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BackgroundTo 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. ObjectiveUsing 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. MethodsA 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. ResultsThe 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. ConclusionsThe 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 RegistrationClinicalTrials.gov NCT03532113; https://clinicaltrials.gov/ct2/show/NCT03532113 International Registered Report Identifier (IRRID)DERR1-10.2196/20430

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. [ABSTRACT FROM AUTHOR]

Background: Little is known regarding the dose‐response function in multidomain interventions for dementia prevention. Method: The Multidomain Alzheimer Preventive Trial is a 3‐year randomized controlled trial comprising cognitive training, physical activity, nutrition, and omega‐3 polyunsaturated fatty acids for at‐risk older adults. The dose delivered (number of sessions attended) was modeled against global cognition, memory, and fluency in 749 participants. Interaction effects were assessed for age, sex, education, dementia score (CAIDE), frailty score, and apolipoprotein E (APOE) ε4 status. Results: The dose‐response models were non‐linear functions indicating benefits up to about 12 to 14 training hours or 15 to 20 multidomain sessions followed by a plateau. Participants who benefited from a higher dose included women, younger participants, frail individuals, and those with lower education or lower risk of dementia. Discussion: The non‐linear function indicates that a higher dose is not necessarily better in multidomain interventions. The optimal dose was about half of the potentially available sessions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Brain hyperactivation — defined as higher level of activation compared to controls — was suggested as a very early signature of prodromal Alzheimer's disease (AD), which would gradually decrease with progression to dementia. Longitudinal studies with people who have mild cognitive impairment (MCI) and subjective cognitive decline (SCD) can be used to capture the temporal dynamics and inter‐individual differences of these very early activation changes. Here, we aimed to identify the temporal trajectory of task‐related activation in participants with SCD and MCI from the CIMA‐Q cohort, which has data collected at multiple time‐points. We thus identified subgroups based on their common activation trajectory and characterized subgroups defined from the activation trajectory. Method: The study included 53 older participants (40 SCD; 13 MCI) from the CIMA‐Q cohort with neuroimaging data collected over at least two time‐points (66‐85 years old; 36 women, 17 men). An fMRI examination was done every two years (2‐4 time‐points; average follow‐up: 3.2 years). Task‐related activation was measured during an associative memory encoding task. Group‐based trajectory models were estimated to identify homogeneous groups of participants based on activation trajectories in the hippocampus and in regions from the cortical signature of AD. Groups defined based on activation trajectories were then compared using Apolipoprotein‐ε4 (ApoE4), baseline cognition and hippocampal volume. Result: Two different trajectories of activation were identified: Trajectory 1 was found in several cortical regions and was characterized by a high level of initial activation, which decreased over time. Trajectory 2 was characterized by a lower activation level, which remained stable over time or increased slightly on time‐point 4. Smaller hippocampal volume and ApoE4 were associated with Trajectory 1 for the left angular gyrus, and left hippocampal and right middle temporal gyrus activation, respectively. Conclusion: An inverted U‐shape trajectory was found with high activation followed by gradually decreasing activation in AD‐signature regions. This trajectory was associated with smaller hippocampal volume and/or the presence of ApoE4 allele, both of which are biomarkers that increase the likelihood of developing AD. This finding supports the hypothesis that the inverted U‐shape trajectory of hyperactivation could be an index of prodromal AD. [ABSTRACT FROM AUTHOR]

Background: Hyperactivation is commonly observed in prodromal Alzheimer's disease (AD). It is however unknown if it relates to functional network dysfunction, and how hyperactivation‐networks relate to cognitive impairment. We used seed‐based connectivity to assess differences in correlations between activation of hyperactive regions, whole‐brain task‐related activation, and memory performance in persons with subjective cognitive decline plus (SCD+) and mild cognitive impairment (MCI). Method: Data from 108 participants from the CIMA‐Q cohort were used in this study: 28 participants with SCD+ which presented with memory complaint and worry in addition to small hippocampal volume and/or were APOE4 carriers, 26 participants with MCI and 54 were healthy controls (HC). Task‐related activation was measured while participants memorized 78 pictures and their location in a four‐position grid. Multivariate seed‐partial least squares (seed‐PLS) analysis was used to identify latent variables (LVs) that assess between‐group differences and similarities in the three‐way association between 1) activation in hyperactive regions of interest (ROIs: left hippocampus, right inferior temporal gyrus (riTG), left superior parietal lobule (lsPL)), 2) whole‐brain activation associated with associative memory encoding, and 3) subsequent associative memory performance. Significance of the seed‐PLS effects were assessed with permutation testing and boostraps. Result: Three LVs were significant (p < 0.05). LV1 (32.11 % of covariance explained) accounted for group similarities in the correlation between activity in all ROIs and activity in the fronto‐parietal and default mode networks. Interestingly, left hippocampus activity did not correlate in SCD+. LV2 (19.17 % of covariance explained) identified a network that was correlated with left hippocampal activity in all three groups; however, left hippocampal activity correlated with better memory in HC but with poorer memory in SCD+. LV3 (10.91 % of covariance explained) identified a network that was positively correlated to lsPL activity in SCD+, and correlated with seed activity in all ROIs and poorer memory performance in MCI. Conclusion: Hyperactivation is associated with latent patterns of connectivity in prodromal AD, but different hyperactivation‐network associations relate to memory in SCD+ and MCI. Hyperactivation could serve as an early marker of network dysfunction in AD, and reflect the incoming cognitive symptomatology associated with the disease. [ABSTRACT FROM AUTHOR]