Attentional Control Training in Older Adults: Efficacy, Transfer and Brain Substrates

Study Overview
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Brief Summary
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Formal education and cognitively stimulating hobbies and profession have a protective effect against age-related cognitive decline and Alzheimer's disease. It is therefore possible that providing cognitively stimulating interventions at a later age increases neuroplasticity and brain resilience. Processes of updating and inhibition are both impaired by aging. Several studies have shown that updating can be improved but very few studies targeted inhibition in spite of the fact that it is impaired in older adults. The aim of this study is to assess the effect of cognitive interventions that will target either of these two components. The investigators will examine the effect on behavior, brain measures and transfer tasks. The investigators will also assess whether the efficacy varies as a function of personal variables such as prior cognitive profile, reserve proxies, genetic polymorphisms and brain markers.

Detailed Description
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Formal education and cognitively stimulating hobbies and profession have a protective effect against age-related cognitive decline and Alzheimer's disease. The cognitive reserve model suggests that engaging in cognitively stimulating activities may induce brain processes and/or morphological characteristics that make individuals more resilient to the effects of brain damage. It is therefore possible that providing cognitive interventions at a later age amplify similar neuroplastic processes and thus reduce the deleterious effects of aging. Cognitive interventions refer to programs and/or strategies aimed at increasing or optimizing cognitive performance. Many of these programs target working memory (WM), which is defined as the ability to control attention in order to keep information active and accessible. Miyake's influential model proposes that WM relies on the coordinated functioning of a small set of attentional control components. Here the investigators will focus on two of these components: inhibition and updating. Training those two components might reveal critical as they are impaired in aging and subtend a range of more complex cognitive processes. Furthermore, they rely on distinct brain networks and are sensitive to cognitive lifestyle. Several studies have shown that updating capacities of older adults can be improved by cognitive training but very few studies targeted inhibition in spite of the fact that it is severly impaired by aging. The aim of this study is to assess the effect of cognitive interventions that will target either of these two components and compare their effect to that of an active control training. The investigators will examine their effect on behavior, brain measures and transfer tasks. The investigators will also assess whether the efficacy varies as a function of personal variables such as prior cognitive profile, reserve proxies, genetic polymorphisms and brain markers. The investigators will also examine the cumulative effect of training by measuring efficacy at three time points for the proximal outcomes and at five time points for the distal outcomes. Finally, a group of younger adults will be tested at baseline to assess whether training normalize performance, that is, whether the performance of older adults after training is improved to the level of typical young adults. 90 healthy older adults (60-85 years) will be recruited for this study, as well as thirty young adults (20-35 years) who will complete only the initial assessment (PRE). All participants will be recruited from the community and living in the Montreal area. A telephone interview will provide initial selection information. Eligible persons will be invited to come to the laboratory for a standardized clinical and neuropsychological battery in order to evaluate their clinical status and cognitive functioning. The older adults will be randomly assigned to one of three intervention conditions (Inhibition, Updating, Active control). Updating will be trained using N-back-like exercises whereas inhibition will be trained with Stroop-like exercises. Different types of stimuli will be used to facilitate transfer. The control intervention will include exercises on general knowledge and vocabulary. All training will be computerized. Training will be provided in 12 half-hours training sessions. Outcome measures will be taken no more than two weeks prior to training (PRE), between Session 6 and 7 (POST1) and no more than one week following Session 12 (POST2). Participants will be trained in small groups of 6 to 10 individuals recruited in about 6 waves. The first two waves will allow to pilot the procedure/team and will be accrued to the whole trial if the training procedure and outcome measures remain unchanged.

Official Title
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Memory and Cognitive Control for Optimal Aging: Study on the Effect of Cognitive Interventions, Cerebral Mechanisms Involved and Processes Promoting Transfer

Conditions
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Updating, Inhibition (Psychology), General Knowledge, No Training

Intervention / Treatment
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* Behavioral: Updating
* Behavioral: Inhibition
* Behavioral: General knowledge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: French-speaking Right-handed Sufficient visual and auditory acuity to undergo neuropsychological tests and to do the interventions. Sufficient delayed recall score above the education-adjusted cut-offs (≥9 for 16+ years of education; ≥5 for 8-15 years of education; ≥3 for 0-7 years of education) at the Logical Memory test (Wechsler Memory Scale, maximum score 25). Exclusion Criteria: Answer 'Yes' to the two following questions: Do you feel like your memory is becoming worse? Does this worry you? (to exclude subjective cognitive decline). The presence of a disease or injury of the central nervous system: moderate to severe chronic static leukoencephalopathy (including previous traumatic injury), multiple sclerosis, a serious developmental handicap, subdural hematoma (past or current), subarachnoid haemorrhage (past or current), primary cerebral tumour or cerebral metastases, epilepsy (current), dementia or another neurodegenerative disease, and other rarer brain illnesses. Symptomatic stroke within the previous year. Alcoholism or substance abuse History of intracranial surgery. Major surgery within last 2 months. General anesthesia in the past 6 months. Serious comorbid condition that, in the opinion of the study investigator, is likely to result in death within a year. Major depression or anxiety. Schizophrenia or other major psychiatric disorder (e.g., bipolar disorder). Individuals where French is not sufficiently proficient for clinical assessment and neuropsychological testing. Unable to undergo MRI scan due to medical contraindications or inability to tolerate the procedure. Plans on moving outside the province within the next 2 months.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Older participants are randomly assigned to one of three intervention conditions (Inhibition ; Updating ; General knowledge). Young participants only complete the initial assessment.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Updating<br>The Updating intervention aims to improve the ability to monitor and quickly add or delete of content of working memory. | Behavioral: Updating<br>* Updating is trained across 12 sessions using N-back-type exercises. Training is performed on a samsung galaxy tab2. Each session lasts 30 minutes. The difficult is reset and the nature of the stimuli (numbers vs. symbols) is changed halfway in each session.<br>|
| Experimental: Inhibition<br>The Inhibition intervention aims to improve the ability to supersede responses that are prepotent or automatic for a given situation. | Behavioral: Inhibition<br>* Inhibition is trained across 12 sessions with Stroop-like exercises. Training is performed on a samsung galaxy tab2. Each session lasts 30 minutes. The difficult is reset and the nature of stimuli (letters vs. numbers) is changed halfway in each session.<br>|
| Active Comparator: General Knowledge<br>The General knowledge intervention allows the learning of information on various topics. It does not involve attentional control but semantic knowledge. | Behavioral: General knowledge<br>* General Knowledge is trained across 12 sessions. Participants complete four-choice questions relating to general knowledge and vocabulary and are provided with the correct answer and a short explanation. Questions are displayed one by one on a computer screen with a maximum of 20 seconds per question. Each session lasts 30 minutes and includes 2 blocks of 40 new questions each (about 220 seconds per block). Questions with wrong answers are displayed again at the end of each block.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes on the updating composite measure (Proximal outcome). | An updating composite score will be computed by averaging z-scores from the Keep track task and the Running span task. | within the 2 weeks before intervention starts; 3rd week after intervention starts (after the 6th training session); 6th week (after the 12th training session) | 
| Changes on the inhibition composite measure (Proximal outcome). | An inhibition composite score will be computed by averaging z-scores from the Anti-saccade and the Victoria Stroop Test. | within the 2 weeks before intervention starts; 3rd week after intervention starts (after the 6th training session); 6th week (after the 12th training session) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfer to complex working memory measure: the Alpha-span task (Distal outcome). | Accuracy on the alphabetic portion of the Alpha-span task | within the 2 weeks before intervention starts; 1st week after intervention starts (after the 3rd training session); 3rd week (after the 6th training session); 4th week (after the 9th training session); 6th week (after the 12th training session). | 
| Transfer to complex working memory measure: the Reading span task (Distal outcome). | Accuracy on the Reading span task. | within the 2 weeks before intervention starts; 1st week after intervention starts (after the 3rd training session); 3rd week (after the 6th training session); 4th week (after the 9th training session); 6th week (after the 12th training session). | 
| Transfer to complex working memory measure: the virtual car ride task (Distal outcome). | Average z-score computed with the verbal and visual (accuracy and RT) components of the divided attention virtual reality task. | within the 2 weeks before intervention starts; 1st week after intervention starts (after the 3rd training session); 3rd week (after the 6th training session); 4th week (after the 9th training session); 6th week (after the 12th training session). | 
| Brain structure: Regional gray matter volumes in Prefrontal and lateral temporal cortices, Basal ganglia and Hippocampi. | A T1-weighted 3D-MPRAGE sequence (TR/TE 2300/2.98ms, Fa 9°, FOV = 256*256, matrix 256*256, voxels 1mm³, 192 slices) will be used to measure regional gray matter volume. | within the 2 weeks before intervention starts; 3rd week after intervention starts (after the 6th training session); 6th week (after the 12th training session) | 
| Brain structure: Cortical thickness in Prefrontal regions and lateral temporal cortices. | A T1-weighted 3D-MPRAGE sequence (TR/TE 2300/2.98ms, Fa 9°, FOV = 256*256, matrix 256*256, voxels 1mm³, 192 slices) will be used to measure cortical thickness (FreeSurfer 5.3). | within the 2 weeks before intervention starts; 3rd week after intervention starts (after the 6th training session); 6th week (after the 12th training session) | 
| Brain function: Updating related activation. | Functional activations. Simultaneous multislice (accelerator factor = 6), echo polar (EPI) imaging: TR/TE 785/30 ms, Fa 54°, FOV 192*192, matrix 64*64, voxels 3 mm³, 39 slices) will be measured in association with a N-back task. | within the 2 weeks before intervention starts; 3rd week after intervention starts (after the 6th training session); 6th week (after the 12th training session) | 
| Brain function: Inhibition related activation. | Functional activations. Simultaneous multislice (accelerator factor = 6), echo polar (EPI) imaging: TR/TE 785/30 ms, Fa 54°, FOV 192*192, matrix 64*64, voxels 3 mm³, 39 slices) will be measured in association with a counting stroop. | within the 2 weeks before intervention starts; 3rd week after intervention starts (after the 6th training session); 6th week (after the 12th training session) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cognitive intervention, Cognitive training, Aging, Working memory, Cognitive reserve, Brain imaging, Brain plasticity, Polymorphisms, Transfer, Inhibition, Updating