Vitamin B6, B12, and Folate's Influence on Neural Networks in the UK Biobank Cohort.

BACKGROUND: One-carbon metabolism coenzymes may influence brain aging in cognitively unimpaired adults. METHODS: Baseline data were used from the UK Biobank cohort. Estimated intake of vitamin B6, B12, and folate was regressed onto neural network functional connectivity in five resting-state neural networks. Linear mixed models tested coenzyme main effects and interactions with Alzheimer's disease (AD) risk factors. RESULTS: Increased B6 and B12 estimated intake were linked with less functional connectivity in most networks, including the posterior portion of the Default Mode Network. Conversely, higher folate was related to more connectivity in similar networks. AD family history modulated these associations: Increased estimated intake was positively associated with stronger connectivity in the Primary Visual Network and Posterior Default Mode Network in participants with an AD family history. In contrast, increased vitamin B12 estimated intake was associated with less connectivity in the Primary Visual Network and the Cerebello-Thalamo-Cortical Network in those without an AD family history. CONCLUSIONS: The differential patterns of association between B vitamins and resting-state brain activity may be important in understanding AD-related changes in the brain. Notably, AD family history appears to play a key role in modulating these relationships.

Neural processing of speech comprehension in noise predicts individual age using fNIRS-based brain-behavior models.

Speech comprehension in noise depends on complex interactions between peripheral sensory and central cognitive systems. Despite having normal peripheral hearing, older adults show difficulties in speech comprehension. It remains unclear whether the brain's neural responses could indicate aging. The current study examined whether individual brain activation during speech perception in different listening environments could predict age. We applied functional near-infrared spectroscopy to 93 normal-hearing human adults (20 to 70 years old) during a sentence listening task, which contained a quiet condition and 4 different signal-to-noise ratios (SNR = 10, 5, 0, -5 dB) noisy conditions. A data-driven approach, the region-based brain-age predictive modeling was adopted. We observed a significant behavioral decrease with age under the 4 noisy conditions, but not under the quiet condition. Brain activations in SNR = 10 dB listening condition could successfully predict individual's age. Moreover, we found that the bilateral visual sensory cortex, left dorsal speech pathway, left cerebellum, right temporal-parietal junction area, right homolog Wernicke's area, and right middle temporal gyrus contributed most to prediction performance. These results demonstrate that the activations of regions about sensory-motor mapping of sound, especially in noisy conditions, could be sensitive measures for age prediction than external behavior measures.

Small effects of olfactory identification and discrimination on global cognitive and executive performance over 1 year in aging people without a history of age-related cognitive impairment.

Olfactory and cognitive performance share neural correlates profoundly affected by physiological aging. However, whether odor identification and discrimination scores predict global cognitive status and executive function in healthy older people with intact cognition is unclear. Therefore, in the present study, we set out to elucidate these links in a convenience sample of 204 independently living, cognitively intact healthy Czech adults aged 77.4 ± 8.7 (61-97 years) over two waves of data collection (one-year interval). We used the Czech versions of the Montreal Cognitive Assessment (MoCA) to evaluate global cognition, and the Prague Stroop Test (PST), Trail Making Test (TMT), and several verbal fluency (VF) tests to assess executive function. As a subsidiary aim, we aimed to examine the contribution of olfactory performance towards achieving a MoCA score above vs. below the published cut-off value. We found that the MoCA scores exhibited moderate associations with both odor identification and discrimination. Furthermore, odor identification significantly predicted PST C and C/D scores. Odor discrimination significantly predicted PST C/D, TMT B/A, and standardized composite VF scores. Our findings demonstrate that olfaction, on the one hand, and global cognition and executive function, on the other, are related even in healthy older people.

Daily fluctuations in blood glucose with normal aging are inversely related to hippocampal synaptic mitochondrial proteins.

Defective brain glucose utilization is a hallmark of Alzheimer's disease (AD) while Type II diabetes and elevated blood glucose escalate the risk for AD in later life. Isolating contributions of normal aging from coincident metabolic or brain diseases could lead to refined approaches to manage specific health risks and optimize treatments targeted to susceptible older individuals. We evaluated metabolic, neuroendocrine, and neurobiological differences between young adult (6 months) and aged (24 months) male rats. Compared to young adults, blood glucose was significantly greater in aged rats at the start of the dark phase of the day but not during the light phase. When challenged with physical restraint, a potent stressor, aged rats effected no change in blood glucose whereas blood glucose increased in young adults. Tissues were evaluated for markers of oxidative phosphorylation (OXPHOS), neuronal glucose transport, and synapses. Outright differences in protein levels between age groups were not evident, but circadian blood glucose was inversely related to OXPHOS proteins in hippocampal synaptosomes, independent of age. The neuronal glucose transporter, GLUT3, was positively associated with circadian blood glucose in young adults whereas aged rats tended to show the opposite trend. Our data demonstrate aging increases daily fluctuations in blood glucose and, at the level of individual differences, negatively associates with proteins related to synaptic OXPHOS. Our findings imply that glucose dyshomeostasis may exacerbate metabolic aspects of synaptic dysfunction that contribute to risk for age-related brain disorders.

[Did entry into nursing home during the health crisis favor the emergence of traumatic symptoms in the elderly?: Entry into nursing home and Covid]. / L'entrée en Ehpad, durant la crise sanitaire, a-t-elle favorisé l'émergence de symptômes traumatiques chez le sujet âgé ?

Our aim is to explore the possible emergence of traumatic symptoms and the identity-related repercussions of the restrictions on elderly, who entered into nursing homes during the Covid-19 health crisis in France. Twenty-five subjects institutionalised before the health crisis and twenty-six subjects institutionalised during the periods of lockdown into nursing homes completed scales assessing anxiety-depressive symptomatology, traumatic symptoms and identity. Anxiety and depression symptoms were similar between the groups. The institutionalised group showed a significantly higher prevalence of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria D and E on the Post traumatic Stress Disorder Checklist version DSM-5 (PCL-5) during lockdown. Entry into an institution during the health crisis would have favored the emergence of traumatic symptoms in the participants. Consideration of the ethical issues raised by this study could make it possible to offer more individualised support to elderly during their transition to a new home.

Comparison between morphometry and radiomics: detecting normal brain aging based on grey matter.

Objective: Voxel-based morphometry (VBM), surface-based morphometry (SBM), and radiomics are widely used in the field of neuroimage analysis, while it is still unclear that the performance comparison between traditional morphometry and emerging radiomics methods in diagnosing brain aging. In this study, we aimed to develop a VBM-SBM model and a radiomics model for brain aging based on cognitively normal (CN) individuals and compare their performance to explore both methods' strengths, weaknesses, and relationships. Methods: 967 CN participants were included in this study. Subjects were classified into the middle-aged group (n = 302) and the old-aged group (n = 665) according to the age of 66. The data of 360 subjects from the Alzheimer's Disease Neuroimaging Initiative were used for training and internal test of the VBM-SBM and radiomics models, and the data of 607 subjects from the Australian Imaging, Biomarker and Lifestyle, the National Alzheimer's Coordinating Center, and the Parkinson's Progression Markers Initiative databases were used for the external tests. Logistics regression participated in the construction of both models. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were used to evaluate the two model performances. The DeLong test was used to compare the differences in AUCs between models. The Spearman correlation analysis was used to observe the correlations between age, VBM-SBM parameters, and radiomics features. Results: The AUCs of the VBM-SBM model and radiomics model were 0.697 and 0.778 in the training set (p = 0.018), 0.640 and 0.789 in the internal test set (p = 0.007), 0.736 and 0.737 in the AIBL test set (p = 0.972), 0.746 and 0.838 in the NACC test set (p < 0.001), and 0.701 and 0.830 in the PPMI test set (p = 0.036). Weak correlations were observed between VBM-SBM parameters and radiomics features (p < 0.05). Conclusion: The radiomics model achieved better performance than the VBM-SBM model. Radiomics provides a good option for researchers who prioritize performance and generalization, whereas VBM-SBM is more suitable for those who emphasize interpretability and clinical practice.

Does the Cognitive Change Index Predict Future Cognitive and Clinical Decline? Longitudinal Analysis in a Demographically Diverse Cohort.

Background: The Cognitive Change Index (CCI) is a widely-used measure of self-perceived cognitive ability and change. Unfortunately, it is unclear if the CCI predicts future cognitive and clinical decline. Objective: We evaluated baseline CCI to predict transition from normal cognition to cognitive impairment in nondemented older adults and in predementia groups including, subjective cognitive decline, motoric cognitive risk syndrome, and mild cognitive impairment. Different versions of the CCI were assessed to uncover any differential risk sensitivity. We also examined the effect of ethnicity/race on CCI. Methods: Einstein Aging Study participants (N = 322, Mage = 77.57±4.96, % female=67.1, Meducation = 15.06±3.54, % non-Hispanic white = 46.3) completed an expanded 40-item CCI version (CCI-40) and neuropsychological evaluation (including Clinical Dementia Rating Scale [CDR], Montreal Cognitive Assessment, and Craft Story) at baseline and annual follow-up (Mfollow - up=3.4 years). CCI-40 includes the original 20 items (CCI-20) and the first 12 memory items (CCI-12). Linear mixed effects models (LME) and generalized LME assessed the association of CCI total scores at baseline with rate of decline in neuropsychological tests and CDR. Results: In the overall sample and across predementia groups, the CCI was associated with rate of change in log odds on CDR, with higher CCI at baseline predicting faster increase in the odds of being impaired on CDR. The predictive validity of the CCI broadly held across versions (CCI-12, 20, 40) and ethnic/racial groups (non-Hispanic black and white). Conclusions: Self-perception of cognitive change on the CCI is a useful marker of dementia risk in demographically/clinically diverse nondemented samples. All CCI versions successfully predicted decline.

Regional differences in the link between water exchange rate across the blood-brain barrier and cognitive performance in normal aging.

The blood-brain barrier (BBB) undergoes functional changes with aging which may contribute to cognitive decline. A novel, diffusion prepared arterial spin labeling-based MRI technique can measure the rate of water exchange across the BBB (kw) and may thus be sensitive to age-related alterations in water exchange at the BBB. However, studies investigating relationships between kw and cognition have reported different directions of association. Here, we begin to investigate the direction of associations between kw and cognition in different brain regions, and their possible underpinnings, by evaluating links between kw, cognitive performance, and MRI markers of cerebrovascular dysfunction and/or damage. Forty-seven healthy older adults (age range 61-84) underwent neuroimaging to obtain whole-brain measures of kw, cerebrovascular reactivity (CVR), and white matter hyperintensity (WMH) volumes. Additionally, participants completed uniform data set (Version 3) neuropsychological tests of executive function (EF) and episodic memory (MEM). Voxel-wise linear regressions were conducted to test associations between kw and cognitive performance, CVR, and WMH volumes. We found that kw in the frontoparietal brain regions was positively associated with cognitive performance but not with CVR or WMH volumes. Conversely, kw in the basal ganglia was negatively associated with cognitive performance and CVR and positively associated with regional, periventricular WMH volume. These regionally dependent associations may relate to different physiological underpinnings in the relationships between kw and cognition in neocortical versus subcortical brain regions in older adults.

Cerebrospinal fluid neurofilament light chain mediates age-associated lower learning and memory in healthy adults.

Multiple cognitive domains, including learning, memory, and psychomotor speed, show significant reductions with age. Likewise, several cerebrospinal fluid (CSF) neurodegenerative biomarkers, including total tau (t-tau, a marker of neuronal body injury) and neurofilament light chain (NfL, a marker of axonal injury) show age-related increases in normal aging. In the current study, we aimed to investigate whether the age-effect within different cognitive domains was mediated by age-associated CSF markers for neurodegenerative changes. We fitted 10 mediation models using structural equation modeling to investigate this in a cohort of 137 healthy adults, aged 40-80 years, from the Norwegian Dementia Disease Initiation (DDI) study. Here, t-tau and NfL were defined as mediators between age and different cognitive tests. The models showed that NfL mediated the age-effect for CERAD learning and memory recall (learning: ß = -0.395, p < 0.05; recall: ß = -0.261, p < 0.01). No such effect was found in the other models. Our findings suggest that the age-related lower performance in verbal learning and memory may be linked to NfL-associated neurodegenerative changes in cognitively healthy adults.

The causal link between cardiometabolic risk factors and gray matter atrophy: An exploratory study.

Although gray matter atrophy is commonly observed with aging, it is highly variable, even among healthy people of the same age. This raises the question of what other factors may contribute to gray matter atrophy. Previous studies have reported that risk factors for cardiometabolic diseases are associated with accelerated brain aging. However, these studies were primarily based on standard correlation analyses, which do not unveil a causal relationship. While randomized controlled trials are typically required to investigate true causality, in this work, we investigated an alternative method by exploring data-driven causal discovery and inference techniques on observational data. Accordingly, this feasibility study used clinical and quantified gray matter volume data from 22,793 subjects from the UK biobank cohort without any known neurological disease. Our method identified that age, sex, body mass index (BMI), body fat percentage (BFP), and smoking exhibit a causal relationship with gray matter volume. Interventions on the causal network revealed that higher BMI and BFP values significantly increased the chance of gray matter atrophy in males, whereas this was not the case in females.

Neural Degeneration in Normal-Aging Human Cochleas: Machine-Learning Counts and 3D Mapping in Archival Sections.

Quantifying the survival patterns of spiral ganglion cells (SGCs), the cell bodies of auditory-nerve fibers, is critical to studies of sensorineural hearing loss, especially in human temporal bones. The classic method of manual counting is tedious, and, although stereology approaches can be faster, they can only be used to estimate total cell numbers per cochlea. Here, a machine-learning algorithm that automatically identifies, counts, and maps the SGCs in digitized images of semi-serial human temporal-bone sections not only speeds the analysis, with no loss of accuracy, but also allows 3D visualization of the SGCs and fine-grained mapping to cochlear frequency. Applying the algorithm to 62 normal-aging human ears shows significantly faster degeneration of SGCs in the basal than the apical half of the cochlea. Comparison to fiber counts in the same ears shows that the fraction of surviving SGCs lacking a peripheral axon steadily increases with age, reaching more than 50% in the apical cochlea and almost 66% in basal regions.

Integrated multi-omics analysis of brain aging in female nonhuman primates reveals altered signaling pathways relevant to age-related disorders.

The prefrontal cortex (PFC) has been implicated as a key brain region responsible for age-related cognitive decline. Little is known about aging-related molecular changes in PFC that may mediate these effects. To date, no studies have used untargeted discovery methods with integrated analyses to determine PFC molecular changes in healthy female primates. We quantified PFC changes associated with healthy aging in female baboons by integrating multiple omics data types (transcriptomics, proteomics, metabolomics) from samples across the adult age span. Our integrated omics approach using unbiased weighted gene co-expression network analysis to integrate data and treat age as a continuous variable, revealed highly interconnected known and novel pathways associated with PFC aging. We found Gamma-aminobutyric acid (GABA) tissue content associated with these signaling pathways, providing 1 potential biomarker to assess PFC changes with age. These highly coordinated pathway changes during aging may represent early steps for aging-related decline in PFC functions, such as learning and memory, and provide potential biomarkers to assess cognitive status in humans.

Association of Cognitive Polygenic Index and Cognitive Performance with Age in Cognitively Healthy Adults.

Genome-wide association studies have discovered common genetic variants associated with cognitive performance. Polygenic scores that summarize these discoveries explain up to 10% of the variance in cognitive test performance in samples of adults. However, the role these genetics play in cognitive aging is not well understood. We analyzed data from 168 cognitively healthy participants aged 23-77 years old, with data on genetics, neuropsychological assessment, and brain-imaging measurements from two large ongoing studies, the Reference Abilities Neural Networks, and the Cognitive Reserve study. We tested whether a polygenic index previously related to cognition (Cog PGI) would moderate the relationship between age and measurements of the cognitive domains extracted from a neuropsychological evaluation: fluid reasoning, memory, vocabulary, and speed of processing. We further explored the relationship of Cog PGI and age on cognition using Johnson-Neyman intervals for two-way interactions. Sex, education, and brain measures of cortical thickness, total gray matter volume, and white matter hyperintensity were considered covariates. The analysis controlled for population structure-ancestry. There was a significant interaction effect of Cog PGI on the association between age and the domains of memory (Standardized coefficient = -0.158, p-value = 0.022), fluid reasoning (Standardized coefficient = -0.146, p-value = 0.020), and vocabulary (Standardized coefficient = -0.191, p-value = 0.001). Higher PGI strengthened the negative relationship between age and the domains of memory and fluid reasoning while PGI weakened the positive relationship between age and vocabulary. Based on the Johnson-Neyman intervals, Cog PGI was significantly associated with domains of memory, reasoning, and vocabulary for younger adults. There is a significant moderation effect of genetic predisposition for cognition for the association between age and cognitive performance. Genetics discovered in genome-wide association studies of cognitive performance show a stronger association in young and midlife older adults.

The effects of pre-cue alpha and cueing strategy on age-related deficits in post-cue alpha activity and target processing during visual spatial attention.

Electroencephalography alpha-band (8-13 Hz) activity during visual spatial attention declines in normal aging. We recently reported the impacts of pre-cue baseline alpha and cueing strategy on post-cue anticipatory alpha activity and target processing in visual spatial attention (Wang et al., Cerebral Cortex, 2023). However, whether these factors affected aging effects remains unaddressed. We investigated this issue in two independent experiments (n = 114) with different cueing strategies (instructional vs. probabilistic). When median-splitting young adults (YA) by their pre-cue alpha power, we found that older adults exhibited similar pre-cue and post-cue alpha activity as YA with lower pre-cue alpha, and only YA with higher pre-cue alpha showed significant post-cue alpha activity, suggesting that diminished anticipatory alpha activity was not specific to aging but likely due to a general decrease with baseline alpha. Moreover, we found that the aging effects on cue-related event-related potentials were dependent on cueing strategy but were relatively independent of pre-cue alpha. However, age-related deficits in target-related N1 attentional modulation might depend on both pre-cue alpha and cueing strategy. By considering the impacts of pre-cue alpha and cueing strategy, our findings offer new insights into age-related deficits in anticipatory alpha activity and target processing during visual spatial attention.

Association of brain tissue cerebrospinal fluid fraction with age in healthy cognitively normal adults.

Background and purpose: Our objective was to apply multi-compartment T2 relaxometry in cognitively normal individuals aged 20-80 years to study the effect of aging on the parenchymal CSF fraction (CSFF), a potential measure of the subvoxel CSF space. Materials and methods: A total of 60 volunteers (age range, 22-80 years) were enrolled. Voxel-wise maps of short-T2 myelin water fraction (MWF), intermediate-T2 intra/extra-cellular water fraction (IEWF), and long-T2 CSFF were obtained using fast acquisition with spiral trajectory and adiabatic T2prep (FAST-T2) sequence and three-pool non-linear least squares fitting. Multiple linear regression analyses were performed to study the association between age and regional MWF, IEWF, and CSFF measurements, adjusting for sex and region of interest (ROI) volume. ROIs include the cerebral white matter (WM), cerebral cortex, and subcortical deep gray matter (GM). In each model, a quadratic term for age was tested using an ANOVA test. A Spearman's correlation between the normalized lateral ventricle volume, a measure of organ-level CSF space, and the regional CSFF, a measure of tissue-level CSF space, was computed. Results: Regression analyses showed that there was a statistically significant quadratic relationship with age for CSFF in the cortex (p = 0.018), MWF in the cerebral WM (p = 0.033), deep GM (p = 0.017) and cortex (p = 0.029); and IEWF in the deep GM (p = 0.033). There was a statistically highly significant positive linear relationship between age and regional CSFF in the cerebral WM (p < 0.001) and deep GM (p < 0.001). In addition, there was a statistically significant negative linear association between IEWF and age in the cerebral WM (p = 0.017) and cortex (p < 0.001). In the univariate correlation analysis, the normalized lateral ventricle volume correlated with the regional CSFF measurement in the cerebral WM (ρ = 0.64, p < 0.001), cortex (ρ = 0.62, p < 0.001), and deep GM (ρ = 0.66, p < 0.001). Conclusion: Our cross-sectional data demonstrate that brain tissue water in different compartments shows complex age-dependent patterns. Parenchymal CSFF, a measure of subvoxel CSF-like water in the brain tissue, is quadratically associated with age in the cerebral cortex and linearly associated with age in the cerebral deep GM and WM.

Functional alterations in bipartite network of white and grey matters during aging.

The effects of normal aging on functional connectivity (FC) within various brain networks of gray matter (GM) have been well-documented. However, the age effects on the networks of FC between white matter (WM) and GM, namely WM-GM FC, remains unclear. Evaluating crucial properties, such as global efficiency (GE), for a WM-GM FC network poses a challenge due to the absence of closed triangle paths which are essential for assessing network properties in traditional graph models. In this study, we propose a bipartite graph model to characterize the WM-GM FC network and quantify these challenging network properties. Leveraging this model, we assessed the WM-GM FC network properties at multiple scales across 1,462 cognitively normal subjects aged 22-96 years from three repositories (ADNI, BLSA and OASIS-3) and investigated the age effects on these properties throughout adulthood and during late adulthood (age ≥70 years). Our findings reveal that (1) heterogeneous alterations occurred in region-specific WM-GM FC over the adulthood and decline predominated during late adulthood; (2) the FC density of WM bundles engaged in memory, executive function and processing speed declined with age over adulthood, particularly in later years; and (3) the GE of attention, default, somatomotor, frontoparietal and limbic networks reduced with age over adulthood, and GE of visual network declined during late adulthood. These findings provide unpresented insights into multi-scale alterations in networks of WM-GM functional synchronizations during normal aging. Furthermore, our bipartite graph model offers an extendable framework for quantifying WM-engaged networks, which may contribute to a wide range of neuroscience research.

Changes in white matter functional networks across late adulthood.

Introduction: The aging brain is characterized by decreases in not only neuronal density but also reductions in myelinated white matter (WM) fibers that provide the essential foundation for communication between cortical regions. Age-related degeneration of WM has been previously characterized by histopathology as well as T2 FLAIR and diffusion MRI. Recent studies have consistently shown that BOLD (blood oxygenation level dependent) effects in WM are robustly detectable, are modulated by neural activities, and thus represent a complementary window into the functional organization of the brain. However, there have been no previous systematic studies of whether or how WM BOLD signals vary with normal aging. We therefore performed a comprehensive quantification of WM BOLD signals across scales to evaluate their potential as indicators of functional changes that arise with aging. Methods: By using spatial independent component analysis (ICA) of BOLD signals acquired in a resting state, WM voxels were grouped into spatially distinct functional units. The functional connectivities (FCs) within and among those units were measured and their relationships with aging were assessed. On a larger spatial scale, a graph was reconstructed based on the pair-wise connectivities among units, modeling the WM as a complex network and producing a set of graph-theoretical metrics. Results: The spectral powers that reflect the intensities of BOLD signals were found to be significantly affected by aging across more than half of the WM units. The functional connectivities (FCs) within and among those units were found to decrease significantly with aging. We observed a widespread reduction of graph-theoretical metrics, suggesting a decrease in the ability to exchange information between remote WM regions with aging. Discussion: Our findings converge to support the notion that WM BOLD signals in specific regions, and their interactions with other regions, have the potential to serve as imaging markers of aging.

Astrogliosis, neuritic microstructure, and sex effects: GFAP is an indicator of neuritic orientation in women.

BACKGROUND: Data from human studies suggest that immune dysregulation is associated with Alzheimer's disease (AD) pathology and cognitive decline and that neurites may be affected early in the disease trajectory. Data from animal studies further indicate that dysfunction in astrocytes and inflammation may have a pivotal role in facilitating dendritic damage, which has been linked with negative cognitive outcomes. To elucidate these relationships further, we have examined the relationship between astrocyte and immune dysregulation, AD-related pathology, and neuritic microstructure in AD-vulnerable regions in late life. METHODS: We evaluated panels of immune, vascular, and AD-related protein markers in blood and conducted in vivo multi-shell neuroimaging using Neurite Orientation Dispersion and Density Imaging (NODDI) to assess indices of neuritic density (NDI) and dispersion (ODI) in brain regions vulnerable to AD in a cohort of older adults (n = 109). RESULTS: When examining all markers in tandem, higher plasma GFAP levels were strongly related to lower neurite dispersion (ODI) in grey matter. No biomarker associations were found with higher neuritic density. Associations between GFAP and neuritic microstructure were not significantly impacted by symptom status, APOE status, or plasma Aß42/40 ratio; however, there was a large sex effect observed for neurite dispersion, wherein negative associations between GFAP and ODI were only observed in females. DISCUSSION: This study provides a comprehensive, concurrent appraisal of immune, vascular, and AD-related biomarkers in the context of advanced grey matter neurite orientation and dispersion methodology. Sex may be an important modifier of the complex associations between astrogliosis, immune dysregulation, and brain microstructure in older adults.

Functional Connectivity Alterations of Cognitive Flexibility in Aging: Different Patterns of Global and Local Switch Costs.

OBJECTIVES: Cognitive flexibility declines with aging and is usually indicated by task switch costs including global and local switch costs. Cognitive flexibility in aging is associated with alterations in functional connectivity. However, whether different task-modulated connectivity mechanisms underlying global and local switch costs remain unclear. METHODS: Here we use the support vector machine to identify age-related functional connectivity in global and local switch costs between older (n = 32) and young adults (n = 33). Participants completed a cued task-switching task during the functional magnetic resonance imaging scan. RESULTS: Results show an age-related decline behaviorally in global but not in local switch costs. Moreover, distinct patterns of age-related alterations of connectivity were observed for each cost. Specifically, only multivariate changes in connectivity patterns were observed for local switch cost, whereas specific age-related connections were revealed for global switch cost. In older adults, the task-modulated left dorsal premotor cortex-left precuneus connectivity decreased, and the left inferior frontal junction-left inferior parietal sulcus connectivity correlated with decreased global switch cost. DISCUSSION: This study provides novel evidence for different neural patterns in global and local switch costs by illuminating connectivity mechanisms underlying cognitive flexibility in aging.

New Directions to Approach Oxidative Stress Related to Physical Activity and Nutraceuticals in Normal Aging and Neurodegenerative Aging.

Oxidative stress (OS) plays, perhaps, the most important role in the advanced aging process, cognitive impairment and pathogenesis of neurodegenerative disorders. The process generates tissue damage via specific mechanisms on proteins, lipids and nucleic acids of the cells. An imbalance between the excessive production of oxygen- and nitrogen-reactive species and antioxidants leads to a progressive decline in physiological, biological and cognitive functions. Accordingly, we need to design and develop favourable strategies for stopping the early aging process as well as the development of neurodegenerative diseases. Exercise training and natural or artificial nutraceutical intake are considered therapeutic interventions that reduce the inflammatory process, increase antioxidant capacities and promote healthy aging by decreasing the amount of reactive oxygen species (ROS). The aim of our review is to present research results in the field of oxidative stress related to physical activity and nutraceutical administration for the improvement of the aging process, but also related to reducing the neurodegeneration process based on analysing the beneficial effects of several antioxidants, such as physical activity, artificial and natural nutraceuticals, as well as the tools by which they are evaluated. In this paper, we assess the recent findings in the field of oxidative stress by analysing intervention antioxidants, anti-inflammatory markers and physical activity in healthy older adults and the elderly population with dementia and Parkinson's disease. By searching for studies from the last few years, we observed new trends for approaching the reduction in redox potential using different tools that evaluate regular physical activity, as well as antioxidant and anti-inflammatory markers preventing premature aging and the progress of disabilities in neurodegenerative diseases. The results of our review show that regular physical activity, supplemented with vitamins and oligomolecules, results in a decrease in IL-6 and an increase in IL-10, and has an influence on the oxidative metabolism capacity. In conclusion, physical activity provides an antioxidant-protective effect by decreasing free radicals and proinflammatory markers.