Youth-like brain activation linked with greater cognitive training gains in older adults: Insights from the ACTOP study.

This study investigates the relationship between inter-individual neurofunctional differences in older adults and cognitive training efficacy, with a specific focus on the association between youth-like task-related brain activation and improvements in working memory (WM) training. The data is part of the Attentional Control Training for Older People (ACTOP) study, 30 older adults completed 12 half-hour WM training sessions. The WM performance slope, assessed at the conclusion of sessions 1 through 6 and sessions 7 to 12, determined early- and late-stage training gains, respectively. Transfer measures were taken before (PRE), midway (MID), and after (POST) training, and the differences in MID-PRE and POST-MID on transfer tasks were used to determine early- and late-stage transfer effects, respectively. The Goodness of Fit (GOF) metric was used to quantify the similarity between each older adult's activation pattern, as measured with functional magnetic resonance imaging (fMRI), to that of a group of younger adults. GOF scores were calculated for activation during low-load (1-0back) and high-load (2-0back) N-back tasks. The results indicated that larger GOF scores in the low-load condition were associated with greater training gains in both the early and late learning stages, and that larger GOF scores in the high-load condition were associated with greater training gains during the late-stage. These findings suggest that a youth-like brain activation pattern in older adults is associated with greater cognitive training benefits, underscoring the role of inter-individual neurofunctional differences to account for variations in training outcomes among older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03532113; https://clinicaltrials.gov/ct2/show/NCT03532113.

Hippocampal Volume and Episodic Associative Memory Identify Memory Risk in Subjective Cognitive Decline Individuals in the CIMA-Q Cohort, Regardless of Cognitive Reserve Level and APOE4 Status.

BACKGROUND: Subjective cognitive decline (SCD) was proposed to identify older adults who complain about their memory but perform within a normal range on standard neuropsychological tests. Persons with SCD are at increased risk of dementia meaning that some SCD individuals experience subthreshold memory decline due to an underlying progression of Alzheimer's disease (AD). OBJECTIVE: Our main goal was to determine whether hippocampal volume and APOE4, which represent typical AD markers, predict inter-individual differences in memory performance among SCD individuals and can be used to identify a meaningful clinical subgroup. METHODS: Neuropsychological assessment, structural MRI, and genetic testing for APOE4 were administered to one hundred and twenty-five older adults over the age of 65 from the CIMAQ cohort: 66 SCD, 29 individuals with mild cognitive impairment (MCI), and 30 cognitively intact controls (CTRLS). Multiple regression models were first used to identify which factor (hippocampal volume, APOE4 allele, or cognitive reserve) best predicted inter-individual differences in a Face-name association memory task within the SCD group. RESULTS: Hippocampal volume was found to be the only and best predictor of memory performance. We then compared the demographic, clinical and cognitive characteristics of two SCD subgroups, one with small hippocampal volume (SCD/SH) and another with normal hippocampal volume (SCD/NH), with MCI and CTRLS. SCD/SH were comparable to MCI on neuropsychological tasks evaluating memory (i.e., test of delayed word recall), whereas SCD/NH were comparable to CTRLS. CONCLUSION: Thus, using hippocampal volume allows identification of an SCD subgroup with a cognitive profile consistent with a higher risk of conversion to AD.

Neural correlates of resilience to the effects of hippocampal atrophy on memory.

INTRODUCTION: Cognitive reserve can be defined as a property of the brain that enables an individual to sustain cognitive performance in spite of age-related neural changes. This study uses brain imaging to identify which cognitive reserve mechanisms protect against the detrimental effect of hippocampal atrophy on associative memory. METHODS: The study included 108 older adults from the Quebec Consortium for the early identification of Alzheimer's disease. They received a magnetic resonance imaging examination to measure memory-related activations and hippocampal volume. Participants also completed a reserve-proxy questionnaire, and received a comprehensive clinical assessment. RESULTS: Higher scores on the reserve questionnaire were associated with more activation in the right inferior temporal and left occipital fusiform gyri. The activation of the right temporal gyrus moderated the relationship between the volume of the hippocampus and face-name memory. A smaller volume was associated with weaker memory in participants with lower activation, but not in those with greater activation. DISCUSSION: Recruitment of the temporal lobe protects against the detrimental effect of hippocampal atrophy on associative memory and contributes to cognitive reserve.

Effects of Computerized Updating and Inhibition Training in Older Adults: The ACTOP Three-Arm Randomized Double-Blind Controlled Trial.

Background: Working memory (WM) capacity declines with advancing age, which impacts the ability to carry out complex cognitive activities in everyday life. Updating and inhibition processes have been identified as some of the most critical attentional control processes of WM and are linked to age-related WM decline. The general aim of the Attentional Control Training in Older People (ACTOP) study was to perform a side-by-side comparison of updating and inhibition training to examine their respective efficacy and transfer in cognitively healthy older adults. Method: The study was a three-arm, double-blind, randomized controlled trial registered with the US National Institutes of Health clinical trials registry. Ninety older adults were randomly assigned to 12 half-hour sessions of updating (N-back type exercises), inhibition (Stroop-like exercises) computerized training or active control (general knowledge quiz game). A group of thirty younger adults completed all proximal and WM transfer tasks without training to assess age-related deficits prior to training and whether training reduces these deficits. Results: Piecewise mixed models show quick improvement of performance during training for both updating and inhibition training. During updating training, the progression was more pronounced for the most difficult (3-back) than for the least (1-back) difficult level until the ninth session. Updating and inhibition training groups improved performance on all proximal and WM transfer measures but these improvements did not differ from the active control group. Younger adults outperformed older ones on all transfer tasks prior to training. However, this was no longer the case following training for two transfer tasks regardless of the training group. Conclusion: The overall results from this study suggest that attentional control training is effective in improving updating and inhibition performance on training tasks. The optimal dose to achieve efficacy is ~9 half-hour sessions and the dose effect was related to difficulty level for updating training. Despite an overall improvement of older adults on all transfer tasks, neither updating nor inhibition training provided additional improvements in comparison with the active control condition. This suggests that the efficacy of process-based training does not directly affect transfer tasks. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03532113.

Assessing the Effect of Training on the Cognition and Brain of Older Adults: Protocol for a Three-Arm Randomized Double-Blind Controlled Trial (ACTOP).

BACKGROUND: To prevent age-related cognitive impairment, many intervention programs offer exercises targeting different central cognitive processes. However, the effects of different process-based training programs are rarely compared within equivalent experimental designs. OBJECTIVE: Using a randomized double-blind controlled trial, this project aims to examine and compare the impact of 2 process-based interventions, inhibition and updating, on the cognition and brain of older adults. METHODS: A total of 90 healthy older adults were randomly assigned to 1 of 3 training conditions: (1) inhibition (Stroop-like exercises), (2) updating (N-back-type exercises), and (3) control active (quiz game exercise). Training was provided in 12 half-hour sessions over 4 weeks. First, the performance gain observed will be measured on the trained tasks. We will then determine the extent of transfer of gain on (1) untrained tasks that rely on the same cognitive process, (2) complex working memory (WM) measurements hypothesized to involve 1 of the 2 trained processes, and (3) virtual reality tasks that were designed to mimic real-life situations that require WM. We will assess whether training increases cortical volume given that the volume of the cortex is determined by cortical area and thickness in regions known to be involved in WM or changes task-related brain activation patterns measured with functional magnetic resonance imaging. Dose effects will be examined by measuring outcomes at different time points during training. We will also determine whether individual characteristics moderate the effect of training on cognitive and cerebral outcomes. Finally, we will evaluate whether training reduces the age-related deficit on transfer and brain outcomes, by comparing study participants to a group of 30 younger adults. RESULTS: The project was funded in January 2017; enrollment began in October 2017 and data collection was completed in April 2019. Data analysis has begun in June 2020 and the first results should be published by the end of 2020 or early 2021. CONCLUSIONS: The results of this study will help understand the relative efficacy of 2 attentional control interventions on the cognition and the brain of older adults, as well as the moderating role of individual characteristics on training efficiency and transfer. TRIAL REGISTRATION: ClinicalTrials.gov NCT03532113; https://clinicaltrials.gov/ct2/show/NCT03532113. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/20430.

Evidence of a Relation Between Hippocampal Volume, White Matter Hyperintensities, and Cognition in Subjective Cognitive Decline and Mild Cognitive Impairment.

OBJECTIVE: The concepts of mild cognitive impairment (MCI) and subjective cognitive decline (SCD) have been proposed to identify individuals in the early stages of Alzheimer's disease (AD), or other neurodegenerative diseases. One approach to validate these concepts is to investigate the relationship between pathological brain markers and cognition in those individuals. METHOD: We included 126 participants from the Consortium for the Early Identification of Alzheimer's disease-Quebec (CIMA-Q) cohort (67 SCD, 29 MCI, and 30 cognitively healthy controls [CH]). All participants underwent a complete cognitive assessment and structural magnetic resonance imaging. Group comparisons were done using cognitive data, and then correlated with hippocampal volumes and white matter hyperintensities (WMHs). RESULTS: Significant differences were found between participants with MCI and CH on episodic and executive tasks, but no differences were found when comparing SCD and CH. Scores on episodic memory tests correlated with hippocampal volumes in both MCI and SCD, whereas performance on executive tests correlated with WMH in all of our groups. DISCUSSION: As expected, the SCD group was shown to be cognitively healthy on tasks where MCI participants showed impairment. However, SCD's hippocampal volume related to episodic memory performances, and WMH to executive functions. Thus, SCD represents a valid research concept and should be used, alongside MCI, to better understand the preclinical/prodromal phase of AD.