Showing papers on "Aging brain published in 2009"
TL;DR: The scaffolding theory of aging and cognition (STAC) is proposed, suggesting that pervasive increased frontal activation with age is a marker of an adaptive brain that engages in compensatory scaffolding in response to the challenges posed by declining neural structures and function.
Abstract: There are declines with age in speed of processing, working memory, inhibitory function, and long-term memory, as well as decreases in brain structure size and white matter integrity. In the face of these decreases, functional imaging studies have demonstrated, somewhat surprisingly, reliable increases in prefrontal activation. To account for these joint phenomena, we propose the scaffolding theory of aging and cognition (STAC). STAC provides an integrative view of the aging mind, suggesting that pervasive increased frontal activation with age is a marker of an adaptive brain that engages in compensatory scaffolding in response to the challenges posed by declining neural structures and function. Scaffolding is a normal process present across the lifespan that involves use and development of complementary, alternative neural circuits to achieve a particular cognitive goal. Scaffolding is protective of cognitive function in the aging brain, and available evidence suggests that the ability to use this mechanism is strengthened by cognitive engagement, exercise, and low levels of default network engagement.
2,171 citations
TL;DR: The lesser affected anterior hippocampal region appears to mark the parting of the ways between normal aging and Alzheimer's disease, which is characterized by early and prominent deterioration of both structures.
360 citations
TL;DR: A proposed intervention trial is described designed to evaluate the behavioral and neural impact of engagement in lifestyle activities that facilitates successful cognitive scaffolding using a controlled experiment where older adult participants are randomly assigned to different conditions of engagement.
Abstract: A recent proposal called the Scaffolding Theory of Cognitive Aging (STAC) postulates that functional changes with aging are part of a lifespan process of compensatory cognitive scaffolding that is an attempt to alleviate the cognitive declines associated with aging. Indeed, behavioral studies have shown that aging is associated with both decline as well as preservation of selective cognitive abilities. Similarly, neuroimaging studies have revealed selective changes in the aging brain that reflect neural decline as well as compensatory neural recruitment. While aging is associated with reductions in cortical thickness, white-matter integrity, dopaminergic activity, and functional engagement in posterior brain regions such as the hippocampus and occipital areas, there are compensatory increases in frontal functional engagement that correlate with better behavioral performance in older adults. In this review, we discuss these age-related behavioral and brain findings that support the STAC model of cognitive scaffolding and additionally integrate the findings on neuroplasticity as a compensatory response in the aging brain. As such, we also examine the impact of external experiences in facilitating neuroplasticity in older adults. Finally, having laid the foundation for STAC, we briefly describe a proposed intervention trial (The Synapse Program) designed to evaluate the behavioral and neural impact of engagement in lifestyle activities that facilitates successful cognitive scaffolding using a controlled experiment where older adult participants are randomly assigned to different conditions of engagement.
209 citations
TL;DR: These observations support the hypothesis of transneuronal spread of neurofibrillary changes from the DR to its interconnected cortical brain areas and indicate that the supratrochlear subnucleus of the DR is affected by neurofibillary changes before the transentorhinal cortex during the disease process underlying AD.
Abstract: AIMS Alzheimer's disease (AD) is a progressive and irreversible disease. There is strong evidence that the progression of the phospho-tau neurofibrillary cytoskeletal changes, rather than the beta-amyloid burden, is crucial in determining the severity of the dementia in AD. The Braak and Braak staging system (BB) focuses mainly on the cortical cytoskeletal pathology and classifies this progressive pathology into six stages, spreading from the transentorhinal region to primary cortices. Although it is reported elsewhere that the midbrain's dorsal raphe nucleus (DR), which is connected with those areas of the cerebral cortex undergoing early changes during BB I and II, exhibits AD-related cytoskeletal pathology, this nucleus has not been considered by the BB. METHODS To determine during which BB stage and how frequently the DR is affected by AD-related neurofibrillary changes, we studied the DR of 118 well-characterized individuals of the Brain Bank of the Brazilian Aging Brain Study Group categorized according to the BB. Thirty-eight of these individuals were staged as BB = 0, and 80 as BB >or= 1. RESULTS In all of the BB >or= 1 individuals (cortical neurofibrillary changes were present at least in the transentorhinal region) and in more than 1/5 of the BB = 0 individuals neurofibrillary changes were detected in the supratrochlear subnucleus of the DR. CONCLUSIONS These observations: (i) support the hypothesis of transneuronal spread of neurofibrillary changes from the DR to its interconnected cortical brain areas; and (ii) indicate that the supratrochlear subnucleus of the DR is affected by neurofibrillary changes before the transentorhinal cortex during the disease process underlying AD.
188 citations
TL;DR: Considerable evidence suggests amyloid deposition precedes declines in cognition and may be the initiator in a cascade of events that indirectly leads to age-related cognitive decline.
Abstract: A central issue in cognitive neuroscience of aging research is pinpointing precise neural mechanisms that determine cognitive outcome in late adulthood as well as identifying early markers of less successful cognitive aging. One promising biomarker is beta amyloid (Aβ) deposition. Several new radiotracers have been developed that bind to fibrillar Aβ providing sensitive estimates of amyloid deposition in various brain regions. Aβ imaging has been primarily used to study patients with Alzheimer’s Disease (AD) and individuals with Mild Cognitive Impairment (MCI); however, there is now building data on Aβ deposition in healthy controls that suggest at least 20% and perhaps as much as a third of healthy older adults show significant deposition. Considerable evidence suggests amyloid deposition precedes declines in cognition and may be the initiator in a cascade of events that indirectly leads to age-related cognitive decline. We review studies of Aβ deposition imaging in AD, MCI, and normal adults, its cognitive consequences, and the role of genetic risk and cognitive reserve.
169 citations
TL;DR: Decreased BBB P-gp function with aging could be a mechanism by which age acts as the main risk factor for the development of neurodegenerative disease.
143 citations
TL;DR: It is shown that the Polycomb group and oncogene Bmi1 is required in neurons to suppress apoptosis and the induction of a premature aging-like program characterized by reduced antioxidant defenses, which provides a molecular mechanism explaining how Bmi 1 regulates free radical concentrations.
Abstract: Aging may be determined by a genetic program and/or by the accumulation rate of molecular damages. Reactive oxygen species (ROS) generated by the mitochondrial metabolism have been postulated to be the central source of molecular damages and imbalance between levels of intracellular ROS and antioxidant defenses is a characteristic of the aging brain. How aging modifies free radicals concentrations and increases the risk to develop most neurodegenerative diseases is poorly understood, however. Here we show that the Polycomb group and oncogene Bmi1 is required in neurons to suppress apoptosis and the induction of a premature aging-like program characterized by reduced antioxidant defenses. Before weaning, Bmi1(-/-) mice display a progeroid-like ocular and brain phenotype, while Bmi1(+/-) mice, although apparently normal, have reduced lifespan. Bmi1 deficiency in neurons results in increased p19(Arf)/p53 levels, abnormally high ROS concentrations, and hypersensitivity to neurotoxic agents. Most Bmi1 functions on neurons' oxidative metabolism are genetically linked to repression of p53 pro-oxidant activity, which also operates in physiological conditions. In Bmi1(-/-) neurons, p53 and corepressors accumulate at antioxidant gene promoters, correlating with a repressed chromatin state and antioxidant gene downregulation. These findings provide a molecular mechanism explaining how Bmi1 regulates free radical concentrations and reveal the biological impact of Bmi1 deficiency on neuronal survival and aging.
141 citations
TL;DR: Investigating the relation between resting cerebral blood flow and cognitive functions (tonic and phasic alertness, selective and divided attention) in two samples of healthy young and older participants found higher resting CBF and better cognitive performances in the young than in the older sample.
119 citations
TL;DR: It is concluded that sex has negligible effects on the age slope of brain volumes both in healthy participants and in AD.
Abstract: Age is associated with substantial macrostructural brain changes. While some recent magnetic resonance imaging studies have reported larger age effects in men than women, others find no sex differences. As brain morphometry is a potentially important tool in diagnosis and monitoring of age-related neurological diseases, e.g., Alzheimer's disease (AD), it is important to know whether sex influences brain aging. We analyzed cross-sectional magnetic resonance scans from 1143 healthy participants from seven subsamples provided by four independent research groups. In addition, 96 patients with mild AD were included. Estimates of cortical thickness continuously across the brain surface, as well as volume of 17 subcortical structures, were obtained by use of automated segmentation tools (FreeSurfer). In the healthy participants, no differences in aging slopes between women and men were found in any part of the cortex. Pallidum corrected for intracranial volume showed slightly higher age correlations for men. The analyses were repeated in each of the seven subsamples, and the lack of age × sex interactions was largely replicated. Analyses of the AD sample showed no interactions between sex and age for any brain region. We conclude that sex has negligible effects on the age slope of brain volumes both in healthy participants and in AD.
116 citations
01 Jan 2009
66 citations
TL;DR: It is demonstrated that the brain and liver exhibit age-dependent decreases in 26S and 20S proteasome activity, and the relationship between proteasomesome composition/biogenesis and prote asome activity in tissues is extremely complex and tissue specific.
TL;DR: Overall, activity in the major components of the default-mode network remains stable in healthy older individuals, a finding which may assist in identifying factors that discriminate between normal and pathological aging.
Abstract: Activity attributed to the default-mode occurs during the resting state and is thought to represent self-referential and other intrinsic processes. Although activity in default-associated regions changes across the lifespan, little is known about the stability of default-mode activity in the healthy aging brain. We investigated changes in rest-specific activity across an 8 year period in older participants in the Baltimore Longitudinal Study of Aging (BLSA) neuroimaging study. Comparison of resting-state and recognition memory PET regional cerebral blood flow conditions from baseline and 8-year follow-up shows relative stability of rest-specific activity over time in medial frontal/anterior cingulate, hippocampal and posterior cingulate regions commonly associated with the default-mode. In contrast, prefrontal, parahippocampal and occipital cortical regions, which are not typically associated with default-mode activity, show changes over time. Overall, activity in the major components of the default-mode network remains stable in healthy older individuals, a finding which may assist in identifying factors that discriminate between normal and pathological aging.
TL;DR: It is revealed that although neural connectivity is generally reduced in the aging brain, prefrontal-parietal resting functional connectivity is better preserved in the left hemisphere while prefrontal DTI fiber pathways are better preservedIn the right hemisphere.
TL;DR: It is found that low-frequency medial nerve stimulation paired with transcranial magnetic stimulation over the contralateral cortex enhances S1 excitability, and the S1 long term potentiation-like plasticity changes as a function of aging, with a significant increase of N20-P25 complex in the elderly compared to young subjects.
TL;DR: It is indicated that a combination of chemokine-cytokines rather than single cytokines may contribute to inflammatory processes associated with cortical atrophy in the aging brain.
Abstract: The association between cytokines (IL-1β, sIL-4R, IL-6, IL-8, IL-10, IL-12, TNF-α) and subcortical white matter lesions, cortical atrophy and lacunar infarctions of the aging brain was investigated among 268 elderly community participants. Single pro- and anti-inflammatory cytokines were neither associated with WML nor with atrophy and lacunar infarction. An association between atrophy and the chemokine-cytokine factor (containing sIL-4R, IL-6, IL-8) remained significant after adjustment for age, gender, education, depressive symptoms, diabetes mellitus, cardiovascular diseases (stroke, TIA, myocardial infarction, myocardial insufficiency, arrhythmic heart), hypertension, body-mass index, smoking status and aggregation inhibitors as opposed to single cytokines. Atrophy of the parietal, temporal and occipital lobes was associated with the same cytokinechemokine factor for both the whole sample or restricted to those without history of stroke/TIA. The results indicate that a combination of chemokine-cytokines rather than single cytokines may contribute to inflammatory processes associated with cortical atrophy in the aging brain.
TL;DR: Results are consistent with the current notion that oxidative stress and cellular damage are characteristic hallmarks of the aging process, and sustain the critical role of cellular stress-response mechanisms as possible targets for novel antiaging strategies.
Abstract: Carnosinase is a dipeptidase found almost exclusively in brain and serum. Its natural substrate carnosine, present at high concentration in the brain, has been proposed as an antioxidant in vivo. We investigated the role of carnosinase in brain aging to establish a possible correlation with age-related changes in cellular stress response and redox status. In addition, a stable HeLa cell line expressing recombinant human serum carnosinase CN1 was established. The enzyme was purified from transfected cells, and specific antibodies were produced against it. Brain expression of CN1, Hsp72, heme oxygenase-1, and thioredoxin reductase increased with age, with a maximal induction in hippocampus and substantia nigra, followed by cerebellum, cortex, septum, and striatum. Hsps induction was associated with significant changes in total SH groups, GSH redox state, carbonyls, and HNE levels. A positive correlation between decrease in GSH and increase in Hsp72 expression was observed in all brain regions exami...
TL;DR: The literature on the possible physiological roles of Abeta and its precursor protein AbetaPP during development with special focus on electrophysiological findings is reviewed, suggesting that this putative function can become pathogenic if activated in the aging brain.
Abstract: Pathological hallmarks of Alzheimer's disease (AD) include synaptic and neuronal degeneration and the presence of extracellular deposits of amyloid-beta (Abeta) in senile plaques in the cerebral cortex. Although these brain lesions may be seen also in aged non-demented individuals, the increase in brain Abeta is believed by many to represent the earliest event in the disease process. Accumulating evidence suggests that Abeta, which is highly conserved by evolution, may have an important physiological role in synapse elimination during brain development. An intriguing idea is that this putative function can become pathogenic if activated in the aging brain. Here, we review the literature on the possible physiological roles of Abeta and its precursor protein AbetaPP during development with special focus on electrophysiological findings.
TL;DR: Age-related decreases in alpha-synuclein were widespread throughout the mouse brain, affecting other regions (e.g., hippocampus) besides the substantia nigra, suggesting that loss of alpha- synuclein could contribute to or be a marker of synaptic dysfunction in the aging brain.
TL;DR: Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years, and reports also support thatitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.
Abstract: With aging, the brain undergoes neuronal loss in many areas. Although the loss of cells in the cerebral cortex, in particular the frontal cortex, has been recognized with aging, the influence of synaptic losses has a larger impact on cognitive decline. Much of the recent research on animals, as well as humans, has been aimed at slowing the cognitive decline through enrichment, and it has been found that the key factors are antioxidants and exercise. Several reports support the concept that regular supplementation of vitamin E and physical activity from as early as middle age can slow the cognitive decline observed during the later years. A few studies have also suggested that exercise is analogous to acetylcholine esterase inhibitors that are also used extensively to treat cognitive impairment and dementia in Alzheimer's disease. In addition, reports also support that vitamin E and exercise may act synergistically to overcome free radical injury and oxidative stress in the aging brain.
TL;DR: Evidence is provided that elevated CSF sICAM-1 and ACE are associated with lower perfusion levels in the parietal cortex of cognitively intact elderly.
TL;DR: A molecular mechanism by which hyper-excitation of the stress axis in turn activates the tumor suppressor p53, which reinforces the loss of stem cell proliferative capacity and interferes with the feedback mechanisms by which the glucocorticoid receptor turns off neuroendocrine pathways and resets the axis.
TL;DR: Results suggest that the effects of MCT‐SDs in the aging brain critically depend on neuronal vulnerability to age, besides MCT percentage, as well as computer‐assisted morphometric methods.
Abstract: Ketogenic diets (KDs) have shown beneficial effects in experimental models of neurodegeneration, designating aged individuals as possible recipients. However, few studies have investigated their consequences on aging brain. Here, late-adult rats (19 months of age) were fed for 8 weeks with two medium chain triglycerides-supplemented diets (MCT-SDs) and the average area (S), numeric density (Nv(s)), and surface density (S(v)) of synapses, as well as the average volume (V), numeric density (Nv(m)), and volume density (V(v)) of synaptic mitochondria were evaluated in granule cell layer of the cerebellar cortex (GCL-CCx) by computer-assisted morphometric methods. MCT content was 10 or 20%. About 10%MCT-SD induced the early appearance of senescent patterns (decreased Nv(s) and Nv(m); increased V), whereas 20%MCT-SD caused no changes. Recently, we have shown that both MCT-SDs accelerate aging in the stratum moleculare of CA1 (SM CA1), but are "antiaging" in the outer molecular layer of dentate gyrus (OML DG). Since GCL-CCx is more vulnerable to age than OML DG but less than SM CA1, present and previous results suggest that the effects of MCT-SDs in the aging brain critically depend on neuronal vulnerability to age, besides MCT percentage.
22 Oct 2009
TL;DR: It is shown that exercise serves as a behavioral intervention to prevent cognitive decline as well as neurodegenerative diseases, and long-term regular exercise in parallel with various learning experiences will be required to prepare successful aging.
Abstract: Arapid increase in the elderly population has raised social awareness for maintaining the health of the elderly and initiated intense research in neurodegenerative diseases. Exercise can improve not only cardiovascular and musculoskeletal fitness, but also suppresses the symptoms of depression and anxiety, suggesting a possible role of exercise in the regulation of brain function. Based on a substantial body of literature, here we introduce the effects of exercise on the structural and functional changes in the aging brain, and also discuss the molecular and cellular effects of exercise and motor learning. Studies show that regular exercise in the elderly promotes neurocognitive function, prevents loss of brain tissue, and reduces the risk for neurodegenerative diseases and brain injury. Although the molecular mechanisms, by which exercise regulates brain function, has not been fully understood, recent cell biological and biochemical studies reveal that exercise increases neurogenesis in the hippocampus, elevates the levels of neurotrophins such as BDNF and IGF-1 to promote the survival of newly generated neurons. Exercise also induces angiogenesis in the motor cortex and cerebellum to enhance delivery of glucose and oxygen to neurons. Furthermore, complex motor skill learning increases the number of synapses to improve cognitive and motor function. Taken together, these findings clearly demonstrate that exercise serves as a behavioral intervention to prevent cognitive decline as well as neurodegenerative diseases. Thus long-term regular exercise in parallel with various learning experiences will be required to prepare successful aging. This study will provide fundamental insights into research in neurodegenerative diseases and a better understanding of the exercise effects in brain function.
01 Jan 2009
TL;DR: More research is needed on mechanisms of increased seizure propensity in elderly, and on anticonvulsant drug effects on the aging brain, to confirm an increased susceptibility of the aged brain to develop seizures.
Abstract: By 2050, elderly people (older than 60 years) will exceed 30% of the total world population. It is now recognized that this population has a high incidence of seizures and epilepsy. Possible reasons include enhanced seizure predisposition, medical comorbidities, structural changes of the brain related to aging, and synergistic effects of concurrent medications. Underlying conditions in aging patients may modify the expression of seizures that have been chronically present in the younger individual, or the aged brain may develop seizures de novo. Metabolism of antiepileptic drugs may be also significantly different in the elderly, with drug interactions becoming a serious issue. The few models in aged animals (mice and rats) that have been investigated to date confirm an increased susceptibility of the aged brain to develop seizures. More research is needed on mechanisms of increased seizure propensity in elderly, and on anticonvulsant drug effects on the aging brain.
13 Jul 2009
TL;DR: It is suggested that age related brain atrophy and perhaps even neurodegenerative atrophy itself can be reduced in magnitude if underlying vascular diseases are either prevented or better managed.
Abstract: Brain aging, the phenomenon by which the passage of chronological time is associated with reduced brain volume, is important because it is regarded as a key component of increased dementia risk. The main purpose of this thesis is to present a model and supporting data that enhances knowledge of the underlying processes that drive brain aging and dementia risk. This has been done using structural and functional MRI scans from the Cardiovascular Health Study-Cognition Study (CHS-CS), a longitudinal community cohort study of elderly individuals that possesses extensive clinical and neuropsychological data. The model defended in this dissertation states that the relationship between older age and lower gray matter volume is not strictly a function of the passage of chronological time. Rather, older age is correlated with vascular diseases that themselves are a driving force behind brain aging. Most importantly, the three entities of aging, vascular disease, and neurodegeneration overlap in key strategic areas of the brain. Thus, a large factor behind dementia risk is that there are common brain areas that serve as sites of synergy by which age, vascular disease, and neurodegeneration can summate and thus amplify the risk for cognitive impairment and dementia. Using a whole brain method for analyzing structural MRI scans, we have found that the age and vascular disease, as reflected by white matter hyperintense lesions (WMHL) jointly affect areas of the brain known to be targeted by age and neurodegeneration and that they interact in these key strategic brain regions. Finally, results from perfusion MRI imaging will be reported showing that hypertension as the main predictor of lower regional cerebral blood flow. Taken together, these data will be interpreted to support the following model: structural and functional changes in an aging brain are modulated by hypertensive vascular disease. Additionally, the damage exerted by neurodegenerative processes on the brain is also modified by vascular disease. Finally, there are common strategic anatomical sites in which this synergy occurs and they include areas with important cognitive functions such as the hippocampus, cingulate gyrus, and precuneus. This model has several broad implications. First, it suggests that age related brain atrophy and perhaps even neurodegenerative atrophy itself can be reduced in magnitude if underlying vascular diseases are either prevented or better managed. Second, such a reduction in brain aging may lower risk for dementia by providing additional brain reserve. Third, key strategic brain regions provide a basis for further study and therapeutic targets.
Journal Article•
01 Jan 2009
TL;DR: Measures of reaction time and electrophysiological brain activity that quantify age-related changes in cognition associated with processing speed, sensory memory, working memory, and episodic memory are presented.
Abstract: We present measures of reaction time and electrophysiological brain activity that quantify age-related changes in cognition associated with processing speed, sensory memory, working memory, and episodic memory. Different components of electrophysiological brain responses that indicate specific aspects of sensory and cognitive processing are introduced and related to changes in memory processes in normal aging. Findings demonstrate the utility of combining overt behavioral measures with covert electrophysiological measures to define brain and cognitive aging.
TL;DR: A history of CABG is an apparent risk factor for developing MCI and dementia as well as for having higher WMH ratings as discussed by the authors, suggesting that there are related mechanisms for developing WMH and neurodegenerative disease among these subjects.
Abstract: FOME scores when compared to those with WMH ratings below the 50 percentile. Conclusions: A history of CABG is an apparent risk factor for developing aMCI and dementia as well as for having higher WMH ratings. Those with CABG who had high WMH ratings had greater medial temporal atrophy, suggesting that there are related mechanisms for developing WMH and neurodegenerative disease among these subjects.