Mental Strategy Training in Mild Cognitive Impairment

Jessica Peter55 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Mild Cognitive Impairment (MCI) Amnestic Mild Cognitive Impairment

Mental Strategy TrainingOTHER

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.

Eligibility

Sex: ALLMin age: 60 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: We assess hippocampal activity 4 times from baseline until the last assessment (approximately 10 weeks later).

Secondary Outcomes

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.

Time frame: 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.

Time frame: 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

Time frame: We will evaluate the LDI 4 times from baseline until the last assessment (approximately 10 weeks later).