a stimulus has been shown before but was different in shape or colour). During each task, we will evaluate their hippocampal activity using similar "lure" trials that rely on pattern separation.	We assess hippocampal activity 4 times from baseline until the last assessment (approximately 10 weeks later).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pattern completion errors	In each 4 fMRI sessions, we apply a pattern separation task (i.e., the mnemonic similarity test, MST). Participants need to answer to specific trial types. These are stimuli of everyday objects and the participants have to identify if a stimulus is "new" (they have not seen it before), "old" (exactly the same stimulus has been presented already) or "similar" (a stimulus has been shown before but was different in shape or colour). Pattern completion errors refer to the mis-identification of similar objects as being old.	We will assess pattern completion errors 4 times from baseline until the last assessment (approximately 10 weeks later).
Pattern Separation success	Correct pattern separation occurs when a participant correctly identifies a similar objects as "similar" in the pattern separation task. Compared to the LDI, here we only focus only on correct responses without considering potential response biases.	We will asssess pattern separation success 4 times from baseline until the last assessment (approximately 10 weeks later).
Lure Discrimination Index	In each 4 fMRI sessions, participants will perform a pattern separation task (i.e., mnemonic similarity test, MST). A widely used metric to report performance in this task is the lure discrimination index (LDI) which is used to determine pattern separation abilities while accounting for response biases	We will evaluate the LDI 4 times from baseline until the last assessment (approximately 10 weeks later).

Collaborators and Investigators

• Sponsor: Jessica Peter
• Investigators: Principal Investigator: Jessica Peter, Professor, University Hospital of Old Age Psychiatry and Psychotherapy

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2024
• Primary Completion (Actual): October 22, 2025
• Study Completion (Actual): October 22, 2025

Study Registration Dates

• First Submitted: July 14, 2026
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 22, 2026

Study Record Updates

• Last Update Posted (Actual): July 22, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: episodic memory; hippocampal hyperactivity; mental strategy
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 50089

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