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Functional magnetic resonance imaging (fMRI) was used to assess the effect of cognitive training on brain activation as a function of the learning phase and level of education. Forty older adults with subjective cognitive decline (SCD) received 6 1-hour memory training sessions with the method of loci. Brain imaging (N = 29) was measured during word list encoding and retrieval before training (PRE), after 3 training sessions (POST3), and after 6 training sessions (POST6). Participants showed increased activation of the left inferior pre-frontal gyrus from PRE to POST6 during encoding and reduced bilateral frontostriatal activation from PRE to POST3 during retrieval, regardless of education. Activation changes from PRE to POST3 varied as a function of education in 2 regions of the right temporal lobe: participants with lower education showed increased activation, while those with higher education showed decreased activation. These regions were initially less active in people with lower education. Results suggest a strategic shift in people with lower education and expertise building in those with higher education, along with a restoration of initial education-related differences.

Brain maintenance refers to the fact that some older adults experience few age-related changes in the brain, which helps maintain their cognition. The goal of this study was to assess maintenance of white matter integrity by testing whether reserve proxies, measuring factors associated to a stimulating lifestyle, affect the maintenance of white matter integrity. Another goal was to measure whether maintenance of white matter integrity explains inter-individual differences in working memory (WM). Forty-one cognitively healthy older adults received a structural magnetic resonance imaging (MRI) examination to measure white matter lesions. They completed an n-back WM task with different loads (1- & 2-back), along with a questionnaire on their lifestyle. There was a positive association between age and volume of white matter lesions. This association was no longer found in those with higher scores on reserve proxies. In addition, smaller volumes of white matter lesions were associated with better performance than expected for age in the 1-back WM task. Better WM is associated with the maintenance of white matter integrity in older adults, which in turn is linked to measures reflecting a stimulating lifestyle throughout life.

The risk of developing Alzheimer's disease dementia is higher in females compared to males and is greater in individuals with subjective cognitive decline and mild cognitive impairment than in healthy controls. We used a multivariate behavioral partial least square correlation analysis to examine how relationships between memory-related activation and associative memory performance vary as a function of sex and clinical status. This was assessed in 182 participants from the Consortium for the Early Identification of Alzheimer's Disease-Quebec cohort, which were stratified according to sex (Male, Female) and clinical status (healthy controls, subjective cognitive decline, mild cognitive impairment). We found 6 significant latent variables mainly expressing: (1) overall sex differences; (2) between-sex differences according to clinical status; and (3) within-sex differences according to clinical status in relationships between whole-brain memory-related activation and memory performance. These patterns of activation mostly involved the default mode and fronto-parietal networks. Our results have implication in understanding the macro-scale functional processes possibly contributing to the higher risk of cognitive decline in females compared to males in the context of aging and early Alzheimer's disease.

Little is known regarding the dose-response function in multidomain interventions for dementia prevention.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.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.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.

Brain maintenance refers to the fact that some older adults experience few age-related changes in the brain, which helps maintain their cognition. Objectives. The goals of this study are to assess maintenance of white matter integrity, test whether lifestyle factors affect the maintenance of white matter integrity, and measure whether maintenance of white matter integrity explains inter-individual differences in working memory (WM). Methods. Forty-one cognitively healthy older adults received a structural magnetic resonance imaging (MRI) examination to measure white matter lesions. They completed an n-back WM task with different loads (1- & 2-back), along with a questionnaire on their lifestyle. Results. There was a positive association between age and volume of white matter lesions. This association was no longer found in those with higher lifestyle scores. In addition, smaller volumes of white matter lesions were associated with better performance than expected for age in the 1-back WM task. Discussion. Better WM in older adults is associated with maintenance of white matter integrity, which in turn is linked to a more stimulating lifestyle throughout life.

Highlights • Hyperactivation relates to memory-related network dysfunction in SCD+ and MCI. • Hippocampal hyperactivation and connectivity relate to worst memory performance. • In contrast, neocortical hyperactivation and connectivity may reflect compensation., The goal of this study was to assess how task-related hyperactivation relates to brain network dysfunction and memory performance in individuals at risk of Alzheimer’s disease (AD). Eighty participants from the CIMA-Q cohort were included, of which 28 had subjective cognitive decline plus (SCD+), as they had memory complaints and worries in addition to a smaller hippocampal volume and/or an APOE4 allele, 26 had amnestic mild cognitive impairment (MCI) and 26 were healthy controls without memory complaints. Functional magnetic resonance imaging (fMRI) activation was measured during an object-location memory task. Seed-partial least square analyses (seed-PLS) were conducted in controls and in the SCD+/MCI groups to yield sets of orthogonal latent variables (LVs) assessing the triple association between: i) seed activity in brain regions found to be hyperactive in individuals at risk of AD (left hippocampus, left superior parietal lobule, right inferior temporal lobe), ii) latent patterns of whole-brain task-related activation, and iii) associative memory performance. Three LVs in the SCD+ and MCI groups (67.88% of total covariance explained) and two LVs in the controls (77.85% of total covariance explained) were significant. While controls and SCD+/MCI groups shared a common pattern of memory-related connectivity, patterns of hyperactivation-networks interactions were unique to the clinical groups. Interestingly, higher hippocampal connectivity was associated with poorer memory performance whereas higher neocortical connectivity predicted better memory performance in SCD+ and MCI groups. Our data provides empirical evidence that early dysfunction in brain activation and connectivity is present in the very early stages of AD and offers new insights on the relationship between functional brain alterations and memory performance.

The goal of this study was to identify the brain mechanisms underlying cognitive reserve using a parametric n-back working memory (WM) task in a sample of healthy older adults. We first identified the WM-related activations associated with years of education and then tested whether these activations mitigated the detrimental impact of age on cognition. Thirty-nine older adults received a magnetic resonance imaging examination while completing an n-back task with different levels of WM load (0-, 1- vs. 2-back). Results show that more education is associated with lower activation of the left medial superior frontal gyrus (BA8) in the 1-back condition and a greater activation of the right caudate nucleus in the 2-back condition. The caudate and frontal activations are task-positive and task-negative regions, respectively. Moderation analyses indicate that the effect of age on performance is less detrimental in participants with higher caudate activation in the 2-back condition. Overall, these results suggest that cognitive reserve is explained by a superior ability to flexibly engage greater or novel activation as cognitive demand increases.

Highlights • Higher reserve scores relate to activation of the right inferior temporal gyri. • Higher reserve scores relate to activation of the left occipital fusiform gyri. • The temporal activation moderates the effect of hippocampal volume on memory. • Recruitment of the temporal lobe protects against hippocampal atrophy. • Temporal activation supports cognitive reserve to sustains memory performance., 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.

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

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. CLINICALTRIAL ClinicalTrials.gov NCT03532113; https://clinicaltrials.gov/ct2/show/NCT03532113 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/20430

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.

Attentional control declines in older adults and is paralleled by changes in event-related brain potentials (ERPs). The N200 is associated with attentional control, thus training-related improvements in attentional control should be paralleled by enhancements to the N200. Older participants were randomly assigned to 1 of 3 groups, which focused on training different levels of attentional control: (1) single-task training (single), where participants trained on 2 tasks in isolation; (2) fixed divided attention training (fixed), where participants trained on 2 tasks simultaneously; and (3) variable divided attention training (variable), where participants trained on 2 tasks simultaneously but were instructed to alternatively prioritize each of the 2 tasks. After training, the amplitude of the N200 wave increased in dual-task conditions for the variable group, and this enhancement was correlated with improved dual-task performance. Participants in the variable group also had the greatest improvement in the ability to modulate their allocation of attention in accordance with task instructions to the less salient and less complex of the 2 tasks. Training older adults to modulate their division of attention between tasks improves neural functions associated with attentional control of the trained tasks.

The aim of this study was to examine the relationships between educational attainment, regional grey matter volume, and functional working memory-related brain activation in older adults. The final sample included 32 healthy older adults with 8 to 22 years of education. Structural magnetic resonance imaging (MRI) was used to measure regional volume and functional MRI was used to measure activation associated with performing an n-back task. A positive correlation was found between years of education and cortical grey matter volume in the right medial and middle frontal gyri, in the middle and posterior cingulate gyri, and in the right inferior parietal lobule. The education by age interaction was significant for cortical grey matter volume in the left middle frontal gyrus and in the right medial cingulate gyrus. In this region, the volume loss related to age was larger in the low than high-education group. The education by age interaction was also significant for task-related activity in the left superior, middle and medial frontal gyri due to the fact that activation increased with age in those with higher education. No correlation was found between regions that are structurally related with education and those that are functionally related with education and age. The data suggest a protective effect of education on cortical volume. Furthermore, the brain regions involved in the working memory network are getting more activated with age in those with higher educational attainment.

Previous studies have shown greater atrophy in grey and white matter of various brain regions in patients with Parkinson’s disease with mild cognitive impairment than in those without. These anatomical differences likely account for the distinct clinical profiles observed between those groups, but do not account for the evolution of regional brain degradation observed as the disease evolves. Although we have shown recently that cortical thinning correlates significantly more with disease duration in Parkinson’s patients with mild cognitive impairment than in those without, to the best of our knowledge no study to date has explored this longitudinally. The present study investigated the longitudinal changes of the cortical and subcortical grey matter in patients with Parkinson’s disease with and without mild cognitive impairment. Additionally, these two groups were compared with healthy controls. We found a higher rate of cortical thinning in the temporal, occipital, parietal and supplementary motor area, in patients with Parkinson’s disease with mild cognitive impairment compared with both cognitively stable patients and healthy controls. On the other hand cognitively stable patients had only one lateral occipital and one fusiform cluster with increased rate of thinning compared with healthy individuals. Correlating the rate of change of cortical thickness with the results of Montreal Cognitive Assessment scores revealed significant thinning associated with cognitive decline in the group of all patients, in similar regions including temporal and medial occipital lobe. Finally, a significant decrease in the volume of the amygdala and nucleus accumbens was observed specifically in patients with Parkinson’s disease with mild cognitive impairment. These results indicate that the early presence of mild cognitive impairment in patients with Parkinson’s disease is associated with a faster rate of grey matter thinning in various cortical regions as well as a significant diminishment of limbic subcortical structures. This specific pattern of brain degradation associated with the early presence of mild cognitive impairment might serve as a marker of development toward dementia. * Abbreviation : MCI : mild cognitive impairment

Hyperactivation, which is defined as a higher level of activation in patients compared to cognitively unimpaired older adults (controls; CTL), might represent an early signature of Alzheimer's Disease (AD). The goal of this study was to assess the presence and location of hyperactivation in individuals with mild cognitive impairment (MCI) who were later diagnosed with dementia, examine how hyperactivation changes longitudinally, and whether it is related to time before dementia. Forty participants, 26 with MCI and 14 CTL were enrolled in the study. Magnetic resonance imaging was used to measure functional activation while participants encoded word-pairs as well as cortical thickness and regional brain volume at study entry (Y0) and two years later (Y2). Clinical follow-up was completed every two years following study entry to identify progressors (pMCI), that is, individuals who later received a diagnosis of dementia. Task-related activation was assessed in pMCI in both hippocampi and in regions showing greater cortical thinning from Y0 to Y2 compared to CTLs. Hyperactivation was found in pMCI individuals in the right supramarginal gyrus. Persons with pMCI also showed hypoactivation in the left hippocampus and left pars opercularis. Both hyper- and hypoactivation were present at Y0 and Y2 and did not change longitudinally. Activation was not associated with time before dementia diagnosis. Smaller volume and thinner cortical thickness were associated with shorter time to diagnosis in the left hippocampus and left pars opercularis. In conclusion, hyperactivation was found in individuals who later progressed to dementia, confirming that it might represent an early biomarker to identify individuals in the prodromal phase of AD and that its understanding could contribute to elucidate the key brain mechanisms that precede dementia., Highlights • Hyperactivation of the right parietal region was found in MCI progressors. • Hypoactivation was found in the hippocampal and frontal regions. • This overall pattern was specific to MCI who progressed to dementia.

Subjects with mild cognitive impairment are at risk of developing Alzheimer's disease. Cognitive stimulation is an emerging intervention in the field of neurology and allied sciences, having already been shown to improve cognition in subjects with mild cognitive impairment. Yet no studies have attempted to unravel the brain mechanisms that support such improvement. This study uses functional magnetic resonance imaging to measure the effect of memory training on brain activation in older adults with mild cognitive impairment and to assess whether it can reverse the brain changes associated with mild cognitive impairment. Brain activation associated with verbal encoding and retrieval was recorded twice prior to training and once after training. In subjects with mild cognitive impairment, increased activation was found after training within a large network that included the frontal, temporal and parietal areas. Healthy controls showed mostly areas of decreased activation following training. Comparison with pre-training indicated that subjects with mild cognitive impairment used a combination of specialized areas; that is, areas activated prior to training and new alternative areas activated following training. However, only activation of the right inferior parietal lobule, a new area of activation, correlated with performance. Furthermore, the differences between the brain activation patterns of subjects with mild cognitive impairment and those of healthy controls were attenuated by training in a number of brain regions. These results indicate that memory training can result in significant neural changes that are measurable with brain imaging. They also show that the brains of people with mild cognitive impairment remain highly plastic.

Discovered for its role in blood coagulation, vitamin K (VK) is emerging as an important nutrient for brain function and cognition. In brain, VK participates in sphingolipid metabolism and activates proteins with cell sigaling actions (Gas6 and protein S) and involved in vascular function (proteins C and S). Recent reports also point to beneficial effects of VK in cognition, notably during aging. To extend our understanding of the action of VK in brain, we investigated, using functional magnetic resonance imaging, the relationship between VK status and brain activity in healthy older adults. Brain activity was investigated in nine healthy older adults using an episodic memory paradigm that involves memorizing pairs of semantically unrelated concrete words (encoding) and indicating in a following block (retrieval) whether words had been presented during encoding (item memory) and whether they were presented as a pair (associative memory).VK status was based on fasting phylloquione concentration (by HPLC). ...