Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

The relationship of obesity predicting decline in executive functioning is attenuated with greater leisure activities in old age.

Objectives: We investigated the longitudinal relationship between obesity and subsequent decline in executive functioning over six years as measured through performance changes in the Trail Making Test (TMT). We also examined whether this longitudinal relationship differed by key markers of cognitive reserve (education, occupation, and leisure activities), taking into account age, sex, and chronic diseases as covariates.Method: We used latent change score modeling based on longitudinal data from 897 older adults tested on TMT parts A and B in two waves six years apart. Mean age in the first wave was 74.33 years. Participants reported their weight and height (to calculate BMI), education, occupation, leisure activities, and chronic diseases.Results: There was a significant interaction of obesity in the first wave of data collection with leisure activities in the first wave on subsequent latent change. Specifically, obesity in the first wave significantly predicted a steeper subsequent decline in executive functioning over six years in individuals with a low frequency of leisure activities in the first wave. In contrast, in individuals with a high frequency of leisure activities in the first wave, this longitudinal relationship between obesity and subsequent decline in executive functioning was not significant.Conclusion: The longitudinal relationship between obesity and subsequent decline in executive functioning may be attenuated in individuals who have accumulated greater cognitive reserve through an engaged lifestyle in old age. Implications for current cognitive reserve and gerontological research are discussed.

Distinct effects of cognitive versus somatic anxiety on cognitive performance in old age: the role of working memory capacity.

Objective: The adverse effects of anxiety on cognition are widely recognized. According to Attentional Control Theory, worry (i.e. facet of cognitive anxiety) is the component that is responsible for these effects, and working memory capacity (WMC) plays an important role in regulating them. Despite the increasing importance of this problem with aging, little is known about how these mechanisms interact in old age. In this study, we explored the distinct contributions of the somatic and cognitive components of anxiety to neuropsychological performance, and the potential moderating role of WMC.Method: We administered cognitive tasks testing processing speed, cognitive flexibility and working memory to 605 older adults, who also underwent depression and test anxiety assessments (data from VLV study).Results: Multiple regression analyses showed that cognitive (but not somatic) aspects of anxiety affected cognitive flexibility. The effect of cognitive anxiety on processing speed was moderated by WMC: the anxiety-performance association was lower for participants with greater WMC.Conclusion: Results confirmed the specific role of worry in the anxiety-performance relationship in old age and supported the hypothesis that working memory resources regulates its deleterious effect on cognition. The absence of a moderation effect in the more costly switching task may reflect a limitation of resources with aging.

Does the insula contribute to emotion-related distortion of time? A neuropsychological approach.

The literature points to a large distributed brain network involved in the estimation of time. Among these regions, the role of the insular cortex is still poorly understood. At the confluence of emotional, interoceptive, and environmental signals, this brain structure has been proposed to underlie awareness of the passage of time and emotion related time dilation. Yet, this assumption has not been tested so far. This study aimed at exploring how a lesion of the insula affects subjective duration, either in an emotional context or in a non-emotional context. Twenty-one patients with a stroke affecting the insula, either left or right, were studied for their perception of sub and supra second durations. A verbal estimation task and a temporal bisection task were used with either pure tones or neutral and emotional sounds lasting between 300 and 1500 ms and presented monaurally. Results revealed that patients with a right insular lesion, showed less temporal sensitivity than both control participants and patients with a left insular lesion. Unexpectedly, emotional effects were similar in patients and control participants. Altogether, these results suggest a specific role of the right insula in the discrimination of durations, but not in emotion related temporal distortion. In addition, an ear × emotion interaction in control participants suggests that temporal processing of positive and negative sounds may be lateralized in the brain.

Nicotine increases sleep spindle activity.

Studies have shown that both nicotine and sleep spindles are associated with enhanced memorisation. Further, a few recent studies have shown how cholinergic input through nicotinic and muscarinic receptors can trigger or modulate sleep processes in general, and sleep spindles in particular. To better understand the interaction between nicotine and sleep spindles, we compared in a single blind randomised study the characteristics of sleep spindles in 10 healthy participants recorded for 2 nights, one with a nicotine patch and one with a sham patch. We investigated differences in sleep spindle duration, amplitude, intra-spindle oscillation frequency and density (i.e. spindles per min). We found that under nicotine, spindles are more numerous (average increase: 0.057 spindles per min; 95% confidence interval: [0.025-0.089]; p = .0004), have higher amplitude (average amplification: 0.260 µV; confidence interval: [0.119-0.402]; p = .0032) and last longer (average lengthening: 0.025 s; confidence interval: [0.017-0.032]; p = 2.7e-11). These results suggest that nicotine can increase spindle activity by acting on nicotinic acetylcholine receptors, and offer an attractive hypothesis for common mechanisms that may support memorisation improvements previously reported to be associated with nicotine and sleep spindles.

Cognitive Reserve Mediates the Relation between Openness to Experience and Smaller Decline in Executive Functioning.

AIMS: We investigated the mediating role of leisure activity engagement in the longitudinal relation between openness to experience and subsequent change in executive functioning over 6 years as measured through performance changes in the Trail Making Test (TMT). METHODS: We analyzed longitudinal data from 897 older adults (mean = 74.33 years in the first wave) tested on TMT parts A and B in two waves 6 years apart. Participants reported information on leisure activity engagement and openness to experience. RESULTS: Latent change score modeling revealed that 37.2% of the longitudinal relation between higher openness to experience in the first wave of data collection and a smaller subsequent increase in TMT completion time from the first to the second wave (i.e., a smaller decline in executive functioning) was mediated via a higher frequency of leisure activities in the first wave. CONCLUSION: Individuals with higher openness to experience show greater activity engagement in old age. By enhancing their cognitive reserve, this activity engagement may finally result in smaller subsequent decline in executive functioning.

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.

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.

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.

Socio-Emotional Competencies and School Performance in Adolescence: What Role for School Adjustment?

There is growing evidence in the literature of positive relationships between socio-emotional competencies and school performance. Several hypotheses have been used to explain how these variables may be related to school performance. In this paper, we explored the role of various school adjustment variables in the relationship between interpersonal socio-emotional competencies and school grades, using a weighted network approach. This network approach allowed us to analyze the structure of interrelations between each variable, pointing to both central and mediatory school and socio-emotional variables within the network. Self-reported data from around 3,400 French vocational high school students were examined. This data included a set of interpersonal socio-emotional competencies (cognitive and affective empathy, socio-emotional behaviors and collective orientation), school adjustment measures (adaptation to the institution, school anxiety, self-regulation at school, and self-perceived competence at school) as well as grades in mathematics and French language. The results showed that self-regulation at school weighted the most strongly on the whole network, and was the most important mediatory pathway. More specifically, self-regulation mediated the relationships between interpersonal socio-emotional competencies and school grades.

Motivation as a Mediator of the Relation Between Cognitive Reserve and Cognitive Performance.

OBJECTIVES: Interindividual differences in cognitive aging may be explained by differences in cognitive reserve (CR) that are built up across the life span. A plausible but underresearched mechanism for these differences is that CR helps compensating cognitive decline by enhancing motivation to cope with challenging cognitive situations. Theories of motivation on cognition suggest that perceived capacity and intrinsic motivation may be key mediators in this respect. METHOD: In 506 older adults, we assessed CR proxies (education, occupation, leisure activities), motivation (perceived capacity, intrinsic motivation), and a global measure of cognitive functioning. RESULTS: Perceived capacity, but not intrinsic motivation, significantly mediated the relation between CR and cognitive performance. DISCUSSION: Complementary with neurobiological and cognitive processes, our results suggest a more comprehensive view of the role of motivational aspects built up across the life span in determining differences in cognitive performance in old age.

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.

Cross-lagged relation of leisure activity participation to Trail Making Test performance 6 years later: Differential patterns in old age and very old age.

OBJECTIVE: We investigated cross-lagged relations between leisure activity participation and Trail Making Test (TMT) performance over 6 years and whether those reciprocal associations differed between individuals. METHOD: We analyzed data from 232 participants tested on performance in TMT Parts A and B as well as interviewed on leisure activity participation in 2 waves 6 years apart. Mean age in the Wave 1 was 73.42 years. Participants were also tested on vocabulary (Mill Hill scale) as a proxy indicator of crystallized intelligence and reported information on early and midlife cognitive reserve markers (education and occupation). Latent cross-lagged models were applied to investigate potential reciprocal activity-TMT relationships. RESULTS: The relation of leisure activity participation predicting TMT performance 6 years later was significantly larger than was the relation of TMT performance predicting later leisure activity participation. Statistically comparing different moderator groups revealed that this pattern was evident both in individuals with low education and in those with high education but, notably, emerged in only young-old adults (but not in old-old adults), in individuals with a low cognitive level of job in midlife (but not in those with a high cognitive level of job in midlife), and in individuals with high scores in vocabulary (but not in those with low scores in vocabulary). CONCLUSIONS: Late-life leisure activity participation may predict later cognitive status in terms of TMT performance, but individuals may markedly differ with respect to such effects. Implications for current cognitive reserve and neuropsychological aging research are discussed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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.

How emotional auditory stimuli modulate time perception.

Emotional and neutral sounds rated for valence and arousal were used to investigate the influence of emotions on timing in reproduction and verbal estimation tasks with durations from 2 s to 6 s. Results revealed an effect of emotion on temporal judgment, with emotional stimuli judged to be longer than neutral ones for a similar arousal level. Within scalar expectancy theory (J. Gibbon, R. Church, & W. Meck, 1984), this suggests that emotion-induced activation generates an increase in pacemaker rate, leading to a longer perceived duration. A further exploration of self-assessed emotional dimensions showed an effect of valence and arousal. Negative sounds were judged to be longer than positive ones, indicating that negative stimuli generate a greater increase of activation. High-arousing stimuli were perceived to be shorter than low-arousing ones. Consistent with attentional models of timing, this seems to reflect a decrease of attention devoted to time, leading to a shorter perceived duration. These effects, robust across the 2 tasks, are limited to short intervals and overall suggest that both activation and attentional processes modulate the timing of emotional events.

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.

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,

Empathy for Pain from Adolescence through Adulthood: An Event-Related Brain Potential Study.

Affective and cognitive empathy are traditionally differentiated, the affective component being concerned with resonating with another's emotional state, whereas the cognitive component reflects regulation of the resulting distress and understanding of another's mental states (see Decety and Jackson, 2004 for a review). Adolescence is a critical period for the development of cognitive control processes necessary to regulate affective processes: it is only in young adulthood that these control processes achieve maturity (Steinberg, 2005). Thus, one should expect adolescents to show greater automatic empathy than young adults. The present study aimed at exploring the neural correlates of affective (automatic) and cognitive empathy for pain from adolescence to young adulthood. With this aim, Event Related Potentials (ERPs) were recorded in 32 participants (aged 11-39) in a task designed to dissociate these components. ERPs results showed an early automatic fronto-central response to pain (that was not modulated by task demand) and a late parietal response to painful stimuli modulated by attention to pain cues. Adolescents exhibited earlier automatic responses to painful situations than young adults did and showed greater activity in the late cognitive component even when viewing neutral stimuli. Results are discussed in the context of the development of regulatory abilities during adolescence.

Subjectivity of time perception: a visual emotional orchestration.

The aim of the present study was to examine how visual emotional content could orchestrate time perception. The experimental design allowed us to single out the share of emotion in the specific processing of content-bearing pictures, i.e., real-life scenes. Two groups of participants had to reproduce the duration (2, 4, or 6 s) of content-deprived stimuli (gray squares) or differentially valenced content-bearing stimuli, which included neutral, pleasant, and unpleasant pictures (International Affective Pictures Systems). Results showed that the effect of content differed according to duration: at 2 s, the reproduced duration was longer for content-bearing than content-deprived stimuli, but the difference between the two types of stimuli decreased as duration increased and was not significant for the longest duration (6 s). At 4 s, emotional (pleasant and unpleasant) stimuli were judged longer than neutral pictures. Furthermore, whatever the duration, the precision of the reproduction was greater for non-emotional than emotional stimuli (pleasant and unpleasant). These results suggest a dissociation within content effect on timing in the visual modality: relative overestimation of all content-bearing pictures limited to short durations (2 s), and delayed overestimation of emotional relative to neutral pictures at 4 s, as well as a lesser precision in the temporal judgment of emotional pictures whatever the duration. Our results underline the relevance for time perception models to integrate two ways of assessing timing in relationship with emotion: accuracy and precision.