Structural Imaging Measures of Brain Aging

PubMed Central

Lockhart, Samuel N.

2014-01-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society. PMID:25146995

Structural imaging measures of brain aging.

PubMed

Lockhart, Samuel N; DeCarli, Charles

2014-09-01

During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily "normal" or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer's disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer's disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between "Normal" and "Healthy" brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

Acute care alternate-level-of-care days due to delayed discharge for traumatic and non-traumatic brain injuries.

PubMed

Amy, Chen; Zagorski, Brandon; Chan, Vincy; Parsons, Daria; Vander Laan, Rika; Colantonio, Angela

2012-05-01

Alternate-level-of-care (ALC) days represent hospital beds that are taken up by patients who would more appropriately be cared for in other settings. ALC days have been found to be costly and may result in worse functional outcomes, reduced motor skills and longer lengths of stay in rehabilitation. This study examines the factors that are associated with acute care ALC days among patients with acquired brain injury (ABI). We used the Discharge Abstract Database to identify patients with ABI using International Classification of Disease-10 codes. From fiscal years 2007/08 to 2009/10, 17.5% of patients with traumatic and 14% of patients with non-traumatic brain injury had at least one ALC day. Significant predictors include having a psychiatric co-morbidity, increasing age and length of stay in acute care. These findings can inform planning for care of people with ABI in a publicly funded healthcare system.

Early parental care is important for hippocampal maturation: evidence from brain morphology in humans.

PubMed

Rao, Hengyi; Betancourt, Laura; Giannetta, Joan M; Brodsky, Nancy L; Korczykowski, Marc; Avants, Brian B; Gee, James C; Wang, Jiongjiong; Hurt, Hallam; Detre, John A; Farah, Martha J

2010-01-01

The effects of early life experience on later brain structure and function have been studied extensively in animals, yet the relationship between childhood experience and normal brain development in humans remains largely unknown. Using a unique longitudinal data set including ecologically valid in-home measures of early experience during childhood (at age 4 and 8 years) and high-resolution structural brain imaging during adolescence (mean age 14 years), we examined the effects on later brain morphology of two dimensions of early experience: parental nurturance and environmental stimulation. Parental nurturance at age 4 predicts the volume of the left hippocampus in adolescence, with better nurturance associated with smaller hippocampal volume. In contrast, environmental stimulation did not correlate with hippocampal volume. Moreover, the association between hippocampal volume and parental nurturance disappears at age 8, supporting the existence of a sensitive developmental period for brain maturation. These findings indicate that variation in normal childhood experience is associated with differences in brain morphology, and hippocampal volume is specifically associated with early parental nurturance. Our results provide neuroimaging evidence supporting the important role of warm parental care during early childhood for brain maturation.

Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

PubMed

Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

2016-07-01

Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. Copyright © 2016 Elsevier Inc. All rights reserved.

Gender effects on age-related changes in brain structure.

PubMed

Xu, J; Kobayashi, S; Yamaguchi, S; Iijima, K; Okada, K; Yamashita, K

2000-01-01

Previous reports have suggested that brain atrophy is associated with aging and that there are gender differences in brain atrophy with aging. These reports, however, neither exclude silent brain lesions in "healthy subjects" nor divide the brain into subregions. The aim of this study is to clarify the effect of gender on age-related changes in brain subregions by MR imaging. A computer-assisted system was used to calculate the brain matter area index (BMAI) of various regions of the brain from MR imaging of 331 subjects without brain lesions. There was significantly more brain atrophy with aging in the posterior parts of the right frontal lobe in male subjects than there was in female subjects. Age-related atrophy in the middle part of the right temporal lobe, the left basal ganglia, the parietal lobe, and the cerebellum also was found in male subjects, but not in female subjects. In the temporal lobe, thalamus, parieto-occipital lobe, and cerebellum, brain volume in the left hemisphere is significantly smaller than in the right hemisphere; sex and age did not affect the hemisphere differences of brain volume in these regions. The effect of gender on brain atrophy with aging varied in different subregions of the brain. There was more brain atrophy with aging in male subjects than in female subjects.

Loss of Brain Aerobic Glycolysis in Normal Human Aging.

PubMed

Goyal, Manu S; Vlassenko, Andrei G; Blazey, Tyler M; Su, Yi; Couture, Lars E; Durbin, Tony J; Bateman, Randall J; Benzinger, Tammie L-S; Morris, John C; Raichle, Marcus E

2017-08-01

The normal aging human brain experiences global decreases in metabolism, but whether this affects the topography of brain metabolism is unknown. Here we describe PET-based measurements of brain glucose uptake, oxygen utilization, and blood flow in cognitively normal adults from 20 to 82 years of age. Age-related decreases in brain glucose uptake exceed that of oxygen use, resulting in loss of brain aerobic glycolysis (AG). Whereas the topographies of total brain glucose uptake, oxygen utilization, and blood flow remain largely stable with age, brain AG topography changes significantly. Brain regions with high AG in young adults show the greatest change, as do regions with prolonged developmental transcriptional features (i.e., neoteny). The normal aging human brain thus undergoes characteristic metabolic changes, largely driven by global loss and topographic changes in brain AG. Copyright © 2017 Elsevier Inc. All rights reserved.

Age-and Brain Region-Specific Differences in Mitochondrial ...

EPA Pesticide Factsheets

Mitochondria are central regulators of energy homeostasis and play a pivotal role in mechanisms of cellular senescence. The objective of the present study was to evaluate mitochondrial bio­-energetic parameters in five brain regions [brainstem (BS), frontal cortex (FC), cerebellum (CER), striatum (STR), hippocampus (HIP)] of four diverse age groups [1 Month (young), 4 Month (adult), 12 Month (middle-aged), 24 Month (old age)] to understand age-related differences in selected brain regions and their contribution to age-related chemical sensitivity. Mitochondrial bioenergetics parameters and enzyme activity were measured under identical conditions across multiple age groups and brain regions in Brown Norway rats (n = 5). The results indicate age- and brain region-specific patterns in mitochondrial functional endpoints. For example, an age-specific decline in ATP synthesis (State 111 respiration) was observed in BS and HIP. Similarly, the maximal respiratory capacities (State V1 and V2) showed age-specific declines in all brain regions examined (young > adult > middle-aged > old age). Amongst all regions, HIP had the greatest change in mitochondrial bioenergetics, showing declines in the 4, 12 and 24 Month age groups. Activities of mitochondrial pyruvate dehydrogenase complex (PDHC) and electron transport chain (ETC) complexes I, II, and IV enzymes were also age- and brain-region specific. In general changes associated with age were more pronounced, with

Do glutathione levels decline in aging human brain?

PubMed

Tong, Junchao; Fitzmaurice, Paul S; Moszczynska, Anna; Mattina, Katie; Ang, Lee-Cyn; Boileau, Isabelle; Furukawa, Yoshiaki; Sailasuta, Napapon; Kish, Stephen J

2016-04-01

For the past 60 years a major theory of "aging" is that age-related damage is largely caused by excessive uncompensated oxidative stress. The ubiquitous tripeptide glutathione is a major antioxidant defense mechanism against reactive free radicals and has also served as a marker of changes in oxidative stress. Some (albeit conflicting) animal data suggest a loss of glutathione in brain senescence, which might compromise the ability of the aging brain to meet the demands of oxidative stress. Our objective was to establish whether advancing age is associated with glutathione deficiency in human brain. We measured reduced glutathione (GSH) levels in multiple regions of autopsied brain of normal subjects (n=74) aged one day to 99 years. Brain GSH levels during the infancy/teenage years were generally similar to those in the oldest examined adult group (76-99 years). During adulthood (23-99 years) GSH levels remained either stable (occipital cortex) or increased (caudate nucleus, frontal and cerebellar cortices). To the extent that GSH levels represent glutathione antioxidant capacity, our postmortem data suggest that human brain aging is not associated with declining glutathione status. We suggest that aged healthy human brains can maintain antioxidant capacity related to glutathione and that an age-related increase in GSH levels in some brain regions might possibly be a compensatory response to increased oxidative stress. Since our findings, although suggestive, suffer from the generic limitations of all postmortem brain studies, we also suggest the need for "replication" investigations employing the new (1)H MRS imaging procedures in living human brain. Copyright © 2016 Elsevier Inc. All rights reserved.

N-terminal pro–brain natriuretic peptide and abnormal brain aging

PubMed Central

Sabayan, Behnam; van Buchem, Mark A.; de Craen, Anton J.M.; Sigurdsson, Sigurdur; Zhang, Qian; Harris, Tamara B.; Gudnason, Vilmundur; Arai, Andrew E.

2015-01-01

Objective: To investigate the independent association of serum N-terminal fragment of the prohormone natriuretic peptide (NT-proBNP) with structural and functional features of abnormal brain aging in older individuals. Methods: In this cross-sectional study based on the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study, we included 4,029 older community-dwelling individuals (born 1907 to 1935) with a measured serum level of NT-proBNP. Outcomes included parenchymal brain volumes estimated from brain MRI, cognitive function measured by tests of memory, processing speed, and executive functioning, and presence of depressive symptoms measured using the Geriatric Depression Scale. In a substudy, cardiac output of 857 participants was assessed using cardiac MRI. Results: In multivariate analyses, adjusted for sociodemographic and cardiovascular factors, higher levels of NT-proBNP were independently associated with lower total (p < 0.001), gray matter (p < 0.001), and white matter (p = 0.001) brain volumes. Likewise, in multivariate analyses, higher levels of NT-proBNP were associated with worse scores in memory (p = 0.005), processing speed (p = 0.001), executive functioning (p < 0.001), and more depressive symptoms (p = 0.002). In the substudy, the associations of higher NT-proBNP with lower brain parenchymal volumes, impaired executive function and processing speed, and higher depressive symptoms were independent of the level of cardiac output. Conclusions: Higher serum levels of NT-proBNP, independent of cardiovascular risk factors and a measure of cardiac function, are linked with alterations in brain structure and function. Roles of natriuretic peptides in the process of brain aging need to be further elucidated. PMID:26231259

Postnatal Brain Growth Assessed by Sequential Cranial Ultrasonography in Infants Born <30 Weeks' Gestational Age.

PubMed

Cuzzilla, R; Spittle, A J; Lee, K J; Rogerson, S; Cowan, F M; Doyle, L W; Cheong, J L Y

2018-06-01

Brain growth in the early postnatal period following preterm birth has not been well described. This study of infants born at <30 weeks' gestational age and without major brain injury aimed to accomplish the following: 1) assess the reproducibility of linear measures made from cranial ultrasonography, 2) evaluate brain growth using sequential cranial ultrasonography linear measures from birth to term-equivalent age, and 3) explore perinatal predictors of postnatal brain growth. Participants comprised 144 infants born at <30 weeks' gestational age at a single center between January 2011 and December 2013. Infants with major brain injury seen on cranial ultrasonography or congenital or chromosomal abnormalities were excluded. Brain tissue and fluid spaces were measured from cranial ultrasonography performed as part of routine clinical care. Brain growth was assessed in 3 time intervals: <7, 7-27, and >27 days' postnatal age. Data were analyzed using intraclass correlation coefficients and mixed-effects regression. A total of 429 scans were assessed for 144 infants. Several linear measures showed excellent reproducibility. All measures of brain tissue increased with postnatal age, except for the biparietal diameter, which decreased within the first postnatal week and increased thereafter. Gestational age of ≥28 weeks at birth was associated with slower growth of the biparietal diameter and ventricular width compared with gestational age of <28 weeks. Postnatal corticosteroid administration was associated with slower growth of the corpus callosum length, transcerebellar diameter, and vermis height. Sepsis and necrotizing enterocolitis were associated with slower growth of the transcerebellar diameter. Postnatal brain growth in infants born at <30 weeks' gestational age can be evaluated using sequential linear measures made from routine cranial ultrasonography and is associated with perinatal predictors of long-term development. © 2018 by American Journal of

The Impact of Traumatic Brain Injury on the Aging Brain.

PubMed

Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

2016-09-01

Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident.

Two hands, one brain, and aging.

PubMed

Maes, Celine; Gooijers, Jolien; Orban de Xivry, Jean-Jacques; Swinnen, Stephan P; Boisgontier, Matthieu P

2017-04-01

Many activities of daily living require moving both hands in an organized manner in space and time. Therefore, understanding the impact of aging on bimanual coordination is essential for prolonging functional independence and well-being in older adults. Here we investigated the behavioral and neural determinants of bimanual coordination in aging. The studies surveyed in this review reveal that aging is associated with cortical hyper-activity (but also subcortical hypo-activity) during performance of bimanual tasks. In addition to changes in activation in local areas, the interaction between distributed brain areas also exhibits age-related effects, i.e., functional connectivity is increased in the resting brain as well as during task performance. The mechanisms and triggers underlying these functional activation and connectivity changes remain to be investigated. This requires further research investment into the detailed study of interactions between brain structure, function and connectivity. This will also provide the foundation for interventional research programs towards preservation of brain health and behavioral performance by maximizing neuroplasticity potential in older adults. Copyright © 2017 Elsevier Ltd. All rights reserved.

Putting the 'care' back into aged care.

PubMed

Beadnell, Cathy

2006-04-01

Aged care is well and truly back on the political agenda in Australia. While the mainstream media has recently exposed a number of horrific cases of alleged abuse in aged care facilities it has done little to highlight the failings of social policy over time or to foster debate on how to improve the care of older Australians. What are the barriers to providing safe and quality aged care to a growing number of our citizens and how do we overcome them? If you relied on the recent media coverage for your impression of aged care you could be forgiven for thinking it is all bad news. But there are facilities providing high quality care and stories of nurses working wonders in the face of adversity. Cathy Beadnell considers some of the broader cultural and workforce issues in aged care.

Mitochondria, Estrogen and Female Brain Aging

PubMed Central

Lejri, Imane; Grimm, Amandine; Eckert, Anne

2018-01-01

Mitochondria play an essential role in the generation of steroid hormones including the female sex hormones. These hormones are, in turn, able to modulate mitochondrial activities. Mitochondria possess crucial roles in cell maintenance, survival and well-being, because they are the main source of energy as well as of reactive oxygen species (ROS) within the cell. The impairment of these important organelles is one of the central features of aging. In women’s health, estrogen plays an important role during adulthood not only in the estrous cycle, but also in the brain via neuroprotective, neurotrophic and antioxidant modes of action. The hypestrogenic state in the peri- as well as in the prolonged postmenopause might increase the vulnerability of elderly women to brain degeneration and age-related pathologies. However, the underlying mechanisms that affect these processes are not well elucidated. Understanding the relationship between estrogen and mitochondria might therefore provide better insights into the female aging process. Thus, in this review, we first describe mitochondrial dysfunction in the aging brain. Second, we discuss the estrogen-dependent actions on the mitochondrial activity, including recent evidence of the estrogen—brain-derived neurotrophic factor and estrogen—sirtuin 3 (SIRT3) pathways, as well as their potential implications during female aging. PMID:29755342

Brain-oriented care in the NICU: a case study.

PubMed

Bader, Lisa

2014-01-01

With the advances of technology and treatment in the field of neonatal care, researchers can now study how the brains of preterm infants are different from full-term infants. The differences are significant, and the outcomes are poor overall for premature infants as a whole. Caregivers at the bedside must know that every interaction with the preterm infant affects brain development-it is critical to the developmental outcome of the infant. The idea of neuroprotection is not new to the medical field but is a fairly new idea to the NICU. Neuroprotection encompasses all interventions that promote normal development of the brain. The concept of brain-oriented care is a necessary extension of developmental care in the NICU. By following the journey of 26-week preterm twin infants through a case study, one can better understand the necessity of brain-oriented care at the bedside.

Aging, Brain Size, and IQ.

ERIC Educational Resources Information Center

Bigler, Erin D.; And Others

1995-01-01

Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

Developing a Family-Centered Care Model for Critical Care After Pediatric Traumatic Brain Injury.

PubMed

Moore, Megan; Robinson, Gabrielle; Mink, Richard; Hudson, Kimberly; Dotolo, Danae; Gooding, Tracy; Ramirez, Alma; Zatzick, Douglas; Giordano, Jessica; Crawley, Deborah; Vavilala, Monica S

2015-10-01

This study examined the family experience of critical care after pediatric traumatic brain injury in order to develop a model of specific factors associated with family-centered care. Qualitative methods with semi-structured interviews were used. Two level 1 trauma centers. Fifteen mothers of children who had an acute hospital stay after traumatic brain injury within the last 5 years were interviewed about their experience of critical care and discharge planning. Participants who were primarily English, Spanish, or Cantonese speaking were included. None. Content analysis was used to code the transcribed interviews and develop the family-centered care model. Three major themes emerged: 1) thorough, timely, compassionate communication, 2) capacity building for families, providers, and facilities, and 3) coordination of care transitions. Participants reported valuing detailed, frequent communication that set realistic expectations and prepared them for decision making and outcomes. Areas for capacity building included strategies to increase provider cultural humility, parent participation in care, and institutional flexibility. Coordinated care transitions, including continuity of information and maintenance of partnerships with families and care teams, were highlighted. Participants who were not primarily English speaking reported particular difficulty with communication, cultural understanding, and coordinated transitions. This study presents a family-centered traumatic brain injury care model based on family perspectives. In addition to communication and coordination strategies, the model offers methods to address cultural and structural barriers to meeting the needs of non-English-speaking families. Given the stress experienced by families of children with traumatic brain injury, careful consideration of the model themes identified here may assist in improving overall quality of care to families of hospitalized children with traumatic brain injury.

Brain death and true patient care

PubMed Central

2016-01-01

The “brain death” standard as a criterion of death is closely associated with the need for transplantable organs from heart-beating donors. Are all of these potential donors really dead, or does the documented evidence of patients destined for organ harvesting who improve, or even recover to live normal lives, call into question the premise underlying “brain death”? The aim of this paper is to re-examine the notion of “brain death,” especially its clinical test-criteria, in light of a broad framework, including medical knowledge in the field of neuro-intensive care and the traditional ethics of the medical profession. I will argue that both the empirical medical evidence and the ethics of the doctor–patient relationship point to an alternative approach toward the severely comatose patient (potential brain-dead donor). Lay Summary: Though legally accepted and widely practiced, the “brain death” standard for the determination of death has remained a controversial issue, especially in view of the occurrence of “chronic brain death” survivors. This paper critically re-evaluates the clinical test-criteria for “brain death,” taking into account what is known about the neuro-critical care of severe brain injury. The medical evidence, together with the understanding of the moral role of the physician toward the patient present before him or her, indicate that an alternative approach should be offered to the deeply comatose patient. PMID:27833207

[The blood-brain barrier in ageing persons].

PubMed

Haaning, Nina; Damsgaard, Else Marie; Moos, Torben

2018-03-26

Brain capillary endothelial cells (BECs) form the ultra-tight blood-brain barrier (BBB). The permeability of the BBB increases with increasing age and neurovascular and neurodegenerative diseases. Major defects of the BBB can be initiated by increased permeability to plasma proteins in small arteriosclerotic arteries and release of proteins from degenerating neurons into the brain extracellular space. These proteins deposit in perivascular spaces, and subsequently negatively influence the BECs leading to decreased expression of barrier proteins. Detection of BBB defects by the use of non-invasive techniques is relevant for clinical use in settings with advanced age and severe brain disorders.

Light-sensitive brain pathways and aging.

PubMed

Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

2016-03-15

Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

Accelerated Brain Aging in Schizophrenia: A Longitudinal Pattern Recognition Study.

PubMed

Schnack, Hugo G; van Haren, Neeltje E M; Nieuwenhuis, Mireille; Hulshoff Pol, Hilleke E; Cahn, Wiepke; Kahn, René S

2016-06-01

Despite the multitude of longitudinal neuroimaging studies that have been published, a basic question on the progressive brain loss in schizophrenia remains unaddressed: Does it reflect accelerated aging of the brain, or is it caused by a fundamentally different process? The authors used support vector regression, a supervised machine learning technique, to address this question. In a longitudinal sample of 341 schizophrenia patients and 386 healthy subjects with one or more structural MRI scans (1,197 in total), machine learning algorithms were used to build models to predict the age of the brain and the presence of schizophrenia ("schizophrenia score"), based on the gray matter density maps. Age at baseline ranged from 16 to 67 years, and follow-up scans were acquired between 1 and 13 years after the baseline scan. Differences between brain age and chronological age ("brain age gap") and between schizophrenia score and healthy reference score ("schizophrenia gap") were calculated. Accelerated brain aging was calculated from changes in brain age gap between two consecutive measurements. The age prediction model was validated in an independent sample. In schizophrenia patients, brain age was significantly greater than chronological age at baseline (+3.36 years) and progressively increased during follow-up (+1.24 years in addition to the baseline gap). The acceleration of brain aging was not constant: it decreased from 2.5 years/year just after illness onset to about the normal rate (1 year/year) approximately 5 years after illness onset. The schizophrenia gap also increased during follow-up, but more pronounced variability in brain abnormalities at follow-up rendered this increase nonsignificant. The progressive brain loss in schizophrenia appears to reflect two different processes: one relatively homogeneous, reflecting accelerated aging of the brain and related to various measures of outcome, and a more variable one, possibly reflecting individual variation and

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging.

PubMed

Zamroziewicz, Marta K; Barbey, Aron K

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

PubMed Central

Zamroziewicz, Marta K.; Barbey, Aron K.

2016-01-01

Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID:27375409

Survival and level of care among breast cancer patients with brain metastases treated with whole brain radiotherapy.

PubMed

Frisk, Gabriella; Tinge, Beatrice; Ekberg, Sara; Eloranta, Sandra; Bäcklund, L Magnus; Lidbrink, Elisabet; Smedby, Karin E

2017-12-01

The benefit of whole brain radiotherapy (WBRT) for late stage breast cancer patients with brain metastases has been questioned. In this study we evaluated survival and level of care (hospital or home) following WBRT in a population-based cohort by personal and tumor characteristics. We identified 241 consecutive patients with breast cancer and brain metastases receiving WBRT in Stockholm, Sweden, 1999-2012. Through review of medical records, we collected data on prognostic determinants including level of care before and after WBRT. Survival was estimated using Cox regression, and odds ratios (OR) of not coming home using logistic regression. Median age at WBRT was 58 years (range 30---88 years). Most patients (n = 212, 88%) were treated with 4 Gray × 5. Median survival following WBRT was 2.9 months (interquartile range 1.1-6.6 months), and 57 patients (24%) were never discharged from hospital. Poor performance status and triple-negative tumors were associated with short survival (WHO 3-4 median survival 0.9 months, HR = 5.96 (3.88-9.17) versus WHO 0-1; triple-negative tumors median survival 2.0 months, HR = 1.87 (1.23-2.84) versus Luminal A). Poor performance status and being hospitalized before WBRT were associated with increased ORs of not coming home whereas cohabitation with children at home was protective. Survival was short following WBRT, and one in four breast cancer patients with brain metastases could never be discharged from hospital. When deciding about WBRT, WHO score, level of care before WBRT, and the patient's choice of level of care in the end-of-life period should be considered.

Genome instability: Linking ageing and brain degeneration.

PubMed

Barzilai, Ari; Schumacher, Björn; Shiloh, Yosef

2017-01-01

Ageing is a multifactorial process affected by cumulative physiological changes resulting from stochastic processes combined with genetic factors, which together alter metabolic homeostasis. Genetic variation in maintenance of genome stability is emerging as an important determinant of ageing pace. Genome instability is also closely associated with a broad spectrum of conditions involving brain degeneration. Similarities and differences can be found between ageing-associated decline of brain functionality and the detrimental effect of genome instability on brain functionality and development. This review discusses these similarities and differences and highlights cell classes whose role in these processes might have been underestimated-glia and microglia. Copyright © 2016. Published by Elsevier B.V.

Aging exacerbates intracerebral hemorrhage-induced brain injury.

PubMed

Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

2009-09-01

Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

Gene expression in the aging human brain: an overview.

PubMed

Mohan, Adith; Mather, Karen A; Thalamuthu, Anbupalam; Baune, Bernhard T; Sachdev, Perminder S

2016-03-01

The review aims to provide a summary of recent developments in the study of gene expression in the aging human brain. Profiling differentially expressed genes or 'transcripts' in the human brain over the course of normal aging has provided valuable insights into the biological pathways that appear activated or suppressed in late life. Genes mediating neuroinflammation and immune system activation in particular, show significant age-related upregulation creating a state of vulnerability to neurodegenerative and neuropsychiatric disease in the aging brain. Cellular ionic dyshomeostasis and age-related decline in a host of molecular influences on synaptic efficacy may underlie neurocognitive decline in later life. Critically, these investigations have also shed light on the mobilization of protective genetic responses within the aging human brain that help determine health and disease trajectories in older age. There is growing interest in the study of pre and posttranscriptional regulators of gene expression, and the role of noncoding RNAs in particular, as mediators of the phenotypic diversity that characterizes human brain aging. Gene expression studies in healthy brain aging offer an opportunity to unravel the intricately regulated cellular underpinnings of neurocognitive aging as well as disease risk and resiliency in late life. In doing so, new avenues for early intervention in age-related neurodegenerative disease could be investigated with potentially significant implications for the development of disease-modifying therapies.

Adaptation of brain functional and structural networks in aging.

PubMed

Lee, Annie; Ratnarajah, Nagulan; Tuan, Ta Anh; Chen, Shen-Hsing Annabel; Qiu, Anqi

2015-01-01

The human brain, especially the prefrontal cortex (PFC), is functionally and anatomically reorganized in order to adapt to neuronal challenges in aging. This study employed structural MRI, resting-state fMRI (rs-fMRI), and high angular resolution diffusion imaging (HARDI), and examined the functional and structural reorganization of the PFC in aging using a Chinese sample of 173 subjects aged from 21 years and above. We found age-related increases in the structural connectivity between the PFC and posterior brain regions. Such findings were partially mediated by age-related increases in the structural connectivity of the occipital lobe within the posterior brain. Based on our findings, it is thought that the PFC reorganization in aging could be partly due to the adaptation to age-related changes in the structural reorganization of the posterior brain. This thus supports the idea derived from task-based fMRI that the PFC reorganization in aging may be adapted to the need of compensation for resolving less distinctive stimulus information from the posterior brain regions. In addition, we found that the structural connectivity of the PFC with the temporal lobe was fully mediated by the temporal cortical thickness, suggesting that the brain morphology plays an important role in the functional and structural reorganization with aging.

Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

PubMed

Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

2016-02-23

We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

Assisted Care Options (Brain Tumors)

MedlinePlus

... Home Care & Hospice National Agency Locator Assisted Living Facilities and Nursing Homes For brain tumor patients who ... activities of daily living (ADLs), an assisted living facility can be a viable option. Your family member ...

Quantitative Machine Learning Analysis of Brain MRI Morphology throughout Aging.

PubMed

Shamir, Lior; Long, Joe

2016-01-01

While cognition is clearly affected by aging, it is unclear whether the process of brain aging is driven solely by accumulation of environmental damage, or involves biological pathways. We applied quantitative image analysis to profile the alteration of brain tissues during aging. A dataset of 463 brain MRI images taken from a cohort of 416 subjects was analyzed using a large set of low-level numerical image content descriptors computed from the entire brain MRI images. The correlation between the numerical image content descriptors and the age was computed, and the alterations of the brain tissues during aging were quantified and profiled using machine learning. The comprehensive set of global image content descriptors provides high Pearson correlation of ~0.9822 with the chronological age, indicating that the machine learning analysis of global features is sensitive to the age of the subjects. Profiling of the predicted age shows several periods of mild changes, separated by shorter periods of more rapid alterations. The periods with the most rapid changes were around the age of 55, and around the age of 65. The results show that the process of brain aging of is not linear, and exhibit short periods of rapid aging separated by periods of milder change. These results are in agreement with patterns observed in cognitive decline, mental health status, and general human aging, suggesting that brain aging might not be driven solely by accumulation of environmental damage. Code and data used in the experiments are publicly available.

Evaluation of the effect of intensity of care on mortality after traumatic brain injury

PubMed Central

Thompson, Hilaire J.; Rivara, Frederick P.; Jurkovich, Gregory J.; Wang, Jin; Nathens, Avery B.; MacKenzie, Ellen J.

2008-01-01

Objectives To evaluate the effect of age on intensity of care provided to traumatically brain-injured adults and to determine the influence of intensity of care on mortality at discharge and 12 months postinjury, controlling for injury severity. Design Cohort study using the National Study on the Costs and Outcomes of Trauma (NSCOT) database. Risk ratio and Poisson regression analyses were performed using data weighted according to the population of eligible patients. Setting and Patients A total of 18 level 1 and 51 level 2 non-trauma centers located in 14 states in the United States and 1,776 adults aged 25−84 yrs with a diagnosis of traumatic brain injury. Measurements Injury severity was determined by the motor component of the Glasgow Coma Scale score, the Injury Severity Score, pupillary reactivity, and presence of midline shift. Factors evaluated as contributing to intensity of care included: admission to the intensive care unit, mechanical ventilation, placement of an intracranial pressure monitor, placement of a jugular bulb catheter, placement of a pulmonary artery catheter, critical care consultation, the number of specialty care consultations, mannitol use, treatment with barbiturate coma, decompressive craniectomy, number of nonneurosurgical procedures performed, the presence of a do-not-resuscitate order, and withdrawal of therapy. Main Results Controlling for injury-related factors, sex, and comorbidity, as age increased, the overall likelihood of receiving various interventions decreased. After controlling for injury severity, sex, and comorbidity, factors associated with higher risk of in-hospital death were: being aged 75−84 yrs (relative risk [RR] 1.32, 95% confidence interval [CI] 1.13, 1.55), pulmonary artery catheter use (RR 1.56, 95% CI 1.30, 1.86), intubation (RR 4.17, 95% CI 2.28, 7.61), the presence of a do-not-resuscitate order (RR 3.21, 95% CI 2.21, 4.65), and withdrawal of therapy (RR 2.33, 95% CI 1.69, 3.23). In contrast, a higher

Non-invasive Brain Stimulation: Probing Intracortical Circuits and Improving Cognition in the Aging Brain

PubMed Central

Gomes-Osman, Joyce; Indahlastari, Aprinda; Fried, Peter J.; Cabral, Danylo L. F.; Rice, Jordyn; Nissim, Nicole R.; Aksu, Serkan; McLaren, Molly E.; Woods, Adam J.

2018-01-01

The impact of cognitive aging on brain function and structure is complex, and the relationship between aging-related structural changes and cognitive function are not fully understood. Physiological and pathological changes to the aging brain are highly variable, making it difficult to estimate a cognitive trajectory with which to monitor the conversion to cognitive decline. Beyond the information on the structural and functional consequences of cognitive aging gained from brain imaging and neuropsychological studies, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) can enable stimulation of the human brain in vivo, offering useful insights into the functional integrity of intracortical circuits using electrophysiology and neuromodulation. TMS measurements can be used to identify and monitor changes in cortical reactivity, the integrity of inhibitory and excitatory intracortical circuits, the mechanisms of long-term potentiation (LTP)/depression-like plasticity and central cholinergic function. Repetitive TMS and tDCS can be used to modulate neuronal excitability and enhance cortical function, and thus offer a potential means to slow or reverse cognitive decline. This review will summarize and critically appraise relevant literature regarding the use of TMS and tDCS to probe cortical areas affected by the aging brain, and as potential therapeutic tools to improve cognitive function in the aging population. Challenges arising from intra-individual differences, limited reproducibility, and methodological differences will be discussed.

Metabolic brain networks in aging and preclinical Alzheimer's disease.

PubMed

Arnemann, Katelyn L; Stöber, Franziska; Narayan, Sharada; Rabinovici, Gil D; Jagust, William J

2018-01-01

Metabolic brain networks can provide insight into the network processes underlying progression from healthy aging to Alzheimer's disease. We explore the effect of two Alzheimer's disease risk factors, amyloid-β and ApoE ε4 genotype, on metabolic brain networks in cognitively normal older adults (N = 64, ages 69-89) compared to young adults (N = 17, ages 20-30) and patients with Alzheimer's disease (N = 22, ages 69-89). Subjects underwent MRI and PET imaging of metabolism (FDG) and amyloid-β (PIB). Normal older adults were divided into four subgroups based on amyloid-β and ApoE genotype. Metabolic brain networks were constructed cross-sectionally by computing pairwise correlations of metabolism across subjects within each group for 80 regions of interest. We found widespread elevated metabolic correlations and desegregation of metabolic brain networks in normal aging compared to youth and Alzheimer's disease, suggesting that normal aging leads to widespread loss of independent metabolic function across the brain. Amyloid-β and the combination of ApoE ε4 led to less extensive elevated metabolic correlations compared to other normal older adults, as well as a metabolic brain network more similar to youth and Alzheimer's disease. This could reflect early progression towards Alzheimer's disease in these individuals. Altered metabolic brain networks of older adults and those at the highest risk for progression to Alzheimer's disease open up novel lines of inquiry into the metabolic and network processes that underlie normal aging and Alzheimer's disease.

Functional neuroimaging of normal aging: Declining brain, adapting brain.

PubMed

Sugiura, Motoaki

2016-09-01

Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain arterial aging and its relationship to Alzheimer dementia

PubMed Central

Honig, Lawrence; Elkind, Mitchell S.V.; Mohr, Jay P.; Goldman, James; Dwork, Andrew J.; Morgello, Susan; Marshall, Randolph S.

2016-01-01

Objective: To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Methods: Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. Results: We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Conclusions: Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. PMID:26984942

Brain arterial aging and its relationship to Alzheimer dementia.

PubMed

Gutierrez, Jose; Honig, Lawrence; Elkind, Mitchell S V; Mohr, Jay P; Goldman, James; Dwork, Andrew J; Morgello, Susan; Marshall, Randolph S

2016-04-19

To test the hypothesis that brain arterial aging is associated with the pathologic diagnosis of Alzheimer disease (AD). Brain large arteries were assessed for diameter, gaps in the internal elastic lamina (IEL), luminal stenosis, atherosclerosis, and lumen-to-wall ratio. Elastin, collagen, and amyloid were assessed with Van Gieson, trichrome, and Congo red staining intensities, and quantified automatically. Brain infarcts and AD (defined pathologically) were assessed at autopsy. We created a brain arterial aging (BAA) score with arterial characteristics associated with aging after adjusting for demographic and clinical variables using cross-sectional generalized linear models. We studied 194 autopsied brains, 25 (13%) of which had autopsy evidence of AD. Brain arterial aging consisted of higher interadventitial and lumen diameters, thickening of the wall, increased prevalence of IEL gaps, concentric intima thickening, elastin loss, increased amyloid deposition, and a higher IEL proportion without changes in lumen-to-wall ratio. In multivariable analysis, a high IEL proportion (B = 1.96, p = 0.030), thick media (B = 3.50, p = 0.001), elastin loss (B = 6.16, p < 0.001), IEL gaps (B = 3.14, p = 0.023), and concentric intima thickening (B = 7.19, p < 0.001) were used to create the BAA score. Adjusting for demographics, vascular risk factors, atherosclerosis, and brain infarcts, the BAA score was associated with AD (B = 0.022, p = 0.002). Aging of brain large arteries is characterized by arterial dilation with a commensurate wall thickening, elastin loss, and IEL gaps. Greater intensity of arterial aging was associated with AD independently of atherosclerosis and brain infarcts. Understanding the drivers of arterial aging may advance the knowledge of the pathophysiology of AD. © 2016 American Academy of Neurology.

Generality and specificity in cognitive aging: a volumetric brain analysis.

PubMed

Staff, Roger T; Murray, Alison D; Deary, Ian J; Whalley, Lawrence J

2006-05-01

To investigate whether, in old age, brain volume differences are associated with age-related change in general mental ability and/or specific cognitive abilities. The authors investigate the association between brain volumes and current cognitive function in a well-characterized sample of healthy old people (aged 79-80) whose intelligence was recorded at age 11. This allowed estimation of intellectual change over the life span. After accounting for childhood intelligence, associations were found between specific cognitive measures and brain volumes. An association was also found between volumes and the general intelligence factor g. After removing the influence of g from each of the specific cognitive measures, no remaining significant associations were found between brain volumes and the specific part of each test. Generalized cognitive aging is associated with brain volume differences, but there is no evidence in this sample that specific components of cognitive aging are associated with differences in brain volume.

Montefiore-Einstein Center for the Aging Brain: Preliminary Data.

PubMed

Verghese, Joe; Malik, Rubina; Zwerling, Jessica

2016-11-01

Given the multifaceted nature of dementia care management, an interdisciplinary comprehensive clinical approach is necessary. We describe our one-year experience with outpatient based dementia care at the Montefiore-Einstein Center for the Aging Brain (CAB) involving an multispecialty team of geriatricians, neurologists, and neuropsychologists, supported by geriatric psychiatrists, physiatrists, and social services. The goals of the CAB is to maximize dementia outcomes, including regular monitoring of patient's health and cognition, education and support to patients, their families and caregivers; initiation of pharmacological and non-pharmacological treatments as appropriate, and the facilitation of access to clinical trials. The CAB follows a consultative model where patients referred to the center receive a comprehensive three step evaluation and management plan from Geriatric, Neuropsychology and Neurology specialists that is shared with patient, caregivers and primary care physicians. Of the 366 patients seen for cognitive complaints in our first year, 71% were women with a mean age of 74 years. Self-identified ethnicity of patients included Caucasian (26%), African-American (25%), Hispanic (18%) and multiracial (5%). Common final diagnoses assigned at the CAB included mild cognitive impairment syndromes (31%), Alzheimer's disease (20%), mixed dementia (11%), vascular dementia (9%), Frontotemporal dementia (4%) and dementia with Lewy bodies (4%). Our one-year progress report indicates that an interdisciplinary clinical dementia care model is feasible in the outpatient setting as well as highly accepted by patients, caregivers and referring physicians. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Reversal of glial and neurovascular markers of unhealthy brain aging by exercise in middle-aged female mice.

PubMed

Latimer, Caitlin S; Searcy, James L; Bridges, Michael T; Brewer, Lawrence D; Popović, Jelena; Blalock, Eric M; Landfield, Philip W; Thibault, Olivier; Porter, Nada M

2011-01-01

Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging.

Reversal of Glial and Neurovascular Markers of Unhealthy Brain Aging by Exercise in Middle-Aged Female Mice

PubMed Central

Latimer, Caitlin S.; Searcy, James L.; Bridges, Michael T.; Brewer, Lawrence D.; Popović, Jelena; Blalock, Eric M.; Landfield, Philip W.; Thibault, Olivier; Porter, Nada M.

2011-01-01

Healthy brain aging and cognitive function are promoted by exercise. The benefits of exercise are attributed to several mechanisms, many which highlight its neuroprotective role via actions that enhance neurogenesis, neuronal morphology and/or neurotrophin release. However, the brain is also composed of glial and vascular elements, and comparatively less is known regarding the effects of exercise on these components in the aging brain. Here, we show that aerobic exercise at mid-age decreased markers of unhealthy brain aging including astrocyte hypertrophy, a hallmark of brain aging. Middle-aged female mice were assigned to a sedentary group or provided a running wheel for six weeks. Exercise decreased hippocampal astrocyte and myelin markers of aging but increased VEGF, a marker of angiogenesis. Brain vascular casts revealed exercise-induced structural modifications associated with improved endothelial function in the periphery. Our results suggest that age-related astrocyte hypertrophy/reactivity and myelin dysregulation are aggravated by a sedentary lifestyle and accompanying reductions in vascular function. However, these effects appear reversible with exercise initiated at mid-age. As this period of the lifespan coincides with the appearance of multiple markers of brain aging, including initial signs of cognitive decline, it may represent a window of opportunity for intervention as the brain appears to still possess significant vascular plasticity. These results may also have particular implications for aging females who are more susceptible than males to certain risk factors which contribute to vascular aging. PMID:22046366

Altered Proteins in the Aging Brain

PubMed Central

Elobeid, Adila; Libard, Sylwia; Leino, Marina; Popova, Svetlana N.

2016-01-01

We assessed the prevalence of common altered brain proteins in 296 cognitively unimpaired subjects ranging from age 50 to 102 years. The incidence and the stage of hyperphosphorylated-τ (HPτ), β-amyloid, α-synuclein (αS), and transactive response DNA (TDP) binding protein 43 (TDP43)-immunoreactivity (-IR) increased with age. HPτ-IR was observed in 98% of the subjects; the locus coeruleus was solely affected in 46%, and 79% of the subjects were in Braak stages a to II. β-Amyloid was seen in 47% of subjects and the Thal phase correlated with the HPτ Braak stage and age. Intermediate Alzheimer disease-related pathology (ADRP) was seen in 12%; 52% of the subjects with HPτ-IR fulfilled criteria for definite primary age-related tauopathy (PART). The incidence of concomitant pathology (αS, TDP43) did not differ between those with PART and those with ADRP but the former were younger. TDP43-IR was observed in 36%; the most frequently affected region was the medulla; αS-IR was observed in 19% of subjects. In 41% of the subjects from 80 to 89 years at death, 3 altered proteins were seen in the brain. Thus, altered proteins are common in the brains of cognitively unimpaired aged subjects; this should be considered while developing diagnostic biomarkers, particularly for identifying subjects at early stages of neurodegenerative diseases. PMID:26979082

[Guidelines for the diagnosis and treatment of severe traumatic brain injury. Part 2. Intensive care and neuromonitoring].

PubMed

Potapov, A A; Krylov, V V; Gavrilov, A G; Kravchuk, A D; Likhterman, L B; Petrikov, S S; Talypov, A E; Zakharova, N E; Oshorov, A V; Sychev, A A; Alexandrova, E V; Solodov, A A

2016-01-01

Traumatic brain injury (TBI) is one of the major causes of death and disability in young and middle-aged people. The most problematic group is comprised of patients with severe TBI who are in a coma. The adequate diagnosis of primary brain injuries and timely prevention and treatment of the secondary injury mechanisms largely define the possibility of reducing mortality and severe disabling consequences. When developing these guidelines, we used our experience in the development of international and national recommendations for the diagnosis and treatment of mild traumatic brain injury, penetrating gunshot wounds to the skull and brain, severe traumatic brain injury, and severe consequences of brain injuries, including a vegetative state. In addition, we used international and national guidelines for the diagnosis, intensive care, and surgical treatment of severe traumatic brain injury, which had been published in recent years. The proposed guidelines concern intensive care of severe TBI in adults and are particularly intended for neurosurgeons, neurologists, neuroradiologists, anesthesiologists, and intensivists who are routinely involved in the treatment of these patients.

Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

PubMed

Mazzeo, A T; Fanelli, V; Mascia, L

2013-03-01

The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

Brain cortical characteristics of lifetime cognitive ageing.

PubMed

Cox, Simon R; Bastin, Mark E; Ritchie, Stuart J; Dickie, David Alexander; Liewald, Dave C; Muñoz Maniega, Susana; Redmond, Paul; Royle, Natalie A; Pattie, Alison; Valdés Hernández, Maria; Corley, Janie; Aribisala, Benjamin S; McIntosh, Andrew M; Wardlaw, Joanna M; Deary, Ian J

2018-01-01

Regional cortical brain volume is the product of surface area and thickness. These measures exhibit partially distinct trajectories of change across the brain's cortex in older age, but it is unclear which cortical characteristics at which loci are sensitive to cognitive ageing differences. We examine associations between change in intelligence from age 11 to 73 years and regional cortical volume, surface area, and thickness measured at age 73 years in 568 community-dwelling older adults, all born in 1936. A relative positive change in intelligence from 11 to 73 was associated with larger volume and surface area in selective frontal, temporal, parietal, and occipital regions (r < 0.180, FDR-corrected q < 0.05). There were no significant associations between cognitive ageing and a thinner cortex for any region. Interestingly, thickness and surface area were phenotypically independent across bilateral lateral temporal loci, whose surface area was significantly related to change in intelligence. These findings suggest that associations between regional cortical volume and cognitive ageing differences are predominantly driven by surface area rather than thickness among healthy older adults. Regional brain surface area has been relatively underexplored, and is a potentially informative biomarker for identifying determinants of cognitive ageing differences.

Brain bank of the Brazilian aging brain study group - a milestone reached and more than 1,600 collected brains.

PubMed

Grinberg, Lea Tenenholz; Ferretti, Renata Eloah de Lucena; Farfel, José Marcelo; Leite, Renata; Pasqualucci, Carlos Augusto; Rosemberg, Sérgio; Nitrini, Ricardo; Saldiva, Paulo Hilário Nascimento; Filho, Wilson Jacob

2007-01-01

Brain banking remains a necessity for the study of aging brain processes and related neurodegenerative diseases. In the present paper, we report the methods applied at and the first results of the Brain Bank of the Brazilian Aging Brain Study Group (BBBABSG) which has two main aims: (1) To collect a large number of brains of elderly comprising non-demented subjects and a large spectrum of pathologies related to aging brain processes, (2) To provide quality material to a multidisciplinar research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases. The subjects are selected from the Sao Paulo Autopsy Service. Brain parts are frozen and fixated. CSF, carotids, kidney, heart and blood are also collected and DNA is extracted. The neuropathological examinations are carried out based on accepted criteria, using immunohistochemistry. Functional status are assessed through a collateral source based on a clinical protocol. Protocols are approved by the local ethics committee and a written informed consent form is obtained. During the first 21 months, 1,602 samples were collected and were classified by Clinical Dementia Rating as CDR0: 65.7%; CDR0.5:12.6%, CDR1:8.2%, CDR2:5.4%, and CDR3:8.1%. On average, the cost for the processing each case stood at 400 US dollars. To date, 14 laboratories have been benefited by the BBBABSG. The high percentage of non- demented subjects and the ethnic diversity of this series may be significantly contributive toward aging brain processes and related neurodegenerative diseases understanding since BBBABSG outcomes may provide investigators the answers to some additional questions.

Spectral Variability in the Aged Brain during Fine Motor Control

PubMed Central

Quandt, Fanny; Bönstrup, Marlene; Schulz, Robert; Timmermann, Jan E.; Zimerman, Maximo; Nolte, Guido; Hummel, Friedhelm C.

2016-01-01

Physiological aging is paralleled by a decline of fine motor skills accompanied by structural and functional alterations of the underlying brain network. Here, we aim to investigate age-related changes in the spectral distribution of neuronal oscillations during fine skilled motor function. We employ the concept of spectral entropy in order to describe the flatness and peaked-ness of a frequency spectrum to quantify changes in the spectral distribution of the oscillatory motor response in the aged brain. Electroencephalogram was recorded in elderly (n = 32) and young (n = 34) participants who performed either a cued finger movement or a pinch or a whole hand grip task with their dominant right hand. Whereas young participant showed distinct, well-defined movement-related power decreases in the alpha and upper beta band, elderly participants exhibited a flat broadband, frequency-unspecific power desynchronization. This broadband response was reflected by an increase of spectral entropy over sensorimotor and frontal areas in the aged brain. Neuronal activation patterns differed between motor tasks in the young brain, while the aged brain showed a similar activation pattern in all tasks. Moreover, we found a wider recruitment of the cortical motor network in the aged brain. The present study adds to the understanding of age-related changes of neural coding during skilled motor behavior, revealing a less predictable signal with great variability across frequencies in a wide cortical motor network in the aged brain. The increase in entropy in the aged brain could be a reflection of random noise-like activity or could represent a compensatory mechanism that serves a functional role. PMID:28066231

The effect of astaxanthin on the aging rat brain: gender-related differences in modulating inflammation.

PubMed

Balietti, Marta; Giannubilo, Stefano R; Giorgetti, Belinda; Solazzi, Moreno; Turi, Angelo; Casoli, Tiziana; Ciavattini, Andrea; Fattorettia, Patrizia

2016-01-30

Astaxanthin (Ax) is a ketocarotenoid of the xanthophyll family with activities such as antioxidation, preservation of the integrity of cell membranes and protection of the redox state and functional integrity of mitochondria. The aim of this study was to investigate potential gender-related differences in the effect of Ax on the aging rat brain. In females, interleukin 1 beta (IL1β) was significantly lower in treated rats in both cerebral areas, and in the cerebellum, treated animals also had significantly higher IL10. In males, no differences were found in the cerebellum, but in the hippocampus, IL1β and IL10 were significantly higher in treated rats. These are the first results to show gender-related differences in the effect of Ax on the aging brain, emphasizing the necessity to carefully analyze female and male peculiarities when the anti-aging potentialities of this ketocarotenoid are evaluated. The observations lead to the hypothesis that Ax exerts different anti-inflammatory effects in female and male brains. © 2015 Society of Chemical Industry.

Caring for Patients with traumatic brain injury: a survey of nurses' perceptions.

PubMed

Oyesanya, Tolu O; Brown, Roger L; Turkstra, Lyn S

2017-06-01

The purpose of this study was to determine nurses' perceptions about caring for patients with traumatic brain injury. Annually, it is estimated that over 10 million people sustain a traumatic brain injury around the world. Patients with traumatic brain injury and their families are often concerned with expectations about recovery and seek information from nurses. Nurses' perceptions of care might influence information provided to patients and families, particularly if inaccurate knowledge and perceptions are held. Thus, nurses must be knowledgeable about care of these patients. A cross-sectional survey, the Perceptions of Brain Injury Survey (PBIS), was completed electronically by 513 nurses between October and December 2014. Data were analysed with structural equation modelling, factor analysis, and pairwise comparisons. Using latent class analysis, authors were able to divide nurses into three homogeneous sub-groups based on perceived knowledge: low, moderate and high. Findings showed that nurses who care for patients with traumatic brain injury the most have the highest perceived confidence but the lowest perceived knowledge. Nurses also had significant variations in training. As there is limited literature on nurses' perceptions of caring for patients with traumatic brain injury, these findings have implications for training and educating nurses, including direction for development of nursing educational interventions. As the incidence of traumatic brain injury is growing, it is imperative that nurses be knowledgeable about care of patients with these injuries. The traumatic brain injury PBIS can be used to determine inaccurate perceptions about caring for patients with traumatic brain injury before educating and training nurses. © 2016 John Wiley & Sons Ltd.

Brain aging and neurodegeneration: from a mitochondrial point of view.

PubMed

Grimm, Amandine; Eckert, Anne

2017-11-01

Aging is defined as a progressive time-related accumulation of changes responsible for or at least involved in the increased susceptibility to disease and death. The brain seems to be particularly sensitive to the aging process since the appearance of neurodegenerative diseases, including Alzheimer's disease, is exponential with the increasing age. Mitochondria were placed at the center of the 'free-radical theory of aging', because these paramount organelles are not only the main producers of energy in the cells, but also to main source of reactive oxygen species. Thus, in this review, we aim to look at brain aging processes from a mitochondrial point of view by asking: (i) What happens to brain mitochondrial bioenergetics and dynamics during aging? (ii) Why is the brain so sensitive to the age-related mitochondrial impairments? (iii) Is there a sex difference in the age-induced mitochondrial dysfunction? Understanding mitochondrial physiology in the context of brain aging may help identify therapeutic targets against neurodegeneration. This article is part of a series "Beyond Amyloid". © 2017 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.

Multiple Brain Markers are Linked to Age-Related Variation in Cognition

PubMed Central

Hedden, Trey; Schultz, Aaron P.; Rieckmann, Anna; Mormino, Elizabeth C.; Johnson, Keith A.; Sperling, Reisa A.; Buckner, Randy L.

2016-01-01

Age-related alterations in brain structure and function have been challenging to link to cognition due to potential overlapping influences of multiple neurobiological cascades. We examined multiple brain markers associated with age-related variation in cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging markers of gray matter thickness and volume, white matter hyperintensities, fractional anisotropy (FA), resting-state functional connectivity, positron emission tomography markers of glucose metabolism and amyloid burden, and cognitive factors of processing speed, executive function, and episodic memory. Partial correlation and mediation analyses estimated age-related variance in cognition shared with individual brain markers and unique to each marker. The largest relationships linked FA and striatum volume to processing speed and executive function, and hippocampal volume to episodic memory. Of the age-related variance in cognition, 70–80% was accounted for by combining all brain markers (but only ∼20% of total variance). Age had significant indirect effects on cognition via brain markers, with significant markers varying across cognitive domains. These results suggest that most age-related variation in cognition is shared among multiple brain markers, but potential specificity between some brain markers and cognitive domains motivates additional study of age-related markers of neural health. PMID:25316342

Age-related apparent diffusion coefficient changes in the normal brain.

PubMed

Watanabe, Memi; Sakai, Osamu; Ozonoff, Al; Kussman, Steven; Jara, Hernán

2013-02-01

To measure the mean diffusional age-related changes of the brain over the full human life span by using diffusion-weighted spin-echo single-shot echo-planar magnetic resonance (MR) imaging and sequential whole-brain apparent diffusion coefficient (ADC) histogram analysis and, secondarily, to build mathematical models of these normal age-related changes throughout human life. After obtaining institutional review board approval, a HIPAA-compliant retrospective search was conducted for brain MR imaging studies performed in 2007 for various clinical indications. Informed consent was waived. The brain data of 414 healthy subjects (189 males and 225 females; mean age, 33.7 years; age range, 2 days to 89.3 years) were obtained with diffusion-weighted spin-echo single-shot echo-planar MR imaging. ADC histograms of the whole brain were generated. ADC peak values, histogram widths, and intracranial volumes were plotted against age, and model parameters were estimated by using nonlinear regression. Four different stages were identified for aging changes in ADC peak values, as characterized by specific mathematical terms: There were age-associated exponential decays for the maturation period and the development period, a constant term for adulthood, and a linear increase for the senescence period. The age dependency of ADC peak value was simulated by using four-term six-coefficient function, including biexponential and linear terms. This model fit the data very closely (R(2) = 0.91). Brain diffusivity as a whole demonstrated age-related changes through four distinct periods of life. These results could contribute to establishing an ADC baseline of the normal brain, covering the full human life span.

Associations between education and brain structure at age 73 years, adjusted for age 11 IQ

PubMed Central

Dickie, David Alexander; Ritchie, Stuart J.; Karama, Sherif; Pattie, Alison; Royle, Natalie A.; Corley, Janie; Aribisala, Benjamin S.; Valdés Hernández, Maria; Muñoz Maniega, Susana; Starr, John M.; Bastin, Mark E.; Evans, Alan C.; Wardlaw, Joanna M.; Deary, Ian J.

2016-01-01

Objective: To investigate how associations between education and brain structure in older age were affected by adjusting for IQ measured at age 11. Methods: We analyzed years of full-time education and measures from an MRI brain scan at age 73 in 617 community-dwelling adults born in 1936. In addition to average and vertex-wise cortical thickness, we measured total brain atrophy and white matter tract fractional anisotropy. Associations between brain structure and education were tested, covarying for sex and vascular health; a second model also covaried for age 11 IQ. Results: The significant relationship between education and average cortical thickness (β = 0.124, p = 0.004) was reduced by 23% when age 11 IQ was included (β = 0.096, p = 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy. Conclusions: The association between years of education and brain structure ≈60 years later was restricted to cortical thickness in this sample; however, the previously reported associations between longer education and a thicker cortex are likely to be overestimates in terms of both magnitude and distribution. This finding has implications for understanding, and possibly ameliorating, life-course brain health. PMID:27664981

Associations between education and brain structure at age 73 years, adjusted for age 11 IQ.

PubMed

Cox, Simon R; Dickie, David Alexander; Ritchie, Stuart J; Karama, Sherif; Pattie, Alison; Royle, Natalie A; Corley, Janie; Aribisala, Benjamin S; Valdés Hernández, Maria; Muñoz Maniega, Susana; Starr, John M; Bastin, Mark E; Evans, Alan C; Wardlaw, Joanna M; Deary, Ian J

2016-10-25

To investigate how associations between education and brain structure in older age were affected by adjusting for IQ measured at age 11. We analyzed years of full-time education and measures from an MRI brain scan at age 73 in 617 community-dwelling adults born in 1936. In addition to average and vertex-wise cortical thickness, we measured total brain atrophy and white matter tract fractional anisotropy. Associations between brain structure and education were tested, covarying for sex and vascular health; a second model also covaried for age 11 IQ. The significant relationship between education and average cortical thickness (β = 0.124, p = 0.004) was reduced by 23% when age 11 IQ was included (β = 0.096, p = 0.041). Initial associations between longer education and greater vertex-wise cortical thickness were significant in bilateral temporal, medial-frontal, parietal, sensory, and motor cortices. Accounting for childhood intelligence reduced the number of significant vertices by >90%; only bilateral anterior temporal associations remained. Neither education nor age 11 IQ was significantly associated with total brain atrophy or tract-averaged fractional anisotropy. The association between years of education and brain structure ≈60 years later was restricted to cortical thickness in this sample; however, the previously reported associations between longer education and a thicker cortex are likely to be overestimates in terms of both magnitude and distribution. This finding has implications for understanding, and possibly ameliorating, life-course brain health. © 2016 American Academy of Neurology.

Determinants of iron accumulation in the normal aging brain.

PubMed

Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2016-07-01

In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. Copyright © 2016 Elsevier Inc. All rights reserved.

[Cognitive advantages of the third age: a neural network model of brain aging].

PubMed

Karpenko, M P; Kachalova, L M; Budilova, E V; Terekhin, A T

2009-01-01

We consider a neural network model of age-related cognitive changes in aging brain based on Hopfield network with a sigmoid function of neuron activation. Age is included in the activation function as a parameter in the form of exponential rate denominator, which makes it possible to take into account the weakening of interneuronal links really observed in the aging brain. Analysis of properties of the Lyapunov function associated with the network shows that, with increasing parameter of age, its relief becomes smoother and the number of local minima (network attractors) decreases. As a result, the network gets less frequently stuck in the nearest local minima of the Lyapunov function and reaches a global minimum corresponding to the most effective solution of the cognitive task. It is reasonable to assume that similar changes really occur in the aging brain. Phenomenologically, these changes can be manifested as emergence in aged people of a cognitive quality such as wisdom i.e. ability to find optimal decisions in difficult controversial situations, to distract from secondary aspects and to see the problem as a whole.

A qualitative assessment of the supportive care and resource needs of patients undergoing craniotomy for benign brain tumours.

PubMed

Wong, Janice; Mendelsohn, Daniel; Nyhof-Young, Joyce; Bernstein, Mark

2011-11-01

As past literature has focused on support needs of patients with malignant brain tumours, the support needs of patients with benign brain tumours have largely been overlooked. The purpose of this study was to evaluate the supportive care and resource needs of patients undergoing craniotomy for benign brain tumours. Individual, semi-structured interviews were conducted with patients who had undergone craniotomy for a benign brain tumour within the past 2 years. Interviews were audio-recorded, transcribed, anonymized and subjected to descriptive thematic analysis by multiple investigators in the grounded theory tradition. Twenty-nine patients (20 women, 20-88 years of age) with World Health Organization grade I brain tumours (25 meningioma) were interviewed. Five overarching themes emerged: (1) need for formal support from diagnosis onwards; (2) complexity of supportive needs during postoperative recovery; (3) importance of regular long-term monitoring by physicians; (4) influence of psychosocial factors on supportive needs; and (5) existence of barriers to equal access to available supports. Patients' supportive care needs are temporally dependent on disease course and treatment, and modifiable by demographic and psychosocial factors. Findings of this study show that patients with benign tumours lacked but needed many supportive care resources currently available to cancer patients. Many of the potential solutions to this current gap in supportive care involve extending support resources already available for cancer patients to patients with benign brain tumours. We thus suggest recommendations to improve service gaps and reduce disparities in supportive care for patients with benign brain tumours.

Mutant Alpha-Synuclein Causes Age-Dependent Neuropathology in Monkey Brain

PubMed Central

Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua

2015-01-01

Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2–3, 7–8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. PMID:26019347

Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

PubMed

Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

2015-05-27

Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD. Copyright © 2015 the authors 0270-6474/15/358345-14$15.00/0.

Plasticity of the aging brain: new directions in cognitive neuroscience.

PubMed

Gutchess, Angela

2014-10-31

Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span. Copyright © 2014, American Association for the Advancement of Science.

Premature infants display increased noxious-evoked neuronal activity in the brain compared to healthy age-matched term-born infants.

PubMed

Slater, Rebeccah; Fabrizi, Lorenzo; Worley, Alan; Meek, Judith; Boyd, Stewart; Fitzgerald, Maria

2010-08-15

This study demonstrates that infants who are born prematurely and who have experienced at least 40days of intensive or special care have increased brain neuronal responses to noxious stimuli compared to healthy newborns at the same postmenstrual age. We have measured evoked potentials generated by noxious clinically-essential heel lances in infants born at term (8 infants; born 37-40weeks) and in infants born prematurely (7 infants; born 24-32weeks) who had reached the same postmenstrual age (mean age at time of heel lance 39.2+/-1.2weeks). These noxious-evoked potentials are clearly distinguishable from shorter latency potentials evoked by non-noxious tactile sensory stimulation. While the shorter latency touch potentials are not dependent on the age of the infant at birth, the noxious-evoked potentials are significantly larger in prematurely-born infants. This enhancement is not associated with specific brain lesions but reflects a functional change in pain processing in the brain that is likely to underlie previously reported changes in pain sensitivity in older ex-preterm children. Our ability to quantify and measure experience-dependent changes in infant cortical pain processing will allow us to develop a more rational approach to pain management in neonatal intensive care. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Obesity and Aging: Consequences for Cognition, Brain Structure, and Brain Function.

PubMed

Bischof, Gérard N; Park, Denise C

2015-01-01

This review focuses on the relationship between obesity and aging and how these interact to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC [Park and Reuter-Lorenz. Annu Rev Psychol 2009;60:173-96]-a conceptual model designed to relate brain structure and function to one's level of cognitive ability. The initial literature search was focused on normal aging and was guided by the key words, "aging, cognition, and obesity" in PubMed. In a second search, we added key words related to neuropathology including words "Alzheimer's disease," "vascular dementia," and "mild cognitive impairment." The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the life span. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in midlife is linked to an increased risk for Alzheimer's disease and vascular dementia, most likely via an increased accumulation of Alzheimer's disease pathology. Although it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the life span.

Obesity and Aging: Consequences for Cognition, Brain Structure and Brain Function

PubMed Central

Bischof, Gérard N.; Park, Denise C.

2017-01-01

Objective This review focuses on the relationship between obesity and aging and how these interact together to affect cognitive function. The topics covered are guided by the Scaffolding Theory of Aging and Cognition (STAC; Park & Reuter-Lorenz, 2009—a conceptual model designed to relate brain structure and function to one’s level of cognitive ability. Methods The initial literature search was focused on normal aging and was guided by the key words, “aging, cognition, and obesity” in “PUBMED”. In a second search we added key words related to neuropathology including words “Alzheimer’s Disease”, “Vascular dementia” (VaD) and “Mild Cognitive Impairment” (MCI). Results The data suggest that being overweight or obese in midlife may be more detrimental to subsequent age-related cognitive decline than being overweight or obese at later stages of the lifespan. These effects are likely mediated by the accelerated effects obesity has on the integrity of neural structures, including both gray and white matter. Further epidemiological studies have provided evidence that obesity in mid-life is linked to an increased risk for AD and VaD, most likely via an increased accumulation of AD pathology. Conclusion While it is clear that obesity negatively affects cognition, more work is needed to better understand how aging plays a role and how brain structure and brain function might mediate the relationship of obesity and age on cognition. Guided by the STAC and the STAC-R models, we provide a roadmap for future investigations of the role of obesity on cognition across the lifespan. PMID:26107577

Brain plasticity, memory, and aging: a discussion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bennett, E.L.; Rosenzweig, M.R.

1977-12-01

It is generally assumed that memory faculties decline with age. A discussion of the relationship of memory and aging and the possibility of retarding the potential decline is hampered by the fact that no satisfactory explanation of memory is available in either molecular or anatomical terms. However, this lack of description of memory does not mean that there is a lack of suggested mechanisms for long-term memory storage. Present theories of memory usually include first, neurophysiological or electrical events, followed by a series of chemical events which ultimately lead to long-lasting anatomical changes in the brain. Evidence is increasing formore » the biochemical and anatomical plasticity of the nervous system and its importance in the normal functioning of the brain. Modification of this plasticity may be an important factor in senescence. This discussion reports experiments which indicate that protein synthesis and anatomical changes may be involved in long-term memory storage. Environmental influences can produce quantitative differences in brain anatomy and in behavior. In experimental animals, enriched environments lead to more complex anatomical patterns than do colony or impoverished environments. This raises fundamental questions about the adequacy of the isolated animal which is frequently being used as a model for aging research. A more important applied question is the role of social and intellectual stimulation in influencing aging of the human brain.« less

Parameterization of the Age-Dependent Whole Brain Apparent Diffusion Coefficient Histogram

PubMed Central

Batra, Marion; Nägele, Thomas

2015-01-01

Purpose. The distribution of apparent diffusion coefficient (ADC) values in the brain can be used to characterize age effects and pathological changes of the brain tissue. The aim of this study was the parameterization of the whole brain ADC histogram by an advanced model with influence of age considered. Methods. Whole brain ADC histograms were calculated for all data and for seven age groups between 10 and 80 years. Modeling of the histograms was performed for two parts of the histogram separately: the brain tissue part was modeled by two Gaussian curves, while the remaining part was fitted by the sum of a Gaussian curve, a biexponential decay, and a straight line. Results. A consistent fitting of the histograms of all age groups was possible with the proposed model. Conclusions. This study confirms the strong dependence of the whole brain ADC histograms on the age of the examined subjects. The proposed model can be used to characterize changes of the whole brain ADC histogram in certain diseases under consideration of age effects. PMID:26609526

Neuroimaging Studies Illustrate the Commonalities Between Ageing and Brain Diseases.

PubMed

Cole, James H

2018-07-01

The lack of specificity in neuroimaging studies of neurological and psychiatric diseases suggests that these different diseases have more in common than is generally considered. Potentially, features that are secondary effects of different pathological processes may share common neurobiological underpinnings. Intriguingly, many of these mechanisms are also observed in studies of normal (i.e., non-pathological) brain ageing. Different brain diseases may be causing premature or accelerated ageing to the brain, an idea that is supported by a line of "brain ageing" research that combines neuroimaging data with machine learning analysis. In reviewing this field, I conclude that such observations could have important implications, suggesting that we should shift experimental paradigm: away from characterizing the average case-control brain differences resulting from a disease toward methods that place individuals in their age-appropriate context. This will also lead naturally to clinical applications, whereby neuroimaging can contribute to a personalized-medicine approach to improve brain health. © 2018 WILEY Periodicals, Inc.

Brain pathologies in extreme old age

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Jicha, Gregory A.; Schmitt, Frederick A.; Patel, Ela; Poon, Leonard W.; Gearing, Marla; Green, Robert C.; Davey, Adam; Johnson, Mary Ann; Jazwinski, S. Michal; Kim, Sangkyu; Davis, Daron; Woodard, John L.; Kryscio, Richard J.; Van Eldik, Linda J.; Nelson, Peter T.

2015-01-01

With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at University of Kentucky (UK-ADC), incorporating data from the Georgia Centenarian Study (N=49 cases included), the Nun Study (N=17), and UK-ADC (N=11) cohorts. Average age of death was 102.0 years (range: 98–107) overall. Alzheimer’s disease (AD) pathology was not universal (62% with “moderate” or “frequent” neuritic amyloid plaque densities) whereas frontotemporal lobar degeneration (FTLD) was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy [PART]) were observed in every case. Lewy body pathology was seen in 16.9% of subjects, hippocampal sclerosis of aging (HS-Aging) in 20.8%. We describe anatomical distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both HS-Aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum. PMID:26597697

Neuroimaging of Cerebrovascular Disease in the Aging Brain

PubMed Central

Gupta, Ajay; Nair, Sreejit; Schweitzer, Andrew D.; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J.; Sanelli, Pina C.

2012-01-01

Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Structural abnormalities related to vascular disease in the brain and vessels have been well characterized with CT and MRI based techniques. We review some of the pathophysiologic mechanisms in the aging brain and cerebral vasculature and the related structural abnormalities detectable on neuroimaging, including evaluation of age-related white matter changes, atherosclerosis of the cerebral vasculature, and cerebral infarction. In addition, newer neuroimaging techniques, such as diffusion tensor imaging, perfusion techniques, and assessment of cerebrovascular reserve, are also reviewed, as these techniques can detect physiologic alterations which complement the morphologic changes that cause cerebrovascular disease in the aging brain.Further investigation of these advanced imaging techniques has potential application to the understanding and diagnosis of cerebrovascular disease in the elderly. PMID:23185721

A study on knowledge and attitude toward brain death and organ retrieval among health care professionals in Korea.

PubMed

Jeon, K O; Kim, B N; Kim, H S; Byeon, N-I; Hong, J J; Bae, S H; Son, S Y

2012-05-01

The practice of retrieving vital organs from brain-dead donors is legally and medically accepted in Korea, but health care professionals' beliefs and opinions regarding these matters have not been sufficiently explored. The purpose of this study was to evaluate the knowledge and attitudes of health care professionals to the concepts of brain death and organ retrieval. Data were collected using a 41-item questionnaire during a week in June 2011. Sixty-one doctors and 109 nurses from five hospitals with more than 2000 beds in Seoul, Korea, participated in the survey. The data was analyzed using SPSS version 17.0 (SPSS Inc. Chicago, Illinois, USA). There were statistically significant differences in the scores on knowledge according to marital status (P = .001) education level (P = .019), whether the participants were informed about organ donation from a brain-dead donor (P = .002), and the participant's experience managing potential brain-dead patients (P = .037). There were statistically significant differences in the scores on the attitude according to gender (P < .001), age (P < .001), marital status (P < .001), education level (P = .003), job position (P < .001), and the participant's experience referring brain-dead patients to the hospital-based organ procurement organization (P = .001). Significantly, attitude's positively correlated with knowledge about brain-dead organ donation (P < .001). Compared with previous studies, the knowledge and attitudes of health care professionals' regarding brain death and organ retrieval were not improved. There are passive attitudes to brain death and organ retrieval. More research must be performed to promote knowledge and understanding toward brain death and organ retrieval among health care professionals. Copyright © 2012 Elsevier Inc. All rights reserved.

Increased White Matter Inflammation in Aging- and Alzheimer's Disease Brain.

PubMed

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R; Olah, Marta; Mantingh-Otter, Ietje J; Van Dam, Debby; De Deyn, Peter P; den Dunnen, Wilfred; Eggen, Bart J L; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer's disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [ 11 C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration.

Life care planning after traumatic brain injury.

PubMed

Zasler, Nathan D; Ameis, Arthur; Riddick-Grisham, Susan N

2013-08-01

A life care plan is a detailed and comprehensive analysis of impairments, realistic needs, and associated costs relevant to providing a lifetime of care to patients. Physicians have a central role in advising life care planners. Within an expertly prepared life care plan, issues must correspond directly with proposed goods and services. A life care plan must clearly cite all relevant caregiver sources and rely on scientific evidence. The central tenets of a life care plan and the ethical and professional roles that physicians may play in the context of traumatic brain injury and a life care plan are reviewed in this article. Copyright © 2013 Elsevier Inc. All rights reserved.

Early Palliative Care for Patients With Brain Metastases Decreases Inpatient Admissions and Need for Imaging Studies.

PubMed

Habibi, Akram; Wu, S Peter; Gorovets, Daniel; Sansosti, Alexandra; Kryger, Marc; Beaudreault, Cameron; Chung, Wei-Yi; Shelton, Gary; Silverman, Joshua; Lowy, Joseph; Kondziolka, Douglas

2018-01-01

Early encounters with palliative care (PC) can influence health-care utilization, clinical outcome, and cost. To study the effect of timing of PC encounters on brain metastasis patients at an academic medical center. All patients diagnosed with brain metastases from January 2013 to August 2015 at a single institution with inpatient and/or outpatient PC records available for review (N = 145). Early PC was defined as having a PC encounter within 8 weeks of diagnosis with brain metastases; late PC was defined as having PC after 8 weeks of diagnosis. Propensity score matched cohorts of early (n = 46) and late (n = 46) PC patients were compared to control for differences in age, gender, and Karnofsky Performance Status (KPS) at diagnosis. Details of the palliative encounter, patient outcomes, and health-care utilization were collected. Early PC versus late PC patients had no differences in baseline KPS, age, or gender. Early PC patients had significantly fewer number of inpatient visits per patient (1.5 vs 2.9; P = .004), emergency department visits (1.2 vs 2.1; P = .006), positron emission tomography/computed tomography studies (1.2 vs 2.7, P = .005), magnetic resonance imaging scans (5.8 vs 8.1; P = .03), and radiosurgery procedures (0.6 vs 1.3; P < .001). There were no differences in overall survival (median 8.2 vs 11.2 months; P = .2). Following inpatient admissions, early PC patients were more likely to be discharged home (59% vs 35%; P = .04). Timely PC consultations are advisable in this patient population and can reduce health-care utilization.

The Brain Response to Peripheral Insulin Declines with Age: A Contribution of the Blood-Brain Barrier?

PubMed Central

Heni, Martin; Maetzler, Walter; Fritsche, Andreas; Häring, Hans-Ulrich; Hennige, Anita M.

2015-01-01

Objectives It is a matter of debate whether impaired insulin action originates from a defect at the neural level or impaired transport of the hormone into the brain. In this study, we aimed to investigate the effect of aging on insulin concentrations in the periphery and the central nervous system as well as its impact on insulin-dependent brain activity. Methods Insulin, glucose and albumin concentrations were determined in 160 paired human serum and cerebrospinal fluid (CSF) samples. Additionally, insulin was applied in young and aged mice by subcutaneous injection or intracerebroventricularly to circumvent the blood-brain barrier. Insulin action and cortical activity were assessed by Western blotting and electrocorticography radiotelemetric measurements. Results In humans, CSF glucose and insulin concentrations were tightly correlated with the respective serum/plasma concentrations. The CSF/serum ratio for insulin was reduced in older subjects while the CSF/serum ratio for albumin increased with age like for most other proteins. Western blot analysis in murine whole brain lysates revealed impaired phosphorylation of AKT (P-AKT) in aged mice following peripheral insulin stimulation whereas P-AKT was comparable to levels in young mice after intracerebroventricular insulin application. As readout for insulin action in the brain, insulin-mediated cortical brain activity instantly increased in young mice subcutaneously injected with insulin but was significantly reduced and delayed in aged mice during the treatment period. When insulin was applied intracerebroventricularly into aged animals, brain activity was readily improved. Conclusions This study discloses age-dependent changes in insulin CSF/serum ratios in humans. In the elderly, cerebral insulin resistance might be partially attributed to an impaired transport of insulin into the central nervous system. PMID:25965336

Age-related functional brain changes in young children.

PubMed

Long, Xiangyu; Benischek, Alina; Dewey, Deborah; Lebel, Catherine

2017-07-15

Brain function and structure change significantly during the toddler and preschool years. However, most studies focus on older or younger children, so the specific nature of these changes is unclear. In the present study, we analyzed 77 functional magnetic resonance imaging datasets from 44 children aged 2-6 years. We extracted measures of both local (amplitude of low frequency fluctuation and regional homogeneity) and global (eigenvector centrality mapping) activity and connectivity, and examined their relationships with age using robust linear correlation analysis and strict control for head motion. Brain areas within the default mode network and the frontoparietal network, such as the middle frontal gyrus, the inferior parietal lobule and the posterior cingulate cortex, showed increases in local and global functional features with age. Several brain areas such as the superior parietal lobule and superior temporal gyrus presented opposite development trajectories of local and global functional features, suggesting a shifting connectivity framework in early childhood. This development of functional connectivity in early childhood likely underlies major advances in cognitive abilities, including language and development of theory of mind. These findings provide important insight into the development patterns of brain function during the preschool years, and lay the foundation for future studies of altered brain development in young children with brain disorders or injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Towards sustainable traumatic brain injury care systems: healthcare leadership imperatives in Canada.

PubMed

Caro, Denis

2011-01-01

Traumatic brain injuries pose strategic population health challenges in the face of burgeoning clinical demands that continue to tax capital, financial, and social resource capacities. The sustainability of traumatic brain injury care systems depends on paradigmatic shifts in healthcare leadership thinking. In quest for high-performance care and sustained quality of life for traumatic brain injury patients, this article presents a unique paradigm of seven care performance layers and seven health leadership imperatives that together form the paradigm for the systemic sustainability of TBI care systems of the future.

Health care of youth aging out of foster care.

PubMed

2012-12-01

Youth transitioning out of foster care face significant medical and mental health care needs. Unfortunately, these youth rarely receive the services they need because of lack of health insurance. Through many policies and programs, the federal government has taken steps to support older youth in foster care and those aging out. The Fostering Connections to Success and Increasing Adoptions Act of 2008 (Pub L No. 110-354) requires states to work with youth to develop a transition plan that addresses issues such as health insurance. In addition, beginning in 2014, the Patient Protection and Affordable Care Act of 2010 (Pub L No. 111-148) makes youth aging out of foster care eligible for Medicaid coverage until age 26 years, regardless of income. Pediatricians can support youth aging out of foster care by working collaboratively with the child welfare agency in their state to ensure that the ongoing health needs of transitioning youth are met.

Comparison of Informal Care Time and Costs in Different Age-Related Dementias: A Review

PubMed Central

Costa, Nadège; Ferlicoq, Laura; Derumeaux-Burel, Hélène; Rapp, Thomas; Garnault, Valérie; Gillette-Guyonnet, Sophie; Andrieu, Sandrine; Vellas, Bruno; Lamure, Michel; Grand, Alain; Molinier, Laurent

2013-01-01

Objectives. Age-related dementia is a progressive degenerative brain syndrome whose prevalence increases with age. Dementias cause a substantial burden on society and on families who provide informal care. This study aims to review the relevant papers to compare informal care time and costs in different dementias. Methods. A bibliographic search was performed on an international medical literature database (MEDLINE). All studies which assessed the social economic burden of different dementias were selected. Informal care time and costs were analyzed in three care settings by disease stages. Results. 21 studies met our criteria. Mean informal care time was 55.73 h per week for Alzheimer disease and 15.8 h per week for Parkinson disease (P = 0.0076), and the associated mean annual informal costs were $17,492 versus $3,284, respectively (P = 0.0393). Conclusion. There is a lack of data about informal care time and costs among other dementias than AD or PD. Globally, AD is the most costly in terms of informal care costs than PD, $17,492 versus $3,284, respectively. PMID:23509789

Brain pathologies in extreme old age.

PubMed

Neltner, Janna H; Abner, Erin L; Jicha, Gregory A; Schmitt, Frederick A; Patel, Ela; Poon, Leonard W; Marla, Gearing; Green, Robert C; Davey, Adam; Johnson, Mary Ann; Jazwinski, S Michal; Kim, Sangkyu; Davis, Daron; Woodard, John L; Kryscio, Richard J; Van Eldik, Linda J; Nelson, Peter T

2016-01-01

With an emphasis on evolving concepts in the field, we evaluated neuropathologic data from very old research volunteers whose brain autopsies were performed at the University of Kentucky Alzheimer's Disease Center, incorporating data from the Georgia Centenarian Study (n = 49 cases included), Nun Study (n = 17), and University of Kentucky Alzheimer's Disease Center (n = 11) cohorts. Average age of death was 102.0 (range: 98-107) years overall. Alzheimer's disease pathology was not universal (62% with "moderate" or "frequent" neuritic amyloid plaque densities), whereas frontotemporal lobar degeneration was absent. By contrast, some hippocampal neurofibrillary tangles (including primary age-related tauopathy) were observed in every case. Lewy body pathology was seen in 16.9% of subjects and hippocampal sclerosis of aging in 20.8%. We describe anatomic distributions of pigment-laden macrophages, expanded Virchow-Robin spaces, and arteriolosclerosis among Georgia Centenarians. Moderate or severe arteriolosclerosis pathology, throughout the brain, was associated with both hippocampal sclerosis of aging pathology and an ABCC9 gene variant. These results provide fresh insights into the complex cerebral multimorbidity, and a novel genetic risk factor, at the far end of the human aging spectrum. Copyright © 2016 Elsevier Inc. All rights reserved.

Diffusion Tensor Tractography Reveals Disrupted Structural Connectivity during Brain Aging

NASA Astrophysics Data System (ADS)

Lin, Lan; Tian, Miao; Wang, Qi; Wu, Shuicai

2017-10-01

Brain aging is one of the most crucial biological processes that entail many physical, biological, chemical, and psychological changes, and also a major risk factor for most common neurodegenerative diseases. To improve the quality of life for the elderly, it is important to understand how the brain is changed during the normal aging process. We compared diffusion tensor imaging (DTI)-based brain networks in a cohort of 75 healthy old subjects by using graph theory metrics to describe the anatomical networks and connectivity patterns, and network-based statistic (NBS) analysis was used to identify pairs of regions with altered structural connectivity. The NBS analysis revealed a significant network comprising nine distinct fiber bundles linking 10 different brain regions showed altered white matter structures in young-old group compare with middle-aged group (p < .05, family-wise error-corrected). Our results might guide future studies and help to gain a better understanding of brain aging.

Advance care planning for older people in Australia presenting to the emergency department from the community or residential aged care facilities.

PubMed

Street, Maryann; Ottmann, Goetz; Johnstone, Megan-Jane; Considine, Julie; Livingston, Patricia M

2015-09-01

The purpose of this retrospective, cross-sectional study was to determine the prevalence of advance care planning (ACP) among older people presenting to an Emergency Department (ED) from the community or a residential aged care facility. The study sample comprised 300 older people (aged 65+ years) presenting to three Victorian EDs in 2011. A total of 150 patients transferred from residential aged care to ED were randomly selected and then matched to 150 people who lived in the community and attended the ED by age, gender, reason for ED attendance and triage category on arrival. Overall prevalence of ACP was 13.3% (n = 40/300); over one-quarter (26.6%, n = 40/150) of those presenting to the ED from residential aged care had a documented Advance Care Plan, compared to none (0%, n = 0/150) of the people from the community. There were no significant differences in the median ED length of stay, number of investigations and interventions undertaken in ED, time seen by a doctor or rate of hospital admission for those with an Advance Care Plan compared to those without. Those with a comorbidity of cerebrovascular disease or dementia and those assessed with impaired brain function were more likely to have a documented Advance Care Plan on arrival at ED. Length of hospital stay was shorter for those with an Advance Care Plan [median (IQR) = 3 days (2-6) vs. 6 days (2-10), P = 0.027] and readmission lower (0% vs. 13.7%). In conclusion, older people from the community transferred to ED were unlikely to have a documented Advance Care Plan. Those from residential aged care who were cognitively impaired more frequently had an Advance Care Plan. In the ED, decisions of care did not appear to be influenced by the presence or absence of Advance Care Plans, but length of hospital admission was shorter for those with an Advance Care Plan. © 2014 John Wiley & Sons Ltd.

MRI assessment of whole-brain structural changes in aging.

PubMed

Guo, Hui; Siu, William; D'Arcy, Ryan Cn; Black, Sandra E; Grajauskas, Lukas A; Singh, Sonia; Zhang, Yunting; Rockwood, Kenneth; Song, Xiaowei

2017-01-01

One of the central features of brain aging is the accumulation of multiple age-related structural changes, which occur heterogeneously in individuals and can have immediate or potential clinical consequences. Each of these deficits can coexist and interact, producing both independent and additive impacts on brain health. Many of the changes can be visualized using MRI. To collectively assess whole-brain structural changes, the MRI-based Brain Atrophy and Lesion Index (BALI) has been developed. In this study, we validate this whole-brain health assessment approach using several clinical MRI examinations. Data came from three independent studies: the Alzheimer's Disease Neuroimaging Initiative Phase II (n=950; women =47.9%; age =72.7±7.4 years); the National Alzheimer's Coordinating Center (n=722; women =55.1%; age =72.7±9.9 years); and the Tianjin Medical University General Hospital Research database on older adults (n=170; women =60.0%; age =62.9±9.3 years). The 3.0-Tesla MRI scans were evaluated using the BALI rating scheme on the basis of T1-weighted (T1WI), T2-weighted (T2WI), T2-weighted fluid-attenuated inversion recovery (T2-FLAIR), and T2*-weighted gradient-recalled echo (T2*GRE) images. Atrophy and lesion changes were commonly seen in each MRI test. The BALI scores based on different sequences were highly correlated (Spearman r 2 >0.69; P <0.00001). They were associated with age ( r 2 >0.29; P <0.00001) and differed by cognitive status ( χ 2 >26.48, P <0.00001). T2-FLAIR revealed a greater level of periventricular ( χ 2 =29.09) and deep white matter ( χ 2 =26.65, P <0.001) lesions than others, but missed revealing certain dilated perivascular spaces that were seen in T2WI ( P <0.001). Microhemorrhages occurred in 15.3% of the sample examined and were detected using only T2*GRE. The T1WI- and T2WI-based BALI evaluations consistently identified the burden of aging and dementia-related decline of structural brain health. Inclusion of additional MRI tests

A common brain network links development, aging, and vulnerability to disease.

PubMed

Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

2014-12-09

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

Personal care workers in Australian aged care: retention and turnover intentions.

PubMed

Radford, Katrina; Shacklock, Kate; Bradley, Graham

2015-07-01

This study examined factors influencing personal care workers' intentions to stay or leave Australian aged care employment - especially for older workers. Retention of personal care workers is particularly important in aged care as they provide the majority of the direct care via community aged care or long-term aged care environments. However, there is limited research on what drives their turnover and retention. A survey was conducted during 2012 collecting 206 responses from workers within community and long-term aged care in four organisations in Australia. Perceived supervisor support, on-the-job embeddedness and area of employment were identified as predictors of both intention to stay and to leave, although the relationship strength differed. Community care workers were more likely to stay and reported more supervisor support than long-term care workers. Unexpectedly, age and health status were not predictors of staying or leaving. While there are similarities between retention and turnover motivators, there are also differences. Within a global context of health worker shortages, such new knowledge is keenly sought to enhance organisational effectiveness and sustain the provision of quality aged care. Retention strategies for older workers should involve increasing supervisor support, and seeking to embed workers more fully within their organisation. © 2013 John Wiley & Sons Ltd.

IGF-1: The Jekyll & Hyde of the aging brain.

PubMed

Gubbi, Sriram; Quipildor, Gabriela Farias; Barzilai, Nir; Huffman, Derek M; Milman, Sofiya

2018-05-08

The IGF-1 signaling pathway has emerged as a major regulator of the aging process, from rodents to humans. However, given the pleiotropic actions of IGF-1, its role in the aging brain remains complex and controversial. While IGF-1 is clearly essential for normal development of the central nervous system, conflicting evidence has emerged from preclinical and human studies regarding its relationship to cognitive function, as well as cerebrovascular and neurodegenerative disorders. This review delves into the current state of the evidence examining the role of IGF-1 in the aging brain, encompassing preclinical and clinical studies. A broad examination of the data indicates that IGF-1 may indeed play opposing roles in the aging brain, depending on the underlying pathology and context. Some evidence suggests that in the setting of neurodegenerative diseases that manifest with abnormal protein deposition in the brain, such as Alzheimer's disease, reducing IGF-1 signaling may serve a protective role by slowing disease progression and augmenting clearance of pathologic proteins to maintain cellular homeostasis. In contrast, inducing IGF-1 deficiency has also been implicated in dysregulated function of cognition and the neurovascular system, suggesting that some IGF-1 signaling may be necessary for normal brain function. Furthermore, states of acute neuronal injury, which necessitate growth, repair and survival signals to persevere, typically demonstrate salutary effects of IGF-1 in that context. Appreciating the dual, at times opposing "Dr. Jekyll" and "Mr. Hyde" characteristics of IGF-1 in the aging brain, will bring us closer to understanding its impact and devising more targeted IGF-1-related interventions.

School-age effects of the newborn individualized developmental care and assessment program for preterm infants with intrauterine growth restriction: preliminary findings.

PubMed

McAnulty, Gloria; Duffy, Frank H; Kosta, Sandra; Weisenfeld, Neil I; Warfield, Simon K; Butler, Samantha C; Alidoost, Moona; Bernstein, Jane Holmes; Robertson, Richard; Zurakowski, David; Als, Heidelise

2013-02-19

The experience in the newborn intensive care nursery results in premature infants' neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother's intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks' lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore, executive function, spectral coherence

The endocannabinoid system in normal and pathological brain ageing

PubMed Central

Bilkei-Gorzo, Andras

2012-01-01

The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing. PMID:23108550

The endocannabinoid system in normal and pathological brain ageing.

PubMed

Bilkei-Gorzo, Andras

2012-12-05

The role of endocannabinoids as inhibitory retrograde transmitters is now widely known and intensively studied. However, endocannabinoids also influence neuronal activity by exerting neuroprotective effects and regulating glial responses. This review centres around this less-studied area, focusing on the cellular and molecular mechanisms underlying the protective effect of the cannabinoid system in brain ageing. The progression of ageing is largely determined by the balance between detrimental, pro-ageing, largely stochastic processes, and the activity of the homeostatic defence system. Experimental evidence suggests that the cannabinoid system is part of the latter system. Cannabinoids as regulators of mitochondrial activity, as anti-oxidants and as modulators of clearance processes protect neurons on the molecular level. On the cellular level, the cannabinoid system regulates the expression of brain-derived neurotrophic factor and neurogenesis. Neuroinflammatory processes contributing to the progression of normal brain ageing and to the pathogenesis of neurodegenerative diseases are suppressed by cannabinoids, suggesting that they may also influence the ageing process on the system level. In good agreement with the hypothesized beneficial role of cannabinoid system activity against brain ageing, it was shown that animals lacking CB1 receptors show early onset of learning deficits associated with age-related histological and molecular changes. In preclinical models of neurodegenerative disorders, cannabinoids show beneficial effects, but the clinical evidence regarding their efficacy as therapeutic tools is either inconclusive or still missing.

The Influence of the Brain on Overpopulation, Ageing and Dependency.

ERIC Educational Resources Information Center

Cape, Ronald D. T.

1989-01-01

With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

Aging and brain rejuvenation as systemic events

PubMed Central

Bouchard, Jill; Villeda, Saul A

2015-01-01

The effects of aging were traditionally thought to be immutable, particularly evident in the loss of plasticity and cognitive abilities occurring in the aged central nervous system (CNS). However, it is becoming increasingly apparent that extrinsic systemic manipulations such as exercise, caloric restriction, and changing blood composition by heterochronic parabiosis or young plasma administration can partially counteract this age-related loss of plasticity in the aged brain. In this review, we discuss the process of aging and rejuvenation as systemic events. We summarize genetic studies that demonstrate a surprising level of malleability in organismal lifespan, and highlight the potential for systemic manipulations to functionally reverse the effects of aging in the CNS. Based on mounting evidence, we propose that rejuvenating effects of systemic manipulations are mediated, in part, by blood-borne ‘pro-youthful’ factors. Thus, systemic manipulations promoting a younger blood composition provide effective strategies to rejuvenate the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged CNS as a means to rejuvenate regenerative, synaptic, and cognitive functions late in life, with potential implications even for extending lifespan. PMID:25327899

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition.

PubMed

Franke, Katja; Clarke, Geoffrey D; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4-7 years; human equivalent 14-24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years ( p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans.

Premature Brain Aging in Baboons Resulting from Moderate Fetal Undernutrition

PubMed Central

Franke, Katja; Clarke, Geoffrey D.; Dahnke, Robert; Gaser, Christian; Kuo, Anderson H.; Li, Cun; Schwab, Matthias; Nathanielsz, Peter W.

2017-01-01

Contrary to the known benefits from a moderate dietary reduction during adulthood on life span and health, maternal nutrient reduction during pregnancy is supposed to affect the developing brain, probably resulting in impaired brain structure and function throughout life. Decreased fetal nutrition delivery is widespread in both developing and developed countries, caused by poverty and natural disasters, but also due to maternal dieting, teenage pregnancy, pregnancy in women over 35 years of age, placental insufficiency, or multiples. Compromised development of fetal cerebral structures was already shown in our baboon model of moderate maternal nutrient reduction. The present study was designed to follow-up and evaluate the effects of moderate maternal nutrient reduction on individual brain aging in the baboon during young adulthood (4–7 years; human equivalent 14–24 years), applying a novel, non-invasive neuroimaging aging biomarker. The study reveals premature brain aging of +2.7 years (p < 0.01) in the female baboon exposed to fetal undernutrition. The effects of moderate maternal nutrient reduction on individual brain aging occurred in the absence of fetal growth restriction or marked maternal weight reduction at birth, which stresses the significance of early nutritional conditions in life-long developmental programming. This non-invasive MRI biomarker allows further longitudinal in vivo tracking of individual brain aging trajectories to assess the life-long effects of developmental and environmental influences in programming paradigms, aiding preventive and curative treatments on cerebral atrophy in experimental animal models and humans. PMID:28443017

Modeling the brain morphology distribution in the general aging population

NASA Astrophysics Data System (ADS)

Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

2016-03-01

Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

Intersection between metabolic dysfunction, high fat diet consumption, and brain aging.

PubMed

Uranga, Romina M; Bruce-Keller, Annadora J; Morrison, Christopher D; Fernandez-Kim, Sun Ok; Ebenezer, Philip J; Zhang, Le; Dasuri, Kalavathi; Keller, Jeffrey N

2010-07-01

Deleterious neurochemical, structural, and behavioral alterations are a seemingly unavoidable aspect of brain aging. However, the basis for these alterations, as well as the basis for the tremendous variability in regards to the degree to which these aspects are altered in aging individuals, remains to be elucidated. An increasing number of individuals regularly consume a diet high in fat, with high-fat diet consumption known to be sufficient to promote metabolic dysfunction, although the links between high-fat diet consumption and aging are only now beginning to be elucidated. In this review we discuss the potential role for age-related metabolic disturbances serving as an important basis for deleterious perturbations in the aging brain. These data not only have important implications for understanding the basis of brain aging, but also may be important to the development of therapeutic interventions which promote successful brain aging.

Functional correlates of brain aging: beta and gamma frequency band responses to age-related cortical changes.

PubMed

Christov, Mario; Dushanova, Juliana

2016-01-01

The brain as a system with gradually declined resources by age maximizes its performance by neural network reorganization for greater efficiency of neuronal oscillations in a given frequency band. Whether event-related high-frequency band responses are related to plasticity in neural recruitment contributed to the stability of sensory/cognitive mechanisms accompanying aging or are underlined pathological changes seen in aging brain remains unknown. Aged effect on brain electrical activity was studied in auditory discrimination task (low-frequency and high-frequency tone) at particular cortical locations in beta (β1: 12.5-20; β2: 20.5-30 Hz) and gamma frequency bands (γ1: 30.5-49; γ2: 52-69 Hz) during sensory (post-stimulus interval 0-250 ms) and cognitive processing (250-600 ms). Beta1 activity less affected by age during sensory processing. Reduced beta1 activity was more widespread during cognitive processing. This difference increased in fronto-parietal direction more expressed after high-frequency tone stimulation. Beta2 and gamma activity were more pronounced with progressive age during sensory processing. Reducing regional-process specificity with progressing age characterized age-related and tone-dependent beta2 changes during sensory, but not during cognitive processing. Beta2 and gamma activity diminished with age on cognitive processes, except the higher frontal tone-dependent gamma activity during cognitive processing. With increasing age, larger gamma2 activity was more expressed over the frontal brain areas to high tone discrimination and hand reaction choice. These gamma2 differences were shifted from posterior to anterior brain regions with advancing age. The aged influence was higher on cognitive processes than on perceptual ones.

BRAIN FUEL METABOLISM, AGING AND ALZHEIMER’S DISEASE

PubMed Central

Cunnane, SC; Nugent, S; Roy, M; Courchesne-Loyer, A; Croteau, E; Tremblay, S; Castellano, A; Pifferi, F; Bocti, C; Paquet, N; Begdouri, H; Bentourkia, M; Turcotte, E; Allard, M; Barberger-Gateau, P; Fulop, T; Rapoport, S

2012-01-01

Lower brain glucose metabolism is present before the onset of clinically-measurable cognitive decline in two groups of people at risk of Alzheimer’s disease (AD) - carriers of apoE4, and in those with a maternal family history of AD. Supported by emerging evidence from in vitro and animal studies, these reports suggest that brain hypometabolism may precede and contribute to the neuropathological cascade leading cognitive decline in AD. The reason for brain hypometabolism is unclear but may include defects in glucose transport at the blood-brain barrier, glycolysis, and/or mitochondrial function. Methodological issues presently preclude knowing with certainty whether or not aging in the absence of cognitive impairment is necessarily associated with lower brain glucose metabolism. Nevertheless, aging appears to increase the risk of deteriorating systemic control of glucose utilization which, in turn, may increase the risk of declining brain glucose uptake, at least in some regions. A contributing role of deteriorating glucose availability to or metabolism by the brain in AD does not exclude the opposite effect, i.e. that neurodegenerative processes in AD further decrease brain glucose metabolism because of reduced synaptic functionality and, hence, reduced energy needs, thereby completing a vicious cycle. Strategies to reduce the risk of AD by breaking this cycle should aim to – (i) improve insulin sensitivity by improving systemic glucose utilization, or (ii) bypass deteriorating brain glucose metabolism using approaches that safely induce mild, sustainable ketonemia. PMID:21035308

Structural MRI markers of brain aging early after ischemic stroke.

PubMed

Werden, Emilio; Cumming, Toby; Li, Qi; Bird, Laura; Veldsman, Michele; Pardoe, Heath R; Jackson, Graeme; Donnan, Geoffrey A; Brodtmann, Amy

2017-07-11

To examine associations between ischemic stroke, vascular risk factors, and MRI markers of brain aging. Eighty-one patients (mean age 67.5 ± 13.1 years, 31 left-sided, 61 men) with confirmed first-ever (n = 66) or recurrent (n = 15) ischemic stroke underwent 3T MRI scanning within 6 weeks of symptom onset (mean 26 ± 9 days). Age-matched controls (n = 40) completed identical testing. Multivariate regression analyses examined associations between group membership and MRI markers of brain aging (cortical thickness, total brain volume, white matter hyperintensity [WMH] volume, hippocampal volume), normalized against intracranial volume, and the effects of vascular risk factors on these relationships. First-ever stroke was associated with smaller hippocampal volume ( p = 0.025) and greater WMH volume ( p = 0.004) relative to controls. Recurrent stroke was in turn associated with smaller hippocampal volume relative to both first-ever stroke ( p = 0.017) and controls ( p = 0.001). These associations remained significant after adjustment for age, sex, education, and, in stroke patients, infarct volume. Total brain volume was not significantly smaller in first-ever stroke patients than in controls ( p = 0.056), but the association became significant after further adjustment for atrial fibrillation ( p = 0.036). Cortical thickness and brain volumes did not differ as a function of stroke type, infarct volume, or etiology. Brain structure is likely to be compromised before ischemic stroke by vascular risk factors. Smaller hippocampal and total brain volumes and increased WMH load represent proxies for underlying vascular brain injury. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Premature brain aging in humans exposed to maternal nutrient restriction during early gestation.

PubMed

Franke, Katja; Gaser, Christian; Roseboom, Tessa J; Schwab, Matthias; de Rooij, Susanne R

2018-06-01

Prenatal exposure to undernutrition is widespread in both developing and industrialized countries, causing irreversible damage to the developing brain, resulting in altered brain structure and decreased cognitive function during adulthood. The Dutch famine in 1944/45 was a humanitarian disaster, now enabling studies of the effects of prenatal undernutrition during gestation on brain aging in late adulthood. We hypothesized that study participants prenatally exposed to maternal nutrient restriction (MNR) would demonstrate altered brain structure resembling premature brain aging in late adulthood, expecting the effect being stronger in men. Utilizing the Dutch famine birth cohort (n = 118; mean age: 67.5 ± 0.9 years), this study implements an innovative biomarker for individual brain aging, using structural neuroimaging. BrainAGE was calculated using state-of-the-art pattern recognition methods, trained on an independent healthy reference sample, then applied to the Dutch famine MRI sample, to evaluate the effects of prenatal undernutrition during early gestation on individual brain aging in late adulthood. Exposure to famine in early gestation was associated with BrainAGE scores indicative of an older-appearing brain in the male sample (mean difference to subjects born before famine: 4.3 years, p < 0.05). Furthermore, in explaining the observed variance in individual BrainAGE scores in the male sample, maternal age at birth, head circumference at birth, medical treatment of hypertension, history of cerebral incidences, actual heart rate, and current alcohol intake emerged to be the most influential variables (adjusted R 2  = 0.63, p < 0.01). The findings of our study on exposure to prenatal undernutrition being associated with a status of premature brain aging during late adulthood, as well as individual brain structure being shaped by birth- and late-life health characteristics, are strongly supporting the critical importance of sufficient nutrient

Ecology of the aging human brain.

PubMed

Sonnen, Joshua A; Santa Cruz, Karen; Hemmy, Laura S; Woltjer, Randall; Leverenz, James B; Montine, Kathleen S; Jack, Clifford R; Kaye, Jeffrey; Lim, Kelvin; Larson, Eric B; White, Lon; Montine, Thomas J

2011-08-01

Alzheimer disease, cerebral vascular brain injury, and isocortical Lewy body disease (LBD) are the major contributors to dementia in community- and population-based studies. To estimate the prevalence of clinically silent forms of these diseases in cognitively normal (CN) adults. Autopsy study. Community- and population based. A total of 1672 brain autopsies from the Adult Changes in Thought study, Honolulu-Asia Aging Study, Nun Study, and Oregon Brain Aging Study, of which 424 met the criteria for CN. Of these, 336 cases had a comprehensive neuropathologic examination of neuritic plaque density, Braak stage for neurofibrillary tangles, LB distribution, and number of cerebral microinfarcts. Forty-seven percent of CN cases had moderate or frequent neuritic plaque density; of these, 6% also had Braak stage V or VI for neurofibrillary tangles. Fifteen percent of CN cases had medullary LBD; 8% also had nigral and 4% isocortical LBD. The presence of any cerebral microinfarcts was identified in 33% and of high-level cerebral microinfarcts in 10% of CN individuals. Overall, the burden of lesions in each individual and their comorbidity varied widely within each study but were similar across studies. These data show an individually varying complex convergence of subclinical diseases in the brain of older CN adults. Appreciating this ecology should help guide future biomarker and neuroimaging studies and clinical trials that focus on community- and population-based cohorts.

Nutritional strategies to optimise cognitive function in the aging brain.

PubMed

Wahl, Devin; Cogger, Victoria C; Solon-Biet, Samantha M; Waern, Rosilene V R; Gokarn, Rahul; Pulpitel, Tamara; Cabo, Rafael de; Mattson, Mark P; Raubenheimer, David; Simpson, Stephen J; Le Couteur, David G

2016-11-01

Old age is the greatest risk factor for most neurodegenerative diseases. During recent decades there have been major advances in understanding the biology of aging, and the development of nutritional interventions that delay aging including calorie restriction (CR) and intermittent fasting (IF), and chemicals that influence pathways linking nutrition and aging processes. CR influences brain aging in many animal models and recent findings suggest that dietary interventions can influence brain health and dementia in older humans. The role of individual macronutrients in brain aging also has been studied, with conflicting results about the effects of dietary protein and carbohydrates. A new approach known as the Geometric Framework (GF) has been used to unravel the complex interactions between macronutrients (protein, fat, and carbohydrate) and total energy on outcomes such as aging. These studies have shown that low-protein, high-carbohydrate (LPHC) diets are optimal for lifespan in ad libitum fed animals, while total calories have minimal effect once macronutrients are taken into account. One of the primary purposes of this review is to explore the notion that macronutrients may have a more translational potential than CR and IF in humans, and therefore there is a pressing need to use GF to study the impact of diet on brain aging. Furthermore, given the growing recognition of the role of aging biology in dementia, such studies might provide a new approach for dietary interventions for optimizing brain health and preventing dementia in older people. Copyright © 2016 Elsevier B.V. All rights reserved.

Care pathways for organ donation after brain death: guidance from available literature?

PubMed

Hoste, Pieter; Vanhaecht, Kris; Ferdinande, Patrick; Rogiers, Xavier; Eeckloo, Kristof; Blot, Stijn; Hoste, Eric; Vogelaers, Dirk; Vandewoude, Koenraad

2016-10-01

A discussion of the literature concerning the impact of care pathways in the complex and by definition multidisciplinary process of organ donation following brain death. Enhancing the quality and safety of organs for transplantation has become a central concern for governmental and professional organizations. At the local hospital level, a donor coordinator can use a range of interventions to improve the donation and procurement process. Care pathways have been proven to represent an effective intervention in several settings for optimizing processes and outcomes. A discussion paper. A systematic review of the Medline, CINAHL, EMBASE and The Cochrane Library databases was conducted for articles published until June 2015, using the keywords donation after brain death and care pathways. Each paper was reviewed to investigate the effects of existing care pathways for donation after brain death. An additional search for unpublished information was conducted. Although literature supports care pathways as an effective intervention in several settings, few studies have explored its use and effectiveness for complex care processes such as donation after brain death. Nurses should be aware of their role in the donation process. Care pathways have the potential to support them, but their effectiveness has been insufficiently explored. Further research should focus on the development and standardization of the clinical content of a care pathway for donation after brain death and the identification of quality indicators. These should be used in a prospective effectiveness assessment of the proposed pathway. © 2016 John Wiley & Sons Ltd.

A Needs Assessment of Brain Death Education in Pediatric Critical Care Medicine Fellowships.

PubMed

Ausmus, Andrew M; Simpson, Pippa M; Zhang, Liyun; Petersen, Tara L

2018-04-12

To assess the current training in brain death examination provided during pediatric critical care medicine fellowship. Internet-based survey. United States pediatric critical care medicine fellowship programs. Sixty-four pediatric critical care medicine fellowship program directors and 230 current pediatric critical care medicine fellows/recent graduates were invited to participate. Participants were asked demographic questions related to their fellowship programs, training currently provided at their fellowship programs, previous experience with brain death examinations (fellows/graduates), and perceptions regarding the adequacy of current training. Twenty-nine program directors (45%) and 91 current fellows/graduates (40%) responded. Third-year fellows reported having performed a median of five examinations (interquartile range, 3-6). On a five-point Likert scale, 93% of program directors responded they "agree" or "strongly agree" that their fellows receive enough instruction on performing brain death examinations compared with 67% of fellows and graduates (p = 0.007). The responses were similar when asked about opportunity to practice brain death examinations (90% vs 54%; p < 0.001). In a regression tree analysis, number of brain death examinations performed was the strongest predictor of trainee satisfaction. Both fellows and program directors preferred bedside demonstration or simulation as educational modalities to add to the fellowship curriculum. Pediatric critical care medicine fellows overall perform relatively few brain death examinations during their training. Pediatric critical care medicine fellows and program directors disagree in their perceptions of the current training in brain death examination, with fellows perceiving a need for increased training. Both program directors and fellows prefer additional training using bedside demonstration or simulation. Since clinical exposure to brain death examinations is variable, adding simulated brain death

Age-related increase of resting metabolic rate in the human brain

PubMed Central

Peng, Shin-Lei; Dumas, Julie A.; Park, Denise C.; Liu, Peiying; Filbey, Francesca M.; McAdams, Carrie J.; Pinkham, Amy E.; Adinoff, Bryon; Zhang, Rong; Lu, Hanzhang

2014-01-01

With age, many aspects of the brain structure undergo a pronounced decline, yet individuals generally function well until advanced old age. There appear to be several compensatory mechanisms in brain aging, but their precise nature is not well characterized. Here we provide evidence that the brain of older adults expends more energy when compared to younger adults, as manifested by an age-related increase (P=0.03) in cerebral metabolic rate of oxygen (CMRO2) (N=118, men=56, ages 18 to 74). We further showed that, before the mean menopausal age of 51 years old, female and male groups have similar rates of CMRO2 increase (P=0.015) and there was no interaction between age and sex effects (P=0.85). However, when using data from the entire age range, women have a slower rate of CMRO2 change when compared to men (P<0.001 for age × sex interaction term). Thus, menopause and estrogen level may have played a role in this sex difference. Our data also revealed a possible circadian rhythm of CMRO2 in that brain metabolic rate is greater at noon than in the morning (P=0.02). This study reveals a potential neurobiological mechanism for age-related compensation in brain function and also suggests a sex-difference in its temporal pattern. PMID:24814209

Energy metabolism and inflammation in brain aging and Alzheimer's disease.

PubMed

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-11-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer's disease. As important cellular sources of H 2 O 2 , mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer's disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer's disease. Interaction of these systems is reviewed based on basic research and clinical studies. Copyright © 2016 Elsevier Inc. All rights reserved.

Genetic mouse models of brain ageing and Alzheimer's disease.

PubMed

Bilkei-Gorzo, Andras

2014-05-01

Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased White Matter Inflammation in Aging- and Alzheimer’s Disease Brain

PubMed Central

Raj, Divya; Yin, Zhuoran; Breur, Marjolein; Doorduin, Janine; Holtman, Inge R.; Olah, Marta; Mantingh-Otter, Ietje J.; Van Dam, Debby; De Deyn, Peter P.; den Dunnen, Wilfred; Eggen, Bart J. L.; Amor, Sandra; Boddeke, Erik

2017-01-01

Chronic neuroinflammation, which is primarily mediated by microglia, plays an essential role in aging and neurodegeneration. It is still unclear whether this microglia-induced neuroinflammation occurs globally or is confined to distinct brain regions. In this study, we investigated microglia activity in various brain regions upon healthy aging and Alzheimer’s disease (AD)-related pathology in both human and mouse samples. In purified microglia isolated from aging mouse brains, we found a profound gene expression pattern related to pro-inflammatory processes, phagocytosis, and lipid homeostasis. Particularly in white matter microglia of 24-month-old mice, abundant expression of phagocytic markers including Mac-2, Axl, CD16/32, Dectin1, CD11c, and CD36 was detected. Interestingly, in white matter of human brain tissue the first signs of inflammatory activity were already detected during middle age. Thus quantification of microglial proteins, such as CD68 (commonly associated with phagocytosis) and HLA-DR (associated with antigen presentation), in postmortem human white matter brain tissue showed an age-dependent increase in immunoreactivity already in middle-aged people (53.2 ± 2.0 years). This early inflammation was also detectable by non-invasive positron emission tomography imaging using [11C]-(R)-PK11195, a ligand that binds to activated microglia. Increased microglia activity was also prominently present in the white matter of human postmortem early-onset AD (EOAD) brain tissue. Interestingly, microglia activity in the white matter of late-onset AD (LOAD) CNS was similar to that of the aged clinically silent AD cases. These data indicate that microglia-induced neuroinflammation is predominant in the white matter of aging mice and humans as well as in EOAD brains. This white matter inflammation may contribute to the progression of neurodegeneration, and have prognostic value for detecting the onset and progression of aging and neurodegeneration. PMID:28713239

Estimated maximal and current brain volume predict cognitive ability in old age

PubMed Central

Royle, Natalie A.; Booth, Tom; Valdés Hernández, Maria C.; Penke, Lars; Murray, Catherine; Gow, Alan J.; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E.; Deary, Ian J.; Wardlaw, Joanna M.

2013-01-01

Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging. PMID:23850342

Estimated maximal and current brain volume predict cognitive ability in old age.

PubMed

Royle, Natalie A; Booth, Tom; Valdés Hernández, Maria C; Penke, Lars; Murray, Catherine; Gow, Alan J; Maniega, Susana Muñoz; Starr, John; Bastin, Mark E; Deary, Ian J; Wardlaw, Joanna M

2013-12-01

Brain tissue deterioration is a significant contributor to lower cognitive ability in later life; however, few studies have appropriate data to establish how much influence prior brain volume and prior cognitive performance have on this association. We investigated the associations between structural brain imaging biomarkers, including an estimate of maximal brain volume, and detailed measures of cognitive ability at age 73 years in a large (N = 620), generally healthy, community-dwelling population. Cognitive ability data were available from age 11 years. We found positive associations (r) between general cognitive ability and estimated brain volume in youth (male, 0.28; females, 0.12), and in measured brain volume in later life (males, 0.27; females, 0.26). Our findings show that cognitive ability in youth is a strong predictor of estimated prior and measured current brain volume in old age but that these effects were the same for both white and gray matter. As 1 of the largest studies of associations between brain volume and cognitive ability with normal aging, this work contributes to the wider understanding of how some early-life factors influence cognitive aging. Copyright © 2013 Elsevier Inc. All rights reserved.

Brain plasticity and motor practice in cognitive aging.

PubMed

Cai, Liuyang; Chan, John S Y; Yan, Jin H; Peng, Kaiping

2014-01-01

For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population.

Influences of brain development and ageing on cortical interactive networks.

PubMed

Zhu, Chengyu; Guo, Xiaoli; Jin, Zheng; Sun, Junfeng; Qiu, Yihong; Zhu, Yisheng; Tong, Shanbao

2011-02-01

To study the effect of brain development and ageing on the pattern of cortical interactive networks. By causality analysis of multichannel electroencephalograph (EEG) with partial directed coherence (PDC), we investigated the different neural networks involved in the whole cortex as well as the anterior and posterior areas in three age groups, i.e., children (0-10 years), mid-aged adults (26-38 years) and the elderly (56-80 years). By comparing the cortical interactive networks in different age groups, the following findings were concluded: (1) the cortical interactive network in the right hemisphere develops earlier than its left counterpart in the development stage; (2) the cortical interactive network of anterior cortex, especially at C3 and F3, is demonstrated to undergo far more extensive changes, compared with the posterior area during brain development and ageing; (3) the asymmetry of the cortical interactive networks declines during ageing with more loss of connectivity in the left frontal and central areas. The age-related variation of cortical interactive networks from resting EEG provides new insights into brain development and ageing. Our findings demonstrated that the PDC analysis of EEG is a powerful approach for characterizing the cortical functional connectivity during brain development and ageing. Copyright © 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

A New Disability-related Health Care Needs Assessment Tool for Persons With Brain Disorders

PubMed Central

Kim, Yoon; Eun, Sang June; Kim, Wan Ho; Lee, Bum-Suk; Leigh, Ja-Ho; Kim, Jung-Eun

2013-01-01

Objectives This study aimed to develop a health needs assessment (HNA) tool for persons with brain disorders and to assess the unmet needs of persons with brain disorders using the developed tool. Methods The authors used consensus methods to develop a HNA tool. Using a randomized stratified systematic sampling method adjusted for sex, age, and districts, 57 registered persons (27 severe and 30 mild cases) with brain disorders dwelling in Seoul, South Korea were chosen and medical specialists investigated all of the subjects with the developed tools. Results The HNA tool for brain disorders we developed included four categories: 1) medical interventions and operations, 2) assistive devices, 3) rehabilitation therapy, and 4) regular follow-up. This study also found that 71.9% of the subjects did not receive appropriate medical care, which implies that the severity of their disability is likely to be exacerbated and permanent, and the loss irrecoverable. Conclusions Our results showed that the HNA tool for persons with brain disorders based on unmet needs defined by physicians can be a useful method for evaluating the appropriateness and necessity of medical services offered to the disabled, and it can serve as the norm for providing health care services for disabled persons. Further studies should be undertaken to increase validity and reliability of the tool. Fundamental research investigating the factors generating or affecting the unmet needs is necessary; its results could serve as basis for developing policies to eliminate or alleviate these factors. PMID:24137530

A new disability-related health care needs assessment tool for persons with brain disorders.

PubMed

Kim, Yoon; Eun, Sang June; Kim, Wan Ho; Lee, Bum-Suk; Leigh, Ja-Ho; Kim, Jung-Eun; Lee, Jin Yong

2013-09-01

This study aimed to develop a health needs assessment (HNA) tool for persons with brain disorders and to assess the unmet needs of persons with brain disorders using the developed tool. The authors used consensus methods to develop a HNA tool. Using a randomized stratified systematic sampling method adjusted for sex, age, and districts, 57 registered persons (27 severe and 30 mild cases) with brain disorders dwelling in Seoul, South Korea were chosen and medical specialists investigated all of the subjects with the developed tools. The HNA tool for brain disorders we developed included four categories: 1) medical interventions and operations, 2) assistive devices, 3) rehabilitation therapy, and 4) regular follow-up. This study also found that 71.9% of the subjects did not receive appropriate medical care, which implies that the severity of their disability is likely to be exacerbated and permanent, and the loss irrecoverable. Our results showed that the HNA tool for persons with brain disorders based on unmet needs defined by physicians can be a useful method for evaluating the appropriateness and necessity of medical services offered to the disabled, and it can serve as the norm for providing health care services for disabled persons. Further studies should be undertaken to increase validity and reliability of the tool. Fundamental research investigating the factors generating or affecting the unmet needs is necessary; its results could serve as basis for developing policies to eliminate or alleviate these factors.

Lipidomics of human brain aging and Alzheimer's disease pathology.

PubMed

Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

2015-01-01

Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

Work ability, age and intention to leave aged care work.

PubMed

Austen, Siobhan; Jefferson, Therese; Lewin, Gill; Ong, Rachel; Sharp, Rhonda

2016-03-01

To describe the work ability of mature age women workers in Australia's aged care sector, and to explore the relationship between ageing, work ability and intention to leave. Logistic regression techniques were applied to a sample of 2721 responses to a survey of mature age women workers in the aged care sector. Mature age women working in the Australian aged care sector have relatively high levels of work ability by international standards. Furthermore, their work ability remains high in their 50s and 60s, in contrast to some prevailing stereotypes. However, work ability is a key determinant of intention to leave in key occupational groups. Our findings challenge some prevailing stereotypes about the work ability of mature age workers. However, they lend support for the development of retention strategies, which incorporate programs that target low work ability. © 2015 AJA Inc.

Music for the ageing brain: Cognitive, emotional, social, and neural benefits of musical leisure activities in stroke and dementia.

PubMed

Särkämö, Teppo

2017-01-01

Music engages an extensive network of auditory, cognitive, motor, and emotional processing regions in the brain. Coupled with the fact that the emotional and cognitive impact of music is often well preserved in ageing and dementia, music is a powerful tool in the care and rehabilitation of many ageing-related neurological diseases. In addition to formal music therapy, there has been a growing interest in self- or caregiver-implemented musical leisure activities or hobbies as a widely applicable means to support psychological wellbeing in ageing and in neurological rehabilitation. This article reviews the currently existing evidence on the cognitive, emotional, and neural benefits of musical leisure activities in normal ageing as well as in the rehabilitation and care of two of the most common and ageing-related neurological diseases: stroke and dementia.

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

PubMed

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

2016-07-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels

PubMed Central

Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F.; Eszes, Marika; Faull, Richard L.M.; Curtis, Maurice A.; Waldvogel, Henry J.; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V.; Coppola, Giovanni; Yang, X. William

2016-01-01

Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=−0.41, p=5.5×10−8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels. PMID:27479945

Acetyl-L-carnitine improves aged brain function.

PubMed

Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

2010-07-01

The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

Association of Structural Global Brain Network Properties with Intelligence in Normal Aging

PubMed Central

Fischer, Florian U.; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

2014-01-01

Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60–85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience. PMID:24465994

A Brain Network Processing the Age of Faces

PubMed Central

Homola, György A.; Jbabdi, Saad; Beckmann, Christian F.; Bartsch, Andreas J.

2012-01-01

Age is one of the most salient aspects in faces and of fundamental cognitive and social relevance. Although face processing has been studied extensively, brain regions responsive to age have yet to be localized. Using evocative face morphs and fMRI, we segregate two areas extending beyond the previously established face-sensitive core network, centered on the inferior temporal sulci and angular gyri bilaterally, both of which process changes of facial age. By means of probabilistic tractography, we compare their patterns of functional activation and structural connectivity. The ventral portion of Wernicke's understudied perpendicular association fasciculus is shown to interconnect the two areas, and activation within these clusters is related to the probability of fiber connectivity between them. In addition, post-hoc age-rating competence is found to be associated with high response magnitudes in the left angular gyrus. Our results provide the first evidence that facial age has a distinct representation pattern in the posterior human brain. We propose that particular face-sensitive nodes interact with additional object-unselective quantification modules to obtain individual estimates of facial age. This brain network processing the age of faces differs from the cortical areas that have previously been linked to less developmental but instantly changeable face aspects. Our probabilistic method of associating activations with connectivity patterns reveals an exemplary link that can be used to further study, assess and quantify structure-function relationships. PMID:23185334

On aging and aged care in Serbia.

PubMed

Sevo, G; Davidovic, M; Erceg, P; Despotovic, N; Milosevic, D P; Tasic, M

2015-06-01

Serbia is a demographically old nation, with 17.4 % of its residents being aged 65 years and older in 2011. The previous two decades of turbulent history have significantly affected the demographic picture of this country, and their ramifications remain visible in Serbia's economic, political, cultural, and health spheres. Major demographic forces behind population aging in Serbia can be attributed to lower fertility rates, migrations, and declining mortality (reflecting improvements in overall health leading to a longer life expectancy). In Serbia, low fertility and migrations appear to play major roles, although the relative contribution of recent migrations cannot be measured with accuracy. Patterns of demographic aging vary considerably across different geographic, socioeconomic, and cultural settings. The common denominator throughout present day Serbia is extensive political and economic transition. One would expect that, given sufficient time, this process will result in improved population health, and yet, at this stage outcomes of major health care reform in Serbia are somewhat perplexing. For the second consecutive year, Serbia's health care system has been ranked at the very bottom of the scale among 34 European countries. It is then no surprise that the elderly represent particularly vulnerable population segment. This paper discusses some of the issues relevant to these demographic patterns of aging and aged care in contemporary Serbia, focusing on the period after 2000.

Comparative proteomic analysis of brains of naturally aging mice.

PubMed

Yang, S; Liu, T; Li, S; Zhang, X; Ding, Q; Que, H; Yan, X; Wei, K; Liu, S

2008-06-26

We used comparative proteomic techniques to identify aging-related brain proteins in normal mice from neonate to old age. By 2-dimensional electrophoresis (2-DE), matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and peptide mass fingerprint (PMF) analysis, 39 proteins were identified, among which 6 stayed unchanged since 3 months, 6 increased and 27 decreased in various manners during aging. They are mainly involved in processes usually with destructive changes during aging, such as metabolism, transport, signaling, stress response and apoptosis. The 27 proteins' decrease may be responsible for brain aging. In particular, decrease of proteasome alpha subunits 3/6, ubiquitin carboxyl-terminal esterase L3, valosin-containing protein and calreticulin may be responsible for the declination of protein quality control; glutamate dehydrogenase 1, isocitrate dehydrogenase 1 and ubiquinol cytochrome c reductase core protein 2 for the shortage of energy and reducing agent; ubiquitin-conjugating enzyme E2N and heterogeneous nuclear ribonucleoprotein A2/B1 for the increase of DNA damage and transcription detuning; calbindin 1 and amphiphysin for the disturbance of synaptic transport and ion signals. The six proteins' increase may be involved in anti-aging processes. In particular, transketolase, mitochondrial creatine kinase 1 and ribosomal protein L37 may help to enhance energy metabolism; triosephosphate isomerase 1 may help to resist oxidative stress. Moreover, most of these proteins were found for the first time to be involved in the natural senescence of brain, which would provide new clues about the mechanism of brain aging.

Executive dysfunction, brain aging, and political leadership.

PubMed

Fisher, Mark; Franklin, David L; Post, Jerrold M

2014-01-01

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.

Evaluation of an aged care nurse practitioner service: quality of care within a residential aged care facility hospital avoidance service.

PubMed

Dwyer, Trudy; Craswell, Alison; Rossi, Dolene; Holzberger, Darren

2017-01-13

Reducing avoidable hospitialisation of aged care facility (ACF) residents can improve the resident experience and their health outcomes. Consequently many variations of hospital avoidance (HA) programs continue to evolve. Nurse practitioners (NP) with expertise in aged care have the potential to make a unique contribution to hospital avoidance programs. However, little attention has been dedicated to service evaluation of this model and the quality of care provided. The purpose of this study was to evaluate the quality of an aged care NP model of care situated within a HA service in a regional area of Australia. Donabedian's structure, process and outcome framework was applied to evaluate the quality of the NP model of care. The Australian Nurse Practitioner Study standardised interview schedules for evaluating NP models of care guided the semi-structured interviews of nine health professionals (including ACF nurses, medical doctors and allied health professionals), four ACF residents and their families and two NPs. Theory driven coding consistent with the Donabedian framework guided analysis of interview data and presentation of findings. Structural dimensions identified included the 'in-reach' nature of the HA service, distance, limitations of professional regulation and the residential care model. These dimensions influenced the process of referring the resident to the NP, the NPs timely response and interactions with other professionals. The processes where the NPs take time connecting with residents, initiating collaborative care plans, up-skilling aged care staff and function as intra and interprofessional boundary spanners all contributed to quality outcomes. Quality outcomes in this study were about timely intervention, HA, timely return home, partnering with residents and family (knowing what they want) and resident and health professional satisfaction. This study provides valuable insights into the contribution of the NP model of care within an aged care

School-age effects of the newborn individualized developmental care and assessment program for preterm infants with intrauterine growth restriction: preliminary findings

PubMed Central

2013-01-01

Background The experience in the newborn intensive care nursery results in premature infants’ neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). Methods Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother’s intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks’ lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. Results Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore

Ageing and brain white matter structure in 3,513 UK Biobank participants

PubMed Central

Cox, Simon R.; Ritchie, Stuart J.; Tucker-Drob, Elliot M.; Liewald, David C.; Hagenaars, Saskia P.; Davies, Gail; Wardlaw, Joanna M.; Gale, Catharine R.; Bastin, Mark E.; Deary, Ian J.

2016-01-01

Quantifying the microstructural properties of the human brain's connections is necessary for understanding normal ageing and disease. Here we examine brain white matter magnetic resonance imaging (MRI) data in 3,513 generally healthy people aged 44.64–77.12 years from the UK Biobank. Using conventional water diffusion measures and newer, rarely studied indices from neurite orientation dispersion and density imaging, we document large age associations with white matter microstructure. Mean diffusivity is the most age-sensitive measure, with negative age associations strongest in the thalamic radiation and association fibres. White matter microstructure across brain tracts becomes increasingly correlated in older age. This may reflect an age-related aggregation of systemic detrimental effects. We report several other novel results, including age associations with hemisphere and sex, and comparative volumetric MRI analyses. Results from this unusually large, single-scanner sample provide one of the most extensive characterizations of age associations with major white matter tracts in the human brain. PMID:27976682

[Direct cost of primary care of mild traumatic brain injury in adults by GRD in third level of care].

PubMed

Barragán-Hervella, Rodolfo; Montiel-Jarquín, Álvaro; Limón-Serrano, Iván; Escobedo-Sosa, Víctor; Loría-Castellanos, Jorge

To describe the direct cost of primary health care for patients with mild traumatic head injury in a third level medical facility. Cross-sectional study in 219 patients with mild traumatic brain injury (GRD 090 S06.0 ICD-10 including uncomplicated concussion without complication and increased comorbidity). A medical unit of tertiary care in the State of Puebla, Mexico. Direct costs were taken from ACDO.AS3.HCT.280115 / 7.P.DF Agreement and its annexes in Mexican pesos, the variables analyzed were age, gender, shift attention, laboratory, radiographic and tomographic studies, length of stay, specialist consultations, emergency care, medicines, and treatment materials. Descriptive statistics on SPSS program IBM v22. 53.4% male, 46.6% female; average age 31.9 years; morning shift attention 58.4%, evening 23.3%, and nightly 18.3%. The cost: $ 1,755 laboratory, plain radiographs $ 202,794, tomographic studies $ 26,720, consultation with neurosurgeon $ 279,174, emergency care $ 501,510; curing material: single steri drape $8,326.38, Micropore $1,307.43, infusion equipment $790.59, venipuncture needle $7,408.77; drugs: diclofenac $946.08, Ketorolac $724.89, 1000 ml. intravenous solution $1,561.47, total cost $ 1,032,293.72, average/patient: 4,713.66 Mexican pesos. The direct cost of primary health care of patients with mild traumatic head injury is high; sticking to the correct handling decreases the cost of attention.

Differentiating the Influences of Aging and Adiposity on Brain Weights, Levels of Serum and Brain Cytokines, Gastrointestinal Hormones, and Amyloid Precursor Protein.

PubMed

Banks, William A; Abrass, Christine K; Hansen, Kim M

2016-01-01

Aging and obesity exert important effects on disease. Differentiating these effects is difficult, however, because weight gain often accompanies aging. Here, we used a nested design of aged, calorically restricted, and refed rats to measure changes in brain and blood levels of cytokines and gastrointestinal hormones, brain amyloid precursor protein levels, and brain and body weights. By comparing groups and using path analysis, we found divergent influences of chronological aging versus body weight, our main findings being (i) changes in whole brain weight and serum macrophage colony-stimulating factor levels correlated better with body weight than with chronological aging, (ii) a decrease in brain cytokines and brain plasminogen activator inhibitor levels correlated better with chronological aging than with body weight, (iii) serum erythropoietin levels were influenced by both body weight and aging, (iv) serum plasminogen activator inhibitor, serum cytokines, and brain tumor necrosis factor were not influenced by aging or body weight, and (v) brain amyloid precursor protein more closely related to body weight and serum levels of gastrointestinal hormones than to brain weight, chronological aging, or cytokines. These findings show that although aging and body weight interact, their influences are distinct not only among various cytokines and hormones but also between the central nervous system and the peripheral tissue compartments. Published by Oxford University Press on behalf of the Gerontological Society of America 2014.

The views of patients with brain cancer about palliative care: a qualitative study.

PubMed

Vierhout, M; Daniels, M; Mazzotta, P; Vlahos, J; Mason, W P; Bernstein, M

2017-12-01

Palliative care, a specialty aimed at providing optimal care to patients with life-limiting and chronic conditions, has several benefits. Although palliative care is appropriate for neurosurgical conditions, including brain cancer, few studies have examined the views of brain cancer patients about palliative care. We aimed to explore the thoughts of brain cancer patients about palliative care, their opinions about early palliative care, and their preferred care setting. Semi-structured interviews and the qualitative research methodologies of grounded theory were used to explore perceptions of palliative care on the part of 39 brain cancer outpatients. Seven overarching actions emerged: ■Patients would prefer to receive palliative care in the home.■Increased time with caregivers and family are the main appeals of home care.■Patients express dissatisfaction with brief and superficial interactions with health care providers.■Patients believe that palliative care can contribute to their emotional well-being.■Patients are open to palliative care if they believe that it will not diminish optimism.■There is a preconceived idea that palliative care is directly linked to active dying, and that supposed link generates fear in some patients.■Patients prefer to be educated about palliative care as an option early in their illness, even if they are fearful of it. Overall, when educated about the true meaning of palliative care, most patients express interest in accessing palliative care services. Although the level of fear concerning palliative care varies in patients, most recognize the associated benefits.

[Research of anti-aging mechanism of ginsenoside Rg1 on brain].

PubMed

Li, Cheng-peng; Zhang, Meng-si; Liu, Jun; Geng, Shan; Li, Jing; Zhu, Jia-hong; Zhang, Yan-yan; Jia, Yan-yan; Wang, Lu; Wang, Shun-he; Wang, Ya-ping

2014-11-01

Neurodegenerative disease is common and frequently occurs in elderly patients. Previous studies have shown that ginsenoside Rg1 was able to inhibit senescent of brain, but the mechanism on the brain during the treatment remains elucidated. To study the mechanism of ginsenoside Rg1 in the process of anti-aging of brain, forty male SD rats were randomly divided into normal group, Rg1 normal group, brain aging model group and Rg1 brain aging model group, each group with 10 rats (brain aging model group: subcutaneous injection of D-galactose (120 mg kg(-1)), qd for 42 consecutive days; Rg1 brain aging model group: while copying the same test as that of brain aging model group, begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Rg1 normal group: subcutaneous injection of the same amount of saline; begin intraperitoneal injection of ginsenosides Rg1 (20 mg x kg(-1)) qd for 27 d from 16 d. Normal: injected with an equal volume of saline within the same time. Perform the related experiment on the second day after finishing copying the model or the completion of the first two days of drug injections). Learning and memory abilities were measured by Morris water maze. The number of senescent cells was detected by SA-beta-Gal staining while the level of IL-1 and IL-6 proinflammatory cytokines in hippocampus were detected by ELISA. The activities of SOD, contents of GSH in hippo- campus were quantified by chromatometry. The change of telomerase activities and telomerase length were performed by TRAP-PCR and southern blotting assay, respectively. It is pointed that, in brain aging model group, the spatial learning and memory capacities were weaken, SA-beta-Gal positive granules increased in section of brain tissue, the activity of antioxidant enzyme SOD and the contents of GSH decreased in hippocampus, the level of IL-1 and IL-6 increased in hippocampus, while the length of telomere and the activity of telomerase decreased in hippocampus

Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

PubMed

Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

2015-12-01

The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Age-Related Gray and White Matter Changes in Normal Adult Brains

PubMed Central

Farokhian, Farnaz; Yang, Chunlan; Beheshti, Iman; Matsuda, Hiroshi; Wu, Shuicai

2017-01-01

Normal aging is associated with both structural changes in many brain regions and functional declines in several cognitive domains with advancing age. Advanced neuroimaging techniques enable explorative analyses of structural alterations that can be used as assessments of such age-related changes. Here we used voxel-based morphometry (VBM) to investigate regional and global brain volume differences among four groups of healthy adults from the IXI Dataset: older females (OF, mean age 68.35 yrs; n=69), older males (OM, 68.43 yrs; n=66), young females (YF, 27.09 yrs; n=71), and young males (YM, 27.91 yrs; n=71), using 3D T1-weighted MRI data. At the global level, we investigated the influence of age and gender on brain volumes using a two-way analysis of variance. With respect to gender, we used the Pearson correlation to investigate global brain volume alterations due to age in the older and young groups. At the regional level, we used a flexible factorial statistical test to compare the means of gray matter (GM) and white matter (WM) volume alterations among the four groups. We observed different patterns in both the global and regional GM and WM alterations in the young and older groups with respect to gender. At the global level, we observed significant influences of age and gender on global brain volumes. At the regional level, the older subjects showed a widespread reduction in GM volume in regions of the frontal, insular, and cingulate cortices compared to the young subjects in both genders. Compared to the young subjects, the older subjects showed a widespread WM decline prominently in the thalamic radiations, in addition to increased WM in pericentral and occipital areas. Knowledge of these observed brain volume differences and changes may contribute to the elucidation of mechanisms underlying aging as well as age-related brain atrophy and disease. PMID:29344423

Information management for aged care provision in Australia: development of an aged care minimum dataset and strategies to improve quality and continuity of care.

PubMed

Davis, Jenny; Morgans, Amee; Burgess, Stephen

2016-04-01

Efficient information systems support the provision of multi-disciplinary aged care and a variety of organisational purposes, including quality, funding, communication and continuity of care. Agreed minimum data sets enable accurate communication across multiple care settings. However, in aged care multiple and poorly integrated data collection frameworks are commonly used for client assessment, government reporting and funding purposes. To determine key information needs in aged care settings to improve information quality, information transfer, safety, quality and continuity of care to meet the complex needs of aged care clients. Modified Delphi methods involving five stages were employed by one aged care provider in Victoria, Australia, to establish stakeholder consensus for a derived minimum data set and address barriers to data quality. Eleven different aged care programs were identified; with five related data dictionaries, three minimum data sets, five program standards or quality frameworks. The remaining data collection frameworks related to diseases classification, funding, service activity reporting, and statistical standards and classifications. A total of 170 different data items collected across seven internal information systems were consolidated to a derived set of 60 core data items and aligned with nationally consistent data collection frameworks. Barriers to data quality related to inconsistencies in data items, staff knowledge, workflow, system access and configuration. The development an internal aged care minimum data set highlighted the critical role of primary data quality in the upstream and downstream use of client information; and presents a platform to build national consistency across the sector.

The emotion paradox in the aging brain

PubMed Central

Mather, Mara

2012-01-01

This paper reviews age differences in emotion processing and how they may relate to age-related changes in the brain. Compared with younger adults, older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information. Older adults’ ability to insulate their thoughts and emotional reactions from negative situations is likely due to a number of factors, such as being less influenced by interoceptive cues, selecting different emotion regulation strategies, having less age-related decline in prefrontal regions associated with emotional control than in other prefrontal regions, and engaging in emotion regulation strategies as a default mode in their everyday lives. Healthy older adults’ avoidance of processing negative stimuli may contribute to their well-maintained emotional well-being. However, when cardiovascular disease leads to additional prefrontal white matter damage, older adults have fewer cognitive control mechanisms available to regulate their emotions, making them more vulnerable to depression. In general, while age-related changes in the brain help shape emotional experience, shifts in preferred strategies and goal priorities are also important influences. PMID:22409159

The Aging Brain and Cognition

PubMed Central

Marchant, Natalie L.; Reed, Bruce R.; Sanossian, Nerses; Madison, Cindee M.; Kriger, Stephen; Dhada, Roxana; Mack, Wendy J.; DeCarli, Charles; Weiner, Michael W.; Mungas, Dan M.; Chui, Helena C.; Jagust, William J.

2013-01-01

Importance β-Amyloid (Aβ) deposition and vascular brain injury (VBI) frequently co-occur and are both associated with cognitive decline in aging. Determining whether a direct relationship exists between them has been challenging. We sought to understand VBI’s influence on cognition and clinical impairment, separate from and in conjunction with pathologic changes associated with Alzheimer disease (AD). Objective To examine the relationship between neuroimaging measures of VBI and brain Aβ deposition and their associations with cognition. Design and Setting A cross-sectional study in a community- and clinic-based sample recruited for elevated vascular disease risk factors. Participants Clinically normal (mean age, 77.1 years [N=30]), cognitively impaired (mean age, 78.0 years [N=24]), and mildly demented (mean age, 79.8 years [N=7]) participants. Interventions Magnetic resonance imaging, Aβ (Pitts-burgh Compound B–positron emission tomographic [PiB-PET]) imaging, and cognitive testing. Main Outcome Measures Magnetic resonance images were rated for the presence and location of infarct (34 infarct-positive participants, 27 infarct-negative participants) and were used to quantify white matter lesion volume. The PiB-PET uptake ratios were used to create a PiB index by averaging uptake across regions vulnerable to early Aβ deposition; PiB positivity (29 PiB-positive participants, 32 PiB-negative participants) was determined from a data-derived threshold. Standardized composite cognitive measures included executive function and verbal and nonverbal memory. Results Vascular brain injury and Aβ were independent in both cognitively normal and impaired participants. Infarction, particularly in cortical and subcortical gray matter, was associated with lower cognitive performance in all domains (P<.05 for all comparisons). Pittsburgh Compound B positivity was neither a significant predictor of cognition nor interacted with VBI. Conclusions and Relevance In this elderly

Neuro-immune dysfunction during brain aging: new insights in microglial cell regulation.

PubMed

Matt, Stephanie M; Johnson, Rodney W

2016-02-01

Microglia, the resident immune cells of the brain, are at the center of communication between the central nervous system and immune system. While these brain-immune interactions are balanced in healthy adulthood, the ability to maintain homeostasis during aging is impaired. Microglia develop a loss of integrated regulatory networks including aberrant signaling from other brain cells, immune sensors, and epigenetic modifiers. The low-grade chronic neuroinflammation associated with this dysfunctional activity likely contributes to cognitive deficits and susceptibility to age-related pathologies. A better understanding of the underlying mechanisms responsible for neuro-immune dysregulation with age is crucial for providing targeted therapeutic strategies to support brain repair and healthy aging. Copyright © 2015 Elsevier Ltd. All rights reserved.

Development and evaluation of an aged care specific Advance Care Plan.

PubMed

Silvester, William; Parslow, Ruth A; Lewis, Virginia J; Fullam, Rachael S; Sjanta, Rebekah; Jackson, Lynne; White, Vanessa; Hudson, Rosalie

2013-06-01

To report on the quality of advance care planning (ACP) documents in use in residential aged care facilities (RACF) in areas of Victoria Australia prior to a systematic intervention; to report on the development and performance of an aged care specific Advance Care Plan template used during the intervention. An audit of the quality of pre-existing documentation used to record resident treatment preferences and end-of-life wishes at participating RACFs; development and pilot of an aged care specific Advance Care Plan template; an audit of the completeness and quality of Advance Care Plans completed on the new template during a systematic ACP intervention. 19 selected RACFs (managed by 12 aged care organisations) in metropolitan and regional areas of Victoria. Documentation in use at facilities prior to the ACP intervention most commonly recorded preferences regarding hospital transfer, life prolonging treatment and personal/cultural/religious wishes. However, 7 of 12 document sets failed to adequately and clearly specify the resident's preferences as regards life prolonging medical treatment. The newly developed aged care specific Advance Care Plan template was met with approval by participating RACFs. Of 203 Advance Care Plans completed on the template throughout the project period, 49% included the appointment of a Medical Enduring Power of Attorney. Requests concerning medical treatment were specified in almost all completed documents (97%), with 73% nominating the option of refusal of life-prolonging treatment. Over 90% of plans included information concerning residents' values and beliefs, and future health situations that the resident would find to be unacceptable were specified in 78% of completed plans. Standardised procedures and documentation are needed to improve the quality of processes, documents and outcomes of ACP in the residential aged care sector.

Gene expression changes in the course of normal brain aging are sexually dimorphic

PubMed Central

Berchtold, Nicole C.; Cribbs, David H.; Coleman, Paul D.; Rogers, Joseph; Head, Elizabeth; Kim, Ronald; Beach, Tom; Miller, Carol; Troncoso, Juan; Trojanowski, John Q.; Zielke, H. Ronald; Cotman, Carl W.

2008-01-01

Gene expression profiles were assessed in the hippocampus, entorhinal cortex, superior-frontal gyrus, and postcentral gyrus across the lifespan of 55 cognitively intact individuals aged 20–99 years. Perspectives on global gene changes that are associated with brain aging emerged, revealing two overarching concepts. First, different regions of the forebrain exhibited substantially different gene profile changes with age. For example, comparing equally powered groups, 5,029 probe sets were significantly altered with age in the superior-frontal gyrus, compared with 1,110 in the entorhinal cortex. Prominent change occurred in the sixth to seventh decades across cortical regions, suggesting that this period is a critical transition point in brain aging, particularly in males. Second, clear gender differences in brain aging were evident, suggesting that the brain undergoes sexually dimorphic changes in gene expression not only in development but also in later life. Globally across all brain regions, males showed more gene change than females. Further, Gene Ontology analysis revealed that different categories of genes were predominantly affected in males vs. females. Notably, the male brain was characterized by global decreased catabolic and anabolic capacity with aging, with down-regulated genes heavily enriched in energy production and protein synthesis/transport categories. Increased immune activation was a prominent feature of aging in both sexes, with proportionally greater activation in the female brain. These data open opportunities to explore age-dependent changes in gene expression that set the balance between neurodegeneration and compensatory mechanisms in the brain and suggest that this balance is set differently in males and females, an intriguing idea. PMID:18832152

Enhancing resilience in registered aged care nurses.

PubMed

Cameron, Fiona; Brownie, Sonya

2010-06-01

To identify the factors that impact the resilience of registered aged care nurses, that is their capacity to adapt to the physical, mental and emotional demands of working in aged care facilities. This study explored the lived experience of nine registered nurses working in residential aged care facilities on the Sunshine Coast, Queensland, who were asked to reflect on the phenomenon of resilience in the workplace. This study found that clinical expertise, a sense of purpose in a holistic care environment, a positive attitude and work-life balance are important determinants of resilience in aged care nurses. Resilience in nurses in residential aged care facilities is enhanced when they are able to maintain long-term, meaningful relationships with residents. Collegial support that provides opportunities to debrief and validate experiences as well as the use of humour to defuse stress promotes well-being and builds resilience in the workplace.

Aging and Gene Expression in the Primate Brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.

2005-02-18

It is well established that gene expression levels in many organisms change during the aging process, and the advent of DNA microarrays has allowed genome-wide patterns of transcriptional changes associated with aging to be studied in both model organisms and various human tissues. Understanding the effects of aging on gene expression in the human brain is of particular interest, because of its relation to both normal and pathological neurodegeneration. Here we show that human cerebral cortex, human cerebellum, and chimpanzee cortex each undergo different patterns of age-related gene expression alterations. In humans, many more genes undergo consistent expression changes inmore » the cortex than in the cerebellum; in chimpanzees, many genes change expression with age in cortex, but the pattern of changes in expression bears almost no resemblance to that of human cortex. These results demonstrate the diversity of aging patterns present within the human brain, as well as how rapidly genome-wide patterns of aging can evolve between species; they may also have implications for the oxidative free radical theory of aging, and help to improve our understanding of human neurodegenerative diseases.« less

Sleep duration and age-related changes in brain structure and cognitive performance.

PubMed

Lo, June C; Loh, Kep Kee; Zheng, Hui; Sim, Sam K Y; Chee, Michael W L

2014-07-01

To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Community-based longitudinal brain and cognitive aging study using a convenience sample. Participants were studied in a research laboratory. Relatively healthy adults aged 55 y and older at study commencement. N/A. Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance.

Genomic integrity and the ageing brain.

PubMed

Chow, Hei-man; Herrup, Karl

2015-11-01

DNA damage is correlated with and may drive the ageing process. Neurons in the brain are postmitotic and are excluded from many forms of DNA repair; therefore, neurons are vulnerable to various neurodegenerative diseases. The challenges facing the field are to understand how and when neuronal DNA damage accumulates, how this loss of genomic integrity might serve as a 'time keeper' of nerve cell ageing and why this process manifests itself as different diseases in different individuals.

Aging and unusual catecholamine-containing structures in the mouse brain.

PubMed

Masuoka, D T; Jonsson, G; Finch, C E

1979-06-22

Brains of C57BL/6J mice, aged 4, 8 and 20--29 months, were examined by the Falck-Hillarp histochemical fluorescence technique. Numerous large, intensely fluorescent green to yellow-green spots (LIFS) were observed in the brains of senescent mice. LIFS were generally round to ovoid in shape and ranged in size from about 10 micrometer to about 30 micrometer. Histochemical and pharmacological procedures and spectral analysis indicated that the formaldehyde-induced fluorescence of the LIFS was due to the presence of catecholamines (CA) rather than aging pigment. Their distribution in the brain suggests an association with nerve axons or terminals rather than cell bodies. The number of LIFS in the hypothalamus increased progressively during aging. It is proposed that LIFS may represent age-related, unusual CA accumulation in enlargements proximal to axonal or terminal portions undergoing spontaneous degeneration.

Energy Metabolism and Inflammation in Brain Aging and Alzheimer’s Disease

PubMed Central

Yin, Fei; Sancheti, Harsh; Patil, Ishan; Cadenas, Enrique

2016-01-01

The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies. PMID:27154981

Lower cognitive reserve in the aging human immunodeficiency virus-infected brain.

PubMed

Chang, Linda; Holt, John L; Yakupov, Renat; Jiang, Caroline S; Ernst, Thomas

2013-04-01

More HIV-infected individuals are living longer; however, how their brain function is affected by aging is not well understood. One hundred twenty-two men (56 seronegative control [SN] subjects, 37 HIV subjects with normal cognition [HIV+NC], 29 with HIV-associated neurocognitive disorder [HAND]) performed neuropsychological tests and had acceptable functional magnetic resonance imaging scans at 3 Tesla during tasks with increasing attentional load. With older age, SN and HIV+NC subjects showed increased activation in the left posterior (reserve, "bottom-up") attention network for low attentional-load tasks, and further increased activation in the left posterior and anterior ("top-down") attention network on intermediate (HIV+NC only) and high attentional-load tasks. HAND subjects had only age-dependent decreases in activation. Age-dependent changes in brain activation differed between the 3 groups, primarily in the left frontal regions (despite similar brain atrophy). HIV and aging act synergistically or interactively to exacerbate brain activation abnormalities in different brain regions, suggestive of a neuroadaptive mechanism in the attention network to compensate for declined neural efficiency. While the SN and HIV+NC subjects compensated for their declining attention with age by using reserve and "top-down" attentional networks, older HAND subjects were unable to compensate which resulted in cognitive decline. Copyright © 2013 Elsevier Inc. All rights reserved.

R2* mapping for brain iron: associations with cognition in normal aging.

PubMed

Ghadery, Christine; Pirpamer, Lukas; Hofer, Edith; Langkammer, Christian; Petrovic, Katja; Loitfelder, Marisa; Schwingenschuh, Petra; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Schmidt, Helena; Fazekas, Franz; Mangin, Jean-Francois; Chabriat, Hugues; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

2015-02-01

Brain iron accumulates during aging and has been associated with neurodegenerative disorders including Alzheimer's disease. Magnetic resonance (MR)-based R2* mapping enables the in vivo detection of iron content in brain tissue. We investigated if during normal brain aging iron load relates to cognitive impairment in region-specific patterns in a community-dwelling cohort of 336 healthy, middle aged, and older adults from the Austrian Stroke Prevention Family Study. MR imaging and R2* mapping in the basal ganglia and neocortex were done at 3T. Comprehensive neuropsychological testing assessed memory, executive function, and psychomotor speed. We found the highest iron concentration in the globus pallidus, and pallidal and putaminal iron was significantly and inversely associated with cognitive performance in all cognitive domains, except memory. These associations were iron load dependent. Vascular brain lesions and brain volume did not mediate the relationship between iron and cognitive performance. We conclude that higher R2*-determined iron in the basal ganglia correlates with cognitive impairment during brain aging independent of concomitant brain abnormalities. The prognostic significance of this finding needs to be determined. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuron-astrocyte signaling is preserved in the aging brain.

PubMed

Gómez-Gonzalo, Marta; Martin-Fernandez, Mario; Martínez-Murillo, Ricardo; Mederos, Sara; Hernández-Vivanco, Alicia; Jamison, Stephanie; Fernandez, Ana P; Serrano, Julia; Calero, Pilar; Futch, Hunter S; Corpas, Rubén; Sanfeliu, Coral; Perea, Gertrudis; Araque, Alfonso

2017-04-01

Astrocytes play crucial roles in brain homeostasis and are emerging as regulatory elements of neuronal and synaptic physiology by responding to neurotransmitters with Ca 2+ elevations and releasing gliotransmitters that activate neuronal receptors. Aging involves neuronal and astrocytic alterations, being considered risk factor for neurodegenerative diseases. Most evidence of the astrocyte-neuron signaling is derived from studies with young animals; however, the features of astrocyte-neuron signaling in adult and aging brain remain largely unknown. We have investigated the existence and properties of astrocyte-neuron signaling in physiologically and pathologically aging mouse hippocampal and cortical slices at different lifetime points (0.5 to 20 month-old animals). We found that astrocytes preserved their ability to express spontaneous and neurotransmitter-dependent intracellular Ca 2+ signals from juvenile to aging brains. Likewise, resting levels of gliotransmission, assessed by neuronal NMDAR activation by glutamate released from astrocytes, were largely preserved with similar properties in all tested age groups, but DHPG-induced gliotransmission was reduced in aged mice. In contrast, gliotransmission was enhanced in the APP/PS1 mouse model of Alzheimer's disease, indicating a dysregulation of astrocyte-neuron signaling in pathological conditions. Disruption of the astrocytic IP 3 R2 mediated-signaling, which is required for neurotransmitter-induced astrocyte Ca 2+ signals and gliotransmission, boosted the progression of amyloid plaque deposits and synaptic plasticity impairments in APP/PS1 mice at early stages of the disease. Therefore, astrocyte-neuron interaction is a fundamental signaling, largely conserved in the adult and aging brain of healthy animals, but it is altered in Alzheimer's disease, suggesting that dysfunctions of astrocyte Ca 2+ physiology may contribute to this neurodegenerative disease. GLIA 2017 GLIA 2017;65:569-580. © 2017 Wiley

Cerebral motor function in very premature-at-birth adolescents: a brain stimulation exploration of kangaroo mother care effects.

PubMed

Schneider, Cyril; Charpak, Nathalie; Ruiz-Peláez, Juan G; Tessier, Réjean

2012-10-01

  Given that prematurity has deleterious effects on brain networking development beyond childhood, the study explored whether an early intervention such as Kangaroo Mother Care (KMC) in very preterm preemies could have influenced brain motor function up to adolescence.   Transcranial magnetic stimulation (TMS) was applied over the primary motor cortex (M1) of 39 adolescents born very prematurely (<33 weeks' gestational age, 21 having received KMC after birth, 18 Controls with no KMC) and nine adolescents born at term (>37 weeks' gestational age, >2500 g) to assess the functional integrity of motor circuits in each hemisphere (motor planning) and between hemispheres (callosal function).   All TMS outcomes were similar between KMC and term adolescents, with typical values as in healthy adults, and better than in Controls. KMC adolescents presented faster conduction times revealing more efficient M1 cell synchronization (p < 0.05) and interhemispheric transfer time (p < 0.0001), more frequent inhibitory processes with a better control between hemispheres (p < 0.0001).   The enhanced synchronization, conduction times and connectivity of cerebral motor pathways in the KMC group suggests that the Kangaroo Mother Care positively influenced the premature brain networks and synaptic efficacy up to adolescence. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Fasting and Fast Food Diet Play an Opposite Role in Mice Brain Aging.

PubMed

Castrogiovanni, Paola; Li Volti, Giovanni; Sanfilippo, Cristina; Tibullo, Daniele; Galvano, Fabio; Vecchio, Michele; Avola, Roberto; Barbagallo, Ignazio; Malaguarnera, Lucia; Castorina, Sergio; Musumeci, Giuseppe; Imbesi, Rosa; Di Rosa, Michelino

2018-01-20

Fasting may be exploited as a possible strategy for prevention and treatment of several diseases such as diabetes, obesity, and aging. On the other hand, high-fat diet (HFD) represents a risk factor for several diseases and increased mortality. The aim of the present study was to evaluate the impact of fasting on mouse brain aging transcriptome and how HFD regulates such pathways. We used the NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable microarray datasets comparing mouse brain transcriptome under fasting or HFD vs aged mouse brain transcriptome. Three microarray datasets were selected for this study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms involved in this process were evaluated. This analysis showed that, regardless of fasting duration, mouse brain significantly expressed 21 and 30 upregulated and downregulated genes, respectively. The involved biological processes were related to cell cycle arrest, cell death inhibition, and regulation of cellular metabolism. Comparing mouse brain transcriptome under fasting and aged conditions, we found out that the number of genes in common increased with the duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain transcriptome under HFD resembles for the 30% the one of the aged mice. Furthermore, several molecular processes were found to be shared between HFD and aging. In conclusion, we suggest that fasting and HFD play an opposite role in brain transcriptome of aged mice. Therefore, an intermittent diet could represent a possible clinical strategy to counteract aging, loss of memory, and neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain degenerative processes triggered by aging.

Redox proteomics and the dynamic molecular landscape of the aging brain.

PubMed

Perluigi, Marzia; Swomley, Aaron M; Butterfield, D Allan

2014-01-01

It is well established that the risk to develop neurodegenerative disorders increases with chronological aging. Accumulating studies contributed to characterize the age-dependent changes either at gene and protein expression level which, taken together, show that aging of the human brain results from the combination of the normal decline of multiple biological functions with environmental factors that contribute to defining disease risk of late-life brain disorders. Finding the "way out" of the labyrinth of such complex molecular interactions may help to fill the gap between "normal" brain aging and development of age-dependent diseases. To this purpose, proteomics studies are a powerful tool to better understand where to set the boundary line of healthy aging and age-related disease by analyzing the variation of protein expression levels and the major post translational modifications that determine "protein" physio/pathological fate. Increasing attention has been focused on oxidative modifications due to the crucial role of oxidative stress in aging, in addition to the fact that this type of modification is irreversible and may alter protein function. Redox proteomics studies contributed to decipher the complexity of brain aging by identifying the proteins that were increasingly oxidized and eventually dysfunctional as a function of age. The purpose of this review is to summarize the most important findings obtained by applying proteomics approaches to murine models of aging with also a brief overview of some human studies, in particular those related to dementia. Copyright © 2014. Published by Elsevier B.V.

Advanced age negatively impacts survival in an experimental brain tumor model.

PubMed

Ladomersky, Erik; Zhai, Lijie; Gritsina, Galina; Genet, Matthew; Lauing, Kristen L; Wu, Meijing; James, C David; Wainwright, Derek A

2016-09-06

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, with an average age of 64 years at the time of diagnosis. To study GBM, a number of mouse brain tumor models have been utilized. In these animal models, subjects tend to range from 6 to 12 weeks of age, which is analogous to that of a human teenager. Here, we examined the impact of age on host immunity and the gene expression associated with immune evasion in immunocompetent mice engrafted with syngeneic intracranial GL261. The data indicate that, in mice with brain tumors, youth conveys an advantage to survival. While age did not affect the tumor-infiltrating T cell phenotype or quantity, we discovered that old mice express higher levels of the immunoevasion enzyme, IDO1, which was decreased by the presence of brain tumor. Interestingly, other genes associated with promoting immunosuppression including CTLA-4, PD-L1 and FoxP3, were unaffected by age. These data highlight the possibility that IDO1 contributes to faster GBM outgrowth with advanced age, providing rationale for future investigation into immunotherapeutic targeting in the future. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

PubMed

Li, Wan; Yang, Chunlan; Shi, Feng; Wang, Qun; Wu, Shuicai; Lu, Wangsheng; Li, Shaowu; Nie, Yingnan; Zhang, Xin

2018-04-16

Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.

Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance

PubMed Central

Lo, June C.; Loh, Kep Kee; Zheng, Hui; Sim, Sam K.Y.; Chee, Michael W.L.

2014-01-01

Study Objectives: To investigate the contribution of sleep duration and quality to age-related changes in brain structure and cognitive performance in relatively healthy older adults. Design: Community-based longitudinal brain and cognitive aging study using a convenience sample. Setting: Participants were studied in a research laboratory. Participants: Relatively healthy adults aged 55 y and older at study commencement. Interventions: N/A. Measurements and Results: Participants underwent magnetic resonance imaging and neuropsychological assessment every 2 y. Subjective assessments of sleep duration and quality and blood samples were obtained. Each hour of reduced sleep duration at baseline augmented the annual expansion rate of the ventricles by 0.59% (P = 0.007) and the annual decline rate in global cognitive performance by 0.67% (P = 0.050) in the subsequent 2 y after controlling for the effects of age, sex, education, and body mass index. In contrast, global sleep quality at baseline did not modulate either brain or cognitive aging. High-sensitivity C-reactive protein, a marker of systemic inflammation, showed no correlation with baseline sleep duration, brain structure, or cognitive performance. Conclusions: In healthy older adults, short sleep duration is associated with greater age-related brain atrophy and cognitive decline. These associations are not associated with elevated inflammatory responses among short sleepers. Citation: Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. SLEEP 2014;37(7):1171-1178. PMID:25061245

The emotion paradox in the aging brain.

PubMed

Mather, Mara

2012-03-01

This paper reviews age differences in emotion processing and how they may relate to age-related changes in the brain. Compared with younger adults, older adults react less to negative situations, ignore irrelevant negative stimuli better, and remember relatively more positive than negative information. Older adults' ability to insulate their thoughts and emotional reactions from negative situations is likely due to a number of factors, such as being less influenced by interoceptive cues, selecting different emotion regulation strategies, having less age-related decline in prefrontal regions associated with emotional control than in other prefrontal regions, and engaging in emotion regulation strategies as a default mode in their everyday lives. Healthy older adults' avoidance of processing negative stimuli may contribute to their well-maintained emotional well-being. However, when cardiovascular disease leads to additional prefrontal white matter damage, older adults have fewer cognitive control mechanisms available to regulate their emotions, making them more vulnerable to depression. In general, although age-related changes in the brain help shape emotional experience, shifts in preferred strategies and goal priorities are also important influences. © 2012 New York Academy of Sciences.

Experiences of giving and receiving care in traumatic brain injury: An integrative review.

PubMed

Kivunja, Stephen; River, Jo; Gullick, Janice

2018-04-01

To synthesise the literature on the experiences of giving or receiving care for traumatic brain injury for people with traumatic brain injury, their family members and nurses in hospital and rehabilitation settings. Traumatic brain injury represents a major source of physical, social and economic burden. In the hospital setting, people with traumatic brain injury feel excluded from decision-making processes and perceive impatient care. Families describe inadequate information and support for psychological distress. Nurses find the care of people with traumatic brain injury challenging particularly when experiencing heavy workloads. To date, a contemporary synthesis of the literature on people with traumatic brain injury, family and nurse experiences of traumatic brain injury care has not been conducted. Integrative literature review. A systematic search strategy guided by the PRISMA statement was conducted in CINAHL, PubMed, Proquest, EMBASE and Google Scholar. Whittemore and Knafl's (Journal of Advanced Nursing, 52, 2005, 546) integrative review framework guided data reduction, data display, data comparison and conclusion verification. Across the three participant categories (people with traumatic brain injury/family members/nurses) and sixteen subcategories, six cross-cutting themes emerged: seeking personhood, navigating challenging behaviour, valuing skills and competence, struggling with changed family responsibilities, maintaining productive partnerships and reflecting on workplace culture. Traumatic brain injury creates changes in physical, cognitive and emotional function that challenge known ways of being in the world for people. This alters relationship dynamics within families and requires a specific skill set among nurses. Recommendations include the following: (i) formal inclusion of people with traumatic brain injury and families in care planning, (ii) routine risk screening for falls and challenging behaviour to ensure that controls are based on

Brain aging: Evaluation of pH using phosphorus magnetic resonance spectroscopy.

PubMed

Cichocka, Monika; Kozub, Justyna; Urbanik, Andrzej

2018-02-02

Very important aspects of aging include age-related changes occurring in the brain. The aim of the present study was to identify the standard pH value in the entire brain volume using phosphorus magnetic resonance spectroscopy in healthy individuals of both sexes in different age groups, and then to determine whether there are differences in these values. A total of 65 individuals aged 20-32 years (mean age 24.5 ± 2.1 years, 31 women and 34 men) and 31 individuals aged 60-81 years (mean age 64.9 ± 5.5 years, 17 women and 14 men) were studied. The phosphorus magnetic resonance spectroscopy examination was carried out using a 1.5-T magnetic resonance system. The signal was acquired from the volume of interest that covered the whole brain. A vast majority of the examined individuals had slightly alkaline brain pH regardless of age. In the ≥20 years group, pH was 7.09 ± 0.11, and in the ≥60 years group, the average pH was 7.03 ± 0.05. This comparison of the pH identified in all the tested individuals shows a negative correlation of pH with age. The present findings might provide a valuable basis for further research into "healthy aging" as well as pathology in older adults. Geriatr Gerontol Int 2018; ••: ••-••. © 2018 Japan Geriatrics Society.

Age-related changes of task-specific brain activity in normal aging.

PubMed

Ho, Ming-Chung; Chou, Chia-Yi; Huang, Chin-Fei; Lin, Yu-Te; Shih, Ching-Sen; Han, Shiang-Yi; Shen, Ming-Hsun; Chen, Tsung-Ching; Liang, Chi-lin; Lu, Ming-Chi; Liu, Chia-Ju

2012-01-17

An important question in healthcare for older patients is whether age-related changes in cortical reorganization can be measured with advancing age. This study investigated the factors behind such age-related changes, using time-frequency analysis of event-related potentials (ERPs). We hypothesized that brain rhythms was affected by age-related changes, which could be reflected in the ERP indices. An oddball task was conducted in two experimental groups, namely young participants (N=15; mean age 23.7±2.8 years) and older participants (N=15; mean age 70.1±7.9 years). Two types of stimuli were used: the target (1 kHz frequency) and standard (2 kHz frequency). We scrutinized three ERP indices: event-related spectral power (ERPSP), inter-trial phase-locking (ITPL), and event-related cross-phase coherence (ERPCOH). Both groups performed equally well for correct response rate. However, the results revealed a statistically significant age difference for inter-trial comparison. Compared with the young, the older participants showed the following age-related changes: (a) power activity decreased; however, an increase was found only in the late (P3, 280-450 ms) theta (4-7 Hz) component over the bilateral frontal and temporo-frontal areas; (b) low phase-locking in the early (N1, 80-140 ms) theta band over the parietal/frontal (right) regions appeared; (c) the functional connections decreased in the alpha (7-13 Hz) and beta (13-30 Hz) bands, but no difference emerged in the theta band between the two groups. These results indicate that age-related changes in task-specific brain activity for a normal aging population can be depicted using the three ERP indices. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

A Long Journey into Aging, Brain Aging, and Alzheimer’s Disease Following the Oxidative Stress Tracks

PubMed Central

Mecocci, Patrizia; Boccardi, Virginia; Cecchetti, Roberta; Bastiani, Patrizia; Scamosci, Michela; Ruggiero, Carmelinda; Baroni, Marta

2018-01-01

The Editors of the Journal of Alzheimer’s Disease invited Professor Patrizia Mecocci to contribute a review article focused on the importance and implications of her research on aging, brain aging, and senile dementias over the last years. This invitation was based on an assessment that she was one of the journal’s top authors and a strong supporter of the concept that oxidative stress is a major contributor to several alterations observed in age-related conditions (sarcopenia, osteoporosis) and, more significantly, in brain aging suggesting a pivotal role in the pathogenesis and progression of one of the most dramatic age-related diseases, Alzheimer’s disease (AD). Her first pioneering research was on the discovery of high level of 8-hydroxy-2’-deoxyguanosine (OH8dG), a marker of oxidation in nucleic acids, in mitochondrial DNA isolated from cerebral cortex. This molecule increases progressively with aging and more in AD brain, supporting the hypothesis that oxidative stress, a condition of unbalance between the production of reactive oxygen species and antioxidants, gives a strong contribution to the high incidence of AD in old age subjects. OH8dG also increases in peripheral lymphocyte from AD subjects, suggesting that AD is not only a cerebral but also a systemic disease. The role of antioxidants, particularly vitamin E and zinc, were also studied in longevity and in cognitive decline and dementia. This review shows the main findings from Mecocci’s laboratory related to oxidative stress in aging, brain aging, and AD and discusses the importance and implications of some of the major achievements in this field of research. PMID:29562533

Brain aging phenomena in migrating sockeye salmon Oncorhynchus nerka nerka.

PubMed

Götz, M E; Malz, C R; Dirr, A; Blum, D; Gsell, W; Schmidt, S; Burger, R; Pohli, S; Riederer, P

2005-09-01

Aging, a process occurring in all vertebrates, is closely related to a loss in physical and functional abilities. There is widespread interest in clarifying the relevance of environmental, metabolic, and genetic factors for vertebrate aging. In the Pacific salmon a dramatic example of aging is known. Looking for changes in the salmon brain, perhaps even in the role of initiating the aging processes, we investigated several biochemical parameters that should reflect brain functional activity and stress response such as the neurotransmitters dopamine, and serotonin, and two of their respective metabolites 3,4-dihydroxyphenylacetic acid, and 5-hydroxyindole acetic acid, as well as glutathione, glutathione disulfide, and the extent of terminal deoxynucleotidyltransferase-mediated dUTP nick end-labelling. The aging of migrating sockeye salmon (Oncorhynchus nerka nerka) is accompanied by gradual increase in dopamine and serotonin turnover and a gradual decrease of brain total protein and glutathione levels. There appears to be an increased need for detoxification of reactive biological intermediates since activities of superoxide dismutase and catalase increase with age. However, our data do not support a major increase in apoptotic cell death during late aging but rather implicate an age related downward regulation of protein and glutathione synthesis and proteolysis increasing the need for autophagocytosis or heterophagocytosis in the course of cell death.

Maintaining brain health by monitoring inflammatory processes: a mechanism to promote successful aging.

PubMed

Rosano, Caterina; Marsland, Anna L; Gianaros, Peter J

2012-02-01

Maintaining brain health promotes successful aging. The main determinants of brain health are the preservation of cognitive function and remaining free from structural and metabolic abnormalities, including loss of neuronal synapses, atrophy, small vessel disease and focal amyloid deposits visible by neuroimaging. Promising studies indicate that these determinants are to some extent modifiable, even among adults seventy years and older. Converging animal and human evidence further suggests that inflammation is a shared mechanism, contributing to both cognitive decline and abnormalities in brain structure and metabolism. Thus, inflammation may provide a target for intervention. Specifically, circulating inflammatory markers have been associated with declines in cognitive function and worsening of brain structural and metabolic characteristics. Additionally, it has been proposed that older brains are characterized by a sensitization to neuroinflammatory responses, even in the absence of overt disease. This increased propensity to central inflammation may contribute to poor brain health and premature brain aging. Still unknown is whether and how peripheral inflammatory factors directly contribute to decline of brain health. Human research is limited by the challenges of directly measuring neuroinflammation in vivo. This review assesses the role that inflammation may play in the brain changes that often accompany aging, focusing on relationships between peripheral inflammatory markers and brain health among well-functioning, community-dwelling adults seventy years and older. We propose that monitoring and maintaining lower levels of systemic and central inflammation among older adults could help preserve brain health and support successful aging. Hence, we also identify plausible ways and novel experimental study designs of maintaining brain health late in age through interventions that target the immune system.

Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujibayashi, Y.; Yamamoto, S.; Waki, A.

DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies.more » In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.« less

Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth

PubMed Central

Aubert-Broche, Bérengère; Fonov, Vladimir; Narayanan, Sridar; Arnold, Douglas L.; Araujo, David; Fetco, Dumitru; Till, Christine; Sled, John G.; Collins, D. Louis

2014-01-01

Objective: To determine the impact of pediatric-onset multiple sclerosis (MS) on age-expected brain growth. Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS. PMID:25378667

Does age matter? Age and rehabilitation of visual field disorders after brain injury.

PubMed

Schuett, Susanne; Zihl, Josef

2013-04-01

Homonymous visual field disorders (HVFD) are frequent and disabling consequences of acquired brain injury, particularly in older age. Their rehabilitation is therefore of great importance. Compensatory oculomotor therapy has been found to be effective in improving the associated functional impairments in reading and visual exploration. But older age is commonly considered to adversely affect practice-dependent functional plasticity and, thus, functional and rehabilitation outcome after acquired brain injury. The effect of age in the compensatory treatment of HVFD, however, has never been investigated hitherto. It remains unknown whether age determines not only patients' functional impairments but also the rehabilitation outcome and the required amount of treatment. We therefore present the first study to determine the effect of age in 38 patients with HVFD receiving compensatory oculomotor treatment for their reading and visual exploration impairments. We investigated whether older patients with HVFD (1) show more pronounced impairments and less spontaneous adaptation, (2) show lesser compensatory treatment-related improvement in reading and visual exploration, and (3) require a higher amount of treatment than younger patients. Our main finding is that older patients achieve the same treatment-induced improvements in reading and visual exploration with the same amount of treatment as younger patients; severity of functional impairment also did not differ between older and younger patients, at least in reading. Age does not seem to be a critical factor determining the functional and rehabilitation outcome in the compensatory treatment of HVFD. Older age per se is not necessarily associated with a decline in practice-dependent functional plasticity and adaptation. To the contrary, the effectiveness of compensatory treatment to reduce the functional impairments to a similar extent in younger and older patients with HVFD adds to the growing evidence for a life

The glia doctrine: addressing the role of glial cells in healthy brain ageing.

PubMed

Nagelhus, Erlend A; Amiry-Moghaddam, Mahmood; Bergersen, Linda H; Bjaalie, Jan G; Eriksson, Jens; Gundersen, Vidar; Leergaard, Trygve B; Morth, J Preben; Storm-Mathisen, Jon; Torp, Reidun; Walhovd, Kristine B; Tønjum, Tone

2013-10-01

Glial cells in their plurality pervade the human brain and impact on brain structure and function. A principal component of the emerging glial doctrine is the hypothesis that astrocytes, the most abundant type of glial cells, trigger major molecular processes leading to brain ageing. Astrocyte biology has been examined using molecular, biochemical and structural methods, as well as 3D brain imaging in live animals and humans. Exosomes are extracelluar membrane vesicles that facilitate communication between glia, and have significant potential for biomarker discovery and drug delivery. Polymorphisms in DNA repair genes may indirectly influence the structure and function of membrane proteins expressed in glial cells and predispose specific cell subgroups to degeneration. Physical exercise may reduce or retard age-related brain deterioration by a mechanism involving neuro-glial processes. It is most likely that additional information about the distribution, structure and function of glial cells will yield novel insight into human brain ageing. Systematic studies of glia and their functions are expected to eventually lead to earlier detection of ageing-related brain dysfunction and to interventions that could delay, reduce or prevent brain dysfunction. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice

PubMed Central

Gauba, Esha; Guo, Lan; Du, Heng

2017-01-01

Brain aging is the known strongest risk factor for Alzheimer’s disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD. The interaction of CypD with OSCP modulates F1FO ATP synthase function and mediates mitochondrial permeability transition pore (mPTP) opening. Here, we have found that increased CypD expression, enhanced CypD/OSCP interaction, and selective loss of OSCP are prominent brain mitochondrial changes in aging mice. Along with these changes, brain mitochondria from the aging mice demonstrated decreased F1FO ATP synthase activity and defective F1FO complex coupling. In contrast, CypD deficient mice exhibited substantially mitigated brain mitochondrial F1FO ATP synthase dysfunction with relatively preserved mitochondrial function during aging. Interestingly, the aging-related OSCP loss was also dramatically attenuated by CypD depletion. Therefore, the simplest interpretation of this study is that CypD promotes F1FO ATP synthase dysfunction and the resultant mitochondrial deficits in aging brains. In addition, in view of CypD and F1FO ATP synthase alterations seen in AD brains, the results further suggest that CypD-mediated F1FO ATP synthase deregulation is a shared mechanism linking mitochondrial deficits in brain aging and AD. PMID:27834780

Cyclophilin D Promotes Brain Mitochondrial F1FO ATP Synthase Dysfunction in Aging Mice.

PubMed

Gauba, Esha; Guo, Lan; Du, Heng

2017-01-01

Brain aging is the known strongest risk factor for Alzheimer's disease (AD). In recent years, mitochondrial deficits have been proposed to be a common mechanism linking brain aging to AD. Therefore, to elucidate the causative mechanisms of mitochondrial dysfunction in aging brains is of paramount importance for our understanding of the pathogenesis of AD, in particular its sporadic form. Cyclophilin D (CypD) is a specific mitochondrial protein. Recent studies have shown that F1FO ATP synthase oligomycin sensitivity conferring protein (OSCP) is a binding partner of CypD. The interaction of CypD with OSCP modulates F1FO ATP synthase function and mediates mitochondrial permeability transition pore (mPTP) opening. Here, we have found that increased CypD expression, enhanced CypD/OSCP interaction, and selective loss of OSCP are prominent brain mitochondrial changes in aging mice. Along with these changes, brain mitochondria from the aging mice demonstrated decreased F1FO ATP synthase activity and defective F1FO complex coupling. In contrast, CypD deficient mice exhibited substantially mitigated brain mitochondrial F1FO ATP synthase dysfunction with relatively preserved mitochondrial function during aging. Interestingly, the aging-related OSCP loss was also dramatically attenuated by CypD depletion. Therefore, the simplest interpretation of this study is that CypD promotes F1FO ATP synthase dysfunction and the resultant mitochondrial deficits in aging brains. In addition, in view of CypD and F1FO ATP synthase alterations seen in AD brains, the results further suggest that CypD-mediated F1FO ATP synthase deregulation is a shared mechanism linking mitochondrial deficits in brain aging and AD.

Patterns of post-acute health care utilization after a severe traumatic brain injury: Results from the PariS-TBI cohort.

PubMed

Jourdan, Claire; Bayen, Eleonore; Darnoux, Emmanuelle; Ghout, Idir; Azerad, Sylvie; Ruet, Alexis; Vallat-Azouvi, Claire; Pradat-Diehl, Pascale; Aegerter, Philippe; Weiss, Jean-Jacques; Azouvi, Philippe

2015-01-01

To assess brain injury services utilization and their determinants using Andersen's model. Prospective follow-up of the PariS-TBI inception cohort. Out of 504 adults with severe traumatic brain injury (TBI), 245 survived and 147 received a 4-year outcome assessment (mean age 33 years, 80% men). Provision rates of medical, rehabilitation, social and re-entry services and their relations to patients' characteristics were assessed. Following acute care discharge, 78% of patients received physiotherapy, 61% speech/cognitive therapy, 50% occupational therapy, 41% psychological assistance, 63% specialized medical follow-up, 21% community re-entry assistance. Health-related need factors, in terms of TBI severity, were the main predictors of services. Provision of each therapy was significantly associated with corresponding speech, motor and psychological impairments. However, care provision did not depend on cognitive impairments and cognitive therapy was related to pre-disposing and geographical factors. Community re-entry assistance was provided to younger and more independent patients. These quantitative findings illustrate strengths and weaknesses of late brain injury care provision in urban France and highlight the need to improve treatment of cognitive impairments.

Emerging ICT implementation issues in aged care.

PubMed

Kapadia, Vasvi; Ariani, Arni; Li, Junhua; Ray, Pradeep K

2015-11-01

Demand for aged care services continues to soar as a result of an aging population. This increasing demand requires more residential aged care facilities and healthcare workforce. One recommended solution is to keep older people in their homes longer and support their independent life through the use of information and communication technologies (ICT). However, the aged care sector is still in the early stages of adopting ICT. The aim of this study was to identify the key issues that affect the adoption of ICT in the aged care sector. A systematic literature review was undertaken and involved four steps. The first two steps aimed to identify and select relevant articles. Data was then extracted from the selected articles and identified issues were analyzed and grouped into three major categories. ICT adoption issues were categorized into different perspectives, representing older people, health professionals and management. Our findings showed that all three groups were mostly concerned with issues around behavior, cost and lack of technical skills. Findings reported in this study will help decision makers at aged care settings to systematically understand issues related to ICT adoption and thus proactively introduce interventions to improve use of ICT in this sector. On the basis of our findings, we suggest future research focus on the examination of aged care workflow and assessment of return on ICT investment. Copyright © 2015. Published by Elsevier Ireland Ltd.

Primary care clinician expectations regarding aging.

PubMed

Davis, Melinda M; Bond, Lynne A; Howard, Alan; Sarkisian, Catherine A

2011-12-01

Expectations regarding aging (ERA) in community-dwelling older adults are associated with personal health behaviors and health resource usage. Clinicians' age expectations likely influence patients' expectations and care delivery patterns; yet, limited research has explored clinicians' age expectations. The Expectations Regarding Aging Survey (ERA-12) was used to assess (a) age expectations in a sample of primary care clinicians practicing in the United States and (b) clinician characteristics associated with ERA-12 scores.  This study was a cross-sectional survey of primary care clinicians affiliated with 5 practice-based research networks, October 2008 to June 2009. A total of 374 of the 1,510 distributed surveys were returned (24.8% response rate); 357 analyzed. Mean respondent age was 48.6 years (SD = 11.6; range 23-87 years); 88.0% physicians, 96.0% family medicine, 94.9% White, and 61.9% male. Female clinicians reported higher ERA-12 scores; clinicians' age expectations decreased with greater years in practice. Among the clinicians, higher ERA-12 scores were associated with higher clinician ratings of the importance of and personal skill in administering preventive counseling and the importance of delivering preventive services. Agreement with individual ERA-12 items varied widely. Unrealistically high or low ERA could negatively influence the quality of care provided to patients and patients' own age expectations. Research should examine the etiology of clinicians' age expectations and their association with older adult diagnoses and treatment. Medical education must incorporate strategies to promote clinician attitudes that facilitate successful patient aging.

Brain volumetric changes and cognitive ageing during the eighth decade of life

PubMed Central

Dickie, David Alexander; Cox, Simon R.; Valdes Hernandez, Maria del C.; Corley, Janie; Royle, Natalie A.; Pattie, Alison; Aribisala, Benjamin S.; Redmond, Paul; Muñoz Maniega, Susana; Taylor, Adele M.; Sibbett, Ruth; Gow, Alan J.; Starr, John M.; Bastin, Mark E.; Wardlaw, Joanna M.; Deary, Ian J.

2015-01-01

Abstract Later‐life changes in brain tissue volumes—decreases in the volume of healthy grey and white matter and increases in the volume of white matter hyperintensities (WMH)—are strong candidates to explain some of the variation in ageing‐related cognitive decline. We assessed fluid intelligence, memory, processing speed, and brain volumes (from structural MRI) at mean age 73 years, and at mean age 76 in a narrow‐age sample of older individuals (n = 657 with brain volumetric data at the initial wave, n = 465 at follow‐up). We used latent variable modeling to extract error‐free cognitive levels and slopes. Initial levels of cognitive ability were predictive of subsequent brain tissue volume changes. Initial brain volumes were not predictive of subsequent cognitive changes. Brain volume changes, especially increases in WMH, were associated with declines in each of the cognitive abilities. All statistically significant results were modest in size (absolute r‐values ranged from 0.114 to 0.334). These results build a comprehensive picture of macrostructural brain volume changes and declines in important cognitive faculties during the eighth decade of life. Hum Brain Mapp 36:4910–4925, 2015. © 2015 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc PMID:26769551

Associations between regional brain volumes at term-equivalent age and development at 2 years of age in preterm children.

PubMed

Lind, Annika; Parkkola, Riitta; Lehtonen, Liisa; Munck, Petriina; Maunu, Jonna; Lapinleimu, Helena; Haataja, Leena

2011-08-01

Altered brain volumes and associations between volumes and developmental outcomes have been reported in prematurely born children. To assess which regional brain volumes are different in very low birth weight (VLBW) children without neurodevelopmental impairments ([NDI] cerebral palsy, hearing loss, blindness and significantly delayed cognitive performance) compared with VLBW children with NDI, and to evaluate the association between regional brain volumes at term-equivalent age and cognitive development and neurological performance at a corrected age of 2 years. The study group consisted of a regional cohort of 164 VLBW children, divided into one group of children without NDI (n = 148) and one group of children with NDI (n = 16). Brain (MRI) was performed at term-equivalent age, from which brain volumes were manually analysed. Cognitive development was assessed with the Bayley Scales of Infant Development II (BSID-II), and neurological performance with the Hammersmith Infant Neurological Examination at the corrected age of 2 years. The volumes of total brain tissue, cerebrum, frontal lobes, basal ganglia and thalami, and cerebellum were significantly smaller, and the volume of the ventricles significantly larger, in the children with NDI than in those without NDI. Even in children without NDI, a smaller cerebellar volume was significantly correlated with poor neurological performance at 2 years of corrected age. Volumetric analysis at brain MRI can provide an additional parameter for early prediction of outcome in VLBW children.

Gene expression changes with age in skin, adipose tissue, blood and brain.

PubMed

Glass, Daniel; Viñuela, Ana; Davies, Matthew N; Ramasamy, Adaikalavan; Parts, Leopold; Knowles, David; Brown, Andrew A; Hedman, Asa K; Small, Kerrin S; Buil, Alfonso; Grundberg, Elin; Nica, Alexandra C; Di Meglio, Paola; Nestle, Frank O; Ryten, Mina; Durbin, Richard; McCarthy, Mark I; Deloukas, Panagiotis; Dermitzakis, Emmanouil T; Weale, Michael E; Bataille, Veronique; Spector, Tim D

2013-07-26

Previous studies have demonstrated that gene expression levels change with age. These changes are hypothesized to influence the aging rate of an individual. We analyzed gene expression changes with age in abdominal skin, subcutaneous adipose tissue and lymphoblastoid cell lines in 856 female twins in the age range of 39-85 years. Additionally, we investigated genotypic variants involved in genotype-by-age interactions to understand how the genomic regulation of gene expression alters with age. Using a linear mixed model, differential expression with age was identified in 1,672 genes in skin and 188 genes in adipose tissue. Only two genes expressed in lymphoblastoid cell lines showed significant changes with age. Genes significantly regulated by age were compared with expression profiles in 10 brain regions from 100 postmortem brains aged 16 to 83 years. We identified only one age-related gene common to the three tissues. There were 12 genes that showed differential expression with age in both skin and brain tissue and three common to adipose and brain tissues. Skin showed the most age-related gene expression changes of all the tissues investigated, with many of the genes being previously implicated in fatty acid metabolism, mitochondrial activity, cancer and splicing. A significant proportion of age-related changes in gene expression appear to be tissue-specific with only a few genes sharing an age effect in expression across tissues. More research is needed to improve our understanding of the genetic influences on aging and the relationship with age-related diseases.

Cardiac index is associated with brain aging: the Framingham Heart Study.

PubMed

Jefferson, Angela L; Himali, Jayandra J; Beiser, Alexa S; Au, Rhoda; Massaro, Joseph M; Seshadri, Sudha; Gona, Philimon; Salton, Carol J; DeCarli, Charles; O'Donnell, Christopher J; Benjamin, Emelia J; Wolf, Philip A; Manning, Warren J

2010-08-17

Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease, theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with preclinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer disease in the community. Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free of clinical stroke, transient ischemic attack, or dementia (age, 61+/-9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent cardiovascular disease were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post hoc comparisons revealed that participants in the bottom cardiac index tertile (values <2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values >2.92). Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging.

Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

PubMed

Banerjee, Soumyabrata; Poddar, Mrinal K

2015-03-01

Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

Risk and protective factors for structural brain ageing in the eighth decade of life.

PubMed

Ritchie, Stuart J; Tucker-Drob, Elliot M; Cox, Simon R; Dickie, David Alexander; Del C Valdés Hernández, Maria; Corley, Janie; Royle, Natalie A; Redmond, Paul; Muñoz Maniega, Susana; Pattie, Alison; Aribisala, Benjamin S; Taylor, Adele M; Clarke, Toni-Kim; Gow, Alan J; Starr, John M; Bastin, Mark E; Wardlaw, Joanna M; Deary, Ian J

2017-11-01

Individuals differ markedly in brain structure, and in how this structure degenerates during ageing. In a large sample of human participants (baseline n = 731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the magnitude of mean change and variability in changes in MRI measures of brain macrostructure (grey matter, white matter, and white matter hyperintensity volumes) and microstructure (fractional anisotropy and mean diffusivity from diffusion tensor MRI). All indices showed significant average change with age, with considerable heterogeneity in those changes. We then tested eleven socioeconomic, physical, health, cognitive, allostatic (inflammatory and metabolic), and genetic variables for their value in predicting these differences in changes. Many of these variables were significantly correlated with baseline brain structure, but few could account for significant portions of the heterogeneity in subsequent brain change. Physical fitness was an exception, being correlated both with brain level and changes. The results suggest that only a subset of correlates of brain structure are also predictive of differences in brain ageing.

Primary Care Clinician Expectations Regarding Aging

PubMed Central

Davis, Melinda M.; Bond, Lynne A.; Howard, Alan; Sarkisian, Catherine A.

2011-01-01

Purpose: Expectations regarding aging (ERA) in community-dwelling older adults are associated with personal health behaviors and health resource usage. Clinicians’ age expectations likely influence patients’ expectations and care delivery patterns; yet, limited research has explored clinicians’ age expectations. The Expectations Regarding Aging Survey (ERA-12) was used to assess (a) age expectations in a sample of primary care clinicians practicing in the United States and (b) clinician characteristics associated with ERA-12 scores. Design and Methods: This study was a cross-sectional survey of primary care clinicians affiliated with 5 practice-based research networks, October 2008 to June 2009. A total of 374 of the 1,510 distributed surveys were returned (24.8% response rate); 357 analyzed. Mean respondent age was 48.6 years (SD = 11.6; range 23–87 years); 88.0% physicians, 96.0% family medicine, 94.9% White, and 61.9% male. Results: Female clinicians reported higher ERA-12 scores; clinicians’ age expectations decreased with greater years in practice. Among the clinicians, higher ERA-12 scores were associated with higher clinician ratings of the importance of and personal skill in administering preventive counseling and the importance of delivering preventive services. Agreement with individual ERA-12 items varied widely. Implications: Unrealistically high or low ERA could negatively influence the quality of care provided to patients and patients’ own age expectations. Research should examine the etiology of clinicians’ age expectations and their association with older adult diagnoses and treatment. Medical education must incorporate strategies to promote clinician attitudes that facilitate successful patient aging. PMID:21430129

Age-dependent changes at the blood-brain barrier. A Comparative structural and functional study in young adult and middle aged rats.

PubMed

Bors, Luca; Tóth, Kinga; Tóth, Estilla Zsófia; Bajza, Ágnes; Csorba, Attila; Szigeti, Krisztián; Máthé, Domokos; Perlaki, Gábor; Orsi, Gergely; Tóth, Gábor K; Erdő, Franciska

2018-05-01

Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Proteomic analysis of specific brain proteins in aged SAMP8 mice treated with alpha-lipoic acid: implications for aging and age-related neurodegenerative disorders.

PubMed

Poon, H Fai; Farr, Susan A; Thongboonkerd, Visith; Lynn, Bert C; Banks, William A; Morley, John E; Klein, Jon B; Butterfield, D Allan

2005-01-01

Free radical-mediated damage to neuronal membrane components has been implicated in the etiology of Alzheimer's disease (AD) and aging. The senescence accelerated prone mouse strain 8 (SAMP8) exhibits age-related deterioration in memory and learning along with increased oxidative markers. Therefore, SAMP8 is a suitable model to study brain aging and, since aging is the major risk factor for AD and SAMP8 exhibits many of the biochemical findings of AD, perhaps as a model for and the early phase of AD. Our previous studies reported higher oxidative stress markers in brains of 12-month-old SAMP8 mice when compared to that of 4-month-old SAMP8 mice. Further, we have previously shown that injecting the mice with alpha-lipoic acid (LA) reversed brain lipid peroxidation, protein oxidation, as well as the learning and memory impairments in SAMP8 mice. Recently, we reported the use of proteomics to identify proteins that are expressed differently and/or modified oxidatively in aged SAMP8 brains. In order to understand how LA reverses the learning and memory deficits of aged SAMP8 mice, in the current study, we used proteomics to compare the expression levels and specific carbonyl levels of proteins in brains from 12-month-old SAMP8 mice treated or not treated with LA. We found that the expressions of the three brain proteins (neurofilament triplet L protein, alpha-enolase, and ubiquitous mitochondrial creatine kinase) were increased significantly and that the specific carbonyl levels of the three brain proteins (lactate dehydrogenase B, dihydropyrimidinase-like protein 2, and alpha-enolase) were significantly decreased in the aged SAMP8 mice treated with LA. These findings suggest that the improved learning and memory observed in LA-injected SAMP8 mice may be related to the restoration of the normal condition of specific proteins in aged SAMP8 mouse brain. Moreover, our current study implicates neurofilament triplet L protein, alpha-enolase, ubiquitous mitochondrial

Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest.

PubMed

Elmer, Jonathan; Flickinger, Katharyn L; Anderson, Maighdlin W; Koller, Allison C; Sundermann, Matthew L; Dezfulian, Cameron; Okonkwo, David O; Shutter, Lori A; Salcido, David D; Callaway, Clifton W; Menegazzi, James J

2018-04-18

Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO 2 ). We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO 2 ). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg. Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO 2 was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO 2 remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01). In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes. Copyright © 2018 Elsevier B.V. All rights reserved.

Aging and functional brain networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tomasi D.; Tomasi, D.; Volkow, N.D.

2011-07-11

Aging is associated with changes in human brain anatomy and function and cognitive decline. Recent studies suggest the aging decline of major functional connectivity hubs in the 'default-mode' network (DMN). Aging effects on other networks, however, are largely unknown. We hypothesized that aging would be associated with a decline of short- and long-range functional connectivity density (FCD) hubs in the DMN. To test this hypothesis, we evaluated resting-state data sets corresponding to 913 healthy subjects from a public magnetic resonance imaging database using functional connectivity density mapping (FCDM), a voxelwise and data-driven approach, together with parallel computing. Aging was associatedmore » with pronounced long-range FCD decreases in DMN and dorsal attention network (DAN) and with increases in somatosensory and subcortical networks. Aging effects in these networks were stronger for long-range than for short-range FCD and were also detected at the level of the main functional hubs. Females had higher short- and long-range FCD in DMN and lower FCD in the somatosensory network than males, but the gender by age interaction effects were not significant for any of the networks or hubs. These findings suggest that long-range connections may be more vulnerable to aging effects than short-range connections and that, in addition to the DMN, the DAN is also sensitive to aging effects, which could underlie the deterioration of attention processes that occurs with aging.« less

Aging, neurodegenerative disease, and traumatic brain injury: the role of neuroimaging.

PubMed

Esopenko, Carrie; Levine, Brian

2015-02-15

Traumatic brain injury (TBI) is a highly prevalent condition with significant effects on cognition and behavior. While the acute and sub-acute effects of TBI recover over time, relatively little is known about the long-term effects of TBI in relation to neurodegenerative disease. This issue has recently garnered a great deal of attention due to publicity surrounding chronic traumatic encephalopathy (CTE) in professional athletes, although CTE is but one of several neurodegenerative disorders associated with a history of TBI. Here, we review the literative on neurodegenerative disorders linked to remote TBI. We also review the evidence for neuroimaging changes associated with unhealthy brain aging in the context of remote TBI. We conclude that neuroimaging biomarkers have significant potential to increase understanding of the mechanisms of unhealthy brain aging and neurodegeneration following TBI, with potential for identifying those at risk for unhealthy brain aging prior to the clinical manifestation of neurodegenerative disease.

An age-related change in susceptibility of rat brain to encephalomyocarditis virus infection

PubMed Central

IKEGAMI, HISASHI; TAKEDA, MAKIO; DOI, KUNIO

1997-01-01

Rats were inoculated intraperitoneally (i.p.) or intracerebrally (i.c.) with 1 × 104 plaque forming units (PFU)/animal of the D variant of encephalomyocarditis virus (EMC-D) at 2, 4, 7, 14, 28 or 56 days of age for virological and histopathological examination. In the i.p.-inoculation study, neither viral replication nor lesions were detected in the animals inoculated at 28 and 56 days of age. In the animals inoculated when younger than 14 days of age, lesions were restricted to the brain although viral replication was detected in the brain, heart and pancreas. The brain lesions were characterized by acute meningoencephalitis with neuronal necrosis in the cerebral cortex, hippocampus and thalamus, and viral RNA was detected in degenerated and/or intact neurons. In the i.c.-inoculation study, similar age-related changes in susceptibility of rat brain to EMC-D infection were observed, but a minor difference was that viral replication and lesions were still detected in the hippocampus of some animals inoculated at 28 days of age. These results suggest that an age-related decrease in the susceptibility of rat brain to EMC virus infection may reflect an age-related change in the susceptibility of neurons themselves as well as in maturation of the immune system. PMID:9203984

Aging Shapes the Population-Mean and -Dispersion of Gene Expression in Human Brains

PubMed Central

Brinkmeyer-Langford, Candice L.; Guan, Jinting; Ji, Guoli; Cai, James J.

2016-01-01

Human aging is associated with cognitive decline and an increased risk of neurodegenerative disease. Our objective for this study was to evaluate potential relationships between age and variation in gene expression across different regions of the brain. We analyzed the Genotype-Tissue Expression (GTEx) data from 54 to 101 tissue samples across 13 brain regions in post-mortem donors of European descent aged between 20 and 70 years at death. After accounting for the effects of covariates and hidden confounding factors, we identified 1446 protein-coding genes whose expression in one or more brain regions is correlated with chronological age at a false discovery rate of 5%. These genes are involved in various biological processes including apoptosis, mRNA splicing, amino acid biosynthesis, and neurotransmitter transport. The distribution of these genes among brain regions is uneven, suggesting variable regional responses to aging. We also found that the aging response of many genes, e.g., TP37 and C1QA, depends on individuals' genotypic backgrounds. Finally, using dispersion-specific analysis, we identified genes such as IL7R, MS4A4E, and TERF1/TERF2 whose expressions are differentially dispersed by aging, i.e., variances differ between age groups. Our results demonstrate that age-related gene expression is brain region-specific, genotype-dependent, and associated with both mean and dispersion changes. Our findings provide a foundation for more sophisticated gene expression modeling in the studies of age-related neurodegenerative diseases. PMID:27536236

Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

PubMed

Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

2008-12-01

Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

Humor-A Rehabilitative Tool in the Post-Intensive Care of Young Adults With Acquired Brain Injury.

PubMed

O'Reilly, Kate

The aim of the study was to describe how paid carers use humor in providing compassionate post-intensive rehabilitation care to young adults with acquired brain injury (ABI) who are unable to perform or direct their own care. This is a qualitative study underpinned by symbolic interactionism. Paid carers in a residential aged care facility were interviewed. Interview data were analyzed using grounded theory methods of coding, comparative analysis, memoing, and theoretical sampling. With young adult's assent, paid carers appropriately used humor, at times even crude humor, as a rehabilitative tool to activate and elicit responses from young people with ABI who could not perform or direct their own care. The use of humor while caring for this population demonstrated that compassion still exists within nursing; however, it may not always be reverent. Humor may be an effective way to provide compassionate care and can be used as a rehabilitative tool to elicit responses from young people with ABI who have no means of verbal communication.

The impact of aging physiology in critical care.

PubMed

Walker, Mandi; Spivak, Mark; Sebastian, Mary

2014-03-01

Aging physiology greatly impacts care delivery in the geriatric patient population. Consideration should be given to addressing the patient-specific needs regarding the systemic changes seen in the aging patient. Each major body system presents its own unique challenges to the critical care practitioner, and a comprehensive understanding of these changes is necessary to effectively care for this patient population. This article summarizes these changes and provides key points for the practitioner to consider when caring for the aging patient in the critical care arena. Copyright © 2014 Elsevier Inc. All rights reserved.

Surgical care for the aged: a retrospective cross-sectional study of a national surgical mortality audit

PubMed Central

Allen, Jennifer; North, John B; Ware, Robert S

2015-01-01

Objectives It is assumed that increased age signifies increased surgical care. Few surgical studies describe the differences in care provided to older patients compared with younger patients. We aimed to examine the relationships between increasing age, preoperative factors and markers of postoperative care in adults who died in-hospital after surgery in Australia. Design This retrospective cross-sectional study extracted data from a national surgical mortality audit—an independent, peer-reviewed process. Setting From January 2009 to December 2012, 111 public and 61 private Australian hospitals notified the audit of in-hospital deaths after general anaesthetic surgery or if the patient was admitted under a surgeon. Participants Notified deaths totalled 19 723. We excluded deaths if patients were brain dead, younger than 17 years or never had an operation (n=11 376). From this baseline population, we divided 11 201 deaths into three patient age groups: youngest (17–64 years), medium (65–79 years) and oldest (≥80 years). Outcome measures Univariable and multivariable logistic regression analyses determined the relationships between increasing age and the measured preoperative factors and postoperative variables. Results The baseline population's median age was 78 years (IQR 66–85), 43.7% (4892/11 201) were 80 years or older and 83.4% (9319/11 173) had emergency admissions. The oldest group had increased trauma and emergency admissions than the medium and youngest age groups. Seven of the eight measured markers of postoperative care demonstrate strong and significant relationships with increasing age. The oldest group compared with the medium group had decreased rates of: unplanned returns to theatre (11.2% (526/4709) vs 20.2% (726/3586)), unplanned intensive care admissions (16.3% (545/3350) vs 24.0% (601/2504)) and treatment in intensive care units (59.7% (2689/4507) vs 76.7% (2754/3590)). Conclusions The oldest patients received

Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice.

PubMed

Maurya, Shashank Kumar; Mishra, Rajnikant

2017-07-01

The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration. This report describes evaluation of expression, co-localization and interactions of Pax6 with Ionized binding protein1 (Iba1) in brain of aging mice by Immunohistochemistry, Chromatin Immuno-precipitation (ChIP) and Co-immunoprecipitation (Co-IP), respectively. The co-localization of Pax6 with Iba1 was observed in the cerebellum, cerebral cortex, hippocampus, midbrain and olfactory lobe. The Pax6 and Iba1 also interact physically. The age-dependent alteration in their expression and co-localization were also observed in mice. Results indicate Pax6-dependent activities of Iba1 in the remodelling of microglia during immunological surveillance of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

PubMed Central

Broekman, Birit F. P.; Wang, Changqing; Li, Yue; Rifkin-Graboi, Anne; Saw, Seang Mei; Chong, Yap-Seng; Kwek, Kenneth; Gluckman, Peter D.; Fortier, Marielle V.; Meaney, Michael J.; Qiu, Anqi

2014-01-01

Objective Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth. Methods A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy. Results Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001). Conclusions Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb. PMID:25535959

Lived Experiences of Iranian Nurses Caring for Brain Death Organ Donor Patients: Caring as “Halo of Ambiguity and Doubt”

PubMed Central

Keshtkaran, Zahra; Sharif, Farkhondeh; Navab, Elham; Gholamzadeh, Sakineh

2016-01-01

Background: Brain death is a concept in which its criteria have been expressed as documentations in Harvard Committee of Brain Death. The various perceptions of caregiver nurses for brain death patients may have effect on the chance of converting potential donors into actual organ donors. Objective: The present study has been conducted in order to perceive the experiences of nurses in care-giving to the brain death of organ donor patients. Methods: This qualitative study was carried out by means of Heidegger’s hermeneutic phenomenology. Eight nurses who have been working in ICU were interviewed. The semi-structured interviews were recorded by a tape-recorder and the given texts were transcribed and the analyses were done by Van-Mannen methodology and (thematic) analysis. Results: One of the foremost themes extracted from this study included ‘Halo of ambiguity and doubt’ that comprised of two sub-themes of ‘having unreasonable hope’ and ‘Conservative acceptance of brain death’. The unreasonable hope included lack of trust (uncertainty) in diagnosis and verification of brain death, passing through denial wall, and avoidance from explicit and direct disclosure of brain death in patients’ family. In this investigation, the nurses were involved in a type of ambiguity and doubt in care-giving to the potentially brain death of organ donor patients, which were also evident in their interaction with patients’ family and for this reason, they did not definitely announce the brain death and so far they hoped for treatment of the given patient. Such confusion and hesitance both caused annoyance of nurses and strengthening the denial of patients’ family to be exposed to death. Conclusion: The results of this study reveal the fundamental perceived care-giving of brain death in organ donor patients and led to developing some strategies to improve care-giving and achievement in donation of the given organ and necessity for presentation of educational and

Promoting oral health care among people living in residential aged care facilities: Perceptions of care staff.

PubMed

Villarosa, Amy R; Clark, Sally; Villarosa, Ariana C; Patterson Norrie, Tiffany; Macdonald, Susan; Anlezark, Jennifer; Srinivas, Ravi; George, Ajesh

2018-04-23

This study aimed to look at the practices and perspectives of residential aged care facility (RACF) care staff regarding the provision of oral health care in RACFs. Emphasis has been placed on the provision of adequate oral health care in RACFs through the Better Oral Health in Residential Aged Care programme. Endorsed by the Australian government, this programme provided oral health education and training for aged care staff. However, recent evidence suggests that nearly five years after the implementation of this programme, the provision of oral care in RACFs in NSW remains inadequate. This project utilised an exploratory qualitative design which involved a focus group with 12 RACF care staff. Participants were asked to discuss the current oral health practices in their facility, and their perceived barriers to providing oral health care. The key findings demonstrated current oral health practices and challenges among care staff. Most care staff had received oral health training and demonstrated positive attitudes towards providing dental care. However, some participants identified that ongoing and regular training was necessary to inform practice and raise awareness among residents. Organisational constraints and access to dental services also limited provision of dental care while a lack of standardised guidelines created confusion in defining their role as oral healthcare providers in the RACF. This study highlighted the need for research and strategies that focus on capacity building care staff in oral health care and improving access of aged care residents to dental services. © 2018 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Structural whole-brain covariance of the anterior and posterior hippocampus: Associations with age and memory.

PubMed

Nordin, Kristin; Persson, Jonas; Stening, Eva; Herlitz, Agneta; Larsson, Elna-Marie; Söderlund, Hedvig

2018-02-01

The hippocampus (HC) interacts with distributed brain regions to support memory and shows significant volume reductions in aging, but little is known about age effects on hippocampal whole-brain structural covariance. It is also unclear whether the anterior and posterior HC show similar or distinct patterns of whole-brain covariance and to what extent these are related to memory functions organized along the hippocampal longitudinal axis. Using the multivariate approach partial least squares, we assessed structural whole-brain covariance of the HC in addition to regional volume, in young, middle-aged and older adults (n = 221), and assessed associations with episodic and spatial memory. Based on findings of sex differences in both memory and brain aging, we further considered sex as a potential modulating factor of age effects. There were two main covariance patterns: one capturing common anterior and posterior covariance, and one differentiating the two regions by capturing anterior-specific covariance only. These patterns were differentially related to associative memory while unrelated to measures of single-item memory and spatial memory. Although patterns were qualitatively comparable across age groups, participants' expression of both patterns decreased with age, independently of sex. The results suggest that the organization of hippocampal structural whole-brain covariance remains stable across age, but that the integrity of these networks decreases as the brain undergoes age-related alterations. © 2017 Wiley Periodicals, Inc.

Health and aged care enabled by information technology.

PubMed

Soar, Jeffrey; Seo, Youngjoon

2007-10-01

One of the challenges facing health and welfare policymakers as well as researchers in most developed countries is the increasing demand for aging services and aged care. Low birth rates and rapid increases in the percentages of elderly people make aging and aged care one of the top-priority issues among the national agenda of many countries. The responses of governments have included initiatives to extend productive working lives and promote self-funded retirement; to promote healthy, active aging; and to encourage more care to be delivered in home and community settings. Technology will be a major enabler of these strategies. People requiring health services are increasingly being offered more care in their own homes and community settings as an alternative to hospital admission and to delay or avoid moving into institutional care. Research is providing intelligent technology to enable care in the home as well as to monitor safety, security, and quality. Innovation will provide greater independence and better access to care in their own homes for the elderly, sufferers of chronic illness, and persons with disability and reduce the incidence of hospital admissions and the length of stay when admissions do occur. Technologies will support families and professional caregivers and are expected to reduce costs. This paper reports on developments in technology to support care for the aged in home and community settings.

Age, Intelligence, and Event-Related Brain Potentials during Late Childhood: A Longitudinal Study.

ERIC Educational Resources Information Center

Stauder, Johannes E. A.; van der Molen, Maurits W.; Molenaar, Peter C. M.

2003-01-01

Studied the relationship between event-related brain activity, age, and intelligence using a visual oddball task presented to girls at 9, 10, and 11 years of age. Findings for 26 girls suggest a qualitative shift in the relation between event-related brain activity and intelligence between 9 and 10 years of age. (SLD)

Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

PubMed

Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

2006-01-01

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in

Histopathological Differences Between the Anterior and Posterior Brain Arteries as a Function of Aging.

PubMed

Roth, William; Morgello, Susan; Goldman, James; Mohr, Jay P; Elkind, Mitchell S V; Marshall, Randolph S; Gutierrez, Jose

2017-03-01

We tested the hypothesis that posterior brain arteries differ pathologically from anterior brain arteries and that this difference varies with age. Brain large arteries from 194 autopsied individuals (mean age 56±17 years, 63% men, 25% nonwhite, 17% with brain infarcts) were analyzed to obtain the areas of arterial layers and lumen as well as the relative content of elastin, collagen, and amyloid. Visual rating was used to determine the prevalence of atheroma, calcification, vasa vasorum , pattern of intima thickening, and internal elastic lamina gaps. We used multilevel models adjusting for age, sex, ethnicity, vascular risk factors, artery type and location, and multiple comparisons. Of 1362 large artery segments, 5% had vasa vasorum, 5% had calcifications, 15% had concentric intimal thickening, and 11% had atheromas. Posterior brain arteries had thinner walls, less elastin, and more concentric intima thickening than anterior brain arteries. Compared to anterior brain arteries, the basilar artery had higher arterial area encircled by the internal elastic lamina, whereas the vertebral arteries had higher prevalence of elastin loss, concentric intima thickening, and nonatherosclerotic stenosis. In younger individuals, vertebral artery calcifications were more likely than calcification in anterior brain arteries, but this difference attenuated with age. Posterior brain arteries differ pathologically from anterior brain arteries in the degree of wall thickening, elastin loss, and concentric intimal thickening. © 2017 American Heart Association, Inc.

Brain atrophy can introduce age-related differences in BOLD response.

PubMed

Liu, Xueqing; Gerraty, Raphael T; Grinband, Jack; Parker, David; Razlighi, Qolamreza R

2017-04-11

Use of functional magnetic resonance imaging (fMRI) in studies of aging is often hampered by uncertainty about age-related differences in the amplitude and timing of the blood oxygenation level dependent (BOLD) response (i.e., hemodynamic impulse response function (HRF)). Such uncertainty introduces a significant challenge in the interpretation of the fMRI results. Even though this issue has been extensively investigated in the field of neuroimaging, there is currently no consensus about the existence and potential sources of age-related hemodynamic alterations. Using an event-related fMRI experiment with two robust and well-studied stimuli (visual and auditory), we detected a significant age-related difference in the amplitude of response to auditory stimulus. Accounting for brain atrophy by circumventing spatial normalization and processing the data in subjects' native space eliminated these observed differences. In addition, we simulated fMRI data using age differences in brain morphology while controlling HRF shape. Analyzing these simulated fMRI data using standard image processing resulted in differences in HRF amplitude, which were eliminated when the data were analyzed in subjects' native space. Our results indicate that age-related atrophy introduces inaccuracy in co-registration to standard space, which subsequently appears as attenuation in BOLD response amplitude. Our finding could explain some of the existing contradictory reports regarding age-related differences in the fMRI BOLD responses. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Brain Mitochondria, Aging, and Parkinson's Disease.

PubMed

Rango, Mario; Bresolin, Nereo

2018-05-11

This paper reconsiders the role of mitochondria in aging and in Parkinson's Disease (PD). The most important risk factor for PD is aging. Alterations in mitochondrial activity are typical of aging. Mitochondrial aging is characterized by decreased oxidative phosphorylation, proteasome activity decrease, altered autophagy, and mitochondrial dysfunction. Beyond declined oxidative phosphorylation, mitochondrial dysfunction consists of a decline of beta-oxidation as well as of the Krebs cycle. Not inherited mitochondrial DNA (mtDNA) mutations are acquired over time and parallel the decrease in oxidative phosphorylation. Many of these mitochondrial alterations are also found in the PD brain specifically in the substantia nigra (SN). mtDNA deletions and development of respiratory chain deficiency in SN neurons of aged individuals as well as of individuals with PD converge towards a shared pathway, which leads to neuronal dysfunction and death. Finally, several nuclear genes that are mutated in hereditary PD are usually implicated in mitochondrial functioning to a various extent and their mutation may cause mitochondrial impairment. In conclusion, a tight link exists between mitochondria, aging, and PD.

Cerebral microhemorrhages due to traumatic brain injury and their effects on the aging human brain.

PubMed

Irimia, Andrei; Van Horn, John D; Vespa, Paul M

2018-06-01

Although cerebral microbleeds (CMBs) are frequently associated with traumatic brain injury (TBI), their effects on clinical outcome after TBI remain controversial and poorly understood, particularly in older adults. Here we (1) highlight major challenges and opportunities associated with studying the effects of TBI-mediated CMBs; (2) review the evidence on their potential effects on cognitive and neural outcome as a function of age at injury; and (3) suggest priorities for future research on understanding the clinical implications of CMBs. Although TBI-mediated CMBs are likely distinct from those due to cerebral amyloid angiopathy or other neurodegenerative diseases, the effects of these 2 CMB types on brain function may share common features. Furthermore, in older TBI victims, the incidence of TBI-mediated CMBs may approximate that of cerebral amyloid angiopathy-related CMBs, and thus warrants detailed study. Because the alterations effected by CMBs on brain structure and function are both unique and age-dependent, it seems likely that novel, age-tailored therapeutic approaches are necessary for the adequate clinical interpretation and treatment of these ubiquitous and underappreciated TBI sequelae. Copyright © 2018 Elsevier Inc. All rights reserved.

Age-related differences in brain network activation and co-activation during multiple object tracking.

PubMed

Dørum, Erlend S; Alnæs, Dag; Kaufmann, Tobias; Richard, Geneviève; Lund, Martina J; Tønnesen, Siren; Sneve, Markus H; Mathiesen, Nina C; Rustan, Øyvind G; Gjertsen, Øivind; Vatn, Sigurd; Fure, Brynjar; Andreassen, Ole A; Nordvik, Jan Egil; Westlye, Lars T

2016-11-01

Multiple object tracking (MOT) is a powerful paradigm for measuring sustained attention. Although previous fMRI studies have delineated the brain activation patterns associated with tracking and documented reduced tracking performance in aging, age-related effects on brain activation during MOT have not been characterized. In particular, it is unclear if the task-related activation of different brain networks is correlated, and also if this coordination between activations within brain networks shows differential effects of age. We obtained fMRI data during MOT at two load conditions from a group of younger ( n  = 25, mean age = 24.4 ± 5.1 years) and older ( n  = 21, mean age = 64.7 ± 7.4 years) healthy adults. Using a combination of voxel-wise and independent component analysis, we investigated age-related differences in the brain network activation. In order to explore to which degree activation of the various brain networks reflect unique and common mechanisms, we assessed the correlations between the brain networks' activations. Behavioral performance revealed an age-related reduction in MOT accuracy. Voxel and brain network level analyses converged on decreased load-dependent activations of the dorsal attention network (DAN) and decreased load-dependent deactivations of the default mode networks (DMN) in the old group. Lastly, we found stronger correlations in the task-related activations within DAN and within DMN components for younger adults, and stronger correlations between DAN and DMN components for older adults. Using MOT as means for measuring attentional performance, we have demonstrated an age-related attentional decline. Network-level analysis revealed age-related alterations in network recruitment consisting of diminished activations of DAN and diminished deactivations of DMN in older relative to younger adults. We found stronger correlations within DMN and within DAN components for younger adults and stronger correlations between

Critical Care Management Focused on Optimizing Brain Function After Cardiac Arrest.

PubMed

Nakashima, Ryuta; Hifumi, Toru; Kawakita, Kenya; Okazaki, Tomoya; Egawa, Satoshi; Inoue, Akihiko; Seo, Ryutaro; Inagaki, Nobuhiro; Kuroda, Yasuhiro

2017-03-24

The discussion of neurocritical care management in post-cardiac arrest syndrome (PCAS) has generally focused on target values used for targeted temperature management (TTM). There has been less attention paid to target values for systemic and cerebral parameters to minimize secondary brain damage in PCAS. And the neurologic indications for TTM to produce a favorable neurologic outcome remain to be determined. Critical care management of PCAS patients is fundamental and essential for both cardiologists and general intensivists to improve neurologic outcome, because definitive therapy of PCAS includes both special management of the cause of cardiac arrest, such as coronary intervention to ischemic heart disease, and intensive management of the results of cardiac arrest, such as ventilation strategies to avoid brain ischemia. We reviewed the literature and the latest research about the following issues and propose practical care recommendations. Issues are (1) prediction of TTM candidate on admission, (2) cerebral blood flow and metabolism and target value of them, (3) seizure management using continuous electroencephalography, (4) target value of hemodynamic stabilization and its method, (5) management and analysis of respiration, (6) sedation and its monitoring, (7) shivering control and its monitoring, and (8) glucose management. We hope to establish standards of neurocritical care to optimize brain function and produce a favorable neurologic outcome.

Intentions to Quit Work among Care Staff Working in the Aged Care Sector

ERIC Educational Resources Information Center

Karantzas, Gery C.; Mellor, David; McCabe, Marita P.; Davison, Tanya E.; Beaton, Paul; Mrkic, Dejan

2012-01-01

Purpose of the Study: The aged care industry experiences high rates of staff turnover. Staff turnover has significant implications for the quality of care provided to care recipients and the financial costs to care agencies. In this study, we applied a model of intention to quit to identify the contextual and personal factors that shape aged care…

Relations of arterial stiffness and endothelial function to brain aging in the community.

PubMed

Tsao, Connie W; Seshadri, Sudha; Beiser, Alexa S; Westwood, Andrew J; Decarli, Charles; Au, Rhoda; Himali, Jayandra J; Hamburg, Naomi M; Vita, Joseph A; Levy, Daniel; Larson, Martin G; Benjamin, Emelia J; Wolf, Philip A; Vasan, Ramachandran S; Mitchell, Gary F

2013-09-10

To determine the association of arterial stiffness and pressure pulsatility, which can damage small vessels in the brain, with vascular and Alzheimer-type brain aging. Stroke- and dementia-free Framingham Offspring Study participants (n = 1,587, 61 ± 9 years, 45% male) underwent study of tonometric arterial stiffness and endothelial function (1998-2001) and brain MRI and cognition (1999-2002). We related carotid-femoral pulse wave velocity (CFPWV), mean arterial and central pulse pressure, and endothelial function to vascular brain aging by MRI (total cerebral brain volume [TCBV], white matter hyperintensity volume, silent cerebral infarcts) and vascular and Alzheimer-type cognitive aging (Trails B minus Trails A and logical memory-delayed recall, respectively). Higher CFPWV was associated with lower TCBV, greater white matter hyperintensity volume, and greater prevalence of silent cerebral infarcts (all p < 0.05). Each SD greater CFPWV was associated with lower TCBV equivalent to 1.2 years of brain aging. Mean arterial and central pulse pressure were associated with greater white matter hyperintensity volume (p = 0.005) and lower TCBV (p = 0.02), respectively, and worse verbal memory (both p < 0.05). Associations of tonometry variables with TCBV and white matter hyperintensity volume were stronger among those aged 65 years and older vs those younger than 65 years (p < 0.10 for interaction). Brachial artery endothelial function was unrelated to MRI measures (all p > 0.05). Greater arterial stiffness and pressure pulsatility are associated with brain aging, MRI vascular insults, and memory deficits typically seen in Alzheimer dementia. Future investigations are warranted to evaluate the potential impact of prevention and treatment of unfavorable arterial hemodynamics on neurocognitive outcomes.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

PubMed

Soreq, Lilach; Rose, Jamie; Soreq, Eyal; Hardy, John; Trabzuni, Daniah; Cookson, Mark R; Smith, Colin; Ryten, Mina; Patani, Rickie; Ule, Jernej

2017-01-10

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Physiological neuronal decline in healthy aging human brain - An in vivo study with MRI and short echo-time whole-brain (1)H MR spectroscopic imaging.

PubMed

Ding, Xiao-Qi; Maudsley, Andrew A; Sabati, Mohammad; Sheriff, Sulaiman; Schmitz, Birte; Schütze, Martin; Bronzlik, Paul; Kahl, Kai G; Lanfermann, Heinrich

2016-08-15

Knowledge of physiological aging in healthy human brain is increasingly important for neuroscientific research and clinical diagnosis. To investigate neuronal decline in normal aging brain eighty-one healthy subjects aged between 20 and 70years were studied with MRI and whole-brain (1)H MR spectroscopic imaging. Concentrations of brain metabolites N-acetyl-aspartate (NAA), choline (Cho), total creatine (tCr), myo-inositol (mI), and glutamine+glutamate (Glx) in ratios to internal water, and the fractional volumes of brain tissue were estimated simultaneously in eight cerebral lobes and in cerebellum. Results demonstrated that an age-related decrease in gray matter volume was the largest contribution to changes in brain volume. Both lobar NAA and the fractional volume of gray matter (FVGM) decreased with age in all cerebral lobes, indicating that the decreased NAA was predominantly associated with decreased gray matter volume and neuronal density or metabolic activity. In cerebral white matter Cho, tCr, and mI increased with age in association with increased fractional volume, showing altered cellular membrane turn-over, energy metabolism, and glial activity in human aging white matter. In cerebellum tCr increased while brain tissue volume decreased with age, showing difference to cerebral aging. The observed age-related metabolic and microstructural variations suggest that physiological neuronal decline in aging human brain is associated with a reduction of gray matter volume and neuronal density, in combination with cellular aging in white matter indicated by microstructural alterations and altered energy metabolism in the cerebellum. Copyright © 2016 Elsevier Inc. All rights reserved.

Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

PubMed Central

Zárate, Sandra; Stevnsner, Tinna; Gredilla, Ricardo

2017-01-01

Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS) owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD). Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain. PMID:29311911

Of Microbes and Minds: A Narrative Review on the Second Brain Aging.

PubMed

Calvani, Riccardo; Picca, Anna; Lo Monaco, Maria Rita; Landi, Francesco; Bernabei, Roberto; Marzetti, Emanuele

2018-01-01

In recent years, an extensive body of literature focused on the gut-brain axis and the possible role played by the gut microbiota in modulating brain morphology and function from birth to old age. Gut microbiota has been proposed as a relevant player during the early phases of neurodevelopment, with possible long-standing effects in later life. The reduction in gut microbiota diversity has also become one of the hallmarks of aging, and disturbances in its composition are associated with several (age-related) neurological conditions, including depression, Alzheimer's disease, and Parkinson's disease. Several pathways have been evoked for gut microbiota-brain communication, including neural connections (vagus nerve), circulating mediators derived by host-bacteria cometabolism, as well as the influence exerted by gut microbiota on host gut function, metabolism, and immune system. Although the most provoking data emerged from animal studies and despite the huge debate around the possible epiphenomenal nature of those findings, the gut microbiota-brain axis still remains a fascinating target to be exploited to attenuate some of the most burdensome consequences of aging.

Aging reduces the stimulating effect of blue light on cognitive brain functions.

PubMed

Daneault, Véronique; Hébert, Marc; Albouy, Geneviève; Doyon, Julien; Dumont, Marie; Carrier, Julie; Vandewalle, Gilles

2014-01-01

Light exposure, particularly blue light, is being recognized as a potent mean to stimulate alertness and cognition in young individuals. Aging is associated with changes in alertness regulation and cognition. Whether the effect of light on cognitive brain function changes with aging is unknown, however. Cross-sectional study. Functional Neuroimaging Unit, University of Montreal Geriatric Institute. Sixteen younger (23 ± 4.1 y) and 14 older (61 ± 4.5 y) healthy participants were recruited in the current study. Blue light administration. We used functional magnetic resonance imaging to record brain responses to an auditory working memory task in young and older healthy individuals, alternatively maintained in darkness or exposed to blue light. Results show that the older brain remains capable of showing sustained responses to light in several brain areas. However, compared to young individuals, the effect of blue light is decreased in the pulvinar, amygdala, and tegmentum as well as in the insular, prefrontal, and occipital cortices in elderly individuals. The effect of blue light on brain responses diminishes with aging in areas typically involved in visual functions and in key regions for alertness regulation and higher executive processes. Our findings provide the first indications that the effect of light on cognition may be reduced in healthy aging.

Are age and sex differences in brain oxytocin receptors related to maternal and infanticidal behavior in naïve mice?

PubMed

Olazábal, Daniel E; Alsina-Llanes, Marcela

2016-01-01

This article is part of a Special Issue "Parental Care". There is significant variability in the behavioral responses displayed by naïve young and adult mice when first exposed to pups. This variability has been associated with differences in the expression of oxytocin receptors (OXTRs) in the brain in several species. Experiment I investigated the behavioral responses of juvenile, adolescent, and adult CB57BL/6 males and females when first exposed to pups. We found an age increase in maternal females (11% of juveniles, 20% of adolescents, and 50% of young adults), and infanticidal males (0% of juveniles, 30% of adolescents, 44.5% of young adults, and 100% of older adults). Experiment II investigated OXTR density in the brain of juvenile and adult mice. Our results revealed an age decline in the density of OXTR in several brain regions, including the lateral septum, cingulated and posterior paraventricular thalamic nucleus in both males and females. Adult females had higher OXTR density in the ventromedial nucleus/postero-ventral hypothalamus (VMH) and the accessory olfactory bulb (AOB), but lower density in the ventral region of the lateral septum (LSv) than juveniles. Males had lower OXTR density in the anterior olfactory area (AOA) compared to juveniles. No age or sex differences were found in the medial preoptic area, and amygdaloid nuclei, among other brain regions. This study suggests that 1) maturation of parental and infanticidal behavioral responses is not reached until adulthood; 2) the pattern of development of OXTR in the mouse brain is unique, region specific, and differs from that observed in other rodents; 3) either up or down regulation of OXTR in a few brain regions (VMH/AOB/LSv/AOA) might contribute to age or sex differences in parental or infanticidal behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Coping with Stress During Aging: The Importance of a Resilient Brain.

PubMed

Sampedro-Piquero, P; Alvarez-Suarez, P; Begega, A

2018-03-05

Resilience is the ability to achieve a positive outcome when we are in the face of adversity. It supposes an active resistance to adversity by coping mechanisms in which genetic, molecular, neural and environmental factors are involved. Resilience has been usually studied in early ages and few is known about it during aging. In this review, we will address the age-related changes in the brain mechanisms involved in regulating the stress response. Furthermore, using the EE paradigm, we analyse the resilient potential of this intervention and its neurobiological basis. In this case, we will focus on identifying the characteristics of a resilient brain (modifications in HPA structure and function, neurogenesis, specific neuron types, glia, neurotrophic factors, nitric oxide synthase or microRNAs, among others). The evidence suggests that a healthy lifestyle has a crucial role to promote a resilient brain during aging. Along with the behavioral changes described, a better regulation of HPA axis, enhanced levels of postmitotic type-3 cells or changes in GABAergic neurotransmission are some of the brain mechanisms involved in resilience. Future research should identify different biomarkers that increase the resistance to develop mood disorders and based on this knowledge, develop new potential therapeutic targets. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Job satisfaction amongst aged care staff: exploring the influence of person-centered care provision.

PubMed

Edvardsson, David; Fetherstonhaugh, Deirdre; McAuliffe, Linda; Nay, Rhonda; Chenco, Carol

2011-10-01

There are challenges in attracting and sustaining a competent and stable workforce in aged care, and key issues of concern such as low staff job satisfaction and feelings of not being able to provide high quality care have been described. This study aimed to explore the association between person-centered care provision and job satisfaction in aged care staff. Residential aged care staff (n = 297) in Australia completed the measure of job satisfaction and the person-centered care assessment tool. Univariate analyses examined relationships between variables, and multiple linear regression analysis explored the extent to whichperceived person-centredness could predict job satisfaction of staff. Perceived person-centred care provision was significantly associated with job satisfaction, and person-centred care provision could explain nearly half of the variation in job satisfaction. The regression model with the three person-centered care subscales as predictor variables accounted for 40% of the variance in job satisfaction. Personalizing care had the largest independent influence on job satisfaction, followed by amount of organizational support and degree of environmental accessibility. Personalizing care and amount of organizational support had a statistically significant unique influence. As person-centered care positively correlated with staff job satisfaction, supporting staff in providing person-centered care can enhance job satisfaction and might facilitate attracting and retaining staff in residential aged care. The findings reiterate a need to shift focus from merely completing care tasks and following organizational routines to providing high quality person-centered care that promotes the good life of residents in aged care.

Aged care managers' perceptions of staff preparedness for caring for older survivors of genocide and mass trauma in Australia: How prepared are aged care workers?

PubMed

Teshuva, Karen; Wells, Yvonne

2017-03-01

To investigate aged care managers' perceptions of staff preparedness for working with older people who experienced genocide or mass trauma earlier in their lives (referred to in this paper as 'older survivors'). A survey of 60 aged care service managers was conducted (50% response rate). Trauma knowledge and skills scales with Cronbach's alpha scores of 0.74 and 0.90 respectively, were used. Scores across groups were compared using Student's t-tests. Three-quarters of the respondents reported that their agency had provided aged care services for older survivors. The majority of these managers perceived their staff to be moderately informed about trauma-related issues and half rated staff trauma-related skills positively. These ratings were positively associated with trauma-related staff training, service type and service location. Results suggest that, overall, managers perceive a need to improve aged care staff's preparedness for providing care for older survivors. © 2016 AJA Inc.

Creating Better School-Age Care Jobs: Model Work Standards.

ERIC Educational Resources Information Center

Haack, Peggy

Built on the premise that good school-age care jobs are the cornerstone of high-quality services for school-age youth and their families, this guide presents model work standards for school-age care providers. The guide begins with a description of the strengths and challenges of the school-age care profession. The model work standards are…

Perceived quality of maternal care in childhood and structure and function of mothers’ brain

PubMed Central

Kim, Pilyoung; Leckman, James F.; Mayes, Linda C.; Newman, Michal-Ann; Feldman, Ruth; Swain, James E.

2014-01-01

Animal studies indicate that early maternal care has long-term effects on brain areas related to social attachment and parenting, whereas neglectful mothering is linked with heightened stress reactivity in the hippocampus across the lifespan. The present study explores the possibility, using magnetic resonance imaging, that perceived quality of maternal care in childhood is associated with brain structure and functional responses to salient infant stimuli among human mothers in the first postpartum month. Mothers who reported higher maternal care in childhood showed larger grey matter volumes in the superior and middle frontal gyri, orbital gyrus, superior temporal gyrus and fusiform gyrus. In response to infant cries, these mothers exhibited higher activations in the middle frontal gyrus, superior temporal gyrus and fusiform gyrus, whereas mothers reporting lower maternal care showed increased hippocampal activations. These findings suggest that maternal care in childhood may be associated with anatomy and functions in brain regions implicated in appropriate responsivity to infant stimuli in human mothers. PMID:20590729

Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

PubMed

Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

2013-10-01

Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly. © 2013 The Anatomical Society and John Wiley & Sons Ltd.

Brain Growth Across the Life Span in Autism: Age-Specific Changes in Anatomical Pathology

PubMed Central

Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie

2014-01-01

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has lead to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism there may also be age-specific changes in gene expression, molecular, synaptic, cellular and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies. PMID:20920490

Indicators of Dysphagia in Aged Care Facilities

ERIC Educational Resources Information Center

Pu, Dai; Murry, Thomas; Wong, May C. M.; Yiu, Edwin M. L.; Chan, Karen M. K.

2017-01-01

Purpose: The current cross-sectional study aimed to investigate risk factors for dysphagia in elderly individuals in aged care facilities. Method: A total of 878 individuals from 42 aged care facilities were recruited for this study. The dependent outcome was speech therapist-determined swallowing function. Independent factors were Eating…

A culture-brain link: Negative age stereotypes predict Alzheimer's disease biomarkers.

PubMed

Levy, Becca R; Ferrucci, Luigi; Zonderman, Alan B; Slade, Martin D; Troncoso, Juan; Resnick, Susan M

2016-02-01

Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer's disease. To consider this possibility, we drew on dementia-free participants, in the Baltimore Longitudinal Study of Aging, whose age stereotypes were assessed decades before yearly magnetic resonance images and brain autopsies were performed. Those holding more-negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss and significantly greater accumulation of neurofibrillary tangles and amyloid plaques, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the pathology of Alzheimer's disease. (c) 2016 APA, all rights reserved).

Nursing care of the brain injury patient on a locked neurobehavioral unit.

PubMed

Becker, Christine

2012-01-01

Behavioral problems after a brain injury can be extremely challenging for those working with brain injured people. Nursing staff must be familiar with commonly used post brain injury medications and their effects, behavioral management plans, appropriate use of restrictive devices, and verbal or physical crisis intervention techniques when necessary. Rehabilitation nurses caring for brain injured patients on a locked neurobehavioral unit must maintain continual training and specific competence in this environment to ensure patient and staff safety. © 2012 Association of Rehabilitation Nurses.

THE LINK NURSE ROLE IN END OF LIFE CARE IN AGED CARE.

PubMed

Rosenberg, John

2016-08-01

The care of older people at the end of life is a key element of primary and community care. The Decision Assist -- Palliative Care Linkages project aimed to improve end of life care given to older Australians through establishing linkages between aged care and specialist palliative care services.

Indestructible plastic: the neuroscience of the new aging brain.

PubMed

Holman, Constance; de Villers-Sidani, Etienne

2014-01-01

In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain's capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static.

The relationship between age and brain response to visual erotic stimuli in healthy heterosexual males.

PubMed

Seo, Y; Jeong, B; Kim, J-W; Choi, J

2010-01-01

The various changes of sexuality, including decreased sexual desire and erectile dysfunction, are also accompanied with aging. To understand the effect of aging on sexuality, we explored the relationship between age and the visual erotic stimulation-related brain response in sexually active male subjects. Twelve healthy, heterosexual male subjects (age 22-47 years) were recorded the functional magnetic resonance imaging (fMRI) signals of their brain activation elicited by passive viewing erotic (ERO), happy-faced (HA) couple, food and nature pictures. Mixed effect analysis and correlation analysis were performed to investigate the relationship between the age and the change of brain activity elicited by erotic stimuli. Our results showed age was positively correlated with the activation of right occipital fusiform gyrus and amygdala, and negatively correlated with the activation of right insula and inferior frontal gyrus. These findings suggest age might be related with functional decline in brain regions being involved in both interoceptive sensation and prefrontal modulation while it is related with the incremental activity of the brain region for early processing of visual emotional stimuli in sexually healthy men.

Mitochondrial Energy Metabolism and Redox Signaling in Brain Aging and Neurodegeneration

PubMed Central

Yin, Fei; Boveris, Alberto

2014-01-01

Abstract Significance: The mitochondrial energy-transducing capacity is essential for the maintenance of neuronal function, and the impairment of energy metabolism and redox homeostasis is a hallmark of brain aging, which is particularly accentuated in the early stages of neurodegenerative diseases. Recent Advances: The communications between mitochondria and the rest of the cell by energy- and redox-sensitive signaling establish a master regulatory device that controls cellular energy levels and the redox environment. Impairment of this regulatory devise is critical for aging and the early stages of neurodegenerative diseases. Critical Issues: This review focuses on a coordinated metabolic network—cytosolic signaling, transcriptional regulation, and mitochondrial function—that controls the cellular energy levels and redox status as well as factors which impair this metabolic network during brain aging and neurodegeneration. Future Directions: Characterization of mitochondrial function and mitochondria-cytosol communications will provide pivotal opportunities for identifying targets and developing new strategies aimed at restoring the mitochondrial energy-redox axis that is compromised in brain aging and neurodegeneration. Antioxid. Redox Signal. 20, 353–371. PMID:22793257

Brain-Derived Neurotrophic Factor Expression in Individuals With Schizophrenia and Healthy Aging: Testing the Accelerated Aging Hypothesis of Schizophrenia.

PubMed

Islam, Farhana; Mulsant, Benoit H; Voineskos, Aristotle N; Rajji, Tarek K

2017-07-01

Schizophrenia has been hypothesized to be a syndrome of accelerated aging. Brain plasticity is vulnerable to the normal aging process and affected in schizophrenia: brain-derived neurotrophic factor (BDNF) is an important neuroplasticity molecule. The present review explores the accelerated aging hypothesis of schizophrenia by comparing changes in BDNF expression in schizophrenia with aging-associated changes. Individuals with schizophrenia show patterns of increased overall mortality, metabolic abnormalities, and cognitive decline normally observed later in life in the healthy population. An overall decrease is observed in BDNF expression in schizophrenia compared to healthy controls and in older individuals compared to a younger cohort. There is a marked decrease in BDNF levels in the frontal regions and in the periphery among older individuals and those with schizophrenia; however, data for BDNF expression in the occipital, parietal, and temporal cortices and the hippocampus is inconclusive. Accelerated aging hypothesis is supported based on frontal regions and peripheral studies; however, further studies are needed in other brain regions.

Age Drives Distortion of Brain Metabolic, Vascular and Cognitive Functions, and the Gut Microbiome

PubMed Central

Hoffman, Jared D.; Parikh, Ishita; Green, Stefan J.; Chlipala, George; Mohney, Robert P.; Keaton, Mignon; Bauer, Bjoern; Hartz, Anika M. S.; Lin, Ai-Ling

2017-01-01

Advancing age is the top risk factor for the development of neurodegenerative disorders, including Alzheimer’s disease (AD). However, the contribution of aging processes to AD etiology remains unclear. Emerging evidence shows that reduced brain metabolic and vascular functions occur decades before the onset of cognitive impairments, and these reductions are highly associated with low-grade, chronic inflammation developed in the brain over time. Interestingly, recent findings suggest that the gut microbiota may also play a critical role in modulating immune responses in the brain via the brain-gut axis. In this study, our goal was to identify associations between deleterious changes in brain metabolism, cerebral blood flow (CBF), gut microbiome and cognition in aging, and potential implications for AD development. We conducted our study with a group of young mice (5–6 months of age) and compared those to old mice (18–20 months of age) by utilizing metabolic profiling, neuroimaging, gut microbiome analysis, behavioral assessments and biochemical assays. We found that compared to young mice, old mice had significantly increased levels of numerous amino acids and fatty acids that are highly associated with inflammation and AD biomarkers. In the gut microbiome analyses, we found that old mice had increased Firmicutes/Bacteroidetes ratio and alpha diversity. We also found impaired blood-brain barrier (BBB) function and reduced CBF as well as compromised learning and memory and increased anxiety, clinical symptoms often seen in AD patients, in old mice. Our study suggests that the aging process involves deleterious changes in brain metabolic, vascular and cognitive functions, and gut microbiome structure and diversity, all which may lead to inflammation and thus increase the risk for AD. Future studies conducting comprehensive and integrative characterization of brain aging, including crosstalk with peripheral systems and factors, will be necessary to define the

Caring for the brain tumor patient: family caregiver burden and unmet needs.

PubMed

Schubart, Jane R; Kinzie, Mable B; Farace, Elana

2008-02-01

The rapid onset and progression of a brain tumor, cognitive and behavioral changes, and uncertainty surrounding prognosis are issues well known to health practitioners in neuro-oncology. We studied the specific challenges that family caregivers face when caring for patients experiencing the significant neurocognitive and neurobehavioral disorders associated with brain tumors. We selected 25 family caregivers of adult brain tumor patients to represent the brain tumor illness trajectory (crisis, chronic, and terminal phases). Interviews documented caregiving tasks and decision-making and information and support needs. Themes were permitted to emerge from the data in qualitative analysis. We found that the family caregivers in this study provided extraordinary uncompensated care involving significant amounts of time and energy for months or years and requiring the performance of tasks that were often physically, emotionally, socially, or financially demanding. They were constantly challenged to solve problems and make decisions as care needs changed, yet they felt untrained and unprepared as they struggled to adjust to new roles and responsibilities. Because the focus was on the patient, their own needs were neglected. Because caregiver information needs are emergent, they are not always known at the time of a clinic visit. Physicians are frequently unable to address caregiver questions, a situation compounded by time constraints and cultural barriers. We provide specific recommendations for (1) improving the delivery of information; (2) enhancing communication among patients, families, and health care providers; and (3) providing psychosocial support for family caregivers.

Caring for the brain tumor patient: Family caregiver burden and unmet needs

PubMed Central

Schubart, Jane R.; Kinzie, Mable B.; Farace, Elana

2008-01-01

The rapid onset and progression of a brain tumor, cognitive and behavioral changes, and uncertainty surrounding prognosis are issues well known to health practitioners in neuro-oncology. We studied the specific challenges that family caregivers face when caring for patients experiencing the significant neurocognitive and neurobehavioral disorders associated with brain tumors. We selected 25 family caregivers of adult brain tumor patients to represent the brain tumor illness trajectory (crisis, chronic, and terminal phases). Interviews documented caregiving tasks and decision-making and information and support needs. Themes were permitted to emerge from the data in qualitative analysis. We found that the family caregivers in this study provided extraordinary uncompensated care involving significant amounts of time and energy for months or years and requiring the performance of tasks that were often physically, emotionally, socially, or financially demanding. They were constantly challenged to solve problems and make decisions as care needs changed, yet they felt untrained and unprepared as they struggled to adjust to new roles and responsibilities. Because the focus was on the patient, their own needs were neglected. Because caregiver information needs are emergent, they are not always known at the time of a clinic visit. Physicians are frequently unable to address caregiver questions, a situation compounded by time constraints and cultural barriers. We provide specific recommendations for (1) improving the delivery of information; (2) enhancing communication among patients, families, and health care providers; and (3) providing psychosocial support for family caregivers. PMID:17993635

Age-specific MRI brain and head templates for healthy adults from 20 through 89 years of age

PubMed Central

Fillmore, Paul T.; Phillips-Meek, Michelle C.; Richards, John E.

2015-01-01

This study created and tested a database of adult, age-specific MRI brain and head templates. The participants included healthy adults from 20 through 89 years of age. The templates were done in five-year, 10-year, and multi-year intervals from 20 through 89 years, and consist of average T1W for the head and brain, and segmenting priors for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). It was found that age-appropriate templates provided less biased tissue classification estimates than age-inappropriate reference data and reference data based on young adult templates. This database is available for use by other investigators and clinicians for their MRI studies, as well as other types of neuroimaging and electrophysiological research.1 PMID:25904864

Age- and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats

EPA Pesticide Factsheets

Differences in various mitochondrial bioenergetics parameters in different brain regions in different age groups.This dataset is associated with the following publication:Pandya, J.D., J. Royland , R.C. McPhail, P.G. Sullivan, and P. Kodavanti. Age-and Brain Region-Specific Differences in Mitochondrial Bioenergetics in Brown Norway Rats. NEUROBIOLOGY OF AGING. Elsevier Science Ltd, New York, NY, USA, 42: 25-34, (2016).

Effects of early intervention and the moderating effects of brain activity on institutionalized children's social skills at age 8.

PubMed

Almas, Alisa N; Degnan, Kathryn A; Radulescu, Anca; Nelson, Charles A; Zeanah, Charles H; Fox, Nathan A

2012-10-16

The present study examined the social skills of previously institutionalized, 8-y-old Romanian children from the Bucharest Early Intervention Project and the influence of attachment security and brain electrical activity (alpha power) on these skills. Participants included children randomized to an intervention involving foster care [Foster Care Group (FCG)], children randomized to remain in institutions [Care As Usual Group (CAUG)], and never-institutionalized children living with their families in the Bucharest community [Never-Institutionalized Group (NIG)]. A continuous rating of children's attachment security to their primary caregiver was assessed at 42 mo of age. When children were 8 y old, teachers rated their social skills, and the children's resting electroencephalogram alpha power was recorded. Teachers rated social skills of FCG children who were placed into foster care before 20 mo of age as no different from NIG children, and both of these groups were higher than CAUG children and FCG children placed after 20 mo. Electroencephalogram alpha power at age 8 significantly moderated the relations between attachment security and social skills. These findings characterize institutionalized children's social skills in middle childhood within the context of a randomized intervention while highlighting the roles of both relational and biological factors in these developmental trajectories.

Brain development and aging: overlapping and unique patterns of change.

PubMed

Tamnes, Christian K; Walhovd, Kristine B; Dale, Anders M; Østby, Ylva; Grydeland, Håkon; Richardson, George; Westlye, Lars T; Roddey, J Cooper; Hagler, Donald J; Due-Tønnessen, Paulina; Holland, Dominic; Fjell, Anders M

2013-03-01

Early-life development is characterized by dramatic changes, impacting lifespan function more than changes in any other period. Developmental origins of neurocognitive late-life functions are acknowledged, but detailed longitudinal magnetic resonance imaging studies of brain maturation and direct comparisons with aging are lacking. To these aims, a novel method was used to measure longitudinal volume changes in development (n=85, 8-22 years) and aging (n=142, 60-91 years). Developmental reductions exceeded 1% annually in much of the cortex, more than double to that seen in aging, with a posterior-to-anterior gradient. Cortical reductions were greater than the subcortical during development, while the opposite held in aging. The pattern of lateral cortical changes was similar across development and aging, but the pronounced medial temporal reduction in aging was not precast in development. Converging patterns of change in adolescents and elderly, particularly in the medial prefrontal areas, suggest that late developed cortices are especially vulnerable to atrophy in aging. A key question in future research will be to disentangle the neurobiological underpinnings for the differences and the similarities between brain changes in development and aging. Copyright © 2012 Elsevier Inc. All rights reserved.

The Adam Williams initiative: collaborating with community resources to improve care for traumatic brain injury.

PubMed

Bader, Mary Kay; Stutzman, Sonja E; Palmer, Sylvain; Nwagwu, Chiedozie I; Goodman, Gary; Whittaker, Margie; Olson, Daiwai M

2014-12-01

The Brain Trauma Foundation has developed treatment guidelines for the care of patients with acute traumatic brain injury. However, a method to provide broad acceptance and application of these guidelines has not been published. To describe methods for the development, funding, and continued educational efforts of the Adam Williams Initiative; the experiences from the first 10 years may serve as a template for hospitals and nurses that seek to engage in long-term quality improvement collaborations with foundations and/or industry. In 2004, the nonprofit Adam Williams Initiative was established with the goal of providing education and resources that would encourage hospitals across the United States to incorporate the Brain Trauma Foundation's guidelines into practice. Between 2004 and 2014, 37 hospitals have been funded by the Adam Williams Initiative and have had staff members participate in an immersion experience at Mission Hospital (Mission Viejo, California) during which team members received both didactic and hands-on education in the care of traumatic brain injury. Carefully cultivated relationships and relentless teamwork have contributed to successful implementation of the Brain Trauma Foundation's guidelines in US hospitals. ©2014 American Association of Critical-Care Nurses.

Brain growth across the life span in autism: age-specific changes in anatomical pathology.

PubMed

Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie

2011-03-22

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has led to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism, there may also be age-specific changes in gene expression, molecular, synaptic, cellular, and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation, and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Brain-Based Teaching in the Digital Age

ERIC Educational Resources Information Center

Sprenger, Marilee

2010-01-01

In the digital age, your students have the ways, means, and speed to gather any information they want. But they need your guidance more than ever. Discover how digital technology is actually changing your students' brains. Learn why this creates new obstacles for teachers, but also opens up potential new pathways for learning. You will understand…

The 2030 Problem: Caring for Aging Baby Boomers

PubMed Central

Knickman, James R; Snell, Emily K

2002-01-01

Objective To assess the coming challenges of caring for large numbers of frail elderly as the Baby Boom generation ages. Study Setting A review of economic and demographic data as well as simulations of projected socioeconomic and demographic patterns in the year 2030 form the basis of a review of the challenges related to caring for seniors that need to be faced by society. Study Design A series of analyses are used to consider the challenges related to caring for elders in the year 2030: (1) measures of macroeconomic burden are developed and analyzed, (2) the literatures on trends in disability, payment approaches for long-term care, healthy aging, and cultural views of aging are analyzed and synthesized, and(3)simulations of future income and assets patterns of the Baby Boom generation are developed. Principal Findings The economic burden of aging in 2030 should be no greater than the economic burden associated with raising large numbers of baby boom children in the 1960s. The real challenges of caring for the elderly in 2030 will involve: (1) making sure society develops payment and insurance systems for long-term care that work better than existing ones, (2) taking advantage of advances in medicine and behavioral health to keep the elderly as healthy and active as possible, (3) changing the way society organizes community services so that care is more accessible, and (4) altering the cultural view of aging to make sure all ages are integrated into the fabric of community life. Conclusions To meet the long-term care needs of Baby Boomers, social and public policy changes must begin soon. Meeting the financial and social service burdens of growing numbers of elders will not be a daunting task if necessary changes are made now rather than when Baby Boomers actually need long-term care. PMID:12236388

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing.

PubMed

Neltner, Janna H; Abner, Erin L; Baker, Steven; Schmitt, Frederick A; Kryscio, Richard J; Jicha, Gregory A; Smith, Charles D; Hammack, Eleanor; Kukull, Walter A; Brenowitz, Willa D; Van Eldik, Linda J; Nelson, Peter T

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer's Disease Centre, Nun Study, and National Alzheimer's Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case-control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

Arteriolosclerosis that affects multiple brain regions is linked to hippocampal sclerosis of ageing

PubMed Central

Neltner, Janna H.; Abner, Erin L.; Baker, Steven; Schmitt, Frederick A.; Kryscio, Richard J.; Jicha, Gregory A.; Smith, Charles D.; Hammack, Eleanor; Kukull, Walter A.; Brenowitz, Willa D.; Van Eldik, Linda J.

2014-01-01

Hippocampal sclerosis of ageing is a prevalent brain disease that afflicts older persons and has been linked with cerebrovascular pathology. Arteriolosclerosis is a subtype of cerebrovascular pathology characterized by concentrically thickened arterioles. Here we report data from multiple large autopsy series (University of Kentucky Alzheimer’s Disease Centre, Nun Study, and National Alzheimer’s Coordinating Centre) showing a specific association between hippocampal sclerosis of ageing pathology and arteriolosclerosis. The present analyses incorporate 226 cases of autopsy-proven hippocampal sclerosis of ageing and 1792 controls. Case–control comparisons were performed including digital pathological assessments for detailed analyses of blood vessel morphology. We found no evidence of associations between hippocampal sclerosis of ageing pathology and lacunar infarcts, large infarcts, Circle of Willis atherosclerosis, or cerebral amyloid angiopathy. Individuals with hippocampal sclerosis of ageing pathology did not show increased rates of clinically documented hypertension, diabetes, or other cardiac risk factors. The correlation between arteriolosclerosis and hippocampal sclerosis of ageing pathology was strong in multiple brain regions outside of the hippocampus. For example, the presence of arteriolosclerosis in the frontal cortex (Brodmann area 9) was strongly associated with hippocampal sclerosis of ageing pathology (P < 0.001). This enables informative evaluation of anatomical regions outside of the hippocampus. To assess the morphology of brain microvasculature far more rigorously than what is possible using semi-quantitative pathological scoring, we applied digital pathological (Aperio ScanScope) methods on a subsample of frontal cortex sections from hippocampal sclerosis of ageing (n = 15) and control (n = 42) cases. Following technical studies to optimize immunostaining methods for small blood vessel visualization, our analyses focused on sections

Ageing in people with autistic spectrum disorder.

PubMed

Mukaetova-Ladinska, E B; Perry, E; Baron, M; Povey, C

2012-02-01

Although autism in children and in adults attracts attention with respect to clinical and research needs, autism in the older individuals has not been considered to any degree. We review the evidence for urgently addressing the question of ageing in people with autistic spectrum disorder (ASD), focusing on those with disability. Perspectives are reviewed in relation to demographics, experiences of relatives or carers, anticipated residential care needs, requirement for specifically designed cognitive assessment tools and importance of initiating new brain ageing research initiatives in this area. With escalating numbers of ASD individuals with disability reaching old age, provision of care is the paramount issue that is only beginning to be addressed in a few European communities and in the USA. How ageing affects cognition in such individuals as they reach an age no longer consistent with parental care is unknown, lacking any published evidence, and there is a clear need to design cognitive and behavioural assessment tools appropriate to ageing in ASD individuals with disability, as was the case with respect to dementia as a whole. Although there is a growing body of evidence on pathological, imaging, neuropharmacological and other key brain abnormalities in ASD, these are, to date, confined to children and young (only rarely to middle aged) adults. The need for new initiatives in research into ageing in ASD is urgent. Apart from a growing care crisis, the prospect of understanding brain ageing in this population may bring potential rewards beyond immediate clinical need given the precedent of Down syndrome. Copyright © 2011 John Wiley & Sons, Ltd.

Global and regional annual brain volume loss rates in physiological aging.

PubMed

Schippling, Sven; Ostwaldt, Ann-Christin; Suppa, Per; Spies, Lothar; Manogaran, Praveena; Gocke, Carola; Huppertz, Hans-Jürgen; Opfer, Roland

2017-03-01

The objective is to estimate average global and regional percentage brain volume loss per year (BVL/year) of the physiologically ageing brain. Two independent, cross-sectional single scanner cohorts of healthy subjects were included. The first cohort (n = 248) was acquired at the Medical Prevention Center (MPCH) in Hamburg, Germany. The second cohort (n = 316) was taken from the Open Access Series of Imaging Studies (OASIS). Brain parenchyma (BP), grey matter (GM), white matter (WM), corpus callosum (CC), and thalamus volumes were calculated. A non-parametric technique was applied to fit the resulting age-volume data. For each age, the BVL/year was derived from the age-volume curves. The resulting BVL/year curves were compared between the two cohorts. For the MPCH cohort, the BVL/year curve of the BP was an increasing function starting from 0.20% at the age of 35 years increasing to 0.52% at 70 years (corresponding values for GM ranged from 0.32 to 0.55%, WM from 0.02 to 0.47%, CC from 0.07 to 0.48%, and thalamus from 0.25 to 0.54%). Mean absolute difference between BVL/year trajectories across the age range of 35-70 years was 0.02% for BP, 0.04% for GM, 0.04% for WM, 0.11% for CC, and 0.02% for the thalamus. Physiological BVL/year rates were remarkably consistent between the two cohorts and independent from the scanner applied. Average BVL/year was clearly age and compartment dependent. These results need to be taken into account when defining cut-off values for pathological annual brain volume loss in disease models, such as multiple sclerosis.

Prudence, pleasure, and cognitive ageing: Configurations of the uses and users of brain training games within UK media, 2005-2015.

PubMed

Pickersgill, Martyn; Broer, Tineke; Cunningham-Burley, Sarah; Deary, Ian

2017-08-01

The use of 'brain training' games is often regarded as relating to wider ideals of self-improvement and youthfulness. Hence, use is intertwined with discourses of 'active' ageing. This paper analyzes how the use and users of brain training games were configured in the UK media, from 2005 to 2015, and examines how notions of active ageing relate to these representations. Game users were rarely constructed solely as gamers, and were more often presented as prudent individuals focused on a serious goal. This configuration related to assumed and enjoined motivations for brain training; specifically, users were commonly framed as seeking to enhance cognition and limit/delay cognitive decline. Scientific evidence about brain training was often deployed to explain how games might work; sometimes, however, it was used to undermine the utility of games and assert the significance and cognitive health-benefits of other activities. A minority of texts explicitly critiqued ideals of self-improvement, arguing that game playing was important for its own sake. Yet, even the pleasure associated with gaming was occasionally instrumentalized as a mechanism for ensuring prudent life choices. The analysis casts fresh light on how debates around health, ageing, and science correspond to configurations of technology uses and users. It presents evidence of the widespread cultural circulation of enjoiners regarding self-care and healthy ageing within British society. However, the paper also provides indications of the limits to such imperatives: discourses of pleasure co-exist with and perhaps supplant logics of prudence in (accounts of) practices ostensibly aimed at ageing 'well'. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Does age influence the intensity of care in a managed care organization?

PubMed

Long, Michael J; Lescoe-Long, Mary

2005-01-01

The primary objective of this study was to determine whether an inverse relationship between age and the intensity of care prevailed in an elderly, functionally impaired population enrolled in a managed care organization. The secondary objective was to determine whether those who died during the study were treated more intensively than the survivors. A total of 278 enrollees in a managed care organization who were 75 years and over, had a severe functional disability, excessive hospital or Emergency Department use, volunteered to take part in a 2-year study. Seventy-seven clients died during the study. We calculated indices of outpatient care intensity and hospital care intensity for the study period. With minor exceptions, the results clearly show that, for this group of clients, the intensity of outpatient care was clearly, inversely related to age. The intensity of hospital care was also inversely related to age, thereby ruling out the hypothesis that it was being substituted for outpatient care. The results also clearly show that, for this population, those who died during the study period were treated more intensively than the survivors. We found strong support for our hypotheses. An investigation of the reasons for these findings was beyond the scope of our data.

Cardiac index is associated with brain aging: The Framingham Heart Study

PubMed Central

Jefferson, Angela L.; Himali, Jayandra J.; Beiser, Alexa S.; Au, Rhoda; Massaro, Joseph M.; Seshadri, Sudha; Gona, Philimon; Salton, Carol J.; DeCarli, Charles; O’Donnell, Christopher J.; Benjamin, Emelia J.; Wolf, Philip A.; Manning, Warren J.

2010-01-01

Background Cardiac dysfunction is associated with neuroanatomic and neuropsychological changes in aging adults with prevalent cardiovascular disease (CVD), theoretically because systemic hypoperfusion disrupts cerebral perfusion, contributing to subclinical brain injury. We hypothesized that cardiac function, as measured by cardiac index, would be associated with pre-clinical brain magnetic resonance imaging (MRI) and neuropsychological markers of ischemia and Alzheimer’s disease in the community. Methods and Results Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected on 1504 Framingham Offspring Cohort participants free from clinical stroke, transient ischemic attack, or dementia (61±9 years; 54% women). Neuropsychological and brain MRI variables were related to cardiac MRI-assessed cardiac index (cardiac output/body surface area). In multivariable-adjusted models, cardiac index was positively related to total brain volume (P=0.03) and information processing speed (P=0.02) and inversely related to lateral ventricular volume (P=0.048). When participants with clinically prevalent CVD were excluded, the relation between cardiac index and total brain volume remained (P=0.02). Post-hoc comparisons revealed that participants in the bottom cardiac index tertile (values<2.54) and middle cardiac index tertile (values between 2.54 and 2.92) had significantly lower brain volumes (P=0.04) than participants in the top cardiac index tertile (values>2.92). Conclusions Although observational data cannot establish causality, our findings are consistent with the hypothesis that decreasing cardiac function, even at normal cardiac index levels, is associated with accelerated brain aging. PMID:20679552

Brain Organochlorines and Lewy Pathology: The Honolulu-Asia Aging Study

PubMed Central

Ross, G. Webster; Duda, John E.; Abbott, Robert D.; Pellizzari, Edo; Petrovitch, Helen; Miller, Diane B.; O’Callaghan, James P.; Tanner, Caroline M.; Noorigian, Joseph V.; Masaki, Kamal; Launer, Lenore; White, Lon R.

2012-01-01

Background Although organochlorines have been reported more frequently in Parkinson’s disease (PD) brains than controls, the association with brain Lewy pathology is unknown. Honolulu-Asia Aging Study (HAAS) participants, exposed to organochlorines from a variety of sources during mid-life, represent a population well suited to determine the relationship of brain organochlorines with Lewy pathology in decedents from the longitudinal HAAS. Methods Study design included the measurement of 21 organochlorine levels in frozen occipital lobe samples from HAAS decedents. Alpha-synuclein immunostaining performed on 225 brains was used to identify Lewy bodies and Lewy neurites. Results With the potential for spurious associations to appear between Lewy pathology and 17 organochlorine compounds found to be present in at least one brain, initial assessments identified heptachlor epoxide isomer b, methoxychlor, and benzene hexachloride b as being most important. Prevalence of Lewy pathology was 75% (6/8) among brains with any 2 of the 3 compounds, 48.8% (79/162) among those with 1, and 32.7% (18/55) for those with neither (P=0.007 test for trend). While findings persisted after removing cases with PD and dementia with Lewy bodies, and when adjustments were made for age at death, body mass index, pack-years of cigarette smoking, and coffee intake (p=0.013), results were insignificant when correcting for multiple testing. Conclusions While consistent with earlier accounts of an association between organochlorines and clinical PD, associations with Lewy pathology warrant further study. PMID:22976848

Brain volume change and cognitive trajectories in aging.

PubMed

Fletcher, Evan; Gavett, Brandon; Harvey, Danielle; Farias, Sarah Tomaszewski; Olichney, John; Beckett, Laurel; DeCarli, Charles; Mungas, Dan

2018-05-01

Examine how longitudinal cognitive trajectories relate to brain baseline measures and change in lobar volumes in a racially/ethnically and cognitively diverse sample of older adults. Participants were 460 older adults enrolled in a longitudinal aging study. Cognitive outcomes were measures of episodic memory, semantic memory, executive function, and spatial ability derived from the Spanish and English Neuropsychological Assessment Scales (SENAS). Latent variable multilevel modeling of the four cognitive outcomes as parallel longitudinal processes identified intercepts for each outcome and a second order global change factor explaining covariance among the highly correlated slopes. We examined how baseline brain volumes (lobar gray matter, hippocampus, and white matter hyperintensity) and change in brain volumes (lobar gray matter) were associated with cognitive intercepts and global cognitive change. Lobar volumes were dissociated into global and specific components using latent variable methods. Cognitive change was most strongly associated with brain gray matter volume change, with strong independent effects of global gray matter change and specific temporal lobe gray matter change. Baseline white matter hyperintensity and hippocampal volumes had significant incremental effects on cognitive decline beyond gray matter change. Baseline lobar gray matter was related to cognitive decline, but did not contribute beyond gray matter change. Cognitive decline was strongly influenced by gray matter volume change and, especially, temporal lobe change. The strong influence of temporal lobe gray matter change on cognitive decline may reflect involvement of temporal lobe structures that are critical for late life cognitive health but also are vulnerable to diseases of aging. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

How bilingualism protects the brain from aging: Insights from bimodal bilinguals.

PubMed

Li, Le; Abutalebi, Jubin; Emmorey, Karen; Gong, Gaolang; Yan, Xin; Feng, Xiaoxia; Zou, Lijuan; Ding, Guosheng

2017-08-01

Bilingual experience can delay cognitive decline during aging. A general hypothesis is that the executive control system of bilinguals faces an increased load due to controlling two languages, and this increased load results in a more "tuned brain" that eventually creates a neural reserve. Here we explored whether such a neuroprotective effect is independent of language modality, i.e., not limited to bilinguals who speak two languages but also occurs for bilinguals who use a spoken and a signed language. We addressed this issue by comparing bimodal bilinguals to monolinguals in order to detect age-induced structural brain changes and to determine whether we can detect the same beneficial effects on brain structure, in terms of preservation of gray matter volume (GMV), for bimodal bilinguals as has been reported for unimodal bilinguals. Our GMV analyses revealed a significant interaction effect of age × group in the bilateral anterior temporal lobes, left hippocampus/amygdala, and left insula where bimodal bilinguals showed slight GMV increases while monolinguals showed significant age-induced GMV decreases. We further found through cortical surface-based measurements that this effect was present for surface area and not for cortical thickness. Moreover, to further explore the hypothesis that overall bilingualism provides neuroprotection, we carried out a direct comparison of GMV, extracted from the brain regions reported above, between bimodal bilinguals, unimodal bilinguals, and monolinguals. Bilinguals, regardless of language modality, exhibited higher GMV compared to monolinguals. This finding highlights the general beneficial effects provided by experience handling two language systems, whether signed or spoken. Hum Brain Mapp 38:4109-4124, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Impairment of paravascular clearance pathways in the aging brain.

PubMed

Kress, Benjamin T; Iliff, Jeffrey J; Xia, Maosheng; Wang, Minghuan; Wei, Helen S; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason A; Plog, Benjamin A; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-12-01

In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal fluid (CSF) and interstitial fluid (ISF). Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular CSF pathways. The objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy and interstitial solute clearance was evaluated by radiotracer clearance assays in young (2-3 months), middle-aged (10-12 months), and old (18-20 months) wild-type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function was evaluated by immunofluorescence. Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparenchymally injected amyloid-β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of misfolded protein aggregates. © 2014 American Neurological Association.

Cellular senescence in honey bee brain is largely independent of chronological age

PubMed Central

Seehuus, Siri-Christine; Krekling, Trygve; Amdam, Gro V.

2008-01-01

Accumulation of oxidative stress-induced damage in brain tissue plays an important role in the pathogenesis of normal aging and neurodegenerative diseases. Neuronal oxidative damage typically increases with age in humans, and also in the invertebrate and vertebrate model species most commonly used in aging research. By use of quantitative immunohistochemistry and Western blot, we show that this aspect of brain senescence is largely decoupled from chronological age in the honey bee (Apis mellifera). The bee is a eusocial insect characterized by the presence of a reproductive queen caste and a caste of functionally sterile female workers that performs various alloparental tasks such as nursing and foraging. We studied patterns of oxidative nitration and carbonylation damage in the brain of worker bees that performed nurse tasks as 8- and 200-day-olds and foraging tasks as 20- and 200-day-olds. In addition, we examined 180-day-old diutinus bees, a stress-resistant temporal worker form that survives unfavorable periods. Our results indicate that nitration damage occurs only at low levels in vivo, but that a 60-kDa protein from honey bee brain is selectively nitrated by peroxynitrite in vitro. Oxidative carbonylation is present at varying levels in the visual and chemosensory neuropiles of worker bees, and this inter-individual variation is better explained by social role than by chronological age. PMID:17052880

Implementing Information and Communication Technology to Support Community Aged Care Service Integration: Lessons from an Australian Aged Care Provider.

PubMed

Douglas, Heather E; Georgiou, Andrew; Tariq, Amina; Prgomet, Mirela; Warland, Andrew; Armour, Pauline; Westbrook, Johanna I

2017-04-10

There is limited evidence of the benefits of information and communication technology (ICT) to support integrated aged care services. We undertook a case study to describe carelink+, a centralised client service management ICT system implemented by a large aged and community care service provider, Uniting. We sought to explicate the care-related information exchange processes associated with carelink+ and identify lessons for organisations attempting to use ICT to support service integration. Our case study included seventeen interviews and eleven observation sessions with a purposive sample of staff within the organisation. Inductive analysis was used to develop a model of ICT-supported information exchange. Management staff described the integrated care model designed to underpin carelink+. Frontline staff described complex information exchange processes supporting coordination of client services. Mismatches between the data quality and the functions carelink+ was designed to support necessitated the evolution of new work processes associated with the system. There is value in explicitly modelling the work processes that emerge as a consequence of ICT. Continuous evaluation of the match between ICT and work processes will help aged care organisations to achieve higher levels of ICT maturity that support their efforts to provide integrated care to clients.

Space age health care delivery

NASA Technical Reports Server (NTRS)

Jones, W. L.

1977-01-01

Space age health care delivery is being delivered to both NASA astronauts and employees with primary emphasis on preventive medicine. The program relies heavily on comprehensive health physical exams, health education, screening programs and physical fitness programs. Medical data from the program is stored in a computer bank so epidemiological significance can be established and better procedures can be obtained. Besides health care delivery to the NASA population, NASA is working with HEW on a telemedicine project STARPAHC, applying space technology to provide health care delivery to remotely located populations.

Communicating for Quality in School Age Care Services

ERIC Educational Resources Information Center

Cartmel, Jennifer; Grieshaber, Susan

2014-01-01

School Age Care (SAC) services have existed in Australia for over 100 years but they have tended to take a back seat when compared with provision for school-aged children and those under school age using early childhood education and care (ECEC) services. Many SAC services are housed in shared premises and many children attending preparatory or…

Lucid dreaming: an age-dependent brain dissociation.

PubMed

Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

2012-12-01

The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation. © 2012 European Sleep Research Society.

Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging.

PubMed

Li, Hui-Jie; Hou, Xiao-Hui; Liu, Han-Hui; Yue, Chun-Lin; Lu, Guang-Ming; Zuo, Xi-Nian

2015-10-01

Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Circulatory miR-34a as an RNA-based, noninvasive biomarker for brain aging

PubMed Central

Li, Xiaoli; Khanna, Amit; Li, Na; Wang, Eugenia

2011-01-01

MicroRNAs in blood samples have been identified as an important class of biomarkers, which can reflect physiological changes from cancer to brain dysfunction. In this report we identify concordant increases in levels of expression of miR-34a in brain and two components of mouse blood samples, peripheral blood mononuclear cells (PBMCs) and plasma, from 2 day old neonates through young adulthood and mid-life to old age at 25 months. Levels of this microRNA's prime target, silent information regulator 1 (SIRT1), in brain and the two blood-derived specimens decrease with age inversely to miR-34a, starting as early as 4 months old, when appreciable tissue aging has not yet begun. Our results suggest that: 1. Increased miR-34a and the reciprocal decrease of its target, SIRT1, in blood specimens are the accessible biomarkers for age-dependent changes in brain; and 2. these changes are predictors of impending decline in brain function, as early as in young adult mice. PMID:22064828

Studying variability in human brain aging in a population-based German cohort-rationale and design of 1000BRAINS.

PubMed

Caspers, Svenja; Moebus, Susanne; Lux, Silke; Pundt, Noreen; Schütz, Holger; Mühleisen, Thomas W; Gras, Vincent; Eickhoff, Simon B; Romanzetti, Sandro; Stöcker, Tony; Stirnberg, Rüdiger; Kirlangic, Mehmet E; Minnerop, Martina; Pieperhoff, Peter; Mödder, Ulrich; Das, Samir; Evans, Alan C; Jöckel, Karl-Heinz; Erbel, Raimund; Cichon, Sven; Nöthen, Markus M; Sturma, Dieter; Bauer, Andreas; Jon Shah, N; Zilles, Karl; Amunts, Katrin

2014-01-01

The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45-75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates.

Differences by age groups in health care spending.

PubMed

Fisher, C R

1980-01-01

This paper presents differences by age in health care spending by type of expenditure and by source of funds through 1978. Use of health care services generally increases with age. The average health bill reached $2,026 for the aged in 1978, $764 for the intermediate age group, and $286 for the young. Biological, demographic, and policy factors determine each age group's share of health spending. Public funds financed over three-fifths of the health expenses of the aged, with Medicare and Medicaid together accounting for 58 percent. Most of the health expenses of the young age groups were paid by private sources.

Association between Dopamine D4 Receptor Polymorphism and Age Related Changes in Brain Glucose Metabolism

PubMed Central

Volkow, Nora D.; Tomasi, Dardo; Wang, Gene-Jack; Telang, Frank; Fowler, Joanna S.; Goldstein, Rita Z.; Klein, Nelly; Wong, Christopher; Swanson, James M.; Shumay, Elena

2013-01-01

Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4) gene (VNTR in exon 3), which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive) including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET) and [18F]fluoro-D-glucose (18FDG) to measure brain glucose metabolism (marker of brain function) under baseline conditions (no stimulation) in 82 healthy individuals (age range 22–55 years). We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R−, n = 53) had a significant (p<0.0001) negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism) in frontal (r = −0.52), temporal (r = −0.51) and striatal regions (r = −0.47, p<0.001); such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29), these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002). Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R− groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism. PMID:23717434

DNA damage in the oligodendrocyte lineage and its role in brain aging.

PubMed

Tse, Kai-Hei; Herrup, Karl

2017-01-01

Myelination is a recent evolutionary addition that significantly enhances the speed of transmission in the neural network. Even slight defects in myelin integrity impair performance and enhance the risk of neurological disorders. Indeed, myelin degeneration is an early and well-recognized neuropathology that is age associated, but appears before cognitive decline. Myelin is only formed by fully differentiated oligodendrocytes, but the entire oligodendrocyte lineage are clear targets of the altered chemistry of the aging brain. As in neurons, unrepaired DNA damage accumulates in the postmitotic oligodendrocyte genome during normal aging, and indeed may be one of the upstream causes of cellular aging - a fact well illustrated by myelin co-morbidity in premature aging syndromes arising from deficits in DNA repair enzymes. The clinical and experimental evidence from Alzheimer's disease, progeroid syndromes, ataxia-telangiectasia and other conditions strongly suggest that oligodendrocytes may in fact be uniquely vulnerable to oxidative DNA damage. If this damage remains unrepaired, as is increasingly true in the aging brain, myelin gene transcription and oligodendrocyte differentiation is impaired. Delineating the relationships between early myelin loss and DNA damage in brain aging will offer an additional dimension outside the neurocentric view of neurodegenerative disease. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cardiac and Carotid Markers Link With Accelerated Brain Atrophy: The AGES-Reykjavik Study (Age, Gene/Environment Susceptibility-Reykjavik).

PubMed

Sabayan, Behnam; van Buchem, Mark A; Sigurdsson, Sigurdur; Zhang, Qian; Meirelles, Osorio; Harris, Tamara B; Gudnason, Vilmundur; Arai, Andrew E; Launer, Lenore J

2016-11-01

Pathologies in the heart-brain axis might, independently or in combination, accelerate the process of brain parenchymal loss. We aimed to investigate the association of serum N-terminal brain natriuretic peptide (NT-proBNP), as a marker of cardiac dysfunction, and carotid intima media thickness (CIMT), as a marker of carotid atherosclerosis burden, with structural brain changes. In the longitudinal population-based AGES-Reykjavik study (Age, Gene/Environment Susceptibility-Reykjavik), we included 2430 subjects (mean age, 74.6 years; 41.4% men) with baseline data on NT-proBNP and CITM (assessed by ultrasound imaging). Participants underwent a high-resolution brain magnetic resonance imaging at baseline and 5 years later to assess total brain (TBV), gray matter, and white matter volumes. Each unit higher log-transformed NT-proBNP was associated with 3.6 mL (95% confidence interval [CI], -6.0 to -1.1) decline in TBV and 3.5 mL (95% CI, -5.7 to -1.3) decline in gray matter volume. Likewise, each millimeter higher CIMT was associated with 10.8 mL (95% CI, -17.3 to -4.2) decline in TBV and 8.6 mL (95% CI, -14.4 to -2.8) decline in gray matter volume. There was no association between NT-proBNP and CIMT and changes in white matter volume. Compared with participants with low NT-proBNP and CIMT, participants with both high NT-proBNP and CIMT had 3.8 mL (95% CI, -6.0 to -1.6) greater decline in their TBV and 4 mL (95% CI, -6.0 to -2.0) greater decline in GMW. These associations were independent of sociodemographic and cardiovascular factors. Older subjects with both cardiac dysfunction and carotid atherosclerosis are at an increased risk for brain parenchymal loss. Accumulated pathologies in the heart-brain axis might accelerate brain atrophy. © 2016 American Heart Association, Inc.

Aging in the Brain: New Roles of Epigenetics in Cognitive Decline.

PubMed

Barter, Jolie D; Foster, Thomas C

2018-06-01

Gene expression in the aging brain depends on transcription signals generated by senescent physiology, interacting with genetic and epigenetic programs. In turn, environmental factors influence epigenetic mechanisms, such that an epigenetic-environmental link may contribute to the accumulation of cellular damage, susceptibility or resilience to stressors, and variability in the trajectory of age-related cognitive decline. Epigenetic mechanisms, DNA methylation and histone modifications, alter chromatin structure and the accessibility of DNA. Furthermore, small non-coding RNA, termed microRNA (miRNA) bind to messenger RNA (mRNA) to regulate translation. In this review, we examine key questions concerning epigenetic mechanisms in regulating the expression of genes associated with brain aging and age-related cognitive decline. In addition, we highlight the interaction of epigenetics with senescent physiology and environmental factors in regulating transcription.

Age-related changes in the ease of dynamical transitions in human brain activity.

PubMed

Ezaki, Takahiro; Sakaki, Michiko; Watanabe, Takamitsu; Masuda, Naoki

2018-06-01

Executive functions, a set of cognitive processes that enable flexible behavioral control, are known to decay with aging. Because such complex mental functions are considered to rely on the dynamic coordination of functionally different neural systems, the age-related decline in executive functions should be underpinned by alteration of large-scale neural dynamics. However, the effects of age on brain dynamics have not been firmly formulated. Here, we investigate such age-related changes in brain dynamics by applying "energy landscape analysis" to publicly available functional magnetic resonance imaging data from healthy younger and older human adults. We quantified the ease of dynamical transitions between different major patterns of brain activity, and estimated it for the default mode network (DMN) and the cingulo-opercular network (CON) separately. We found that the two age groups shared qualitatively the same trajectories of brain dynamics in both the DMN and CON. However, in both of networks, the ease of transitions was significantly smaller in the older than the younger group. Moreover, the ease of transitions was associated with the performance in executive function tasks in a doubly dissociated manner: for the younger adults, the ability of executive functions was mainly correlated with the ease of transitions in the CON, whereas that for the older adults was specifically associated with the ease of transitions in the DMN. These results provide direct biological evidence for age-related changes in macroscopic brain dynamics and suggest that such neural dynamics play key roles when individuals carry out cognitively demanding tasks. © 2018 Wiley Periodicals, Inc.

White matter hyperintensities and imaging patterns of brain ageing in the general population.

PubMed

Habes, Mohamad; Erus, Guray; Toledo, Jon B; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J; Davatzikos, Christos

2016-04-01

White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer's disease in a large populatison-based sample (n = 2367) encompassing a wide age range (20-90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer's disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly (P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer's disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant (P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66.0% of the SPARE

School-Age Child Care Trend Report: Part 2

ERIC Educational Resources Information Center

Neugebauer, Roger

2007-01-01

According to the author, school-age care is the fastest growing segment of the early childhood arena and possibly the least visible. While programs have been serving school-age children in out-of-school hours since the turn of the century, it is only in recent years that professionals have started to view school-age care as a distinct discipline…

Effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients.

PubMed

Hung, Man-Hsin; Liu, Chun-Yu; Shiau, Cheng-Ying; Hsu, Chin-Yi; Tsai, Yi-Fang; Wang, Yu-Ling; Tai, Ling-Chen; King, Kuang-Liang; Chao, Ta-Chung; Chiu, Jen-Hwey; Su, Cheng-Hsi; Lo, Su-Shun; Tzeng, Cheng-Hwai; Shyr, Yi-Ming; Tseng, Ling-Ming

2014-01-01

Brain metastasis is a major complication of breast cancer. This study aimed to analyze the effect of age and biological subtype on the risk and timing of brain metastasis in breast cancer patients. We identified subtypes of invasive ductal carcinoma of the breast by determining estrogen receptor, progesterone receptor and HER2 status. Time to brain metastasis according to age and cancer subtype was analyzed by Cox proportional hazard analysis. Of the 2248 eligible patients, 164 (7.3%) developed brain metastasis over a median follow-up of 54.2 months. Age 35 or younger, HER2-enriched subtype, and triple-negative breast cancer were significant risk factors of brain metastasis. Among patients aged 35 or younger, the risk of brain metastasis was independent of biological subtype (P = 0.507). Among patients aged 36-59 or >60 years, those with triple-negative or HER2-enriched subtypes had consistently increased risk of brain metastasis, as compared with those with luminal A tumors. Patients with luminal B tumors had higher risk of brain metastasis than luminal A only in patients >60 years. Breast cancer subtypes are associated with differing risks of brain metastasis among different age groups. Patients age 35 or younger are particularly at risk of brain metastasis independent of biological subtype.

Brain metabolism in health, aging, and neurodegeneration.

PubMed

Camandola, Simonetta; Mattson, Mark P

2017-06-01

Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.

CircRNAs in the tree shrew (Tupaia belangeri) brain during postnatal development and aging.

PubMed

Lu, CaiXia; Sun, XiaoMei; Li, Na; Wang, WenGuang; Kuang, DeXuan; Tong, PinFen; Han, YuanYuan; Dai, JieJie

2018-04-30

Circular RNAs (circRNAs) are a novel type of non-coding RNA expressed across different species and tissues. At present, little is known about the expression and function of circRNAs in the tree shrew brain. In this study, we used RNA-seq to identify 35,007 circRNAs in hippocampus and cerebellum samples from infant (aged 47-52 days), young (aged 15-18 months), and old (aged 78-86 months) tree shrews. We observed no significant changes in the total circRNA expression profiles in different brain regions over time. However, circRNA tended to be downregulated in the cerebellum over time. Real-time RT-PCR analysis verified the presence of circRNAs. KEGG analysis indicated the occurrence of ubiquitin-mediated proteolysis, the MAPK signaling pathway, phosphatidylinositol signaling system, long-term depression, the rap1 signaling pathway, and long-term potentiation in both brain regions. We also observed that 29,087 (83.1%) tree shrew circRNAs shared homology with human circRNAs. The competing endogenous RNA networks suggested novel_circRNA_007362 potential functions as a 24-miRNAs sponge to regulate UBE4B expression. Thus, we obtained comprehensive circRNA expression profiles in the tree shrew brain during postnatal development and aging, which might help to elucidate the functions of circRNAs during brain aging and in age-related diseases.

Anxiety and the aging brain: stressed out over p53?

PubMed

Scrable, Heidi; Burns-Cusato, Melissa; Medrano, Silvia

2009-12-01

We propose a model in which cell loss in the aging brain is seen as a root cause of behavioral changes that compromise quality of life, including the onset of generalized anxiety disorder, in elderly individuals. According to this model, as stem cells in neurogenic regions of the adult brain lose regenerative capacity, worn-out, dead, or damaged neurons fail to be replaced, leaving gaps in function. As most replacement involves inhibitory interneurons, either directly or indirectly, the net result is the acquisition over time of a hyper-excitable state. The stress axis is subserved by all three neurogenic regions in the adult brain, making it particularly susceptible to these age-dependent changes. We outline a molecular mechanism by which hyper-excitation of the stress axis in turn activates the tumor suppressor p53. This reinforces the loss of stem cell proliferative capacity and interferes with the feedback mechanism by which the glucocorticoid receptor turns off neuroendocrine pathways and resets the axis.

Age differences in the brain mechanisms of good taste.

PubMed

Rolls, Edmund T; Kellerhals, Michele B; Nichols, Thomas E

2015-06-01

There is strong evidence demonstrating age-related differences in the acceptability of foods and beverages. To examine the neural foundations underlying these age-related differences in the acceptability of different flavors and foods, we performed an fMRI study to investigate brain and hedonic responses to orange juice, orange soda, and vegetable juice in three different age groups: Young (22), Middle (40) and Elderly (60 years). Orange juice and orange soda were found to be liked by all age groups, while vegetable juice was disliked by the Young, but liked by the Elderly. In the insular primary taste cortex, the activations to these stimuli were similar in the 3 age groups, indicating that the differences in liking for these stimuli between the 3 groups were not represented in this first stage of cortical taste processing. In the agranular insula (anterior to the insular primary taste cortex) where flavor is represented, the activations to the stimuli were similar in the Elderly, but in the Young the activations were larger to the vegetable juice than to the orange drinks; and the activations here were correlated with the unpleasantness of the stimuli. In the anterior midcingulate cortex, investigated as a site where the activations were correlated with the unpleasantness of the stimuli, there was again a greater activation to the vegetable than to the orange stimuli in the Young but not in the Elderly. In the amygdala (and orbitofrontal cortex), investigated as sites where the activations were correlated with the pleasantness of the stimuli, there was a smaller activation to the vegetable than to the orange stimuli in the Young but not in the Elderly. The Middle group was intermediate with respect to the separation of their activations to the stimuli in the brain areas that represent the pleasantness or unpleasantness of flavors. Thus age differences in the activations to different flavors can in some brain areas be related to, and probably cause, the

Brain white matter structure and information processing speed in healthy older age.

PubMed

Kuznetsova, Ksenia A; Maniega, Susana Muñoz; Ritchie, Stuart J; Cox, Simon R; Storkey, Amos J; Starr, John M; Wardlaw, Joanna M; Deary, Ian J; Bastin, Mark E

2016-07-01

Cognitive decline, especially the slowing of information processing speed, is associated with normal ageing. This decline may be due to brain cortico-cortical disconnection caused by age-related white matter deterioration. We present results from a large, narrow age range cohort of generally healthy, community-dwelling subjects in their seventies who also had their cognitive ability tested in youth (age 11 years). We investigate associations between older age brain white matter structure, several measures of information processing speed and childhood cognitive ability in 581 subjects. Analysis of diffusion tensor MRI data using Tract-based Spatial Statistics (TBSS) showed that all measures of information processing speed, as well as a general speed factor composed from these tests (g speed), were significantly associated with fractional anisotropy (FA) across the white matter skeleton rather than in specific tracts. Cognitive ability measured at age 11 years was not associated with older age white matter FA, except for the g speed-independent components of several individual processing speed tests. These results indicate that quicker and more efficient information processing requires global connectivity in older age, and that associations between white matter FA and information processing speed (both individual test scores and g speed), unlike some other aspects of later life brain structure, are generally not accounted for by cognitive ability measured in youth.

White matter hyperintensities and imaging patterns of brain ageing in the general population

PubMed Central

Erus, Guray; Toledo, Jon B.; Zhang, Tianhao; Bryan, Nick; Launer, Lenore J.; Rosseel, Yves; Janowitz, Deborah; Doshi, Jimit; Van der Auwera, Sandra; von Sarnowski, Bettina; Hegenscheid, Katrin; Hosten, Norbert; Homuth, Georg; Völzke, Henry; Schminke, Ulf; Hoffmann, Wolfgang; Grabe, Hans J.; Davatzikos, Christos

2016-01-01

Abstract White matter hyperintensities are associated with increased risk of dementia and cognitive decline. The current study investigates the relationship between white matter hyperintensities burden and patterns of brain atrophy associated with brain ageing and Alzheimer’s disease in a large populatison-based sample ( n = 2367) encompassing a wide age range (20–90 years), from the Study of Health in Pomerania. We quantified white matter hyperintensities using automated segmentation and summarized atrophy patterns using machine learning methods resulting in two indices: the SPARE-BA index (capturing age-related brain atrophy), and the SPARE-AD index (previously developed to capture patterns of atrophy found in patients with Alzheimer’s disease). A characteristic pattern of age-related accumulation of white matter hyperintensities in both periventricular and deep white matter areas was found. Individuals with high white matter hyperintensities burden showed significantly ( P < 0.0001) lower SPARE-BA and higher SPARE-AD values compared to those with low white matter hyperintensities burden, indicating that the former had more patterns of atrophy in brain regions typically affected by ageing and Alzheimer’s disease dementia. To investigate a possibly causal role of white matter hyperintensities, structural equation modelling was used to quantify the effect of Framingham cardiovascular disease risk score and white matter hyperintensities burden on SPARE-BA, revealing a statistically significant ( P < 0.0001) causal relationship between them. Structural equation modelling showed that the age effect on SPARE-BA was mediated by white matter hyperintensities and cardiovascular risk score each explaining 10.4% and 21.6% of the variance, respectively. The direct age effect explained 70.2% of the SPARE-BA variance. Only white matter hyperintensities significantly mediated the age effect on SPARE-AD explaining 32.8% of the variance. The direct age effect explained 66

DNA methylation age is not accelerated in brain or blood of subjects with schizophrenia.

PubMed

McKinney, Brandon C; Lin, Huang; Ding, Ying; Lewis, David A; Sweet, Robert A

2017-10-05

Individuals with schizophrenia (SZ) exhibit multiple premature age-related phenotypes and die ~20years prematurely. The accelerated aging hypothesis of SZ has been advanced to explain these observations, it posits that SZ-associated factors accelerate the progressive biological changes associated with normal aging. Testing the hypothesis has been limited by the absence of robust, meaningful, and multi-tissue measures of biological age. Recently, a method was described in which DNA methylation (DNAm) levels at 353 genomic sites are used to produce "DNAm age", an estimate of biological age with advantages over existing measures. We used this method and 3 publicly-available DNAm datasets, 1 from brain and 2 from blood, to test the hypothesis. The brain dataset was composed of data from the dorsolateral prefrontal cortex of 232 non-psychiatric control (NPC) and 195 SZ subjects. Blood dataset #1 was composed of data from whole blood of 304 NPC and 332 SZ subjects, and blood dataset #2 was composed of data from whole blood of 405 NPC and 260 SZ subjects. DNAm age and chronological age correlated strongly (r=0.92-0.95, p<0.0001) in both NPC and SZ subjects in all 3 datasets. DNAm age acceleration did not differ between NPC and SZ subjects in the brain dataset (t=0.52, p=0.60), blood dataset #1 (t=1.51, p=0.13), or blood dataset #2 (t=0.93, p=0.35). Consistent with our previous findings from a smaller study of postmortem brains, our findings suggest there is no acceleration of brain or blood aging in SZ and, thus, do not support the accelerated aging hypothesis of SZ. Copyright © 2017 Elsevier B.V. All rights reserved.

Bayesian Optimization for Neuroimaging Pre-processing in Brain Age Classification and Prediction

PubMed Central

Lancaster, Jenessa; Lorenz, Romy; Leech, Rob; Cole, James H.

2018-01-01

Neuroimaging-based age prediction using machine learning is proposed as a biomarker of brain aging, relating to cognitive performance, health outcomes and progression of neurodegenerative disease. However, even leading age-prediction algorithms contain measurement error, motivating efforts to improve experimental pipelines. T1-weighted MRI is commonly used for age prediction, and the pre-processing of these scans involves normalization to a common template and resampling to a common voxel size, followed by spatial smoothing. Resampling parameters are often selected arbitrarily. Here, we sought to improve brain-age prediction accuracy by optimizing resampling parameters using Bayesian optimization. Using data on N = 2003 healthy individuals (aged 16–90 years) we trained support vector machines to (i) distinguish between young (<22 years) and old (>50 years) brains (classification) and (ii) predict chronological age (regression). We also evaluated generalisability of the age-regression model to an independent dataset (CamCAN, N = 648, aged 18–88 years). Bayesian optimization was used to identify optimal voxel size and smoothing kernel size for each task. This procedure adaptively samples the parameter space to evaluate accuracy across a range of possible parameters, using independent sub-samples to iteratively assess different parameter combinations to arrive at optimal values. When distinguishing between young and old brains a classification accuracy of 88.1% was achieved, (optimal voxel size = 11.5 mm3, smoothing kernel = 2.3 mm). For predicting chronological age, a mean absolute error (MAE) of 5.08 years was achieved, (optimal voxel size = 3.73 mm3, smoothing kernel = 3.68 mm). This was compared to performance using default values of 1.5 mm3 and 4mm respectively, resulting in MAE = 5.48 years, though this 7.3% improvement was not statistically significant. When assessing generalisability, best performance was achieved when applying the entire Bayesian

Sex differences in normal age trajectories of functional brain networks.

PubMed

Scheinost, Dustin; Finn, Emily S; Tokoglu, Fuyuze; Shen, Xilin; Papademetris, Xenophon; Hampson, Michelle; Constable, R Todd

2015-04-01

Resting-state functional magnetic resonance image (rs-fMRI) is increasingly used to study functional brain networks. Nevertheless, variability in these networks due to factors such as sex and aging is not fully understood. This study explored sex differences in normal age trajectories of resting-state networks (RSNs) using a novel voxel-wise measure of functional connectivity, the intrinsic connectivity distribution (ICD). Males and females showed differential patterns of changing connectivity in large-scale RSNs during normal aging from early adulthood to late middle-age. In some networks, such as the default-mode network, males and females both showed decreases in connectivity with age, albeit at different rates. In other networks, such as the fronto-parietal network, males and females showed divergent connectivity trajectories with age. Main effects of sex and age were found in many of the same regions showing sex-related differences in aging. Finally, these sex differences in aging trajectories were robust to choice of preprocessing strategy, such as global signal regression. Our findings resolve some discrepancies in the literature, especially with respect to the trajectory of connectivity in the default mode, which can be explained by our observed interactions between sex and aging. Overall, results indicate that RSNs show different aging trajectories for males and females. Characterizing effects of sex and age on RSNs are critical first steps in understanding the functional organization of the human brain. © 2014 Wiley Periodicals, Inc.

Sex differences in metabolic aging of the brain: insights into female susceptibility to Alzheimer's disease.

PubMed

Zhao, Liqin; Mao, Zisu; Woody, Sarah K; Brinton, Roberta D

2016-06-01

Despite recent advances in the understanding of clinical aspects of sex differences in Alzheimer's disease (AD), the underlying mechanisms, for instance, how sex modifies AD risk and why the female brain is more susceptible to AD, are not clear. The purpose of this study is to elucidate sex disparities in brain aging profiles focusing on 2 major areas-energy and amyloid metabolism-that are most significantly affected in preclinical development of AD. Total RNA isolated from hippocampal tissues of both female and male 129/C57BL/6 mice at ages of 6, 9, 12, or 15 months were comparatively analyzed by custom-designed Taqman low-density arrays for quantitative real-time polymerase chain reaction detection of a total of 182 genes involved in a broad spectrum of biological processes modulating energy production and amyloid homeostasis. Gene expression profiles revealed substantial differences in the trajectory of aging changes between female and male brains. In female brains, 44.2% of genes were significantly changed from 6 months to 9 months and two-thirds showed downregulation. In contrast, in male brains, only 5.4% of genes were significantly altered at this age transition. Subsequent changes in female brains were at a much smaller magnitude, including 10.9% from 9 months to 12 months and 6.1% from 12 months to 15 months. In male brains, most changes occurred from 12 months to 15 months and the majority were upregulated. Furthermore, gene network analysis revealed that clusterin appeared to serve as a link between the overall decreased bioenergetic metabolism and increased amyloid dyshomeostasis associated with the earliest transition in female brains. Together, results from this study indicate that: (1) female and male brains follow profoundly dissimilar trajectories as they age; (2) female brains undergo age-related changes much earlier than male brains; (3) early changes in female brains signal the onset of a hypometabolic phenotype at risk for AD. These

Aging leads to altered microglial function that reduces brain resiliency increasing vulnerability to neurodegenerative diseases.

PubMed

Bickford, Paula C; Flowers, Antwoine; Grimmig, Bethany

2017-08-01

Aging is the primary risk factor for many neurodegenerative diseases. Thus, understanding the basic biological changes that take place with aging that lead to the brain being less resilient to disease progression of neurodegenerative diseases such as Parkinson's disease or Alzheimer's disease or insults to the brain such as stroke or traumatic brain injuries. Clearly this will not cure the disease per se, yet increasing the ability of the brain to respond to injury could improve long term outcomes. The focus of this review is examining changes in microglia with age and possible therapeutic interventions involving the use of polyphenol rich dietary supplements. Published by Elsevier Inc.

Seating in aged care: Physical fit, independence and comfort

PubMed Central

Brophy, Claire; O’Reilly, Maria

2018-01-01

Objectives: This research was intended to provide a greater understanding of the context and needs of aged care seating, specifically: To conduct an audit of typical chairs used in aged care facilities; To collect data about resident and staff experiences and behaviour around chairs in order to gain a deeper understanding of the exact issues that residents and staff have with the chairs they use at aged care facilities; To identify positive and negative issues influencing use of chairs in aged care facilities; To deliver evidence-based recommendations for the design of chairs for aged care facilities. Methods: Methods included a chair dimension audit, interviews with residents, experts and carers and observations of aged care residents getting into chairs, sitting in them and getting out. Results: Results showed that residents, experts and carers all prefer chairs which are above the recommended height for older people so that they will be able to get out of them more easily. Armrests were essential for ease of entry and egress. However, many residents struggled with chairs which were also too deep in the seat pan so that they could not easily touch the floor or sit comfortably and were forced to slump. Most residents used cushions and pillows to relieve discomfort where possible. Conclusion: The implications of these issues for chair design and selection are discussed. Variable height chairs, a range of chairs of different heights in each space and footrests could all address the height problem. Chair designers need to address the seat depth problem by reducing depth in most aged care specific chairs, even when they are higher. Armrests must be provided but could be made easier to grip. Addressing these issues would increase access to comfortable yet easy-to-use chairs for a wider range of the aged care population. PMID:29326817

[Long-term care of Parkinson patients with deep brain stimulation].

PubMed

Allert, N; Barbe, M T; Timmermann, L; Coenen, V A

2011-12-01

For more than 15 years deep brain stimulation of the subthalamic nucleus and globus pallidus internus have become therapeutic options in advanced Parkinson's disease. The number of patients with long-term treatment is increasing steadily. This review focuses on issues of the long-term care of these Parkinson's patients, including differences of the available deep brain stimulation systems, recommendations for follow-up examinations, implications for medical diagnostics and therapies and an algorithm for symptom deterioration. Today, there is no profound evidence that deep brain stimulation prevents disease progression. However, symptomatic relief from motor symptoms is maintained during long-term follow-up and interruption of the therapy remains an exception. © Georg Thieme Verlag KG Stuttgart · New York.

Implementing Information and Communication Technology to Support Community Aged Care Service Integration: Lessons from an Australian Aged Care Provider

PubMed Central

Georgiou, Andrew; Tariq, Amina; Prgomet, Mirela; Warland, Andrew; Armour, Pauline; Westbrook, Johanna I

2017-01-01

Introduction: There is limited evidence of the benefits of information and communication technology (ICT) to support integrated aged care services. Objectives: We undertook a case study to describe carelink+, a centralised client service management ICT system implemented by a large aged and community care service provider, Uniting. We sought to explicate the care-related information exchange processes associated with carelink+ and identify lessons for organisations attempting to use ICT to support service integration. Methods: Our case study included seventeen interviews and eleven observation sessions with a purposive sample of staff within the organisation. Inductive analysis was used to develop a model of ICT-supported information exchange. Results: Management staff described the integrated care model designed to underpin carelink+. Frontline staff described complex information exchange processes supporting coordination of client services. Mismatches between the data quality and the functions carelink+ was designed to support necessitated the evolution of new work processes associated with the system. Conclusions: There is value in explicitly modelling the work processes that emerge as a consequence of ICT. Continuous evaluation of the match between ICT and work processes will help aged care organisations to achieve higher levels of ICT maturity that support their efforts to provide integrated care to clients. PMID:29042851

Caloric restriction increases ketone bodies metabolism and preserves blood flow in aging brain.

PubMed

Lin, Ai-Ling; Zhang, Wei; Gao, Xiaoli; Watts, Lora

2015-07-01

Caloric restriction (CR) has been shown to increase the life span and health span of a broad range of species. However, CR effects on in vivo brain functions are far from explored. In this study, we used multimetric neuroimaging methods to characterize the CR-induced changes of brain metabolic and vascular functions in aging rats. We found that old rats (24 months of age) with CR diet had reduced glucose uptake and lactate concentration, but increased ketone bodies level, compared with the age-matched and young (5 months of age) controls. The shifted metabolism was associated with preserved vascular function: old CR rats also had maintained cerebral blood flow relative to the age-matched controls. When investigating the metabolites in mitochondrial tricarboxylic acid cycle, we found that citrate and α-ketoglutarate were preserved in the old CR rats. We suggest that CR is neuroprotective; ketone bodies, cerebral blood flow, and α-ketoglutarate may play important roles in preserving brain physiology in aging. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Age-related reduction of adaptive brain response during semantic integration is associated with gray matter reduction.

PubMed

Zhu, Zude; Yang, Fengjun; Li, Dongning; Zhou, Lianjun; Liu, Ying; Zhang, Ying; Chen, Xuezhi

2017-01-01

While aging is associated with increased knowledge, it is also associated with decreased semantic integration. To investigate brain activation changes during semantic integration, a sample of forty-eight 25-75 year-old adults read sentences with high cloze (HC) and low cloze (LC) probability while functional magnetic resonance imaging was conducted. Significant age-related reduction of cloze effect (LC vs. HC) was found in several regions, especially the left middle frontal gyrus (MFG) and right inferior frontal gyrus (IFG), which play an important role in semantic integration. Moreover, when accounting for global gray matter volume reduction, the age-cloze correlation in the left MFG and right IFG was absent. The results suggest that brain structural atrophy may disrupt brain response in aging brains, which then show less brain engagement in semantic integration.

A Culture-Brain Link: Negative Age Stereotypes Predict Alzheimer’s-disease Biomarkers

PubMed Central

Levy, Becca R.; Ferrucci, Luigi; Zonderman, Alan B.; Slade, Martin D.; Troncoso, Juan; Resnick, Susan M.

2016-01-01

Although negative age stereotypes have been found to predict adverse outcomes among older individuals, it was unknown whether the influence of stereotypes extends to brain changes associated with Alzheimer’s disease. To consider this possibility, we drew on the age stereotypes of dementia-free participants in the Baltimore Longitudinal Study of Aging that had been measured decades before yearly MRIs and brain autopsies were performed. Those with more negative age stereotypes earlier in life had significantly steeper hippocampal-volume loss, and significantly greater accumulation of neurofibrillary tangles and amyloid plaques at autopsy, adjusting for relevant covariates. These findings suggest a new pathway to identifying mechanisms and potential interventions related to the neuropathology of Alzheimer’s disease. PMID:26641877

Impairment of paravascular clearance pathways in the aging brain

PubMed Central

Kress, Benjamin T.; Iliff, Jeffrey J.; Xia, Maosheng; Wang, Minghuan; Wei, Helen; Zeppenfeld, Douglas; Xie, Lulu; Kang, Hongyi; Xu, Qiwu; Liew, Jason; Plog, Benjamin A.; Ding, Fengfei; Deane, Rashid; Nedergaard, Maiken

2014-01-01

Objective In the brain, protein waste removal is partly performed by paravascular pathways that facilitate convective exchange of water and soluble contents between cerebrospinal and interstitial fluids. Several lines of evidence suggest that bulk flow drainage via the glymphatic system is driven by cerebrovascular pulsation, and is dependent on astroglial water channels that line paravascular cerebrospinal fluid (CSF) pathways. The Objective of this study was to evaluate whether the efficiency of CSF-ISF exchange and interstitial solute clearance is impaired in the aging brain. Methods CSF-ISF exchange was evaluated by in vivo and ex vivo fluorescence microscopy while interstitial solute clearance was evaluated by radio-tracer clearance assays in young (2–3 month), middle age (10–12 month) and old (18–20 month) wild type mice. The relationship between age-related changes in the expression of the astrocytic water channel aquaporin-4 (AQP4) and changes in glymphatic pathway function were evaluated by immunofluorescence. Results Advancing age was associated with a dramatic decline in the efficiency of exchange between the subarachnoid CSF and the brain parenchyma. Relative to the young, clearance of intraparechamally injected amyloid β was impaired by 40% in the old mice. A 27% reduction in the vessel wall pulsatility of intracortical arterioles and widespread loss of perivascular AQP4 polarization along the penetrating arteries accompanied the decline in CSF-ISF exchange. Interpretation We propose that impaired glymphatic clearance contributes to cognitive decline among the elderly and may represent a novel therapeutic target for the treatment of neurodegenerative diseases associated with accumulation of mis-folded protein aggregates. PMID:25204284

Functional brain imaging of episodic memory decline in ageing.

PubMed

Nyberg, L

2017-01-01

The episodic long-term memory system supports remembering of events. It is considered to be the most age-sensitive system, with an average onset of decline around 60 years of age. However, there is marked interindividual variability, such that some individuals show faster than average change and others show no or very little change. This variability may be related to the risk of developing dementia, with elevated risk for individuals with accelerated episodic memory decline. Brain imaging with functional magnetic resonance imaging (MRI) of blood oxygen level-dependent (BOLD) signalling or positron emission tomography (PET) has been used to reveal the brain bases of declining episodic memory in ageing. Several studies have demonstrated a link between age-related episodic memory decline and the hippocampus during active mnemonic processing, which is further supported by studies of hippocampal functional connectivity in the resting state. The hippocampus interacts with anterior and posterior neocortical regions to support episodic memory, and alterations in hippocampus-neocortex connectivity have been shown to contribute to impaired episodic memory. Multimodal MRI studies and more recently hybrid MRI/PET studies allow consideration of various factors that can influence the association between the hippocampal BOLD signal and memory performance. These include neurovascular factors, grey and white matter structural alterations, dopaminergic neurotransmission, amyloid-Β and glucose metabolism. Knowledge about the brain bases of episodic memory decline can guide interventions to strengthen memory in older adults, particularly in those with an elevated risk of developing dementia, with promising results for combinations of cognitive and physical stimulation. © 2016 The Association for the Publication of the Journal of Internal Medicine.

Age-dependent association of thyroid function with brain morphology and microstructural organization: evidence from brain imaging.

PubMed

Chaker, Layal; Cremers, Lotte G M; Korevaar, Tim I M; de Groot, Marius; Dehghan, Abbas; Franco, Oscar H; Niessen, Wiro J; Ikram, M Arfan; Peeters, Robin P; Vernooij, Meike W

2018-01-01

Thyroid hormone (TH) is crucial during neurodevelopment, but high levels of TH have been linked to neurodegenerative disorders. No data on the association of thyroid function with brain imaging in the general population are available. We therefore investigated the association of thyroid-stimulating hormone and free thyroxine (FT4) with magnetic resonance imaging (MRI)-derived total intracranial volume, brain tissue volumes, and diffusion tensor imaging measures of white matter microstructure in 4683 dementia- and stroke-free participants (mean age 60.2, range 45.6-89.9 years). Higher FT4 levels were associated with larger total intracranial volumes (β = 6.73 mL, 95% confidence interval = 2.94-9.80). Higher FT4 levels were also associated with larger total brain and white matter volumes in younger individuals, but with smaller total brain and white matter volume in older individuals (p-interaction 0.02). There was a similar interaction by age for the association of FT4 with mean diffusivity on diffusion tensor imaging (p-interaction 0.026). These results are in line with differential effects of TH during neurodevelopmental and neurodegenerative processes and can improve the understanding of the role of thyroid function in neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

Linking brain imaging and genomics in the study of Alzheimer's disease and aging.

PubMed

Reiman, Eric M

2007-02-01

My colleagues and I have been using positron emission tomography (PET) and magnetic resonance imaging (MRI) to detect and track the brain changes associated with Alzheimer's disease (AD) and normal brain aging in cognitively normal persons with two copies, one copy, and no copies of the apolipoprotein E (APOE) epsilon4 allele, a common AD susceptibility gene. In this review article, I consider how brain imaging techniques could be used to evaluate putative AD prevention therapies in cognitively normal APOE epsilon4 carriers and putative age-modifying therapies in cognitively normal APOE epsilon4 noncarriers, how they could help investigate the individual and aggregate effects of putative AD risk modifiers, and how they could help guide the investigation of a molecular mechanism associated with AD vulnerability and normal neurological aging. I suggest how high-resolution genome-wide genetic and transcriptomic studies could further help in the scientific understanding of AD, aging, and other common and genetically complex phenotypes, such as variation in normal human memory performance, and in the discovery and evaluation of promising treatments for these phenotypes. Finally, I illustrate the push-pull relationship between brain imaging, genomics research, and other neuroscientific research in the study of AD and aging.

Fluid intelligence and brain functional organization in aging yoga and meditation practitioners

PubMed Central

Gard, Tim; Taquet, Maxime; Dixit, Rohan; Hölzel, Britta K.; de Montjoye, Yves-Alexandre; Brach, Narayan; Salat, David H.; Dickerson, Bradford C.; Gray, Jeremy R.; Lazar, Sara W.

2014-01-01

Numerous studies have documented the normal age-related decline of neural structure, function, and cognitive performance. Preliminary evidence suggests that meditation may reduce decline in specific cognitive domains and in brain structure. Here we extended this research by investigating the relation between age and fluid intelligence and resting state brain functional network architecture using graph theory, in middle-aged yoga and meditation practitioners, and matched controls. Fluid intelligence declined slower in yoga practitioners and meditators combined than in controls. Resting state functional networks of yoga practitioners and meditators combined were more integrated and more resilient to damage than those of controls. Furthermore, mindfulness was positively correlated with fluid intelligence, resilience, and global network efficiency. These findings reveal the possibility to increase resilience and to slow the decline of fluid intelligence and brain functional architecture and suggest that mindfulness plays a mechanistic role in this preservation. PMID:24795629

Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus

PubMed Central

Braidy, Nady; Poljak, Anne; Marjo, Chris; Rutlidge, Helen; Rich, Anne; Jugder, Bat-Erdene; Jayasena, Tharusha; Inestrosa, Nibaldo C.; Sachdev, Perminder S.

2017-01-01

The accumulation of redox-active transition metals in the brain and metal dyshomeostasis are thought to be associated with the etiology and pathogenesis of several neurodegenerative diseases, and Alzheimer’s disease (AD) in particular. As well, distinct biometal imaging and role of metal uptake transporters are central to understanding AD pathogenesis and aging but remain elusive, due inappropriate detection methods. We therefore hypothesized that Octodon degus develop neuropathological abnormalities in the distribution of redox active biometals, and this effect may be due to alterations in the expression of lysosomal protein, major Fe/Cu transporters, and selected Zn transporters (ZnTs and ZIPs). Herein, we report the distribution profile of biometals in the aged brain of the endemic Chilean rodent O. degus—a natural model to investigate the role of metals on the onset and progression of AD. Using laser ablation inductively coupled plasma mass spectrometry, our quantitative images of biometals (Fe, Ca, Zn, Cu, and Al) appear significantly elevated in the aged O. degus and show an age-dependent rise. The metals Fe, Ca, Zn, and Cu were specifically enriched in the cortex and hippocampus, which are the regions where amyloid plaques, tau phosphorylation and glial alterations are most commonly reported, whilst Al was enriched in the hippocampus alone. Using whole brain extracts, age-related deregulation of metal trafficking pathways was also observed in O. degus. More specifically, we observed impaired lysosomal function, demonstrated by increased cathepsin D protein expression. An age-related reduction in the expression of subunit B2 of V-ATPase, and significant increases in amyloid beta peptide 42 (Aβ42), and the metal transporter ATP13a2 were also observed. Although the protein expression levels of the zinc transporters, ZnT (1,3,4,6, and 7), and ZIP7,8 and ZIP14 increased in the brain of aged O. degus, ZnT10, decreased. Although no significant age

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

PubMed

Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P; Strosznajder, Joanna B

2017-03-01

Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD + levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD + -dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

Brain morphology in school-aged children with prenatal opioid exposure: A structural MRI study.

PubMed

Sirnes, Eivind; Oltedal, Leif; Bartsch, Hauke; Eide, Geir Egil; Elgen, Irene B; Aukland, Stein Magnus

Both animal and human studies have suggested that prenatal opioid exposure may be detrimental to the developing fetal brain. However, results are somewhat conflicting. Structural brain changes in children with prenatal opioid exposure have been reported in a few studies, and such changes may contribute to neuropsychological impairments observed in exposed children. To investigate the association between prenatal opioid exposure and brain morphology in school-aged children. A cross-sectional magnetic resonance imaging (MRI) study of prenatally opioid-exposed children and matched controls. A hospital-based sample (n=16) of children aged 10-14years with prenatal exposure to opioids and 1:1 sex- and age-matched unexposed controls. Automated brain volume measures obtained from T1-weighted MRI scans using FreeSurfer. Volumes of the basal ganglia, thalamus, and cerebellar white matter were reduced in the opioid-exposed group, whereas there were no statistically significant differences in global brain measures (total brain, cerebral cortex, and cerebral white matter volumes). In line with the limited findings reported in the literature to date, our study showed an association between prenatal opioid exposure and reduced regional brain volumes. Adverse effects of opioids on the developing fetal brain may explain this association. However, further research is needed to explore the causal nature and functional consequences of these findings. Copyright © 2017 Elsevier B.V. All rights reserved.

Real-Time fMRI in Neuroscience Research and Its Use in Studying the Aging Brain

PubMed Central

Rana, Mohit; Varan, Andrew Q.; Davoudi, Anis; Cohen, Ronald A.; Sitaram, Ranganatha; Ebner, Natalie C.

2016-01-01

Cognitive decline is a major concern in the aging population. It is normative to experience some deterioration in cognitive abilities with advanced age such as related to memory performance, attention distraction to interference, task switching, and processing speed. However, intact cognitive functioning in old age is important for leading an independent day-to-day life. Thus, studying ways to counteract or delay the onset of cognitive decline in aging is crucial. The literature offers various explanations for the decline in cognitive performance in aging; among those are age-related gray and white matter atrophy, synaptic degeneration, blood flow reduction, neurochemical alterations, and change in connectivity patterns with advanced age. An emerging literature on neurofeedback and Brain Computer Interface (BCI) reports exciting results supporting the benefits of volitional modulation of brain activity on cognition and behavior. Neurofeedback studies based on real-time functional magnetic resonance imaging (rtfMRI) have shown behavioral changes in schizophrenia and behavioral benefits in nicotine addiction. This article integrates research on cognitive and brain aging with evidence of brain and behavioral modification due to rtfMRI neurofeedback. We offer a state-of-the-art description of the rtfMRI technique with an eye towards its application in aging. We present preliminary results of a feasibility study exploring the possibility of using rtfMRI to train older adults to volitionally control brain activity. Based on these first findings, we discuss possible implementations of rtfMRI neurofeedback as a novel technique to study and alleviate cognitive decline in healthy and pathological aging. PMID:27803662

Upregulation of Aβ42 in the Brain and Bodily Fluids of Rhesus Monkeys with Aging.

PubMed

Zhao, Qiao; Lu, Jing; Yao, Zitong; Wang, Shubo; Zhu, Liming; Wang, Ju; Chen, Baian

2017-01-01

The cerebral accumulation of amyloid beta (Aβ) is one of the key pathological hallmarks of Alzheimer's disease (AD). Aβ is also found in bodily fluids such as the cerebrospinal fluid (CSF) and plasma. However, the significance of Aβ accumulation in the brain and different bodily pools, as well as its correlation with aging and cerebral amyloid pathology, is not completely understood. To better understand this question, we selected the rhesus monkey, which is phylogenetically and physiologically highly similar to the human, as a model to study. We quantified the levels of the two main Aβ isoforms (Aβ42 and Aβ40) in different sections of the brain (frontal cortex, temporal cortex, and hippocampus) and bodily fluids (CSF and plasma) of rhesus monkeys at different developmental phases (young, 5-9 years of age; mature, 10-19 years of age; and old, 21-24 years of age). We found that the levels of neuronal and insoluble Aβ42 increased significantly in the brain with aging, suggesting that this specific isoform might be directly involved in aging and AD-like pathophysiology. There was no significant change in the Aβ40 level in the brain with aging. In addition, the Aβ42 level, but not the Aβ40 level, in both the CSF and plasma increased with aging. We also identified a positive correlation between Aβ42 in the CSF and plasma and Aβ42 in the brain. Taken collectively, our results indicate that there is an association between Aβ accumulation and age. These results support the increased incidence of AD with aging.

Differences between chronological and brain age are related to education and self-reported physical activity.

PubMed

Steffener, Jason; Habeck, Christian; O'Shea, Deirdre; Razlighi, Qolamreza; Bherer, Louis; Stern, Yaakov

2016-04-01

This study investigated the relationship between education and physical activity and the difference between a physiological prediction of age and chronological age (CA). Cortical and subcortical gray matter regional volumes were calculated from 331 healthy adults (range: 19-79 years). Multivariate analyses identified a covariance pattern of brain volumes best predicting CA (R(2) = 47%). Individual expression of this brain pattern served as a physiologic measure of brain age (BA). The difference between CA and BA was predicted by education and self-report measures of physical activity. Education and the daily number of flights of stairs climbed (FOSC) were the only 2 significant predictors of decreased BA. Effect sizes demonstrated that BA decreased by 0.95 years for each year of education and by 0.58 years for 1 additional FOSC daily. Effects of education and FOSC on regional brain volume were largely driven by temporal and subcortical volumes. These results demonstrate that higher levels of education and daily FOSC are related to larger brain volume than predicted by CA which supports the utility of regional gray matter volume as a biomarker of healthy brain aging. Copyright © 2016 Elsevier Inc. All rights reserved.

Patients' experiences and care needs during the diagnostic phase of an Integrated Brain Cancer Pathway: A Case Study.

PubMed

Vedelø, Tina Wang; Sørensen, Jens Christian Hedemann; Delmar, Charlotte

2018-03-31

To identify and describe patients' experiences and care needs throughout the diagnostic phase of an Integrated Brain Cancer Pathway. A malignant brain tumour is a devastating diagnosis, which may cause psychical symptoms and cognitive deficits. Studies have shown that the shock of the diagnosis, combined with the multiple symptoms, affect patients' ability to understand information and express needs of care and support. Unmet needs have been reported within this group of patients, however, the experiences and care needs of patients going through the diagnostic phase of a standardised Integrated Brain Cancer Pathway have not previously been explored. A Case Study design was used to provide detailed information of the complex needs of patients being diagnosed with a malignant brain tumour. Research interviews and direct participant observation of four patients during hospital admission, brain surgery and discharge were conducted in a Danish university hospital. Systematic text condensation was used to analyse the data material. Four major themes were identified: information needs, balancing hope and reality while trying to perceive the unknown reality of brain cancer, not knowing what to expect and participants' perceptions of the relationship with the health care providers. The analysis revealed that participants were in risk of having unmet information needs and that contextual factors seemed to cause fragmented care that led to feelings of uncertainty and loss of control. Brain tumour patients have complex care needs and experience a particular state of vulnerability during the diagnostic phase. Through personal relationships based on trust with skilled health care providers, participants experienced an existential recognition and alleviation of emotional distress. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Age-related variation in primary care-type presentations to emergency departments.

PubMed

Freed, Gary; Gafforini, Sarah; Carson, Norman

2015-08-01

A significant amount of attention has been paid to the increase in emergency department (ED) presentations in Australia. Questions have arisen regarding whether all of those presenting to the ED are actually in need of true emergency services. Under-standing the characteristics of those patients who may be cared for in non-emergency settings is important for future health system strategies. The aim of this study was to identify age-related variation in primary care type emergency department (ED) presentations over time. A secondary analysis of data from the Victorian emergency minimum dataset (VEMD) between 2002-13 was conducted. The main outcomes were patterns of primary care type ED presentations for different ages groups over time, age-specific patterns of specific primary care type exclusion criteria and primary care type ED presentations by residents from aged care facilities. The proportion of triage category 4 or 5 ED presentations that met the criteria for a primary care type visit was greatest in the 0-4-year age group and tended to decrease as the age of the patient increased. Triage category 4 or 5 presentation by ambulance was uncommon in the younger age groups, surpassed 10% in the 50-54-year age group, and was >70% for those aged >90 years. The greater proportion of residential aged care facility patients who arrived by ambulance resulted in a much smaller proportion of primary care type visits. There are marked differences by age in the proportion of triage category 4 or 5 ED presentations that met the criteria for primary care type visits. These results indicate it was primarily younger patients who presented to the ED with non-urgent conditions. Most might be able to safely receive care in a primary care setting.

Spatiotemporal Dependency of Age-Related Changes in Brain Signal Variability

PubMed Central

McIntosh, A. R.; Vakorin, V.; Kovacevic, N.; Wang, H.; Diaconescu, A.; Protzner, A. B.

2014-01-01

Recent theoretical and empirical work has focused on the variability of network dynamics in maturation. Such variability seems to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into healthy aging. Two different data sets, one EEG (total n = 48, ages 18–72) and one magnetoencephalography (n = 31, ages 20–75) were analyzed for such spatiotemporal dependency using multiscale entropy (MSE) from regional brain sources. In both data sets, the changes in MSE were timescale dependent, with higher entropy at fine scales and lower at more coarse scales with greater age. The signals were parsed further into local entropy, related to information processed within a regional source, and distributed entropy (information shared between two sources, i.e., functional connectivity). Local entropy increased for most regions, whereas the dominant change in distributed entropy was age-related reductions across hemispheres. These data further the understanding of changes in brain signal variability across the lifespan, suggesting an inverted U-shaped curve, but with an important qualifier. Unlike earlier in maturation, where the changes are more widespread, changes in adulthood show strong spatiotemporal dependence. PMID:23395850

Patients With Brain Tumors: Who Receives Postacute Occupational Therapy Services?

PubMed

Chan, Vincy; Xiong, Chen; Colantonio, Angela

2015-01-01

Data on the utilization of occupational therapy among patients with brain tumors have been limited to those with malignant tumors and small samples of patients outside North America in specialized palliative care settings. We built on this research by examining the characteristics of patients with brain tumors who received postacute occupational therapy services in Ontario, Canada, using health care administrative data. Between fiscal years 2004-2005 and 2008-2009, 3,199 patients with brain tumors received occupational therapy services in the home care setting after hospital discharge; 12.4% had benign brain tumors, 78.2% had malignant brain tumors, and 9.4% had unspecified brain tumors. However, patients with benign brain tumors were older (mean age=63.3 yr), and a higher percentage were female (65.2%). More than 90% of patients received in-home occupational therapy services. Additional research is needed to examine the significance of these differences and to identify factors that influence access to occupational therapy services in the home care setting. Copyright © 2015 by the American Occupational Therapy Association, Inc.

Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

PubMed

Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

2016-01-01

As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Predictors of informal care burden 1 year after a severe traumatic brain injury: results from the PariS-TBI study.

PubMed

Bayen, Eleonore; Pradat-Diehl, Pascale; Jourdan, Claire; Ghout, Idir; Bosserelle, Vanessa; Azerad, Sylvie; Weiss, Jean-Jacques; Joël, Marie-Eve; Aegerter, Philippe; Azouvi, Philippe

2013-01-01

To investigate predictors of informal care burden 1 year after a severe traumatic brain injury (TBI). Patients (N = 66) aged 15 years or older with severe TBI (Glasgow Coma Scale score of 8 or less) and their primary informal caregivers. Multicenter inception cohort study over 22 months in Paris and the surrounding area (PariS-TBI study). Patients' preinjury characteristics; injury severity data; outcome measures at discharge from intensive care and 1 year after the injury; Dysexecutive Questionnaire; Medical Outcome Study Short Form-36; Zarit Burden Inventory. Among the 257 survivors at discharge from acute care, 66 patient-caregiver couples were included. Primary informal caregivers were predominantly women (73%), of middle age (age, 50 years), supporting male patients (79%), of mean age of 38 years. The majority (56%) of caregivers experienced significant burden, and 44% were at risk of depression. Caregivers' impaired health status and perceived burden significantly correlated with patients' global disability (as assessed with the Glasgow Outcome Scale-Extended) and impairments of executive functions (as assessed with the Dysexecutive Questionnaire). A focused principal component analysis suggested that disability and executive dysfunctions were independent predictors of perceived burden, whereas demographics, injury severity, and Glasgow Outcome Scale at discharge from acute care did not significantly correlate with caregiver's burden. Global handicap and impairments of executive functions are independent significant predictors of caregiver burden 1 year after TBI.

Correlations among Brain Gray Matter Volumes, Age, Gender, and Hemisphere in Healthy Individuals

PubMed Central

Taki, Yasuyuki; Thyreau, Benjamin; Kinomura, Shigeo; Sato, Kazunori; Goto, Ryoi; Kawashima, Ryuta; Fukuda, Hiroshi

2011-01-01

To determine the relationship between age and gray matter structure and how interactions between gender and hemisphere impact this relationship, we examined correlations between global or regional gray matter volume and age, including interactions of gender and hemisphere, using a general linear model with voxel-based and region-of-interest analyses. Brain magnetic resonance images were collected from 1460 healthy individuals aged 20–69 years; the images were linearly normalized and segmented and restored to native space for analysis of global gray matter volume. Linearly normalized images were then non-linearly normalized and smoothed for analysis of regional gray matter volume. Analysis of global gray matter volume revealed a significant negative correlation between gray matter ratio (gray matter volume divided by intracranial volume) and age in both genders, and a significant interaction effect of age × gender on the gray matter ratio. In analyzing regional gray matter volume, the gray matter volume of all regions showed significant main effects of age, and most regions, with the exception of several including the inferior parietal lobule, showed a significant age × gender interaction. Additionally, the inferior temporal gyrus showed a significant age × gender × hemisphere interaction. No regional volumes showed significant age × hemisphere interactions. Our study may contribute to clarifying the mechanism(s) of normal brain aging in each brain region. PMID:21818377

Recent Developments in Understanding Brain Aging: Implications for Alzheimer’s Disease and Vascular Cognitive Impairment

PubMed Central

Deak, Ferenc; Freeman, Willard M.; Ungvari, Zoltan; Csiszar, Anna

2016-01-01

As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer’s disease. PMID:26590911

Child health-related quality of life following neurocritical care for traumatic brain injury: an analysis of preference-weighted outcomes.

PubMed

Tilford, John M; Aitken, Mary E; Goodman, Allen C; Fiser, Debra H; Killingsworth, Jeffrey B; Green, Jerril W; Adelson, P David

2007-01-01

Cost-effectiveness analysis relies on preference-weighted health outcome measures as they form the basis for quality adjusted life years. Studies of preference-weighted outcomes for children following traumatic brain injury are lacking. This study seeks to describe the preference-weighted health outcomes of children following a traumatic brain injury at 3- and 6-months following pediatric intensive care unit (ICU) discharge. Children aged 5-17 who required ICU admission and endotracheal intubation or mechanical ventilation. The Quality of Well-being (QWB) score was used to describe preference-weighted outcomes. Clinical measures from the intensive care unit stay were used to estimate risk of mortality. Risk of mortality, Glasgow coma scores, patient length of stay in the intensive care unit, and parent-reported items from the Child Health Questionnaire (CHQ) were used to test construct validity. Subject data were obtained from nine pediatric intensive care units with consent procedures approved by representative institutional review boards. Medical records containing clinical information from the ICU stay were abstracted by the study coordinating center. Caregivers of children were contacted by telephone for follow-up interviews at 3- and 6-months following ICU discharge. All interviews were conducted by telephone with the primary caregiver of the injured child. Preference score statistics are presented overall and in relation to characteristics of the patient and their ICU admission. A response rate of 59% was achieved for the 3-month interviews (N = 56) and 67% for the 6-month interviews (N = 65) for caregivers of children aged 5 years and above that consented to participate. Overall, QWB scores averaged 0.508 (95% CI: 0.454-0.562) at the 3-month interview and 0.582 (95% CI: 0.526-0.639) at the 6-month interview. For both interview periods, scores ranged from 0.093 to 1.0 on a 0-1 value scale, where 0 represents death and 1 represents perfect health. Specific

Detection of Normal Aging Effects on Human Brain Metabolite Concentrations and Microstructure with Whole-Brain MR Spectroscopic Imaging and Quantitative MR Imaging.