Mapping of Structure-Function Age-Related Connectivity Changes on Cognition Using Multimodal MRI.

The relationship between age-related changes in brain structural connectivity (SC) and functional connectivity (FC) with cognition is not well understood. Furthermore, it is not clear whether cognition is represented via a similar spatial pattern of FC and SC or instead is mapped by distinct sets of distributed connectivity patterns. To this end, we used a longitudinal, within-subject, multimodal approach aiming to combine brain data from diffusion-weighted MRI (DW-MRI), and functional MRI (fMRI) with behavioral evaluation, to better understand how changes in FC and SC correlate with changes in cognition in a sample of older adults. FC and SC measures were derived from the multimodal scans acquired at two time points. Change in FC and SC was correlated with 13 behavioral measures of cognitive function using Partial Least Squares Correlation (PLSC). Two of the measures indicate an age-related change in cognition and the rest indicate baseline cognitive performance. FC and SC-cognition correlations were expressed across several cognitive measures, and numerous structural and functional cortical connections, mainly cingulo-opercular, dorsolateral prefrontal, somatosensory and motor, and temporo-parieto-occipital, contributed both positively and negatively to the brain-behavior relationship. Whole-brain FC and SC captured distinct and independent connections related to the cognitive measures. Overall, we examined age-related function-structure associations of the brain in a comprehensive and integrated manner, using a multimodal approach. We pointed out the behavioral relevance of age-related changes in FC and SC. Taken together, our results highlight that the heterogeneity in distributed FC and SC connectivity patterns provide unique information about the variable nature of healthy cognitive aging.

Moderating Effect of Cortical Thickness on BOLD Signal Variability Age-Related Changes.

The time course of neuroanatomical structural and functional measures across the lifespan is commonly reported in association with aging. Blood oxygen-level dependent signal variability, estimated using the standard deviation of the signal, or "BOLDSD," is an emerging metric of variability in neural processing, and has been shown to be positively correlated with cognitive flexibility. Generally, BOLDSD is reported to decrease with aging, and is thought to reflect age-related cognitive decline. Additionally, it is well established that normative aging is associated with structural changes in brain regions, and that these predict functional decline in various cognitive domains. Nevertheless, the interaction between alterations in cortical morphology and BOLDSD changes has not been modeled quantitatively. The objective of the current study was to investigate the influence of cortical morphology metrics [i.e., cortical thickness (CT), gray matter (GM) volume, and cortical area (CA)] on age-related BOLDSD changes by treating these cortical morphology metrics as possible physiological confounds using linear mixed models. We studied these metrics in 28 healthy older subjects scanned twice at approximately 2.5 years interval. Results show that BOLDSD is confounded by cortical morphology metrics. Respectively, changes in CT but not GM volume nor CA, show a significant interaction with BOLDSD alterations. Our study highlights that CT changes should be considered when evaluating BOLDSD alternations in the lifespan.

Individual Differences in Developmental Change: Quantifying the Amplitude and Heterogeneity in Cognitive Change across Old Age.

It is well known that cognitive decline in older adults is of smaller amplitude in longitudinal than in cross-sectional studies. Yet, the measure of interest rests generally with aggregated group data. A focus on individual developmental trajectories is rare, mainly because it is difficult to assess intraindividual change reliably. Individual differences in developmental trajectories may differ quantitatively (e.g., larger or smaller decline) or qualitatively (e.g., decline vs improvement), as well as in the degree of heterogeneity of change across different cognitive domains or different tasks. The present paper aims at exploring, within the Geneva Variability Study, individual change across several cognitive domains in 92 older adults (aged 59-89 years at baseline) over a maximum of seven years and a half. Two novel, complementary methods were used to explore change in cognitive performance while remaining entirely at the intra-individual level. A bootstrap based confidence interval was estimated, for each participant and for each experimental condition, making it possible to define three patterns: stability, increase or decrease in performance. Within-person ANOVAs were also conducted for each individual on all the tasks. Those two methods allowed quantifying the direction, the amplitude and the heterogeneity of change for each individual. Results show that trajectories differed widely among individuals and that decline is far from being the rule.

Intra-Individual Variability from a Lifespan Perspective: A Comparison of Latency and Accuracy Measures.

Within-task variability across trials (intra-individual variability (IIV)) has been mainly studied using latency measures but rarely with accuracy measures. The aim of the Geneva Variability Study was to examine IIV in both latency and accuracy measures of cognitive performance across the lifespan, administering the same tasks to children, younger adults, and older adults. Six processing speed tasks (Response Time (RT) tasks, 8 conditions) and two working memory tasks scored in terms of the number of correct responses (Working Memory (WM)-verbal and visuo-spatial, 6 conditions), as well as control tasks, were administered to over 500 individuals distributed across the three age periods. The main questions were whether age differences in IIV would vary throughout the lifespan according (i) to the type of measure used (RTs vs. accuracy); and (ii) to task complexity. The objective of this paper was to present the general experimental design and to provide an essentially descriptive picture of the results. For all experimental tasks, IIV was estimated using intra-individual standard deviation (iSDr), controlling for the individual level (mean) of performance and for potential practice effects. As concerns RTs, and in conformity with a majority of the literature, younger adults were less variable than both children and older adults, and the young children were often the most variable. In contrast, IIV in the WM accuracy scores pointed to different age trends-age effects were either not observed or, when found, they indicated that younger adults were the more variable group. Overall, the findings suggest that IIV provides complementary information to that based on a mean performance, and that the relation of IIV to cognitive development depends on the type of measure used.

On the Importance of Intraindividual Variability in Cognitive Development.

Developmental cognitive psychology (as well as cognitive psychology in general) has a long-standing tradition to ignore all variations other than age, as if individual variations were only measurement error or noise[...].

Leisure Activities and Change in Cognitive Stability: A Multivariate Approach.

Aging is traditionally associated with cognitive decline, attested by slower reaction times and poorer performance in various cognitive tasks, but also by an increase in intraindividual variability (IIV) in cognitive performance. Results concerning how lifestyle activities protect from cognitive decline are mixed in the literature and all focused on how it affects mean performance. However, IIV has been proven to be an index more sensitive to age differences, and very little is known about the relationships between lifestyle activities and change in IIV in aging. This longitudinal study explores the association between frequency of physical, social, intellectual, artistic, or cultural activities and age-related change in various cognitive abilities, considering both mean performance and IIV. Ninety-six participants, aged 64-93 years, underwent a battery of cognitive tasks at four measurements over a seven-year period, and filled out a lifestyle activity questionnaire. Linear multilevel models were used to analyze the associations between change in cognitive performance and five types of activities. Results showed that the practice of leisure activities was more strongly associated with IIV than with mean performance, both when considering overall level and change in performance. Relationships with IIV were dependent of the cognitive tasks considered and overall results showed protective effects of cultural, physical and intellectual activities on IIV. These results underline the need for considering IIV in the study of age-related cognitive change.

Intelligence and Cognitive Development: Three Sides of the Same Coin.

Research on intelligence, mainly based on correlational and factor-analytical work, research on cognitive development, and research in cognitive psychology are not to be opposed as has traditionally been the case, but are pursuing the same goal, that is, understand how the human being adapts to his/her own, complex environment. Each tradition of research has been focusing on one source of variation, namely situational differences for cognitive psychology, individual differences for psychometrics, and age differences for developmental psychology, while usually neglecting the two other sources of variation. The present paper compares those trends of research with respect to the constructs of fluid intelligence, working memory, processing speed, inhibition, and executive schemes. Two studies are very briefly presented to support the suggestion that tasks issued from these three traditions are very similar, if not identical, and that theoretical issues are also similar. We conclude in arguing that a unified vision is possible, provided one is (a) interested in the underlying processes and not only in the experimental variations of conditions; (b) willing to adopt a multidimensional view according to which few general mechanisms are at work, such as working memory or processing capacity, inhibition, and executive schemes; and (c) granting a fundamental role to individual differences.

Dispersion in cognitive functioning: Age differences over the lifespan.

INTRODUCTION: A growing body of research suggests that intraindividual variability (IIV) may bring specific information on cognitive functioning, additional to that provided by the mean. The present paper focuses on dispersion, that is IIV across tasks, and its developmental trend across the lifespan. METHOD: A total of 557 participants (9-89 years) were administered a battery of response time (RT) tasks and of working memory (WM) tasks. Dispersion was analyzed separately for the two types of tasks. RESULTS: Dispersion across RT tasks showed a U-shaped age differences trend, young adults being less variable than both children and older adults. Dispersion across WM tasks (using accuracy scores) presented an opposite developmental trend. A cluster analysis revealed a group of individuals showing relatively little dispersion and good overall performance (faster in RTs and better in WM), contrasted with a group of individuals showing a large dispersion in the RT tasks as well as poorer overall performance. All young adults were grouped in the first cluster; children and older adults were distributed in both clusters. CONCLUSION: It is concluded that (a) across-task IIV is relatively large in the entire sample and should not be neglected, (b) children and older adults show a larger dispersion than young adults, but only as far as the RT tasks are concerned,

Working memory and intraindividual variability in processing speed: A lifespan developmental and individual-differences study.

Working memory (WM) and intraindividual variability (IIV) in processing speed are both hypothesized to reflect general attentional processes. In the present study, we aimed at exploring the relationship between WM capacity and IIV in reaction times (RTs) and its possible variation with development across the lifespan. Two WM tasks and six RT tasks of varying complexity were analyzed in a sample of 539 participants, consisting of five age groups: two groups of children (9-10 and 11-12 years of age), one group of young adults, and two groups of older adults (59-69 and 70-89 years of age). Two approaches were adopted. First, low-span and high-span individuals were identified, and analyses of variance were conducted comparing these two groups within each age group and for each RT task. The results consistently showed a span effect in the youngest children and oldest adults: High-span individuals were significantly faster and less variable than low-span individuals. In contrast, in young adults no difference was observed between high- and low-span individuals, whether in terms of their means or IIV. Second, multivariate analyses were conducted on the entire set of tasks, to determine whether IIV in RTs brought different information than the mean RT. The results showed that, although very strongly correlated, the mean and IIV in speed should be kept separate in terms of how they account for individual differences in WM. Overall, our results support the assumption of a link between WM capacity and IIV in RT, more strongly so in childhood and older adulthood.

Personality, psychosocial and health-related predictors of quality of life in old age.

OBJECTIVES: Beyond its well-documented association with depressive symptoms across the lifespan, at an individual level, quality of life may be determined by multiple factors: psychosocial characteristics, current physical health and long-term personality traits. METHOD: Quality of life was assessed in two distinct community-based age groups (89 young adults aged 36.2 ± 6.3 and 92 older adults aged 70.4 ± 5.5 years), each group equally including adults with and without acute depressive symptoms. Regression models were applied to explore the association between quality of life assessed with the World Health Organization Quality of Life - Bref (WHOQOL-Bref) and depression severity, education, social support, physical illness, as well as personality dimensions as defined by the Five-Factor Model. RESULTS: In young age, higher quality of life was uniquely associated with lower severity of depressive symptoms. In contrast, in old age, higher quality of life was related to both lower levels of depressive mood and of physical illness. In this age group, a positive association was also found between quality of life and higher levels of Openness to experience and Agreeableness personality dimensions. CONCLUSION: Our data indicated that, in contrast to young cohorts, where acute depression is the main determinant of poor quality of life, physical illness and personality dimensions represent additional independent predictors of this variable in old age. This observation points to the need for concomitant consideration of physical and psychological determinants of quality of life in old age.

Individual differences in cognitive plasticity: an investigation of training curves in younger and older adults.

To date, cognitive intervention research has provided mixed but nevertheless promising evidence with respect to the effects of cognitive training on untrained tasks (transfer). However, the mechanisms behind learning, training effects and their predictors are not fully understood. Moreover, individual differences, which may constitute an important factor impacting training outcome, are usually neglected. We suggest investigating individual training performance across training sessions in order to gain finer-grained knowledge of training gains, on the one hand, and assessing the potential impact of predictors such as age and fluid intelligence on learning rate, on the other hand. To this aim, we propose to model individual learning curves to examine the intra-individual change in training as well as inter-individual differences in intra-individual change. We recommend introducing a latent growth curve model (LGCM) analysis, a method frequently applied to learning data but rarely used in cognitive training research. Such advanced analyses of the training phase allow identifying factors to be respected when designing effective tailor-made training interventions. To illustrate the proposed approach, a LGCM analysis using data of a 10-day working memory training study in younger and older adults is reported.

Stressful life events and neuroticism as predictors of late-life versus early-life depression.

BACKGROUND: The occurrence of depression in younger adults is related to the combination of long-standing factors such as personality traits (neuroticism) and more acute factors such as the subjective impact of stressful life events. Whether an increase in physical illnesses changes these associations in old age depression remains a matter of debate. METHODS: We compared 79 outpatients with major depression and 102 never-depressed controls; subjects included both young (mean age: 35 years) and older (mean age: 70 years) adults. Assessments included the Social Readjustment Rating Scale, NEO Personality Inventory and Cumulative Illness Rating Scale. Logistic regression models analyzed the association between depression and subjective impact of stressful life events while controlling for neuroticism and physical illness. RESULTS: Patients and controls experienced the same number of stressful life events in the past 12 months. However, in contrast to the controls, patients associated the events with a subjective negative emotional impact. Negative stress impact and levels of neuroticism, but not physical illness, significantly predicted depression in young age. In old age, negative stress impact was weakly associated with depression. In this age group, depressive illness was also determined by physical illness burden and neuroticism. CONCLUSIONS: Our data suggest that the subjective impact of life stressors, although rated as of the same magnitude, plays a less important role in accounting for depression in older age compared to young age. They also indicate an increasing weight of physical illness burden in the prediction of depression occurrence in old age.

Cognitive intraindividual variability and white matter integrity in aging.

The intraindividual variability (IIV) of cognitive performance has been shown to increase with aging. While brain research has generally focused on mean performance, little is known about neural correlates of cognitive IIV. Nevertheless, some studies suggest that IIV relates more strongly than mean level of performance to the quality of white matter (WM). Our study aims to explore the relation between WM integrity and cognitive IIV by combining functional (fMRI) and structural (diffusion tensor imaging, DTI) imaging. Twelve young adults (aged 18-30 years) and thirteen older adults (61-82 years) underwent a battery of neuropsychological tasks, along with fMRI and DTI imaging. Their behavioral data were analyzed and correlated with the imaging data at WM regions of interest defined on the basis of (1) the fMRI-activated areas and (2) the Johns Hopkins University (JHU) WM tractography atlas. For both methods, fractional anisotropy, along with the mean, radial, and axial diffusivity parameters, was computed. In accord with previous studies, our results showed that the DTI parameters were more related to IIV than to mean performance. Results also indicated that age differences in the DTI parameters were more pronounced in the regions activated primarily by young adults during a choice reaction-time task than in those also activated in older adults.

Beyond interference control impairment in ADHD: evidence from increased intraindividual variability in the color-stroop test.

The present study investigates intraindividual variability (IIV) in the Color-Stroop test and in a simple reaction time (SRT) task. Performance level and variability in reaction times (RTs)-quantified with different measures such as individual standard deviation (ISD) and coefficient of variation (ICV), as well as ex-Gaussian parameters (mu, sigma, tau)-were analyzed in 24 children with attention deficit/hyperactivity disorder (ADHD) and 24 typically developing children (TDC). Children with ADHD and TDC presented equivalent Color-Stroop interference effects when mean RTs were considered, and the two groups did not differ in the SRT task. Interestingly, compared to TDC, children with ADHD were more variable in their responses, showing increased ISD and ICV in the Color-Stroop interference condition and in the SRT task. Moreover, children with ADHD exhibited higher tau values-that is, more frequent abnormally long RTs-in the Color-Stroop interference condition than did the TDC, but comparable tau values in the SRT, suggesting more variable responses. These results speak in favor of a general deficit in more basic and central processes that only secondarily may affect the efficiency of inhibitory processes in children with ADHD. Overall the present findings confirm the role of IIV as a cornerstone in the ADHD cognitive profile and support the search for fine-grained analysis of performance fluctuations.

Personality traits are associated with acute major depression across the age spectrum.

OBJECTIVES: Psychological predictors, such as personality traits, have aroused growing interest as possible predictors of late-life depression outcome in old age. It remains, however, unclear whether the cross-sectional relationship between personality traits and depression occurrence reported in younger samples is also present in the elderly. METHODS: Comparisons amongst 79 outpatients with DSM-IV major depression and 102 healthy controls included assessment of the five-factor model of personality (NEO PI-R), socio-demographic variables, physical health status, as well as depression features. Two sub-groups were considered, defined as young (25-50 years) and old (60-85 years) patients. RESULTS: Depressed patients showed significantly higher levels of Neuroticism and lower levels of Extraversion, Openness to Experience and Conscientiousness compared to controls. Sequential logistic regression models confirmed that the combination of increased physical burden, levels of dependency, and increased Neuroticism strongly predicts the occurrence of acute depressive symptoms. In contrast, the levels of Neuroticism did not allow for differentiating late-life from young age depression. Increased physical burden and decreased depression severity were the main predictors for this distinction. CONCLUSION: Our data indicate that personality factors and depression are related, independently of patients' age. Differences in this relationship are mainly due to the intensity of depressive symptoms rather than the patients' life period. They also stress the need to consider physical health, level of dependency and severity of symptoms when studying the relationship between personality traits and mood disorders.

Age differences in text processing: the role of working memory, inhibition, and processing speed.

OBJECTIVES: Age-related changes in the efficiency of various general cognitive mechanisms have been evoked to account for age-related differences between young and older adults in text comprehension performance. Using structural equation modeling, we investigate the relationship between age, working memory (WM), inhibition-related mechanisms, processing speed, and text comprehension, focusing on surface and text-based levels of processing. METHODS: Eighty-nine younger (M = 23.11 years) and 102 older (M = 70.50 years) adults were presented text comprehension, WM, inhibition, and processing speed tasks. In the text comprehension task, the demand on the memory system was manipulated, by allowing (text present) or not (text absent) viewing the text during the answering phase. RESULTS: As expected, age differences were larger when the text was absent. The best fitting model showed that WM mediated the influence of age on both text processing conditions, whereas age-related variance in WM was, in turn, accounted for by processing speed and inhibition. DISCUSSION: These findings confirm the hypothesis that WM capacity explains age differences in text processing, while it is itself accounted for by the efficiency of inhibiting irrelevant information and by speed of processing.

The influence of time of testing on interference, working memory, processing speed, and vocabulary: age differences in adulthood.

This research examines the effect of time of testing on adult age differences in resistance to interference, working memory, processing speed, and vocabulary. Results show that time of testing modulates age-related differences only in the ability to resist automatic and prepotent responses. Older adults tested in the afternoon were more susceptible to interference than young adults tested at the same time of the day, and than their peers tested in the morning. In contrast, age-related differences in working memory, processing speed, and vocabulary were not modulated by time of the day. Our findings suggest that age-related modulation of performance as a function of the time of the day is specific to resistance to interference.

Working memory and inhibitory control across the life span: Intrusion errors in the Reading Span Test.

The aim of this study was to examine to what extent inhibitory control and working memory capacity are related across the life span. Intrusion errors committed by children and younger and older adults were investigated in two versions of the Reading Span Test. In Experiment 1, a mixed Reading Span Test with items of various list lengths was administered. Older adults and children recalled fewer correct words and produced more intrusions than did young adults. Also, age-related differences were found in the type of intrusions committed. In Experiment 2, an adaptive Reading Span Test was administered, in which the list length of items was adapted to each individual's working memory capacity. Age groups differed neither on correct recall nor on the rate of intrusions, but they differed on the type of intrusions. Altogether, these findings indicate that the availability of attentional resources influences the efficiency of inhibition across the life span.

Functional imaging studies of cognition using 99mTc-HMPAO SPECT: empirical validation using the n-back working memory paradigm.

PURPOSE: Functional activation protocols are widely applied for the study of brain-cognition relations. Only few take advantage of the intrinsic characteristics of SPECT, particularly those allowing cognitive assessment outside of the camera, in settings close to the standard clinical or laboratory ones. The purpose of the study was to assess the feasibility of a split-dose activation protocol with (99m)Tc-HMPAO using low irradiation dose. MATERIALS AND METHODS: A two-scans protocol was applied to 12 healthy young volunteers using 270 MBq of (99m)Tc-HMPAO per scan, with each image associated to a particular experimental condition of the verbal n-back working memory task (0-back, 2-back). Subtraction method was used to identify regional brain activity related to the task. RESULTS: Voxel-wise statistical analysis showed left lateralized activity associated with the 2-back task, compared to the 0-back task. Activated regions, mainly prefrontal and parietal, were similar to those observed in previous fMRI and (15)O-PET studies. CONCLUSION: The results support the use of (99m)Tc-HMPAO SPECT for the investigation of brain-cognition relations and demonstrate the feasibility of optimal quality images despite low radiopharmaceutical doses. The findings also acknowledge the use of HMPAO as a radioligand to capture neuro-energetic modulations linked to cognitive activity. They encourage extending the application of the described activation protocol to clinical populations.

A dynamic investigation of cognitive dedifferentiation with control for retest: evidence from the Swiss Interdisciplinary Longitudinal Study on the Oldest Old.

Empirical examinations of the hypothesis of dedifferentiation of cognitive abilities in old and very old age (a) do not account for possible retest effects, which consequently may yield biased estimates of age effects, and (b) focus on time-independent relations (e.g., number of latent constructs, correlations between latent or measured variables). The authors applied a structural equation model with statistical control for retest effects to investigate the dynamic relations between a marker of perceptual speed (cross out) and a marker of verbal fluency (category-fruits). Longitudinal data are from 5 waves of the Swiss Interdisciplinary Longitudinal Study on the Oldest Old (N = 377, baseline age range = 79.5- 84.5 years). The authors found that, independently of retest effects, performance on the cross-out task affected changes in performance on the category task while the opposite did not hold true. This analytical technique could be applied to various markers of broad fluid-mechanic and broad crystallized-pragmatic components of cognition.