Age-related Decline In Executive Function Research Articles

Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial.

Alzheimer's disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65-80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved.

Auditory cognitive aging in amateur singers and non-singers

The notion that lifestyle factors, such as music-making activities, can affect cognitive functioning and reduce cognitive decline in aging is often referred to as the mental exercise hypothesis. One ubiquitous musical activity is choir singing. Like other musical activities, singing is hypothesized to impact cognitive and especially executive functions. Despite the commonness of choir singing, little is known about the extent to which singing can affect cognition in adulthood. In this cross-sectional group study, we examined the relationship between age and four auditory executive functions to test hypotheses about the relationship between the level of mental activity and cognitive functioning. We also examined pitch discrimination capabilities. A non-probabilistic sample of 147 cognitively healthy adults was recruited, which included 75 non-singers (mean age 52.5 ± 20.3; 20–98 years) and 72 singers (mean age 55.5 ± 19.2; 21–87 years). Tests of selective attention, processing speed, inhibitory control, and working memory were administered to all participants. Our main hypothesis was that executive functions and age would be negatively correlated, and that this relationship would be stronger in non-singers than singers, consistent with the differential preservation hypothesis. The alternative hypothesis - preserved differentiation – predicts that the difference between singers and non-singers in executive functions is unaffected by age. Our results reveal a detrimental effect of age on processing speed, selective attention, inhibitory control and working memory. The effect of singing was comparatively more limited, being positively associated only with frequency discrimination, processing speed, and, to some extent, inhibitory control. Evidence of differential preservation was limited to processing speed. We also found a circumscribed positive impact of age of onset and a negative impact of singing experience on cognitive functioning in singers. Together, these findings were interpreted as reflecting an age-related decline in executive function in cognitively healthy adults, with specific and limited positive impacts of singing, consistent with the preserved differentiation hypothesis, but not with the differential preservation hypothesis.

Multi-compartment analysis of the complex gradient-echo signal quantifies myelin breakdown in premanifest Huntington's disease

White matter (WM) alterations have been identified as a relevant pathological feature of Huntington’s disease (HD). Increasing evidence suggests that WM changes in this disorder are due to alterations in myelin‐associated biological processes. Multi-compartmental analysis of the complex gradient-echo MRI signal evolution in WM has been shown to quantify myelin in vivo, therefore pointing to the potential of this technique for the study of WM myelin changes in health and disease. This study first characterized the reproducibility of metrics derived from the complex multi-echo gradient-recalled echo (mGRE) signal across the corpus callosum in healthy participants, finding highest reproducibility in the posterior callosal segment. Subsequently, the same analysis pipeline was applied in this callosal region in a sample of premanifest HD patients (n = 19) and age, sex and education matched healthy controls (n = 21). In particular, we focused on two myelin-associated derivatives: i. the myelin water signal fraction (fm), a parameter dependent on myelin content; and ii. The difference in frequency between myelin and intra-axonal water pools (Δω), a parameter dependent on the ratio between the inner and the outer axonal radii. fm was found to be lower in HD patients (β = −0.13, p = 0.03), while Δω did not show a group effect. Performance in tests of working memory, executive function, social cognition and movement was also assessed, and a greater age-related decline in executive function was detected in HD patients (β = −0.06, p = 0.006), replicating previous evidence of executive dysfunction in HD. Finally, the correlation between fm, executive function, and proximity to disease onset was explored in patients, and a positive correlation between executive function and fm was detected (r = 0.542; p = 0.02). This study emphasises the potential of complex mGRE signal analysis for aiding understanding of HD pathogenesis and progression. Moreover, expanding on evidence from pathology and animal studies, it provides novel in vivo evidence supporting myelin breakdown as an early feature of HD.

Age-related decline in executive function as a hallmark of cognitive ageing in primates: An overview of cognitive and neurobiological studies: Aging of executive function in primates

Age-related decline in executive function as a hallmark of cognitive ageing in primates: An overview of cognitive and neurobiological studies: Aging of executive function in primates

Age-related decline in executive function as a hallmark of cognitive ageing in primates: an overview of cognitive and neurobiological studies.

Executive function (EF) is a complex construct that reflects multiple higher-order cognitive processes such as planning, updating, inhibiting and set-shifting. Decline in these functions is a hallmark of cognitive ageing in humans, and age differences and changes in EF correlate with age-related differences and changes in association cortices, particularly the prefrontal areas. Here, we review evidence for age-related decline in EF and associated neurobiological changes in prosimians, New World and Old World monkeys, apes and humans. While EF declines with age in all primate species studied, the relationship of this decline with age-related alterations in the prefrontal cortex remains unclear, owing to the scarcity of neurobiological studies focusing on the ageing brain in most primate species. In addition, the influence of sex, vascular and metabolic risk, and hormonal status has rarely been considered. We outline several methodological limitations and challenges with the goal of producing a comprehensive integration of cognitive and neurobiological data across species and elucidating how ageing shapes neurocognitive trajectories in primates with different life histories, lifespans and brain architectures. Such comparative investigations are critical for fostering translational research and understanding healthy and pathological ageing in our own species. This article is part of the theme issue 'Evolution of the primate ageing process'.

Influence of structural and functional brain connectivity on age-related differences in fluid cognition

We used graph theoretical measures to investigate the hypothesis that structural brain connectivity constrains the influence of functional connectivity on the relation between age and fluid cognition. Across 143 healthy, community-dwelling adults 19–79 years of age, we estimated structural network properties from diffusion-weighted imaging and functional network properties from resting-state functional magnetic resonance imaging. We confirmed previous reports of age-related decline in the strength and efficiency of structural networks, as well as in the connectivity strength within and between structural network modules. Functional networks, in contrast, exhibited age-related decline only in system segregation, a measure of the distinctiveness among network modules. Aging was associated with decline in a composite measure of fluid cognition, particularly tests of executive function. Functional system segregation was a significant mediator of age-related decline in executive function. Structural network properties did not directly influence the age-related decline in functional system segregation. The raw correlational data underlying the graph theoretical measures indicated that structural connectivity exerts a limited constraint on age-related decline in functional connectivity.

Short video game play improves executive function in the oldest old living in residential care

Action video game play as a form of cognitive training shows promise, but has not been widely tested with participants exclusively over age 80 years. Age-related decline in executive function produces widely varying levels of ability to function independently. This study aimed to examine the change in executive functioning after a 3-week action video game intervention in healthy adults aged 80–97 years living in residential care. Participants were randomly assigned to either an experimental or care-as-usual control group: experimental participants played Star Wars Battlefront©, a commercially available video game, for six supervised sessions of 30 min each. Participants completed neuropsychological and quality of life assessments pre-training, post-training, and one month later. The experimental group showed significant improvement in the visual attention and task switching domains, in both post-test and follow-up sessions. Working memory also improved in the experimental group; however, after one month of no game play, memory performance regressed toward baseline levels. Results support the incorporation of video game play as a leisure option for older adults, which may also play a role in enhancing cognitive health. The findings extend previous research conducted below age 80 years to the oldest-old, an age group in which longitudinal follow up data is limited.

Lifetime physical activity and late-life cognitive function: the Rancho Bernardo study.

physical activity in older age has been associated with better cognitive function, but the role of earlier life physical activity is less well understood. determine associations between physical activity throughout the lifespan and cognitive function in older age. cross-sectional study. the Rancho Bernardo Study of Healthy Aging in southern California. A total of 1,826 community-dwelling men and women (60-99 years) who attended a research visit in 1988-92. participants underwent cognitive testing at older age, and reported physical activity as a teenager, at age 30 years, 50 years and currently. For each time-point, participants were classified as regularly active (3+ times/week) or inactive. regular physical activity was associated with better cognitive function, with physical activity at older ages showing the strongest associations. Physical activity in older age was associated with better global cognitive function, executive function and episodic memory, regardless of intensity. Intense physical activity in teenage years was associated with better late-life global cognitive function in women. Teenage physical activity interacted with older age physical activity on executive function; those active at both periods performed better than those active at only one period. Similar patterns of associations were observed after excluding individuals with poor health. regular physical activity in older age, regardless of intensity, is associated with better cognitive function. Physical activity in teenage years may enhance cognitive reserve to protect against age-related decline in executive function. Further research is needed to assess the effect of physical activity across the lifespan on healthy brain ageing.

Behavior Model for Assessing Decline in Executive Function During Aging and Neurodegenerative Diseases.

Executive dysfunction is a characteristic of several psychiatric and neurodegenerative diseases. Interestingly, executive function, which is mediated by the prefrontal cortex (PFC), commonly declines during aging. The attentional set-shifting task (AST) is commonly and extensively used to assess executive function in rodents, primates, and humans. When properly employed, this task can behaviorally assess attention, response inhibition, and cognitive flexibility. The following section uses research on age-related decline in executive function to demonstrate the methods employed and highlight areas that can confound a study if not employed properly.

Dissociable Effects of Aging on Salience Subnetwork Connectivity Mediate Age-Related Changes in Executive Function and Affect.

Aging is associated with both changes in affective experience and attention. An intrinsic brain network subserving these functions, the salience network, has not shown clear evidence of a corresponding age-related change. We propose a solution to this discrepancy: that aging differentially affects the connectivity of two dissociated subsystems of the salience network identified in our prior research (Touroutoglou et al., 2012). We examined the age-related changes in intrinsic connectivity between a dorsal and a ventral salience subsystem in a sample of 111 participants ranging in age from 18 years to 81 years old. We predicted that connectivity within the ventral subsystem is relatively preserved with age, while connectivity in the dorsal subsystem declines. Our findings showed that the connectivity within the ventral subsystem was not only preserved but it actually increased with age, whereas the connectivity within the dorsal subsystem decreased with age. Furthermore, age-related increase in arousal experience was partially mediated by age-related increases in ventral salience subsystem, whereas age-related decline in executive function was fully mediated by age-related decreases in dorsal salience subsystem connectivity. These findings explain previously conflicting results on age-related changes in the salience network, and suggest a mechanism for relatively preserved affective function in the elderly.

Sources of disconnection in neurocognitive aging: cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume

Age-related decline in fluid cognition can be characterized as a disconnection among specific brain structures, leading to a decline in functional efficiency. The potential sources of disconnection, however, are unclear. We investigated imaging measures of cerebral white-matter integrity, resting-state functional connectivity, and white-matter hyperintensity volume as mediators of the relation between age and fluid cognition, in 145 healthy, community-dwelling adults 19–79 years of age. At a general level of analysis, with a single composite measure of fluid cognition and single measures of each of the 3 imaging modalities, age exhibited an independent influence on the cognitive and imaging measures, and the imaging variables did not mediate the age-cognition relation. At a more specific level of analysis, resting-state functional connectivity of sensorimotor networks was a significant mediator of the age-related decline in executive function. These findings suggest that different levels of analysis lead to different models of neurocognitive disconnection, and that resting-state functional connectivity, in particular, may contribute to age-related decline in executive function.

Combined Cognitive Training vs. Memory Strategy Training in Healthy Older Adults.

As mnemonic utilization deficit in older adults associates with age-related decline in executive function, we hypothesized that memory strategy training combined with executive function training might induce larger training effect in memory and broader training effects in non-memory outcomes than pure memory training. The present study compared the effects of combined cognitive training (executive function training plus memory strategy training) to pure memory strategy training. Forty healthy older adults were randomly assigned to a combined cognitive training group or a memory strategy training group. A control group receiving no training was also included. Combined cognitive training group received 16 sessions of training (eight sessions of executive function training followed by eight sessions of memory strategy training). Memory training group received 16 sessions of memory strategy training. The results partly supported our hypothesis in that indeed improved performance on executive function was only found in combined training group, whereas memory performance increased less in combined training compared to memory strategy group. Results suggest that combined cognitive training may be less efficient than pure memory training in memory outcomes, though the influences from insufficient training time and less closeness between trained executive function and working memory could not be excluded; however it has broader training effects in non-memory outcomes. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR-OON-16007793.

The Disconnected Brain and Executive Function Decline in Aging.

Higher order speeded cognitive abilities depend on efficient coordination of activity across the brain, rendering them vulnerable to age reductions in structural and functional brain connectivity. The concept of "disconnected aging" has been invoked, suggesting that degeneration of connections between distant brain regions cause cognitive reductions. However, it has not been shown that changes in cognitive functions over time can be explained by simultaneous changes in brain connectivity. We followed 119 young and middle-aged (23-52 years) and older (63-86 years) adults for 3.3 years with repeated assessments of structural and functional brain connectivity and executive functions. We found unique age-related longitudinal reductions in executive function over and above changes in more basic cognitive processes. Intriguingly, 82.5% of the age-related decline in executive function could be explained by changes in connectivity over time. While both structural and functional connectivity changes were related to longitudinal reductions in executive function, only structural connectivity change could explain the age-specific decline. This suggests that the major part of the age-related reductions in executive function can be attributed to micro- and macrostructural alterations in brain connectivity. Although correlational in nature, we believe the present results constitute evidence for a "disconnected brain" view on cognitive aging.

Fiber bundle length and cognition: a length-based tractography MRI study.

Executive function (EF) and cognitive processing speed (CPS) are two cognitive performance domains that decline with advanced age. Reduced EF and CPS are known to correlate with age-related frontal-lobe volume loss. However, it remains unclear whether white matter microstructure in these regions is associated with age-related decline in EF and/or CPS. We utilized quantitative tractography metrics derived from diffusion-tensor MRI to investigate the relationship between the mean fiber bundle lengths (FBLs) projecting to different lobes, and EF/CPS performance in 73 healthy aging adults. We measured aspects of EF and CPS with the Trail Making Test (TMT), Color-Word Interference Test, Letter-Number Sequencing (L-N Seq), and Symbol Coding. Results revealed that parietal and occipital FBLs explained a significant portion of variance in EF. Frontal, temporal, and occipital FBLs explained a significant portion of variance in CPS. Shorter occipital FBLs were associated with poorer performance on the EF tests TMT-B and CWIT 3. Shorter frontal, parietal, and occipital FBLs were associated with poorer performance on L-N Seq and Symbol Coding. Shorter frontal and temporal FBLs were associated with lower performance on CPS tests TMT-A and CWIT 1. Shorter FBLs were also associated with increased age. Results suggest an age-related FBL shortening in specific brain regions related to poorer EF and CPS performance among older adults. Overall, results support both the frontal aging hypothesis and processing speed theory, suggesting that each mechanism is contributing to age-related cognitive decline.

Executive dysfunction, brain aging, and political leadership.

Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

Overview of aging research using nonhuman primate models

Overview of aging research using nonhuman primate models

Neuronal and morphological bases of cognitive decline in aged rhesus monkeys.

Rhesus monkeys provide a valuable model for studying the basis of cognitive aging because they are vulnerable to age-related decline in executive function and memory in a manner similar to humans. Some of the behavioral tasks sensitive to the effects of aging are the delayed response working memory test, recognition memory tests including the delayed nonmatching-to-sample and the delayed recognition span task, and tests of executive function including reversal learning and conceptual set-shifting task. Much effort has been directed toward discovering the neurobiological parameters that are coupled to individual differences in age-related cognitive decline. Area 46 of the dorsolateral prefrontal cortex (dlPFC) has been extensively studied for its critical role in executive function while the hippocampus and related cortical regions have been a major target of research for memory function. Some of the key age-related changes in area 46 include decreases in volume, microcolumn strength, synapse density, and α1- and α2-adrenergic receptor binding densities. All of these measures significantly correlate with cognitive scores. Interestingly, the critical synaptic subtypes associated with cognitive function appear to be different between the dlPFC and the hippocampus. For example, the dendritic spine subtype most critical to task acquisition and vulnerable to aging in area 46 is the thin spine, whereas in the dentate gyrus, the density of large mushroom spines with perforated synapses correlates with memory performance. This review summarizes age-related changes in anatomical, neuronal, and synaptic parameters within brain areas implicated in cognition and whether these changes are associated with cognitive decline.

Age-related decline in executive function predicts better advice-giving in uncomfortable social contexts

Conventional wisdom suggests that older adults are more likely than young adults to speak their mind. Age-related executive function (EF) decline is believed to underlie this tendency by weakening older adults' capacity to inhibit responses. While age-related EF decline disrupts social and cognitive functioning in many domains, such degeneration may also carry the unforeseen benefit of improving communication in uncomfortable social contexts. We examined the performance of relatively low and high EF older adults and young adults on the socially distressing task of providing critical advice to a troubled obese teenager. Relative to higher EF older adults and younger adults, lower EF older adults were more open, provided more advice, and were seen as more empathic. Moreover, doctors specializing in obesity treatment rated lower EF older adults’ advice to the teen as having greater potential for prompting a lifestyle change. Our findings suggest a potential silver lining to age-related cognitive decline.

Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single-nucleotide polymorphism (SNP) in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.

Genetic contributions to age-related decline in executive function: a 10-year longitudinal study of COMT and BDNF polymorphisms

Genetic variability in the dopaminergic and neurotrophic systems could contribute to age-related impairments in executive control and memory function. In this study we examined whether genetic polymorphisms for catechol-O-methyltransferase (COMT) and brain-derived neurotrophic factor (BDNF) were related to the trajectory of cognitive decline occurring over a 10-year period in older adults. A single nucleotide polymorphism in the COMT (Val158/108Met) gene affects the concentration of dopamine in the prefrontal cortex. In addition, a Val/Met substitution in the pro-domain for BDNF (Val66Met) affects the regulated secretion and trafficking of BDNF with Met carriers showing reduced secretion and poorer cognitive function. We found that impairments over the 10-year span on a task-switching paradigm did not vary as a function of the COMT polymorphism. However, for the BDNF polymorphism the Met carriers performed worse than Val homozygotes at the first testing session but only the Val homozygotes demonstrated a significant reduction in performance over the 10-year span. Our results argue that the COMT polymorphism does not affect the trajectory of age-related executive control decline, whereas the Val/Val polymorphism for BDNF may promote faster rates of cognitive decay in old age. These results are discussed in relation to the role of BDNF in senescence and the transforming impact of the Met allele on cognitive function in old age.