Dietary Tyrosine Intake (FFQ) Is Associated with Locus Coeruleus, Attention and Grey Matter Maintenance: An MRI Structural Study on 398 Healthy Individuals of the Berlin Aging Study-II.

BACKGROUND AND OBJECTIVE: It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus-Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer's disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC signal intensity 2) whether LC mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test - TMT), and 3) whether LC signal intensity relates to an objective measure of brain maintenance (BrainPAD). METHODS: The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC signal intensity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA - measured with Food Frequency Questionnaire - FFQ). As a control procedure, the same analyses were repeated on other main seeds of the neuromodulators' subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. RESULTS: Results show that HD-Tyr-IDA is positively associated with LC signal intensity. Similarly, LC disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. CONCLUSIONS: These findings provide the first evidence linking tyrosine intake with LC-NA system signal intensity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts ("Lifebrain").

The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5,000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.

Military deployment correlates with smaller prefrontal gray matter volume and psychological symptoms in a subclinical population.

Research investigating the effects of trauma exposure on brain structure and function in adults has mainly focused on post-traumatic stress disorder (PTSD), whereas trauma-exposed individuals without a clinical diagnoses often serve as controls. However, this assumes a dichotomy between clinical and subclinical populations that may not be supported at the neural level. In the current study we investigate whether the effects of repeated or long-term stress exposure on brain structure in a subclinical sample are similar to previous PTSD neuroimaging findings. We assessed 27 combat trauma-exposed individuals by means of whole-brain voxel-based morphometry on 3 T magnetic resonance imaging scans and identified a negative association between duration of military deployment and gray matter volumes in ventromedial prefrontal cortex (vmPFC) and dorsal anterior cingulate cortex (ACC). We also found a negative relationship between deployment-related gray matter volumes and psychological symptoms, but not between military deployment and psychological symptoms. To our knowledge, this is the first whole-brain analysis showing that longer military deployment is associated with smaller regional brain volumes in combat-exposed individuals without PTSD. Notably, the observed gray matter associations resemble those previously identified in PTSD populations, and concern regions involved in emotional regulation and fear extinction. These findings question the current dichotomy between clinical and subclinical populations in PTSD neuroimaging research. Instead, neural correlates of both stress exposure and PTSD symptomatology may be more meaningfully investigated at a continuous level.

Association between exploratory activity and social individuality in genetically identical mice living in the same enriched environment.

We previously reported that inbred, genetically identical mice living in one enriched environment develop individual behavioral trajectories, indicating increasingly different levels of spatial exploratory behavior as quantified by roaming entropy. Cumulative roaming entropy (cRE) correlated positively with adult hippocampal neurogenesis, a type of plasticity involved in the flexible integration of new information into existing contexts (Freund et al., 2013). The study on which we report here was done in parallel to that first experiment, but here we acquired detailed observational data on the behavior of individual mice. Roaming entropy (RE) was again assessed in real-time with an antenna-based system over the entire experimental period of 3months. Compared to the least active mice in the enclosure (low number of antenna contacts), the most active animals showed tendencies of increased socially interactive behavior in the final observation block whereas least active mice displayed more self-related behavior (non-social local exploration and play). When looking at roaming behavior, we discovered that RE correlated negatively with latent factors representing social exploratory and non-social exploratory and play behavior. Adult neurogenesis could not be studied in the present cohort but we do know that under identical conditions, cumulative RE correlated positively with adult hippocampal neurogenesis. We can thus hypothesize that the mice with more exploratory experience in terms of areal coverage (as quantified by RE) and related greater levels of adult hippocampal plasticity, might also be the ones that were less involved in interactions within the group and, hence, more individualistic. While this remains to be confirmed experimentally, the present data suggest that the described mechanism of individualization, which has previously been shown to be hippocampus-dependent, has a social component.

COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition.

Cognitive decline is a characteristic feature of normal human aging. Previous work has demonstrated marked interindividual variability in onset and rate of decline. Such variability has been linked to factors such as maintenance of functional and structural brain integrity, genetics, and lifestyle. Still, few, if any, studies have combined a longitudinal design with repeated multimodal imaging and a comprehensive assessment of cognition as well as genetic and lifestyle factors. The present paper introduces the Cognition, Brain, and Aging (COBRA) study, in which cognitive performance and brain structure and function are measured in a cohort of 181 older adults aged 64 to 68 years at baseline. Participants will be followed longitudinally over a 10-year period, resulting in a total of three equally spaced measurement occasions. The measurement protocol at each occasion comprises a comprehensive set of behavioral and imaging measures. Cognitive performance is evaluated via computerized testing of working memory, episodic memory, perceptual speed, motor speed, implicit sequence learning, and vocabulary. Brain imaging is performed using positron emission tomography with [(11)C]-raclopride to assess dopamine D2/D3 receptor availability. Structural magnetic resonance imaging (MRI) is used for assessment of white and gray-matter integrity and cerebrovascular perfusion, and functional MRI maps brain activation during rest and active task conditions. Lifestyle descriptives are collected, and blood samples are obtained and stored for future evaluation. Here, we present selected results from the baseline assessment along with a discussion of sample characteristics and methodological considerations that determined the design of the study. This article is part of a Special Issue entitled SI: Memory & Aging.

Vascular hippocampal plasticity after aerobic exercise in older adults.

Aerobic exercise in young adults can induce vascular plasticity in the hippocampus, a critical region for recall and recognition memory. In a mechanistic proof-of-concept intervention over 3 months, we investigated whether healthy older adults (60-77 years) also show such plasticity. Regional cerebral blood flow (rCBF) and volume (rCBV) were measured with gadolinium-based perfusion imaging (3 Tesla magnetic resonance image (MRI)). Hippocampal volumes were assessed by high-resolution 7 Tesla MRI. Fitness improvement correlated with changes in hippocampal perfusion and hippocampal head volume. Perfusion tended to increase in younger, but to decrease in older individuals. The changes in fitness, hippocampal perfusion and volume were positively related to changes in recognition memory and early recall for complex spatial objects. Path analyses indicated that fitness-related changes in complex object recognition were modulated by hippocampal perfusion. These findings indicate a preserved capacity of the aging human hippocampus for functionally relevant vascular plasticity, which decreases with progressing age.

No association between CTNNBL1 and episodic memory performance.

Polymorphisms in the gene encoding catenin-ß-like 1 (CTNNBL1) were recently reported to be associated with verbal episodic memory performance--in particular, delayed verbal free recall assessed between 5 and 30 min after encoding--in a genome-wide association study on healthy young adults. To further examine the genetic effects of CTNNBL1, we tested for association between 455 single-nucleotide polymorphisms (SNPs) in or near CTNNBL1 and 14 measures of episodic memory performance from three different tasks in 1743 individuals. Probands were part of a population-based study of mentally healthy adult men and women, who were between 20 and 70 years old and were recruited as participants for the Berlin Aging Study II. Associations were assessed using linear regression analysis. Despite having sufficient power to detect the previously reported effect sizes, we found no evidence for statistically significant associations between the tested CTNNBL1 SNPs and any of the 14 measures of episodic memory. The previously reported effects of genetic polymorphisms in CTNNBL1 on episodic memory performance do not generalize to the broad range of tasks assessed in our cohort. If not altogether spurious, the effects may be limited to a very narrow phenotypic domain (that is, verbal delayed free recall between 5 and 30 min). More studies are needed to further clarify the role of CTNNBL1 in human memory.

Playing Super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial video game.

Video gaming is a highly pervasive activity, providing a multitude of complex cognitive and motor demands. Gaming can be seen as an intense training of several skills. Associated cerebral structural plasticity induced has not been investigated so far. Comparing a control with a video gaming training group that was trained for 2 months for at least 30 min per day with a platformer game, we found significant gray matter (GM) increase in right hippocampal formation (HC), right dorsolateral prefrontal cortex (DLPFC) and bilateral cerebellum in the training group. The HC increase correlated with changes from egocentric to allocentric navigation strategy. GM increases in HC and DLPFC correlated with participants' desire for video gaming, evidence suggesting a predictive role of desire in volume change. Video game training augments GM in brain areas crucial for spatial navigation, strategic planning, working memory and motor performance going along with evidence for behavioral changes of navigation strategy. The presented video game training could therefore be used to counteract known risk factors for mental disease such as smaller hippocampus and prefrontal cortex volume in, for example, post-traumatic stress disorder, schizophrenia and neurodegenerative disease.

Microstructure of frontoparietal connections predicts cortical responsivity and working memory performance.

We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.

Age-related differences in white matter microstructure: region-specific patterns of diffusivity.

We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.

[Age-associated interactions of sensorimotor and cognitive functions]. / Wechselwirkungen zwischen Sensomotorik und Kognition im Alter: Uberblick über ein internationales Forschungsfeld.

Research on cross-domain couplings between sensorimotor and cognitive functions in older adults has gained momentum during recent years. Results of most studies point to increasing interdependencies between the two functional domains with advancing adult age. The causes of this increase are complex and show dynamic interactions across adult development. This review integrates experimental, correlational, and neurophysiological evidence, with an eye on implications for maintaining an independent and mobile lifestyle in old age.

Walking while memorizing: age-related differences in compensatory behavior.

This study investigated predictions of the life-span theory of selection, optimization, and compensation, focusing on different patterns of task priority during dual-task performance in younger and older adults. Cognitive (memorizing) and sensorimotor (walking a narrow track) performance were measured singly, concurrently, and when task difficulty was manipulated. Use of external aids was measured to provide another index of task priority. Before dual-task testing, participants received extensive training with each component task and external aid. Age differences in dual-task costs were greater in memory performance than walking, suggesting that older adults prioritized walking over memory. Further, when given a choice of compensatory external aids to use, older adults optimized walking, whereas younger adults optimized memory performance. The results have broad implications for systemic theories of cognitive and sensorimotor aging, and the costs and benefits of assistive devices and environmental support for older populations.

The strong connection between sensory and cognitive performance in old age: not due to sensory acuity reductions operating during cognitive assessment.

Cognitive aging research has documented a strong increase in the covariation between sensory and cognitive functioning with advancing age. In part, this finding may reflect sensory acuity reductions operating during cognitive assessment. To examine this possibility, the authors administered cognitive tasks used in prior studies (e.g., Lindenberger & Baltes, 1994) to middle-aged adults under age-simulation conditions of reduced visual acuity, auditory acuity, or both. Visual acuity was lowered through partial occlusion filters, and auditory acuity through headphone-shaped noise protectors. Acuity manipulations reduced visual acuity and auditory acuity in the speech range to values reaching or approximating old-age acuity levels, respectively, but did not lower cognitive performance relative to control conditions. Results speak against assessment-related sensory acuity accounts of the age-related increase in the connection between sensory and cognitive functioning and underscore the need to explore alternative explanations, including a focus on general aspects of brain aging.

Memorizing while walking: increase in dual-task costs from young adulthood to old age.

The dual task of memorizing word lists while walking was predicted to become more difficult with age because balance and gait are in greater need of "attentional resources." Forty-seven young (ages 20-30 years), 45 middle-aged (40-50), and 48 old (60-70) adults were trained to criterion in a mnemonic technique and instructed to walk quickly and accurately on 2 narrow tracks of different path complexity. Then. participants encoded the word lists while sitting, standing, or walking on either track; likewise, speed and accuracy of walking performance were assessed with and without concurrent memory encoding. Dual-task costs increased with age in both domains; relative to young adults, the effect size of the overall increase was 0.98 standard deviation units for middle-aged and 1.47 standard deviation units for old adults. It is argued that sensory and motor aspects of behavior are increasingly in need of cognitive control with advancing age.

The role of inhibition in the regulation of sequential action.

We investigated the regulation of sequential action using a new paradigm. Participants learned a sequence of seven stimulus categories and then monitored for them during successive displays. All displays were instances of these categories, presented in pseudorandom order. On each trial, participants monitored for an instance of Category 1, pressed a key on a computer keyboard, then monitored for an instance of Category 2, pressed a key on the keyboard, and so on for all seven categories. Thus, a perfect trial contained exactly seven responses. Intrusion errors were classified as a function of ordinal distance from the current serial position (n). Fewer intrusion errors were made at near serial positions than at far ones, suggesting a gradient of lateral inhibition. In addition, more intrusions were made on n + 1 categories than n - 1 categories, suggesting greater availability of intended than completed goals. In accord with current models of sequential action, the results indicate lateral and self-inhibition as important mechanisms in regulation of sequential action.

Adult age differences in task switching.

Age differences in 2 components of task-set switching speed were investigated in 118 adults aged 20 to 80 years using task-set homogeneous (e.g., AAAA ...) and task-set heterogeneous (e.g., AABBAABB ... ) blocks. General switch costs were defined as latency differences between heterogeneous and homogeneous blocks. whereas specific switch costs were defined as differences between switch and nonswitch trials within heterogeneous blocks. Both types of costs generalized over verbal, figural, and numeric stimulus materials; were more highly correlated to fluid than to crystallized abilities; and were not eliminated after 6 sessions of practice, indicating that they reflect basic and domain-general aspects of cognitive control. Most important, age-associated increments in costs were significantly greater for general than for specific switch costs, suggesting that the ability to efficiently maintain and coordinate 2 alternating task sets in working memory instead of 1 is more negatively affected by advancing age than the ability to execute the task switch itself.

Lifespan psychology: theory and application to intellectual functioning.

The focus of this review is on theory and research of lifespan (lifespan developmental) psychology. The theoretical analysis integrates evolutionary and ontogenetic perspectives on cultural and human development across several levels of analysis. Specific predictions are advanced dealing with the general architecture of lifespan ontogeny, including its directionality and age-differential allocation of developmental resources into the three major goals of developmental adaptation: growth, maintenance, and regulation of loss. Consistent with this general lifespan architecture, a meta-theory of development is outlined that is based on the orchestrated and adaptive interplay between three processes of behavioral regulation: selection, optimization, and compensation. Finally, these propositions and predictions about the general nature of lifespan development are examined and supported by empirical evidence on the development of cognition and intelligence across the life span.

Intellectual functioning in old and very old age: cross-sectional results from the Berlin Aging Study.

This study documents age trends, interrelations, and correlates of intellectual abilities in old and very old age (70-103 years) from the Berlin Aging Study (N = 516). Fourteen tests were used to assess 5 abilities: reasoning, memory, and perceptual speed from the mechanic (broad fluid) domain and knowledge and fluency from the pragmatic (broad crystallized) domain. Intellectual abilities had negative linear age relations, with more pronounced age reductions in mechanic than in pragmatic abilities. Interrelations among intellectual abilities were highly positive and did not follow the mechanic-pragmatic distinction. Sociobiographical indicators were less closely linked to intellectual functioning than sensory-sensorimotor variables, which predicted 59% of the total reliable variance in general intelligence. Results suggest that aging-induced biological factors are a prominent source of individual differences in intelligence in old and very old age.

Emergence of a powerful connection between sensory and cognitive functions across the adult life span: a new window to the study of cognitive aging?

Six hundred eighty seven individuals ages 25-103 years were studied cross-sectionally to examine the relationship between measures of sensory functioning (visual and auditory acuity) and intelligence (14 cognitive tasks representing a 5-factor space of psychometric intelligence). As predicted, the average proportion of individual differences in intellectual functioning connected to sensory functioning increased from 11% in adulthood (25-69 years) to 31% in old age (70-103 years). However, the link between fluid intellectual abilities and sensory functioning, albeit of different size, displayed a similarly high connection to age in both age groups. Several explanations are discussed, including a "common cause" hypothesis. In this vein, we argue that the increase in the age-associated link between sensory and intellectual functioning may reflect brain aging and that the search for explanations of cognitive aging phenomena would benefit from attending to factors that are shared between the 2 domains.