scholarly journals Targeting Age-Related Differences in Brain and Cognition with Multimodal Imaging and Connectome Topography Profiling

2019 ◽  
Author(s):  
Alexander J. Lowe ◽  
Casey Paquola ◽  
Reinder Vos de Wael ◽  
Manesh Girn ◽  
Sara Lariviere ◽  
...  
Keyword(s):  
Fluid Intelligence ◽  
Functional Differentiation ◽  
Aging Brain ◽  
Apical Position ◽  
Biomarkers Of Aging ◽  
Age Related ◽  
Cortical Hierarchy ◽  
Healthy Cohort ◽  
Age Range ◽  
The Brain

I.AbstractAging is characterised by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesise, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n=102, age range = 30-89 years) with MRI and Aβ PET data, we estimated age-related cortical thinning, hippocampal atrophy and Aβ deposition. In addition to carrying out surface-based morphological and metabolic mapping, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased Aβ deposition occurred across the entire cortical topography, increased Aβ deposition was especially pronounced towards higher-order transmodal regions. Age-related atrophy was greater towards the posterior end of the hippocampal long-axis. No significant effect of age on Aβ deposition in the hippocampus was observed. Imaging markers correlated with behavioural measures of fluid intelligence and episodic memory in a topography-specific manner. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyse and conceptualize brain-based biomarkers of aging.

scholarly journals The aging mind: neuroplasticity in response to cognitive training

2013 ◽  
Vol 15 (1) ◽  
pp. 109-119 ◽  
Keyword(s):  
Cognitive Function ◽  
Cognitive Training ◽  
Neural Plasticity ◽  
Cognitive Effort ◽  
Aging Brain ◽  
Cognitive Domains ◽  
Training Techniques ◽  
Age Related ◽  
Strategy Change ◽  
The Brain

Is it possible to enhance neural and cognitive function with cognitive training techniques? Can we delay age-related decline in cognitive function with interventions and stave off Alzheimer's disease? Does an aged brain really have the capacity to change in response to stimulation? In the present paper, we consider the neuroplasticity of the aging brain, that is, the brain's ability to increase capacity in response to sustained experience. We argue that, although there is some neural deterioration that occurs with age, the brain has the capacity to increase neural activity and develop neural scaffolding to regulate cognitive function. We suggest that increase in neural volume in response to cognitive training or experience is a clear indicator of change, but that changes in activation in response to cognitive training may be evidence of strategy change rather than indicative of neural plasticity. We note that the effect of cognitive training is surprisingly durable over time, but that the evidence that training effects transfer to other cognitive domains is relatively limited. We review evidence which suggests that engagement in an environment that requires sustained cognitive effort may facilitate cognitive function.

scholarly journals Impaired Mitophagy in Neurons and Glial Cells during Aging and Age-Related Disorders

2021 ◽  
Vol 22 (19) ◽  
pp. 10251
Author(s):  
Vladimir Sukhorukov ◽  
Dmitry Voronkov ◽  
Tatiana Baranich ◽  
Natalia Mudzhiri ◽  
Alina Magnaeva ◽  
...  
Keyword(s):  
Glial Cells ◽  
Brain Aging ◽  
Cellular Level ◽  
Aging Brain ◽  
The Past ◽  
Age Related ◽  
Accumulation Of Damage ◽  
Quantity Control ◽  
The Brain

Aging is associated with a decline in cognitive function, which can partly be explained by the accumulation of damage to the brain cells over time. Neurons and glia undergo morphological and ultrastructure changes during aging. Over the past several years, it has become evident that at the cellular level, various hallmarks of an aging brain are closely related to mitophagy. The importance of mitochondria quality and quantity control through mitophagy is highlighted by the contribution that defects in mitochondria–autophagy crosstalk make to aging and age-related diseases. In this review, we analyze some of the more recent findings regarding the study of brain aging and neurodegeneration in the context of mitophagy. We discuss the data on the dynamics of selective autophagy in neurons and glial cells during aging and in the course of neurodegeneration, focusing on three mechanisms of mitophagy: non-receptor-mediated mitophagy, receptor-mediated mitophagy, and transcellular mitophagy. We review the role of mitophagy in neuronal/glial homeostasis and in the molecular pathogenesis of neurodegenerative disorders, such as Parkinson’s disease, Alzheimer’s disease, and other disorders. Common mechanisms of aging and neurodegeneration that are related to different mitophagy pathways provide a number of promising targets for potential therapeutic agents.

scholarly journals Chronic administration of a positive allosteric modulator at the α5-GABAA receptor reverses age-related dendritic shrinkage

2020 ◽  
Author(s):  
Thomas D. Prevot ◽  
Akiko Sumitomo ◽  
Toshifumi Tomoda ◽  
Daniel E. Knutson ◽  
Guanguan Li ◽  
...  
Keyword(s):  
Life Expectancy ◽  
Cognitive Decline ◽  
Neuronal Morphology ◽  
Aging Brain ◽  
Primary Neuronal Culture ◽  
Efficient Treatment ◽  
Gaba A ◽  
Age Related ◽  
Β Amyloid ◽  
The Brain

ABSTRACTOver the last 15 years, worldwide life expectancy increased by 5 years jumping from 66 years to 71 years. With progress in science, medicine, and care we tend to live longer. Such extended life expectancy is still associated with age-related changes, including in the brain. The aging brain goes through various changes that can be called morphomolecular senescence. Overall, the brain volume changes, neuronal activity is modified and plasticity of the cells diminishes, sometimes leading to neuronal atrophy and death. Altogether, these changes contribute to the emergence of cognitive decline that still does not have an efficient treatment available. Many studies in the context of cognitive decline focused on pathological aging, targeting β-amyloid in Alzheimer’s disease, for example. However, β-amyloid plaques are also present in healthy adults and treatments targeting plaques have failed to improve cognitive functions. In order to improve the quality of life of aging population, it is crucial to focus on the development of novel therapies targeting different systems altered during aging, such as the GABAergic system. In previous studies, it has been shown that positive allosteric modulators (PAM) acting at the α5-containing GABA-A receptors improve cognitive performances, and that these α5-GABA-A receptors are implicated in dendritic growth of pyramidal neurons. Here, we hypothesized that targeting the α5-GABA-A receptors could contribute to the reduction of cognitive decline, directly through activity of the receptors, and indirectly by increasing neuronal morphology. Using primary neuronal culture and chronic treatment in mice, we demonstrated that an α5-PAM increased dendritic length, spine count and spine density in brain regions involved in cognitive processes (prefrontal cortex and hippocampus). We also confirmed the procognitive efficacy of the α5-PAM and showed that the washout period diminishes the precognitive effects without altering the effect on neuronal morphology. Future studies will be needed to investigate what downstream mechanisms responsible for the neurotrophic effect of the α5-PAM.

scholarly journals Whole-Brain Dynamics in Aging: Disruptions in Functional Connectivity and the Role of the Rich Club

2020 ◽  
Author(s):  
Anira Escrichs ◽  
Carles Biarnes ◽  
Josep Garre-Olmo ◽  
José Manuel Fernández-Real ◽  
Rafel Ramos ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Functional Network ◽  
Brain Dynamics ◽  
Whole Brain ◽  
Rich Club ◽  
Brain Functional Network ◽  
Age Related ◽  
Age Range ◽  
The Brain

Abstract Normal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state functional magnetic resonance imaging studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here, we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent signals to analyze resting-state fMRI data from 620 subjects divided into two groups (middle-age group (n = 310); age range, 50–64 years versus older group (n = 310); age range, 65–91 years). Applying the intrinsic-ignition framework to assess the effect of spontaneous local activation events on local–global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

N-acetyl-l-cysteine attenuates oxidative damage and neurodegeneration in rat brain during aging

2018 ◽  
Vol 96 (12) ◽  
pp. 1189-1196 ◽  
Author(s):  
Geetika Garg ◽  
Sandeep Singh ◽  
Abhishek Kumar Singh ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Rat Brain ◽  
Neuroprotective Effect ◽  
Neuron Specific Enolase ◽  
Sirtuin 1 ◽  
Marker Genes ◽  
Aging Brain ◽  
Age Related ◽  
Nonenzymatic Antioxidants ◽  
Old Rats ◽  
The Brain

N-acetyl-l-cysteine (NAC) is a precursor of cysteine, which is known to increase the level of glutathione (GSH) in the brain. Several neurodegenerative changes linked to oxidative stress take place in the aging brain. This study aimed to assess the neuroprotective effect of NAC supplementation on age-dependent neurodegeneration in the rat brain. Young (4 months) and old (24 months) Wistar rats (n = 6 rats/group) were supplemented with NAC (100 mg/kg b.w. orally) for 14 days. Enzymatic and nonenzymatic antioxidants such as superoxide dismutase and catalase, and GSH and total thiol respectively, prooxidants such as protein carbonyl, advanced oxidation protein products, reactive oxygen species, and malondialdehyde were assessed in the brain homogenates. Furthermore, nitric oxide level, acetylcholinesterase activity, and Na+/K+–ATPase activity were measured and gene expression studies were also performed. The results indicated that NAC augmented the level of enzymatic and nonenzymatic antioxidants with a significant reduction in prooxidant levels in old rats. NAC supplementation also downregulated the expression of inflammatory markers (TNF-α, IL-1β, IL-6) and upregulated the expression of marker genes associated with aging (sirtuin-1) and neurodegeneration (neuron-specific enolase, neuroglobin, synapsin-I, myelin basic protein 2) in old rats. The present findings support a neuroprotective role of NAC which has therapeutic implication in controlling age-related neurological disorders.

scholarly journals Whole-brain dynamics in aging: disruptions in functional connectivity and the role of the rich club

2020 ◽  
Author(s):  
Anira Escrichs ◽  
Carles Biarnes ◽  
Josep Garre-Olmo ◽  
José Manuel Fernández-Real ◽  
Rafel Ramos ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Resting State ◽  
Resting State Fmri ◽  
Brain Dynamics ◽  
Whole Brain ◽  
Rich Club ◽  
Brain Functional Network ◽  
Age Related ◽  
Age Range ◽  
The Brain

AbstractNormal aging causes disruptions in the brain that can lead to cognitive decline. Resting-state fMRI studies have found significant age-related alterations in functional connectivity across various networks. Nevertheless, most of the studies have focused mainly on static functional connectivity. Studying the dynamics of resting-state brain activity across the whole-brain functional network can provide a better characterization of age-related changes. Here we employed two data-driven whole-brain approaches based on the phase synchronization of blood-oxygen-level-dependent (BOLD) signals to analyze resting-state fMRI data from 620 subjects divided into two groups (‘middle-age group’ (n=310); age range, 50-65 years vs. ‘older group’ (n=310); age range, 66-91 years). Applying the Intrinsic-Ignition Framework to assess the effect of spontaneous local activation events on local-global integration, we found that the older group showed higher intrinsic ignition across the whole-brain functional network, but lower metastability. Using Leading Eigenvector Dynamics Analysis, we found that the older group showed reduced ability to access a metastable substate that closely overlaps with the so-called rich club. These findings suggest that functional whole-brain dynamics are altered in aging, probably due to a deficiency in a metastable substate that is key for efficient global communication in the brain.

scholarly journals The Biology and Pathobiology of Glutamatergic, Cholinergic, and Dopaminergic Signaling in the Aging Brain

2021 ◽  
Vol 13 ◽  
Author(s):  
Anna Gasiorowska ◽  
Malgorzata Wydrych ◽  
Patrycja Drapich ◽  
Maciej Zadrozny ◽  
Marta Steczkowska ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Experimental Studies ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
The Elderly ◽  
Aging Brain ◽  
Detailed Knowledge ◽  
Age Related ◽  
Parkinson’S Diseases ◽  
The Brain

The elderly population is growing worldwide, with important health and socioeconomic implications. Clinical and experimental studies on aging have uncovered numerous changes in the brain, such as decreased neurogenesis, increased synaptic defects, greater metabolic stress, and enhanced inflammation. These changes are associated with cognitive decline and neurobehavioral deficits. Although aging is not a disease, it is a significant risk factor for functional worsening, affective impairment, disease exaggeration, dementia, and general disease susceptibility. Conversely, life events related to mental stress and trauma can also lead to accelerated age-associated disorders and dementia. Here, we review human studies and studies on mice and rats, such as those modeling human neurodegenerative diseases, that have helped elucidate (1) the dynamics and mechanisms underlying the biological and pathological aging of the main projecting systems in the brain (glutamatergic, cholinergic, and dopaminergic) and (2) the effect of defective glutamatergic, cholinergic, and dopaminergic projection on disabilities associated with aging and neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases. Detailed knowledge of the mechanisms of age-related diseases can be an important element in the development of effective ways of treatment. In this context, we briefly analyze which adverse changes associated with neurodegenerative diseases in the cholinergic, glutaminergic and dopaminergic systems could be targeted by therapeutic strategies developed as a result of our better understanding of these damaging mechanisms.

scholarly journals Age-Related EEG Power Reductions Cannot Be Explained by Changes of the Conductivity Distribution in the Head Due to Brain Atrophy

2021 ◽  
Vol 13 ◽  
Author(s):  
Mingjian He ◽  
Feng Liu ◽  
Aapo Nummenmaa ◽  
Matti Hämäläinen ◽  
Bradford C. Dickerson ◽  
...  
Keyword(s):  
Neural Activity ◽  
Underlying Mechanism ◽  
Elderly Subjects ◽  
Aging Brain ◽  
Signal Attenuation ◽  
Electrical Currents ◽  
Age Related ◽  
Eeg Power ◽  
Electroencephalogram Eeg ◽  
The Brain

Electroencephalogram (EEG) power reductions in the aging brain have been described by numerous previous studies. However, the underlying mechanism for the observed brain signal power reduction remains unclear. One possible cause for reduced EEG signals in elderly subjects might be the increased distance from the primary neural electrical currents on the cortex to the scalp electrodes as the result of cortical atrophies. While brain shrinkage itself reflects age-related neurological changes, the effects of changes in the distribution of electrical conductivity are often not distinguished from altered neural activity when interpreting EEG power reductions. To address this ambiguity, we employed EEG forward models to investigate whether brain shrinkage is a major factor for the signal attenuation in the aging brain. We simulated brain shrinkage in spherical and realistic brain models and found that changes in the conductor geometry cannot fully account for the EEG power reductions even when the brain was shrunk to unrealistic sizes. Our results quantify the extent of power reductions from brain shrinkage and pave the way for more accurate inferences about deficient neural activity and circuit integrity based on EEG power reductions in the aging population.

scholarly journals Age-related declines in neural distinctiveness correlate across brain areas and result from both decreased reliability and increased confusability

2021 ◽  
Author(s):  
Molly Simmonite ◽  
Thad A Polk
Keyword(s):  
Neural Activity ◽  
Healthy Aging ◽  
Brain Regions ◽  
Aging Brain ◽  
Activation Patterns ◽  
Neural Representations ◽  
Age Related ◽  
Behavioural Performance ◽  
The Difference ◽  
The Brain

According to the neural dedifferentiation hypothesis, age-related reductions in the distinctiveness of neural representations contribute to sensory, cognitive, and motor declines associated with aging: neural activity associated with different stimulus categories becomes more confusable with age and behavioural performance suffers as a result. Initial studies investigated age-related dedifferentiation in the visual cortex, but subsequent research has revealed declines in other brain regions, suggesting that dedifferentiation may be a general feature of the aging brain. In the present study, we used functional magnetic resonance imaging to investigate age-related dedifferentiation in the visual, auditory, and motor cortices. Participants were 58 young adults and 79 older adults. The similarity of activation patterns across different blocks of the same condition was calculated (within-condition correlation, a measure of reliability) as was the similarity of activation patterns elicited by different conditions (between-category correlations, a measure of confusability). Neural distinctiveness was defined as the difference between the mean within- and between-condition similarity. We found age-related reductions in neural distinctiveness in the visual, auditory, and motor cortices, which were driven by both decreases in within-category similarity and increases in between-category similarity. There were significant positive cross-region correlations between neural distinctiveness in different regions. These correlations were driven by within-category similarities, a finding that indicates that declines in the reliability of neural activity appear to occur in tandem across the brain. These findings suggest that the changes in neural distinctiveness that occur in healthy aging result from changes in both the reliability and confusability of patterns of neural activity.

scholarly journals Therapeutic potential of systemic brain rejuvenation strategies for neurodegenerative disease

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1291 ◽  
Author(s):  
Alana M. Horowitz ◽  
Saul A. Villeda
Keyword(s):  
Neurodegenerative Disease ◽  
Therapeutic Potential ◽  
Aging Brain ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Functional Changes ◽  
Aged Brain ◽  
Age Related ◽  
New Findings ◽  
The Brain

Neurodegenerative diseases are a devastating group of conditions that cause progressive loss of neuronal integrity, affecting cognitive and motor functioning in an ever-increasing number of older individuals. Attempts to slow neurodegenerative disease advancement have met with little success in the clinic; however, a new therapeutic approach may stem from classic interventions, such as caloric restriction, exercise, and parabiosis. For decades, researchers have reported that these systemic-level manipulations can promote major functional changes that extend organismal lifespan and healthspan. Only recently, however, have the functional effects of these interventions on the brain begun to be appreciated at a molecular and cellular level. The potential to counteract the effects of aging in the brain, in effect rejuvenating the aged brain, could offer broad therapeutic potential to combat dementia-related neurodegenerative disease in the elderly. In particular, results from heterochronic parabiosis and young plasma administration studies indicate that pro-aging and rejuvenating factors exist in the circulation that can independently promote or reverse age-related phenotypes. The recent demonstration that human umbilical cord blood similarly functions to rejuvenate the aged brain further advances this work to clinical translation. In this review, we focus on these blood-based rejuvenation strategies and their capacity to delay age-related molecular and functional decline in the aging brain. We discuss new findings that extend the beneficial effects of young blood to neurodegenerative disease models. Lastly, we explore the translational potential of blood-based interventions, highlighting current clinical trials aimed at addressing therapeutic applications for the treatment of dementia-related neurodegenerative disease in humans.

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