Age-associated Cognitive Decline Research Articles

Age-associated changes of nitric oxide concentration dynamics in the central nervous system of Fisher 344 rats.

The increase in life expectancy is accompanied by an increased risk of developing neurodegenerative disorders and age is the most relevant risk factor for the appearance of cognitive decline. While decreased neuronal count has been proposed to be a major contributing factor to the appearance of age-associated cognitive decline, it appears to be insufficient to fully account for the decay in mental function in aged individuals. Nitric oxide ((•)NO) is a ubiquitous signaling molecule in the mammalian central nervous system. Closely linked to the activation of glutamatergic transmission in several structures of the brain, neuron-derived (•)NO can act as a neuromodulator in synaptic plasticity but has also been linked to neuronal toxicity and degenerative processes. Many studies have proposed that changes in the glutamate-(•)NO signaling pathway may be implicated in age-dependent cognitive decline and that the exact effect of such changes may be region specific. Due to its peculiar physical-chemical properties, namely hydrophobicity, small size, and rapid diffusion properties, the rate and pattern of (•)NO concentration changes are critical determinants for the understanding of its bioactivity in the brain. Here we show a detailed study of how (•)NO concentration dynamics change in the different regions of the brain of Fisher 344 rats (F344) during aging. Using microelectrodes inserted into the living brain of anesthetized F344 rats, we show here that glutamate-induced (•)NO concentration dynamics decrease in the hippocampus, striatum, and cerebral cortex as animals age. performance in behavior testing of short-term and spatial memory, suggesting that the impairment in the glutamate:nNOS pathway represents a functional critical event in cognitive decline during aging.

Cognitive performance among older individuals associated with the peripheral effector memory CD4 + T cells

Progressive decline in immune function (immunosenescence) and in cognitive performance are common alterations accompanying aging. The interaction between these two systems has been highlighted in recent years mainly in studies using animal models. It has been shown that mice lacking B and T lymphocytes display cognitive impairments that are reverted by T cell replenishment. In fact, aging is accompanied by defined alterations in the adaptive immune system, namely in the T cell compartments. Taking into consideration the link between T cells and cognition, and since both age-associated cognitive decline and immunosenescence vary greatly between individuals we hypothesized that alterations in lymphocytes and cognitive performance are associated.

Cerebrospinal fluid metabolomics reveals altered waste clearance and accelerated aging in HIV patients with neurocognitive impairment.

Objective(s):HIV-associated neurocognitive disorders (HAND) remain prevalent in HIV-infected patients on antiretroviral therapy (ART), but the underlying mechanisms are unclear. Some features of HAND resemble those of age-associated cognitive decline in the absence of HIV, suggesting that overlapping mechanisms may contribute to neurocognitive impairment.Design:Cross-sectional analysis of cerebrospinal fluid (CSF) from 100 individuals (46 HIV-positive patients and 54 HIV-negative controls).Methods:Untargeted CSF metabolite profiling was performed using liquid/gas chromatography followed by mass spectrometry. Cytokine profiling was performed by Bioplex. Bioinformatic analyses were performed in Metaboanalyst and R.Results:Alterations in the CSF metabolome of HIV patients on ART mapped to pathways associated with neurotransmitter production, mitochondrial function, oxidative stress, and metabolic waste. Many CSF metabolites altered in HIV overlapped with those altered with advanced age in HIV-negative controls, suggesting a pattern indicative of accelerated aging. Machine learning models identified neurotransmitters (glutamate, N-acetylaspartate), markers of glial activation (myo-inositol), and ketone bodies (beta-hydroxybutyric acid, 1,2-propanediol) as top-ranked classifiers of HAND. These CSF metabolites correlated with worse neurocognitive test scores, plasma inflammatory biomarkers [interferon (IFN)-α, IFN-γ, interleukin (IL)-8, IL-1β, IL-6, IL-2Ra], and intrathecal IFN responses (IFN-γ and kynurenine : tryptophan ratio), suggesting inter-relationships between systemic and intrathecal inflammation and metabolic alterations in CSF.Conclusions:Alterations in the CSF metabolome of HIV patients on ART suggest that persistent inflammation, glial responses, glutamate neurotoxicity, and altered brain waste disposal systems contribute to mechanisms involved in HAND that may be augmented with aging.

Enhanced defense against mitochondrial hydrogen peroxide attenuates age-associated cognition decline

Increased mitochondrial hydrogen peroxide (H2O2) is associated with Alzheimer's disease and brain aging. Peroxiredoxin 3 (Prdx3) is the key mitochondrial antioxidant defense enzyme in detoxifying H2O2. To investigate the importance of mitochondrial H2O2 in age-associated cognitive decline, we compared cognition between aged (17–19 months) APP transgenic mice and APP/Prdx3 double transgenic mice (dTG) and between old (24 months) wild-type mice and Prdx3 transgenic mice (TG). Compared with aged APP mice, aged dTG mice showed improved cognition that was correlated with reduced brain amyloid beta levels and decreased amyloid beta production. Old TG mice also showed significantly increased cognitive ability compared with old wild-type mice. Both aged dTG mice and old TG mice had reduced mitochondrial oxidative stress and increased mitochondrial function. Moreover, CREB signaling, a signaling pathway important for cognition was enhanced in both aged dTG mice and old TG mice. Thus, our results indicate that mitochondrial H2O2 is a key culprit of age-associated cognitive impairment, and that a reduction of mitochondrial H2O2 could improve cognition by maintaining mitochondrial health and enhancing CREB signaling.

Specific ablation of Nampt in adult neural stem cells recapitulates their functional defects during aging

Neural stem/progenitor cell (NSPC) proliferation and self-renewal, as well as insult-induced differentiation, decrease markedly with age. The molecular mechanisms responsible for these declines remain unclear. Here, we show that levels of NAD(+) and nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in mammalian NAD(+) biosynthesis, decrease with age in the hippocampus. Ablation of Nampt in adult NSPCs reduced their pool and proliferation in vivo. The decrease in the NSPC pool during aging can be rescued by enhancing hippocampal NAD(+) levels. Nampt is the main source of NSPC NAD(+) levels and required for G1/S progression of the NSPC cell cycle. Nampt is also critical in oligodendrocytic lineage fate decisions through a mechanism mediated redundantly by Sirt1 and Sirt2. Ablation of Nampt in the adult NSPCs in vivo reduced NSPC-mediated oligodendrogenesis upon insult. These phenotypes recapitulate defects in NSPCs during aging, giving rise to the possibility that Nampt-mediated NAD(+) biosynthesis is a mediator of age-associated functional declines in NSPCs.

Cognitive decline and brain pathology in aging--need for a dimensional, lifespan and systems vulnerability view.

Changes in brain structure and activity as well as cognitive function are commonly seen in aging. However, it is not known when aging of brain and cognition starts, and how much of the changes observed in seemingly healthy older adults that can be ascribed to incipient neurodegenerative disease. Recent research has yielded evidence that the borders between development and aging sometimes can be fuzzy, as can the borders between dementing disease and normal age changes. In this review, we argue that many factors affecting cognitive decline and dementia represents quantitative rather than qualitative differences in characteristics that commonly exist in the population. Further, factors known to affect brain and cognition in aging will often do so through a life-long accumulation of impact, and does not need to be specific to aging. And finally, a host of environmental and genetic factors and their interplay determine optimal aging, leaving room for potential for environmental interventions to affect the outcome of the aging process. Together, we argue that these factors call for a dimensional rather than categorical, lifespan rather than aging, and multidimensional systems-vulnerability rather than simple "hypothetical biomarker" model of age-associated cognitive decline and dementia. This has implications for how we should view lifespan trajectories of change in brain and cognitive function, and how we can study, prevent, diagnose and treat age-associated cognitive deficits.

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

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.

Omega-3 PUFA supplementation differentially affects behavior and cognition in the young and aged non-human primate Grey mouse lemur (Microcebus murinus)

Data are divergent about the ability of dietary ω3 fatty acids to prevent age-associated cognitive decline. Most of the clinical trials failed to demonstrate a protective effect of ω3 fatty acids against cognitive decline and methodological issues are still under debate. Conversely to human studies, experiments performed in adult rodents clearly indicate that long chain ω3 fatty acids play a beneficial role in behavioral and cognitive functions. Inconsistent observations between human and rodent studies highlight the importance of the use of non-human primate models. We recently started a series of experiments on Grey mouse lemurs, an emerging non-human primate model of aging in order to assess the impact of ω3 fatty acids dietary supplementation on several brain functions. These experiments started with the determination of the fatty acids composition of target organs (brain, adipose tissue, liver, plasma) of animals fed under control diet. We then explored the impact of ω3 polyunsaturated fatty acids (PUFA) supplementation on cognition and behavior in young and aged grey mouse lemurs. The aim of the present review is to compare the observations made in young and aged grey mouse lemurs and to explore the possibilities of new experiments in order to bridge the gap between rodents and Humans.

Association of basal forebrain volumes and cognition in normal aging

The basal forebrain cholinergic system (BFCS) is known to undergo moderate neurodegenerative alterations during normal aging and severe atrophy in Alzheimer's disease (AD). It has been suggested that functional and structural alterations of the BFCS mediate cognitive performance in normal aging and AD. But, it is still unclear to what extend age-associated cognitive decline can be related to BFCS in normal aging. We analyzed the relationship between BFCS volume and cognition using MRI and a comprehensive neuropsychological test battery in a cohort of 43 healthy elderly subjects spanning the age range from 60 to 85 years.Most notably, we found significant associations between general intelligence and BFCS volumes, specifically within areas corresponding to posterior nuclei of the nucleus basalis of Meynert (Ch4p) and the nucleus subputaminalis (NSP). Associations between specific cognitive domains and BFCS volumes were less pronounced. Supplementary analyses demonstrated that especially the volume of NSP but also the volume of Ch4p was related to the volume of widespread temporal, frontal, and parietal gray and white matter regions. Volumes of these gray and white matter regions were also related to general intelligence. Higher volumes of Ch4p and NSP may enhance the effectiveness of acetylcholine supply in related gray and white matter regions underlying general intelligence and hence explain the observed association between the volume of Ch4p as well as NSP and general intelligence. Since general intelligence is known to attenuate the degree of age-associated cognitive decline and the risk of developing late-onset AD, the BFCS might, besides the specific contribution to the pathophysiology in AD, constitute a mechanism of brain resilience in normal aging.

Omega-3 fatty acids and domain-specific cognitive aging

To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time. We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.

Early stress evokes temporally distinct consequences on the hippocampal transcriptome, anxiety and cognitive behaviour

The early stress of maternal separation (ES) exerts long-lasting effects on cognition and anxiety. Recent evidence indicates enhanced hippocampus-dependent spatial learning in young adult ES animals, which shifts towards a decline in long-term memory in middle-aged life. Further, we find that ES animals exhibit enhanced anxiety in young adulthood that does not persist into middle-aged life. Here, we demonstrate unique, predominantly non-overlapping, hippocampal transcriptomes in young adult and middle-aged ES animals that accompany the temporally-specific behavioural consequences. Strikingly, the extent of gene dysregulation in middle-aged ES animals was substantially higher than in young adulthood. Functional analysis revealed distinct biological processes enriched at the two ages, highlighting the temporal shift in ES-evoked gene regulation. Our results suggest that ES history interacts with aging to exacerbate age-associated transcriptional changes and cognitive decline. qPCR profiling of histone deacetylases (Hdacs) and histone methyltransferases (HMTs) revealed an age-dependent, opposing regulation with decreased expression noted in young adult ES animals (Hdac 2, 7, 8, 9 and Suv39h1) and enhanced levels in middle-aged life (Hdac 2, 6, 8 and Suv39h1). While altered expression of histone modifying enzymes did not translate into global histone acetylation or methylation changes, we noted differential enrichment of histone acetylation and methylation modifications at the promoters of multiple genes regulated in the hippocampi of young adult and middle-aged ES animals. Our results highlight the differential molecular and behavioural consequences of ES across a life-span, and suggest a possible role for epigenetic mechanisms in contributing to the temporally-specific transcriptional changes following ES.

OP19 Increased Adherence to the Mediterranean Diet Protects Memory Decline over 20 years in a Longitudinal Study

BackgroundCognitive decline is the first outward sign of dementia and represents a major public health effect. Evidence suggests that dietary patterns are associated with cardiovascular and cerebrovascular risk factors. A...

Anodal Transcranial Direct Current Stimulation Temporarily Reverses Age-Associated Cognitive Decline and Functional Brain Activity Changes

The rising proportion of elderly people worldwide will yield an increased incidence of age-associated cognitive impairments, imposing major burdens on societies. Consequently, growing interest emerged to evaluate new strategies to delay or counteract cognitive decline in aging. Here, we assessed immediate effects of anodal transcranial direct current stimulation (atDCS) on cognition and previously described detrimental changes in brain activity attributable to aging. Twenty healthy elderly adults were assessed in a crossover sham-controlled design using functional magnetic resonance imaging (fMRI) and concurrent transcranial DCS administered to the left inferior frontal gyrus. Effects on performance and task-related brain activity were evaluated during overt semantic word generation, a task that is negatively affected by advanced age. Task-absent resting-state fMRI (RS-fMRI) assessed atDCS-induced changes at the network level independent of performance. Twenty matched younger adults served as controls. During sham stimulation, task-related fMRI demonstrated that enhanced bilateral prefrontal activity in older adults was associated with reduced performance. RS-fMRI revealed enhanced anterior and reduced posterior functional brain connectivity. atDCS significantly improved performance in older adults up to the level of younger controls; significantly reduced task-related hyperactivity in bilateral prefrontal cortices, the anterior cingulate gyrus, and the precuneus; and induced a more "youth-like" connectivity pattern during RS-fMRI. Our results provide converging evidence from behavioral analysis and two independent functional imaging paradigms that a single session of atDCS can temporarily reverse nonbeneficial effects of aging on cognition and brain activity and connectivity. These findings may translate into novel treatments to ameliorate cognitive decline in normal aging in the future.

The protective effect of geniposide on human neuroblastoma cells in the presence of formaldehyde

BackgroundFormaldehyde can induce misfolding and aggregation of Tau protein and β amyloid protein, which are characteristic pathological features of Alzheimer’s disease (AD). An increase in endogenous formaldehyde concentration in the brain is closely related to dementia in aging people. Therefore, the discovery of effective drugs to counteract the adverse impact of formaldehyde on neuronal cells is beneficial for the development of appropriate treatments for age-associated cognitive decline.MethodsIn this study, we assessed the neuroprotective properties of TongLuoJiuNao (TLJN), a traditional Chinese medicine preparation, against formaldehyde stress in human neuroblastoma cells (SH-SY5Y cell line). The effect of TLJN and its main ingredients (geniposide and ginsenoside Rg1) on cell viability, apoptosis, intracellular antioxidant activity and the expression of apoptotic-related genes in the presence of formaldehyde were monitored.ResultsCell counting studies showed that in the presence of TLJN, the viability of formaldehyde-treated SH-SY5Y cells significantly recovered. Laser scanning confocal microscopy revealed that the morphology of formaldehyde-injured cells was rescued by TLJN and geniposide, an effective ingredient of TLJN. Moreover, the inhibitory effect of geniposide on formaldehyde-induced apoptosis was dose-dependent. The activity of intracellular antioxidants (superoxide dismutase and glutathione peroxidase) increased, as did mRNA and protein levels of the antiapoptotic gene Bcl-2 after the addition of geniposide. In contrast, the expression of the apoptotic-related gene - P53, apoptotic executer - caspase 3 and apoptotic initiator - caspase 9 were downregulated after geniposide treatment.ConclusionsOur results indicate that geniposide can protect SH-SY5Y cells against formaldehyde stress through modulating the expression of Bcl-2, P53, caspase 3 and caspase 9, and by increasing the activity of intracellular superoxide dismutase and glutathione peroxidase.

The brain-in-motion study: effect of a 6-month aerobic exercise intervention on cerebrovascular regulation and cognitive function in older adults.

BackgroundAging and physical inactivity are associated with declines in some cognitive domains and cerebrovascular function, as well as an elevated risk of cerebrovascular disease and other morbidities. With the increase in the number of sedentary older Canadians, promoting healthy brain aging is becoming an increasingly important population health issue. Emerging research suggests that higher levels of physical fitness at any age are associated with better cognitive functioning and this may be mediated, at least in part, by improvements in cerebrovascular reserve. We are currently conducting a study to determine: if a structured 6-month aerobic exercise program is associated with improvements or maintenance of both cerebrovascular function and cognitive abilities in older individuals; and, the extent to which any changes seen persist 6 months after the completion of the structured exercise program.Methods/designTwo hundred and fifty men and women aged 55–80 years are being enrolled into an 18-month combined quasi-experimental and prospective cohort study. Participants are eligible for enrollment into the study if they are inactive (i.e., not participating in regular physical activity), non-smokers, have a body mass index <35.0 kg/m2, are free of significant cognitive impairment (defined as a Montreal Cognitive Assessment score of 24 or more), and do not have clinically significant cardiovascular, cerebrovascular disease, or chronic obstructive pulmonary airway disease. Repeated measurements are done during three sequential six-month phases: 1) pre-intervention; 2) aerobic exercise intervention; and 3) post-intervention. These outcomes include: cardiorespiratory fitness, resting cerebral blood flow, cerebrovascular reserve, and cognitive function.DiscussionThis is the first study to our knowledge that will examine contemporaneously the effect of an exercise intervention on both cerebrovascular reserve and cognition in an older population. This study will further our understanding of whether cerebrovascular mechanisms might explain how exercise promotes healthy brain aging. In addition our study will address the potential of increasing physical activity to prevent age-associated cognitive decline.

Targeting specific HATs for neurodegenerative disease treatment: translating basic biology to therapeutic possibilities

Dynamic epigenetic regulation of neurons is emerging as a fundamental mechanism by which neurons adapt their transcriptional responses to specific developmental and environmental cues. While defects within the neural epigenome have traditionally been studied in the context of early developmental and heritable cognitive disorders, recent studies point to aberrant histone acetylation status as a key mechanism underlying acquired inappropriate alterations of genome structure and function in post-mitotic neurons during the aging process. Indeed, it is becoming increasingly evident that chromatin acetylation status can be impaired during the lifetime of neurons through mechanisms related to loss of function of histone acetyltransferase (HAT) activity. Several HATs have been shown to participate in vital neuronal functions such as regulation of neuronal plasticity and memory formation. As such, dysregulation of such HATs has been implicated in the pathogenesis associated with age-associated neurodegenerative diseases and cognitive decline. In order to counteract the loss of HAT function in neurodegenerative diseases, the current therapeutic strategies involve the use of small molecules called histone deacetylase (HDAC) inhibitors that antagonize HDAC activity and thus enhance acetylation levels. Although this strategy has displayed promising therapeutic effects, currently used HDAC inhibitors lack target specificity, raising concerns about their applicability. With rapidly evolving literature on HATs and their respective functions in mediating neuronal survival and higher order brain function such as learning and memory, modulating the function of specific HATs holds new promises as a therapeutic tool in neurodegenerative diseases. In this review, we focus on the recent progress in research regarding epigenetic histone acetylation mechanisms underlying neuronal activity and cognitive function. We discuss the current understanding of specific HDACs and HATs in neurodegenerative diseases and the future promising prospects of using specific HAT based therapeutic approaches.

The role of dietary choices in cognitive behaviour: a prospective population-based study

BackgroundCognitive decline is the first outward sign of dementia and has a major public health effect. Evidence suggests that dietary patterns are associated with cardiovascular and cerebrovascular risk factors. A high quality diet or Mediterranean diet might protect against Alzheimer's disease, but its association with age-associated cognitive decline has not been fully explored. We aimed to examine the association between two ways of quantifying dietary patterns (a healthy dietary scale and a Mediterranean diet) and 20 years of cognitive decline from age 43 years to 60–64 (>60) years in a prospective longitudinal population-based study. MethodsWe included 1018 participants from the MRC National Survey of Health and Development (the British 1946 birth cohort) regularly followed up over 23 times across their entire life since birth in 1946. Cognitive functioning was measured at age 43 years and older than 60 years by tests of verbal memory (maximum words recalled 45) and timed visual search (maximum letter searched 600). The two dietary patterns were constructed with information from a 5 day estimated diet diary at both 36 and 43 years. The healthy dietary scale represents an overall score of healthy food choices: frequency of breakfast; type of milk; type of bread; number of daily portions of fruit and vegetables; and average percentage of energy from fat. The total score was dichotomised by median split at each age to represent lower or higher quality diet. An adherence scale to the Mediterranean diet was also derived with the Trichopoulou model (2005). Participants were divided into three groups of adherence to Mediterranean diet (low, middle, and high tertiles). A cumulative midlife score was further derived for each dietary pattern. Confounding variables were father's social class, childhood cognition, educational attainment, adult social class, affective symptoms, smoking, and physical activity. FindingsBoth dietary patterns showed significant associations with memory decline in fully adjusted models. High quality diet predicted slower verbal memory decline compared with lower quality dietary choice; highest adherence to Mediterranean diet was similarly associated with slower memory decline compared with lowest adherence. These associations remained significant after adjustment for all covariates (regression coefficient 0·70, 95% CI 0·02–1·38, for the healthy dietary scale and 1·48, 0·17–2·80, for the highest adherence to Mediterranean diet). There were no associations at the 5% level between dietary choices and visual search decline. InterpretationOur results suggest that a healthy dietary choice, measured with either Mediterranean diet or healthy dietary scale in early midlife is protective of verbal memory decline from midlife to later life. Public health interventions based on healthy diets should be regarded as an important line of defence against cognitive decline and dementia. FundingDC, WN, AS, DK, and MR are funded by the UK Medical Research Council. HP is is supported by the Higher Education Funding Council for England. GM receives support from the Australian National Health and Medical Research Council (APP1000986).

Association between Tobacco Smoking and Cognitive Functioning in Young Adults

Tobacco smoking represents a considerable public health burden globally. Smoking in older adults is associated with cognitive impairment and more rapid age-associated cognitive decline, but there is a paucity of studies in younger people. Adults aged 18-29 years were recruited from a longitudinal study investigating impulsivity in young people. Exclusion criteria were presence of any axis-I morbidity or cannabis use. Subjects undertook neurocognitive assessment using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Demographic, clinical, and cognitive differences between smokers (N = 37) and nonsmokers (N = 177) were characterized. Groups were well matched in terms of age, education, income, and gender. In comparison to nonsmokers, nicotine users showed significant cognitive impairments on sustained attention (target detection: p= .005), spatial working memory (errors: p= .023, strategy use: p= .004), executive planning (p= .002), and did not appropriately adjust behavior as a function of risk (Gamble task risk adjustment: p= .004). Smokers were intact on general response speeds and response inhibition. These data, using objective translational paradigms, support an association between tobacco smoking and cognitive problems in young people, with implications for such individuals and for society. Future studies should extend these results longitudinally to explore causality, and evaluate effects of nicotinic agents (including anti-smoking medications) on cognition.

The Involvement of the GH/IGF-I Axis in Cognitive Functions of Adult Patients and Healthy Subjects

The growth hormone/insulin-like growth factor I (GH/IGF-I) axis is an important regulator of brain function which view is based on the evidence that 1) GH and IGF-I can cross the blood brain barrier, 2) GH and IGF-I can bind to sites in various brain structures, including the hippocampus, 3) GH can alter the dopamine turnover in the hippocampus and IGF-I the acetylcholine release, and 4) GH and IGF-I can activate the NMDA receptor in the hippocampus. These mechanisms may underlie the relationship between the GH/IGF-I axis and cognitive functioning. A reduced activity of the GH/IGF-I axis seems associated with cognitive dysfunction in adult patients with GH deficiency (GHD), Prader-Willi syndrome, traumatic brain injury (TBI), dementia and also with age-associated cognitive decline in healthy elderly. Moreover, IGF-I deficiency may be involved in the aetiology of schizophrenia. Treatment with GH appears to have a beneficial effect on cognitive functions in patients with GHD, Prader-Willi and TBI. However, as evidence of GH replacement on cognition in distinct groups is limited and diet, exercise, and specific medicines have known effects on the GH/IGF-I axis, future studies on the relationship between GH-, diet-, exercise-, or medication-induced GH/IGF-I increase and cognition are required.

In the Rush for Green Gold: Can Green Tea Delay Age-Progressive Brain Neurodegeneration?

It is evident that brain aging engages changes in biological systems linked to synaptic function and cell metabolism and in the capacity to cope with different stresses that are either idiopathic in nature, or subject to environmental insults. In a substantial segment of the aging population there is a pathological transition to cognitive and behavioral dysfunction and thus, age constitutes the primary risk factor for Alzheimer's disease and other neurodegenerative disorders. To address the etiological complexity of aging and age-associated conditions, a new paradigm gaining increasing acceptance considers the use of multi-targeted ligands or combination of drugs to modulate several targets at once. During the past years intensive efforts are dedicated to the implementation of life style habits such as exercise and dietary compounds/supplements in combination with symptomatic treatment drugs to improve age-related cognitive decline and to attenuate motor and neurological dysfunction in neurodegenerative diseases. The catechin polyphenols constituents of green tea, which were for long time regarded merely as dietary antioxidants, have caught our and other scientist's attention because of their diverse pharmacological activities, which have been allied to a possible beneficial action on brain health. This review will elaborate on the impact of nutritional supplementation on brain function in general, and provide a compilation of the most updated literature on epidemiology, clinical and animal studies with green tea polyphenols in age-associated cognitive decline and in fighting neurodegenerative diseases. To conclude, a future perspective on the utility and assigned patents with green tea constituents will be presented.