<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03271190</url>
  </required_header>
  <id_info>
    <org_study_id>CRIUGM-004</org_study_id>
    <nct_id>NCT03271190</nct_id>
  </id_info>
  <brief_title>Impact of a Cognitive Intervention Enriched With Leisure Activities in Persons With Subjective Cognitive Decline</brief_title>
  <official_title>Impact of a Cognitive Intervention Enriched With Leisure Activities on Cognition, Daily Life Functioning and Brain Structure and Function in Persons With Subjective Cognitive Decline: The ENGAGE Program</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Rotman Research Institute at Baycrest</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Canadian Institutes of Health Research (CIHR)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The team &quot;Cognitive intervention, cognitive reserve and brain plasticity&quot;, Team 10, is part&#xD;
      of the Canadian Consortium on Neurodegeneration in Aging (CCNA). The team's aim is to develop&#xD;
      and test a multi-faceted intervention program meant to increase cognitive and brain reserve&#xD;
      by providing cognitive stimulation through participation in cognitive training sessions and&#xD;
      engaging leisure activities. This will be done with a partially randomized controlled&#xD;
      double-blind preference trial with a comprehensive cohort design, in participants with&#xD;
      subjective cognitive decline (SCD) recruited in Montreal and Toronto.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the absence of a cure for Alzheimer's disease (AD), there is paramount interest for&#xD;
      non-pharmacological cognitive interventions that are designed to restore, increase, or&#xD;
      optimize capacities and adaptation. Numerous epidemiological studies have shown that&#xD;
      education, cognitively engaging leisure activities, and cognitively demanding professions are&#xD;
      associated with a lower risk of cognitive decline and dementia. When estimating the&#xD;
      proportion of AD cases attributable to modifiable risk factors, it was found that cognitive&#xD;
      inactivity was the factor that contributed to many of the cases worldwide (19.1% or 6.5&#xD;
      million cases). Thus, the level of cognitive stimulation that individuals receive throughout&#xD;
      their life is a critical protective factor against cognitive decline and AD, which suggests&#xD;
      potentially powerful avenues for intervention. In a number of influential papers, Stern&#xD;
      suggested that differences in cognitive lifestyle contribute to cognitive reserve, defined as&#xD;
      the built-up resilience of the brain against the detrimental effect of age-related brain&#xD;
      damage. Cognitive stimulation is thought to create richer brain networks and facilitate the&#xD;
      recruitment of alternative regions or networks. Barnes and Yaffe projected that 1.375 million&#xD;
      AD cases worldwide might be prevented by reducing by 25% the prevalence of cognitive&#xD;
      inactivity. These findings have tremendous consequences when designing strategies against&#xD;
      dementia. Thus, the goal of Team 10 is to design and test an innovative cognitive training&#xD;
      program to increase cognitive reserve and reduce decline in persons with a high risk of AD.&#xD;
&#xD;
      Many studies have shown that cognitive training can increase cognitive abilities in healthy&#xD;
      older adults, or persons with mild cognitive impairment (MCI). Studies with MCI also show&#xD;
      that cognitive training in MCI results in greater brain activation and connectivity, as well&#xD;
      as the recruitment of alternative networks, which supports the view that it contributes to&#xD;
      the creation of cognitive reserve.&#xD;
&#xD;
      There are different types of cognitive interventions that are potentially available. Choosing&#xD;
      the proper one necessitates a fine understanding of their mechanisms of action and their&#xD;
      match to the individual's needs and capabilities. Furthermore, many of the existing programs&#xD;
      have not received empirical support from studies relying on good quality methodology and&#xD;
      there is a lack of evidence regarding their capacity to reduce cognitive decline and&#xD;
      dementia. Hence, previous studies have been limited by some or all of the following&#xD;
      methodological issues: 1) they most often relied on a small number of participants; 2) they&#xD;
      had time-limited follow-up; 3) many did not use a randomized controlled design or provided&#xD;
      limited information on their randomization process; 4) very few have assessed the participant&#xD;
      characteristics that define best responders (i.e., the profile of individuals that benefit&#xD;
      the most from the intervention). Another important aspect is that the programs that are&#xD;
      typically used in those studies are often not optimally adapted to seniors' needs and&#xD;
      preferences and are not grounded in real life, limiting adherence and generalization to&#xD;
      everyday life. Emotional and cognitive engagement refers to participants enjoying as well as&#xD;
      actively participating to the learning experience and has been shown to be a critical factor&#xD;
      in determining learning outcomes. Thus, our program will be designed to promote engagement,&#xD;
      which is absent in the previous studies. Finally, one other important gap is that there are&#xD;
      still a lot that is unknown about the brain processes involved in these interventions and how&#xD;
      they alter brain structure and/or function, especially in healthy older adults. Thus, an&#xD;
      additional important issue is to understand the brain plasticity processes resulting from&#xD;
      cognitive training. Brain plasticity refers to the remarkable ability of the central nervous&#xD;
      system to spontaneously re-organize or expand during normal learning processes, or to&#xD;
      self-repair in acute or progressive brain diseases. This is critical given that an increasing&#xD;
      number of studies has revealed that non-pharmacological interventions can have a positive&#xD;
      impact in AD and that intermediate mechanisms of neural plasticity and functional&#xD;
      compensation likely modulate the detrimental effect of the disease on symptoms.&#xD;
&#xD;
      The investigators will develop ENGAGE, a program to increase cognitive reserve and reduce&#xD;
      decline over a 2-year period in persons with a high risk of AD. The investigators propose a&#xD;
      multi-faceted intervention program meant to increase reserve by providing cognitive&#xD;
      stimulation through participation in engaging cognitive and leisure activities. This&#xD;
      ground-breaking program proposes for the first time to combine (1) hands-on training to&#xD;
      improve memory and attention through teaching strategies to optimize efficiency, and (2)&#xD;
      selected engaging leisure activities that are known to increase brain functions in younger&#xD;
      and older adults, such as learning music, learning a second language, and playing carefully&#xD;
      selected casual video-games. There are many reasons to combine brain training and leisure&#xD;
      activities. First, one limitation of brain training for memory and attention is that&#xD;
      participants sometimes fail to generalize the strategies learned in a lab setting and to&#xD;
      apply them in their everyday life. Thus, the investigators propose to practice these&#xD;
      strategies in the leisure activities, e.g., to learn information relevant to the music or&#xD;
      Spanish lessons. Providing natural, ecologically-valid situations to apply and practice the&#xD;
      cognitive strategies is done to train participants to use them more spontaneously outside the&#xD;
      formal brain training setting. Second, these leisure activities correspond to the cognitively&#xD;
      demanding activities that are identified as protective in epidemiological studies, and thus&#xD;
      likely to promote brain plasticity. Third, they are attractive and will therefore improve&#xD;
      motivation for training. The enjoyable characteristic of the leisure activities will also&#xD;
      make them attractive to older adults with lower education, a segment of population which may&#xD;
      especially benefit from such intervention. Finally, if proven effective, the training program&#xD;
      will have the important advantage of being easy to implement in the community and will be&#xD;
      relatively low-cost relative to formal health care. Another objective of this research&#xD;
      project is to provide recommendations regarding profiles of participants which may benefit&#xD;
      the most from the intervention. The investigators will thus measure whether the effect of the&#xD;
      training is modulated by sex differences as women have been suggested to have less brain&#xD;
      reserve than men as well as age, education or socio-cultural background, lifestyle habits,&#xD;
      genetic factors and other markers of cognitive reserve.&#xD;
&#xD;
      The research team benefits from the contribution of clinicians and researchers from across&#xD;
      Canada who will combine their unique expertise on brain training and on the effects of&#xD;
      leisure activities on the brain to provide the most innovative and potentially meaningful&#xD;
      approach to cognitive intervention. Overall, this innovative program will provide brain&#xD;
      training through specific cognitive training and carefully selected leisure activities that&#xD;
      are known to have a positive impact on cognition and will be particularly attractive to older&#xD;
      adults from varied backgrounds.&#xD;
&#xD;
      Objectives&#xD;
&#xD;
        -  Develop a multi-faceted intervention program that combines brain-based cognitive&#xD;
           training and engaging leisure activities to increase cognitive reserve.&#xD;
&#xD;
        -  Examine whether the program improves cognition and well-being, and prevents cognitive&#xD;
           decline.&#xD;
&#xD;
        -  Assess its effect on brain structure and function using structural and functional&#xD;
           Magnetic Resonance Imaging (fMRI).&#xD;
&#xD;
        -  Determine if individual differences (demographics, reserve level, genetic background)&#xD;
           modulate outcomes.&#xD;
&#xD;
        -  Provide empirical evidence that cognitively-engaging activities provided later in life&#xD;
           can increase brain reserve, promote cognitive health and reduce cognitive decline.&#xD;
&#xD;
      Hypotheses. The investigators hypothesize that participants who will be engaged in the&#xD;
      intervention program will show better behavioral and brain outcomes than participants from&#xD;
      the control group who will receive an active control program. More specifically, improved&#xD;
      behavioral performance following the intervention is expected in neuropsychological tests&#xD;
      measuring cognitive components that are targeted in the program (mainly memory and&#xD;
      attention), as well as a transfer effects to an ecologically-valid test measuring functioning&#xD;
      in a simulated real-life situation. The investigators also expect improvement in&#xD;
      participants' subjective evaluation of their proficiency and satisfaction with life&#xD;
      (questionnaires). Regarding retention of training benefits, the hypothesis is that the&#xD;
      experimental group will show better cognition at the follow up testing, 2 years from the&#xD;
      beginning of the study, and less cognitive decline when comparing 0- to 2-year performance.&#xD;
      Regarding fMRI testing, the investigators expect more task-related activation following&#xD;
      training and correlations between brain changes and cognitive gain, which would be considered&#xD;
      as a marker of enhanced neurocompensation processes.&#xD;
&#xD;
      Design. The consort guidelines will be used to organize and report the trial&#xD;
      (http://www.consort-statement.org). The study uses a randomized controlled double-blind&#xD;
      preference trial with a comprehensive cohort design. Outcomes will be tested by assessors who&#xD;
      will not be involved in the intervention, and who will be blind to training assignment. One&#xD;
      hundred forty-four (144) participants with subjective cognitive decline (SCD), but no&#xD;
      objective impairment based on cognitive tests, will be recruited and randomly assigned to&#xD;
      either the cognitive program (ENGAGE SPANISH or ENGAGE MUSIC) or the active control program&#xD;
      (ENGAGE DISCOVERY). Participants in the ENGAGE DISCOVERY program will undergo the same amount&#xD;
      of activities as proposed in the ENGAGE SPANISH/MUSIC programs, but those activities will be&#xD;
      designed not to be cognitively challenging. Behavioral measures (objective and subjective&#xD;
      measures of cognition and efficiency in everyday life functioning) as well as neuroimaging&#xD;
      measures (fMRI scan during a memory task) will be collected at 3 time points: before the&#xD;
      intervention (PRE), immediately after the intervention (POST-1), and 2 years after PRE&#xD;
      (POST-2). PRE tests will be administered within a 12-week window before the beginning of the&#xD;
      intervention. POST-1 and POST-2 will each be administered within a 8-week window.&#xD;
&#xD;
      To ensure that participants will not be enrolled in an activity that they dislike, and thus&#xD;
      remain the 'leisure' aspect, they will be able to exclude either the 'Music' or 'Spanish'&#xD;
      activity prior to randomization to the intervention or control conditions. This was decided&#xD;
      to personalize the intervention as people vary considerably in how attracted they are by&#xD;
      different leisure activities, and to give participants a sense of choice, which was found to&#xD;
      reduce disappointment related to randomization, and thus to reduce attrition. This will be&#xD;
      done in a manner that will allow preserving double blindness. If participants who are&#xD;
      randomized in the cognitive program did not wish to exclude an activity, then a second&#xD;
      randomization will assign them in one of the 2 activities (either music or Spanish). Thus,&#xD;
      the training vs active control comparison is fully randomized but further comparison of the&#xD;
      two leisure activities will rely on a partially randomized comparison cohort. In that case,&#xD;
      the randomized cohorts will be first compared, followed by a comparison of the entire cohort,&#xD;
      including those in the preference arm.&#xD;
&#xD;
      The results of this intervention will be analyzed at three-endpoints: 1) at baseline (PRE);&#xD;
      2) immediately after the intervention (POST-1); and 3) 2 years after baseline, i.e., about 18&#xD;
      months after the end of the intervention (POST-2).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 15, 2017</start_date>
  <completion_date type="Anticipated">March 31, 2024</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in episodic memory (composite score)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>A composite score will be computed by averaging z-scores from the delayed recall of the Rey Auditory Verbal Learning Test (RAVLT) and the delayed recall of the face-name association task (an associative memory test adapted from Simona Brambati's task for the Consortium pour l'Identification precoce de la Maladie d'Alzheimer (CIMA-Q) study currently running in Quebec).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in attention control (composite score)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>A composite score will be computed by averaging the z-scores from the Number-letter task (switching cost), the complex (4-choice) reaction time from the Canadian Longitudinal Study on Aging (CLSA) Reaction Time Task, and an adapted Flanker task comprising a dual-task condition (congruency effect and dual task cost).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in psychological health: Anxiety and depression (composite score)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>A composite score will be computed by averaging the z-scores from the Geriatric Anxiety Inventory (GAI) + Geriatric Depression Scale (GDS).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in psychological health: Apathy</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>A composite score will be computed that averaging the z-scores from the participant + informant versions of the Apathy Inventory Scale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in psychological health: Quality of life (composite score)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>A composite score will be computed by averaging the z-scores from the 36-item Short Form Survey (SF-36), assessing activities and well-being, and the Quality of Life Alzheimer's Disease questionnaire (QoL-AD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in psychological health: Help-seeking behaviour</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Mean scores from the medical care section from the Stanford Chronic Disease questionnaire, related to medical help-seeking behavior.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in brain structure: Hippocampal Volume (for a subgroup of participants)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Participants will be scanned on a Siemens Total Imaging Matrix (TIM) Trio 3 T magnetic resonance imaging (MRI) system (Siemens Medical Solutions, Erlangen, Germany). Hippocampal volume (mm3) will be measured, as this is an early biomarker of AD and is found to be a sensitive marker of memory training.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in brain structure: Cortical Thickness (for a subgroup of participants)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Participants will be scanned on a Siemens TIM Trio 3 T magnetic resonance imaging (MRI) system (Siemens Medical Solutions, Erlangen, Germany). Cortical thickness (mm) will be measured, as this is an early biomarker of AD and is found to be a sensitive marker of memory training.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in brain function: Brain activation (for a subgroup of participants)</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention)</time_frame>
    <description>fMRI activity while participants are doing an associative memory task. Participants will be presented a sequence of 80 images (e.g., animals, vegetables, etc.). They appear within one of the four quadrants of the screen. People are asked to remember the images and their position among the 4 quadrants (either top-left, top right, bottom-left or bottom-right). Retrieval is done 10 minutes after the encoding, outside of the scanner. People are presented with the same 78 images in a new order and 39 new images, appearing one at a time in the center of the screen. They have to determine whether each image has been previously presented, and if 'Yes', where it was located.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (self-reported): Meta-memory rating</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Mean scores from the Meta-memory questionnaire (MMQ).</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (self-reported): Attention and recent memory rating</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Mean scores from the Auto-administered Memory Questionnaire (AMQ, short version).</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (self-reported): Activities of daily living</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>A composite score will be computed that aggregates the average z-scores from the participant + informant versions of the Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADL-PI).</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (self-reported): Cognitive activities</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Mean scores from the Cognitive Activities questionnaire.</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (self-reported): Jessen's Questions</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>The number of participants that do not have a memory complaint.</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (performance-based): Instrumental Activities of Daily Living</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Mean scores from the Direct Assessment of Functional Status - Revised (DAFS-R), an ecologically-valid task assessing everyday life situations.</description>
  </other_outcome>
  <other_outcome>
    <measure>Transfer to everyday life (performance-based): Memory Strategies</measure>
    <time_frame>PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)</time_frame>
    <description>Mean scores from the Memory Toolbox Test, a questionnaire assessing the knowledge of memory strategies.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">144</enrollment>
  <condition>Subjective Cognitive Decline</condition>
  <arm_group>
    <arm_group_label>ENGAGE SPANISH/MUSIC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cognitive strategies to improve attention and memory skills and application in selected leisure activities (music or Spanish lessons, and videogames) over 4 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ENGAGE DISCOVERY</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Educational program about brain and healthy aging complemented by learning of new information with videogames, documentaries and group discussions over 4 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>ENGAGE SPANISH/MUSIC</intervention_name>
    <description>Cognitive strategies to improve attention and memory skills (21 hours), leisure activities (music lessons or Spanish lessons) (27 hours), selected videogames to practice variable attention strategies (4 hours in class + about 10 hours at home). Total of 24 2-hour in class sessions over 4 months. The training will be delivered to small groups of 5 to 8 participants by a trained therapist for formal sessions and a professional music or Spanish teacher for leisure sessions.</description>
    <arm_group_label>ENGAGE SPANISH/MUSIC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>ENGAGE DISCOVERY</intervention_name>
    <description>Educational content about brain and healthy aging (21 hours), leisure activities (watching documentaries followed by group discussion and debate) (27 hours), selected non-stimulating videogames (4 hours in class + about 10 hours at home). Total of 24 2-hour in class sessions over 4 months. The training will be delivered to small groups of 5 to 8 participants by the same trained therapist as in the ENGAGE arm.</description>
    <arm_group_label>ENGAGE DISCOVERY</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Possess sufficient visual and auditory acuity to undergo neuropsychological tests and&#xD;
             to do the intervention.&#xD;
&#xD;
          -  Commit for the whole intervention + 2 follow-up sessions 2 years from pre-test.&#xD;
&#xD;
          -  Have an internet connection at home.&#xD;
&#xD;
          -  Answer 'Yes' to both following questions: &quot;Do you feel like your memory is becoming&#xD;
             worse?&quot; &quot;Does this worry you?&quot;&#xD;
&#xD;
          -  Have a delayed recall score above the education-adjusted cut-offs (≥9 for 16+ years of&#xD;
             education; ≥5 for 8-15 years of education; ≥3 for 0-7 years of education) at the&#xD;
             Logical Memory test (Wechsler Memory Scale, maximum score 25).&#xD;
&#xD;
          -  Have a Montreal Cognitive Assessment (MoCA) total score of 20 and above (≥20/30).&#xD;
&#xD;
          -  Have a delayed recall score at the Consortium to Establish a Registry for Alzheimer's&#xD;
             Disease (CERAD) Word List task above 4 (&gt;4).&#xD;
&#xD;
          -  Have a global Clinical Dementia Rating score (CDR) equal to 0 or 0.5 (=0 to 0.5).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  The presence of disease or injury of the central nervous system, such as: moderate to&#xD;
             severe chronic static leukoencephalopathy (including previous traumatic injury),&#xD;
             multiple sclerosis, a serious developmental handicap, subdural hematoma (past or&#xD;
             current), subarachnoid haemorrhage (past or current), primary cerebral tumour or&#xD;
             cerebral metastases, epilepsy (current), dementia or another neurodegenerative&#xD;
             disease, and other rarer brain illnesses.&#xD;
&#xD;
          -  Symptomatic stroke within the previous year.&#xD;
&#xD;
          -  History of intracranial surgery.&#xD;
&#xD;
          -  Major surgery within last 2 months.&#xD;
&#xD;
          -  Serious comorbid condition that, in the opinion of the study investigator, is likely&#xD;
             to result in death within a year.&#xD;
&#xD;
          -  Major depression or anxiety.&#xD;
&#xD;
          -  Schizophrenia or other major psychiatric disorder.&#xD;
&#xD;
          -  Ongoing alcohol or drug abuse that in the opinion of the investigator may interfere&#xD;
             with the subject's ability to comply with the study procedures.&#xD;
&#xD;
          -  Subject does not have a study partner who can provide corroborative information.&#xD;
&#xD;
          -  Individuals where English (Toronto) or French (Montreal) is not sufficiently&#xD;
             proficient for clinical assessment and neuropsychological testing.&#xD;
&#xD;
          -  Unable to undergo MRI scan due to medical contraindications or inability to tolerate&#xD;
             the procedure.&#xD;
&#xD;
          -  Plans on moving outside the province within the next 2 years.&#xD;
&#xD;
          -  Musicianship: more than 5 years of formal music training in total life or more than 10&#xD;
             years of choir experience.&#xD;
&#xD;
          -  Fluency in Spanish: has learned Spanish after secondary school for more than 5 years,&#xD;
             speaks Spanish at home, has ever lived in a Hispanic country.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sylvie Belleville, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rotman Research Institute, Baycrest</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6A 2E1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CRIUGM</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>h3w 1w4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>December 15, 2016</study_first_submitted>
  <study_first_submitted_qc>August 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>February 13, 2023</last_update_submitted>
  <last_update_submitted_qc>February 13, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal</investigator_affiliation>
    <investigator_full_name>Sylvie Belleville</investigator_full_name>
    <investigator_title>Ph.D, Full professor, University of Montreal, and Scientific Director, Institut Universitaire de Geriatrie de Montreal (IUGM)</investigator_title>
  </responsible_party>
  <keyword>aging</keyword>
  <keyword>memory complaint</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03271190
org study id: CRIUGM-004
nct id: NCT03271190
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The team "Cognitive intervention, cognitive reserve and brain plasticity", Team 10, is part
      of the Canadian Consortium on Neurodegeneration in Aging (CCNA). The team's aim is to develop
      and test a multi-faceted intervention program meant to increase cognitive and brain reserve
      by providing cognitive stimulation through participation in cognitive training sessions and
      engaging leisure activities. This will be done with a partially randomized controlled
      double-blind preference trial with a comprehensive cohort design, in participants with
      subjective cognitive decline (SCD) recruited in Montreal and Toronto.
In the absence of a cure for Alzheimer's disease (AD), there is paramount interest for
      non-pharmacological cognitive interventions that are designed to restore, increase, or
      optimize capacities and adaptation. Numerous epidemiological studies have shown that
      education, cognitively engaging leisure activities, and cognitively demanding professions are
      associated with a lower risk of cognitive decline and dementia. When estimating the
      proportion of AD cases attributable to modifiable risk factors, it was found that cognitive
      inactivity was the factor that contributed to many of the cases worldwide (19.1% or 6.5
      million cases). Thus, the level of cognitive stimulation that individuals receive throughout
      their life is a critical protective factor against cognitive decline and AD, which suggests
      potentially powerful avenues for intervention. In a number of influential papers, Stern
      suggested that differences in cognitive lifestyle contribute to cognitive reserve, defined as
      the built-up resilience of the brain against the detrimental effect of age-related brain
      damage. Cognitive stimulation is thought to create richer brain networks and facilitate the
      recruitment of alternative regions or networks. Barnes and Yaffe projected that 1.375 million
      AD cases worldwide might be prevented by reducing by 25% the prevalence of cognitive
      inactivity. These findings have tremendous consequences when designing strategies against
      dementia. Thus, the goal of Team 10 is to design and test an innovative cognitive training
      program to increase cognitive reserve and reduce decline in persons with a high risk of AD.

      Many studies have shown that cognitive training can increase cognitive abilities in healthy
      older adults, or persons with mild cognitive impairment (MCI). Studies with MCI also show
      that cognitive training in MCI results in greater brain activation and connectivity, as well
      as the recruitment of alternative networks, which supports the view that it contributes to
      the creation of cognitive reserve.

      There are different types of cognitive interventions that are potentially available. Choosing
      the proper one necessitates a fine understanding of their mechanisms of action and their
      match to the individual's needs and capabilities. Furthermore, many of the existing programs
      have not received empirical support from studies relying on good quality methodology and
      there is a lack of evidence regarding their capacity to reduce cognitive decline and
      dementia. Hence, previous studies have been limited by some or all of the following
      methodological issues: 1) they most often relied on a small number of participants; 2) they
      had time-limited follow-up; 3) many did not use a randomized controlled design or provided
      limited information on their randomization process; 4) very few have assessed the participant
      characteristics that define best responders (i.e., the profile of individuals that benefit
      the most from the intervention). Another important aspect is that the programs that are
      typically used in those studies are often not optimally adapted to seniors' needs and
      preferences and are not grounded in real life, limiting adherence and generalization to
      everyday life. Emotional and cognitive engagement refers to participants enjoying as well as
      actively participating to the learning experience and has been shown to be a critical factor
      in determining learning outcomes. Thus, our program will be designed to promote engagement,
      which is absent in the previous studies. Finally, one other important gap is that there are
      still a lot that is unknown about the brain processes involved in these interventions and how
      they alter brain structure and/or function, especially in healthy older adults. Thus, an
      additional important issue is to understand the brain plasticity processes resulting from
      cognitive training. Brain plasticity refers to the remarkable ability of the central nervous
      system to spontaneously re-organize or expand during normal learning processes, or to
      self-repair in acute or progressive brain diseases. This is critical given that an increasing
      number of studies has revealed that non-pharmacological interventions can have a positive
      impact in AD and that intermediate mechanisms of neural plasticity and functional
      compensation likely modulate the detrimental effect of the disease on symptoms.

      The investigators will develop ENGAGE, a program to increase cognitive reserve and reduce
      decline over a 2-year period in persons with a high risk of AD. The investigators propose a
      multi-faceted intervention program meant to increase reserve by providing cognitive
      stimulation through participation in engaging cognitive and leisure activities. This
      ground-breaking program proposes for the first time to combine (1) hands-on training to
      improve memory and attention through teaching strategies to optimize efficiency, and (2)
      selected engaging leisure activities that are known to increase brain functions in younger
      and older adults, such as learning music, learning a second language, and playing carefully
      selected casual video-games. There are many reasons to combine brain training and leisure
      activities. First, one limitation of brain training for memory and attention is that
      participants sometimes fail to generalize the strategies learned in a lab setting and to
      apply them in their everyday life. Thus, the investigators propose to practice these
      strategies in the leisure activities, e.g., to learn information relevant to the music or
      Spanish lessons. Providing natural, ecologically-valid situations to apply and practice the
      cognitive strategies is done to train participants to use them more spontaneously outside the
      formal brain training setting. Second, these leisure activities correspond to the cognitively
      demanding activities that are identified as protective in epidemiological studies, and thus
      likely to promote brain plasticity. Third, they are attractive and will therefore improve
      motivation for training. The enjoyable characteristic of the leisure activities will also
      make them attractive to older adults with lower education, a segment of population which may
      especially benefit from such intervention. Finally, if proven effective, the training program
      will have the important advantage of being easy to implement in the community and will be
      relatively low-cost relative to formal health care. Another objective of this research
      project is to provide recommendations regarding profiles of participants which may benefit
      the most from the intervention. The investigators will thus measure whether the effect of the
      training is modulated by sex differences as women have been suggested to have less brain
      reserve than men as well as age, education or socio-cultural background, lifestyle habits,
      genetic factors and other markers of cognitive reserve.

      The research team benefits from the contribution of clinicians and researchers from across
      Canada who will combine their unique expertise on brain training and on the effects of
      leisure activities on the brain to provide the most innovative and potentially meaningful
      approach to cognitive intervention. Overall, this innovative program will provide brain
      training through specific cognitive training and carefully selected leisure activities that
      are known to have a positive impact on cognition and will be particularly attractive to older
      adults from varied backgrounds.

      Objectives

        -  Develop a multi-faceted intervention program that combines brain-based cognitive
           training and engaging leisure activities to increase cognitive reserve.

        -  Examine whether the program improves cognition and well-being, and prevents cognitive
           decline.

        -  Assess its effect on brain structure and function using structural and functional
           Magnetic Resonance Imaging (fMRI).

        -  Determine if individual differences (demographics, reserve level, genetic background)
           modulate outcomes.

        -  Provide empirical evidence that cognitively-engaging activities provided later in life
           can increase brain reserve, promote cognitive health and reduce cognitive decline.

      Hypotheses. The investigators hypothesize that participants who will be engaged in the
      intervention program will show better behavioral and brain outcomes than participants from
      the control group who will receive an active control program. More specifically, improved
      behavioral performance following the intervention is expected in neuropsychological tests
      measuring cognitive components that are targeted in the program (mainly memory and
      attention), as well as a transfer effects to an ecologically-valid test measuring functioning
      in a simulated real-life situation. The investigators also expect improvement in
      participants' subjective evaluation of their proficiency and satisfaction with life
      (questionnaires). Regarding retention of training benefits, the hypothesis is that the
      experimental group will show better cognition at the follow up testing, 2 years from the
      beginning of the study, and less cognitive decline when comparing 0- to 2-year performance.
      Regarding fMRI testing, the investigators expect more task-related activation following
      training and correlations between brain changes and cognitive gain, which would be considered
      as a marker of enhanced neurocompensation processes.

      Design. The consort guidelines will be used to organize and report the trial
      (http://www.consort-statement.org). The study uses a randomized controlled double-blind
      preference trial with a comprehensive cohort design. Outcomes will be tested by assessors who
      will not be involved in the intervention, and who will be blind to training assignment. One
      hundred forty-four (144) participants with subjective cognitive decline (SCD), but no
      objective impairment based on cognitive tests, will be recruited and randomly assigned to
      either the cognitive program (ENGAGE SPANISH or ENGAGE MUSIC) or the active control program
      (ENGAGE DISCOVERY). Participants in the ENGAGE DISCOVERY program will undergo the same amount
      of activities as proposed in the ENGAGE SPANISH/MUSIC programs, but those activities will be
      designed not to be cognitively challenging. Behavioral measures (objective and subjective
      measures of cognition and efficiency in everyday life functioning) as well as neuroimaging
      measures (fMRI scan during a memory task) will be collected at 3 time points: before the
      intervention (PRE), immediately after the intervention (POST-1), and 2 years after PRE
      (POST-2). PRE tests will be administered within a 12-week window before the beginning of the
      intervention. POST-1 and POST-2 will each be administered within a 8-week window.

      To ensure that participants will not be enrolled in an activity that they dislike, and thus
      remain the 'leisure' aspect, they will be able to exclude either the 'Music' or 'Spanish'
      activity prior to randomization to the intervention or control conditions. This was decided
      to personalize the intervention as people vary considerably in how attracted they are by
      different leisure activities, and to give participants a sense of choice, which was found to
      reduce disappointment related to randomization, and thus to reduce attrition. This will be
      done in a manner that will allow preserving double blindness. If participants who are
      randomized in the cognitive program did not wish to exclude an activity, then a second
      randomization will assign them in one of the 2 activities (either music or Spanish). Thus,
      the training vs active control comparison is fully randomized but further comparison of the
      two leisure activities will rely on a partially randomized comparison cohort. In that case,
      the randomized cohorts will be first compared, followed by a comparison of the entire cohort,
      including those in the preference arm.

      The results of this intervention will be analyzed at three-endpoints: 1) at baseline (PRE);
      2) immediately after the intervention (POST-1); and 3) 2 years after baseline, i.e., about 18
      months after the end of the intervention (POST-2).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Outcomes Assessor)
measure: Changes in episodic memory (composite score)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: A composite score will be computed by averaging z-scores from the delayed recall of the Rey Auditory Verbal Learning Test (RAVLT) and the delayed recall of the face-name association task (an associative memory test adapted from Simona Brambati's task for the Consortium pour l'Identification precoce de la Maladie d'Alzheimer (CIMA-Q) study currently running in Quebec).
measure: Changes in attention control (composite score)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: A composite score will be computed by averaging the z-scores from the Number-letter task (switching cost), the complex (4-choice) reaction time from the Canadian Longitudinal Study on Aging (CLSA) Reaction Time Task, and an adapted Flanker task comprising a dual-task condition (congruency effect and dual task cost).
measure: Changes in psychological health: Anxiety and depression (composite score)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: A composite score will be computed by averaging the z-scores from the Geriatric Anxiety Inventory (GAI) + Geriatric Depression Scale (GDS).
measure: Changes in psychological health: Apathy
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: A composite score will be computed that averaging the z-scores from the participant + informant versions of the Apathy Inventory Scale.
measure: Changes in psychological health: Quality of life (composite score)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: A composite score will be computed by averaging the z-scores from the 36-item Short Form Survey (SF-36), assessing activities and well-being, and the Quality of Life Alzheimer's Disease questionnaire (QoL-AD).
measure: Changes in psychological health: Help-seeking behaviour
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Mean scores from the medical care section from the Stanford Chronic Disease questionnaire, related to medical help-seeking behavior.
measure: Changes in brain structure: Hippocampal Volume (for a subgroup of participants)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Participants will be scanned on a Siemens Total Imaging Matrix (TIM) Trio 3 T magnetic resonance imaging (MRI) system (Siemens Medical Solutions, Erlangen, Germany). Hippocampal volume (mm3) will be measured, as this is an early biomarker of AD and is found to be a sensitive marker of memory training.
measure: Changes in brain structure: Cortical Thickness (for a subgroup of participants)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Participants will be scanned on a Siemens TIM Trio 3 T magnetic resonance imaging (MRI) system (Siemens Medical Solutions, Erlangen, Germany). Cortical thickness (mm) will be measured, as this is an early biomarker of AD and is found to be a sensitive marker of memory training.
measure: Changes in brain function: Brain activation (for a subgroup of participants)
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention)
description: fMRI activity while participants are doing an associative memory task. Participants will be presented a sequence of 80 images (e.g., animals, vegetables, etc.). They appear within one of the four quadrants of the screen. People are asked to remember the images and their position among the 4 quadrants (either top-left, top right, bottom-left or bottom-right). Retrieval is done 10 minutes after the encoding, outside of the scanner. People are presented with the same 78 images in a new order and 39 new images, appearing one at a time in the center of the screen. They have to determine whether each image has been previously presented, and if 'Yes', where it was located.
measure: Transfer to everyday life (self-reported): Meta-memory rating
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Mean scores from the Meta-memory questionnaire (MMQ).
measure: Transfer to everyday life (self-reported): Attention and recent memory rating
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Mean scores from the Auto-administered Memory Questionnaire (AMQ, short version).
measure: Transfer to everyday life (self-reported): Activities of daily living
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: A composite score will be computed that aggregates the average z-scores from the participant + informant versions of the Alzheimer's Disease Cooperative Study - Activities of Daily Living - Prevention Instrument (ADCS-ADL-PI).
measure: Transfer to everyday life (self-reported): Cognitive activities
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Mean scores from the Cognitive Activities questionnaire.
measure: Transfer to everyday life (self-reported): Jessen's Questions
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: The number of participants that do not have a memory complaint.
measure: Transfer to everyday life (performance-based): Instrumental Activities of Daily Living
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Mean scores from the Direct Assessment of Functional Status - Revised (DAFS-R), an ecologically-valid task assessing everyday life situations.
measure: Transfer to everyday life (performance-based): Memory Strategies
time frame: PRE (within 12 weeks before intervention starts) + POST-1 (within 8 weeks after the end of intervention) + POST-2 (2 years from PRE, +/- 3 months)
description: Mean scores from the Memory Toolbox Test, a questionnaire assessing the knowledge of memory strategies.
arm group label: ENGAGE SPANISH/MUSIC
arm group type: Experimental
description: Cognitive strategies to improve attention and memory skills and application in selected leisure activities (music or Spanish lessons, and videogames) over 4 months.
arm group label: ENGAGE DISCOVERY
arm group type: Active Comparator
description: Educational program about brain and healthy aging complemented by learning of new information with videogames, documentaries and group discussions over 4 months.
intervention type: Behavioral
intervention name: ENGAGE SPANISH/MUSIC
description: Cognitive strategies to improve attention and memory skills (21 hours), leisure activities (music lessons or Spanish lessons) (27 hours), selected videogames to practice variable attention strategies (4 hours in class + about 10 hours at home). Total of 24 2-hour in class sessions over 4 months. The training will be delivered to small groups of 5 to 8 participants by a trained therapist for formal sessions and a professional music or Spanish teacher for leisure sessions.
arm group label: ENGAGE SPANISH/MUSIC
intervention type: Behavioral
intervention name: ENGAGE DISCOVERY
description: Educational content about brain and healthy aging (21 hours), leisure activities (watching documentaries followed by group discussion and debate) (27 hours), selected non-stimulating videogames (4 hours in class + about 10 hours at home). Total of 24 2-hour in class sessions over 4 months. The training will be delivered to small groups of 5 to 8 participants by the same trained therapist as in the ENGAGE arm.
arm group label: ENGAGE DISCOVERY
criteria: 
gender: All
minimum age: 60 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Sylvie Belleville, PhD
role: Principal Investigator
affiliation: Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal
facility: 
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Centre de Recherche de l'Institut Universitaire de Geriatrie de Montreal
investigator full name: Sylvie Belleville
investigator title: Ph.D, Full professor, University of Montreal, and Scientific Director, Institut Universitaire de Geriatrie de Montreal (IUGM)
mesh term: Cognitive Dysfunction
sharing ipd: No