Clinical trial NCT06549517: Study on the Effectiveness of the MTT24.5 Cognitive Training Program on Cognitive Skills, Brain Volume, and Activation
Official title: Analysis of Efficacy of the Mental Training Tech 245: a Novel Method of Cognitive Stimulation Based on Brain Neuroplastic Ability
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Dysfunction
Keywords: ageing
cognitive dysfunction
cerebral neuroplasticiy
Lead sponsor: Institute for Biomedical Research, CONICET
Sponsor class: OTHER
First posted: 2024-08-12
Enrollment: 75
Sex: ALL
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multisite, prospective, and open-label study involving two arms. Subjects from the general adult population were randomly assigned to either a cognitive intervention group or a no-intervention control group. The intervention consisted of in-person cognitive training over 12 weeks, with baseline and final cognitive evaluations. A sub-study will investigate neuroimaging changes in brain volume and activation as parameters of neuroplasticity stimulation
Primary purpose: PREVENTION

Brief summary: The goal of this study is to evaluate the effectiveness of a cognitive training program called Mental Training Tech 24.5 (MTT24.5). The program aims to enhance brain function and neuronal plasticity in adults who do not have any clinical cognitive impairment. This study will help determine if MTT24.5 improves cognitive abilities and affects brain volume and activation.

The Main Questions it aims to answer are:

Does MTT24.5 improve overall cognitive performance and specific areas like memory, attention, and language skills? What effects does MTT24.5 have on brain volume and activation? How well do participants follow the program, and what are their response patterns?

Study Design

* Researchers will compare the results of participation in the MTT24.5 training versus a control group with no intervention. Participants will be randomly assigned to either the MTT24.5 program or the control group.
* The study involves adults aged 30 and older from the general population who do not have clinical cognitive impairment.
* The intervention includes attending 12 weekly in-person sessions, each lasting about 2 hours, for a total of 24.5 hours.
* The study will assess cognitive performance, brain volume, and activation, as well as monitor adherence to the program and response patterns.

Participants will:

* Engage in the MTT24.5 program or the control condition as assigned.
* Complete cognitive assessments to measure performance in various domains.
* Undergo brain imaging to evaluate changes in brain volume and activation.

Detailed description: Neuronal plasticity presents a promising approach to addressing a pressing contemporary challenge: the intersection of increased life expectancy with the risks of cognitive decline, dementia, and loss of independence. A wealth of literature highlights the potential of various neuronal plasticity stimulation strategies in bolstering cognitive abilities. However, while much focus has been dedicated to using these techniques for neurological rehabilitation, there remains a paucity of evidence regarding their efficacy in maintaining and enhancing cognitive functions in the generally healthy population. In line with this, the cognitive training protocol 'Mental Training Tech 24.5' (MTT24.5) is grounded in the principles of neuronal plasticity and aims to improve cognitive development. It specifically focuses on enhancing memory, reasoning speed, and attention in adults through a conceptual model that posits explicit learning as a direct stimulus for neuronal plasticity.

II) AIMS:

Primary Objectives:

Evaluate the effects of MTT24.5 on cognitive abilities such as memory, attention, orientation, verbal fluency, language, and visuospatial skills.

Assess the effects of MTT24.5 on brain structure and activation, including brain volumes in globally standardized areas and those associated with cognitive abilities, according to cognitive brain areas with taxonomic mapping.

Determine if there are response phenotypes based on individual baseline characteristics, such as age, gender, lifestyle factors, medical history, medications, family history of dementia, diet, and baseline cognitive reserve score.

Secondary Objective:

Analyze the tolerance and adherence to MTT24.5 and its association with outcomes related to cognitive variables, as well as structural and/or functional brain changes.

III) METHODS

Design:

This is a multisite, prospective, randomized open clinical study conducted between March and October 2023.

Regulatory Approvals:

The trial was approved by the review board and the local ethics committee. All participants provided written consent. This study followed the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.

Evaluations:

* Cognitive Reserve Score (CRS): A validated cognitive reserve scale authorized from Roldan L. et al. The CRS records the frequency of cognitively stimulating activities carried out throughout life. It includes 24 items distributed across four aspects: activities of daily living, education/information, hobbies, and social life. The CRS will be obtained for each subject at baseline (pre-intervention) and after 12 weeks of participation.
* Medical and Lifestyle History Form: A self-administered medical and lifestyle history form called STEPS 5, adapted from www.who.int/chp/steps, and previously used in the Latin American OPTIMO study. This form will be administered to each subject at baseline (pre-intervention).
* The Addenbrooke's Cognitive Examination-III (ACE-III): A brief cognitive test that evaluates five cognitive abilities: attention, memory, verbal fluency, language, and visuospatial skills. The ACE-III score will be obtained for each subject at baseline (pre-intervention) and post-intervention.
* Brain Magnetic Resonance Imaging (BMRI): Brain volume and activation information will be obtained from this study, conducted on a subset of subjects at baseline (pre-intervention) and post-intervention.

Description of the Intervention:

MTT24.5 is a structured program consisting of 40 new pieces of knowledge and 100 learning techniques.developed as a binomial DATA/TECH program, provides the brain with new knowledge (DATA) classified into formal, natural, social, and cultural areas. The TECH consists of 100 high-impact cognitive stimulation modalities designed to enhance memory, attention, verbal fluency, and visuospatial skills. Techniques include methods such as learning to read the information in Braille, writing it with the non-dominant hand, or reinforcing the concept across various domains simultaneously. Each piece of new information and technique is codified and identified with a number throughout the protocol. This integration is intended to promotes changes in brain functionality, improves synaptic efficiency, and achieves permanent plastic changes. The program spans approximately 24.5 hours over 12 weeks, comprising weekly in-person training sessions of 1.5 hours each, supplemented by an additional average of 4 hours of weekly online activities.

The data or new knowledges were selected through an extensive search of relevant knowledge from the basic sciences (natural, cultural, formal, and social sciences). To be included, the data should be expressible in a concise concept stated in a maximum of 15 words, around which an explanation is built using visual animation and emotional aspects or experiential learning during a 10-minute session. The second part of the session aims to promote the integration of the new knowledge into an individual's cognitive reserve, employing cognitive TECHS, which consist of exercises designed for this purpose. TECHS selection was based on a review of peer-reviewed articles demonstrating the effectiveness of cognitive training in improving specific cognitive abilities investigated in the study. We identified 25 cognitive training studies with appropriate tools published between 2000 and 2022. The possible combinations of these tools yielded 75 possibilities regarding the association between 2 to 5 techniques for learning the same data, indicating either consecutive or simultaneous actions.

24.5 represents the total hours assigned to the program duration, based on similar training distributions reported in the ACTIVE TRIAL (The Advanced Cognitive Training for Independent and Vital Elderly).

Detailed descriptions of the statistical analysis plan can be found in the attached document, SA

Eligibility criteria: Inclusion Criteria:

* Adults aged 21 years and above.
* Ability to understand instructions for the training tasks.
* Addenbrooke Cognitive Examination score \>70.

Exclusion Criteria:

* Planned absences that would hinder participation in the program.
* Hearing, visual, or motor deficits that would impede participation in the program.
* History of severe degenerative neurological diseases, as these conditions may significantly impact brain plasticity and cognitive abilities.
* History of severe psychiatric disorders, as they may influence brain reorganization and complicate the interpretation of results.
* Unstable treatment or planned changes in medication that may affect brain function and alter results.
* History of current or recent excessive substance use (within the past 6 months), including alcohol or drugs, as these substances may influence brain function and neuroplasticity.

Primary outcomes:
measure: Change in Global Cognitive Ability
timeFrame: immediately after the intervention
Secondary outcomes:
measure: Change in memory, and /or attention, and/or verbal fluency, and/or language, and/or visuospatial skills abilities.
timeFrame: immediately after the intervention
measure: Rate of Adherence
timeFrame: immediately after the intervention
measure: Change in Brain Volume and Activation
timeFrame: immediately after the intervention
Other outcomes:
Locations:
city: San Isidro
country: Argentina
facility: Espacio Santa Maria
state: Buenos Aires
Study officials:
affiliation: BIO
name: Carol V Kotliar, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Institute for Biomedical Research, CONICET
name: Carol V Kotliar, PhD
role: PRINCIPAL_INVESTIGATOR
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