The Indirect Effect of Age Group on Switch Costs Via Gray Matter Volume and Task-Related Brain Activity

Healthy aging simultaneously affects brain structure, brain function, and cognition. These effects are often investigated in isolation ignoring any relationships between them. It is plausible that age related declines in cognitive performance are the result of age-related structural and functional changes. This straightforward idea is tested in within a conceptual research model of cognitive aging. The current study tested whether age-related declines in task-performance were explained by age-related differences in brain structure and brain function using a task-switching paradigm in 175 participants. Sixty-three young and 112 old participants underwent MRI scanning of brain structure and brain activation. The experimental task was an executive context dual task with switch costs in response time as the behavioral measure. A serial mediation model was applied voxel-wise throughout the brain testing all pathways between age group, gray matter volume, brain activation and increased switch costs, worsening performance. There were widespread age group differences in gray matter volume and brain activation. Switch costs also significantly differed by age group. There were brain regions demonstrating significant indirect effects of age group on switch costs via the pathway through gray matter volume and brain activation. These were in the bilateral precuneus, bilateral parietal cortex, the left precentral gyrus, cerebellum, fusiform, and occipital cortices. There were also significant indirect effects via the brain activation pathway after controlling for gray matter volume. These effects were in the cerebellum, occipital cortex, left precentral gyrus, bilateral supramarginal, bilateral parietal, precuneus, middle cingulate extending to medial superior frontal gyri and the left middle frontal gyri. There were no significant effects through the gray matter volume alone pathway. These results demonstrate that a large proportion of the age group effect on switch costs can be attributed to individual differences in gray matter volume and brain activation. Therefore, age-related neural effects underlying cognitive control are a complex interaction between brain structure and function. Furthermore, the analyses demonstrate the feasibility of utilizing multiple neuroimaging modalities within a conceptual research model of cognitive aging

Aging Does Not Affect Brain Patterns of Repetition Effects Associated with Perceptual Priming of Novel Objects

This study examined how aging affects the spatial patterns of repetition effects associated with perceptual priming of unfamiliar visual objects. Healthy young (n = 14) and elderly adults (n = 13) viewed four repetitions of structurally possible and impossible figures while being scanned with blood oxygenation level-dependent functional magnetic resonance imaging. Although explicit recognition memory for the figures was reduced in the elder subjects, repetition priming did not differ across the two age groups. Using multivariate linear modeling, we found that the spatial networks of regions that demonstrated repetition-related increases and decreases in activity were identical in both age groups, although there was a trend for smaller magnitude repetition effects in these networks in the elder adults for objects that had been repeated thrice. Furthermore, repetition-related reductions in activity in the left inferior frontal cortex for possible objects correlated with repetition-related facilitation in reaction time across both young and elder subjects. Repetition-related increases of an initially negative response were observed for both object types in both age groups in parts of the default network, suggesting that less attention was required for processing repeated stimuli. These findings extend prior studies using verbal and semantic picture priming tasks and support the view that perceptual repetition priming remains intact in later adulthood because the same spatial networks of regions continue to show repetition-related neural plasticity across the adult life span

Examining the Multifactorial Nature of Cognitive Aging with Covariance Analysis of Positron Emission Tomography Data

Research has indicated that there may be age-related and Alzheimer's disease (AD) -related reductions in regional cerebral blood flow (rCBF) in the brain. This study explored differences in age- and AD-related rCBF patterns in the context of cognitive aging using a multivariate approach to the analysis of H215O PET data. First, an rCBF covariance pattern that distinguishes between a group of younger and older adults was identified. Individual subject's expression of the identified age-related pattern was significantly correlated with their performance on tests of memory, even after controlling for the effect of age. This finding suggests that subject expression of the covariance pattern explained additional variation in performance on the memory tasks. The age-related covariance pattern was then compared to an AD-related covariance pattern. There was little evidence that the two covariance patterns were similar, and the age-related pattern did a poor job of differentiating between cognitively-healthy older adults and those with probable AD. The findings from this study are consistent with the multifactorial nature of cognitive aging

The Impact of Age-Related Changes on Working Memory Functional Activity

This work investigated associations of age-related brain atrophy and functional neural networks identified using multivariate analyses of BOLD fMRI data in young and elder participants (young, N=37; mean age=25; elders, N=15; mean age=74). Two networks were involved in retaining increasing loads of verbal information in working memory. Network utilizations were used to test associations between function and indices of grey matter volume changes using voxel based morphometry. Global changes in brain volume were not associated with the secondary network. Lower regional grey matter volume in the left pre-central gyrus within the primary network was associated with increased secondary network utilization independent of age group. Decreased regional grey matter volume was associated with increased age only in the elders. Increased secondary network expression was associated with increased slope of reaction times across memory load, in the elders. These results support the theory of neural compensation, that elder participants recruit additional neural resources to maintain task performance in the face of age-related decreases in regional grey matter volume

Age Differences of Multivariate Network Expressions During Task-Switching and Their Associations with Behavior

The effect of aging on functional network activation associated with task-switching was examined in 24 young (age=25.2+/-2.73 years) and 23 older adults (age=65.2+/-2.65 years) using functional magnetic resonance imaging (fMRI). The study goals were to (1) identify a network shared by both young and older adults, (2) identify additional networks in each age group, and (3) examine the relationship between the networks identified and behavioral performance in task-switching. Ordinal trend covariance analysis was used to identify the networks, which takes advantage of increasing activation with greater task demand to isolate the network of regions recruited by task-switching. Two task-related networks were found: a shared network that was strongly expressed by both young and older adults and a second network identified in the young data that was residualized from the shared network. Both networks consisted of regions associated with task-switching in previous studies including the middle frontal gyrus, the precentral gyrus, the anterior cingulate, and the superior parietal lobule. Not only was pattern expression of the shared network associated with reaction time in both age groups, the difference in the pattern expression across task conditions (task-switch minus single-task) was also correlated with the difference in RT across task conditions. On the contrary, expression of the young-residual network showed a large age effect such that older adults do not increase expression of the network with greater task demand as young adults do and correlation between expression and accuracy was significant only for young adults. Thus, while a network related to RT is preserved in older adults, a different network related to accuracy is disrupted

Cortical thickness and its associations with age, total cognition and education across the adult lifespan

Early-life education (years of schooling) has been investigated in regards to cognition, health outcomes and mortality. It has been shown to confer cognitive reserve that might lessen the impact of brain pathology and its impact on cognitive and motor functioning in a variety of neurodegenerative diseases and, for instance, to influence electrical activity [Begum, T., Reza, F., Ahmed, I., & Abdullah, J. M. (2014). Influence of education level on design-induced N170 and P300 components of event related potentials in the human brain. J Integr Neurosci, 13(1), 71–88. doi:10.1142/S0219635214500058]. On the other hand, demonstrations of a direct association between education and brain-structural measures have been more equivocal and scant. The current study sought to identify univariate cortical-thickness patterns underlying education and general intelligence after adjusting for age, gender and possible in-scanner movement in 353 individuals aged 40 to 80. We followed up this idea with multivariate analyses as well. For univariate analyses, our analyses yielded no robust associations between education and general intelligence beyond confounding effects of gender, age and extraneous in-scanner movement. A subsequent multivariate analyses showed a relationship between education and regional cortical thickness with a robust pattern of negative as well as positive loadings in several right-sided brain areas, speaking to a subtle but robust distributed effect of education on cortical thickness. Cortical thickness variance that is the residual of this education-related pattern was shown to be positively associated with age and extraneous in-scanner movement. Our study thus presents a complex picture of the association of education with regional cortical thickness: education was associated with a distributed brain-wide pattern of positive as well as negative loadings with unaccounted residuals being larger for older participants. Focal regional associations beyond demographic and age covariates were not identified

White Matter Tract Covariance Patterns Predict Age-Declining Cognitive Abilities

Previous studies investigating the relationship of white matter (WM) integrity to cognitive abilities and aging have either focused on a global measure or a few selected WM tracts. Ideally, contribution from all of the WM tracts should be evaluated at the same time. However, the high collinearity among WM tracts precludes systematic examination of WM tracts simultaneously without sacrificing statistical power due to stringent multiple-comparison corrections. Multivariate covariance techniques enable comprehensive simultaneous examination of all WM tracts without being penalized for high collinearity among observations. METHOD: In this study, Scaled Subprofile Modeling (SSM) was applied to the mean integrity of 18 major WM tracts to extract covariance patterns that optimally predicted four cognitive abilities (perceptual speed, episodic memory, fluid reasoning, and vocabulary) in 346 participants across ages 20 to 79years old. Using expression of the covariance patterns, age-independent effects of white matter integrity on cognition and the indirect effect of WM integrity on age-related differences in cognition were tested separately, but inferences from the indirect analyses were cautiously made given that cross-sectional data set was used in the analysis. RESULTS: A separate covariance pattern was identified that significantly predicted each cognitive ability after controlling for age except for vocabulary, but the age by WM covariance pattern interaction was not significant for any of the three abilities. Furthermore, each of the patterns mediated the effect of age on the respective cognitive ability. A distinct set of WM tracts was most influential in each of the three patterns. The WM covariance pattern accounting for fluid reasoning showed the most number of influential WM tracts whereas the episodic memory pattern showed the least number. CONCLUSION: Specific patterns of WM tracts make significant contributions to the age-related differences in perceptual speed, episodic memory, and fluid reasoning but not vocabulary. Other measures of brain health will need to be explored to reveal the major influences on the vocabulary ability

Tracing brain amyloid-β in asymptomatic older adults relying on a memory marker for Alzheimer's disease

Recent approaches to the early diagnosis of Alzheimer’s disease (AD) are aimed at detecting neuropathological signatures of this type of dementia in still healthy older adults. Should these efforts prove fruitful, strategies then focus on identifying the cognitive and functional decline that ensue. These approaches have proved both little effective and costly. In the present study, we investigated the hypothesis that effective cognitive markers for AD could help detect among still healthy older adults who would have likely started to accumulate the neuropathological changes pursued by costly neuroimaging procedures. A sample of 39 healthy older adults was recruited and assessed with an extensive neuropsychological and neuroimaging protocol. As the memory marker, we used the Visual Short-Term Memory Binding Task. Using existing data, participants were divided in two groups depending on whether or not they displayed the typical binding profile seen in AD subjects (i.e., strong binders – SB and weak binders - WB). The results show that in addition to the increased binding cost seen in WB, SB and WB could only be differentiated by the amount of Amyloid- accumulated in brain regions known to be involved in this cognitive function. No other neuropsychological tests proved informative, and neither volumetric nor cortical thickness metrics provided meaningful neuropathological signals. Our findings have significant implications for our understanding of the transition from normal ageing to preclinical AD and methodological approaches currently used to ascertain it. These are discussed at length

Functional Network Mediates Age-Related Differences in Reaction Time: A Replication and Extension Study

INTRODUCTION: A functional activation (i.e., ordinal trend) pattern was previously identified in both young and older adults during task-switching performance, the expression of which correlated with reaction time. The current study aimed to (1) replicate this functional activation pattern in a new group of fMRI activation data, and (2) extend the previous study by specifically examining whether the effect of aging on reaction time can be explained by differences in the activation of the functional activation pattern. METHOD: A total of 47 young and 50 older participants were included in the extension analysis. Participants performed task-switching as the activation task and were cued by the color of the stimulus for the task to be performed in each block. To test for replication, two approaches were implemented. The first approach tested the replicability of the predictive power of the previously identified functional activation pattern by forward applying the pattern to the Study II data and the second approach was rederivation of the activation pattern in the Study II data. RESULTS: Both approaches showed successful replication in the new data set. Using mediation analysis, expression of the pattern from the first approach was found to partially mediate age-related effects on reaction time such that older age was associated with greater activation of the brain pattern and longer reaction time, suggesting that brain activation efficiency (defined as "the rate of activation increase with increasing task difficulty" in Neuropsychologia 47, 2009, 2015) of the regions in the Ordinal trend pattern directly accounts for age-related differences in task performance. DISCUSSION: The successful replication of the functional activation pattern demonstrates the versatility of the Ordinal Trend Canonical Variates Analysis, and the ability to summarize each participant's brain activation map into one number provides a useful metric in multimodal analysis as well as cross-study comparisons

A task-invariant cognitive reserve network

The concept of cognitive reserve (CR) can explain individual differences in susceptibility to cognitive or functional impairment in the presence of age or disease-related brain changes. Epidemiologic evidence indicates that CR helps maintain performance in the face of pathology across multiple cognitive domains. We therefore tried to identify a single, “task-invariant” CR network that is active during the performance of many disparate tasks. In imaging data acquired from 255 individuals age 20–80 while performing 12 different cognitive tasks, we used an iterative approach to derive a multivariate network that was expressed during the performance of all tasks, and whose degree of expression correlated with IQ, a proxy for CR. When applied to held out data or forward applied to fMRI data from an entirely different activation task, network expression correlated with IQ. Expression of the CR pattern accounted for additional variance in fluid reasoning performance over and above the influence of cortical thickness, and also moderated between cortical thickness and reasoning performance, consistent with the behavior of a CR network. The identification of a task-invariant CR network supports the idea that life experiences may result in brain processing differences that might provide reserve against age- or disease-related changes across multiple tasks