Improving Neurological Health in Aging Via Neuroplasticity-Based Computerized Exercise: Protocol for a Randomized Controlled Trial.

BACKGROUND: Our current understanding of how computerized brain training drives cognitive and functional benefits remains incomplete. This paper describes the protocol for Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE), a randomized controlled trial in healthy older adults designed to evaluate whether brain training improves cholinergic signaling. OBJECTIVE: INHANCE evaluates whether 2 computerized training programs alter acetylcholine binding using the vesicular acetylcholine transporter ligand [18F] fluoroethoxybenzovesamicol ([18F] FEOBV) and positron emission tomography (PET). METHODS: In this phase IIb, prospective, double-blind, parallel-arm, active-controlled randomized trial, a minimum of 92 community-dwelling healthy adults aged 65 years and older are randomly assigned to a brain training program designed using the principles of neuroplasticity (BrainHQ by Posit Science) or to an active control program of computer games designed for entertainment (eg, Solitaire). Both programs consist of 30-minute sessions, 7 times per week for 10 weeks (35 total hours), completed remotely at home using either loaned or personal devices. The primary outcome is the change in FEOBV binding in the anterior cingulate cortex, assessed at baseline and posttest. Exploratory cognitive and behavioral outcomes sensitive to acetylcholine are evaluated before, immediately after, and 3 months following the intervention to assess the maintenance of observed effects. RESULTS: The trial was funded in September 2019. The study received approval from the Western Institutional Review Board in October 2020 with Research Ethics Board of McGill University Health Centre and Health Canada approvals in June 2021. The trial is currently ongoing. The first participant was enrolled in July 2021, enrollment closed when 93 participants were randomized in December 2023, and the trial will conclude in June 2024. The study team will be unblinded to conduct analyses after the final participant exits the study. We expect to publish the results in the fourth quarter of 2024. CONCLUSIONS: There remains a critical need to identify effective and scalable nonpharmaceutical interventions to enhance cognition in older adults. This trial contributes to our understanding of brain training by providing a potential neurochemical explanation of cognitive benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT04149457; https://clinicaltrials.gov/ct2/show/NCT04149457. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59705.

Negative global metacognitive biases are associated with depressive and posttraumatic stress disorder symptoms and improve with targeted or game-based cognitive training.

OBJECTIVE: Metacognition is disrupted in several clinical populations. One aspect of metacognition, global metacognitive bias (difference between objective and self-reported abilities), has shown to be particularly relevant to clinical functioning. However, previous studies of global metacognitive biases in populations with elevated depressive/posttraumatic stress disorder (PTSD) symptoms have not measured objective and self-reported abilities relative to normative samples, limiting the quantification of biases. Additionally, few studies have examined whether cognitive interventions can improve metacognitive biases or how this relates to depressive/PTSD symptom severity. METHOD: A total of 84 participants with mild traumatic brain injury (77% veterans) performed PTSD and depression assessments along with self-reported and objective measures of global cognition. Age-adjusted norm-based z scores were used for self-reported and objective cognition, and bias was calculated by subtracting objective minus self-report scores. Participants then received 13 weeks of targeted cognitive training or entertainment games training (both providing performance feedback). Participants were assessed at baseline, immediately posttraining, and 3 months posttraining. RESULTS: We found large negative metacognitive biases in those with clinically significant severity of depressive symptoms (z score difference = -1.77), PTSD symptoms (-1.47), and depressive + PTSD symptoms (-2.29). Metacognitive biases improved after both targeted and entertainment training and was associated with reductions in depressive/PTSD symptom severity (r = -.41/-.42, respectively), led by the entertainment training group (r = -.54/-.46, respectively). CONCLUSIONS: These findings show that clinically significant severity of depressive/PTSD symptoms is associated with substantial negative global metacognitive biases and preliminarily suggests that cognitive training may improve these biases and depressive/PTSD symptom severity. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Effects of Computerized Cognitive Training in Older Adults' Cognitive Performance and Biomarkers of Structural Brain Aging.

OBJECTIVES: Cognitive training (CT) has been investigated as a means of delaying age-related cognitive decline in older adults. However, its impact on biomarkers of age-related structural brain atrophy has rarely been investigated, leading to a gap in our understanding of the linkage between improvements in cognition and brain plasticity. This study aimed to explore the impact of CT on cognitive performance and brain structure in older adults. METHODS: One hundred twenty-four cognitively normal older adults recruited from 2 study sites were randomly assigned to either an adaptive CT (n = 60) or a casual game training (active control, AC, n = 64). RESULTS: After 10 weeks of training, CT participants showed greater improvements in the overall cognitive composite score (Cohen's d = 0.66, p < .01) with nonsignificant benefits after 6 months from the completion of training (Cohen's d = 0.36, p = .094). The CT group showed significant maintenance of the caudate volume as well as significant maintained fractional anisotropy in the left internal capsule and in left superior longitudinal fasciculus compared to the AC group. The AC group displayed an age-related decrease in these metrics of brain structure. DISCUSSION: Results from this multisite clinical trial demonstrate that the CT intervention improves cognitive performance and helps maintain caudate volume and integrity of white matter regions that are associated with cognitive control, adding to our understanding of the changes in brain structure contributing to changes in cognitive performance from adaptive CT. CLINICAL TRIAL REGISTRATION: NCT03197454.