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Sample records for age-related cognitive deficits

  1. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning.

    PubMed

    Crowley, Olga V; Kimhy, David; McKinley, Paula S; Burg, Matthew M; Schwartz, Joseph E; Lachman, Margie E; Tun, Patricia A; Ryff, Carol D; Seeman, Teresa E; Sloan, Richard P

    2016-05-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35-86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65-86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35-54) and middle-aged (aged 55-64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  2. Vagal Recovery From Cognitive Challenge Moderates Age-Related Deficits in Executive Functioning

    PubMed Central

    Crowley, Olga V.; Kimhy, David; McKinley, Paula S.; Burg, Matthew M.; Schwartz, Joseph E.; Lachman, Margie E.; Tun, Patricia A.; Ryff, Carol D.; Seeman, Teresa E.; Sloan, Richard P.

    2015-01-01

    Decline in executive functioning (EF) is a hallmark of cognitive aging. We have previously reported that faster vagal recovery from cognitive challenge is associated with better EF. This study examined the association between vagal recovery from cognitive challenge and age-related differences in EF among 817 participants in the Midlife in the U.S. study (aged 35–86). Cardiac vagal control was measured as high-frequency heart rate variability. Vagal recovery moderated the association between age and EF (β = .811, p = .004). Secondary analyses revealed that older participants (aged 65–86) with faster vagal recovery had superior EF compared to their peers who had slower vagal recovery. In contrast, among younger (aged 35–54) and middle-aged (aged 55–64) participants, vagal recovery was not associated with EF. We conclude that faster vagal recovery from cognitive challenge is associated with reduced deficits in EF among older, but not younger individuals. PMID:26303063

  3. High cognitive reserve is associated with a reduced age-related deficit in spatial conflict resolution

    PubMed Central

    Puccioni, Olga; Vallesi, Antonino

    2012-01-01

    Several studies support the existence of a specific age-related difficulty in suppressing potentially distracting information. The aim of the present study is to investigate whether spatial conflict resolution is selectively affected by aging. The way aging affects individuals could be modulated by many factors determined by the socieconomic status: we investigated whether factors such as cognitive reserve (CR) and years of education may play a compensatory role against age-related deficits in the spatial domain. A spatial Stroop task with no feature repetitions was administered to a sample of 17 non-demented older adults (69–79 years-old) and 18 younger controls (18–34 years-old) matched for gender and years of education. The two age groups were also administered with measures of intelligence and CR. The overall spatial Stroop effect did not differ according to age, neither for speed nor for accuracy. The two age groups equally showed sequential effects for congruent trials: reduced response times (RTs) if another congruent trial preceded them, and accuracy at ceiling. For incongruent trials, older adults, but not younger controls, were influenced by congruency of trialn−1, since RTs increased with preceding congruent trials. Interestingly, such an age-related modulation negatively correlated with CR. These findings suggest that spatial conflict resolution in aging is predominantly affected by general slowing, rather than by a more specific deficit. However, a high level of CR seems to play a compensatory role for both factors. PMID:23248595

  4. Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

    PubMed

    Maimaiti, Shaniya; Anderson, Katie L; DeMoll, Chris; Brewer, Lawrence D; Rauh, Benjamin A; Gant, John C; Blalock, Eric M; Porter, Nada M; Thibault, Olivier

    2016-01-01

    Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP. PMID:25659889

  5. Intrinsic Hippocampal Excitability Changes of Opposite Signs and Different Origins in CA1 and CA3 Pyramidal Neurons Underlie Aging-Related Cognitive Deficits

    PubMed Central

    Oh, M. Matthew; Simkin, Dina; Disterhoft, John F.

    2016-01-01

    Aging-related cognitive deficits have been attributed to dysfunction of neurons due to failures at synaptic or intrinsic loci, or both. Given the importance of the hippocampus for successful encoding of memory and that the main output of the hippocampus is via the CA1 pyramidal neurons, much of the research has been focused on identifying the aging-related changes of these CA1 pyramidal neurons. We and others have discovered that the postburst afterhyperpolarization (AHP) following a train of action potentials is greatly enlarged in CA1 pyramidal neurons of aged animals. This enlarged postburst AHP is a significant factor in reducing the intrinsic excitability of these neurons, and thus limiting their activity in the neural network during learning. Based on these data, it has largely been thought that aging-related cognitive deficits are attributable to reduced activity of pyramidal neurons. However, recent in vivo and ex vivo studies provide compelling evidence that aging-related deficits could also be due to a converse change in CA3 pyramidal neurons, which show increased activity with aging. In this review, we will incorporate these recent findings and posit that an interdependent dynamic dysfunctional change occurs within the hippocampal network, largely due to altered intrinsic excitability in CA1 and CA3 hippocampal pyramidal neurons, which ultimately leads to the aging-related cognitive deficits. PMID:27375440

  6. Hippocampal expression of myelin-associated inhibitors is induced with age-related cognitive decline and correlates with deficits of spatial learning and memory

    PubMed Central

    VanGuilder, Heather D.; Bixler, Georgina V.; Sonntag, William E.; Freeman, Willard M.

    2012-01-01

    Impairment of cognitive functions including hippocampus-dependent spatial learning and memory affects nearly half of the aged population. Age-related cognitive decline is associated with synaptic dysfunction that occurs in the absence of neuronal cell loss, suggesting that impaired neuronal signaling and plasticity may underlie age-related deficits of cognitive function. Expression of myelin-associated inhibitors (MAIs) of synaptic plasticity, including the ligands MAG, Nogo-A, and OMgp, and their common receptor, NgR1, was examined in hippocampal synaptosomes and CA1, CA3 and DG subregions derived from adult (12–13 months) and aged (26–28 months) Fischer 344 × Brown Norway rats. Rats were behaviorally phenotyped by Morris water maze testing and classified as aged cognitively intact (n=7–8) or aged cognitively impaired (n=7–10) relative to adults (n=5–7). MAI protein expression was induced in cognitively impaired, but not cognitively intact, aged rats and correlated with cognitive performance in individual rats. Immunohistochemical experiments demonstrated that upregulation of MAIs occurs, in part, in hippocampal neuronal axons and somata. While a number of pathways and processes are altered with brain aging, we report a coordinated induction of myelin-associated inhibitors of functional and structural plasticity only in cognitively impaired aged rats. Induction of MAIs may decrease stimulus-induced synaptic strengthening and structural remodeling, ultimately impairing synaptic mechanisms of spatial learning and memory and resulting in cognitive decline. PMID:22269040

  7. Consequences of Age-Related Cognitive Declines

    PubMed Central

    Salthouse, Timothy

    2013-01-01

    Adult age differences in a variety of cognitive abilities are well documented, and many of those abilities have been found to be related to success in the workplace and in everyday life. However, increased age is seldom associated with lower levels of real-world functioning, and the reasons for this lab-life discrepancy are not well understood. This article briefly reviews research concerned with relations of age to cognition, relations of cognition to successful functioning outside the laboratory, and relations of age to measures of work performance and achievement. The final section discusses several possible explanations for why there are often little or no consequences of age-related cognitive declines in everyday functioning. PMID:21740223

  8. Oxidative stress and age-related neuronal deficits.

    PubMed

    Joseph, J A; Denisova, N; Villalobos-Molina, R; Erat, S; Strain, J

    1996-01-01

    Research from our laboratory has indicated that the loss of sensitivity that occurs in several receptor systems as a function of age may be an index of an increasing inability to respond to oxidative stress (OS). This loss occurs partially as a result of altered signal transduction (ST). Assessments have involved determining the nature of age-related reductions in oxotremorine enhancement of K(+)-evoked dopamine release (K(+)-ERDA) from superfused striatal slices. Using this model, we have found that 1. Reductions can be restored with in vivo administration of the free-radical trapping agent, N-tert-butyl-alpha-phenylnitrone (PBN); 2. Decrements in DA release induced by NO or H2O2 from striatal slices from both young and old animals could be restored with alpha-tocopherol or PBN; 3. ST decrements, such as those seen in aging, could be induced with radiation exposure; and 4. Pre-incubation of the striatal slices with cholesterol decreased subsequent deleterious effects of NO or OH. on DA release. Thus, cholesterol, which increases in neuronal membranes as a function of age, may function as a potent antioxidant and protectant against neuronal damage. These results suggest that therapeutic efforts to restore cognitive deficits in aging and age-related disease might begin with antioxidant reversal of ST decrements. PMID:8871939

  9. Can DRYAD explain age-related associative memory deficits?

    PubMed

    Smyth, Andrea C; Naveh-Benjamin, Moshe

    2016-02-01

    A recent interesting theoretical account of aging and memory judgments, the DRYAD (density of representations yields age-related deficits; Benjamin, 2010; Benjamin, Diaz, Matzen, & Johnson, 2012), attributes the extensive findings of disproportional age-related deficits in memory for source, context, and associations, to a global decline in memory fidelity. It is suggested that this global deficit, possibly due to a decline in attentional processes, is moderated by weak representation of contextual information to result in disproportional age-related declines. In the current article, we evaluate the DRYAD model, comparing it to specific age-related deficits theories, in particular, the ADH (associative deficit hypothesis, Naveh-Benjamin, 2000). We question some of the main assumptions/hypotheses of DRYAD in light of data reported in the literature, and we directly assess the role of attention in age-related deficits by manipulations of divided attention and of the instructions regarding what to pay attention to in 2 experiments (one from the literature and a new one). The results of these experiments fit the predictions of the ADH and do not support the main assumption/hypotheses of DRYAD. PMID:25961878

  10. Altered Hippocampal Transcript Profile Accompanies an Age-Related Spatial Memory Deficit in Mice

    ERIC Educational Resources Information Center

    Verbitsky, Miguel; Yonan, Amanda L.; Malleret, Gael; Kandel, Eric R.; Gilliam, T. Conrad; Pavlidis, Paul

    2004-01-01

    We have carried out a global survey of age-related changes in mRNA levels in the 57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged…

  11. Nutritional interventions protect against age-related deficits in behavior: from animals to humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks. Similar changes in behavior occur in humans with age, and the development of methods to retard or reverse these age-related neuronal and behavioral deficits could increase healthy aging and decrease health care costs. In the present s...

  12. Neuroanatomical Substrates of Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Salthouse, Timothy A.

    2011-01-01

    There are many reports of relations between age and cognitive variables and of relations between age and variables representing different aspects of brain structure and a few reports of relations between brain structure variables and cognitive variables. These findings have sometimes led to inferences that the age-related brain changes cause the…

  13. Veterans have less age-related cognitive decline.

    PubMed

    McLay, R N; Lyketsos, C G

    2000-08-01

    Military service involves exposure to a number of stresses, both psychological and physical. On the other hand, military personnel generally maintain excellent fitness, and veterans have increased access to education and health care. The overall effect on age-related cognitive decline, whether for good or ill, of having served in the armed forces has not been investigated previously. In this study, we examined a diverse population of 208 veterans and 1,216 civilians followed as part of the Epidemiologic Catchment Area Study in 1981, 1982, and 1993 to 1996. We examined change in Mini-Mental State Examination (MMSE) score after a median of 11.5 years. Veterans were found to have significantly less decrease in MMSE scores at follow-up even after sex, race, and education were taken into account. These results suggest an overall positive effect of military service on the rate of age-related cognitive decline. PMID:10957857

  14. Molecular aspects of age-related cognitive decline: the role of GABA signaling

    PubMed Central

    McQuail, Joseph A.; Frazier, Charles J.; Bizon, Jennifer L.

    2015-01-01

    Alterations in inhibitory interneurons contribute to cognitive deficits associated with several psychiatric and neurological diseases. Phasic and tonic inhibition imparted by γ-amino-butyric acid (GABA) receptors regulates neural activity and helps to establish the appropriate network dynamics in cortical circuits that support normal cognition. This review highlights basic science demonstrating that inhibitory signaling is altered in aging, and discusses the impact of age-related shifts in inhibition on different forms of memory function, including hippocampus-dependent spatial reference memory and prefrontal cortex (PFU)-dependent working memory. The clinical appropriateness and tractability of select therapeutic candidates for cognitive aging that target receptors mediating inhibition are also discussed. PMID:26070271

  15. Hippocampal dysregulation of synaptic plasticity-associated proteins with age-related cognitive decline

    PubMed Central

    VanGuilder, Heather D.; Farley, Julie A.; Yan, Han; Van Kirk, Colleen A.; Mitschelen, Matthew; Sonntag, William E.; Freeman, Willard M.

    2011-01-01

    Age-related cognitive decline occurs without frank neurodegeneration and is the most common cause of memory impairment in aging individuals. With increasing longevity, cognitive deficits, especially in hippocampus-dependent memory processes, are increasing in prevalence. Nevertheless, the neurobiological basis of age-related cognitive decline remains unknown. While concerted efforts have led to the identification of neurobiological changes with aging, few age-related alterations have been definitively correlated to behavioral measures of cognitive decline. In this work, adult (12 Months) and aged (28 months) rats were categorized by Morris water maze performance as Adult cognitively Intact, Aged cognitively Intact or Aged cognitively Impaired, and protein expression was examined in hippocampal synaptosome preparations. Previously described differences in synaptic expression of neurotransmission-associated proteins (Dnm1, Hpca, Stx1, Syn1, Syn2, Syp, SNAP25, VAMP2 and 14-3-3 eta, gamma, and zeta) were confirmed between Adult and Aged rats, with no further dysregulation associated with cognitive impairment. Proteins related to synaptic structural stability (MAP2, drebrin, Nogo-A) and activity-dependent signaling (PSD-95, 14-3-3θ, CaMKIIα) were up- and down-regulated, respectively, with cognitive impairment but were not altered with increasing age. Localization of MAP2, PSD-95, and CaMKIIα demonstrated protein expression alterations throughout the hippocampus. The altered expression of activity- and structural stability-associated proteins suggests that impaired synaptic plasticity is a distinct phenomenon that occurs with age-related cognitive decline, and demonstrates that cognitive decline is not simply an exacerbation of the aging phenotype. PMID:21440628

  16. Epigenetic modification of PKMζ rescues aging-related cognitive impairment

    PubMed Central

    Chen, Chen; Meng, Shi-Qiu; Xue, Yan-Xue; Han, Ying; Sun, Cheng-Yu; Deng, Jia-Hui; Chen, Na; Bao, Yan-Ping; Zhang, Fei-Long; Cao, Lin-Lin; Zhu, Wei-Guo; Shi, Jie; Song, Wei-Hong; Lu, Lin

    2016-01-01

    Cognition is impacted by aging. However, the mechanisms that underlie aging-associated cognitive impairment are unclear. Here we showed that cognitive decline in aged rats was associated with changes in DNA methylation of protein kinase Mζ (PKMζ) in the prelimbic cortex (PrL). PKMζ is a crucial molecule involved in the maintenance of long-term memory. Using different behavioral models, we confirmed that aged rats exhibited cognitive impairment in memory retention test 24 h after training, and overexpression of PKMζ in the PrL rescued cognitive impairment in aged rats. After fear conditioning, the protein levels of PKMζ and the membrane expression of GluR2 increased in the PrL in young and adult rats but not in aged rats, and the levels of methylated PKMζ DNA in the PrL decreased in all age groups, whereas the levels of unmethylated PKMζ DNA increased only in young and adult rats. We also found that environmentally enriched housing reversed the hypermethylation of PKMζ and restored cognitive performance in aged rats. Inactivation of PKMζ prevented the potentiating effects of environmental enrichment on memory retention in aged rats. These results indicated that PKMζ might be a potential target for the treatment of aging-related cognitive impairment, suggesting a potential therapeutic avenue. PMID:26926225

  17. Age-related deficit in a bimanual joint position matching task is amplitude dependent

    PubMed Central

    Boisgontier, Matthieu P.; Swinnen, Stephan P.

    2015-01-01

    The cognitive load associated with joint position sense increases with age but does not necessarily result in impaired performance in a joint position matching task. It is still unclear which factors interact with age to predict matching performance. To test whether movement amplitude and direction are part of such predictors, young and older adults performed a bimanual wrist joint position matching task. Results revealed an age-related deficit when the target limb was positioned far from (25°) the neutral position, but not when close to (15°, 5°) the neutral joint position, irrespective of the direction. These results suggest that the difficulty associated with the comparison of two musculoskeletal states increases towards extreme joint amplitude and that older adults are more vulnerable to this increased difficulty. PMID:26347649

  18. Age-related deficit accumulation and the risk of late-life dementia

    PubMed Central

    2014-01-01

    Introduction Many age-related health problems have been associated with dementia, leading to the hypothesis that late-life dementia may be determined less by specific risk factors, and more by the operation of multiple health deficits in the aggregate. Our study addressed (a) how the predictive value of dementia risk varies by the number of deficits considered and (b) how traditional (for example. vascular risks) and nontraditional risk factors (for example, foot problems, nasal congestion) compare in their predictive effects. Methods Older adults in the Canadian Study of Health and Aging who were cognitively healthy at baseline were analyzed (men, 2,902; women, 4,337). Over a 10-year period, 44.8% of men and 33.4% of women died; 7.4% of men and 9.1% of women without baseline cognitive impairment developed dementia. Self-rated health problems, including, but not restricted to, dementia risk factors, were coded as deficit present/absent. Different numbers of randomly selected variables were used to calculate various iterations of the index (that is, the proportion of deficits present in an individual. Risks for 10-year mortality and dementia outcomes were evaluated separately for men and women by using logistic regression, adjusted for age. The prediction accuracy was evaluated by using C-statistics. Results Age-adjusted odds ratios per additional deficit were 1.22 (95% confidence interval (CI), 1.18 to 1.26) in men and 1.14 (1.11 to 1.16) in women in relation to death, and 1.18 (1.12 to 1.25) in men and 1.08 (1.04 to 1.11) in women in relation to dementia. The predictive value increased with the number (n) of deficits considered, regardless of whether they were known dementia risks, and stabilized at n > 25. The all-factor index best predicted dementia (C-statistics, 0.67 ± 0.03). Conclusions The variety of items associated with dementias suggests that some part of the risk might relate more to aberrant repair processes, than to specifically toxic results

  19. Closed-Loop Rehabilitation of Age-Related Cognitive Disorders

    PubMed Central

    Mishra, Jyoti; Gazzaley, Adam

    2015-01-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual’s neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  20. Closed-loop rehabilitation of age-related cognitive disorders.

    PubMed

    Mishra, Jyoti; Gazzaley, Adam

    2014-11-01

    Cognitive deficits are common in older adults, as a result of both the natural aging process and neurodegenerative disease. Although medical advancements have successfully prolonged the human lifespan, the challenge of remediating cognitive aging remains. The authors discuss the current state of cognitive therapeutic interventions and then present the need for development and validation of more powerful neurocognitive therapeutics. They propose that the next generation of interventions be implemented as closed-loop systems that target specific neural processing deficits, incorporate quantitative feedback to the individual and clinician, and are personalized to the individual's neurocognitive capacities using real-time performance-adaptive algorithms. This approach should be multimodal and seamlessly integrate other treatment approaches, including neurofeedback and transcranial electrical stimulation. This novel approach will involve the generation of software that engages the individual in an immersive and enjoyable game-based interface, integrated with advanced biosensing hardware, to maximally harness plasticity and assure adherence. Introducing such next-generation closed-loop neurocognitive therapeutics into the mainstream of our mental health care system will require the combined efforts of clinicians, neuroscientists, bioengineers, software game developers, and industry and policy makers working together to meet the challenges and opportunities of translational neuroscience in the 21st century. PMID:25520029

  1. Changes in pattern completion – a key mechanism to explain age-related recognition memory deficits?

    PubMed Central

    Vieweg, Paula; Stangl, Matthias; Howard, Lorelei R.; Wolbers, Thomas

    2016-01-01

    Accurate memory retrieval from partial or degraded input requires the reactivation of memory traces, a hippocampal mechanism termed pattern completion. Age-related changes in hippocampal integrity have been hypothesized to shift the balance of memory processes in favor of the retrieval of already stored information (pattern completion), to the detriment of encoding new events (pattern separation). Using a novel behavioral paradigm, we investigated the impact of cognitive aging (1) on recognition performance across different levels of stimulus completeness, and (2) on potential response biases. Participants were required to identify previously learned scenes among new ones. Additionally, all stimuli were presented in gradually masked versions to alter stimulus completeness. Both young and older adults performed increasingly poorly as the scenes became less complete, and this decline in performance was more pronounced in elderly participants indicative of a pattern completion deficit. Intriguingly, when novel scenes were shown, only the older adults showed an increased tendency to identify these as familiar scenes. In line with theoretical models, we argue that this reflects an age-related bias towards pattern completion. PMID:25597525

  2. Age-related difference in relationships between cognitive processing speed and general cognitive status.

    PubMed

    Tam, Helena M K; Lam, Charlene L M; Huang, Haixia; Wang, Baolan; Lee, Tatia M C

    2015-01-01

    General cognitive status (GCS) is a composite of cognitive abilities reflecting full function. The literature suggests a relationship between cognitive processing speed and GCS, as well as age-related changes of processing speed on cognitive performance. Therefore, this study recruited 34 younger and 39 older adults to verify age-related differences in relationships between cognitive processing speed and GCS. We measured cognitive processing speed with the Processing Speed Index of the Wechsler Adult Intelligence Scale. Findings indicated that cognitive processing speed predicted GCS in older but not younger adults. Future research may be needed to verify the training effect of processing speed on GCS. This study also further examined cognitive factors related to processing speed in aging and the relationships between cognitive processing speed and verbal fluency, cognitive inhibition, and divided attention. A stepwise regression analysis indicated that only verbal fluency contributed significantly to cognitive processing speed in older adults, accounting for 21% of the variance. These observations suggest that age-related changes of prefrontal regions may not fully explain age-related decline in cognitive processing speed. PMID:24927241

  3. Dynamical network model for age-related health deficits and mortality

    NASA Astrophysics Data System (ADS)

    Taneja, Swadhin; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-02-01

    How long people live depends on their health, and how it changes with age. Individual health can be tracked by the accumulation of age-related health deficits. The fraction of age-related deficits is a simple quantitative measure of human aging. This quantitative frailty index (F ) is as good as chronological age in predicting mortality. In this paper, we use a dynamical network model of deficits to explore the effects of interactions between deficits, deficit damage and repair processes, and the connection between the F and mortality. With our model, we qualitatively reproduce Gompertz's law of increasing human mortality with age, the broadening of the F distribution with age, the characteristic nonlinear increase of the F with age, and the increased mortality of high-frailty individuals. No explicit time-dependence in damage or repair rates is needed in our model. Instead, implicit time-dependence arises through deficit interactions—so that the average deficit damage rates increase, and deficit repair rates decrease, with age. We use a simple mortality criterion, where mortality occurs when the most connected node is damaged.

  4. Aging and associative recognition: A view from the DRYAD model of age-related memory deficits.

    PubMed

    Benjamin, Aaron S

    2016-02-01

    How do we best characterize the memory deficits that accompany aging? A popular hypothesis, articulated originally by Naveh-Benjamin (2000) and reviewed in the accompanying article by Smyth and Naveh-Benjamin (2016), suggests that older adults are selectively deficient in establishing associations between to-be-learned memoranda and as a result have deficits in memory for sources or contexts. An alternative proposal, called density of representations yields age-related deficits (DRYAD) and outlined in recent articles by Benjamin (2010) and colleagues (Benjamin, Diaz, Matzen, & Johnson, 2012), attributes disproportionate deficits in memory to a global, rather than a selective, deficit of memory. In an attempt to adjudicate between these competing positions, Smyth and Naveh-Benjamin (2016) discussed 2 sets of experimental data that they claim speak against the global deficit model. Here I review some general principles of how the global-deficit view is applied to experimental paradigms and demonstrate that even a simplified form of DRYAD can comfortably accommodate the critical findings cited by Smyth and Naveh-Benjamin. I also evaluate aspects of their results that may be problematic for DRYAD and describe ways in which DRYAD's account of associative recognition can be falsified. I end with a discussion of the complementary strengths and weaknesses of the 2 approaches and consider ways in which the associative deficit hypothesis and DRYAD might work more profitably together than apart. PMID:26866587

  5. Age-Related Declines in General Cognitive Abilities of Balb/C Mice and General Activity Are Associated with Disparities in Working Memory, Body Weight, and General Activity

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Grossman, Henya; Light, Kenneth; Townsend, David; Kolata, Stefan

    2008-01-01

    A defining characteristic of age-related cognitive decline is a deficit in general cognitive performance. Here we use a testing and analysis regimen that allows us to characterize the general learning abilities of young (3-5 mo old) and aged (19-21 mo old) male and female Balb/C mice. Animals' performance was assessed on a battery of seven diverse…

  6. The role of cognition in age-related hearing loss.

    PubMed

    Craik, Fergus I M

    2007-01-01

    The article presents a commentary on the accompanying six papers from the perspective of a cognitive psychologist. Treisman's (1964, 1969) levels of analysis model of selective attention is suggested as a framework within which the interactions between 'bottom-up' auditory factors and 'top-down' cognitive factors may be understood. The complementary roles of auditory and cognitive aspects of hearing are explored, and their mutually compensatory properties discussed. The findings and ideas reported in the six accompanying papers fit well into such a 'levels of processing' framework, which may therefore be proposed as a model for understanding the effects of aging on speech processing and comprehension. PMID:18236642

  7. [Cognitive deficits in bipolar disorder].

    PubMed

    Sachs, Gabriele; Schaffer, Markus; Winklbaur, Bernadette

    2007-01-01

    Bipolar disorders are often associated with cognitive deficits which have an influence on social functioning and the course of the illness. These deficits have an impact on occupational ability and social integration. To date, specific cognitive domains have been found which characterize bipolar affective disorders. However, there is evidence of stable and lasting cognitive impairment in all phases of the disorder, including the remission phase, in the following domains: sustained attention, memory and executive functions (e.g. cognitive flexibility and problem solving). Although their cognitive deficits are comparable the deficits in patients with schizophrenia are more severe than those with bipolar disorder. Recent brain imaging findings indicate structural and functional abnormalities in the cortical and limbic networks of the brain in patients with bipolar disorder compared to healthy controls. Mood stabilizer and atypical antipsychotics may reduce cognitive deficits in certain domains (e.g. executive functions and word fluency) and may have a positive effect on quality of life and social functioning. PMID:17640495

  8. Longitudinal Attentional Engagement Rescues Mice from Age-Related Cognitive Declines and Cognitive Inflexibility

    ERIC Educational Resources Information Center

    Matzel, Louis D.; Light, Kenneth R.; Wass, Christopher; Colas-Zelin, Danielle; Denman-Brice, Alexander; Waddel, Adam C.; Kolata, Stefan

    2011-01-01

    Learning, attentional, and perseverative deficits are characteristic of cognitive aging. In this study, genetically diverse CD-1 mice underwent longitudinal training in a task asserted to tax working memory capacity and its dependence on selective attention. Beginning at 3 mo of age, animals were trained for 12 d to perform in a dual radial-arm…

  9. Age-related differences in gap detection: Effects of task difficulty and cognitive ability

    PubMed Central

    Harris, Kelly C.; Eckert, Mark A.; Ahlstrom, Jayne B.; Dubno, Judy R.

    2009-01-01

    Differences in gap detection for younger and older adults have been shown to vary with the complexity of the task or stimuli, but the factors that contribute to these differences remain unknown. To address this question, we examined the extent to which age-related differences in processing speed and workload predicted age-related differences in gap detection. Gap detection thresholds were measured for 10 younger and 11 older adults in two conditions that varied in task complexity but used identical stimuli: (1) gap location fixed at the beginning, middle, or end of a noise burst and (2) gap location varied randomly from trial to trial from the beginning, middle, or end of the noise. We hypothesized that gap location uncertainty would place increased demands on cognitive and attentional resources and result in significantly higher gap detection thresholds for older but not younger adults. Overall, gap detection thresholds were lower for the middle location as compared to beginning and end locations and were lower for the fixed than the random condition. In general, larger age-related differences in gap detection were observed for more challenging conditions. That is, gap detection thresholds for older adults were significantly larger for the random condition than for the fixed condition when the gap was at the beginning and end locations but not the middle. In contrast, gap detection thresholds for younger adults were not significantly different for the random and fixed condition at any location. Subjective ratings of workload indicated that older adults found the gap-detection task more mentally demanding than younger adults. Consistent with these findings, results of the Purdue Pegboard and Connections tests revealed age-related slowing of processing speed. Moreover, age group differences in workload and processing speed predicted gap detection in younger and older adults when gap location varied from trial to trial; these associations were not observed when gap

  10. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates

    PubMed Central

    Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc

    2015-01-01

    The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination. PMID:26716699

  11. Jumping Stand Apparatus Reveals Rapidly Specific Age-Related Cognitive Impairments in Mouse Lemur Primates.

    PubMed

    Picq, Jean-Luc; Villain, Nicolas; Gary, Charlotte; Pifferi, Fabien; Dhenain, Marc

    2015-01-01

    The mouse lemur (Microcebus murinus) is a promising primate model for investigating normal and pathological cerebral aging. The locomotor behavior of this arboreal primate is characterized by jumps to and from trunks and branches. Many reports indicate insufficient adaptation of the mouse lemur to experimental devices used to evaluate its cognition, which is an impediment to the efficient use of this animal in research. In order to develop cognitive testing methods appropriate to the behavioral and biological traits of this species, we adapted the Lashley jumping stand apparatus, initially designed for rats, to the mouse lemur. We used this jumping stand apparatus to compare performances of young (n = 12) and aged (n = 8) adults in acquisition and long-term retention of visual discriminations. All mouse lemurs completed the tasks and only 25 trials, on average, were needed to master the first discrimination problem with no age-related differences. A month later, all mouse lemurs made progress for acquiring the second discrimination problem but only the young group reached immediately the criterion in the retention test of the first discrimination problem. This study shows that the jumping stand apparatus allows rapid and efficient evaluation of cognition in mouse lemurs and demonstrates that about half of the old mouse lemurs display a specific deficit in long-term retention but not in acquisition of visual discrimination. PMID:26716699

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

    PubMed

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

    2016-04-01

    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

  13. From mind wandering to involuntary retrieval: Age-related differences in spontaneous cognitive processes.

    PubMed

    Maillet, David; Schacter, Daniel L

    2016-01-01

    The majority of studies that have investigated the effects of healthy aging on cognition have focused on age-related differences in voluntary and deliberately engaged cognitive processes. Yet many forms of cognition occur spontaneously, without any deliberate attempt at engaging them. In this article we review studies that have assessed age-related differences in four such types of spontaneous thought processes: mind-wandering, involuntary autobiographical memory, intrusive thoughts, and spontaneous prospective memory retrieval. These studies suggest that older adults exhibit a reduction in frequency of both mind-wandering and involuntary autobiographical memory, whereas findings regarding intrusive thoughts have been more mixed. Additionally, there is some preliminary evidence that spontaneous prospective memory retrieval may be relatively preserved in aging. We consider the roles of age-related differences in cognitive resources, motivation, current concerns and emotional regulation in accounting for these findings. We also consider age-related differences in the neural correlates of spontaneous cognitive processes. PMID:26617263

  14. Shared and Unique Genetic and Environmental Influences on Aging-Related Changes in Multiple Cognitive Abilities

    ERIC Educational Resources Information Center

    Tucker-Drob, Elliot M.; Reynolds, Chandra A.; Finkel, Deborah; Pedersen, Nancy L.

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying…

  15. Age-Related Declines in Visuospatial Working Memory Correlate With Deficits in Explicit Motor Sequence Learning

    PubMed Central

    Bo, J.; Borza, V.

    2009-01-01

    Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning. PMID:19726728

  16. Age-related declines in visuospatial working memory correlate with deficits in explicit motor sequence learning.

    PubMed

    Bo, J; Borza, V; Seidler, R D

    2009-11-01

    Numerous studies have shown that older adults exhibit deficits in motor sequence learning, but the mechanisms underlying this effect remain unclear. Our recent work has shown that visuospatial working-memory capacity predicts the rate of motor sequence learning and the length of motor chunks formed during explicit sequence learning in young adults. In the current study, we evaluate whether age-related deficits in working memory explain the reduced rate of motor sequence learning in older adults. We found that older adults exhibited a correlation between visuospatial working-memory capacity and motor sequence chunk length, as we observed previously in young adults. In addition, older adults exhibited an overall reduction in both working-memory capacity and motor chunk length compared with that of young adults. However, individual variations in visuospatial working-memory capacity did not correlate with the rate of learning in older adults. These results indicate that working memory declines with age at least partially explain age-related differences in explicit motor sequence learning. PMID:19726728

  17. The potential effects of meditation on age-related cognitive decline: a systematic review

    PubMed Central

    Gard, Tim; Hölzel, Britta K.; Lazar, Sara W.

    2014-01-01

    With a rapidly aging society it becomes increasingly important to counter normal age-related decline in cognitive functioning. Growing evidence suggests that cognitive training programs may have the potential to counteract this decline. On the basis of a growing body of research that shows that meditation has positive effects on cognition in younger and middle-aged adults, meditation may be able to offset normal age-related cognitive decline or even enhance cognitive function in older adults. In this paper, we review studies investigating the effects of meditation on age-related cognitive decline. We searched the Web of Science (1900 to present), PsycINFO (1597 to present), MEDLINE (1950 to present), and CABI (1910 to present) to identify original studies investigating the effects of meditation on cognition and cognitive decline in the context of aging. Twelve studies were included in the review, six of which were randomized controlled trials. Studies involved a wide variety of meditation techniques and reported preliminary positive effects on attention, memory, executive function, processing speed, and general cognition. However, most studies had a high risk of bias and small sample sizes. Reported dropout rates were low and compliance rates high. We conclude that meditation interventions for older adults are feasible, and preliminary evidence suggests that meditation can offset age-related cognitive decline. PMID:24571182

  18. Proactive interference and concurrent inhibitory processes do not differentially affect item and associative recognition: Implication for the age-related associative memory deficit.

    PubMed

    Guez, Jonathan; Naveh-Benjamin, Moshe

    2016-09-01

    Previous studies have suggested an associative deficit hypothesis [Naveh-Benjamin, M. ( 2000 ). Adult age differences in memory performance: Tests of an associative deficit hypothesis. Journal of Experimental Psychology: Learning, Memory, and Cognition, 26, 1170-1187] to explain age-related episodic memory declines. The hypothesis attributes part of the deficient episodic memory performance in older adults to a difficulty in creating and retrieving cohesive episodes. In this article, we further evaluate this hypothesis by testing two alternative processes that potentially mediate associative memory deficits in older adults. Four experiments are presented that assess whether failure of inhibitory processes (proactive interference in Experiments 1 and 2), and concurrent inhibition (in Experiments 3 and 4) are mediating factors in age-related associative deficits. The results suggest that creating conditions that require the operation of inhibitory processes, or that interfere with such processes, cannot simulate associative memory deficit in older adults. Instead, such results support the idea that associative memory deficits reflect a unique binding failure in older adults. This failure seems to be independent of other cognitive processes, including inhibitory and other resource-demanding processes. PMID:26230249

  19. Age-related differences in cognition across the adult lifespan in autism spectrum disorder.

    PubMed

    Lever, Anne G; Geurts, Hilde M

    2016-06-01

    It is largely unknown how age impacts cognition in autism spectrum disorder (ASD). We investigated whether age-related cognitive differences are similar, reduced or increased across the adult lifespan, examined cognitive strengths and weaknesses, and explored whether objective test performance is related to subjective cognitive challenges. Neuropsychological tests assessing visual and verbal memory, generativity, and theory of mind (ToM), and a self-report measure assessing cognitive failures were administered to 236 matched participants with and without ASD, aged 20-79 years (IQ > 80). Group comparisons revealed that individuals with ASD had higher scores on visual memory, lower scores on generativity and ToM, and similar performance on verbal memory. However, ToM impairments were no longer present in older (50+ years) adults with ASD. Across adulthood, individuals with ASD demonstrated similar age-related effects on verbal memory, generativity, and ToM, while age-related differences were reduced on visual memory. Although adults with ASD reported many cognitive failures, those were not associated with neuropsychological test performance. Hence, while some cognitive abilities (visual and verbal memory) and difficulties (generativity and semantic memory) persist across adulthood in ASD, others become less apparent in old age (ToM). Age-related differences characteristic of typical aging are reduced or parallel, but not increased in individuals with ASD, suggesting that ASD may partially protect against an age-related decrease in cognitive functioning. Despite these findings, adults with ASD experience many cognitive daily challenges, which highlights the need for adequate social support and the importance of further research into this topic, including longitudinal studies. Autism Res 2016, 9: 666-676. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. PMID:26333004

  20. 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

  1. Age-related decline in cognitive control: the role of fluid intelligence and processing speed

    PubMed Central

    2014-01-01

    Background Research on cognitive control suggests an age-related decline in proactive control abilities whereas reactive control seems to remain intact. However, the reason of the differential age effect on cognitive control efficiency is still unclear. This study investigated the potential influence of fluid intelligence and processing speed on the selective age-related decline in proactive control. Eighty young and 80 healthy older adults were included in this study. The participants were submitted to a working memory recognition paradigm, assessing proactive and reactive cognitive control by manipulating the interference level across items. Results Repeated measures ANOVAs and hierarchical linear regressions indicated that the ability to appropriately use cognitive control processes during aging seems to be at least partially affected by the amount of available cognitive resources (assessed by fluid intelligence and processing speed abilities). Conclusions This study highlights the potential role of cognitive resources on the selective age-related decline in proactive control, suggesting the importance of a more exhaustive approach considering the confounding variables during cognitive control assessment. PMID:24401034

  2. Age-related deficits in generation and manipulation of mental images: II. The role of dorsolateral prefrontal cortex.

    PubMed

    Raz, N; Briggs, S D; Marks, W; Acker, J D

    1999-09-01

    The authors investigated neural substrates of age-related declines in mental imagery. Healthy adult participants (ages 19 to 77) performed a series of visual-spatial mental imagery tasks that varied in apparent difficulty and involved stimuli of varying graphic complexity. The volumes of the dorsolateral frontal cortex (DLPFC) and posterior visual processing areas were estimated from magnetic resonance imaging scans. The volume of the DLPFC and the fusiform cortex, working-memory capacity, and performance on the tasks involving image generation and manipulation were significantly reduced with age. Further analyses suggested that age-related deficits in performance on mental imagery tasks may stem in part from age-related shrinkage of the prefrontal cortex and age-related declines in working memory but not from age-related slowing of sensorimotor reaction time. The volume of cortical regions associated with modality-specific visual information processing did not show a consistent relationship with specific mental imagery processes. PMID:10509698

  3. Are delta-aminolevulinate dehydratase inhibition and metal concentrations additional factors for the age-related cognitive decline?

    PubMed

    Baierle, Marília; Charão, Mariele F; Göethel, Gabriela; Barth, Anelise; Fracasso, Rafael; Bubols, Guilherme; Sauer, Elisa; Campanharo, Sarah C; Rocha, Rafael C C; Saint'Pierre, Tatiana D; Bordignon, Suelen; Zibetti, Murilo; Trentini, Clarissa M; Avila, Daiana S; Gioda, Adriana; Garcia, Solange C

    2014-01-01

    Aging is often accompanied by cognitive impairments and influenced by oxidative status and chemical imbalances. Thus, this study was conducted to examine whether age-related cognitive deficit is associated with oxidative damage, especially with inhibition of the enzyme delta-aminolevulinate dehydratase (ALA-D), as well as to verify the influence of some metals in the enzyme activity and cognitive performance. Blood ALA-D activity, essential (Fe, Zn, Cu, Se) and non-essential metals (Pb, Cd, Hg, As, Cr, Ni, V) were measured in 50 elderly and 20 healthy young subjects. Cognitive function was assessed by tests from Consortium to Establish a Registry for Alzheimer's Disease (CERAD) battery and other. The elderly group presented decreased ALA-D activity compared to the young group. The index of ALA-D reactivation was similar to both study groups, but negatively associated with metals. The mean levels of essential metals were within the reference values, while the most toxic metals were above them in both groups. Cognitive function impairments were observed in elderly group and were associated with decreased ALA-D activity, with lower levels of Se and higher levels of toxic metals (Hg and V). Results suggest that the reduced ALA-D activity in elderly can be an additional factor involved in cognitive decline, since its inhibition throughout life could lead to accumulation of the neurotoxic compound ALA. Toxic metals were found to contribute to cognitive decline and also to influence ALA-D reactivation. PMID:25329536

  4. Disconnected aging: cerebral white matter integrity and age-related differences in cognition.

    PubMed

    Bennett, I J; Madden, D J

    2014-09-12

    Cognition arises as a result of coordinated processing among distributed brain regions and disruptions to communication within these neural networks can result in cognitive dysfunction. Cortical disconnection may thus contribute to the declines in some aspects of cognitive functioning observed in healthy aging. Diffusion tensor imaging (DTI) is ideally suited for the study of cortical disconnection as it provides indices of structural integrity within interconnected neural networks. The current review summarizes results of previous DTI aging research with the aim of identifying consistent patterns of age-related differences in white matter integrity, and of relationships between measures of white matter integrity and behavioral performance as a function of adult age. We outline a number of future directions that will broaden our current understanding of these brain-behavior relationships in aging. Specifically, future research should aim to (1) investigate multiple models of age-brain-behavior relationships; (2) determine the tract-specificity versus global effect of aging on white matter integrity; (3) assess the relative contribution of normal variation in white matter integrity versus white matter lesions to age-related differences in cognition; (4) improve the definition of specific aspects of cognitive functioning related to age-related differences in white matter integrity using information processing tasks; and (5) combine multiple imaging modalities (e.g., resting-state and task-related functional magnetic resonance imaging; fMRI) with DTI to clarify the role of cerebral white matter integrity in cognitive aging. PMID:24280637

  5. Myelin Breakdown Mediates Age-Related Slowing in Cognitive Processing Speed in Healthy Elderly Men

    ERIC Educational Resources Information Center

    Lu, Po H.; Lee, Grace J.; Tishler, Todd A.; Meghpara, Michael; Thompson, Paul M.; Bartzokis, George

    2013-01-01

    Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer's disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of…

  6. Recent Advances in Berry Supplementation and Age-Related Cognitive Decline

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To summarize recent findings and current concepts in the beneficial effects of berry consumption on brain function during aging. Berryfruit supplementation has continued to demonstrate efficacy in reversing age-related cognitive decline in animal studies. In terms of the mechanisms behind the effe...

  7. Cognitive Abilities Explaining Age-Related Changes in Time Perception of Short and Long Durations

    ERIC Educational Resources Information Center

    Zelanti, Pierre S.; Droit-Volet, Sylvie

    2011-01-01

    The current study investigated how the development of cognitive abilities explains the age-related changes in temporal judgment over short and long duration ranges from 0.5 to 30 s. Children (5- and 9-year-olds) as well as adults were given a temporal bisection task with four different duration ranges: a duration range shorter than 1 s, two…

  8. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering

    PubMed Central

    Pereira, Ana C.; Lambert, Hilary K.; Grossman, Yael S.; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K.; Calakos, Katina; Janssen, William G.; McEwen, Bruce S.; Morrison, John H.

    2014-01-01

    The dementia of Alzheimer’s disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  9. Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering.

    PubMed

    Pereira, Ana C; Lambert, Hilary K; Grossman, Yael S; Dumitriu, Dani; Waldman, Rachel; Jannetty, Sophia K; Calakos, Katina; Janssen, William G; McEwen, Bruce S; Morrison, John H

    2014-12-30

    The dementia of Alzheimer's disease (AD) results primarily from degeneration of neurons that furnish glutamatergic corticocortical connections that subserve cognition. Although neuron death is minimal in the absence of AD, age-related cognitive decline does occur in animals as well as humans, and it decreases quality of life for elderly people. Age-related cognitive decline has been linked to synapse loss and/or alterations of synaptic proteins that impair function in regions such as the hippocampus and prefrontal cortex. These synaptic alterations are likely reversible, such that maintenance of synaptic health in the face of aging is a critically important therapeutic goal. Here, we show that riluzole can protect against some of the synaptic alterations in hippocampus that are linked to age-related memory loss in rats. Riluzole increases glutamate uptake through glial transporters and is thought to decrease glutamate spillover to extrasynaptic NMDA receptors while increasing synaptic glutamatergic activity. Treated aged rats were protected against age-related cognitive decline displayed in nontreated aged animals. Memory performance correlated with density of thin spines on apical dendrites in CA1, although not with mushroom spines. Furthermore, riluzole-treated rats had an increase in clustering of thin spines that correlated with memory performance and was specific to the apical, but not the basilar, dendrites of CA1. Clustering of synaptic inputs is thought to allow nonlinear summation of synaptic strength. These findings further elucidate neuroplastic changes in glutamatergic circuits with aging and advance therapeutic development to prevent and treat age-related cognitive decline. PMID:25512503

  10. Contribution of changes in ubiquitin and myelin basic protein to age-related cognitive decline.

    PubMed

    Wang, Deng-Shun; Bennett, David A; Mufson, Elliott J; Mattila, Petri; Cochran, Elizabeth; Dickson, Dennis W

    2004-01-01

    The structural substrates for age-associated cognitive and motor slowing are not known, but age-related white matter changes, such as ubiquitin (UBQ)-immunoreactive granular degeneration of myelin, might contribute to this slowing. To address this hypothesis we measured immunoreactivity for UBQ and myelin basic protein (MBP) in frontal white matter of age-, sex- and postmortem interval-matched cases with no cognitive impairment (NCI; N=12), mild cognitive impairment (MCI; N=14) and Alzheimer disease (AD; N=12). There were no significant correlations between UBQ in white matter and cognitive measures, but MBP was significantly lower in AD compared with NCI and MCI. MBP correlated with overall cognition as assessed by neuropsychological summary scores, as well as with timed cognitive tests and those that reflect frontal functions. An age-related decrease in MBP immunoreactivity was detected in NCI cases (r=0.71). These results support the hypothesis that white matter pathology may contribute to age-associated decline in cognition. PMID:14687885

  11. Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research

    PubMed Central

    Antoniou, Mark; Gunasekera, Geshri; Wong, Patrick C. M.

    2014-01-01

    Over the next fifty years, the number of older adults is set to reach record levels. Protecting older adults from the age-related effects of cognitive decline is one of the greatest challenges of the next few decades as it places increasing pressure on families, health systems, and economies on a global scale. The disease-state of age-related cognitive decline—Alzheimer's disease and other dementias—hijacks our consciousness and intellectual autonomy. However, there is evidence that cognitively stimulating activities protect against the adverse effects of cognitive decline. Similarly, bilingualism is also considered to be a safeguard. We propose that foreign language learning programs aimed at older populations are an optimal solution for building cognitive reserve because language learning engages an extensive brain network that is known to overlap with the regions negatively affected by the aging process. It is recommended that future research should test this potentially fruitful hypothesis. PMID:24051310

  12. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice.

    PubMed

    Villeda, Saul A; Plambeck, Kristopher E; Middeldorp, Jinte; Castellano, Joseph M; Mosher, Kira I; Luo, Jian; Smith, Lucas K; Bieri, Gregor; Lin, Karin; Berdnik, Daniela; Wabl, Rafael; Udeochu, Joe; Wheatley, Elizabeth G; Zou, Bende; Simmons, Danielle A; Xie, Xinmin S; Longo, Frank M; Wyss-Coray, Tony

    2014-06-01

    As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts--in which circulatory systems of young and aged animals are connected--identified synaptic plasticity-related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function. PMID:24793238

  13. Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice

    PubMed Central

    Villeda, Saul A; Plambeck, Kristopher E; Middeldorp, Jinte; Castellano, Joseph M; Mosher, Kira I; Luo, Jian; Smith, Lucas K; Bieri, Gregor; Lin, Karin; Berdnik, Daniela; Wabl, Rafael; Udeochu, Joe; Wheatley, Elizabeth G; Zou, Bende; Simmons, Danielle A; Xie, Xinmin S; Longo, Frank M; Wyss-Coray, Tony

    2014-01-01

    As human lifespan increases, a greater fraction of the population is suffering from age-related cognitive impairments, making it important to elucidate a means to combat the effects of aging1,2. Here we report that exposure of an aged animal to young blood can counteract and reverse pre-existing effects of brain aging at the molecular, structural, functional and cognitive level. Genome-wide microarray analysis of heterochronic parabionts—in which circulatory systems of young and aged animals are connected—identified synaptic plasticity–related transcriptional changes in the hippocampus of aged mice. Dendritic spine density of mature neurons increased and synaptic plasticity improved in the hippocampus of aged heterochronic parabionts. At the cognitive level, systemic administration of young blood plasma into aged mice improved age-related cognitive impairments in both contextual fear conditioning and spatial learning and memory. Structural and cognitive enhancements elicited by exposure to young blood are mediated, in part, by activation of the cyclic AMP response element binding protein (Creb) in the aged hippocampus. Our data indicate that exposure of aged mice to young blood late in life is capable of rejuvenating synaptic plasticity and improving cognitive function. PMID:24793238

  14. Prevention of Age-Related Cognitive Decline: Which Strategies, When, and for Whom?

    PubMed

    Shatenstein, Bryna; Barberger-Gateau, Pascale; Mecocci, Patrizia

    2015-01-01

    Brain aging is characterized by the progressive and gradual accumulation of detrimental changes in structure and function, which increase risk of age-related cognitive decline and dementia. This devastating chronic condition generates a huge social and economic burden and accounts for 11.2% of years of disability. The increase in lifespan has contributed to the increase in dementia prevalence; however, there is currently no curative treatment for most causes of dementias. This paper reviews evidence-based strategies to build, enhance, and preserve cognition over the lifespan by examining approaches that work best, proposing when in the life course they should be implemented, and in which population group(s). Recent work shows a tendency to decreased age-specific prevalence and incidence of cognitive problems and dementia among people born later in the first half of the 20th century, citing higher educational levels, improvements in lifestyle, and better handling of vascular risk factors. This implies that we can target modifiable environmental, lifestyle, and health risk factors to modify the trajectory of cognitive decline before the onset of irreversible dementia. Because building cognitive reserve and prevention of cognitive decline are of critical importance, interventions are needed at every stage of the life course to foster cognitive stimulation, and enable healthy eating habits and physical activity throughout the lifespan. Preventive interventions to decrease and delay cognitive decline and its consequences in old age will also require collaboration and action on the part of policy-makers at the political and social level. PMID:26401926

  15. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review

    PubMed Central

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-01-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  16. Can psychosocial work conditions protect against age-related cognitive decline? Results from a systematic review.

    PubMed

    Nexø, Mette Andersen; Meng, Annette; Borg, Vilhelm

    2016-07-01

    According to the use it or lose it hypothesis, intellectually stimulating activities postpone age-related cognitive decline. A previous systematic review concluded that a high level of mental work demands and job control protected against cognitive decline. However, it did not distinguish between outcomes that were measured as cognitive function at one point in time or as cognitive decline. Our study aimed to systematically review which psychosocial working conditions were prospectively associated with high levels of cognitive function and/or changes in cognitive function over time. Articles were identified by a systematic literature search (MEDLINE, Web of Science (WOS), PsycNET, Occupational Safety and Health (OSH)). We included only studies with longitudinal designs examining the impact of psychosocial work conditions on outcomes defined as cognitive function or changes in cognitive function. Two independent reviewers compared title-abstract screenings, full-text screenings and quality assessment ratings. Eleven studies were included in the final synthesis and showed that high levels of mental work demands, occupational complexity or job control at one point in time were prospectively associated with higher levels of cognitive function in midlife or late life. However, the evidence to clarify whether these psychosocial factors also affected cognitive decline was insufficient, conflicting or weak. It remains speculative whether job control, job demands or occupational complexity can protect against cognitive decline. Future studies using methodological advancements can reveal whether workers gain more cognitive reserve in midlife and late life than the available evidence currently suggests. The public health implications of a previous review should thereby be redefined accordingly. PMID:27178844

  17. Cognitive deficits and functional outcome in schizophrenia

    PubMed Central

    Bowie, Christopher R; Harvey, Philip D

    2006-01-01

    Cognitive dysfunction is a core feature of schizophrenia. Deficits are moderate to severe across several domains, including attention, working memory, verbal learning and memory, and executive functions. These deficits pre-date the onset of frank psychosis and are stable throughout the course of the illness in most patients. Over the past decade, the focus on these deficits has increased dramatically with the recognition that they are consistently the best predictor of functional outcomes across outcome domains and patient samples. Recent treatment studies, both pharmacological and behavioral, suggest that cognitive deficits are malleable. Other research calls into question the meaningfulness of cognitive change in schizophrenia. In this article, we review cognitive deficits in schizophrenia and focus on their treatment and relationship to functional outcome. PMID:19412501

  18. Fruits, Nuts, and Brain Aging: Nutritional Interventions Targeting Age-Related Neuronal and Behavioral Deficits

    Technology Transfer Automated Retrieval System (TEKTRAN)

    By the year 2050, 30% of the total population of the US will be over 65 years of age. As the aged population expands, the economic burden of care and treatment of those with age-related health disorders also increases, necessitating the immediate implementation of therapeutics to prevent or even rev...

  19. Shared and unique genetic and environmental influences on aging-related changes in multiple cognitive abilities.

    PubMed

    Tucker-Drob, Elliot M; Reynolds, Chandra A; Finkel, Deborah; Pedersen, Nancy L

    2014-01-01

    Aging-related declines occur in many different domains of cognitive function during middle and late adulthood. However, whether a global dimension underlies individual differences in changes in different domains of cognition and whether global genetic influences on cognitive changes exist is less clear. We addressed these issues by applying multivariate growth curve models to longitudinal data from 857 individuals from the Swedish Adoption/Twin Study of Aging, who had been measured on 11 cognitive variables representative of verbal, spatial, memory, and processing speed abilities up to 5 times over up to 16 years between ages 50 and 96 years. Between ages 50 and 65 years scores on different tests changed relatively independently of one another, and there was little evidence for strong underlying dimensions of change. In contrast, over the period between 65 and 96 years of age, there were strong interrelations among rates of change both within and across domains. During this age period, variability in rates of change were, on average, 52% domain-general, 8% domain-specific, and 39% test-specific. Quantitative genetic decomposition indicated that 29% of individual differences in a global domain-general dimension of cognitive changes during this age period were attributable to genetic influences, but some domain-specific genetic influences were also evident, even after accounting for domain-general contributions. These findings are consistent with a balanced global and domain-specific account of the genetics of cognitive aging. PMID:23586942

  20. An age-related deficit in spatial-feature reference memory in homing pigeons (Columba livia).

    PubMed

    Coppola, Vincent J; Flaim, Mary E; Carney, Samantha N; Bingman, Verner P

    2015-03-01

    Age-related memory decline in mammals has been well documented. By contrast, very little is known about memory decline in birds as they age. In the current study we trained younger and older homing pigeons on a reference memory task in which a goal location could be encoded by spatial and feature cues. Consistent with a previous working memory study, the results revealed impaired acquisition of combined spatial-feature reference memory in older compared to younger pigeons. Following memory acquisition, we used cue-conflict probe trials to provide an initial assessment of possible age-related differences in cue preference. Both younger and older pigeons displayed a similarly modest preference for feature over spatial cues. PMID:25449841

  1. Age-related deficits in a forebrain-dependent task, trace-eyeblink conditioning

    PubMed Central

    Galvez, Roberto; Cua, Sabrina; Disterhoft, John F.

    2009-01-01

    Trace-eyeblink conditioning is a forebrain-dependent learning paradigm that has assisted in our understanding of age-related hippocampal neuronal plasticity; however, the hippocampus is not believed to be the permanent site for most long-term-memory storage. Studies in adult subjects have suggested the neocortex as one such site. Whisker plucking studies have further suggested that the ability for plasticity in the neocortex declines with age. Mice were trained in trace- and delay-eyeblink conditioning with whisker or auditory stimulation as the conditioned stimulus to examine possible age-related behavioral and neocortical abnormalities. Whisker stimulation was determined to be a more effective stimulus for examining age-related behavioral abnormalities in C57 mice. Additionally, neocortical barrel expansion, observed in trace conditioned adult mice and rabbits, does not occur in mice conditioned on a delay paradigm or in old mice unable to learn the whisker trace association. Abnormalities in neocortical memory storage in the elderly could contribute to normal age-dependent declines in associative learning abilities. PMID:20018411

  2. Relationships between default-mode network connectivity, medial temporal lobe structure, and age-related memory deficits.

    PubMed

    Ward, Andrew M; Mormino, Elizabeth C; Huijbers, Willem; Schultz, Aaron P; Hedden, Trey; Sperling, Reisa A

    2015-01-01

    Advanced aging negatively impacts memory performance. Brain aging has been associated with shrinkage in medial temporal lobe structures essential for memory--including hippocampus and entorhinal cortex--and with deficits in default-mode network connectivity. Yet, whether and how these imaging markers are relevant to age-related memory deficits remains a topic of debate. Using a sample of 182 older (age 74.6 ± 6.2 years) and 66 young (age 22.2 ± 3.6 years) participants, this study examined relationships among memory performance, hippocampus volume, entorhinal cortex thickness, and default-mode network connectivity across aging. All imaging markers and memory were significantly different between young and older groups. Each imaging marker significantly mediated the relationship between age and memory performance and collectively accounted for most of the variance in age-related memory performance. Within older participants, default-mode connectivity and hippocampus volume were independently associated with memory. Structural equation modeling of cross-sectional data within older participants suggest that entorhinal thinning may occur before reduced default-mode connectivity and hippocampal volume loss, which in turn lead to deficits in memory performance. PMID:25113793

  3. Age-related differences in white matter integrity and cognitive function are related to APOE status

    PubMed Central

    Ryan, Lee; Walther, Katrin; Bendlin, Barbara B.; Lue, Lih-Fen; Walker, Douglas G.; Glisky, Elizabeth L.

    2010-01-01

    While an extensive literature is now available on age-related differences in white matter integrity measured by diffusion MRI, relatively little is known about the relationships between diffusion and cognitive functions in older adults. Even less is known about whether these relationships are influenced by the apolipoprotein (APOE) ε4 allele, despite growing evidence that ε4 increases cognitive impairment in older adults. The purpose of the present study was to examine these relationships in a group of community-dwelling cognitively normal older adults. Data were obtained from a sample of 126 individuals (ages 52–92) that included 32 ε4 heterozygotes, 6 ε4 homozygotes, and 88 non-carriers. Two measures of diffusion, the apparent diffusion coefficient (ADC) and fractional anisotropy (FA), were obtained from six brain regions – frontal white matter, lateral parietal white matter, the centrum semiovale, the genu and splenium of the corpus callosum, and the temporal stem white matter – and were used to predict composite scores of cognitive function in two domains, executive function and memory function. Results indicated that ADC and FA differed with increasing age in all six brain regions, and these differences were significantly greater for ε4 carriers compared to noncarriers. Importantly, after controlling for age, diffusion measures predicted cognitive function in a region-specific way that was also influenced by ε4 status. Regardless of APOE status, frontal ADC and FA independently predicted executive function scores for all participants, while temporal lobe ADC additionally predicted executive function for ε4 carriers, but not noncarriers. Memory scores were predicted by temporal lobe ADC but not frontal diffusion for all participants, and this relationship was significantly stronger in ε4 carriers compared to noncarriers. Taken together, age and temporal lobe ADC accounted for a striking 53% of the variance in memory scores within the ε4 carrier

  4. Inspection Time and Cognitive Abilities in Twins Aged 7 to 17 Years: Age-Related Changes, Heritability and Genetic Covariance

    ERIC Educational Resources Information Center

    Edmonds, Caroline J.; Isaacs, Elizabeth B.; Visscher, Peter M.; Rogers, Mary; Lanigan, Julie; Singhal, Atul; Lucas, Alan; Gringras, Paul; Denton, Jane; Deary, Ian J.

    2008-01-01

    We studied the age-related differences in inspection time and multiple cognitive domains in a group of monozygotic (MZ) and dizygotic (DZ) twins aged 7 to 17 years. Data from 111 twin pairs and 19 singleton siblings were included. We found clear age-related trends towards more efficient visual information processing in older participants. There…

  5. Age-related cognitive decline during normal aging: the complex effect of education.

    PubMed

    Ardila, A; Ostrosky-Solis, F; Rosselli, M; Gómez, C

    2000-08-01

    The purpose of this study was to further analyze the effects of education on cognitive decline during normal aging. An 806-subject sample was taken from five different Mexican regions. Participants ranged in age from 16 to 85 years. Subjects were grouped into four educational levels: illiterate, 1-4, 5-9, and 10 or more years of education, and four age ranges: 16-30, 31-50, 51-65, and 66-85 years. A brief neuropsychological test battery (NEUROPSI), standardized and normalized in Spanish, was administered. The NEUROPSI test battery includes assessment of orientation, attention, memory, language, visuoperceptual abilities, motor skills, and executive functions. In general, test scores were strongly associated with level of educational, and differences among age groups were smaller than differences among education groups. However, there was an interaction between age and education such as that among illiterate individuals scores of participants 31-50 years old were higher than scores of participants 16-30 years old for over 50% of the tests. Different patterns of interaction among educational groups were distinguished. It was concluded that: (a) The course of life-span changes in cognition are affected by education. Among individuals with a low level of education, best neuropsychological test performance is observed at an older age than among higher-educated subjects; and (b) there is not a single relationship between age-related cognitive decline and education, but different patterns may be found, depending upon the specific cognitive domain. PMID:14590204

  6. The effectiveness of unitization in mitigating age-related relational learning impairments depends on existing cognitive status.

    PubMed

    D'Angelo, Maria C; Smith, Victoria M; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A; Barense, Morgan D; Ryan, Jennifer D

    2016-11-01

    Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals' failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878

  7. The effectiveness of unitization in mitigating age-related relational learning impairments depends on existing cognitive status

    PubMed Central

    D’Angelo, Maria C.; Smith, Victoria M.; Kacollja, Arber; Zhang, Felicia; Binns, Malcolm A.; Barense, Morgan D.; Ryan, Jennifer D.

    2016-01-01

    ABSTRACT Binding relations among items in the transverse patterning (TP) task is dependent on the integrity of the hippocampus and its extended network. Older adults have impaired TP learning, corresponding to age-related reductions in hippocampal volumes. Unitization is a training strategy that can mitigate TP impairments in amnesia by reducing reliance on hippocampal-dependent relational binding and increasing reliance on fused representations. Here we examined whether healthy older adults and those showing early signs of cognitive decline would also benefit from unitization. Although both groups of older adults had neuropsychological performance within the healthy range, their TP learning differed both under standard and unitized training conditions. Healthy older adults with impaired TP learning under standard training benefited from unitized training. Older adults who failed the Montreal Cognitive Assessment (MoCA) showed greater impairments under standard conditions, and showed no evidence of improvement with unitization. These individuals’ failures to benefit from unitization may be a consequence of early deficits not seen in older adults who pass the MoCA. PMID:27049878

  8. Perspective: A Critical Look at the Ancillary Age-Related Eye Disease Study 2: Nutrition and Cognitive Function Results in Older Individuals with Age-Related Macular Degeneration.

    PubMed

    Hammond, Billy R; Renzi-Hammond, Lisa M

    2016-05-01

    A large body of literature suggests that the dietary carotenoids lutein and zeaxanthin and long-chain polyunsaturated fatty acids such as docosahexaenoic acid are related to improved cognitive function across the life span. A recent report by the Age-Related Eye Disease Study (AREDS) group appears to contradict the general findings of others in the field. In this review, we look critically at the methods, study designs, and analysis techniques used in the larger body of literature and compare them with the recent AREDS reports. PMID:27184270

  9. Effects of a computer-based cognitive exercise program on age-related cognitive decline.

    PubMed

    Bozoki, Andrea; Radovanovic, Mirjana; Winn, Brian; Heeter, Carrie; Anthony, James C

    2013-01-01

    We developed a 'senior friendly' suite of online 'games for learning' with interactive calibration for increasing difficulty, and evaluated the feasibility of a randomized clinical trial to test the hypothesis that seniors aged 60-80 can improve key aspects of cognitive ability with the aid of such games. Sixty community-dwelling senior volunteers were randomized to either an online game suite designed to train multiple cognitive abilities, or to a control arm with online activities that simulated the look and feel of the games but with low level interactivity and no calibration of difficulty. Study assessment included measures of recruitment, retention and play-time. Cognitive change was measured with a computerized assessment battery administered just before and within two weeks after completion of the six-week intervention. Impediments to feasibility included: limited access to in-home high-speed internet, large variations in the amount of time devoted to game play, and a reluctance to pursue more challenging levels. Overall analysis was negative for assessed performance (transference effects) even though subjects improved on the games themselves. Post hoc analyses suggest that some types of games may have more value than others, but these effects would need to be replicated in a study designed for that purpose. We conclude that a six-week, moderate-intensity computer game-based cognitive intervention can be implemented with high-functioning seniors, but the effect size is relatively small. Our findings are consistent with Owen et al. (2010), but there are open questions about whether more structured, longer duration or more intensive 'games for learning' interventions might yield more substantial cognitive improvement in seniors. PMID:23542053

  10. How age-related strategy switching deficits affect wayfinding in complex environments.

    PubMed

    Harris, Mathew A; Wolbers, Thomas

    2014-05-01

    Although most research on navigation in aging focuses on allocentric processing deficits, impaired strategy switching may also contribute to navigational decline. Using a specifically designed task involving navigating a town-like virtual environment, we assessed the ability of young and old participants to switch from following learned routes to finding novel shortcuts. We found large age differences in the length of routes taken during testing and in use of shortcuts, as, while nearly all young participants switched from the egocentric route-following strategy to the allocentric wayfinding strategy, none of the older participants stably switched. Although secondary tasks confirmed that older participants were impaired both at strategy switching and allocentric processing, the difficulty in using shortcuts was selectively related to impaired strategy switching. This may in turn relate to dysfunction of the prefrontal-noradrenergic network responsible for coordinating switching behavior. We conclude that the large age difference in performance at the shortcutting task demonstrates for the first time, how strategy switching deficits can have a severe impact on navigation in aging. PMID:24239438

  11. Reversal of aging-related emotional memory deficits by norepinephrine via regulating the stability of surface AMPA receptors.

    PubMed

    Luo, Yi; Zhou, Jun; Li, Ming-Xing; Wu, Peng-Fei; Hu, Zhuang-Li; Ni, Lan; Jin, You; Chen, Jian-Guo; Wang, Fang

    2015-04-01

    Aging-related emotional memory deficit is a well-known complication in Alzheimer's disease and normal aging. However, little is known about its molecular mechanism. To address this issue, we examined the role of norepinephrine (NE) and its relevant drug desipramine in the regulation of hippocampal long-term potentiation (LTP), surface expression of AMPA receptor, and associative fear memory in rats. We found that there was a defective regulation of NE content and AMPA receptor trafficking during fear conditioning, which were accompanied by impaired emotional memory and LTP in aged rats. Furthermore, we also found that the exogenous upregulation of NE ameliorated the impairment of LTP and emotional memory via enhancing AMPA receptor trafficking in aged rats, and the downregulation of NE impaired LTP in adult rats. Finally, acute treatment with NE or desipramine rescued the impaired emotional memory in aged rats. These results imply a pivotal role for NE in synaptic plasticity and associative fear memory in aging rats and suggest that desipramine is a potential candidate for treating aging-related emotional memory deficit. PMID:25564942

  12. Epigenetic alterations in the suprachiasmatic nucleus and hippocampus contribute to age-related cognitive decline

    PubMed Central

    Deibel, Scott H.; Zelinski, Erin L.; Keeley, Robin J.; Kovalchuk, Olga; McDonald, Robert J.

    2015-01-01

    Circadian rhythm dysfunction and cognitive decline, specifically memory loss, frequently accompany natural aging. Circadian rhythms and memory are intertwined, as circadian rhythms influence memory formation and recall in young and old rodents. Although, the precise relationship between circadian rhythms and memory is still largely unknown, it is hypothesized that circadian rhythm disruption, which occurs during aging, contributes to age-associated cognitive decline, specifically memory loss. While there are a variety of mechanisms that could mediate this effect, changes in the epigenome that occur during aging has been proposed as a potential candidate. Interestingly, epigenetic mechanisms, such as DNA methylation and sirtuin1 (SIRT1) are necessary for both circadian rhythms and memory. During aging, similar alterations of epigenetic mechanisms occur in the suprachiasmatic nucleus (SCN) and hippocampus, which are necessary for circadian rhythm generation and memory, respectively. Recently, circadian rhythms have been linked to epigenetic function in the hippocampus, as some of these epigenetic mechanisms oscillate in the hippocampus and are disrupted by clock gene deletion. The current paper will review how circadian rhythms and memory change with age, and will suggest how epigenetic changes in these processes might contribute to age-related cognitive decline. PMID:26252151

  13. Like cognitive function, decision making across the life span shows profound age-related changes

    PubMed Central

    Tymula, Agnieszka; Rosenberg Belmaker, Lior A.; Ruderman, Lital; Glimcher, Paul W.; Levy, Ifat

    2013-01-01

    It has long been known that human cognitive function improves through young adulthood and then declines across the later life span. Here we examined how decision-making function changes across the life span by measuring risk and ambiguity attitudes in the gain and loss domains, as well as choice consistency, in an urban cohort ranging in age from 12 to 90 y. We identified several important age-related patterns in decision making under uncertainty: First, we found that healthy elders between the ages of 65 and 90 were strikingly inconsistent in their choices compared with younger subjects. Just as elders show profound declines in cognitive function, they also show profound declines in choice rationality compared with their younger peers. Second, we found that the widely documented phenomenon of ambiguity aversion is specific to the gain domain and does not occur in the loss domain, except for a slight effect in older adults. Finally, extending an earlier report by our group, we found that risk attitudes across the life span show an inverted U-shaped function; both elders and adolescents are more risk-averse than their midlife counterparts. Taken together, these characterizations of decision-making function across the life span in this urban cohort strengthen the conclusions of previous reports suggesting a profound impact of aging on cognitive function in this domain. PMID:24082105

  14. Modulation of Intestinal Microbiota by the Probiotic VSL#3 Resets Brain Gene Expression and Ameliorates the Age-Related Deficit in LTP

    PubMed Central

    Distrutti, Eleonora; O’Reilly, Julie-Ann; McDonald, Claire; Cipriani, Sabrina; Renga, Barbara; Lynch, Marina A.; Fiorucci, Stefano

    2014-01-01

    The intestinal microbiota is increasingly recognized as a complex signaling network that impacts on many systems beyond the enteric system modulating, among others, cognitive functions including learning, memory and decision-making processes. This has led to the concept of a microbiota-driven gut–brain axis, reflecting a bidirectional interaction between the central nervous system and the intestine. A deficit in synaptic plasticity is one of the many changes that occurs with age. Specifically, the archetypal model of plasticity, long-term potentiation (LTP), is reduced in hippocampus of middle-aged and aged rats. Because the intestinal microbiota might change with age, we have investigated whether the age-related deficit in LTP might be attenuated by changing the composition of intestinal microbiota with VSL#3, a probiotic mixture comprising 8 Gram-positive bacterial strains. Here, we report that treatment of aged rats with VSL#3 induced a robust change in the composition of intestinal microbiota with an increase in the abundance of Actinobacteria and Bacterioidetes, which was reduced in control-treated aged rats. VSL#3 administration modulated the expression of a large group of genes in brain tissue as assessed by whole gene expression, with evidence of a change in genes that impact on inflammatory and neuronal plasticity processes. The age-related deficit in LTP was attenuated in VSL#3-treated aged rats and this was accompanied by a modest decrease in markers of microglial activation and an increase in expression of BDNF and synapsin. The data support the notion that intestinal microbiota can be manipulated to positively impact on neuronal function. PMID:25202975

  15. Integrative and semantic relations equally alleviate age-related associative memory deficits.

    PubMed

    Badham, Stephen P; Estes, Zachary; Maylor, Elizabeth A

    2012-03-01

    Two experiments compared effects of integrative and semantic relations between pairs of words on lexical and memory processes in old age. Integrative relations occur when two dissimilar and unassociated words are linked together to form a coherent phrase (e.g., horse-doctor). In Experiment 1, older adults completed a lexical-decision task where prime and target words were related either integratively or semantically. The two types of relation both facilitated responses compared to a baseline condition, demonstrating that priming can occur in older adults with minimal preexisting associations between primes and targets. In Experiment 2, young and older adults completed a cued recall task with integrative, semantic, and unrelated word pairs. Both integrative and semantic pairs showed significantly smaller age differences in associative memory compared to unrelated pairs. Integrative relations facilitated older adults' memory to a similar extent as semantic relations despite having few preexisting associations in memory. Integratability of stimuli is therefore a new factor that reduces associative deficits in older adults, most likely by supporting encoding and retrieval mechanisms. PMID:21639644

  16. Lower cognitive function in patients with age-related macular degeneration: a meta-analysis

    PubMed Central

    Zhou, Li-Xiao; Sun, Cheng-Lin; Wei, Li-Juan; Gu, Zhi-Min; Lv, Liang; Dang, Yalong

    2016-01-01

    Objective To investigate the cognitive impairment in patients with age-related macular degeneration (AMD). Methods Relevant articles were identified through a search of the following electronic databases through October 2015, without language restriction: 1) PubMed; 2) the Cochrane Library; 3) EMBASE; 4) ScienceDirect. Meta-analysis was conducted using STATA 12.0 software. Standardized mean differences with corresponding 95% confidence intervals were calculated. All of the included studies met the following four criteria: 1) the study design was a case–control or randomized controlled trial (RCT) study; 2) the study investigated cognitive function in the patient with AMD; 3) the diagnoses of AMD must be provided; 4) there were sufficient scores data to extract for evaluating cognitive function between cases and controls. The Newcastle–Ottawa Scale criteria were used to assess the methodological quality of the studies. Results Of the initial 278 literatures, only six case–control and one RCT studies met all of the inclusion criteria. A total of 794 AMD patients and 1,227 controls were included in this study. Five studies were performed with mini-mental state examination (MMSE), two studies with animal fluency, two studies with trail making test (TMT)-A and -B, one study with Mini-Cog. Results of the meta-analysis revealed lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test (P≤0.001 for all). The results also showed that differences in the TMT-A (except AMD [total] vs controls) and TMT-B test had no statistical significance (P>0.01). The Newcastle–Ottawa Scale score was ≥5 for all of the included studies. Based on the sensitivity analysis, no single study influenced the overall pooled estimates. Conclusion This meta-analysis suggests lower cognitive function test scores in patients with AMD, especially with MMSE and Mini-Cog test. The other cognitive impairment screening tests, such as animal fluency test and

  17. Cognitive Load and Listening Effort: Concepts and Age-Related Considerations.

    PubMed

    Lemke, Ulrike; Besser, Jana

    2016-01-01

    Listening effort has been recognized as an important dimension of everyday listening, especially with regard to the comprehension of spoken language. At constant levels of comprehension performance, the level of effort exerted and perceived during listening can differ considerably across listeners and situations. In this article, listening effort is used as an umbrella term for two different types of effort that can arise during listening. One of these types is processing effort, which is used to denote the utilization of "extra" mental processing resources in listening conditions that are adverse for an individual. A conceptual description is introduced how processing effort could be defined in terms of situational influences, the listener's auditory and cognitive resources, and the listener's personal state. Also, the proposed relationship between processing effort and subjectively perceived listening effort is discussed. Notably, previous research has shown that the availability of mental resources, as well as the ability to use them efficiently, changes over the course of adult aging. These common age-related changes in cognitive abilities and their neurocognitive organization are discussed in the context of the presented concept, especially regarding situations in which listening effort may be increased for older people. PMID:27355774

  18. ROLE OF SOLUBLE EPOXIDE HYDROLASE IN AGE-RELATED VASCULAR COGNITIVE DECLINE

    PubMed Central

    Nelson, Jonathan W.; Young, Jennifer M.; Borkar, Rohan; Woltjer, Randy L.; Quinn, Joseph F.; Silbert, Lisa C.; Grafe, Marjorie R.; Alkayed, Nabil J.

    2014-01-01

    P450 eicosanoids are important regulators of the cerebral microcirculation, but their role in cerebral small vessel disease is unclear. We tested the hypothesis that vascular cognitive impairment (VCI) is linked to reduced cerebral microvascular eicosanoid signaling. We analyzed human brain tissue from individuals formerly enrolled in the Oregon Brain Aging Study, who had a history of cognitive impairment histopathological evidence of microvascular disease. VCI subjects had significantly higher lesion burden both on premortem MRI and postmortem histopathology compared to age- and sex-matched controls. Mass spectrometry-based eicosanoid analysis revealed that 14,15-dihydroxyeicosatrienoic acid (DHET) was elevated in cortical brain tissue from VCI subjects. Immunoreactivity of soluble epoxide hydrolase (sEH), the enzyme responsible for 14,15-DHET formation, was localized to cerebral microvascular endothelium, and was enhanced in microvessels of affected tissue. Finally, we evaluated the genotype frequency of two functional single nucleotide polymorphisms of sEH gene EPHX2 in VCI and control groups. Our findings support a role for sEH and a potential benefit from sEH inhibitors in age-related VCI. PMID:25277097

  19. Age-related differences in the course of cognitive skill acquisition: the role of regional cortical shrinkage and cognitive resources.

    PubMed

    Head, Denise; Raz, Naftali; Gunning-Dixon, Faith; Williamson, Adrienne; Acker, James D

    2002-03-01

    This study examined the impact of age-related differences in regional cerebral volumes and cognitive resources on acquisition of a cognitive skill. Volumes of brain regions were measured on magnetic resonance images of healthy adults (aged 22-80). At the early stage of learning to solve the Tower of Hanoi puzzle, speed and efficiency were associated with age, prefrontal cortex volume, and working memory. A similar pattern of brain-behavior associations was observed with perseveration measured on the Wisconsin Card Sorting Test. None of the examined structural brain variables were important at the later stages of skill acquisition. When hypertensive participants were excluded, the effect of prefrontal shrinkage on executive aspects of performance was no longer significant, but the effect of working memory remained. PMID:11931289

  20. Microstructural white matter changes mediate age-related cognitive decline on the Montreal Cognitive Assessment (MoCA).

    PubMed

    Jolly, Todd A D; Cooper, Patrick S; Badwi, Syarifah Azizah Wan Ahmadul; Phillips, Natalie A; Rennie, Jaime L; Levi, Christopher R; Drysdale, Karen A; Parsons, Mark W; Michie, Patricia T; Karayanidis, Frini

    2016-02-01

    Although the relationship between aging and cognitive decline is well established, there is substantial individual variability in the degree of cognitive decline in older adults. The present study investigates whether variability in cognitive performance in community-dwelling older adults is related to the presence of whole brain or tract-specific changes in white matter microstructure. Specifically, we examine whether age-related decline in performance on the Montreal Cognitive Assessment (MoCA), a cognitive screening tool, is mediated by the white matter microstructural decline. We also examine if this relationship is driven by the presence of cardiovascular risk factors or variability in cerebral arterial pulsatility, an index of cardiovascular risk. Sixty-nine participants (aged 43-87) completed behavioral and MRI testing including T1 structural, T2-weighted FLAIR, and diffusion-weighted imaging (DWI) sequences. Measures of white matter microstructure were calculated using diffusion tensor imaging analyses on the DWI sequence. Multiple linear regression revealed that MoCA scores were predicted by radial diffusivity (RaD) of white matter beyond age or other cerebral measures. While increasing age and arterial pulsatility were associated with increasing RaD, these factors did not mediate the relationship between total white matter RaD and MoCA. Further, the relationship between MoCA and RaD was specific to participants who reported at least one cardiovascular risk factor. These findings highlight the importance of cardiovascular risk factors in the presentation of cognitive decline in old age. Further work is needed to establish whether medical or lifestyle management of these risk factors can prevent or reverse cognitive decline in old age. PMID:26511789

  1. The Relation between canine cognitive dysfunction and age-related brain lesions

    PubMed Central

    OZAWA, Makiko; CHAMBERS, James K.; UCHIDA, Kazuyuki; NAKAYAMA, Hiroyuki

    2016-01-01

    Canine cognitive dysfunction (CCD) is a syndrome that manifests itself in abnormal behaviors, such as disorientation and wandering. β-amyloid deposition in the brain, including the senile plaque (SP) and cerebral amyloid angiopathy (CAA), has been suggested as a major cause of the syndrome. However, the pathological significance of β-amyloid deposition in CCD dogs remains unclear. The present study was conducted using 16 dogs aged 10 years or older to clarify the relationship between the age-related histopathological lesions, such as β-amyloid deposition, in the brain and the clinical symptoms of CCD as evaluated in a questionnaire previously established in a large survey. In addition, age-related brain lesions were assessed in 37 dogs. The pathological lesions were evaluated by the severity of β-amyloid deposition (SP and CAA), the amount of ubiquitin-positive granules (UBQ), GFAP-positive astrocytes, Iba-1-positive microglia and Nissle stain-positive nerve cells. The results revealed that there was no significant correlation between the severities of canine SP and CCD. The SP increased until 14 years old, but decreased thereafter, although the incidence of CCD is high at these ages. The CAA consistently increased with age, but did not correlate greatly with the CCD score. In contrast, the increases of UBQ, astrocytes and microglia were significantly correlated with CCD. Thus, the impairment in the synapse and/or myelin suggested by increased UBQ and glial activation might be involved in CCD pathogenesis, but β-amyloid deposition, especially SP, is not a direct pathogenic factor of CCD. PMID:26922972

  2. Age-related deficits in voluntary control over saccadic eye movements: consideration of electrical brain stimulation as a therapeutic strategy.

    PubMed

    Chen, Po Ling; Machado, Liana

    2016-05-01

    Sudden changes in our visual environment trigger reflexive eye movements, so automatically they often go unnoticed. Consequently, voluntary control over reflexive eye movements entails considerable effort. In relation to frontal-lobe deterioration, adult aging adversely impacts voluntary saccadic eye movement control in particular, which compromises effective performance of daily activities. Here, we review the nature of age-related changes in saccadic control, focusing primarily on the antisaccade task because of its assessment of 2 key age-sensitive control functions: reflexive saccade inhibition and voluntary saccade generation. With an ultimate view toward facilitating development of therapeutic strategies, we systematically review the neuroanatomy underpinning voluntary control over saccadic eye movements and natural mechanisms that kick in to compensate for age-related declines. We then explore the potential of noninvasive electrical brain stimulation to counteract aging deficits. Based on evidence that anodal transcranial direct current stimulation can confer a range of benefits specifically relevant to aging brains, we put forward this neuromodulation technique as a therapeutic strategy for improving voluntary saccadic eye movement control in older adults. PMID:27103518

  3. Effects of Stimulant Drugs on Attention and Cognitive Deficits.

    ERIC Educational Resources Information Center

    Gadow, Kenneth D.

    1981-01-01

    Research on the effects of stimulant drugs on attention and cognitive deficits in children with hyperactivity is reviewed. Topics covered include: attention and impulsivity, paired associate learning, school achievement, and drug induced attention and cognitive deficits. (CL)

  4. Sex-dependent modulation of age-related cognitive decline by the L-type calcium channel gene Cacna1c (Cav 1.2).

    PubMed

    Zanos, Panos; Bhat, Shambhu; Terrillion, Chantelle E; Smith, Robert J; Tonelli, Leonardo H; Gould, Todd D

    2015-10-01

    Increased calcium influx through L-type voltage-gated calcium channels has been implicated in the neuronal dysfunction underlying age-related memory declines. The present study aimed to test the specific role of Cacna1c (which encodes Cav 1.2) in modulating age-related memory dysfunction. Short-term, spatial and contextual/emotional memory was evaluated in young and aged, wild-type as well as mice with one functional copy of Cacna1c (haploinsufficient), using the novel object recognition, Y-maze and passive avoidance tasks, respectively. Hippocampal expression of Cacna1c mRNA was measured by quantitative polymerase chain reaction. Ageing was associated with object recognition and contextual/emotional memory deficits, and a significant increase in hippocampal Cacna1c mRNA expression. Cacna1c haploinsufficiency was associated with decreased Cacna1c mRNA expression in both young and old animals. However, haploinsufficient mice did not manifest an age-related increase in expression of this gene. Behaviourally, Cacna1c haploinsufficiency prevented object recognition deficits during ageing in both male and female mice. A significant correlation between higher Cacna1c levels and decreased object recognition performance was observed in both sexes. Also, a sex-dependent protective role of decreased Cacna1c levels in contextual/emotional memory loss has been observed, specifically in male mice. These data provide evidence for an association between increased hippocampal Cacna1c expression and age-related cognitive decline. Additionally, they indicate an interaction between the Cacna1c gene and sex in the modulation of age-related contextual memory declines. PMID:25989111

  5. Temperature affects longevity and age-related locomotor and cognitive decay in the short-lived fish Nothobranchius furzeri.

    PubMed

    Valenzano, Dario R; Terzibasi, Eva; Cattaneo, Antonino; Domenici, Luciano; Cellerino, Alessandro

    2006-06-01

    Temperature variations are known to modulate aging and life-history traits in poikilotherms as different as worms, flies and fish. In invertebrates, temperature affects lifespan by modulating the slope of age-dependent acceleration in death rate, which is thought to reflect the rate of age-related damage accumulation. Here, we studied the effects of temperature on aging kinetics, aging-related behavioural deficits, and age-associated histological markers of senescence in the short-lived fish Nothobranchius furzeri. This species shows a maximum captive lifespan of only 3 months, which is tied with acceleration in growth and expression of aging biomarkers. These biological peculiarities make it a very convenient animal model for testing the effects of experimental manipulations on life-history traits in vertebrates. Here, we show that (i) lowering temperature from 25 degrees C to 22 degrees C increases both median and maximum lifespan; (ii) life extension is due to reduction in the slope of the age-dependent acceleration in death rate; (iii) lowering temperature from 25 degrees C to 22 degrees C retards the onset of age-related locomotor and learning deficits; and (iv) lowering temperature from 25 degrees C to 22 degrees C reduces the accumulation of the age-related marker lipofuscin. We conclude that lowering water temperature is a simple experimental manipulation which retards the rate of age-related damage accumulation in this short-lived species. PMID:16842500

  6. Touchscreen-Based Cognitive Tasks Reveal Age-Related Impairment in a Primate Aging Model, the Grey Mouse Lemur (Microcebus murinus)

    PubMed Central

    2014-01-01

    Mouse lemurs are suggested to represent promising novel non-human primate models for aging research. However, standardized and cross-taxa cognitive testing methods are still lacking. Touchscreen-based testing procedures have proven high stimulus control and reliability in humans and rodents. The aim of this study was to adapt these procedures to mouse lemurs, thereby exploring the effect of age. We measured appetitive learning and cognitive flexibility of two age groups by applying pairwise visual discrimination (PD) and reversal learning (PDR) tasks. On average, mouse lemurs needed 24 days of training before starting with the PD task. Individual performances in PD and PDR tasks correlate significantly, suggesting that individual learning performance is unrelated to the respective task. Compared to the young, aged mouse lemurs showed impairments in both PD and PDR tasks. They needed significantly more trials to reach the task criteria. A much higher inter-individual variation in old than in young adults was revealed. Furthermore, in the PDR task, we found a significantly higher perseverance in aged compared to young adults, indicating an age-related deficit in cognitive flexibility. This study presents the first touchscreen-based data on the cognitive skills and age-related dysfunction in mouse lemurs and provides a unique basis to study mechanisms of inter-individual variation. It furthermore opens exciting perspectives for comparative approaches in aging, personality, and evolutionary research. PMID:25299046

  7. Processing Speed, Inhibitory Control, and Working Memory: Three Important Factors to Account for Age-Related Cognitive Decline

    ERIC Educational Resources Information Center

    Pereiro Rozas, Arturo X.; Juncos-Rabadan, Onesimo; Gonzalez, Maria Soledad Rodriguez

    2008-01-01

    Processing speed, inhibitory control and working memory have been identified as the main possible culprits of age-related cognitive decline. This article describes a study of their interrelationships and dependence on age, including exploration of whether any of them mediates between age and the others. We carried out a LISREL analysis of the…

  8. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey.

    PubMed

    Ngwenya, Laura B; Heyworth, Nadine C; Shwe, Yamin; Moore, Tara L; Rosene, Douglas L

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  9. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

    PubMed Central

    Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara L.; Rosene, Douglas L.

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  10. A genome-wide scan for common variants affecting the rate of age-related cognitive decline

    PubMed Central

    De Jager, Philip L.; Shulman, Joshua M.; Chibnik, Lori B.; Keenan, Brendan T.; Raj, Towfique; Wilson, Robert S.; Yu, Lei; Leurgans, Sue E.; Tran, Dong; Aubin, Cristin; Anderson, Christopher D.; Biffi, Alessandro; Corneveaux, Jason J.; Huentelman, Matthew J.; Rosand, Jonathan; Daly, Mark J.; Myers, Amanda J.; Reiman, Eric M.; Bennett, David A.; Evans, Denis A.

    2011-01-01

    Age-related cognitive decline is likely promoted by accumulated brain injury due to chronic conditions of aging, including neurodegenerative and vascular disease. Since common neuronal mechanisms may mediate the adaptation to diverse cerebral insults, we hypothesized that susceptibility for age-related cognitive decline may be due in part to a shared genetic network. We have therefore performed a genome-wide association study using a quantitative measure of global cognitive decline slope, based on repeated measures of 17 cognitive tests in 749 subjects from the Religious Orders Study. Top results were evaluated in three independent replication cohorts, consisting of 2,279 additional subjects with repeated cognitive testing. As expected, we find that the Alzheimer’s disease (AD) susceptibility locus, APOE, is strongly associated with rate of cognitive decline (PDISC=5.6×10−9; PJOINT=3.7×10−27). We additionally discover a variant, rs10808746, which shows consistent effects in the replication cohorts and modestly improved evidence of association in the joint analysis (PDISC=6.7×10−5; PREP=9.4×10−3; PJOINT=2.3×10−5). This variant influences the expression of two adjacent genes, PDE7A and MTFR1, which are potential regulators of inflammation and oxidative injury, respectively. Using aggregate measures of genetic risk, we find that known susceptibility loci for cardiovascular disease, type II diabetes, and inflammatory diseases are not significantly associated with cognitive decline in our cohort. Our results suggest that intermediate phenotypes, when coupled with larger sample sizes, may be a useful tool to dissect susceptibility loci for age-related cognitive decline and uncover shared molecular pathways with a role in neuronal injury. PMID:22054870

  11. Age-related deficits in selective attention during encoding increase demands on episodic reconstruction during context retrieval: An ERP study.

    PubMed

    James, Taylor; Strunk, Jonathan; Arndt, Jason; Duarte, Audrey

    2016-06-01

    Previous event-related potential (ERP) and neuroimaging evidence suggests that directing attention toward single item-context associations compared to intra-item features at encoding improves context memory performance and reduces demands on strategic retrieval operations in young and older adults. In everyday situations, however, there are multiple event features competing for our attention. It is not currently known how selectively attending to one contextual feature while attempting to ignore another influences context memory performance and the processes that support successful retrieval in the young and old. We investigated this issue in the current ERP study. Young and older participants studied pictures of objects in the presence of two contextual features: a color and a scene, and their attention was directed to the object's relationship with one of those contexts. Participants made context memory decisions for both attended and unattended contexts and rated their confidence in those decisions. Behavioral results showed that while both groups were generally successful in applying selective attention during context encoding, older adults were less confident in their context memory decisions for attended features and showed greater dependence in context memory accuracy for attended and unattended contextual features (i.e., hyper-binding). ERP results were largely consistent between age groups but older adults showed a more pronounced late posterior negativity (LPN) implicated in episodic reconstruction processes. We conclude that age-related suppression deficits during encoding result in reduced selectivity in context memory, thereby increasing subsequent demands on episodic reconstruction processes when sought after details are not readily retrieved. PMID:27094851

  12. Guidelines for the Evaluation of Dementia and Age-Related Cognitive Change

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Dementia in its many forms is a leading cause of functional limitation among older adults worldwide and will continue to ascend in global health importance as populations continue to age and effective cures remain elusive. The following guidelines were developed for psychologists who perform evaluations of dementia and age-related cognitive…

  13. Age-Related Changes in Sleep and Circadian Rhythms: Impact on Cognitive Performance and Underlying Neuroanatomical Networks

    PubMed Central

    Schmidt, Christina; Peigneux, Philippe; Cajochen, Christian

    2012-01-01

    Circadian and homeostatic sleep-wake regulatory processes interact in a fine tuned manner to modulate human cognitive performance. Dampening of the circadian alertness signal and attenuated deterioration of psychomotor vigilance in response to elevated sleep pressure with aging change this interaction pattern. As evidenced by neuroimaging studies, both homeostatic sleep pressure and circadian sleep-wake promotion impact on cognition-related cortical and arousal-promoting subcortical brain regions including the thalamus, the anterior hypothalamus, and the brainstem locus coeruleus (LC). However, how age-related changes in circadian and homeostatic processes impact on the cerebral activity subtending waking performance remains largely unexplored. Post-mortem studies point to neuronal degeneration in the SCN and age-related modifications in the arousal-promoting LC. Alongside, cortical frontal brain areas are particularly susceptible both to aging and misalignment between circadian and homeostatic processes. In this perspective, we summarize and discuss here the potential neuroanatomical networks underlying age-related changes in circadian and homeostatic modulation of waking performance, ranging from basic arousal to higher order cognitive behaviors. PMID:22855682

  14. Age-related changes in the cerebral substrates of cognitive procedural learning.

    PubMed

    Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

    2009-04-01

    Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative, and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus, and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, the engagement of frontal and cingulate regions persisted in the older group as learning continued, whereas it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure. PMID:18537110

  15. Age-related changes in the cerebral substrates of cognitive procedural learning

    PubMed Central

    Hubert, Valérie; Beaunieux, Hélène; Chételat, Gaël; Platel, Hervé; Landeau, Brigitte; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

    2009-01-01

    Cognitive procedural learning occurs in three qualitatively different phases (cognitive, associative and autonomous). At the beginning of this process, numerous cognitive functions are involved, subtended by distinct brain structures such as the prefrontal and parietal cortex and the cerebellum. As the learning progresses, these cognitive components are gradually replaced by psychomotor abilities, reflected by the increasing involvement of the cerebellum, thalamus and occipital regions. In elderly subjects, although cognitive studies have revealed a learning effect, performance levels differ during the acquisition of a procedure. The effects of age on the learning of a cognitive procedure have not yet been examined using functional imaging. The aim of this study was therefore to characterize the cerebral substrates involved in the learning of a cognitive procedure, comparing a group of older subjects with young controls. For this purpose, we performed a positron emission tomography activation study using the Tower of Toronto task. A direct comparison of the two groups revealed the involvement of a similar network of brain regions at the beginning of learning (cognitive phase). However, whereas the engagement of frontal and cingulate regions persisted in the older group as learning continued, it ceased in the younger controls. We assume that this additional activation in the older group during the associative and autonomous phases reflected compensatory processes and the fact that some older subjects failed to fully automate the procedure. PMID:18537110

  16. Video Games as a Means to Reduce Age-Related Cognitive Decline: Attitudes, Compliance, and Effectiveness

    PubMed Central

    Boot, Walter R.; Champion, Michael; Blakely, Daniel P.; Wright, Timothy; Souders, Dustin J.; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a “brain fitness” game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants’ ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  17. Video games as a means to reduce age-related cognitive decline: attitudes, compliance, and effectiveness.

    PubMed

    Boot, Walter R; Champion, Michael; Blakely, Daniel P; Wright, Timothy; Souders, Dustin J; Charness, Neil

    2013-01-01

    Recent research has demonstrated broad benefits of video game play to perceptual and cognitive abilities. These broad improvements suggest that video game-based cognitive interventions may be ideal to combat the many perceptual and cognitive declines associated with advancing age. Furthermore, game interventions have the potential to induce higher rates of intervention compliance compared to other cognitive interventions as they are assumed to be inherently enjoyable and motivating. We explored these issues in an intervention that tested the ability of an action game and a "brain fitness" game to improve a variety of abilities. Cognitive abilities did not significantly improve, suggesting caution when recommending video game interventions as a means to reduce the effects of cognitive aging. However, the game expected to produce the largest benefit based on previous literature (an action game) induced the lowest intervention compliance. We explain this low compliance by participants' ratings of the action game as less enjoyable and by their prediction that training would have few meaningful benefits. Despite null cognitive results, data provide valuable insights into the types of video games older adults are willing to play and why. PMID:23378841

  18. Computer Simulations of Loss of Organization of Neurons as a Model for Age-related Cognitive Decline

    NASA Astrophysics Data System (ADS)

    Cruz, Luis; Fengometidis, Elene; Jones, Frank; Jampani, Srinivas

    2011-03-01

    In normal aging, brains suffer from progressive cognitive decline not linked with loss of neurons common in neurodegenerative disorders such as Alzheimer's disease. However, in some brain areas neurons have lost positional organization specifically within microcolumns: arrays of interconnected neurons which may constitute fundamental computational units in the brain. This age-related loss of organization, likely a result of micron-sized random displacements in neuronal positions, is hypothesized to be a by-product of the loss of support from the surrounding medium, including dendrites. Using a dynamical model applied to virtual 3D representation of neuronal arrangements, that previously showed loss of organization in brains of cognitively tested rhesus monkeys, the relationship between these displacements and changes to the surrounding dendrite network are presented. The consequences of these displacements on the structure of the dendritic network, with possible disruptions in signal synchrony important to cognitive function, are discussed. NIH R01AG021133.

  19. APOE and aging-related cognitive change in a longitudinal cohort of men.

    PubMed

    Rantalainen, Ville; Lahti, Jari; Henriksson, Markus; Kajantie, Eero; Tienari, Pentti; Eriksson, Johan G; Raikkonen, Katri

    2016-08-01

    We examined associations between APOE major isoforms, rs405509 promoter and rs440446 intron-1 polymorphisms, and nonpathologic cognitive aging. Men from the Helsinki Birth Cohort Study took the Finnish Defence Forces Basic Intellectual Ability Test twice, at age 20.1 (n = 404) and 67.6 years (n = 247). APOE major isoforms did not associate with cognitive ability. In the APOE major isoform-adjusted analyses, the number of rs405509 minor alleles was associated with a higher cognitive ability total and verbal, arithmetic, and visuospatial subtest scores at 67.6 years (p-values < 0.004). In the analyses of cognitive change, the visuospatial subtest score increased across time in rs440446 minor allele carriers but decreased in noncarriers (p = 0.007). Associations in the APOE major isoform-stratified analyses were significant in the APOE ε3/3 homozygotes only. The APOE locus harbors additional modifying alleles, independent of APOE major isoforms that are associated with better preserved general cognitive ability in nondemented elderly men and change in visuospatial ability across 5 decades. These results suggest that at least 2 distinct mechanisms link the APOE locus with cognitive ability. PMID:27318143

  20. Formaldehyde as a trigger for protein aggregation and potential target for mitigation of age-related, progressive cognitive impairment.

    PubMed

    Su, Tao; Monte, Woodrow C; Hu, Xintian; He, Yingge; He, Rongqiao

    2016-01-01

    Recently, formaldehyde (FA), existing in a number of different cells including neural cells, was found to affect age-related cognitive impairment. Oral administration of methanol (the metabolic precursor of FA) triggers formation of senile plaques (SPs) and Tau hyperphosphorylation in the brains of monkeys with memory decline. Intraperitoneal injection of FA leads to hyperphosphorylation of Tau in wild-type mouse brains and N2a cells through activation of glycogen synthase kinase-3β (GSK-3β). Furthermore, formaldehyde at low concentrations can directly induce Tau aggregation and amyloid β (Aβ) peptide deposits in vitro. Formaldehyde-induced Tau aggregation is implicated in cytotoxicity and neural cell apoptosis. Clarifying how FA triggers Aβ deposits and Tau hyperphosphorlyation will not only improve our understanding of the molecular and cellular mechanisms of age-related cognitive impairment but will also contribute to the ongoing investigation of alternate targets for new drugs. Here, we review the role of FA, particularly that of endogenous origin, in protein aggregation and as a potential drug intervention in the development of agerelated cognitive impairment. PMID:26268337

  1. A Multiple Deficit Model of Reading Disability and Attention-Deficit/Hyperactivity Disorder: Searching for Shared Cognitive Deficits

    ERIC Educational Resources Information Center

    McGrath, Lauren M.; Pennington, Bruce F.; Shanahan, Michelle A.; Santerre-Lemmon, Laura E.; Barnard, Holly D.; Willcutt, Erik G.; DeFries, John C.; Olson, Richard K.

    2011-01-01

    Background: This study tests a multiple cognitive deficit model of reading disability (RD), attention-deficit/hyperactivity disorder (ADHD), and their comorbidity. Methods: A structural equation model (SEM) of multiple cognitive risk factors and symptom outcome variables was constructed. The model included phonological awareness as a unique…

  2. Should cognitive deficit be a diagnostic criterion for schizophrenia?

    PubMed Central

    Lewis, Ralph

    2004-01-01

    This review examines the question of whether cognitive deficits in schizophrenia are sufficiently reliable, stable and specific to warrant inclusion in the diagnostic criteria for schizophrenia. The literature provides evidence that cognitive deficits are highly prevalent and fairly marked in adult patients with schizophrenia. Similar deficits have been found in children and adolescents with schizophrenia, and in children before they exhibit the signs and symptoms of schizophrenia. These deficits may in fact be central to the pathophysiology underlying the development of overt psychosis in schizophrenia. The deficits appear to be relatively stable across the course of the illness. They are generally more severe in schizophrenia than in affective disorders and may have a relatively specific pattern in schizophrenia. It is concluded that the evidence that cognitive deficits are a core feature of schizophrenia is sufficiently compelling to warrant inclusion of these deficits in the diagnostic criteria for schizophrenia, at least as a nonessential criterion. PMID:15069464

  3. Age-Related Changes in Cognitive Processing of Moral and Social Conventional Violations

    ERIC Educational Resources Information Center

    Lahat, Ayelet; Helwig, Charles C.; Zelazo, Philip David

    2012-01-01

    Moral and conventional violations are usually judged differently: Only moral violations are treated as independent of social rules. To investigate the cognitive processing involved in the development of this distinction, undergraduates (N = 34), adolescents (N = 34), and children (N = 14) read scenarios presented on a computer that had 1 of 3…

  4. Cognitive deficits triggered by early life stress: The role of histone deacetylase 1.

    PubMed

    Adler, Samantha M; Schmauss, Claudia

    2016-10-01

    Studies showed that histone deacetylase (HDAC) inhibitors can reverse cognitive deficits found in neurodegenerative disorders and age-related memory decline. However, the role of HDACs in stress-induced cognitive deficits has not been investigated. In the stress-susceptible mouse strain Balb/c, early life stress triggers a persistent decrease in HDAC expression in the forebrain neocortex, including reduced expression of class I HDACs. The same mice show pronounced cognitive deficits in adulthood, namely deficits in working memory and attention set-shifting. Here we show that these mice also exhibit reduced association of HDAC1 with promotor III of the brain-derived neurotrophic factor (Bdnf) gene, and that cognitive testing leads to abnormally increased Bdnf mRNA expression. A pharmacological reduction of Bdnf-tropomyosine kinase B receptor signaling effectively reverses the cognitive deficits, indicating that enhanced transcriptional activation of the Bdnf gene contributes to their emergence. In contrast to Balb/c mice, C57Bl/6 mice only develop attention set-shifting deficits when raised by Balb/c foster mothers during the time the pups are exposed to early life stress. HDAC1 levels at Bdnf promotor III are unaltered in such C57Bl/6 mice, although they exhibit decreased levels of HDAC1 at the promotor of the early-growth response gene 2 (Egr2) and abnormally increased Egr2 mRNA expression after cognitive testing. Hence, contrary to the beneficial effects of HDAC inhibition in neurodegenerative diseases, the reduced HDAC1 levels at promotors of distinct plasticity-associated genes predispose animals exposed to early life stress to enhanced expression of these genes upon cognitive challenge, an effect that negatively influences cognitive task performance. PMID:27260837

  5. A blueberry-enriched antioxidant diet reduces an age-related deficit in one trial per day discriminative reward learning

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been reported that an antioxidant-rich, blueberry-supplemented rat diet may slow brain aging in the rat and protect against age-related memory impairment as measured by such tasks as the water maze and visual object recognition. The present study determined whether such supplementation could ...

  6. Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment

    PubMed Central

    2014-01-01

    Background Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995–2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant’s address. Results Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions The association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects. PMID:24884505

  7. Age-Related Decline in Cognitive Pain Modulation Induced by Distraction: Evidence From Event-Related Potentials.

    PubMed

    Zhou, Shu; Després, Olivier; Pebayle, Thierry; Dufour, André

    2015-09-01

    Distraction is known to reduce perceived pain but not always efficiently. Overlapping cognitive resources play a role in both pain processing and executive functions. We hypothesized that with aging, the analgesic effects of cognitive modulation induced by distraction would be reduced as a result of functional decline of frontal networks. Twenty-eight elderly and 28 young participants performed a tonic heat pain test with and without distraction (P + D vs P condition), and 2 executive tasks involving the frontal network (1-back [working memory] and go/no-go [response inhibition]), during which event-related potentials were recorded. A significant age-related difference in modulatory effect was observed during the pain-distraction test, with the older group reporting higher pain perception than the younger group during the P + D than during the P condition. Greater brain activity of early processes (P2 component) in both go/no-go and 1-back tasks correlated with less perceived pain during distraction in younger participants. For later processes, more cognitive control and attentional resources (increased N2 and P3 amplitude) needed for working memory processes were associated with greater pain perception in the older group. Inhibition processes were related to conscious distraction estimation in both groups. These findings indicate that cognitive processes subtended by resources in the frontal network, particularly working memory processes, are elicited more in elderly than in younger individuals for pain tolerance when an irrelevant task is performed simultaneously. Perspective: This study suggests that age-related declines in pain modulation are caused by functional degeneration of frontal cerebral networks, which may contribute to a higher prevalence of chronic pain. Analyzing the impact of frontal network function on pain modulation may assist in the development of more effective targeted treatment plans. PMID:26080043

  8. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition

    PubMed Central

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17–88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  9. Examining age-related shared variance between face cognition, vision, and self-reported physical health: a test of the common cause hypothesis for social cognition.

    PubMed

    Olderbak, Sally; Hildebrandt, Andrea; Wilhelm, Oliver

    2015-01-01

    The shared decline in cognitive abilities, sensory functions (e.g., vision and hearing), and physical health with increasing age is well documented with some research attributing this shared age-related decline to a single common cause (e.g., aging brain). We evaluate the extent to which the common cause hypothesis predicts associations between vision and physical health with social cognition abilities specifically face perception and face memory. Based on a sample of 443 adults (17-88 years old), we test a series of structural equation models, including Multiple Indicator Multiple Cause (MIMIC) models, and estimate the extent to which vision and self-reported physical health are related to face perception and face memory through a common factor, before and after controlling for their fluid cognitive component and the linear effects of age. Results suggest significant shared variance amongst these constructs, with a common factor explaining some, but not all, of the shared age-related variance. Also, we found that the relations of face perception, but not face memory, with vision and physical health could be completely explained by fluid cognition. Overall, results suggest that a single common cause explains most, but not all age-related shared variance with domain specific aging mechanisms evident. PMID:26321998

  10. A Mid-Life Vitamin A Supplementation Prevents Age-Related Spatial Memory Deficits and Hippocampal Neurogenesis Alterations through CRABP-I

    PubMed Central

    Touyarot, Katia; Bonhomme, Damien; Roux, Pascale; Alfos, Serge; Lafenêtre, Pauline; Richard, Emmanuel; Higueret, Paul; Pallet, Véronique

    2013-01-01

    Age-related memory decline including spatial reference memory is considered to begin at middle-age and coincides with reduced adult hippocampal neurogenesis. Moreover, a dysfunction of vitamin A hippocampal signalling pathway has been involved in the appearance of age-related memory deficits but also in adult hippocampal neurogenesis alterations. The present study aims at testing the hypothesis that a mid-life vitamin A supplementation would be a successful strategy to prevent age-related memory deficits. Thus, middle-aged Wistar rats were submitted to a vitamin A enriched diet and were tested 4 months later in a spatial memory task. In order to better understand the potential mechanisms mediating the effects of vitamin A supplementation on hippocampal functions, we studied different aspects of hippocampal adult neurogenesis and evaluated hippocampal CRABP-I expression, known to modulate differentiation processes. Here, we show that vitamin A supplementation from middle-age enhances spatial memory and improves the dendritic arborisation of newborn immature neurons probably resulting in a better survival and neuronal differentiation in aged rats. Moreover, our results suggest that hippocampal CRABP-I expression which controls the intracellular availability of retinoic acid (RA), may be an important regulator of neuronal differentiation processes in the aged hippocampus. Thus, vitamin A supplementation from middle-age could be a good strategy to maintain hippocampal plasticity and functions. PMID:23977218

  11. Hyperactivity in the Gunn rat model of neonatal jaundice: age-related attenuation and emergence of gait deficits

    PubMed Central

    Stanford, John A.; Shuler, Jeffrey M.; Fowler, Stephen C.; Stanford, Kimberly G.; Ma, Delin; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Shapiro, Steven M.

    2014-01-01

    Background Neonatal jaundice resulting from elevated unconjugated bilirubin (UCB) occurs in 60–80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention deficit-hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND. Methods Using a sensitive force plate actometer, we measured locomotor activity and gait in jaundiced (jj) Gunn rats versus their non-jaundiced (Nj) littermates. Data were analyzed for young adult (3–4 months), early middle-aged (9–10 months), and late middle-aged (17–20 months) male rats. Results jj rats exhibited lower body weights at all ages and a hyperactivity that resolved at 17–20 months of age. Increased propulsive force and gait velocity accompanied hyperactivity during locomotor bouts at 9–10 months in jj rats. Stride length did not differ between the two groups at this age. Hyperactivity normalized and gait deficits, including decreased stride length, propulsive force, and gait velocity, emerged in the 17–20-month-old jj rats. Conclusions These results demonstrate that, in aging, hyperactivity decreases with the onset of gait deficits in the Gunn rat model of BIND. PMID:25518009

  12. Combined effects of physical exercise and education on age-related cortical thinning in cognitively normal individuals

    PubMed Central

    Lee, Jin San; Shin, Hee Young; Kim, Hee Jin; Jang, Young Kyoung; Jung, Na-Yeon; Lee, Juyoun; Kim, Yeo Jin; Chun, Phillip; Yang, Jin-Ju; Lee, Jong-Min; Kang, Mira; Park, Key-Chung; Na, Duk L.; Seo, Sang Won

    2016-01-01

    We investigated the association between self-reported physical exercise and cortical thickness in a large sample of cognitively normal individuals. We also determined whether a combination of physical exercise and education had more protective effects on age-related cortical thinning than either parameter alone. A total of 1,842 participants were included in this analysis. Physical exercise was assessed using a questionnaire regarding intensity, frequency, and duration. Cortical thickness was measured using a surface-based method. Longer duration of exercise (≥1 hr/day), but not intensity or frequency, was associated with increased mean cortical thickness globally (P-value = 0.013) and in the frontal regions (P-value = 0.007). In particular, the association of exercise with cortical thinning had regional specificity in the bilateral dorsolateral prefrontal, precuneus, left postcentral, and inferior parietal regions. The combination of higher exercise level and higher education level showed greater global and frontal mean thickness than either parameter alone. Testing for a trend with the combination of high exercise level and high education level confirmed this finding (P-value = 0.001–0.003). Our findings suggest that combined exercise and education have important implications for brain health, especially considering the paucity of known protective factors for age-related cortical thinning. PMID:27063336

  13. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions

    PubMed Central

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  14. Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

    PubMed

    De Oliveira, Thaís Cristina Galdino; Soares, Fernanda Cabral; De Macedo, Liliane Dias E Dias; Diniz, Domingos Luiz Wanderley Picanço; Bento-Torres, Natáli Valim Oliver; Picanço-Diniz, Cristovam Wanderley

    2014-01-01

    The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons. PMID:24600211

  15. Common Cognitive Deficits in Children with Attention-Deficit/Hyperactivity Disorder and Autism: Working Memory and Visual-Motor Integration

    ERIC Educational Resources Information Center

    Englund, Julia A.; Decker, Scott L.; Allen, Ryan A.; Roberts, Alycia M.

    2014-01-01

    Cognitive deficits in working memory (WM) are characteristic features of Attention-Deficit/Hyperactivity Disorder (ADHD) and autism. However, few studies have investigated cognitive deficits using a wide range of cognitive measures. We compared children with ADHD ("n" = 49) and autism ("n" = 33) with a demographically matched…

  16. Computer-Based Cognitive Programs for Improvement of Memory, Processing Speed and Executive Function during Age-Related Cognitive Decline: A Meta-Analysis

    PubMed Central

    Shao, Yan-kun; Mang, Jing; Li, Pei-lan; Wang, Jie; Deng, Ting; Xu, Zhong-xin

    2015-01-01

    Background Several studies have assessed the effects of computer-based cognitive programs (CCP) in the management of age-related cognitive decline, but the role of CCP remains controversial. Therefore, this systematic review evaluated the evidence on the efficacy of CCP for age-related cognitive decline in healthy older adults. Methods Six electronic databases (through October 2014) were searched. The risk of bias was assessed using the Cochrane Collaboration tool. The standardized mean difference (SMD) and 95% confidence intervals (CI) of a random-effects model were calculated. The heterogeneity was assessed using the Cochran Q statistic and quantified with the I2 index. Results Twelve studies were included in the current review and were considered as moderate to high methodological quality. The aggregated results indicate that CCP improves memory performance (SMD, 0.31; 95% CI 0.16 to 0.45; p < 0.0001) and processing speed (SMD, 0.50; 95% CI 0.14 to 0.87; p = 0.007) but not executive function (SMD, -0.12; 95% CI -0.33 to 0.09; p = 0.27). Furthermore, there were long-term gains in memory performance (SMD, 0.59; 95% CI 0.13 to 1.05; p = 0.01). Conclusion CCP may be a valid complementary and alternative therapy for age-related cognitive decline, especially for memory performance and processing speed. However, more studies with longer follow-ups are warranted to confirm the current findings. PMID:26098943

  17. Age-Related Changes in Electrophysiological and Neuropsychological Indices of Working Memory, Attention Control, and Cognitive Flexibility

    PubMed Central

    Peltz, Carrie Brumback; Gratton, Gabriele; Fabiani, Monica

    2011-01-01

    Older adults exhibit great variability in their cognitive abilities, with some maintaining high levels of performance on executive control tasks and others showing significant deficits. Previous event-related potential (ERP) work has shown that some of these performance differences are correlated with persistence of the novelty/frontal P3 in older adults elicited by task-relevant events, presumably reflecting variability in the capacity to suppress orienting to unexpected but no longer novel events. In recent ERP work in young adults, we showed that the operation-span (OSPAN) task (a measure of attention control) is predictive of the ability of individuals to keep track of stimulus sequencing and to maintain running mental representations of task stimuli, as indexed by the parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of frontal function (cognitive flexibility and attention control, respectively). To investigate these phenomena we sorted both younger and older adults into low- and high-working memory spans and low- and high-cognitive flexibility subgroups, and examined ERPs during an equal-probability choice reaction time task. For both age groups (a) participants with high OSPAN scores were better able to keep track of stimulus sequencing, as indicated by their smaller P3b to sequential changes; and (b) participants with lower cognitive flexibility had larger P3a than their high-scoring counterparts. However, these two phenomena did not interact suggesting that they manifest dissociable control mechanisms. Further, the fact that both effects are already visible in younger adults suggests that at least some of the brain mechanisms underlying individual differences in cognitive aging may already operate early in life. PMID:21887150

  18. Oculomotor Performance Identifies Underlying Cognitive Deficits in Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Loe, Irene M.; Feldman, Heidi M.; Yasui, Enami; Luna, Beatriz

    2009-01-01

    The evaluation of the cognitive control in children with attention-deficit hyperactivity disorder through the use of oculomotor tests reveal that this group showed susceptibility to peripheral distractors and deficits in response inhibition. All subjects were found to have intact sensorimotor function and working memory.

  19. Cognitive Mapping Deficits in Schizophrenia: A Critical Overview

    PubMed Central

    Bose, Anushree; Agarwal, Sri Mahavir; Kalmady, Sunil V.; Venkatasubramanian, Ganesan

    2014-01-01

    Hippocampal deficits are an established feature of schizophrenia and are complementary with recent evidences of marked allocentric processing deficits being reported in this disorder. By “Cognitive mapping” we intend to refer to the concepts from the seminal works of O’Keefe and Nadel (1978) that led to the development of cognitive map theory of hippocampal function. In this review, we summarize emerging evidences and issues that indicate that “Cognitive mapping deficits” form one of the important cognitive aberrations in schizophrenia. The importance has been placed upon hippocampally mediated allocentric processing deficits and their role in pathology of schizophrenia, for spatial/representational cognitive deficits and positive symptoms in particular. It is modestly summarized that emerging evidences point toward a web of spatial and cognitive representation errors concurrent with pronounced hippocampal dysfunction. In general, it can be stated that there are clear and consistent evidences that favor the cognitive mapping theory in explaining certain deficits of schizophrenia and for drawing out a possible and promising endophenotype/biomarkers. Further research in this regard demands attention. PMID:24701005

  20. Cognitive control in alcohol use disorder: deficits and clinical relevance

    PubMed Central

    Wilcox, Claire E.; Dekonenko, Charlene J.; Mayer, Andrew R.; Bogenschutz, Michael P.; Turner, Jessica A.

    2014-01-01

    Cognitive control refers to the internal representation, maintenance, and updating of context information in the service of exerting control over thoughts and behavior. Deficits in cognitive control likely contribute to difficulty in maintaining abstinence in individuals with alcohol use disorders (AUD). In this article, we define three cognitive control processes in detail (response inhibition, distractor interference control, and working memory), review the tasks measuring performance in these areas, and summarize the brain networks involved in carrying out these processes. Next, we review evidence of deficits in these processes in AUD, including both metrics of task performance and functional neuroimaging. Finally, we explore the clinical relevance of these deficits by identifying predictors of clinical outcome and markers that appear to change (improve) with treatment. We observe that individuals with AUD experience deficits in some, but not all, metrics of cognitive control. Deficits in cognitive control may predict clinical outcome in AUD, but more work is necessary to replicate findings. It is likely that performance on tasks requiring cognitive control improves with abstinence, and with some psychosocial and medication treatments. Future work should clarify which aspects of cognitive control are most important to target during treatment of AUD. PMID:24361772

  1. Glutamatergic treatment strategies for age-related memory disorders.

    PubMed

    Müller, W E; Scheuer, K; Stoll, S

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7997073

  2. Aging-related 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurochemial and behavioral deficits and redox dysfunction: improvement by AK-7.

    PubMed

    Guan, Qiang; Wang, Meihua; Chen, Hanqing; Yang, Liu; Yan, Zhiqiang; Wang, Xijin

    2016-09-01

    Aging is a prominent risk factor for the occurrence and progression of Parkinson disease (PD). Aging animals are more significant for PD research than young ones. It is promising to develop effective treatments for PD through modulation of aging-related molecules. Sirtuin 2 (SIRT2), a strong deacetylase highly expressed in the brain, has been implicated in the aging process. In our present study, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 12mg/kg once daily) was observed to bring about significant behavioral deficits and striatal dopamine depletion in aging male and female mice, while it did not do so in young animals. MPTP did not cause significant reduction in striatal 5-hydroxytryptamine content in aging male and female mice. Furthermore, we observed that MPTP treatment resulted in significant reduction in GSH content and significant increase in MDA content and SIRT2 expression in the substantia nigra (SN) of aging mice, while it did not do so in young animals. Importantly, we observed that AK-7 (a selective SIRT2 inhibitor) significantly improved behavior abnormality and neurochemical deficits in aging male and female mice treated with MPTP. Significant increase in GSH content and significant decrease in MDA content were also observed in the SN of aging male and female mice co-treated with MPTP and AK-7 compared with the MPTP-treated animals. Our results indicated that MPTP induce aging-related neurochemical and behavioural deficits and dysfunction of redox network in male and female mice and AK-7 may be neuroprotective in PD through modulating redox network. PMID:27235848

  3. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition.

    PubMed

    Pichora-Fuller, M Kathleen; Mick, Paul; Reed, Marilyn

    2015-08-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  4. Hearing, Cognition, and Healthy Aging: Social and Public Health Implications of the Links between Age-Related Declines in Hearing and Cognition

    PubMed Central

    Pichora-Fuller, M. Kathleen; Mick, Paul; Reed, Marilyn

    2015-01-01

    Sensory input provides the signals used by the brain when listeners understand speech and participate in social activities with other people in a range of everyday situations. When sensory inputs are diminished, there can be short-term consequences to brain functioning, and long-term deprivation can affect brain neuroplasticity. Indeed, the association between hearing loss and cognitive declines in older adults is supported by experimental and epidemiologic evidence, although the causal mechanisms remain unknown. These interactions of auditory and cognitive aging play out in the challenges confronted by people with age-related hearing problems when understanding speech and engaging in social interactions. In the present article, we use the World Health Organization's International Classification of Functioning, Disability and Health and the Selective Optimization with Compensation models to highlight the importance of adopting a healthy aging perspective that focuses on facilitating active social participation by older adults. First, we examine epidemiologic evidence linking ARHL to cognitive declines and other health issues. Next, we examine how social factors influence and are influenced by auditory and cognitive aging and if they may provide a possible explanation for the association between ARHL and cognitive decline. Finally, we outline how audiologists could reposition hearing health care within the broader context of healthy aging. PMID:27516713

  5. Over the hill at 24: persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood.

    PubMed

    Thompson, Joseph J; Blair, Mark R; Henrey, Andrew J

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  6. Over the Hill at 24: Persistent Age-Related Cognitive-Motor Decline in Reaction Times in an Ecologically Valid Video Game Task Begins in Early Adulthood

    PubMed Central

    Thompson, Joseph J.; Blair, Mark R.; Henrey, Andrew J.

    2014-01-01

    Typically studies of the effects of aging on cognitive-motor performance emphasize changes in elderly populations. Although some research is directly concerned with when age-related decline actually begins, studies are often based on relatively simple reaction time tasks, making it impossible to gauge the impact of experience in compensating for this decline in a real world task. The present study investigates age-related changes in cognitive motor performance through adolescence and adulthood in a complex real world task, the real-time strategy video game StarCraft 2. In this paper we analyze the influence of age on performance using a dataset of 3,305 players, aged 16-44, collected by Thompson, Blair, Chen & Henrey [1]. Using a piecewise regression analysis, we find that age-related slowing of within-game, self-initiated response times begins at 24 years of age. We find no evidence for the common belief expertise should attenuate domain-specific cognitive decline. Domain-specific response time declines appear to persist regardless of skill level. A second analysis of dual-task performance finds no evidence of a corresponding age-related decline. Finally, an exploratory analyses of other age-related differences suggests that older participants may have been compensating for a loss in response speed through the use of game mechanics that reduce cognitive load. PMID:24718593

  7. Premorbid Cognitive Deficits in Young Relatives of Schizophrenia Patients

    PubMed Central

    Keshavan, Matcheri S.; Kulkarni, Shreedhar; Bhojraj, Tejas; Francis, Alan; Diwadkar, Vaibhav; Montrose, Debra M.; Seidman, Larry J.; Sweeney, John

    2009-01-01

    Neurocognitive deficits in schizophrenia (SZ) are thought to be stable trait markers that predate the illness and manifest in relatives of patients. Adolescence is the age of maximum vulnerability to the onset of SZ and may be an opportune “window” to observe neurocognitive impairments close to but prior to the onset of psychosis. We reviewed the extant studies assessing neurocognitive deficits in young relatives at high risk (HR) for SZ and their relation to brain structural alterations. We also provide some additional data pertaining to the relation of these deficits to psychopathology and brain structural alterations from the Pittsburgh Risk Evaluation Program (PREP). Cognitive deficits are noted in the HR population, which are more severe in first-degree relatives compared to second-degree relatives and primarily involve psychomotor speed, memory, attention, reasoning, and social-cognition. Reduced general intelligence is also noted, although its relationship to these specific domains is underexplored. Premorbid cognitive deficits may be related to brain structural and functional abnormalities, underlining the neurobiological basis of this illness. Cognitive impairments might predict later emergence of psychopathology in at-risk subjects and may be targets of early remediation and preventive strategies. Although evidence for neurocognitive deficits in young relatives abounds, further studies on their structural underpinnings and on their candidate status as endophenotypes are needed. PMID:20300465

  8. [Differentiation of deficit and non-deficit schizophrenia based on cognitive functions].

    PubMed

    Polgár, Patrícia

    2011-03-30

    Cognitive dysfunction is a core feature in schizophrenia and has a great impact on psychosocial functioning. Still it remains unclear, whether the different diagnostic subgroups have a specific cognitive profile. The topic of this research was to investigate the neurocognitive characteristics of deficit and non-deficit schizophrenia, and to examine if the two diagnostic subgroups have a qualitative difference in cognitive functioning. In Study 1., 275 patient and 130 healthy controls completed the WCST (Wisconsin Card Sorting Test). We performed an exploratory factor analytic study on the variables for the total group and each subgroups, then we assessed the ability of the factors to distinguish between the deficit, non deficit and control groups. In Study 2., I used the Kilroy-test to investigate procedural and context-dependent learning. 78 patients and 30 healthy controls completed the test, which has two phases: while the training phase is dominantly related to basal ganglia circuits, the context-dependent probe phase requires intact medial-temporal lobe functioning. Thus the two interactive memory systems can be examined separately within one test. Study 1.: Results of the exploratory factor analysis of the whole sample yielded two factors which together explained approximately 95% of the total variance. Comparison of the diagnostic groups on each of the factors revealed that both schizophrenia groups showed executive function impairment in comparison to controls. Deficit patients suffer from a more severe degree of impairment on the "General executive function" factor (conceptualization, flexibility, set shifting) than non-deficit patients. On the other hand, non-perseverative error type (factor 2.) seems to be less typical to deficit than to the non-deficit patients. Study 2.: Results revealed that deficit and non-deficit patients were similarly impaired on the probe phase compared with controls. However, the training phase was not compromised in non-deficit

  9. Speech deficits in serious mental illness: a cognitive resource issue?

    PubMed

    Cohen, Alex S; McGovern, Jessica E; Dinzeo, Thomas J; Covington, Michael A

    2014-12-01

    Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifest as a function of cognitive resource limitations. We examined natural speech from 52 patients meeting criteria for serious mental illnesses (i.e., severe functional deficits with a concomitant diagnosis of schizophrenia, unipolar and/or bipolar affective disorders) and 30 non-psychiatric controls using a range of objective, computer-based measures tapping speech production ("alogia"), variability ("blunted vocal affect") and content ("poverty of content of speech"). Subjects produced natural speech during a baseline condition and while engaging in an experimentally-manipulated cognitively-effortful task. For correlational analysis, cognitive ability was measured using a standardized battery. Generally speaking, speech deficits did not differ as a function of SMI diagnosis. However, every speech production and content measure was significantly abnormal in SMI versus control groups. Speech variability measures generally did not differ between groups. For both patients and controls as a group, speech during the cognitively-effortful task was sparser and less rich in content. Relative to controls, patients were abnormal under cognitive load with respect only to average pause length. Correlations between the speech variables and cognitive ability were only significant for this same variable: average pause length. Results suggest that certain speech deficits, notably involving pause length, may manifest as a function of cognitive resource limitations. Implications for treatment, research and assessment are discussed. PMID:25464920

  10. Speech Deficits in Serious mental Illness: A Cognitive Resource Issue?

    PubMed Central

    Cohen, Alex S.; McGovern, Jessica E.; Dinzeo, Thomas J.; Covington, Michael A.

    2014-01-01

    Speech deficits, notably those involved in psychomotor retardation, blunted affect, alogia and poverty of content of speech, are pronounced in a wide range of serious mental illnesses (e.g., schizophrenia, unipolar depression, bipolar disorders). The present project evaluated the degree to which these deficits manifest as a function of cognitive resource limitations. We examined natural speech from 52 patients meeting criteria for serious mental illnesses (i.e., severe functional deficits with a concomitant diagnosis of schizophrenia, unipolar and/or bipolar affective disorders) and 30 non-psychiatric controls using a range of objective, computer-based measures tapping speech production (“alogia”), variability (“blunted vocal affect”) and content (“poverty of content of speech”). Subjects produced natural speech during a baseline condition and while engaging in an experimentally-manipulated cognitively-effortful task. For correlational analysis, cognitive ability was measured using a standardized battery. Generally speaking, speech deficits did not differ as a function of SMI diagnosis. However, every speech production and content measure was significantly abnormal in SMI versus control groups. Speech variability measures generally did not differ between groups. For both patients and controls as a group, speech during the cognitively-effortful task was sparser and less rich in content. Relative to controls, patients were abnormal under cognitive load with respect only to average pause length. Correlations between the speech variables and cognitive ability were only significant for this same variable: average pause length. Results suggest that certain speech deficits, notably involving pause length, may manifest as a function of cognitive resource limitations. Implications for treatment, research and assessment are discussed. PMID:25464920

  11. [Neurocognitive and social cognition deficits in patients with anorexia nervosa].

    PubMed

    Kułakowska, Dorota; Biernacka, Katarzyna; Wilkos, Ewelina; Rybakowski, Filip; Kucharska-Pietura, Katarzyna

    2014-01-01

    In the first part of the article the authors present a set of the actual concepts explaining problems of cognitive functions and social cognition currently observed in patients with anorexia nervosa (AN). It is possible; through the neuroimaging research, to get better understanding of the brain specifics in these individuals. Even though, the AN remains a disease with very complex and multifactorial etiology which remains a huge medical challenge. Currently, popular is the view that takes into consideration the integrating role of the insula and subcortical structures (such as hippocampus, amygdala, thalamus) in the regulation of cognitive and emotional processes in people suffering from AN. There is still an open problem, however, of the selection of therapeutic interventions targeting these deficits. The second part of the article presents the attempt to describe deficits in neurocognitive and social cognition in people with AN occurring prior to illness, during and after the recovery. Particular attention has been paid to the most frequently described in the literature--neurocognitive deficits such as rigidity of thinking, weak central coherence, and deficits in social cognition, including mental processes of perception and expression of emotions, disorders of the theory of mind (ToM) and empathy. The results of previous studies, their scarcity in Poland, do not give a satisfactory answer to the question whether the above mentioned disorders are a feature of endophenotype or condition in an episode of the disease. Research point to the more permanent nature, which may be more resistant to therapeutic modifications. PMID:25204093

  12. The molecular basis of cognitive deficits in pervasive developmental disorders

    PubMed Central

    Bhattacharya, Aditi; Klann, Eric

    2012-01-01

    Persons with pervasive developmental disorders (PDD) exhibit a range of cognitive deficits that hamper their quality of life, including difficulties involving communication, sociability, and perspective-taking. In recent years, a variety of studies in mice that model genetic syndromes with a high risk of PDD have provided insights into the underlying molecular mechanisms associated with these disorders. What is less appreciated is how the molecular anomalies affect neuronal and circuit function to give rise to the cognitive deficits associated with PDD. In this review, we describe genetic mutations that cause PDD and discuss how they alter fundamental social and cognitive processes. We then describe efforts to correct cognitive impairments associated with these disorders and identify areas of further inquiry in the search for molecular targets for therapeutics for PDD. PMID:22904374

  13. Cognitive Deficits in Adults with ADHD Go beyond Comorbidity Effects

    ERIC Educational Resources Information Center

    Silva, Katiane L.; Guimaraes-da-Silva, Paula O.; Grevet, Eugenio H.; Victor, Marcelo M.; Salgado, Carlos A. I.; Vitola, Eduardo S.; Mota, Nina R.; Fischer, Aline G.; Contini, Veronica; Picon, Felipe A.; Karam, Rafael G.; Belmonte-de-Abreu, Paulo; Rohde, Luis A.; Bau, Claiton H. D.

    2013-01-01

    Objective: This study addresses if deficits in cognitive, attention, and inhibitory control performance in adults with ADHD are better explained by the disorder itself or by comorbid conditions. Method Adult patients with ADHD ("n" = 352) and controls ("n" = 94) were evaluated in the ADHD program of a tertiary hospital. The…

  14. Performances on a cognitive theory of mind task: specific decline or general cognitive deficits? Evidence from normal aging.

    PubMed

    Fliss, Rafika; Lemerre, Marion; Mollard, Audrey

    2016-06-01

    Compromised theory of mind (ToM) can be explained either by a failure to implement specific representational capacities (mental state representations) or by more general executive selection demands. In older adult populations, evidence supporting affected executive functioning and cognitive ToM in normal aging are reported. However, links between these two functions remain unclear. In the present paper, we address these shortcomings by using a specific task of ToM and classical executive tasks. We studied, using an original cognitive ToM task, the effect of age on ToM performances, in link with the progressive executive decline. 96 elderly participants were recruited. They were asked to perform a cognitive ToM task, and 5 executive tests (Stroop test and Hayling Sentence Completion Test to appreciate inhibitory process, Trail Making Test and Verbal Fluency for shifting assessment and backward span dedicated to estimate working memory capacity). The results show changes in cognitive ToM performance according to executive demands. Correlational studies indicate a significant relationship between ToM performance and the selected executive measures. Regression analyzes demonstrates that level of vocabulary and age as the best predictors of ToM performance. The results are consistent with the hypothesis that ToM deficits are related to age-related domain-general decline rather than as to a breakdown in specialized representational system. The implications of these findings for the nature of social cognition tests in normal aging are also discussed. PMID:27277154

  15. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory

    PubMed Central

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  16. Age-related changes in brain activity are specific for high order cognitive processes during successful encoding of information in working memory.

    PubMed

    Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

    2015-01-01

    Memory capacity suffers an age-related decline, which is supposed to be due to a generalized slowing of processing speed and to a reduced availability of processing resources. Information encoding in memory has been demonstrated to be very sensitive to age-related changes, especially when carried out through self-initiated strategies or under high cognitive demands. However, most event-related potentials (ERP) research on age-related changes in working memory (WM) has used tasks that preclude distinction between age-related changes in encoding and retrieval processes. Here, we used ERP recording and a delayed match to sample (DMS) task with two levels of memory load to assess age-related changes in electrical brain activity in young and old adults during successful information encoding in WM. Age-related decline was reflected in lower accuracy rates and longer reaction times in the DMS task. Beside, only old adults presented lower accuracy rates under high than low memory load conditions. However, effects of memory load on brain activity were independent of age and may indicate an increased need of processing after stimulus classification as reflected in larger mean voltages in high than low load conditions between 550 and 1000 ms post-stimulus for young and old adults. Regarding age-related effects on brain activity, results also revealed smaller P2 and P300 amplitudes that may signal the existence of an age dependent reduction in the processing resources available for stimulus evaluation and categorization. Additionally, P2 and N2 latencies were longer in old than in young participants. Furthermore, longer N2 latencies were related to greater accuracy rates on the DMS task, especially in old adults. These results suggest that age-related slowing of processing speed may be specific for target stimulus analysis and evaluation processes. Thus, old adults seem to improve their performance the longer they take to evaluate the stimulus they encode in visual WM. PMID

  17. Age-related deficits in skeletal muscle recovery following disuse are associated with neuromuscular junction instability and ER stress, not impaired protein synthesis

    PubMed Central

    Baehr, Leslie M.; West, Daniel W.D.; Marcotte, George; Marshall, Andrea G.; De Sousa, Luis Gustavo; Baar, Keith; Bodine, Sue C.

    2016-01-01

    Age-related loss of muscle mass and strength can be accelerated by impaired recovery of muscle mass following a transient atrophic stimulus. The aim of this study was to identify the mechanisms underlying the attenuated recovery of muscle mass and strength in old rats following disuse-induced atrophy. Adult (9 month) and old (29 month) male F344BN rats underwent hindlimb unloading (HU) followed by reloading. HU induced significant atrophy of the hindlimb muscles in both adult (17-38%) and old (8-29%) rats, but only the adult rats exhibited full recovery of muscle mass and strength upon reloading. Upon reloading, total RNA and protein synthesis increased to a similar extent in adult and old muscles. At baseline and upon reloading, however, proteasome-mediated degradation was suppressed leading to an accumulation of ubiquitin-tagged proteins and p62. Further, ER stress, as measured by CHOP expression, was elevated at baseline and upon reloading in old rats. Analysis of mRNA expression revealed increases in HDAC4, Runx1, myogenin, Gadd45a, and the AChRs in old rats, suggesting neuromuscular junction instability/denervation. Collectively, our data suggests that with aging, impaired neuromuscular transmission and deficits in the proteostasis network contribute to defects in muscle fiber remodeling and functional recovery of muscle mass and strength. PMID:26826670

  18. Cognitive Deficits, Changes in Synaptic Function, and Brain Pathology in a Mouse Model of Normal Aging1,2,3

    PubMed Central

    Wu, Tiffany; Hanson, Jesse E.; Alam, Nazia M.; Ngu, Hai; Lauffer, Benjamin E.; Lin, Han H.; Dominguez, Sara L.; Reeder, Jens; Tom, Jennifer; Steiner, Pascal; Foreman, Oded; Prusky, Glen T.

    2015-01-01

    Abstract Age is the main risk factor for sporadic Alzheimer’s disease. Yet, cognitive decline in aged rodents has been less well studied, possibly due to concomitant changes in sensory or locomotor function that can complicate cognitive tests. We tested mice that were 3, 11, and 23 months old in cognitive, sensory, and motor measures, and postmortem measures of gliosis and neural activity (c-Fos). Hippocampal synaptic function was also examined. While age-related impairments were detectable in tests of spatial memory, greater age-dependent effects were observed in tests of associative learning [active avoidance (AA)]. Gross visual function was largely normal, but startle responses to acoustic stimuli decreased with increased age, possibly due to hearing impairments. Therefore, a novel AA variant in which light alone served as the conditioning stimuli was used. Age-related deficits were again observed. Mild changes in vision, as measured by optokinetic responses, were detected in 19- versus 4-month-old mice, but these were not correlated to AA performance. Thus, deficits in hearing or vision are unlikely to account for the observed deficits in cognitive measures. Increased gliosis was observed in the hippocampal formation at older ages. Age-related changes in neural function and plasticity were observed with decreased c-Fos in the dentate gyrus, and decreased synaptic strength and paired-pulse facilitation in CA1 slices. This work, which carefully outlines age-dependent impairments in cognitive and synaptic function, c-Fos activity, and gliosis during normal aging in the mouse, suggests robust translational measures that will facilitate further study of the biology of aging. PMID:26473169

  19. Assessment of basic cognitive abilities in relation to cognitive deficits.

    PubMed

    Detterman, D K; Mayer, J D; Caruso, D R; Legree, P J; Conners, F A; Taylor, R

    1992-11-01

    A modal model of information-processing was used to select a battery of nine tasks of basic cognitive ability (learning, relearning, reaction time, probe recall, Sternberg search, self-paced probe, stimulus discrimination, tachistoscopic full report, tachistoscopic partial report). Parameters from these tasks operationalized the model. After extensive pilot testing of the tasks to establish reliability, we tested 40 subjects (20 with mental retardation and 20 college students) on all tasks and the WAIS-R. The parameters from the tasks were generally reliable (.7 through .9) and had low correlations with IQ (average about .37). Nearly all of the major cognitive parameters differentiated significantly between groups. A subset of the basic cognitive parameters predicted IQ with an estimated multiple correlation in the general population of .72. Prediction of IQ using basic cognitive parameters was better for subjects with mental retardation than for college students. A modified version of the modal model was supported. Results show that individual differences in higher mental processes are highly dependent on basic cognitive abilities and can be predicted from them. These findings have substantial implications for the development of models of information-processing. PMID:1449729

  20. Long-term moderate alcohol consumption does not exacerbate age-related cognitive decline in healthy, community-dwelling older adults

    PubMed Central

    Moussa, Malaak N.; Simpson, Sean L.; Mayhugh, Rhiannon E.; Grata, Michelle E.; Burdette, Jonathan H.; Porrino, Linda J.; Laurienti, Paul J.

    2015-01-01

    Recent census data has found that roughly 40% of adults 65 years and older not only consume alcohol but also drink more of it than previous generations. Older drinkers are more vulnerable than younger counterparts to the psychoactive effects of alcohol due to natural biological changes that occur with aging. This study was specifically designed to measure the effect of long-term moderate alcohol consumption on cognitive health in older adult drinkers. An extensive battery of validated tests commonly used in aging and substance use literature was used to measure performance in specific cognitive domains, including working memory and attention. An age (young, old) * alcohol consumption (light, moderate) factorial study design was used to evaluate the main effects of age and alcohol consumption on cognitive performance. The focus of the study was then limited to light and moderate older drinkers, and whether or not long-term moderate alcohol consumption exacerbated age-related cognitive decline. No evidence was found to support the idea that long-term moderate alcohol consumption in older adults exacerbates age-related cognitive decline. Findings were specific to healthy community dwelling social drinkers in older age and they should not be generalized to individuals with other consumption patterns, like heavy drinkers, binge drinkers or ex-drinkers. PMID:25601835

  1. Cognitive planning deficit in patients with cerebellar atrophy.

    PubMed

    Grafman, J; Litvan, I; Massaquoi, S; Stewart, M; Sirigu, A; Hallett, M

    1992-08-01

    We compared the performance of 12 patients with cerebellar atrophy (CA) and 12 normal controls matched for age and education on the Tower of Hanoi, a nine-problem task that requires cognitive planning. CA patients performed significantly worse than controls on this task despite no difference in planning and between-move pause times. A reanalysis of the data using just the subgroup of patients with pure cerebellar cortical atrophy (CCA) (N = 9) replicated the above results and also showed that CCA patients had significantly increased planning times compared with controls. Neither age, sex, education level, severity of dementia, word fluency, response time, memory, nor visuomotor procedural learning predicted CA or CCA performance. This deficit in cognitive planning suggests a functional link between the cerebellum, basal ganglia, and the frontal lobe concerning specific cognitive processes. However, the exact role of the cerebellum in cognitive planning remains undetermined. PMID:1641142

  2. Gastrodin Attenuates Cognitive Deficits Induced by 3,3'-Iminodipropionitrile.

    PubMed

    Wang, Xiaona; Li, Peng; Liu, Jingsheng; Jin, Xunbo; Li, Lianjun; Zhang, Dong; Sun, Peng

    2016-06-01

    3,3'-Iminodipropionitrile (IDPN), one of the nitrile derivatives, can induce persistent neurotoxicity, and therefore cause dyskinesia and cognitive impairments. Gastrodin, a main bioactive ingredient of Gastrodia elata Blume, is shown to greatly improve cognitive function. The aim of this study was to further determine whether administration of gastrodin can ameliorate IDPN-induced cognitive deficits in the Morris water maze (MWM) and novel object recognition (NOR) task, and to explore the underlying mechanisms. Results showed that exposure to IDPN (100 mg/kg/day, for 8 days) significantly impaired spatial and object recognition memory and that repeated treatment with gastrodin (150 mg/kg/day, for 6 weeks) could effectively alleviate the IDPN-induced cognitive impairments as indicated by increased spatial memory and discrimination ratio in the MWM and NOR tests. Gastrodin treatment also reverted IDPN-induced decreases of γ-aminobutyric acid (GABA) levels and increases of a2 GABAA receptor protein expression in the prefrontal cortex and hippocampus of IDPN-treated rats. These results suggest that gastrodin treatment may provide a novel pharmacological strategy for IDPN-induced cognitive deficits, which was mediated, at least in part, by normalizing the GABAergic system. PMID:26869041

  3. Neurally dissociable cognitive components of reading deficits in subacute stroke.

    PubMed

    Boukrina, Olga; Barrett, A M; Alexander, Edward J; Yao, Bing; Graves, William W

    2015-01-01

    According to cognitive models of reading, words are processed by interacting orthographic (spelling), phonological (sound), and semantic (meaning) information. Despite extensive study of the neural basis of reading in healthy participants, little group data exist on patients with reading deficits from focal brain damage pointing to critical neural systems for reading. Here, we report on one such study. We have performed neuropsychological testing and magnetic resonance imaging on 11 patients with left-hemisphere stroke (<=5 weeks post-stroke). Patients completed tasks assessing cognitive components of reading such as semantics (matching picture or word choices to a target based on meaning), phonology (matching word choices to a target based on rhyming), and orthography (a two-alternative forced choice of the most plausible non-word). They also read aloud pseudowords and words with high or low levels of usage frequency, imageability, and spelling-sound consistency. As predicted by the cognitive model, when averaged across patients, the influence of semantics was most salient for low-frequency, low-consistency words, when phonological decoding is especially difficult. Qualitative subtraction analyses revealed lesion sites specific to phonological processing. These areas were consistent with those shown previously to activate for phonology in healthy participants, including supramarginal, posterior superior temporal, middle temporal, inferior frontal gyri, and underlying white matter. Notable divergence between this analysis and previous functional imaging is the association of lesions in the mid-fusiform gyrus and anterior temporal lobe with phonological reading deficits. This study represents progress toward identifying brain lesion-deficit relationships in the cognitive components of reading. Such correspondences are expected to help not only better understand the neural mechanisms of reading, but may also help tailor reading therapy to individual neurocognitive

  4. Neurally dissociable cognitive components of reading deficits in subacute stroke

    PubMed Central

    Boukrina, Olga; Barrett, A. M.; Alexander, Edward J.; Yao, Bing; Graves, William W.

    2015-01-01

    According to cognitive models of reading, words are processed by interacting orthographic (spelling), phonological (sound), and semantic (meaning) information. Despite extensive study of the neural basis of reading in healthy participants, little group data exist on patients with reading deficits from focal brain damage pointing to critical neural systems for reading. Here, we report on one such study. We have performed neuropsychological testing and magnetic resonance imaging on 11 patients with left-hemisphere stroke (<=5 weeks post-stroke). Patients completed tasks assessing cognitive components of reading such as semantics (matching picture or word choices to a target based on meaning), phonology (matching word choices to a target based on rhyming), and orthography (a two-alternative forced choice of the most plausible non-word). They also read aloud pseudowords and words with high or low levels of usage frequency, imageability, and spelling-sound consistency. As predicted by the cognitive model, when averaged across patients, the influence of semantics was most salient for low-frequency, low-consistency words, when phonological decoding is especially difficult. Qualitative subtraction analyses revealed lesion sites specific to phonological processing. These areas were consistent with those shown previously to activate for phonology in healthy participants, including supramarginal, posterior superior temporal, middle temporal, inferior frontal gyri, and underlying white matter. Notable divergence between this analysis and previous functional imaging is the association of lesions in the mid-fusiform gyrus and anterior temporal lobe with phonological reading deficits. This study represents progress toward identifying brain lesion-deficit relationships in the cognitive components of reading. Such correspondences are expected to help not only better understand the neural mechanisms of reading, but may also help tailor reading therapy to individual neurocognitive

  5. Relations of symptoms to cognitive deficits in schizophrenia.

    PubMed

    Strauss, M E

    1993-01-01

    Schizophrenia is characterized by a variety of cognitive dysfunctions. Information-processing dysfunctions differ between clinical subtypes such that nonparanoid schizophrenia patients attend less than paranoid schizophrenia patients to connotative or contextual aspects of stimuli. The positive and negative symptom dimensions are also associated with distinct cognitive deficits. In general, positive symptoms are related to auditory-processing deficits and negative symptoms to visual/motor dysfunctions. The interaction of frontal and septohippocampal brain systems, and failures of information-processing automaticity and self-monitoring, have been proposed as the bases of positive symptoms. Negative symptoms are thought to arise from abnormalities in the complex interactions of frontal and striatal systems. Recent theoretical analyses have recommended a focus on the cognitive and neuropsychological analysis of specific symptoms (e.g., hallucinations and delusions) instead of on the more heterogeneous symptom clusters or dimensions. Studies of specific symptoms indicate that patients with hallucinations have deficits in discriminating the source of information. Delusions have been related to abnormal inference processes as well as abnormal perceptual experiences. Studies should now examine the links between information-processing abnormalities and symptoms over time, as the latter change, within the framework of explicit, disconfirmable theoretical models. PMID:8322033

  6. Age-Related Cognitive Impairments in Mice with a Conditional Ablation of the Neural Cell Adhesion Molecule

    ERIC Educational Resources Information Center

    Bisaz, Reto; Boadas-Vaello, Pere; Genoux, David; Sandi, Carmen

    2013-01-01

    Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However,…

  7. Cognitive deficits in bipolar disorder: from acute episode to remission.

    PubMed

    Volkert, J; Schiele, M A; Kazmaier, Julia; Glaser, Friederike; Zierhut, K C; Kopf, J; Kittel-Schneider, S; Reif, A

    2016-04-01

    Considerable evidence demonstrates that neuropsychological deficits are prevalent in bipolar disorder during both acute episodes and euthymia. However, it is less clear whether these cognitive disturbances are state- or trait-related. We here present the first longitudinal study employing a within-subject pre- and post-testing examining acutely admitted bipolar patients (BP) in depression or mania and during euthymia, aiming to identify cognitive performance from acute illness to remission. Cognitive performance was measured during acute episodes and repeated after at least 3 months of remission. To do so, 55 BP (35 depressed, 20 hypo-/manic) and 55 healthy controls (HC) were tested with a neuropsychological test battery (attention, working memory, verbal memory, executive functioning). The results showed global impairments in acutely ill BP compared to HC: depressed patients showed a characteristic psychomotor slowing, while manic patients had severe deficits in executive functioning. Twenty-nine remitted BP could be measured in the follow-up (dropout rate 48 %), whose cognitive functions partially recovered, whereas working memory and verbal memory were still impaired. However, we found that subthreshold depressive symptoms and persisting sleep disturbances in euthymic BP were associated with reduced speed, deficits in attention and verbal memory, while working memory was correlated with psychotic symptoms (lifetime). This result indicates working memory as trait related for a subgroup of BP with psychotic symptoms. In contrast, attention and verbal memory are negatively influenced by state factors like residual symptoms, which should be more considered as possible confounders in the search of cognitive endophenotypes in remitted BP. PMID:26611783

  8. Donepezil Improved Cognitive Deficits in a Patient With Neurosyphilis.

    PubMed

    Wu, Yi-Shan; Lane, Hsien-Yuan; Lin, Chieh-Hsin

    2015-01-01

    A large number of patients with neurosyphilis present dementia with a progressive course and psychiatric symptoms such as depression, mania, and psychosis. Despite prompt and proper antibiotic treatment, the recovery is often incomplete, especially when tissue damage has occurred. We reported a patient with persisted cognitive decline associated with neurosyphilis that improved substantially after donepezil therapy. A 43-year-old man manifested significant psychiatric symptoms such as mania, psychosis, and cognitive impairment due to neurosyphilis. Subsequently, the patient was treated with antipsychotics and donepezil concurrent with an adequate antibiotic treatment for neurosyphilis. During the 1-year follow-up, his rapid plasma reagin titer approached from 1:256 to 1:64. His Mini-Mental State Examination (MMSE) and Alzheimer's Disease Assessment Scale-cognitive subscale scores improved from 12 to 25 and 42.3 to 6.3, respectively, after a 6-month donepezil treatment. Donepezil was discontinued. Three months later, worsening of cognitive impairment (MMSE score, 23) was noted. After donepezil was started again for 3 months, his MMSE score improved to 26. Persistent cognitive impairment is commonly associated with neurosyphilis despite adequate penicillin treatment. Treatment of the cognitive impairment is important but difficult. Cholinergic pathways are considered as involving in the cognitive deficit induced by neurosyphilis and donepezil, a cholinesterase inhibitor, which may be useful for the improvement of cognition. In this case report, we described for the first time the successful use of donepezil in treating cognitive impairment associated with neurosyphilis. The role of cholinesterase inhibitors in the treatment of cognitive impairments caused by neurosyphilis needs further studies. PMID:26166240

  9. Age-related decline in verbal learning is moderated by demographic factors, working memory capacity, and presence of amnestic mild cognitive impairment.

    PubMed

    Constantinidou, Fofi; Zaganas, Ioannis; Papastefanakis, Emmanouil; Kasselimis, Dimitrios; Nidos, Andreas; Simos, Panagiotis G

    2014-09-01

    Age-related memory changes are highly varied and heterogeneous. The study examined the rate of decline in verbal episodic memory as a function of education level, auditory attention span and verbal working memory capacity, and diagnosis of amnestic mild cognitive impairment (a-MCI). Data were available on a community sample of 653 adults aged 17-86 years and 70 patients with a-MCI recruited from eight broad geographic areas in Greece and Cyprus. Measures of auditory attention span and working memory capacity (digits forward and backward) and verbal episodic memory (Auditory Verbal Learning Test [AVLT]) were used. Moderated mediation regressions on data from the community sample did not reveal significant effects of education level on the rate of age-related decline in AVLT indices. The presence of a-MCI was a significant moderator of the direct effect of Age on both immediate and delayed episodic memory indices. The rate of age-related decline in verbal episodic memory is normally mediated by working memory capacity. Moreover, in persons who display poor episodic memory capacity (a-MCI group), age-related memory decline is expected to advance more rapidly for those who also display relatively poor verbal working memory capacity. PMID:25156204

  10. Diet-induced obesity attenuates endotoxin-induced cognitive deficits

    PubMed Central

    Setti, Sharay E.; Littlefield, Alyssa M.; Johnson, Samantha W.; Kohman, Rachel A.

    2015-01-01

    Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system (CNS). Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. PMID:25542778

  11. Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study.

    PubMed

    Shaw, Marnie E; Sachdev, Perminder S; Anstey, Kaarin J; Cherbuin, Nicolas

    2016-03-01

    Although it is recognized that the human cortex thins with age, longitudinal estimates of thinning patterns specific to healthy young-old age (<75 years) individuals are lacking. Importantly, many neurodegenerative disorders first manifest between midlife and old age, and normative estimates may provide a reference for differential change associated with such disorders. Here, we provide longitudinal estimates of cortical thinning observed over 12 years in a large group (n = 396) of healthy individuals, aged 60-66 years at baseline scan, who were scanned with magnetic resonance imaging (1.5T) on 4 occasions. Longitudinal age-related thinning was observed across most of the cortices, with a mean change of -0.3% per year. We measured significant thinning in heteromodal association cortex, with less thinning in regions expected to atrophy later in life (e.g., primary sensory cortex). Men showed more extensive thinning than women. Our comparison of cross-sectional and longitudinal estimates adds to growing evidence that cross-sectional designs may underestimate age-related changes in cortical thickness. PMID:26923417

  12. Cognitive Deficits as a Mediator of Poor Occupational Function in Remitted Major Depressive Disorder Patients

    PubMed Central

    Woo, Young Sup; Rosenblat, Joshua D.; Kakar, Ron; Bahk, Won-Myong; McIntyre, Roger S.

    2016-01-01

    Cognitive deficits in major depressive disorder (MDD) patients have been described in numerous studies. However, few reports have aimed to describe cognitive deficits in the remitted state of MDD and the mediational effect of cognitive deficits on occupational outcome. The aim of the current review is to synthesize the literature on the mediating and moderating effects of specific domains of cognition on occupational impairment among people with remitted MDD. In addition, predictors of cognitive deficits found to be vocationally important will be examined. Upon examination of the extant literature, attention, executive function and verbal memory are areas of consistent impairment in remitted MDD patients. Cognitive domains shown to have considerable impact on vocational functioning include deficits in memory, attention, learning and executive function. Factors that adversely affect cognitive function related to occupational accommodation include higher age, late age at onset, residual depressive symptoms, history of melancholic/psychotic depression, and physical/psychiatric comorbidity, whereas higher levels of education showed a protective effect against cognitive deficit. Cognitive deficits are a principal mediator of occupational impairment in remitted MDD patients. Therapeutic interventions specifically targeting cognitive deficits in MDD are needed, even in the remitted state, to improve functional recovery, especially in patients who have a higher risk of cognitive deficit. PMID:26792035

  13. Age-related Changes in Respiratory Function and Daily Living. A Tentative Model Including Psychosocial Variables, Respiratory Diseases and Cognition.

    PubMed

    Facal, David; González-Barcala, Francisco-Javier

    2016-01-01

    Changes in respiratory function are common in older populations and affect quality of life, social relationships, cognitive function and functional capacity. This paper reviews evidence reported in medical and psychological journals between 2000 and 2014 concerning the impact of changes in respiratory function on daily living in older adults. A tentative model establishes relationships involving respiratory function, cognitive function and functional capacities. The conclusion stresses the need for both longitudinal studies, to establish causal pathways between respiratory function and psychosocial aspects in aging, and intervention studies. PMID:26593253

  14. Neurocomputational models of motor and cognitive deficits in Parkinson's disease.

    PubMed

    Wiecki, Thomas V; Frank, Michael J

    2010-01-01

    We review the contributions of biologically constrained computational models to our understanding of motor and cognitive deficits in Parkinson's disease (PD). The loss of dopaminergic neurons innervating the striatum in PD, and the well-established role of dopamine (DA) in reinforcement learning (RL), enable neural network models of the basal ganglia (BG) to derive concrete and testable predictions. We focus in this review on one simple underlying principle - the notion that reduced DA increases activity and causes long-term potentiation in the indirect pathway of the BG. We show how this theory can provide a unified account of diverse and seemingly unrelated phenomena in PD including progressive motor degeneration as well as cognitive deficits in RL, decision making and working memory. DA replacement therapy and deep brain stimulation can alleviate some aspects of these impairments, but can actually introduce negative effects such as motor dyskinesias and cognitive impulsivity. We discuss these treatment effects in terms of modulation of specific mechanisms within the computational framework. In addition, we review neurocomputational interpretations of increased impulsivity in the face of response conflict in patients with deep-brain-stimulation. PMID:20696325

  15. Cognitive Deficits in Geriatric Depression: Clinical Correlates and Implications for Current and Future Treatment

    PubMed Central

    Morimoto, Sarah Shizuko; Alexopoulos, George S.

    2013-01-01

    Synopsis The purpose of this article is to identify the cognitive deficits commonly associated with geriatric depression, and describe their clinical significance. We then summarize the complex relationship between geriatric depression and dementia and discuss possible shared mechanisms. Last, we present evidence regarding whether the cognitive deficits in depression may be mitigated with medication or with computerized cognitive remediation. PMID:24229654

  16. Cognitive Neuroscience of Attention Deficit Hyperactivity Disorder: Current Status and Working Hypotheses

    ERIC Educational Resources Information Center

    Vaidya, Chandan J.; Stollstorff, Melanie

    2008-01-01

    Cognitive neuroscience studies of Attention Deficit Hyperactivity Disorder (ADHD) suggest multiple loci of pathology with respect to both cognitive domains and neural circuitry. Cognitive deficits extend beyond executive functioning to include spatial, temporal, and lower-level "nonexecutive" functions. Atypical functional anatomy extends beyond…

  17. Age-related cognitive decline and electroencephalogram slowing in Down's syndrome as a model of Alzheimer's disease.

    PubMed

    Soininen, H; Partanen, J; Jousmäki, V; Helkala, E L; Vanhanen, M; Majuri, S; Kaski, M; Hartikainen, P; Riekkinen, P

    1993-03-01

    We studied quantitative electroencephalogram and neuropsychological performance in an aging series of 31 patients with Down's syndrome and compared the findings with those of 36 patients with probable Alzheimer's disease and age-matched controls. We found an age-related decline of cortical functions and slowing of the electroencephalogram in Down's syndrome patients aged from 20 to 60 years. Slowing of the electroencephalogram, i.e. the decrease of the peak frequency, was significantly related to Mini-Mental status scores, and visual, praxic and speech functions, as well as memory in the Down patients, similar to the Alzheimer patients. Similar correlations were not demonstrated for young or elderly controls. This study provides neuropsychological and electrophysiological data to suggest that studying Down's syndrome patients of different ages can serve as a model for progression of Alzheimer's disease. PMID:8469312

  18. Age-Related Cognitive Impairment as a Sign of Geriatric Neurocardiovascular Interactions: May Polyphenols Play a Protective Role?

    PubMed Central

    Jagla, Fedor; Pechanova, Olga

    2015-01-01

    It is known that endothelial dysfunction plays an important role in the development and progression of cardiovascular diseases implicated also in cognitive decline. Experimental studies pointed to the fact that the modification of NO levels via NOS activity may affect the blood pressure level as well as several higher nervous functions—for example, learning and memory. There are emerging evidences from in vitro and animal studies suggesting that polyphenols may potentially have a protective effect on the development of neurodegenerative diseases and may improve cognitive function as well as positively affecting the blood pressure regulatory mechanisms. This review accentuates the need for precisely defined clinically controlled studies as well as for use of adequate experimental procedures discriminating between the human higher brain functions and the only overall activation of the brain cortex. The physiological neurocardiovascular interactions are implicated in the increased healthy life span as well. PMID:26180593

  19. Operationalizing diagnostic criteria for Alzheimer’s disease and other age-related cognitive impairment—Part 2*

    PubMed Central

    Seshadri, Sudha; Beiser, Alexa; Au, Rhoda; Wolf, Philip A.; Evans, Denis A.; Wilson, Robert S.; Petersen, Ronald C.; Knopman, David S.; Rocca, Walter A.; Kawas, Claudia H.; Corrada, Maria M.; Plassman, Brenda L.; Langa, Kenneth M.; Chui, Helena C.

    2011-01-01

    This article focuses on the effects of operational differences in case ascertainment on estimates of prevalence and incidence of cognitive impairment/dementia of the Alzheimer type. Experience and insights are discussed by investigators from the Framingham Heart Study, the East Boston Senior Health Project, the Chicago Health and Aging Project, the Mayo Clinic Study of Aging, the Baltimore Longitudinal Study of Aging, and the Aging, Demographics, and Memory Study. There is a general consensus that the single most important factor regulating prevalence estimates of Alzheimer’s disease (AD) is the severity of cognitive impairment used for case ascertainment. Studies that require a level of cognitive impairment in which persons are unable to provide self-care will have much lower estimates than studies aimed at identifying persons in the earliest stages of AD. There is limited autopsy data from the above-mentioned epidemiologic studies to address accuracy in the diagnosis of etiologic subtype, namely the specification of AD alone or in combination with other types of pathology. However, other community-based cohort studies show that many persons with mild cognitive impairment (MCI) meet pathologic criteria for AD, and a large minority of persons without dementia or MCI also meets pathologic criteria for AD, thereby suggesting that the number of persons who would benefit from an effective secondary prevention intervention is probably higher than the highest published prevalence estimates. Improved accuracy in the clinical diagnosis of AD is anticipated with the addition of molecular and structural biomarkers in the next generation of epidemiologic studies. PMID:21255742

  20. The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease.

    PubMed

    Butterfield, D Allan; Poon, H Fai

    2005-10-01

    The senescence-accelerated mouse (SAM) is an accelerated aging model that was established through phenotypic selection from a common genetic pool of AKR/J strain of mice. The SAM model was established in 1981, including nine major senescence-accelerated mouse prone (SAMP) substrains and three major senescence-accelerated mouse resistant (SAMR) substrains, each of which exhibits characteristic disorders. Recently, SAMP8 have drawn attention in gerontological research due to its characteristic learning and memory deficits at old age. Many recent reports provide insight into mechanisms of the cognitive impairment and pathological changes in SAMP8. Therefore, this mini review examines the recent findings of SAMP8 mice abnormalities at the gene and protein levels. The genes and proteins described in this review are functionally categorized into neuroprotection, signal transduction, protein folding/degradation, cytoskeleton/transport, immune response and reactive oxygen species (ROS) production. All of these processes are involved in learning and memory. Although these studies provide insight into the mechanisms that contribute to the learning and memory decline in aged SAMP8 mice, higher throughput techniques of proteomics and genomics are necessary to study the alterations of gene expression and protein abnormalities in SAMP8 mice brain in order to more completely understand the central nervous system dysfunction in this mouse model. The SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits at the gene and protein levels. PMID:16026957

  1. Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice.

    PubMed

    Chen, Shuang-qing; Cai, Qing; Shen, Yu-ying; Wang, Pei-jun; Teng, Gao-jun; Zhang, Wei; Zang, Feng-chao

    2012-11-01

    Proton magnetic resonance spectroscopy ((1)H-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether (1)H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. (1)H-MRS was performed in 20 tg mice and 15 wild-type mice at 3, 5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The (1)H-MRS revealed that mI levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p<0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that (1)H-MRS is a more sensitive biomarker for assessing early AD. PMID:22828014

  2. Age-related differences in neural recruitment during the use of cognitive reappraisal and selective attention as emotion regulation strategies

    PubMed Central

    Allard, Eric S.; Kensinger, Elizabeth A.

    2014-01-01

    The present study examined age differences in the timing and neural recruitment within lateral and medial PFC while younger and older adults hedonically regulated their responses to unpleasant film clips. When analyses focused on activity during the emotional peak of the film clip (the most emotionally salient portion of the film), several age differences emerged. When comparing regulation to passive viewing (combined effects of selective attention and reappraisal) younger adults showed greater regulation related activity in lateral PFC (DLPFC, VLPFC, OFC) and medial PFC (ACC) while older adults showed greater activation within a region DLPFC. When assessing distinct effects of the regulation conditions, an ANOVA revealed a significant Age × Regulation Condition interaction within bilateral DLPFC and ACC; older adults but not young adults showed greater recruitment within these regions for reappraisal than selective attention. When examining activity at the onset of the film clip and at its emotional peak, the timing of reappraisal-related activity within VLPFC differed between age groups: younger adults showed greater activity at film onset while older adults showed heightened activity during the peak. Our results suggest that older adults rely more heavily on PFC recruitment when engaging cognitively demanding reappraisal strategies while PFC-mediated regulation might not be as task-specific for younger adults. Older adults' greater reliance on cognitive control processing during emotion regulation may also be reflected in the time needed to implement these strategies. PMID:24782800

  3. Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: a 3-year follow-up of the LADIS study cohort.

    PubMed

    Ryberg, C; Rostrup, E; Paulson, O B; Barkhof, F; Scheltens, P; van Straaten, E C W; van der Flier, W M; Fazekas, F; Schmidt, R; Ferro, J M; Baezner, H; Erkinjuntti, T; Jokinen, H; Wahlund, L-O; Poggesi, A; Pantoni, L; Inzitari, D; Waldemar, G

    2011-08-15

    The aim of this 3-year follow-up study was to investigate whether corpus callosum (CC) atrophy may predict future motor and cognitive impairment in an elderly population. On baseline MRI from 563 subjects with age-related white matter changes (ARWMC) from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented and subdivided into five anterior-posterior regions (CC1-CC5). Associations between the CC areas and decline in motor performance and cognitive functions over a 3-year period were analyzed. CC atrophy at baseline was significantly associated with impaired cognitive performance (p<0.01 for CC1, p<0.05 for CC5), motor function (p<0.05 for CC2 and CC5), and walking speed (p<0.01 for CC2 and CC5, p<0.05 for CC3 and total CC), and with development of dementia at 3 years (p<0.05 for CC1) after correction for appropriate confounders (ARWMC volume, atrophy, age, gender and handedness). In conclusion, CC atrophy, an indicator of reduced functional connectivity between cortical areas, seems to contribute, independently of ARWMC load, to future cognitive and motor decline in the elderly. PMID:21621224

  4. Characterization of cognitive deficits in a transgenic mouse model of Alzheimer's disease and effects of donepezil and memantine.

    PubMed

    Nagakura, Akira; Shitaka, Yoshitsugu; Yarimizu, Junko; Matsuoka, Nobuya

    2013-03-01

    Alzheimer's disease is characterized by a progressive decline in cognitive function and involves β-amyloid (Aβ) in its pathogenesis. To characterize cognitive deficits associated with Aβ accumulation, we analyzed PS1/APP mice overexpressing mutant presenilin-1 (PS1, M146L; line 6.2) and amyloid precursor protein (APP, K670N/M671L; line Tg2576), a mouse model of Alzheimer's disease with accelerated Aβ production. Age-dependent changes in working and spatial memory behaviors were investigated using Y-maze and Morris water maze tasks, respectively, in female PS1/APP mice at ages of 2, 4, 6, and 12 months. Significant deficits in working and spatial memory were observed from 4 and 6 months of age, respectively. Acute single-dose administrations of memantine, a low-to-moderate-affinity N-methyl-d-aspartate (NMDA) antagonist, showed improvements in working memory deficits at 4 months of age, whereas donepezil, an acetylcholinesterase (AChE) inhibitor, did not. However, both drugs improved spatial memory dysfunction at 6 months of age at therapeutically relevant doses. No age-related dramatic changes were observed in expression levels of several proteins relating to memory dysfunction and also the mechanisms of donepezil and memantine in the cerebral cortex of PS1/APP mice until 6 months of age. Taken together, these results suggest dysfunctions in cholinergic and/or glutamatergic transmissions may be involved in the cognitive deficits associated with Aβ toxicity. Since donepezil and memantine have been widely used for treating patients of Alzheimer's disease, these results also suggest that cognitive deficits in PS1/APP mice assessed in the Y-maze and Morris water maze tasks are a useful animal model for evaluating novel Alzheimer's disease therapeutics. PMID:23276665

  5. Puerarin ameliorates cognitive deficits in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Xianchu; Mo, Yanzhi; Gong, Jingbo; Li, Zhuang; Peng, Huan; Chen, Jiaxue; Wang, Qichao; Ke, Zhaowen; Xie, Jingtao

    2016-04-01

    Previous research has indicated that Diabetes is a high risk of learning and memory deficits. Puerarin, an isoflavonoid extracted from Kudzu roots, has been reported to possess antioxidant, anti-inflammatory, anti-apoptotic and anti-diabetic properties which are useful in the treatment of various diseases. Recently, Puerarin was found to have the effects on learning and memory performances in humans and animal models. However, up to now, there is no detailed evidence on the effect of Puerarin on diabetes-associated cognitive decline (DACD). In this study, we designed to assess the effects of Puerarin on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model and exploring its potential mechanism. Diabetic rats were treated with Puerarin (100 mg/kg per d) for 7 days. The learning and memory function was evaluated by morris water maze test. The acetylcholinesterase (AChE), choline acetylase (ChAT), oxidative indicators [malondialdehyde (MDA) and superoxide dismutase (SOD)] and inflammatory cytokine (TNF-a, IL-1β and IL-6) were measured in hippocampus by using corresponding commercial kits. mRNA and Protein levels of Bcl-2 were analyzed by RT-PCR and Westernblot. The results showed that supplementation of Puerarin improved the learning and memory performances compared with the STZ group by the morris water maze test. In addition, Puerarin supplement significantly prevented AChE and MDA activities, increased ChAT and SOD activities, and alleviated the protein level of TNF-α, IL-1β and IL-6 in the hippocampus compared with the STZ group. Moreover, the pretreatment with Puerarin also significantly increased the Bcl-2 expression. It is concluded that Puerarin possesses neuroprotection to ameliorate cognitive deficits in streptozotocin-induced diabetic rats by anti-inflammatory, antioxidant and antiapototic effects. PMID:26686502

  6. Motor Control and Aging: Links to Age-Related Brain Structural, Functional, and Biochemical Effects

    PubMed Central

    Seidler, Rachael D.; Bernard, Jessica A.; Burutolu, Taritonye B.; Fling, Brett W.; Gordon, Mark T.; Gwin, Joseph T.; Kwak, Youngbin; Lipps, David B.

    2009-01-01

    Although connections between cognitive deficits and age-associated brain differences have been elucidated, relationships with motor performance are less well understood. Here, we broadly review age-related brain differences and motor deficits in older adults in addition to cognition-action theories. Age-related atrophy of the motor cortical regions and corpus callosum may precipitate or coincide with motor declines such as balance and gait deficits, coordination deficits, and movement slowing. Correspondingly, degeneration of neurotransmitter systems—primarily the dopaminergic system—may contribute to age-related gross and fine motor declines, as well as to higher cognitive deficits. In general, older adults exhibit involvement of more widespread brain regions for motor control than young adults, particularly the prefrontal cortex and basal ganglia networks. Unfortunately these same regions are the most vulnerable to age-related effects, resulting in an imbalance of “supply and demand”. Existing exercise, pharmaceutical, and motor training interventions may ameliorate motor deficits in older adults. PMID:19850077

  7. Naringin ameliorates cognitive deficits in streptozotocin-induced diabetic rats

    PubMed Central

    Liu, Xianchu; Liu, Ming; Mo, Yanzhi; Peng, Huan; Gong, Jingbo; Li, Zhuang; Chen, Jiaxue; Xie, Jingtao

    2016-01-01

    Objective(s): Previous research demonstrated that diabetes is one of the leading causes of learning and memory deficits. Naringin, a bioflavonoid isolated from grapefruits and oranges, has potent protective effects on streptozotocin (STZ)-induced diabetic rats. Recently, the effects of naringin on learning and memory performances were monitored in many animal models of cognitive impairment. However, to date, no studies have investigated the ameliorative effects of naringin on diabetes-associated cognitive decline (DACD). In this study, we investigated the effects of naringin, using a STZ-injected rat model and explored its potential mechanism. Materials and Methods: Diabetic rats were treated with naringin (100 mg/kg/d) for 7 days. The learning and memory function were assessed by Morris water maze test. The oxidative stress indicators [superoxide dismutase (SOD) and malondialdehyde (MDA)] and inflammatory cytokines (TNF-a, IL-1β, and IL-6) were measured in hippocampus using corresponding commercial kits. The mRNA and protein levels of PPARγ were evaluated by real time (RT)-PCR and Western blot analysis. Results: The results showed that supplementation of naringin improved learning and memory performances compared with the STZ group. Moreover, naringin supplement dramatically increased SOD levels, reduced MDA levels, and alleviated TNF-α, IL-1β, and IL-6 compared with the STZ group in the hippocampus. The pretreatment with naringin also significantly increased PPARγ expression. Conclusion: Our results showed that naringin may be a promising therapeutic agent for improving cognitive decline in DACD. PMID:27279986

  8. Attention and Other Cognitive Deficits in Aphasia: Presence and Relation to Language and Communication Measures

    ERIC Educational Resources Information Center

    Murray, Laura L.

    2012-01-01

    Purpose: This study was designed to further elucidate the relationship between cognition and aphasia, with a focus on attention. It was hypothesized that individuals with aphasia would display variable deficit patterns on tests of attention and other cognitive functions and that their attention deficits, particularly those of complex attention…

  9. Offenders with Cognitive Deficits in a Canadian Prison Population: Prevalence, Profile, and Outcomes.

    PubMed

    Stewart, Lynn A; Wilton, Geoff; Sapers, Jeremy

    2016-01-01

    Impaired cognitive function has been associated with criminal behavior. In Canada it is unknown the extent to which this disorder affects federal inmates or its impact on key correctional outcomes. In this study, 488 incoming male offenders were assessed on the Cognistat, a neuropsychological screening tool. Twenty-five percent of offenders were found to have some level of cognitive deficit. Lower levels of educational achievement, unstable employment history, learning disability, serious alcohol problems, and symptoms of Attention Deficit Hyperactivity Disorder (ADHD) were significantly associated with the presence of cognitive deficits in this sample. Although there was a significant trend for offenders with cognitive deficits to have more admissions to segregation, level of cognitive deficit was not consistently related to rates of institutional charges or rates of completion of required correctional programs. On release, cognitive deficits were not related to returns to custody or returns to custody with an offence. These results indicate that while offenders with cognitive deficits may require assistance with educational upgrading and employment to improve their reintegration potential, they do not pose a particular management problem in the community after release relative to offenders without cognitive deficits. PMID:26341309

  10. Models of cognitive deficit and statistical hypotheses: multiple sclerosis, an example.

    PubMed

    Ryan, L; Clark, C M; Klonoff, H; Paty, D

    1993-07-01

    The purpose of the current study was to describe four models of cognitive deficit and to outline the statistical hypotheses underlying each model. The four models of cognitive deficit were (a) specific deficit; (b) subgroup deficit; (c) a syndrome dissociation model; and (d) a global function dissociation model. Neuropsychological data are analyzed to examine each of these four models in a sample of mild Multiple Sclerosis (MS) patients. The results suggest that for these subjects and tests, the specific deficit model best fits the data. The results are reviewed initially in the context of MS. There follows a consideration of statistical caveats and finally, general applications of the proposed procedures. PMID:8354709

  11. Self-Instructional Cognitive Training to Reduce Impulsive Cognitive Style in Children with Attention Deficit with Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Rivera-Flores, Gladys Wilma

    2015-01-01

    Introduction: Children with attention deficit with hyperactivity disorder (ADHD) have an impulsive, rigid and field-dependent cognitive style. This study examines whether self-instructional cognitive training reduces impulsive cognitive style in children diagnosed with this disorder. Method: The subjects were 10 children between the ages of 6 and…

  12. Impaired retention is responsible for temporal order memory deficits in mild cognitive impairment.

    PubMed

    Gillis, M Meredith; Quinn, Kristen M; Phillips, Pamela A T; Hampstead, Benjamin M

    2013-05-01

    Temporal order memory, or remembering the order of events, is critical for everyday functioning and is difficult for patients with mild cognitive impairment (MCI). It is currently unclear whether these patients have difficulty acquiring and/or retaining such information and whether deficits in these patients are in excess of "normal" age-related declines. Therefore, the current study examined age and disease-related changes in temporal order memory as well as whether memory load played a role in such changes. Young controls (n=25), older controls (n=34), and MCI patients (n=32) completed an experimental task that required the reconstruction of sequences that were 3, 4, or 5 items in length both immediately after presentation (i.e., immediate recall) and again after a 10-min delay (i.e., delayed recall). During the immediate recall phase, there was an effect of age largely due to reduced performance at the two longest span lengths. Older controls and MCI patients only differed during the five span (controls>MCI). During the delayed recall, however, there were significant effects of both age and MCI regardless of span length. In MCI patients, immediate recall was significantly correlated with measures of executive functioning, whereas delayed recall performance was only related to other memory tests. These findings suggest that MCI patients experience initial temporal order memory deficits at the point when information begins to exceed working memory capacity and become dependent on medial temporal lobe functioning. Longer-term deficits are due to an inability to retain information, consistent with the characteristic medial temporal lobe dysfunction in MCI. PMID:23542809

  13. Behavioral Response Inhibition in Psychotic Disorders: Diagnostic Specificity, Familiality and Relation to Generalized Cognitive Deficit

    PubMed Central

    Ethridge, Lauren E.; Soilleux, Melanie; Nakonezny, Paul A.; Reilly, James L.; Hill, S. Kristian; Keefe, Richard S. E.; Gershon, Elliot S.; Pearlson, Godfrey D.; Tamminga, Carol A.; Keshavan, Matcheri S.; Sweeney, John A.

    2014-01-01

    Difficulty inhibiting context-inappropriate behavior is a common deficit in psychotic disorders. The diagnostic specificity of this impairment, its familiality, and its degree of independence from the generalized cognitive deficit associated with psychotic disorders remain to be clarified. Schizophrenia, schizoaffective and bipolar patients with history of psychosis (n=523), their available first-degree biological relatives (n=656), and healthy participants (n=223) from the multi-site B-SNIP study completed a manual Stop Signal task. A nonlinear mixed model was used to fit logistic curves to success rates on Stop trials as a function of parametrically varied Stop Signal Delay. While schizophrenia patients had greater generalized cognitive deficit than bipolar patients, their deficits were similar on the Stop Signal task. Further, only bipolar patients showed impaired inhibitory control relative to healthy individuals after controlling for generalized cognitive deficit. Deficits accounted for by the generalized deficit were seen in relatives of schizophrenia and schizoaffective patients, but not in relatives of bipolar patients. In clinically stable patients with psychotic bipolar disorder, impaired inhibitory behavioral control was a specific cognitive impairment, distinct from the generalized neuropsychological impairment associated with psychotic disorders. Thus, in bipolar disorder with psychosis, a deficit in inhibitory control may contribute to risk for impulsive behavior. Because the deficit was not familial in bipolar families and showed a lack of independence from the generalized cognitive deficit in schizophrenia spectrum disorders, it appears to be a trait related to illness processes rather than one tracking familial risk factors. PMID:25261042

  14. Cerebrolysin Ameloriates Cognitive Deficits in Type III Diabetic Rats.

    PubMed

    Georgy, Gehan S; Nassar, Noha N; Mansour, Hanaa A; Abdallah, Dalaal M

    2013-01-01

    Cerebrolysin (CBL), a mixture of several active peptide fragments and neurotrophic factors including brain-derived neurotrophic factor (BDNF), is currently used in the management of cognitive alterations in patients with dementia. Since Cognitive decline as well as increased dementia are strongly associated with diabetes and previous studies addressed the protective effect of BDNF in metabolic syndrome and type 2 diabetes; hence this work aimed to evaluate the potential neuroprotective effect of CBL in modulating the complications of hyperglycaemia experimentally induced by streptozotocin (STZ) on the rat brain hippocampus. To this end, male adult Sprague Dawley rats were divided into (i) vehicle- (ii) CBL- and (iii) STZ diabetic-control as well as (iv) STZ+CBL groups. Diabetes was confirmed by hyperglycemia and elevated glycated haemoglobin (HbA1c%), which were associated by weight loss, elevated tumor necrosis factor (TNF)-α and decreased insulin growth factor (IGF)-1β in the serum. Uncontrolled hyperglycemia caused learning and memory impairments that corroborated degenerative changes, neuronal loss and expression of caspase (Casp)-3 in the hippocampal area of STZ-diabetic rats. Behavioral deficits were associated by decreased hippocampal glutamate (GLU), glycine, serotonin (5-HT) and dopamine. Moreover, diabetic rats showed an increase in hippocampal nitric oxide and thiobarbituric acid reactive substances versus decreased non-protein sulfhydryls. Though CBL did not affect STZ-induced hyperglycemia, it partly improved body weight as well as HbA1c%. Such effects were associated by enhancement in both learning and memory as well as apparent normal cellularity in CA1and CA3 areas and reduced Casp-3 expression. CBL improved serum TNF-α and IGF-1β, GLU and 5-HT as well as hampering oxidative biomarkers. In conclusion, CBL possesses neuroprotection against diabetes-associated cerebral neurodegeneration and cognitive decline via anti-inflammatory, antioxidant and

  15. Age-Related Changes in Creative Thinking

    ERIC Educational Resources Information Center

    Roskos-Ewoldsen, Beverly; Black, Sheila R.; Mccown, Steven M.

    2008-01-01

    Age-related differences in cognitive processes were used to understand age-related declines in creativity. According to the Geneplore model (Finke, Ward, & Smith, 1992), there are two phases of creativity--generating an idea and exploring the implications of the idea--each with different underlying cognitive processes. These two phases are…

  16. Blind rats are not profoundly impaired in the reference memory Morris water maze and cannot be clearly discriminated from rats with cognitive deficits in the cued platform task.

    PubMed

    Lindner, M D; Plone, M A; Schallert, T; Emerich, D F

    1997-06-01

    The Morris water maze is commonly used to test cognitive function in rodent models of neurological disorders including age-related cognitive deficits. It is often assumed that the most profoundly impaired aged rats may be blind due to retinal degeneration, and it has been reported that animals with visual sensory deficits can be identified based on their performance in a cued platform task. The results of the present study demonstrate that blind rats can perform surprisingly well in the reference memory version of the Morris water maze, and that blind rats cannot be selectively excluded based on performance in the cued platform task since atropine-treated rats also perform poorly in the cued platform task. Future studies may be able to develop screening procedures that help to eliminate subjects with non-cognitive deficits, but the present results do not support the use of the cued platform or straight swim task as screening procedures. Experimenters must be careful to consider the role that visual sensory function and other non-cognitive factors may have in performance of the spatial learning Morris water maze, and also the role that severe cognitive deficits may have in performance of the cued platform task. PMID:9197520

  17. Effect of exercise-induced neurogenesis on cognitive function deficit in a rat model of vascular dementia

    PubMed Central

    CHOI, DONG-HEE; LEE, KYOUNG-HEE; LEE, JONGMIN

    2016-01-01

    Chronic cerebral hypoperfusion (CCH) is strongly correlated with progressive cognitive decline in neurological diseases, such as vascular dementia (VaD) and Alzheimer's disease. Exercise can enhance learning and memory, and delay age-related cognitive decline. However, exercise-induced hippocampal neurogenesis in experimental animals submitted to CCH has not been investigated. The present study aimed to investigate whether hippocampal neurogenesis induced by exercise can improve cognitive deficit in a rat model of VaD. Male Wistar rats (age, 8 weeks; weight, 292±3.05 g; n=12–13/group) were subjected to bilateral common carotid artery occlusion (2VO) or sham-surgery and each group was then subdivided randomly into no exercise and treadmill exercise groups. Exercise groups performed treadmill exercise daily at 15 m/min for 30 min for 4 weeks from the third to the seventh week after 2VO. It was demonstrated that the number of neural progenitor cells and mature neurons in the subgranular zone of 2VO rats was increased by exercise, and cognitive impairment in 2VO rats was attenuated by treadmill exercise. In addition, mature brain-derived neurotrophic factor (BDNF) levels in the hippocampus were increased in the exercise groups. Thus the present study suggests that exercise delays cognitive decline by the enhancing neurogenesis and increasing BDNF expression in the context of VaD. PMID:26934837

  18. Pharmacological Cognitive Enhancement in Healthy Individuals: A Compensation for Cognitive Deficits or a Question of Personality?

    PubMed Central

    Maier, Larissa J.; Wunderli, Michael D.; Vonmoos, Matthias; Römmelt, Andreas T.; Baumgartner, Markus R.; Seifritz, Erich

    2015-01-01

    The ongoing bioethical debate on pharmacological cognitive enhancement (PCE) in healthy individuals is often legitimated by the assumption that PCE will widely spread and become desirable for the general public in the near future. This assumption was questioned as PCE is not equally save and effective in everyone. Additionally, it was supposed that the willingness to use PCE is strongly personality-dependent likely preventing a broad PCE epidemic. Thus, we investigated whether the cognitive performance and personality of healthy individuals with regular nonmedical methylphenidate (MPH) use for PCE differ from stimulant-naïve controls. Twenty-five healthy individuals using MPH for PCE were compared with 39 age-, sex-, and education-matched healthy controls regarding cognitive performance and personality assessed by a comprehensive neuropsychological test battery including social cognition, prosocial behavior, decision-making, impulsivity, and personality questionnaires. Substance use was assessed through self-report in an interview and quantitative hair and urine analyses. Recently abstinent PCE users showed no cognitive impairment but superior strategic thinking and decision-making. Furthermore, PCE users displayed higher levels of trait impulsivity, novelty seeking, and Machiavellianism combined with lower levels of social reward dependence and cognitive empathy. Finally, PCE users reported a smaller social network and exhibited less prosocial behavior in social interaction tasks. In conclusion, the assumption that PCE use will soon become epidemic is not supported by the present findings as PCE users showed a highly specific personality profile that shares a number of features with illegal stimulant users. Lastly, regular MPH use for PCE is not necessarily associated with cognitive deficits. PMID:26107846

  19. Age-related Decline in Kv3.1b Expression in the Mouse Auditory Brainstem Correlates with Functional Deficits in the Medial Olivocochlear Efferent System

    PubMed Central

    Zhu, Xiaoxia; O’Neill, William E.; Frisina, Robert D.

    2007-01-01

    Kv3.1b channel protein is widely distributed in the mammalian auditory brainstem, but studies have focused mainly on regions critical for temporal processing, including the medial nucleus of the trapezoid body (MNTB) and anteroventral cochlear nucleus (AVCN). Because temporal processing declines with age, this study was undertaken to determine if the expression of Kv3.1b likewise declines, and if changes are specific to these nuclei. Immunocytochemistry using an anti-Kv3.1b antibody was performed, and the relative optical density of cells and neuropil was determined from CBA/CaJ mice of four age groups. Declines in expression in AVCN, MNTB, and lateral superior olive (35, 26, and 23%) were found, but changes were limited to neuropil. Interestingly, cellular optical density declines were found in superior paraolivary nucleus, ventral nucleus of the trapezoid body, and lateral nucleus of the trapezoid body (24, 29, and 26%), which comprise the medial olivocochlear (MOC) feedback system. All declines occurred by middle age (15 months old). No age-related changes were found in the remaining regions of cochlear nucleus or in the inferior colliculus. Contralateral suppression of distortion-product otoacoustic emission amplitudes of age-matched littermates also declined by middle age, suggesting a correlation between Kv3.1 expression and MOC function. In search of more direct evidence for such a correlation, Kv3.1b knockout mice were examined. Knockouts show poor MOC function as compared to +/+ and +/− genotypes. Thus, Kv3.1b expression declines in MOC neurons by middle age, and these changes appear to correlate with functional declines in efferent activity in both middle-aged CBA mice and Kv3.1b knockout mice. PMID:17453307

  20. The Boehm Test of Basic Concepts: Exploring the Test Results for Cognitive Deficits.

    ERIC Educational Resources Information Center

    Spector, Cecile C.

    1979-01-01

    Analysis of errors by more than 300 kindergarten children on the Boehm Test of Basic Concepts suggested seven cognitive factors that appear to be involved, including complexity of directions, deficits in spatial perception, and inadequate auditory memory for sentences. (CL)

  1. Cognitive Patterns and Learning Disabilities in Cleft Palate Children with Verbal Deficits.

    ERIC Educational Resources Information Center

    Richman, Lynn C.

    1980-01-01

    The study examined patterns of cognitive ability in 57 cleft lip and palate children (ages 7 to 9) with verbal deficit, but without general intellectual retardation to evaluate whether the verbal disability displayed by these children was related primarily to a specific verbal expression deficit or a more general symbolic mediation problem.…

  2. Number Processing and Heterogeneity of Developmental Dyscalculia: Subtypes with Different Cognitive Profiles and Deficits

    ERIC Educational Resources Information Center

    Skagerlund, Kenny; Träff, Ulf

    2016-01-01

    This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with…

  3. Age-Related Changes in 1/f Neural Electrophysiological Noise

    PubMed Central

    Kramer, Mark A.; Case, John; Lepage, Kyle Q.; Tempesta, Zechari R.; Knight, Robert T.; Gazzaley, Adam

    2015-01-01

    Aging is associated with performance decrements across multiple cognitive domains. The neural noise hypothesis, a dominant view of the basis of this decline, posits that aging is accompanied by an increase in spontaneous, noisy baseline neural activity. Here we analyze data from two different groups of human subjects: intracranial electrocorticography from 15 participants over a 38 year age range (15–53 years) and scalp EEG data from healthy younger (20–30 years) and older (60–70 years) adults to test the neural noise hypothesis from a 1/f noise perspective. Many natural phenomena, including electrophysiology, are characterized by 1/f noise. The defining characteristic of 1/f is that the power of the signal frequency content decreases rapidly as a function of the frequency (f) itself. The slope of this decay, the noise exponent (χ), is often <−1 for electrophysiological data and has been shown to approach white noise (defined as χ = 0) with increasing task difficulty. We observed, in both electrophysiological datasets, that aging is associated with a flatter (more noisy) 1/f power spectral density, even at rest, and that visual cortical 1/f noise statistically mediates age-related impairments in visual working memory. These results provide electrophysiological support for the neural noise hypothesis of aging. SIGNIFICANCE STATEMENT Understanding the neurobiological origins of age-related cognitive decline is of critical scientific, medical, and public health importance, especially considering the rapid aging of the world's population. We find, in two separate human studies, that 1/f electrophysiological noise increases with aging. In addition, we observe that this age-related 1/f noise statistically mediates age-related working memory decline. These results significantly add to this understanding and contextualize a long-standing problem in cognition by encapsulating age-related cognitive decline within a neurocomputational model of 1/f noise

  4. Effect of Treating Anxiety Disorders on Cognitive Deficits and Behaviors Associated with Attention Deficit Hyperactivity Disorder: A Preliminary Study.

    PubMed

    Denis, Isabelle; Guay, Marie-Claude; Foldes-Busque, Guillaume; BenAmor, Leila

    2016-06-01

    Twenty-five percent of children with ADHD also have an anxiety disorder (AD). As per Quay and in light of Barkley's model, anxiety may have a protective effect on cognitive deficits and behaviors associated with ADHD. This study aimed to evaluate the effect of treating AD on cognitive deficits and behaviors associated with ADHD in children with both disorders. Twenty-four children with ADHD and AD were divided into two groups: treatment for AD, and wait list. Participants were assessed at pre-treatment, post-treatment, and 6-month follow-up with the ADIS-C, the CBCL, and neuropsychological measures. The results revealed a significant improvement in automatic response inhibition and flexibility, and a decrease in inattention/hyperactivity behaviors following the treatment for AD. No significant differences were observed in motor response inhibition, working memory, or attention deficits. The results do not seem to support Quay's hypothesis: treating AD did not exacerbate cognitive deficits and behaviors associated with ADHD in our sample. PMID:26323585

  5. Age-related changes in prefrontal norepinephrine transporter density: The basis for improved cognitive flexibility after low doses of atomoxetine in adolescent rats.

    PubMed

    Bradshaw, Sarah E; Agster, Kara L; Waterhouse, Barry D; McGaughy, Jill A

    2016-06-15

    Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning. While both of these drugs act as norepinephrine reuptake inhibitors, higher doses of atomoxetine and all doses of methylphenidate also block dopamine transporters (DAT). Low doses of atomoxetine, were effective at remediating cognitive rigidity found in adolescents. In contrast, methylphenidate improved performance in rats unable to form an attentional set due to distractibility but was without effect in normal subjects. We also assessed the effects of GBR 12909, a selective DAT inhibitor, but found no effect of any dose on behavior. A second study in adolescent rats investigated changes in norepinephrine transporter (NET) and dopamine beta hydroxylase (DBH) density in five functionally distinct sub-regions of the prefrontal cortex: infralimbic, prelimbic, anterior cingulate, medial and lateral orbitofrontal cortices. These regions are implicated in impulsivity and distractibility. We found that NET, but not DBH, changed across adolescence in a regionally selective manner. The prelimbic cortex, which is critical to cognitive rigidity, and the lateral orbitofrontal cortex, critical to reversal learning and some forms of response inhibition, showed higher levels of NET at early than mid- to late adolescence. This article is part of a Special Issue entitled SI: Noradrenergic System. PMID:26774596

  6. [Presbycusis - Age Related Hearing Loss].

    PubMed

    Fischer, N; Weber, B; Riechelmann, H

    2016-07-01

    Presbycusis or age related hearing loss can be defined as a progressive, bilateral and symmetrical sensorineural hearing loss due to age related degeneration of inner ear structures. It can be considered a multifactorial complex disorder with environmental and genetic factors. The molecular, electrophysiological and histological damage at different levels of the inner ear cause a progressive hearing loss, which usually affects the high frequencies of hearing. The resulting poor speech recognition has a negative impact on cognitive, emotional and social function in older adults. Recent investigations revealed an association between hearing impairment and social isolation, anxiety, depression and cognitive decline in elderly. These findings emphasize the importance of diagnosis and treating hearing loss in the elderly population. Hearing aids are the most commonly used devices for treating presbycusis. The technical progress of implantable hearing devices allows an effective hearing rehabilitation even in elderly with severe hearing loss. However, most people with hearing impairments are not treated adequately. PMID:27392191

  7. High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion.

    PubMed

    Zuloaga, Kristen L; Johnson, Lance A; Roese, Natalie E; Marzulla, Tessa; Zhang, Wenri; Nie, Xiao; Alkayed, Farah N; Hong, Christine; Grafe, Marjorie R; Pike, Martin M; Raber, Jacob; Alkayed, Nabil J

    2016-07-01

    Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology. PMID:26661233

  8. Dissociable long-term cognitive deficits after frontal versus sensorimotor cortical contusions.

    PubMed

    Lindner, M D; Plone, M A; Cain, C K; Frydel, B; Francis, J M; Emerich, D F; Sutton, R L

    1998-03-01

    Cognitive deficits are the most enduring and disabling sequelae of human traumatic brain injury (TBI), but quantifying the magnitude, duration, and pattern of cognitive deficits produced by different types of TBI has received little emphasis in preclinical animal models. The objective of the present study was to use a battery of behavioral tests to determine if different impact sites produce different patterns of behavioral deficits and to determine how long behavioral deficits can be detected after TBI. Prior to surgery, rats were trained to criteria on delayed nonmatching to position, radial arm maze, and rotarod tasks. Rats received sham surgery (controls), midline frontal contusions (frontal TBI, 2.25 m/sec impact), or unilateral sensorimotor cortex contusions (lateral TBI, 3.22 m/sec impact) at 12 months of age and were tested throughout the next 12 months. Cognitive deficits were more robust and more enduring than sensorimotor deficits for both lateral TBI and frontal TBI groups. Lateral TBI rats exhibited transient deficits in the forelimb placing and in the rotarod test of motor/ambulatory function, but cognitive deficits were apparent throughout the 12-month postsurgery period on tests of spatial learning and memory including: (1)reacquisition of a working memory version of the radial arm maze 6-7 months post-TBI, (2) performance in water maze probe trials 8 months post-TBI, and (3) repeated acquisition of the Morris water maze 8 and 11 months post-TBI. Frontal TBI rats exhibited a different pattern of deficits, with the most robust deficits in tests of attention/orientation such as: (1) the delayed nonmatching to position task (even with no delays) 1-11 weeks post-TBI, (2) the repeated acquisition version of the water maze--especially on the first "information" trial 8 months post-TBI, (3) a test of sensorimotor neglect or inattention 8.5 months post-TBI, and (4) a DRL20 test of timing and/or sustained attention 11 months after surgery. These results

  9. Should Sluggish Cognitive Tempo Symptoms Be Included in the Diagnosis of Attention-Deficit/hyperactivity Disorder?

    ERIC Educational Resources Information Center

    Todd, Richard D.; Rasmussen, Erik R.; Wood, Catherine; Levy, Florence; Hay, David A.

    2004-01-01

    Objective: To determine the impact of including sluggish cognitive tempo items on the factor and latent class structure of attention-deficit/hyperactivity disorder (ADHD) subtypes in boys and girls. Method: Parent report of two sluggish cognitive tempo items on a population-based sample of 1,430 female twins and 1,414 male twins were analyzed…

  10. Cognitive-Linguistic Deficit and Speech Intelligibility in Chronic Progressive Multiple Sclerosis

    ERIC Educational Resources Information Center

    Mackenzie, Catherine; Green, Jan

    2009-01-01

    Background: Multiple sclerosis is a disabling neurological disease with varied symptoms, including dysarthria and cognitive and linguistic impairments. Association between dysarthria and cognitive-linguistic deficit has not been explored in clinical multiple sclerosis studies. Aims: In patients with chronic progressive multiple sclerosis, the…

  11. Specific cognitive deficits and differential domains of social functioning impairment in schizophrenia.

    PubMed

    Cohen, Alex S; Forbes, Courtney B; Mann, Monica C; Blanchard, Jack J

    2006-01-31

    There is considerable inconsistency in findings regarding the relationship between specific cognitive deficits and social impairment in patients with schizophrenia. This inconsistency may relate to variability across studies in how social functioning is measured and preliminary evidence suggests that different indices of social functioning (e.g., laboratory test, community assessment) may have different cognitive correlates. The present study examined this issue by evaluating the relationships between cognitive deficits (including social cognitive deficits), role-play test performance, and community social functioning in 28 inpatients with schizophrenia. We expected the two measures of social functioning to have only modest convergence with each other. Moreover, informed by the literature on cognitive functioning in schizophrenia, we identified specific cognitive processes that were hypothesized to be associated with role-play performance (delayed verbal memory and attentional vigilance) and social functioning in the community (delayed verbal memory and executive functioning). As expected, the two measures of social functioning were modestly correlated with each other. Community social functioning was associated with a relatively constrained pattern of cognitive deficits and received a significant contribution (Deltar2=0.24) from specific cognitive processes beyond that of general cognitive functioning and symptom severity. In contrast to our hypotheses, role-play test performance was associated with a wide range of cognitive impairments and received little contribution from the specific cognitive processes beyond the effects of general cognitive functioning. Community social functioning, but not role-play test performance, was significantly associated with social cognition. These findings highlight the importance of conceptualizing social functioning as a multidimensional construct for schizophrenia research. PMID:16260120

  12. Reversal of age-related neural timing delays with training.

    PubMed

    Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

    2013-03-12

    Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills. PMID:23401541

  13. Reversal of age-related neural timing delays with training

    PubMed Central

    Anderson, Samira; White-Schwoch, Travis; Parbery-Clark, Alexandra; Kraus, Nina

    2013-01-01

    Neural slowing is commonly noted in older adults, with consequences for sensory, motor, and cognitive domains. One of the deleterious effects of neural slowing is impairment of temporal resolution; older adults, therefore, have reduced ability to process the rapid events that characterize speech, especially in noisy environments. Although hearing aids provide increased audibility, they cannot compensate for deficits in auditory temporal processing. Auditory training may provide a strategy to address these deficits. To that end, we evaluated the effects of auditory-based cognitive training on the temporal precision of subcortical processing of speech in noise. After training, older adults exhibited faster neural timing and experienced gains in memory, speed of processing, and speech-in-noise perception, whereas a matched control group showed no changes. Training was also associated with decreased variability of brainstem response peaks, suggesting a decrease in temporal jitter in response to a speech signal. These results demonstrate that auditory-based cognitive training can partially restore age-related deficits in temporal processing in the brain; this plasticity in turn promotes better cognitive and perceptual skills. PMID:23401541

  14. GM1 ganglioside reverses the cognitive deficits induced by MK801 in mice.

    PubMed

    Ni, Yu-Fei; Zhang, Wei; Bao, Xiao-Feng; Wang, Wei; Song, Lu; Jiang, Bo

    2016-08-01

    Cognitive deficits are core symptoms of schizophrenia, but effective treatments are still lacking. Previous studies have reported that the brain-derived neurotrophic factor (BDNF) signaling is closely involved in learning and memory. Monosialotetrahexosylganglioside (GM1) is a ganglioside with wide-ranging pharmacologic effects that enhances the BDNF signaling cascade. This study aimed to assess the effects of GM1 on schizophrenia-related cognitive impairments. A brief disruption of N-methyl-D-aspartate receptors with MK801 was used to generate the animal model for cognitive deficits in schizophrenia. It was found that MK801-treated mice showed significant deficits in memory ability compared with control mice in different behavior tests, and this was accompanied by decreased hippocampal BDNF signaling pathway. Consecutive administration of GM1 fully restored the MK801-induced cognitive deficits and the impaired BDNF signaling in the hippocampus. Furthermore, a BDNF system inhibitor abolished the effects of GM1 in the MK801 model. Taken together, our results show that GM1 could reverse the MK801-induced cognitive deficits, suggesting a potential usefulness of GM1 in treating the schizophrenia-related cognitive impairments. PMID:26960162

  15. Review of recent studies on interventions for cognitive deficits in patients with cancer.

    PubMed

    Gehring, Karin; Roukema, Jan Anne; Sitskoorn, Margriet M

    2012-02-01

    Research has demonstrated that patients with cancer experience cognitive deficits, often due to aggressive anticancer treatments. In this article, we critically review the interventional studies that have been conducted to investigate beneficial effects on cognitive function in cancer patients. Pharmacological agents that have been studied include psychostimulants, such as methylphenidate and modafinil, erythropoietin, and hormonal (supplement) treatments for patients who receive hormonal suppression therapy. In addition, several cognitive rehabilitation programs have been evaluated in cancer patients. Recently, the approach of physical exercise to treat cognitive deficits has received great interest, and findings from novel studies are keenly anticipated. Although, in general, the studies reviewed were well designed, future studies may wish to include larger sample sizes and pay more attention to the accurate assessment of cognitive function. PMID:22316373

  16. Characterization of Cognitive Deficits in Mice With an Alternating Hemiplegia-Linked Mutation

    PubMed Central

    2015-01-01

    Cognitive impairment is a prominent feature in a range of different movement disorders. Children with Alternating Hemiplegia of Childhood are prone to developmental delay, with deficits in cognitive functioning becoming progressively more evident as they grow older. Heterozygous mutations of the ATP1A3 gene, encoding the Na+,K+-ATPase α3 subunit, have been identified as the primary cause of Alternating Hemiplegia. Heterozygous Myshkin mice have an amino acid change (I810N) in Na+,K+-ATPase α3 that is also found in Alternating Hemiplegia. To investigate whether Myshkin mice exhibit learning and memory deficits resembling the cognitive impairments of patients with Alternating Hemiplegia, we subjected them to a range of behavioral tests that interrogate various cognitive domains. Myshkin mice showed impairments in spatial memory, spatial habituation, locomotor habituation, object recognition, social recognition, and trace fear conditioning, as well as in the visible platform version of the Morris water maze. Increasing the duration of training ameliorated the deficit in social recognition but not in spatial habituation. The deficits of Myshkin mice in all of the learning and memory tests used are consistent with the cognitive impairment of the vast majority of AHC patients. These mice could thus help advance our understanding of the underlying neural mechanisms influencing cognitive impairment in patients with ATP1A3-related disorders. PMID:26501181

  17. Ursolic acid improves domoic acid-induced cognitive deficits in mice

    SciTech Connect

    Wu, Dong-mei; Lu, Jun; Zhang, Yan-qiu; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng; Li, Meng-qiu

    2013-09-01

    Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders. - Highlights: • Ursolic acid (UA) is a naturally triterpenoid compound. • UA attenuated the mitochondrial dysfunction and cognitive deficits. • Mechanistically, UA activates PI3K/Akt signaling and suppresses FoxO1 activity. • UA could be recommended as a possible candidate for anti-excitotoxic brain disorders.

  18. Cognitive Deficits in Nonretarded Adults with Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Kerns, Kimberley A.; Don, Audrey; Mateer, Catherine A.; Streissguth, Ann P.

    1997-01-01

    Sixteen nonretarded young adults with fetal alcohol syndrome were divided into two groups, one with average to above average IQ and one with borderline to low average IQ. Subjects in both groups manifested clear deficits on neuropsychological measures sensitive to complex attention, verbal learning, and executive function at a frequency and…

  19. Static and Dynamic Cognitive Deficits in Childhood Preceding Adult Schizophrenia: A 30-Year Study

    PubMed Central

    Reichenberg, Abraham; Caspi, Avshalom; Harrington, HonaLee; Houts, Renate; Keefe, Richard S.E.; Murray, Robin M.; Poulton, Richie; Moffitt, Terrie E.

    2013-01-01

    Objective Premorbid cognitive deficits in schizophrenia are well documented and have been interpreted as supporting a neurodevelopmental etiological model. The authors investigated the following three unresolved questions about premorbid cognitive deficits: What is their developmental course? Do all premorbid cognitive deficits follow the same course? Are premorbid cognitive deficits specific to schizophrenia or shared by other psychiatric disorders? Methods Participants were members of a representative cohort of 1,037 males and females born between 1972 and 1973 in Dunedin, New Zealand. Cohort members underwent follow-up evaluations at specific intervals from age 3 to 32 years, with a 96% retention rate. Cognitive development was analyzed and compared in children who later developed schizophrenia or recurrent depression as well as in healthy comparison subjects. Results Children who developed adult schizophrenia exhibited developmental deficits (i.e., static cognitive impairments that emerge early and remain stable) on tests indexing verbal and visual knowledge acquisition, reasoning, and conceptualization. In addition, these children exhibited developmental lags (i.e., growth that is slower relative to healthy comparison subjects) on tests indexing processing speed, attention, visual-spatial problem solving ability, and working memory. These two premorbid cognitive patterns were not observed in children who later developed recurrent depression. Conclusions These findings suggest that the origins of schizophrenia include two interrelated developmental processes evident from childhood to early adolescence (ages 7–13 years). Children who will grow up to develop adult schizophrenia enter primary school struggling with verbal reasoning and lag further behind their peers in working memory, attention, and processing speed as they get older. PMID:20048021

  20. Icariside II, a novel phosphodiesterase-5 inhibitor, attenuates streptozotocin-induced cognitive deficits in rats.

    PubMed

    Yin, Caixia; Deng, Yuanyuan; Gao, Jianmei; Li, Xiaohui; Liu, Yuangui; Gong, Qihai

    2016-07-22

    Beta-amyloid (Aβ) deposition and neuroinflammation are involved in Alzheimer's disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and Aβ levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive deficits, Aβ levels and neuroinflammation induced by intracerebroventricular-streptozotocin (ICV-STZ) in rats. The results demonstrated that ICV-STZ exhibited cognitive deficits and neuronal morphological damage, along with Aβ increase and neuroinflammation in the rat hippocampus. ICS II improved cognitive deficits, attenuated neuronal death, and decreased the levels of Aβ1-40, Aβ1-42 and PDE5 in the hippocampus of STZ rats. Furthermore, administration of ICS II at the dose of 10mg/kg for 21days significantly suppressed the expression of beta-amyloid precursor protein (APP), beta-secretase1 (BACE1) and increased the expressions of neprilysin (NEP) together with inhibited interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) and transforming growth factor-β1 (TGF-β1) levels. In addition, ICS II exerted a beneficial effect on inhibition of IκB-α degradation and NF-κB activation induced by STZ. Taken together, the present study demonstrated that ICS II was a potential therapeutic agent for AD treatment. PMID:27109920

  1. Deficits in Domains of Social Cognition in Schizophrenia: A Meta-Analysis of the Empirical Evidence

    PubMed Central

    Savla, Gauri N.

    2013-01-01

    Objective: Social cognition is strongly associated with functional outcome in schizophrenia, making it an important target for treatment. Our goal was to examine the average magnitude of differences between schizophrenia patients (SCs) and normal comparison (NCs) patients across multiple domains of social cognition recognized by the recent NIMH consensus statement: theory of mind (ToM), social perception, social knowledge, attributional bias, emotion perception, and emotion processing. Method: We conducted a meta-analysis of peer-reviewed studies of social cognition in schizophrenia, published between 1980 and November, 2011. Results: 112 studies reporting results from 3908 SCs and 3570 NCs met our inclusion criteria. SCs performed worse than NCs across all domains, with large effects for social perception (g = 1.04), ToM (g = 0.96), emotion perception (g = 0.89), and emotion processing (g = 0.88). Regression analyses showed that statistically significant heterogeneity in effects within domains was not explained by age, education, or gender. Greater deficits in social and emotion perception were associated with inpatient status, and greater deficits in emotion processing were associated with longer illness duration. Conclusions: Despite the limitations of existing studies, including lack of standardization or psychometric validation of measures, the evidence for deficits across multiple social cognitive domains in schizophrenia is clear. Future research should examine the role of neurobiological and psychosocial factors in models linking various aspects of deficit in schizophrenia, including social cognition, in order to identify targets for intervention. PMID:22949733

  2. Amusia and cognitive deficits in schizophrenia: is there a relationship?

    PubMed

    Wen, Yi; Nie, Xueqing; Wu, Daxing; Liu, Hong; Zhang, Pin; Lu, Xuejing

    2014-08-01

    The current study explored the music perception ability of individuals diagnosed with schizophrenia and its relationship with other cognitive abilities and psychotic symptom severity. The persons with schizophrenia performed significantly worse than the control group on the Montreal Battery of Evaluation of Amusia (MBEA) (p<0.001). The music perception ability of persons with schizophrenia was related to other cognitive abilities (attention, verbal memory, spatial memory, and executive function) and the severity of psychotic symptoms. PMID:24957355

  3. Glatiramer acetate reverses cognitive deficits from cranial-irradiated rat by inducing hippocampal neurogenesis.

    PubMed

    He, Fen; Zou, Jun-Tao; Zhou, Qiong-Fang; Niu, Dao-Li; Jia, Wei-Hua

    2014-06-15

    Patients received cranial-irradiation can be affected with cognitive deficits and decreasing hippocampal neurogenesis. In this work, we characterized the cognitive ability and immune-induced neurogenesis of the pre- and post-treated cranial-irradiated rats with Glatiramer acetate (GA), known as a weak CNS auto-antigen. The GA-treated rats displayed better cognitive abilities in Morris water maze (MWM). The numbers of Iba-I-positive microglia, BrdU(+)/DCX(+) cells and BrdU(+)/NeuN(+) cells in hippocampus increased, which are accompanied with increased IFN-γ and decreased IL-6, IL-4. Furthermore, GA reverted the Th1/Th2 balance. GA treatment can reverse the cognitive deficits caused by cranial irradiation through a mechanism that likely involves immunomodulation. PMID:24713401

  4. Social cognitive deficits and their neural correlates in progressive supranuclear palsy

    PubMed Central

    Calder, Andrew J.; Peers, Polly V.; Lawrence, Andrew D.; Acosta-Cabronero, Julio; Pereira, João M.; Hodges, John R.; Rowe, James B.

    2012-01-01

    Although progressive supranuclear palsy is defined by its akinetic rigidity, vertical supranuclear gaze palsy and falls, cognitive impairments are an important determinant of patients’ and carers’ quality of life. Here, we investigate whether there is a broad deficit of modality-independent social cognition in progressive supranuclear palsy and explore the neural correlates for these. We recruited 23 patients with progressive supranuclear palsy (using clinical diagnostic criteria, nine with subsequent pathological confirmation) and 22 age- and education-matched controls. Participants performed an auditory (voice) emotion recognition test, and a visual and auditory theory of mind test. Twenty-two patients and 20 controls underwent structural magnetic resonance imaging to analyse neural correlates of social cognition deficits using voxel-based morphometry. Patients were impaired on the voice emotion recognition and theory of mind tests but not auditory and visual control conditions. Grey matter atrophy in patients correlated with both voice emotion recognition and theory of mind deficits in the right inferior frontal gyrus, a region associated with prosodic auditory emotion recognition. Theory of mind deficits also correlated with atrophy of the anterior rostral medial frontal cortex, a region associated with theory of mind in health. We conclude that patients with progressive supranuclear palsy have a multimodal deficit in social cognition. This deficit is due, in part, to progressive atrophy in a network of frontal cortical regions linked to the integration of socially relevant stimuli and interpretation of their social meaning. This impairment of social cognition is important to consider for those managing and caring for patients with progressive supranuclear palsy. PMID:22637582

  5. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions

    PubMed Central

    Beilharz, Jessica E.; Maniam, Jayanthi; Morris, Margaret J.

    2015-01-01

    It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments. PMID:26274972

  6. Female mice heterozygous for creatine transporter deficiency show moderate cognitive deficits.

    PubMed

    Hautman, Emily R; Kokenge, Amanda N; Udobi, Kenea C; Williams, Michael T; Vorhees, Charles V; Skelton, Matthew R

    2014-01-01

    Creatine transporter (CrT) deficiency (CTD) is an X-linked disorder characterized by intellectual disability and speech delay. There have been reports that show female carriers have clinical symptoms. We have created CrT knockout (CrT(-/y)) mice in which males show severe cognitive deficits as a model of this disorder. The purpose of this study was to examine if the female carrier mice show cognitive deficits. Reductions in Cr levels as well as CrT transcript were observed in the brains of the female CrT(+/-) mice. CrT(+/-) mice show hyperactivity and increased latency to find the cued platform in the Morris water maze (MWM). CrT(+/-) female mice showed deficits in MWM hidden platform acquisition but not during reversal testing. Memory deficits on probe trials were observed during both phases. Novel object recognition memory and contextual fear memory were not affected in female CrT(+/-) mice. Female CrT(+/-) mice show moderate cognitive deficits, which is consistent with some of the human data. Female CrT(+/-) mice could prove to be beneficial in further understanding CTD and testing therapeutic approaches. PMID:23716276

  7. The Relationship between Sluggish Cognitive Tempo, Subtypes of Attention-Deficit/Hyperactivity Disorder, and Anxiety Disorders

    ERIC Educational Resources Information Center

    Skirbekk, Benedicte; Hansen, Berit Hjelde; Oerbeck, Beate; Kristensen, Hanne

    2011-01-01

    The objective of the present study was to examine the relationship between sluggish cognitive tempo (SCT), subtypes of attention-deficit/hyperactivity disorder (ADHD), and anxiety disorders (AnxDs). One hundred and forty-one children (90 males, 51 females) aged 7-13 years were assigned to four groups, i.e., referred children with comorbid AnxDs…

  8. Mitochondria-Targeted Peptide Reverses Mitochondrial Dysfunction and Cognitive Deficits in Sepsis-Associated Encephalopathy.

    PubMed

    Wu, Jing; Zhang, Mingqiang; Hao, Shuangying; Jia, Ming; Ji, Muhuo; Qiu, Lili; Sun, Xiaoyan; Yang, Jianjun; Li, Kuanyu

    2015-08-01

    Sepsis-associated encephalopathy (SAE) is associated with increased mortality, morbidity, and long-term cognitive impairments. Its pathophysiology remains to be determined and an effective pharmacologic treatment is lacking. The goal of this study was to investigate the effects of the mitochondria-targeted peptide SS-31 on mitochondrial function and cognitive deficits in SAE mice. C57BL/6 male mice were randomly divided into sham, sham + SS-31, cecal ligation and puncture (CLP), and CLP + SS-31 groups. Peptide SS-31 (5 mg/kg) was intraperitoneally administrated immediately after operation and afterwards once daily for six consecutive days. Surviving mice were subjected to behavioral tests and the hippocampus was collected for biochemical analysis 7 days after operation. The results showed that CLP resulted in high mortality rate and cognitive deficits, representative characteristics of SAE. A physiological mechanistic investigation revealed that mitochondrial function of hippocampus was severely impaired, coupled with reactive oxygen species (ROS) generation, triggering neuronal apoptosis and inflammation. Notably, administration of peptide SS-31 protected the integrity of mitochondria, reversed the mitochondrial dysfunction, inhibited the apoptosis resulting from the release of cytochrome c, diminished the response of inflammation, and ultimately reversed the behavior deficits in the SAE mice. In conclusion, our data demonstrate that daily treatment with mitochondria-targeted peptide SS-31 reduces mortality rate and ameliorates cognitive deficits, which is possibly through a mechanism of reversing mitochondrial dysfunction and partial inhibition of neuronal apoptosis and inflammation in the hippocampus of the SAE mice. PMID:25288156

  9. Understanding Cognitive Deficits in Parkinson's Disease: Lessons from Preclinical Animal Models

    ERIC Educational Resources Information Center

    Solari, Nicola; Bonito-Oliva, Alessandra; Fisone, Gilberto; Brambilla, Riccardo

    2013-01-01

    Parkinson's disease (PD) has been, until recently, mainly defined by the presence of characteristic motor symptoms, such as rigidity, tremor, bradykinesia/akinesia, and postural instability. Accordingly, pharmacological and surgical treatments have so far addressed these motor disturbances, leaving nonmotor, cognitive deficits an unmet…

  10. The Cognitive Profile and Multiple-Deficit Hypothesis in Chinese Developmental Dyslexia.

    ERIC Educational Resources Information Center

    Ho, Connie Suk-Han; Chan, David Wai-Ock; Tsang, Suk-Man; Lee, Suk-Han

    2002-01-01

    Examined cognitive profile and multiple-deficit hypothesis in Chinese developmental dyslexia. Compared 30 Chinese dyslexic children with average readers of the same chronological age (CA) and 30 average readers at the same reading level (RL) in several rapid naming, visual, phonological, and orthographic tasks. Found that dyslexic children…

  11. Specific Cognitive Deficits in ADHD: A Diagnostic Concern in Differential Diagnosis

    ERIC Educational Resources Information Center

    Gupta, Rashmi; Kar, Bhoomika R.

    2010-01-01

    We present a critical account of existing tools used to diagnose children with Attention Deficit Hyperactivity Disorder and to make a case for the assessment of cognitive impairments as a part of diagnostic system. Surveys have shown that clinicians rely almost entirely upon subjective reports or their own clinical judgment when arriving at…

  12. Age-Related Differences and Cognitive Correlates of Self-Reported and Direct Navigation Performance: The Effect of Real and Virtual Test Conditions Manipulation

    PubMed Central

    Taillade, Mathieu; N'Kaoua, Bernard; Sauzéon, Hélène

    2016-01-01

    The present study investigated the effect of aging on direct navigation measures and self-reported ones according to the real-virtual test manipulation. Navigation (wayfinding tasks) and spatial memory (paper-pencil tasks) performances, obtained either in real-world or in virtual-laboratory test conditions, were compared between young (n = 32) and older (n = 32) adults who had self-rated their everyday navigation behavior (SBSOD scale). Real age-related differences were observed in navigation tasks as well as in paper-pencil tasks, which investigated spatial learning relative to the distinction between survey-route knowledge. The manipulation of test conditions (real vs. virtual) did not change these age-related differences, which are mostly explained by age-related decline in both spatial abilities and executive functioning (measured with neuropsychological tests). In contrast, elderly adults did not differ from young adults in their self-reporting relative to everyday navigation, suggesting some underestimation of navigation difficulties by elderly adults. Also, spatial abilities in young participants had a mediating effect on the relations between actual and self-reported navigation performance, but not for older participants. So, it is assumed that the older adults carried out the navigation task with fewer available spatial abilities compared to young adults, resulting in inaccurate self-estimates. PMID:26834666

  13. The Turner Syndrome: Cognitive Deficits, Affective Discrimination, and Behavior Problems.

    ERIC Educational Resources Information Center

    McCauley, Elizabeth; And Others

    1987-01-01

    The study attemped to link cognitive and social problems seen in girls with Turner syndrome by assessing the girls' ability to process affective cues. Seventeen 9- to 17-year-old girls diagnosed with Turner syndrome were compared to a matched control group on a task which required interpretation of affective intention from facial expression.…

  14. Cognitive mechanisms underlying achievement deficits in children with mathematical learning disability.

    PubMed

    Geary, David C; Hoard, Mary K; Byrd-Craven, Jennifer; Nugent, Lara; Numtee, Chattavee

    2007-01-01

    Using strict and lenient mathematics achievement cutoff scores to define a learning disability, respective groups of children who are math disabled (MLD, n=15) and low achieving (LA, n=44) were identified. These groups and a group of typically achieving (TA, n=46) children were administered a battery of mathematical cognition, working memory, and speed of processing measures (M=6 years). The children with MLD showed deficits across all math cognition tasks, many of which were partially or fully mediated by working memory or speed of processing. Compared with the TA group, the LA children were less fluent in processing numerical information and knew fewer addition facts. Implications for defining MLD and identifying underlying cognitive deficits are discussed. PMID:17650142

  15. Pyrroloquinoline quinone prevents MK-801-induced stereotypical behavior and cognitive deficits in mice.

    PubMed

    Zhou, Xingqin; Chen, Quancheng; Hu, Xindai; Mao, Shishi; Kong, Yanyan

    2014-01-01

    Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator, and nerve growth factor, prevents cognitive deficits associated with oxidative stress-induced neurodegeneration. Previous molecular imaging studies also demonstrate that PQQ binds to N-methyl D-aspartate (NMDA) receptors. In this study, we investigated the effects of PQQ on stereotypical behaviors and cognitive deficits induced by MK-801, a non-competitive NMDA antagonist used to model schizophrenia. Mice were given repeated injections of MK-801 (0.5mg/kg/d) and PQQ (0.2, 2.0, or 20 μg/kg/d) for 60 days. Behavior was evaluated using a variety of motor, social, and cognitive tests. We found that PQQ administration significantly attenuated MK-801-induced increases in stereotypical behavior and ataxia, suggesting a protective role of PQQ against MK-801-induced neuronal dysfunction and psychiatric disorders. Future studies are necessary to elucidate the underlying mechanisms of PQQ. PMID:24149067

  16. Cognitive deficits induced by 56Fe radiation exposure.

    PubMed

    Shukitt-Hale, B; Casadesus, G; Cantuti-Castelvetri, I; Rabin, B M; Joseph, J A

    2003-01-01

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. PMID:12577981

  17. Cognitive deficits induced by 56Fe radiation exposure

    NASA Astrophysics Data System (ADS)

    Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere.

  18. Cognitive deficits induced by 56Fe radiation exposure

    NASA Technical Reports Server (NTRS)

    Shukitt-Hale, B.; Casadesus, G.; Cantuti-Castelvetri, I.; Rabin, B. M.; Joseph, J. A.

    2003-01-01

    Exposing rats to particles of high energy and charge (e.g., 56Fe) disrupts neuronal systems and the behaviors mediated by them; these adverse behavioral and neuronal effects are similar to those seen in aged animals. Because cognition declines with age, and our previous study showed that radiation disrupted Morris water maze spatial learning and memory performance, the present study used an 8-arm radial maze (RAM) to further test the cognitive behavioral consequences of radiation exposure. Control rats or rats exposed to whole-body irradiation with 1.0 Gy of 1 GeV/n high-energy 56Fe particles (delivered at the alternating gradient synchrotron at Brookhaven National Laboratory) were tested nine months following exposure. Radiation adversely affected RAM performance, and the changes seen parallel those of aging. Irradiated animals entered baited arms during the first 4 choices significantly less than did controls, produced their first error sooner, and also tended to make more errors as measured by re-entries into non-baited arms. These results show that irradiation with high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts to perform critical tasks during long-term space travel beyond the magnetosphere. Published by Elsevier Science Ltd on behalf of COSPAR.

  19. Social Cognition Deficits and Associations with Drinking History in Alcoholic Men and Women

    PubMed Central

    Valmas, Mary M.; Ruiz, Susan Mosher; Gansler, David A.; Sawyer, Kayle S.; Oscar-Berman, Marlene

    2014-01-01

    . These findings extend into the social cognition domain, previous literature demonstrating the presence of cognitive deficits in alcoholism, their association with alcoholism severity, and variability by gender. Moreover, because impairments in social cognition can persist despite extended abstinence, they have important implications for relapse prevention. PMID:25581654

  20. Distinguishing Sources of L2 Development Problems in K-12: Language Deficit, Cognitive Deficit, and Cognitive Distance

    ERIC Educational Resources Information Center

    Stapp, Yvonne

    2007-01-01

    K-12 students with limited L2 proficiency who do not progress satisfactorily are often referred to special education and/or speech pathology services. Like the teachers who refer such students, the representatives of each service have a specific expertise (e.g., cognition) with little knowledge of the other types of proficiencies (e.g., L1…

  1. The profile of executive functioning in amnestic mild cognitive impairment: disproportionate deficits in inhibitory control.

    PubMed

    Johns, Erin K; Phillips, Natalie A; Belleville, Sylvie; Goupil, Diane; Babins, Lennie; Kelner, Nora; Ska, Bernadette; Gilbert, Brigitte; Massoud, Fadi; de Boysson, Chloé; Duncan, Hilary D; Chertkow, Howard

    2012-05-01

    Amnestic mild cognitive impairment (aMCI) represents a group of individuals who are highly likely to develop Alzheimer's disease (AD). Although aMCI is typically conceptualized as involving predominantly deficits in episodic memory, recent studies have demonstrated that deficits in executive functioning may also be present, and thorough categorization of cognitive functioning in MCI may improve early diagnosis and treatment of AD. We first provide an extensive review of neuropsychology studies that examined executive functioning in MCI. We then present data on executive functioning across multiple sub-domains (divided attention, working memory, inhibitory control, verbal fluency, and planning) in 40 aMCI patients (single or multiple domain) and 32 normal elderly controls (NECs). MCI patients performed significantly worse than NECs in all 5 sub-domains, and there was impairment (>1.0 SD below the mean of NECs) in all sub-domains. Impairment on each test was frequent, with 100% of MCI patients exhibiting a deficit in at least one sub-domain of executive functioning. Inhibitory control was the most frequently and severely impaired. These results indicate that executive dysfunction in multiple sub-domains is common in aMCI and highlights the importance of a comprehensive neuropsychological evaluation for fully characterizing the nature and extent of cognitive deficits in MCI. PMID:22370245

  2. Testing sensory and cognitive explanations of the antisaccade deficit in schizophrenia.

    PubMed

    Leonard, Carly J; Robinson, Benjamin M; Kaiser, Samuel T; Hahn, Britta; McClenon, Clara; Harvey, Alex N; Luck, Steven J; Gold, James M

    2013-11-01

    Recent research has suggested that people with schizophrenia (PSZ) have sensory deficits, especially in the magnocellular pathway, and this has led to the proposal that dysfunctional sensory processing may underlie higher-order cognitive deficits. Here we test the hypothesis that the antisaccade deficit in PSZ reflects dysfunctional magnocellular processing rather than impaired cognitive processing, as indexed by working memory capacity. This is a plausible hypothesis because oculomotor regions have direct magnocellular inputs, and the stimuli used in most antisaccade tasks strongly activate the magnocellular visual pathway. In the current study, we examined both prosaccade and antisaccade performance in PSZ (N = 22) and matched healthy control subjects (HCS; N = 22) with Gabor stimuli designed to preferentially activate the magnocellular pathway, the parvocellular pathway, or both pathways. We also measured working memory capacity. PSZ exhibited impaired antisaccade performance relative to HCS across stimulus types, with impairment even for stimuli that minimized magnocellular activation. Although both sensory thresholds and working memory capacity were impaired in PSZ, only working memory capacity was correlated with antisaccade accuracy, consistent with a cognitive rather than sensory origin for the antisaccade deficit. PMID:24364614

  3. Dissociations in visual attention deficits among persons with mild cognitive impairment.

    PubMed

    Okonkwo, Ozioma C; Wadley, Virginia G; Ball, Karlene; Vance, David E; Crowe, Michael

    2008-07-01

    Impairments in visual attention and visual information processing have been identified as part of the neuropsychological features of Alzheimer's disease (AD), even in its earliest stages. There is increasing recognition that these deficits may be selective rather than global, with some attentional subtypes being more vulnerable than others. The few studies that have investigated attentional deficits in mild cognitive impairment (MCI), a putatively prodromal phase of AD, have not satisfactorily addressed the possible selectivity in attentional deficits in MCI. This study examined potential dissociations in visual attention deficits in MCI using a measure that assesses simple, divided, and selective attention. The results indicated a hierarchy of attentional impairments, with divided attention being the most affected and simple attention the least. Among participants with MCI, 53% showed evidence of impairment in divided attention compared to 19% of controls (OR = 4.81, p < .001). Poorer visual attention was also associated with poorer overall cognitive status. The implications of these findings for early identification of MCI, prevention of functional decline in MCI, and delay/reversal of cognitive degradation in MCI are discussed. PMID:18584341

  4. Interaction of Cognitive Distortions and Cognitive Deficits in the Formulation and Treatment of Obsessive-Compulsive Behaviours in a Woman with an Intellectual Disability

    ERIC Educational Resources Information Center

    Willner, Paul; Goodey, Rebecca

    2006-01-01

    Aims: This case study describes the formulation and cognitive-behavioural treatment (CBT) of obsessive-compulsive thoughts and behaviours in a woman with an intellectual disability. The report aimed to distinguish the cognitive deficits that reflect her disability from the cognitive distortions integral to her obsessive-compulsive disorder. Case…

  5. Cognitive Rehabilitation for Attention Deficit/Hyperactivity Disorder (ADHD): Promises and Problems

    PubMed Central

    Tajik-Parvinchi, Diana; Wright, Leah; Schachar, Russell

    2014-01-01

    Objective: Cognitive training entails the repeated exercise of a specific cognitive process over a period of time to improve performance on the trained task as well as on tasks that were not specifically trained (transfer effect). Cognitive training shows promise in remediating deficits in children with attention deficit/hyperactivity disorder (ADHD) – a disorder believed to stem from deficient cognitive processes – where the focus has been primarily on training working memory and attention. We discuss evidence from studies that have produced broad, limited, or no transfer effects with the goal of identifying factors that may be responsible for this heterogeneity. Results: There are several implicit assumptions that appear to drive researchers’ decisions regarding both the selection of cognitive abilities to train as well as the training tasks chosen to target those abilities. We identify these implicit assumptions and their weaknesses. We also draw attention to design limitations that may be contributing to lack of transfer. Conclusion: Although the overall pattern of findings from these studies is promising, the methodological and theoretical limitations associated with the literature limit conclusions about the efficacy of cognitive training as a rehabilitation method for ADHD. We hypothesize several suggestions that may improve training effects and summarize the evidence which led to our hypotheses. PMID:25320614

  6. Reactive oxygen species mediate cognitive deficits in experimental temporal lobe epilepsy.

    PubMed

    Pearson, Jennifer N; Rowley, Shane; Liang, Li-Ping; White, Andrew M; Day, Brian J; Patel, Manisha

    2015-10-01

    Cognitive dysfunction is an important comorbidity of temporal lobe epilepsy (TLE). However, no targeted therapies are available and the mechanisms underlying cognitive impairment, specifically deficits in learning and memory associated with TLE remain unknown. Oxidative stress is known to occur in the pathogenesis of TLE but its functional role remains to be determined. Here, we demonstrate that oxidative stress and resultant processes contribute to cognitive decline associated with epileptogenesis. Using a synthetic catalytic antioxidant, we show that pharmacological removal of reactive oxygen species (ROS) prevents 1) oxidative stress, 2) deficits in mitochondrial oxygen consumption rates, 3) hippocampal neuronal loss and 4) cognitive dysfunction without altering the intensity of the initial status epilepticus (SE) or epilepsy development in a rat model of SE-induced TLE. Moreover, the effects of the catalytic antioxidant on cognition persisted beyond the treatment period suggestive of disease-modification. The data implicate oxidative stress as a novel mechanism by which cognitive dysfunction can arise during epileptogenesis and suggest a potential disease-modifying therapeutic approach to target it. PMID:26184893

  7. A cognitive psychometric model for the psychodiagnostic assessment of memory-related deficits.

    PubMed

    Alexander, Gregory E; Satalich, Timothy A; Shankle, W Rodman; Batchelder, William H

    2016-03-01

    Clinical tests used for psychodiagnostic purposes, such as the well-known Alzheimer's Disease Assessment Scale: Cognitive subscale (ADAS-Cog), include a free-recall task. The free-recall task taps into latent cognitive processes associated with learning and memory components of human cognition, any of which might be impaired with the progression of Alzheimer's disease (AD). A Hidden Markov model of free recall is developed to measure latent cognitive processes used during the free-recall task. In return, these cognitive measurements give us insight into the degree to which normal cognitive functions are differentially impaired by medical conditions, such as AD and related disorders. The model is used to analyze the free-recall data obtained from healthy elderly participants, participants diagnosed as having mild cognitive impairment, and participants diagnosed with early AD. The model is specified hierarchically to handle item differences because of the serial position curve in free recall, as well as within-group individual differences in participants' recall abilities. Bayesian hierarchical inference is used to estimate the model. The model analysis suggests that the impaired patients have the following: (1) long-term memory encoding deficits, (2) short-term memory (STM) retrieval deficits for all but very short time intervals, (3) poorer transfer into long-term memory for items successfully retrieved from STM, and (4) poorer retention of items encoded into long-term memory after longer delays. Yet, impaired patients appear to have no deficit in immediate recall of encoded words in long-term memory or for very short time intervals in STM. PMID:26214016

  8. The Outcome of a Social Cognitive Training for Mainstream Adolescents with Social Communication Deficits in a Chinese Community

    ERIC Educational Resources Information Center

    Lee, Kathy Y. S.; Crooke, Pamela J.; Lui, Aster L. Y.; Kan, Peggy P. K.; Mark, Yuen-mai; van Hasselt, Charles Andrew; Tong, Michael C. F.

    2016-01-01

    The use of cognitive-based strategies for improving social communication behaviours for individuals who have solid language and cognition is an important question. This study investigated the outcome of teaching Social Thinking®, a framework based in social-cognition, to Chinese adolescents with social communication deficits. Thirty-nine students…

  9. RPS23RG1 reduces Aβ oligomer-induced synaptic and cognitive deficits

    PubMed Central

    Yan, Li; Chen, Yaomin; Li, Wubo; Huang, Xiumei; Badie, Hedieh; Jian, Fan; Huang, Timothy; Zhao, Yingjun; Cohen, Stanley N.; Li, Limin; Zhang, Yun-wu; Luo, Huanmin; Tu, Shichun; Xu, Huaxi

    2016-01-01

    Alzheimer’s disease (AD) is the most common form of dementia in the elderly. It is generally believed that β-amyloidogenesis, tau-hyperphosphorylation, and synaptic loss underlie cognitive decline in AD. Rps23rg1, a functional retroposed mouse gene, has been shown to reduce Alzheimer’s β-amyloid (Aβ) production and tau phosphorylation. In this study, we have identified its human homolog, and demonstrated that RPS23RG1 regulates synaptic plasticity, thus counteracting Aβ oligomer (oAβ)-induced cognitive deficits in mice. The level of RPS23RG1 mRNA is significantly lower in the brains of AD compared to non-AD patients, suggesting its potential role in the pathogenesis of the disease. Similar to its mouse counterpart, human RPS23RG1 interacts with adenylate cyclase, activating PKA/CREB, and inhibiting GSK-3. Furthermore, we show that human RPS23RG1 promotes synaptic plasticity and offsets oAβ-induced synaptic loss in a PKA-dependent manner in cultured primary neurons. Overexpression of Rps23rg1 in transgenic mice consistently prevented oAβ-induced PKA inactivation, synaptic deficits, suppression of long-term potentiation, and cognitive impairment as compared to wild type littermates. Our study demonstrates that RPS23RG1 may reduce the occurrence of key elements of AD pathology and enhance synaptic functions to counteract oAβ-induced synaptic and cognitive deficits in AD. PMID:26733416

  10. Epilepsy, cognitive deficits and neuroanatomy in males with ZDHHC9 mutations

    PubMed Central

    Baker, Kate; Astle, Duncan E; Scerif, Gaia; Barnes, Jessica; Smith, Jennie; Moffat, Georgina; Gillard, Jonathan; Baldeweg, Torsten; Raymond, F Lucy

    2015-01-01

    Objective Systematic investigation of individuals with intellectual disability after genetic diagnosis can illuminate specific phenotypes and mechanisms relevant to common neurodevelopmental disorders. We report the neurological, cognitive and neuroanatomical characteristics of nine males from three families with loss-of-function mutations in ZDHHC9 (OMIM #300799). Methods All known cases of X-linked intellectual disability (XLID) due to ZDHHC9 mutation in the United Kingdom were invited to participate in a study of neurocognitive and neuroimaging phenotypes. Results Seven out of nine males with ZDHHC9 mutations had been diagnosed with epilepsy, exceeding epilepsy risk in XLID comparison subjects (P = 0.01). Seizure histories and EEG features amongst ZDHHC9 mutation cases shared characteristics with rolandic epilepsy (RE). Specific cognitive deficits differentiated males with ZDHHC9 mutations from XLID comparison subjects and converged with reported linguistic and nonlinguistic deficits in idiopathic RE: impaired oromotor control, reduced verbal fluency, and impaired inhibitory control on visual attention tasks. Consistent neuroanatomical abnormalities included thalamic and striatal volume reductions and hypoplasia of the corpus callosum. Interpretation Mutations in ZDHHC9 are associated with susceptibility to focal seizures and specific cognitive impairments intersecting with the RE spectrum. Neurocognitive deficits are accompanied by consistent abnormalities of subcortical structures and inter-hemispheric connectivity. The biochemical, cellular and network-level mechanisms responsible for the ZDHHC9-associated neurocognitive phenotype may be relevant to cognitive outcomes in RE. PMID:26000327

  11. Identifying learning disabilities through a cognitive deficit framework: can verbal memory deficits explain similarities between learning disabled and low achieving students?

    PubMed

    Callinan, Sarah; Theiler, Stephen; Cunningham, Everarda

    2015-01-01

    Traditionally, students with learning disabilities (LD) have been identified using an aptitude-achievement discrepancy or response to intervention approach. As profiles of the cognitive deficits of discrepancy-defined students with LD have already been developed using these approaches, these deficits can in turn be used to identify LD using the discrepancy approach as a benchmark for convergent validity. Australian Grade 3 (N = 172) students were administered cognitive processing tests to ascertain whether scores in these tests could accurately allocate students into discrepancy-defined groups using discriminant function analysis. Results showed that 77% to 82% of students could be correctly allocated into LD, low achievement, and regular achievement groups using only measures of phonological processing, rapid naming, and verbal memory. Furthermore, verbal memory deficits were found, along with phonological processing and rapid naming deficits, in students that would be designated as low achieving by the discrepancy method. Because a significant discrepancy or lack of response to intervention is a result of cognitive deficits rather than the other way around, it is argued that LD should be identified via cognitive deficits. PMID:23886581

  12. Pharmacological treatment of cognitive deficits in Alzheimer's disease.

    PubMed

    Brodaty, H; Ames, D; Boundy, K L; Hecker, J; Snowdon, J; Storey, E; Yates, M W

    2001-09-17

    Clinical trials and independent reviews support the use of cholinesterase inhibitors for treating the symptoms of patients with mild to moderate Alzheimer's disease (AD). Before initiating cholinesterase inhibitor therapy, patients should be thoroughly assessed, and the diagnosis confirmed, preferably by a specialist. Compliance with cholinesterase inhibitor therapy should be monitored and the response (in global, cognitive, functional and behavioural domains) reassessed after 2-3 months of treatment. Vitamin E may be protective against AD, and therapy with 1000 IU twice daily may be considered. There is insufficient evidence to support the use of other antioxidant agents, anti-inflammatory agents, monoamine oxidase B inhibitors, folate/homocysteine or antihypertensive drugs in patients with AD, or hormone replacement therapy in affected women. PMID:11665948

  13. Flavonoid Chrysin prevents age-related cognitive decline via attenuation of oxidative stress and modulation of BDNF levels in aged mouse brain.

    PubMed

    Souza, Leandro Cattelan; Antunes, Michelle Silva; Filho, Carlos Borges; Del Fabbro, Lucian; de Gomes, Marcelo Gomes; Goes, André Tiago Rossito; Donato, Franciele; Prigol, Marina; Boeira, Silvana Peterini; Jesse, Cristiano R

    2015-07-01

    In this study, the effect of Chrysin (5,7-dihydroxyflavone), an important member of the flavonoid family, on memory impairment, oxidative stress and BDNF reduction generated by aging in mice were investigated. Young and aged mice were treated daily per 60days with Chrysin (1 and 10mg/kg; per oral, p.o.) or veichle (10ml/kg; p.o.). Mice were trained and tested in Morris Water Maze task. After the behavioural test, the levels of reactive species (RS), the activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as the activity of Na(+), K(+)-ATPase and the levels of brain-derived neurotrophic factor (BDNF) were determined in the prefrontal cortex (PFC) and hippocampus (HC) of mice. Results demonstrated that the age-related memory decline was partially protected by Chrysin at a dose of 1mg/kg, and normalized at the dose of 10mg/kg (p<0.001). Treatment with Chrysin significantly attenuated the increase of RS levels and the inhibition of SOD, CAT and GPx activities of aged mice. Inhibition of Na(+), K(+)-ATPase activity in PFC and HP of aged mice was also attenuated by Chrysin treatment. Moreover, Chrysin marked mitigated the decrease of BDNF levels in the PFC and HC of aged mice. These results demonstrated that flavonoid Chrysin, an antioxidant compound, was able to prevent age-associated memory probably by their free radical scavenger action and modulation of BDNF production. Thus, this study indicates that Chrysin may represent a new pharmacological approach to alleviate the age-related declines during normal age, acting as an anti-aging agent. PMID:25931267

  14. Cognitive rehabilitation training in patients with brain tumor-related epilepsy and cognitive deficits: a pilot study.

    PubMed

    Maschio, Marta; Dinapoli, Loredana; Fabi, Alessandra; Giannarelli, Diana; Cantelmi, Tonino

    2015-11-01

    The aim of this pilot observational study was to evaluate effect of cognitive rehabilitation training (RehabTr) on cognitive performances in patients with brain tumor-related epilepsy (BTRE) and cognitive disturbances. Medical inclusion criteria: patients (M/F) ≥ 18 years ≤ 75 with symptomatic seizures due to primary brain tumors or brain metastases in stable treatment with antiepileptic drugs; previous surgical resection or biopsy; >70 Karnofsky Performance Status; stable oncological disease. Eligible patients recruited from 100 consecutive patients with BTRE at first visit to our Center from 2011 to 2012. All recruited patients were administered battery of neuropsychological tests exploring various cognitive domains. Patients considered to have a neuropsychological deficit were those with at least one test score for a given domain indicative of impairment. Thirty patients out of 100 showed cognitive deficits, and were offered participation in RehabTr, of which 16 accepted (5 low grade glioma, 4 high grade glioma, 2 glioblastoma, 2 meningioma and 3 metastases) and 14 declined for various reasons. The RehabTr consisted of one weekly individual session of 1 h, for a total of 10 weeks, carried out by a trained psychologist. The functions trained were: memory, attention, visuo-spatial functions, language and reasoning by means of Training NeuroPsicologico (TNP(®)) software. To evaluate the effect of the RehabTr, the same battery of tests was administered directly after cognitive rehabilitation (T1), and at six-month follow-up (T2). Statistical analysis with Student T test for paired data showed that short-term verbal memory, episodic memory, fluency and long term visuo-spatial memory improved immediately after the T1 and remained stable at T2. At final follow-up all patients showed an improvement in at least one domain that had been lower than normal at baseline. Our results demonstrated a positive effect of rehabilitative training at different times, and, for

  15. Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer's disease.

    PubMed

    Xiao, Rong

    2016-01-01

    Levetiracetam is a homologue of piracetam with an a-ethyl side-chain substitution and it is a Food and Drug Administration (FDA) approved antiepileptic drug. Recently, several studies have found that levetiracetam was able to reduce seizure frequency in epileptic seizures patients without affecting their cognitive functions. In the present review, the effects of levetiracetam on cognitive improvement were summarized in epileptic seizures patients with or without Alzheimer's disease (AD), high-grade glioma (HGG) patients and amnestic mild cognitive impairment (aMCI) patients. In addition, levetiracetam was observed to improve the cognitive deficits in normal aged animals and the transgenic animal models with AD, suggesting that levetiracetam may be a better choice for the prevention or treatment of AD. PMID:26268327

  16. Chronic oleoylethanolamide treatment improves spatial cognitive deficits through enhancing hippocampal neurogenesis after transient focal cerebral ischemia.

    PubMed

    Yang, Li-Chao; Guo, Han; Zhou, Hao; Suo, Da-Qin; Li, Wen-Jun; Zhou, Yu; Zhao, Yun; Yang, Wu-Shuang; Jin, Xin

    2015-04-15

    Oleoylethanolamide (OEA) has been shown to have neuroprotective effects after acute cerebral ischemic injury. The aim of this study was to investigate the effects of chronic OEA treatment on ischemia-induced spatial cognitive impairments, electrophysiology behavior and hippocampal neurogenesis. Daily treatments of 30 mg/kg OEA significantly ameliorated spatial cognitive deficits and attenuated the inhibition of long-term potentiation (LTP) in the middle cerebral artery occlusion (MCAO) rat model. Moreover, OEA administration improved cognitive function in a manner associated with enhanced neurogenesis in the hippocampus. Further study demonstrated that treatment with OEA markedly increased the expressions of brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptors α (PPARα). Our data suggest that chronic OEA treatment can exert functional recovery of cognitive impairments and neuroprotective effects against cerebral ischemic insult in rats via triggering of neurogenesis in the hippocampus, which supports the therapeutic use of OEA for cerebral ischemia. PMID:25748831

  17. Social Cognition Deficits and Psychopathic Traits in Young People Seeking Mental Health Treatment

    PubMed Central

    van Zwieten, Anita; Meyer, Johanna; Hermens, Daniel F.; Hickie, Ian B.; Hawes, David J.; Glozier, Nicholas; Naismith, Sharon L.; Scott, Elizabeth M.; Lee, Rico S. C.; Guastella, Adam J.

    2013-01-01

    Antisocial behaviours and psychopathic traits place an individual at risk for criminality, mental illness, substance dependence, and psychosocial dysfunction. Social cognition deficits appear to be associated with psychopathic traits and are believed to contribute to interpersonal dysfunction. Most research investigating the relationship of these traits with social cognition has been conducted either in children or adult forensic settings. We investigated whether psychopathic traits were associated with social cognition in 91 young people presenting for mental healthcare (aged between 15 and 25 years). Participants completed symptom severity measures, neuropsychological tests, the Reading the Mind in the Eyes Test of social cognition (RMET), and the Antisocial Process Screening Device (APSD) to assess psychopathic personality traits. Correlation analyses showed poorer social cognition was associated with greater psychopathic traits (r = −.36, p = .01). Interestingly, social cognition performance predicted unique variance in concurrent psychopathic personality traits above gender, IQ sustained attention, and working memory performance. These findings suggest that social cognitive impairments are associated with psychopathic tendencies in young people presenting for community mental healthcare. Research is needed to establish the directionality of this relationship and to determine whether social cognition training is an effective treatment amongst young people with psychopathic tendencies. PMID:23861799

  18. Pretreatment cognitive deficits and treatment effects on attention in childhood absence epilepsy

    PubMed Central

    Masur, David; Shinnar, Shlomo; Cnaan, Avital; Shinnar, Ruth C.; Clark, Peggy; Wang, Jichuan; Weiss, Erica F.; Hirtz, Deborah G.

    2013-01-01

    Objective: To determine the neurocognitive deficits associated with newly diagnosed untreated childhood absence epilepsy (CAE), develop a model describing the factorial structure of items measuring academic achievement and 3 neuropsychological constructs, and determine short-term differential neuropsychological effects on attention among ethosuximide, valproic acid, and lamotrigine. Methods: Subjects with newly diagnosed CAE entering a double-blind, randomized controlled clinical trial had neuropsychological testing including assessments of general intellectual functioning, attention, memory, executive function, and achievement. Attention was reassessed at the week 16–20 visit. Results: At study entry, 36% of the cohort exhibited attention deficits despite otherwise intact neurocognitive functioning. Structural equation modeling of baseline neuropsychological data revealed a direct sequential effect among attention, memory, executive function, and academic achievement. At the week 16–20 visit, attention deficits persisted even if seizure freedom was attained. More subjects receiving valproic acid (49%) had attention deficits than subjects receiving ethosuximide (32%) or lamotrigine (24%) (p = 0.0006). Parental assessment did not reliably detect attention deficits before or after treatment (p < 0.0001). Conclusions: Children with CAE have a high rate of pretreatment attentional deficits that persist despite seizure freedom. Rates are disproportionately higher for valproic acid treatment compared with ethosuximide or lamotrigine. Parents do not recognize these attentional deficits. These deficits present a threat to academic achievement. Vigilant cognitive and behavioral assessment of these children is warranted. Classification of evidence: This study provides Class I evidence that valproic acid is associated with more significant attentional dysfunction than ethosuximide or lamotrigine in children with newly diagnosed CAE. PMID:24089388

  19. Resting fMRI measures are associated with cognitive deficits in schizophrenia assessed by the MATRICS consensus cognitive battery

    NASA Astrophysics Data System (ADS)

    He, Hao; Bustillo, Juan; Du, Yuhui; Yu, Qingbao; Jones, Thomas R.; Jiang, Tianzi; Calhoun, Vince D.; Sui, Jing

    2015-03-01

    The cognitive deficits of schizophrenia are largely resistant to current treatment, and are thus a life-long burden to patients. The MATRICS consensus cognitive battery (MCCB) provides a reliable and valid assessment of cognition across a comprehensive set of cognitive domains for schizophrenia. In resting-state fMRI, functional connectivity associated with MCCB has not yet been examined. In this paper, the interrelationships between MCCB and the abnormalities seen in two types of functional measures from resting-state fMRI—fractional amplitude of low frequency fluctuations (fALFF) and functional network connectivity (FNC) maps were investigated in data from 47 schizophrenia patients and 50 age-matched healthy controls. First, the fALFF maps were generated and decomposed by independent component analysis (ICA), and then the component showing the highest correlation with MCCB composite scores was selected. Second, the whole brain was separated into functional networks by group ICA, and the FNC maps were calculated. The FNC strengths with most significant correlations with MCCB were displayed and spatially overlapped with the fALFF component of interest. It demonstrated increased cognitive performance associated with higher fALFF values (intensity of regional spontaneous brain activity) in prefrontal regions, inferior parietal lobe (IPL) but lower ALFF values in thalamus, striatum, and superior temporal gyrus (STG). Interestingly, the FNC showing significant correlations with MCCB were in well agreement with the activated regions with highest z-values in fALFF component. Our results support the view that functional deficits in distributed cortico-striato-thalamic circuits and inferior parietal lobe may account for several aspects of cognitive impairment in schizophrenia.

  20. The allusive cognitive deficit in paranoia: the case for mental time travel or cognitive self-projection.

    PubMed

    Corcoran, R

    2010-08-01

    Delusional beliefs are characteristic of psychosis and, of the delusions, the paranoid delusion is the single most common type associated with psychosis. The many years of research focused on neurocognition in schizophrenia, using standardized neurocognitive tests, have failed to find conclusive cognitive deficits in relation to positive symptoms. However, UK-based psychological research has identified sociocognitive anomalies in relation to paranoid thinking in the form of theory of mind (ToM), causal reasoning and threat-related processing anomalies. Drawing from recent neuroscientific research on the default mode network, this paper asserts that the common theme running through the psychological tests that are sensitive to the cognitive impairment of paranoia is the need to cognitively project the self through time, referred to as mental time travel. Such an understanding of the cognitive roots of paranoid ideation provides a synthesis between psychological and biological accounts of psychosis while also retaining the powerful argument that understanding abnormal thinking must start with models of normal cognition. This is the core theme running through the cognitive psychological literature of psychiatric disorders that enables research from this area to inform psychological therapy. PMID:20594394

  1. PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid β-Induced Cognitive Deficits through Modulation of Neuroinflammation.

    PubMed

    Park, Min Young; Jung, Yeon Suk; Park, Jung Hwa; Choi, Young Whan; Lee, Jaewon; Kim, Cheol Min; Baek, Jin Ung; Choi, Byung Tae; Shin, Hwa Kyoung

    2015-01-01

    PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ 25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ 25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD. PMID:25945111

  2. PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid β-Induced Cognitive Deficits through Modulation of Neuroinflammation

    PubMed Central

    Park, Min Young; Jung, Yeon Suk; Park, Jung Hwa; Lee, Jaewon; Kim, Cheol Min; Baek, Jin Ung; Shin, Hwa Kyoung

    2015-01-01

    PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ-) induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS-) stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ25−35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day) in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ25−35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD. PMID:25945111

  3. Spatial cognition following early-life seizures in rats: Performance deficits are dependent on task demands.

    PubMed

    Barry, Jeremy M; Tian, Chengju; Spinella, Anthony; Page, Matias; Holmes, Gregory L

    2016-07-01

    Cognitive impairment is a common comorbidity in childhood epilepsy. Studies in rodents have demonstrated that frequent seizures during the first weeks of life result in impaired spatial cognition when the rats are tested as juvenile or adults. To determine if spatial cognitive deficits following early-life seizures are task-specific or similar across spatial tasks, we compared the effects of early-life seizures in two spatial assays: 1) the Morris water maze, a hippocampal-dependent task of spatial cognition and 2) the active avoidance task, a task that associates an aversive shock stimulus with a static spatial location that requires intact hippocampal-amygdala networks. Rats with early-life seizures tested as adults did not differ from control rats in the water maze. However, while animals with early-life seizures showed some evidence of learning the active avoidance task, they received significantly more shocks in later training trials, particularly during the second training day, than controls. One possibility for the performance differences between the tasks is that the active avoidance task requires multiple brain regions and that interregional communication could be affected by alterations in white matter integrity. However, there were no measurable group differences with regard to levels of myelination. The study suggests that elucidation of mild cognitive deficits seen following early-life seizures may be dependent on task features of active avoidance. PMID:27152463

  4. Cognitive deficits in schizophrenia: an updated metanalysis of the scientific evidence

    PubMed Central

    2012-01-01

    Background This is an update of a previous meta-analysis published in 2005. Methods It includes the data published up to march 2010 for a total of 247 papers and 18,300 cases. Cognitive deficits are examined in 5 different domains: Memory functioning (128 studies), Global cognitive functioning (131 studies), Language (70 studies), Executive function (67 studies), Attention (76 studies). Only controlled studies were included: patients vs. normal subjects. Results Results evidence that in all domains and in all different analyses performed within each domain, patients show a significant reduction of cognitive efficiency with respect to normal subjects. The between studies heterogeneity is very high in almost all domains. There are various sources of this heterogeneity (age, sex, sample size, type of patients, and type of measurement) which contribute to the high degree of not-overlapping information offered by the single studies. Conclusions Our results, based on the current scientific evidence, confirm the previous findings that there is a generalized impairment of various cognitive functions in patients with schizophrenia when compared to normal cases. The modalities with which these results are obtained have not changed over the years and the more recent studies do not modify the high heterogeneity previously found between the studies. This reduces the methodological quality of the results. In order to improve the methodological quality of the studies performed in the field of cognitive deficits of patients with schizophrenia, various factors should be taken into account and better managed in designing future studies. PMID:22715980

  5. Reelin supplementation recovers synaptic plasticity and cognitive deficits in a mouse model for Angelman syndrome

    PubMed Central

    Hethorn, Whitney R; Ciarlone, Stephanie L; Filonova, Irina; Rogers, Justin T; Aguirre, Daniela; Ramirez, Raquel A; Grieco, Joseph C; Peters, Melinda M; Gulick, Danielle; Anderson, Anne E; L Banko, Jessica; Lussier, April L; Weeber, Edwin J

    2015-01-01

    The Reelin signaling pathway is implicated in processes controlling synaptic plasticity and hippocampus-dependent learning and memory. A single direct in vivo application of Reelin enhances long-term potentiation, increases dendritic spine density and improves associative and spatial learning and memory. Angelman syndrome (AS) is a neurological disorder that presents with an overall defect in synaptic function, including decreased long-term potentiation, reduced dendritic spine density, and deficits in learning and memory, making it an attractive model in which to examine the ability of Reelin to recover synaptic function and cognitive deficits. In this study, we investigated the effects of Reelin administration on synaptic plasticity and cognitive function in a mouse model of AS and demonstrated that bilateral, intraventricular injections of Reelin recover synaptic function and corresponding hippocampus-dependent associative and spatial learning and memory. Additionally, we describe alteration of the Reelin profile in tissue from both the AS mouse and post-mortem human brain. PMID:25864922

  6. Central catecholamine metabolism in vivo and the cognitive and motor deficits in Parkinson's disease.

    PubMed Central

    Mann, J J; Stanley, M; Kaplan, R D; Sweeney, J; Neophytides, A

    1983-01-01

    Cerebrospinal fluid levels of homovanillic acid (HVA) in unmedicated patients with Parkinson's disease were 45% of levels in control subjects. Levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) and platelet monoamine oxidase activity (MAO) did not differ. Within the Parkinson's disease group platelet MAO B activity correlated with HVA (an MAO B substrate) but not MHPG (an MAO A substrate). A mild global dementia was found that did not correlate with the more severe motor deficit. There was a negative correlation between the motor deficit and HVA levels but not with MHPG. Cognitive functioning correlated positively with platelet MAO, and the ratio of HVA to MHPG levels and negatively with MHPG alone. It is postulated that dopaminergic and noradrenergic activity or the functional balance between these systems may contribute to the observed cognitive dysfunction. PMID:6644314

  7. Self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia

    PubMed Central

    Shin, Yeon-Jeong; Joo, Yo-Han; Kim, Jong-Hoon

    2016-01-01

    Background We investigated self-perceived cognitive deficits and their relationship with internalized stigma and quality of life in patients with schizophrenia in order to shed light on the clinical correlates of subjective cognitive deficits in schizophrenia. Methods Seventy outpatients with schizophrenia were evaluated. Patients’ self-perceived cognitive deficits, internalized stigma, and subjective quality of life were assessed using the Scale to Investigate Cognition in Schizophrenia (SSTICS), the Internalized Stigma of Mental Illness Scale (ISMI), and the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4), respectively. Correlation and regression analyses controlling for the severity of symptoms of schizophrenia were performed, and a mediation analysis was conducted to examine the hypothesis that internalized stigma mediates the relationship between self-perceived cognitive deficits and subjective quality of life. Results Pearson’s partial correlation analysis showed significant correlations among the SSTICS, ISMI, and SQLS-R4 scores (P<0.01). Multiple regression analysis showed that the SSTICS and ISMI scores significantly predicted the SQLS-R4 score (P<0.01). Mediation analysis revealed that the strength of the association between the SSTICS and SQLS-R4 scores decreased from β=0.74 (P<0.01) to β=0.56 (P<0.01), when the ISMI score was statistically controlled. The Sobel test revealed that this difference was significant (P<0.01), indicating that internalized stigma partially mediated the relationship between self-perceived cognitive deficits and quality of life. Conclusion The present study indicates that self-perceived cognitive deficits are significantly associated with internalized stigma and quality of life. Furthermore, internalized stigma was identified as a partial mediator of the relationship between self-perceived cognitive deficits and quality of life. These findings suggest that clinicians should be aware that patients with

  8. Cognitive flexibility deficits in a mouse model for the absence of full-length dystrophin.

    PubMed

    Remmelink, E; Aartsma-Rus, A; Smit, A B; Verhage, M; Loos, M; van Putten, M

    2016-07-01

    Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disorder, caused by mutations in the DMD gene and the resulting lack of dystrophin. The DMD gene has seven promoters, giving rise to multiple full-length and shorter isoforms. Besides the expression of dystrophin in muscles, the majority of dystrophin isoforms is expressed in brain and dystrophinopathy can lead to cognitive deficits, including intellectual impairments and deficits in executive function. In contrast to the muscle pathology, the impact of the lack of dystrophin on the brain is not very well studied. Here, we study the behavioral consequences of a lack of full-length dystrophin isoforms in mdx mice, particularly with regard to domains of executive functions and anxiety. We observed a deficit in cognitive flexibility in mdx mice in the absence of motor dysfunction or general learning impairments using two independent behavioral tests. In addition, increased anxiety was observed, but its expression depended on the context. Overall, these results suggest that the absence of full-length dystrophin in mice has specific behavioral effects that compare well to deficits observed in DMD patients. PMID:27220066

  9. Modeling neurodevelopmental cognitive deficits in tasks with cross-species translational validity.

    PubMed

    Cope, Z A; Powell, S B; Young, J W

    2016-01-01

    Numerous psychiatric disorders whose cognitive dysfunction links to functional outcome have neurodevelopmental origins including schizophrenia, autism and bipolar disorder. Treatments are needed for these cognitive deficits, which require development using animal models. Models of neurodevelopmental disorders are as varied and diverse as the disorders themselves, recreating some but not all aspects of the disorder. This variety may in part underlie why purported procognitive treatments translated from these models have failed to restore functioning in the targeted patient populations. Further complications arise from environmental factors used in these models that can contribute to numerous disorders, perhaps only impacting specific domains, while diagnostic boundaries define individual disorders, limiting translational efficacy. The Research Domain Criteria project seeks to 'develop new ways to classify mental disorders based on behavioral dimensions and neurobiological measures' in hopes of facilitating translational research by remaining agnostic toward diagnostic borders derived from clinical presentation in humans. Models could therefore recreate biosignatures of cognitive dysfunction irrespective of disease state. This review highlights work within the field of neurodevelopmental models of psychiatric disorders tested in cross-species translational cognitive paradigms that directly inform this newly developing research strategy. By expounding on this approach, the hopes are that a fuller understanding of each model may be attainable in terms of the cognitive profile elicited by each manipulation. Hence, conclusions may begin to be drawn on the nature of cognitive neuropathology on neurodevelopmental and other disorders, increasing the chances of procognitive treatment development for individuals affected in specific cognitive domains. PMID:26667374

  10. Cognitive executive impairment and dopaminergic deficits in de novo Parkinson's disease.

    PubMed

    Siepel, Françoise J; Brønnick, Kolbjørn S; Booij, Jan; Ravina, Bernard M; Lebedev, Alexander V; Pereira, Joana B; Grüner, Renate; Aarsland, Dag

    2014-12-01

    Cognitive impairment in Parkinson's disease (PD) is common and does directly impact patients' everyday functioning. However, the underlying mechanisms of early cognitive decline are not known. This study explored the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naïve PD patients and tested the hypothesis that executive dysfunction in PD is associated with striatal dopaminergic depletion. A cross-sectional multicenter cohort of 339 PD patients and 158 healthy controls from the Parkinson's Progression Markers Initiative study was analyzed. Each individual underwent cerebral single-photon emission CT (SPECT) and a standardized neuropsychological assessment with tests of memory as well as visuospatial and executive function. SPECT imaging was performed with [(123) I]FP-CIT, and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios, cognitive domain scores, and age was analyzed using Pearson's correlations, partial correlation, and conditional process analysis. A small, but significant, positive association between total striatal dopamine transporter binding and the attention/executive domain was found (r = 0.141; P = 0.009) in PD, but this was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with PD were mediated by an age-moderated striatal dopaminergic deficit. Our findings support the hypothesis that nigrostriatal dopaminergic deficit is associated with executive impairment, but not to memory or visuospatial impairment, in early PD. PMID:25284687

  11. Pharmacological and genetic reversal of age dependent cognitive deficits due to decreased presenilin function

    PubMed Central

    McBride, Sean M. J.; Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Liebelt, David A.; Ferreiro, David; Choi, Richard J.; Hinchey, Paul; Kollaros, Maria; Terlizzi, Allison M.; Ferrick, Neal J.; Koenigsberg, Eric; Rudominer, Rebecca L.; Sumida, Ai; Chiorean, Stephanie; Siwicki, Kathleen K.; Nguyen, Hanh T.; Fortini, Mark E.; McDonald, Thomas V.; Jongens, Thomas A.

    2010-01-01

    Alzheimer's disease is the leading cause of cognitive loss and neurodegeneration in the developed world. Although its genetic and environmental causes are not generally known, familial forms of the disease (FAD) are due to mutations in a single copy of the Presenilin (PS) and Amyloid Precursor Protein (APP) genes. The dominant inheritance pattern of FAD indicates that it may be due to gain or change of function mutations. Studies of FAD-linked forms of presenilin in model organisms, however, indicate that they are loss of function, leading to the possibility that a reduction in PS activity might contribute to FAD and that proper psn levels are important for maintaining normal cognition throughout life. To explore this issue further, we have tested the effect of reducing psn activity during aging in Drosophila melanogaster males. We have found that flies in which the dosage of psn function is reduced by 50% display age-onset impairments in learning and memory. Treatment with metabotropic glutamate receptor (mGluR) antagonists or lithium during the aging process prevented the onset of these deficits, and treatment of aged flies reversed the age-dependent deficits. Genetic reduction of DmGluRA, the inositol trisphosphate receptor (InsP3R) or IPPase also prevented these age-onset cognitive deficits. These findings suggest that reduced psn activity may contribute to the age onset cognitive loss observed with FAD. They also indicate that enhanced mGluR signaling and calcium release regulated by InsP3R as underlying causes of the age-dependent cognitive phenotypes observed when psn activity is reduced. PMID:20631179

  12. Cognitive and olfactory deficits in Machado-Joseph disease: a dopamine transporter study.

    PubMed

    Braga-Neto, Pedro; Felicio, Andre C; Hoexter, Marcelo Q; Pedroso, José Luiz; Dutra, Lívia Almeida; Alessi, Helena; Minett, Thaís; Santos-Galduroz, Ruth F; da Rocha, Antônio José; Garcia, Lucas A L; Bertolucci, Paulo Henrique F; Bressan, Rodrigo A; Barsottini, Orlando Graziani Povoas

    2012-08-01

    Cognitive and olfactory impairments have been demonstrated in patients with Machado-Joseph disease (MJD), and a possible relationship with dopaminergic dysfunction is implicated. However, there is still controversy regarding the pattern of striatal dopaminergic dysfunction in patients with MJD. In this study, we investigated whether these patients had different dopamine transporter (DAT) densities as compared to healthy subjects, and correlated these data with cognitive performance and sense of smell. Twenty-two MJD patients and 20 control subjects were enrolled. The neuropsychological assessment comprised the spatial span, symbol search, picture completion, stroop color word test, trail making test and phonemic verbal fluency test. The 16-item Sniffin' Sticks was used to evaluate odor identification. DAT imaging was performed using the SPECT radioligand [(99m)Tc]-TRODAT-1, alongside with Magnetic Resonance imaging. Patients with MJD showed significantly lower DAT density in the caudate (1.34 ± 0.27 versus 2.02 ± 0.50, p < 0.001), posterior putamen (0.81 ± 0.32 versus 1.32 ± 0.34, p < 0.001) and anterior putamen (1.10 ± 0.31 versus 1.85 ± 0.45, p < 0.001) compared with healthy controls. The putamen/caudate ratio was also significantly lower in patients compared with controls (0.73 ± 0.038 versus 0.85 ± 0.032, p = 0.027). Even though we had only two patients with parkinsonism, we detected striatal dopaminergic deficits in those patients. No significant correlations were detected between DAT density and cognitive performance or Sniffin' Sticks scores. The data suggests that striatal dopamine deficit is not involved in cognitive or sense of smell deficits. This finding raises the possibility of extra-striatal dopamine and other neurotransmitter system involvement or of cerebellum neurodegeneration exerting a direct influence on cognitive and sensorial information processing in MJD. PMID:22575233

  13. Cognitive deficits of executive functions and decision-making in obsessive-compulsive disorder.

    PubMed

    Dittrich, Winand H; Johansen, Thomas

    2013-10-01

    The nature of cognitive deficits in obsessive-compulsive disorder (OCD) is characterized by contradictory findings in terms of specific neuropsychological deficits. Selective impairments have been suggested to involve visuospatial memory, set shifting, decision-making and response inhibition. The aim of this study was to investigate cognitive deficits in decision-making and executive functioning in OCD. It was hypothesized that the OCD patients would be less accurate in their responses compared to the healthy controls in rational decision-making on a version of the Cambridge gambling task (CGT) and on the color-word interference test and on a version of the Tower of Hanoi test (tower test) of executive functioning. Thirteen participants with OCD were compared to a group of healthy controls (n = 13) matched for age, gender, education and verbal IQ. Results revealed significant differences between the OCD group and the healthy control group on quality of decision-making on the CGT and for achievement score on the tower test. On these two tasks the OCD group performed worse than the healthy control group. The symptom-dimension analysis revealed performance differences where safety checking patients were impaired on the tower test compared to contamination patients. Results are discussed in the framework of cognition and emotion processing and findings implicate that OCD models should address, specifically, the interaction between cognition and emotion. Here the emotional disruption hypothesis is forwarded to account for the dysfunctional behaviors in OCD. Further implications regarding methodological and inhibitory factors affecting cognitive information processing are highlighted. PMID:23841985

  14. Emotional bias of cognitive control in adults with childhood attention-deficit/hyperactivity disorder.

    PubMed

    Schulz, Kurt P; Bédard, Anne-Claude V; Fan, Jin; Clerkin, Suzanne M; Dima, Danai; Newcorn, Jeffrey H; Halperin, Jeffrey M

    2014-01-01

    Affect recognition deficits found in individuals with attention-deficit/hyperactivity disorder (ADHD) across the lifespan may bias the development of cognitive control processes implicated in the pathophysiology of the disorder. This study aimed to determine the mechanism through which facial expressions influence cognitive control in young adults diagnosed with ADHD in childhood. Fourteen probands with childhood ADHD and 14 comparison subjects with no history of ADHD were scanned with functional magnetic resonance imaging while performing a face emotion go/no-go task. Event-related analyses contrasted activation and functional connectivity for cognitive control collapsed over face valence and tested for variations in activation for response execution and inhibition as a function of face valence. Probands with childhood ADHD made fewer correct responses and inhibitions overall than comparison subjects, but demonstrated comparable effects of face emotion on response execution and inhibition. The two groups showed similar frontotemporal activation for cognitive control collapsed across face valence, but differed in the functional connectivity of the right dorsolateral prefrontal cortex, with fewer interactions with the subgenual cingulate cortex, inferior frontal gyrus, and putamen in probands than in comparison subjects. Further, valence-dependent activation for response execution was seen in the amygdala, ventral striatum, subgenual cingulate cortex, and orbitofrontal cortex in comparison subjects but not in probands. The findings point to functional anomalies in limbic networks for both the valence-dependent biasing of cognitive control and the valence-independent cognitive control of face emotion processing in probands with childhood ADHD. This limbic dysfunction could impact cognitive control in emotional contexts and may contribute to the social and emotional problems associated with ADHD. PMID:24918067

  15. A Method for Investigating Age-related Differences in the Functional Connectivity of Cognitive Control Networks Associated with Dimensional Change Card Sort Performance

    PubMed Central

    DeBenedictis, Bianca; Morton, J. Bruce

    2014-01-01

    The ability to adjust behavior to sudden changes in the environment develops gradually in childhood and adolescence. For example, in the Dimensional Change Card Sort task, participants switch from sorting cards one way, such as shape, to sorting them a different way, such as color. Adjusting behavior in this way exacts a small performance cost, or switch cost, such that responses are typically slower and more error-prone on switch trials in which the sorting rule changes as compared to repeat trials in which the sorting rule remains the same. The ability to flexibly adjust behavior is often said to develop gradually, in part because behavioral costs such as switch costs typically decrease with increasing age. Why aspects of higher-order cognition, such as behavioral flexibility, develop so gradually remains an open question. One hypothesis is that these changes occur in association with functional changes in broad-scale cognitive control networks. On this view, complex mental operations, such as switching, involve rapid interactions between several distributed brain regions, including those that update and maintain task rules, re-orient attention, and select behaviors. With development, functional connections between these regions strengthen, leading to faster and more efficient switching operations. The current video describes a method of testing this hypothesis through the collection and multivariate analysis of fMRI data from participants of different ages. PMID:24837515

  16. Developmental trajectories of aggression, prosocial behavior, and social-cognitive problem solving in emerging adolescents with clinically elevated attention-deficit/hyperactivity disorder symptoms.

    PubMed

    Kofler, Michael J; Larsen, Ross; Sarver, Dustin E; Tolan, Patrick H

    2015-11-01

    Middle school is a critical yet understudied period of social behavioral risks and opportunities that may be particularly difficult for emerging adolescents with attention-deficit/hyperactivity disorder (ADHD) given their childhood social difficulties. Relatively few ADHD studies have examined social behavior and social-cognitive problem solving beyond the elementary years, or examined aspects of positive (prosocial) behavior. The current study examined how middle school students with clinically elevated ADHD symptoms differ from their non-ADHD peers on baseline (6th grade) and age-related changes in prosocial and aggressive behavior, and the extent to which social-cognitive problem solving strategies mediate these relations. Emerging adolescents with (n = 178) and without (n = 3,806) clinically elevated, teacher-reported ADHD-combined symptoms were compared longitudinally across 6th through 8th grades using parallel process latent growth curve modeling, accounting for student demographic characteristics, oppositional-defiant disorder (ODD) symptoms, deviant peer association, school climate, and parental monitoring. Sixth graders with elevated ADHD symptoms engaged in somewhat fewer prosocial behaviors (d = -0.44) and more aggressive behavior (d = 0.20) relative to their peers. These small social behavioral deficits decreased but were not normalized across the middle school years. Contrary to hypotheses, social-cognitive problem solving was not impaired in the ADHD group after accounting for co-occurring ODD symptoms and did not mediate the association between ADHD and social behavior during the middle school years. ADHD and social-cognitive problem solving contributed independently to social behavior, both in 6th grade and across the middle school years; the influence of social-cognitive problem solving on social behavior was highly similar for the ADHD and non-ADHD groups. PMID:26595479

  17. The aging memory: Modulating epigenetic modifications to improve cognitive function.

    PubMed

    Fonseca, Rosalina

    2016-09-01

    Age-related cognitive decline is a major concern in society. Here, I discuss recent evidence that shows an age-related modulation of gene transcription by epigenetic modifications. Epigenetic modifications, such as histone acetylation, is unbalanced in aging, with an increase in histone deacetylation, that limits the expression of plasticity-related genes. By modifying the balance towards histone acetylation, histone deacetylase inhibitors present a new pharmacological approach to ameliorate age-related cognitive deficits. PMID:27390098

  18. Cognitive Impairments of Children with Severe Arithmetic Difficulties: Cognitive Deficit or Developmental Lag?

    ERIC Educational Resources Information Center

    Berg, Derek H.

    2008-01-01

    An age-matched/achievement-matched design was utilized to examine the cognitive functioning of children with severe arithmetic difficulties. A battery of cognitive tasks was administered to three groups of elementary aged children: 20 children with severe arithmetic difficulties (SAD), 20 children matched in age (CAM) to the children with SAD, and…

  19. A Cross-Sectional Study of the Relationship of Physical Activity with Depression and Cognitive Deficit in Older Adults.

    PubMed

    Paulo T, R S; Tribess, Sheilla; Sasaki, Jeffer Eidi; Meneguci, Joilson; Martins, Cristiane A; Freitas, Ismael F; Romo-Perez, Vicente; Virtuoso, Jair S

    2016-04-01

    The aim of this study was to examine the association of physical activity with depression and cognition deficit, separately and combined, in Brazilian older adults. We analyzed data from 622 older adults. Physical activity was assessed using the International Physical Activity Questionnaire. Depressive symptoms were assessed using the Geriatric Depression Scale, while cognitive deficit was assessed using the Mini-Mental State Examination. Multinomial logistic regressions were used to assess associations of depression and cognitive deficit with sociodemographic, health, and behavioral variables. Prevalence of physical inactivity (< 150 min of moderate-to-vigorous physical activity/ week), depression, and cognitive deficit were 35.7%, 37.4%, and 16.7%. Physical inactivity was associated with depression (OR: 1.83, 95% CI: 1.14-2.94) and with depression and cognitive deficit combined (OR: 4.23, 95% CI: 2.01-8.91). Physically inactive participants were also more likely to present limitations in orientation and language functions. Physical inactivity was associated with depression and also with depression and cognitive deficit combined in older adults. PMID:26439455

  20. Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

    PubMed

    Nakagawa, Yutaka; Chiba, Kenji

    2016-09-01

    Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. PMID:27384073

  1. Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs.

    PubMed

    Calderón-Garcidueñas, Lilian; Mora-Tiscareño, Antonieta; Ontiveros, Esperanza; Gómez-Garza, Gilberto; Barragán-Mejía, Gerardo; Broadway, James; Chapman, Susan; Valencia-Salazar, Gildardo; Jewells, Valerie; Maronpot, Robert R; Henríquez-Roldán, Carlos; Pérez-Guillé, Beatriz; Torres-Jardón, Ricardo; Herrit, Lou; Brooks, Diane; Osnaya-Brizuela, Norma; Monroy, Maria E; González-Maciel, Angelica; Reynoso-Robles, Rafael; Villarreal-Calderon, Rafael; Solt, Anna C; Engle, Randall W

    2008-11-01

    Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children. PMID:18550243

  2. Correlations among central serotonergic parameters and age-related emotional and cognitive changes assessed through the elevated T-maze and the Morris water maze

    PubMed Central

    Oliveira, Luciana; Graeff, Frederico G.; Pereira, Silvia R. C.; Oliveira-Silva, Ieda F.; Franco, Glaura C.

    2010-01-01

    Emotion and spatial cognitive aspects were assessed in adult and middle-aged rats using the elevated T-maze (ETM) and the Morris water maze (MWM) tasks. Both adult and middle-aged rats were able to acquire inhibitory avoidance behaviour, though the middle-aged subjects showed larger latencies along the trials, including the baseline, which was significantly longer than that showed by adult rats. Further, compared to adult rats, middle-aged rats had longer escape latency. In spite of the worse performance in the second session of the spatial cognitive task, the middle-aged rats were able to learn the task and remember the information along the whole probe trial test. Both thalamic serotonin (5-HT) concentration and amygdala serotonergic activity (5-HIAA/5-HT) are significantly correlated, respectively, to escape latency and behavioural extinction in the MWM only for middle-aged rats. A significant correlation between the 5-HIAA/5-HT ratio in the amygdala and behavioural extinction for middle-aged, but not for adult, rats was observed. This result suggests that serotonergic activity in the amygdala may regulate behavioural flexibility in aged animals. In addition, a significant negative correlation was found between hippocampal 5-HIAA/5-HT ratio and the path length at the second training session of the MWM task, although only for adult subjects. This was the only session where a significant difference between the performance of middle-aged and adult rats has occurred. Although the involvement of the hippocampus in learning and memory is well established, the present work shows, for the first time, a correlation between a serotonergic hippocampal parameter and performance of a spatial task, which is lost with ageing. PMID:20431986

  3. Age-Related Macular Degeneration

    MedlinePlus

    ... this page please turn Javascript on. Age-related Macular Degeneration What is AMD? Click for more information Age-related macular degeneration, ... the macula allows you to see fine detail. AMD Blurs Central Vision AMD blurs the sharp central ...

  4. Overstimulation of newborn mice leads to behavioral differences and deficits in cognitive performance

    PubMed Central

    Christakis, D. A.; Ramirez, J. S. B.; Ramirez, J. M.

    2012-01-01

    Observational studies in humans have found associations between overstimulation in infancy via excessive television viewing and subsequent deficits in cognition and attention. We developed and tested a mouse model of overstimulation whereby p10 mice were subjected to audio (70 db) and visual stimulation (flashing lights) for six hours per day for a total of 42 days. 10 days later cognition and behavior were tested using the following tests: Light Dark Latency, Elevated Plus Maze, Novel Object Recognition, and Barnes Maze. In all tests, overstimulated mice performed significantly worse compared to controls suggesting increased activity and risk taking, diminished short term memory, and decreased cognitive function. These findings suggest that excessive non-normative stimulation during critical periods of brain development can have demonstrable untoward effects on subsequent neurocognitive function. PMID:22855702

  5. The smallest stroke: Occlusion of one penetrating vessel leads to infarction and a cognitive deficit

    PubMed Central

    Shih, Andy Y.; Blinder, Pablo; Tsai, Philbert S.; Friedman, Beth; Stanley, Geoffrey; Lyden, Patrick D.; Kleinfeld, David

    2014-01-01

    Microinfarctions are present in the aged and injured human brain. Their clinical significance is controversial, with postulated sequelae ranging from cognitive sparing to vascular dementia. To address the consequences of microinfarcts, we used controlled optical methods to create occlusions of individual penetrating arterioles or venules within rat cortex. Single microinfarcts, targeted to encompass all or part of a cortical column, impaired performance in a macrovibrissa-based behavioral task. Further, multiple targeted vessels caused tissue damage that coalesced across cortex, even though the intervening penetrating vessels were acutely patent. Post-occlusion administration of Memantine, a glutamate receptor antagonist that reduces cognitive decline in Alzheimer’s disease, ameliorated tissue damage and perceptual deficits. Collectively, these data imply that microinfarcts are likely contributors to cognitive decline. Strategies that have received limited success in the treatment of ischemic injury, which include therapeutics against excitotoxicity, may be successful against the progressive nature of vascular dementia. PMID:23242312

  6. Prevention, Rehabilitation, and Mitigation Strategies of Cognitive Deficits in Aging with HIV: Implications for Practice and Research

    PubMed Central

    Vance, David E.

    2013-01-01

    Highly active antiretroviral therapy has given the chance to those living with HIV to keep on living, allowing them the opportunity to age and perhaps age successfully. Yet, there are severe challenges to successful aging with HIV, one of which is cognitive deficits. Nearly half of those with HIV experience cognitive deficits that can interfere with everyday functioning, medical decision making, and quality of life. Given that cognitive deficits develop with more frequency and intensity with increasing age, concerns mount that as people age with HIV, they may experience more severe cognitive deficits. These concerns become especially germane given that by 2015, 50% of those with HIV will be 50 and older, and this older cohort of adults is expected to grow. As such, this paper focuses on the etiologies of such cognitive deficits within the context of cognitive reserve and neuroplasticity. From this, evidence-based and hypothetical prevention (i.e., cognitive prescriptions), rehabilitation (i.e., speed of processing training), and mitigation (i.e., spaced retrieval method) strategies are reviewed. Implications for nursing practice and research are posited. PMID:23431469

  7. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population.

    PubMed

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer's disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer's disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer's disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer's disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision disorders but

  8. Cognitive Impairment and Age-Related Vision Disorders: Their Possible Relationship and the Evaluation of the Use of Aspirin and Statins in a 65 Years-and-Over Sardinian Population

    PubMed Central

    Mandas, Antonella; Mereu, Rosa Maria; Catte, Olga; Saba, Antonio; Serchisu, Luca; Costaggiu, Diego; Peiretti, Enrico; Caminiti, Giulia; Vinci, Michela; Casu, Maura; Piludu, Stefania; Fossarello, Maurizio; Manconi, Paolo Emilio; Dessí, Sandra

    2014-01-01

    Neurological disorders (Alzheimer’s disease, vascular and mixed dementia) and visual loss (cataract, age-related macular degeneration, glaucoma, and diabetic retinopathy) are among the most common conditions that afflict people of at least 65 years of age. An increasing body of evidence is emerging, which demonstrates that memory and vision impairment are closely, significantly, and positively linked and that statins and aspirin may lessen the risk of developing age-related visual and neurological problems. However, clinical studies have produced contradictory results. Thus, the intent of the present study was to reliably establish whether a relationship exist between various types of dementia and age-related vision disorders, and to establish whether statins and aspirin may or may not have beneficial effects on these two types of disorders. We found that participants with dementia and/or vision problems were more likely to be depressed and displayed worse functional ability in basic and instrumental activities of daily living than controls. Mini mental state examination scores were significantly lower in patients with vision disorders compared to subjects without vision disorders. A closer association with macular degeneration was found in subjects with Alzheimer’s disease than in subjects without dementia or with vascular dementia, mixed dementia, or other types of age-related vision disorders. When we considered the associations between different types of dementia and vision disorders and the use of statins and aspirin, we found a significant positive association between Alzheimer’s disease and statins on their own or in combination with aspirin, indicating that these two drugs do not appear to reduce the risk of Alzheimer’s disease or improve its clinical evolution and may, on the contrary, favor its development. No significant association in statin use alone, aspirin use alone, or the combination of these was found in subjects without vision

  9. Cognitive deficits in patients with obsessive–compulsive disorder – electroencephalography correlates

    PubMed Central

    Kamaradova, Dana; Hajda, Miroslav; Prasko, Jan; Taborsky, Jiri; Grambal, Ales; Latalova, Klara; Ociskova, Marie; Brunovsky, Martin; Hlustik, Petr

    2016-01-01

    Background Obsessive–compulsive disorder (OCD) is associated with cognitive dysfunction. Although there are several studies focused on the neurobiology of OCD, little is known about the biological correlates of the cognitive deficit linked to this disorder. The aim of our study was to examine the association between cognitive impairment and current source density markers in patients with OCD. Methods Resting-state eyes-closed electroencephalography (EEG) data were recorded in 20 patients with OCD and 15 healthy controls who were involved in the study. Cortical EEG sources were estimated by standardized low-resolution electromagnetic tomography in seven frequency bands: delta (1.5–6 Hz), theta (6.5–8 Hz), alpha-1 (8.5–10 Hz), alpha-2 (10.5–12 Hz), beta-1 (12.5–18 Hz), beta-2 (18.5–21 Hz), and beta-3 (21.5–30 Hz). Cognitive performance was measured by the Trail-Making Test (versions A and B), Stroop CW Test, and D2 Test. Results Frontal delta and theta EEG sources showed significantly higher activity in the whole group of patients with OCD (N=20) than in control subjects (N=15). Subsequent analysis revealed that this excess of low-frequency activity was present only in the subgroup of eleven patients with cognitive impairment (based on the performance in the Trail-Making Test – A). The subgroup of patients with normal cognitive functions (N=9) did not differ in cortical EEG sources from healthy controls. Conclusion The present results suggest that frontal low-frequency cortical sources of resting-state EEG rhythms can distinguish groups of cognitively impaired and cognitively intact patients with OCD. Based on our results, future studies should consider whether the present methodological approach provides clinically useful information for the revelation of cognitive impairment in patients with OCD. PMID:27226716

  10. Mount Everest: a space analogue for speech monitoring of cognitive deficits and stress.

    PubMed

    Lieberman, Philip; Morey, Angie; Hochstadt, Jesse; Larson, Mara; Mather, Sandra

    2005-06-01

    In deep-space missions, the basal ganglia and hippocampus, subcortical structures of the brain that play critical roles in motor activity, cognition, and memory, will be vulnerable to damage from cosmic rays. These metabolically active structures are also sensitive to damage arising from the low oxygen content of air at extreme altitudes. We have, therefore, used Mount Everest as an analogue for deep space, where astronauts will be subject to danger and stress as well as neural damage. We can ethically obtain data because our climber-subjects already intend to climb Mt. Everest. We record speech and test cognitive and linguistic performance before, during, and after exposure to hypoxic conditions. From these data we have derived and validated computer-implemented acoustic voice measures that track slight as well as profound cognitive impairment. Vowel duration and speech motor sequencing errors increase as climbers ascend, reflecting degraded basal ganglia activity. These metrics detect deficits in language comprehension and the ability to change plans in changing circumstances. Preliminary analyses also reveal memory deficits reflecting hippocampal damage. Our speech metrics are unobtrusive and do not reveal the content of a verbal message; they could be derived automatically, allowing space crews to detect subtle motor and cognitive deficits and invoke countermeasures before performance is profoundly impaired. In future work we will be validating the voice metrics of stress in collaboration with the Dinges NSBRI laboratory study of task-induced stress. Our procedures can also be applied in general aviation and in the treatment of Parkinson's disease, Alzheimer's dementia, and other neurological disorders. PMID:15943213

  11. Age-Related White Matter Changes

    PubMed Central

    Xiong, Yun Yun; Mok, Vincent

    2011-01-01

    Age-related white matter changes (WMC) are considered manifestation of arteriolosclerotic small vessel disease and are related to age and vascular risk factors. Most recent studies have shown that WMC are associated with a host of poor outcomes, including cognitive impairment, dementia, urinary incontinence, gait disturbances, depression, and increased risk of stroke and death. Although the clinical relevance of WMC has been extensively studied, to date, only very few clinical trials have evaluated potential symptomatic or preventive treatments for WMC. In this paper, we reviewed the current understanding in the pathophysiology, epidemiology, clinical importance, chemical biomarkers, and treatments of age-related WMC. PMID:21876810

  12. Effect of Neuroscience-Based Cognitive Skill Training on Growth of Cognitive Deficits Associated with Learning Disabilities in Children Grades 2-4

    ERIC Educational Resources Information Center

    Avtzon, Sarah Abitbol

    2012-01-01

    Working memory, executive functions, and cognitive processes associated with specific academic areas, are empirically identified as being the core underlying cognitive deficits in students with specific learning disabilities. Using Hebb's theory of neuroplasticity and the principle of automaticity as theoretical bases, this experimental study…

  13. Prospective study of Dietary Approaches to Stop Hypertension– and Mediterranean-style dietary patterns and age-related cognitive change: the Cache County Study on Memory, Health and Aging123

    PubMed Central

    Munger, Ronald G; Cutler, Adele; Quach, Anna; Bowles, Austin; Corcoran, Christopher; Tschanz, JoAnn T; Norton, Maria C; Welsh-Bohmer, Kathleen A

    2013-01-01

    Background: Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent. Objective: We examined associations between Dietary Approaches to Stop Hypertension (DASH)– and Mediterranean-style dietary patterns and age-related cognitive change in a prospective, population-based study. Design: Participants included 3831 men and women ≥65 y of age who were residents of Cache County, UT, in 1995. Cognitive function was assessed by using the Modified Mini-Mental State Examination (3MS) ≤4 times over 11 y. Diet-adherence scores were computed by summing across the energy-adjusted rank-order of individual food and nutrient components and categorizing participants into quintiles of the distribution of the diet accordance score. Mixed-effects repeated-measures models were used to examine 3MS scores over time across increasing quintiles of dietary accordance scores and individual food components that comprised each score. Results: The range of rank-order DASH and Mediterranean diet scores was 1661–25,596 and 2407–26,947, respectively. Higher DASH and Mediterranean diet scores were associated with higher average 3MS scores. People in quintile 5 of DASH averaged 0.97 points higher than those in quintile 1 (P = 0.001). The corresponding difference for Mediterranean quintiles was 0.94 (P = 0.001). These differences were consistent over 11 y. Higher intakes of whole grains and nuts and legumes were also associated with higher average 3MS scores [mean quintile 5 compared with 1 differences: 1.19 (P < 0.001), 1.22 (P < 0.001), respectively]. Conclusions: Higher levels of accordance with both the DASH and Mediterranean dietary patterns were associated with consistently higher levels of cognitive function in elderly men and women over an 11-y period. Whole grains and nuts and legumes were positively associated with higher cognitive functions and may be core neuroprotective foods common to various healthy plant

  14. Cognitive Deficits Associated with Nav1.1 Alterations: Involvement of Neuronal Firing Dynamics and Oscillations

    PubMed Central

    Bender, Alex C.; Luikart, Bryan W.; Lenck-Santini, Pierre-Pascal

    2016-01-01

    Brain oscillations play a critical role in information processing and may, therefore, be essential to uncovering the mechanisms of cognitive impairment in neurological disease. In Dravet syndrome (DS), a mutation in SCN1A, coding for the voltage-gated sodium channel Nav1.1, is associated with severe cognitive impairment and seizures. While seizure frequency and severity do not correlate with the extent of impairment, the slowing of brain rhythms may be involved. Here we investigate the role of Nav1.1 on brain rhythms and cognition using RNA interference. We demonstrate that knockdown of Nav1.1 impairs fast- and burst-firing properties of neurons in the medial septum in vivo. The proportion of neurons that fired phase-locked to hippocampal theta oscillations was reduced, and medial septal regulation of theta rhythm was disrupted. During a working memory task, this deficit was characterized by a decrease in theta frequency and was negatively correlated with performance. These findings suggest a fundamental role for Nav1.1 in facilitating fast-firing properties in neurons, highlight the importance of precise temporal control of theta frequency for working memory, and imply that Nav1.1 deficits may disrupt information processing in DS via a dysregulation of brain rhythms. PMID:26978272

  15. Emotion recognition and cognitive empathy deficits in adolescent offenders revealed by context-sensitive tasks

    PubMed Central

    Gonzalez-Gadea, Maria Luz; Herrera, Eduar; Parra, Mario; Gomez Mendez, Pedro; Baez, Sandra; Manes, Facundo; Ibanez, Agustin

    2014-01-01

    Emotion recognition and empathy abilities require the integration of contextual information in real-life scenarios. Previous reports have explored these domains in adolescent offenders (AOs) but have not used tasks that replicate everyday situations. In this study we included ecological measures with different levels of contextual dependence to evaluate emotion recognition and empathy in AOs relative to non-offenders, controlling for the effect of demographic variables. We also explored the influence of fluid intelligence (FI) and executive functions (EFs) in the prediction of relevant deficits in these domains. Our results showed that AOs exhibit deficits in context-sensitive measures of emotion recognition and cognitive empathy. Difficulties in these tasks were neither explained by demographic variables nor predicted by FI or EFs. However, performance on measures that included simpler stimuli or could be solved by explicit knowledge was either only partially affected by demographic variables or preserved in AOs. These findings indicate that AOs show contextual social-cognition impairments which are relatively independent of basic cognitive functioning and demographic variables. PMID:25374529

  16. Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder.

    PubMed

    Cai, Chenxi; Yuan, Kai; Yin, Junsen; Feng, Dan; Bi, Yanzhi; Li, Yangding; Yu, Dahua; Jin, Chenwang; Qin, Wei; Tian, Jie

    2016-03-01

    Internet gaming disorder (IGD), identified in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) Section III as a condition warranting more clinical research, may be associated with impaired cognitive control. Previous IGD-related studies had revealed structural abnormalities in the prefrontal cortex, an important part of prefrontal-striatal circuits, which play critical roles in cognitive control. However, little is known about the relationship between the striatal nuclei (caudate, putamen, and nucleus accumbens) volumes and cognitive control deficit in individuals with IGD. Twenty-seven adolescents with IGD and 30 age-, gender- and education-matched healthy controls participated in this study. The volume differences of the striatum were assessed by measuring subcortical volume in FreeSurfer. Meanwhile, the Stroop task was used to detect cognitive control deficits. Correlation analysis was used to investigate the relationship between striatal volumes and performance in the Stroop task as well as severity in IGD. Relative to controls, the IGD committed more incongruent condition response errors during the Stroop task and showed increased volumes of dorsal striatum (caudate) and ventral striatum (nucleus accumbens). In addition, caudate volume was correlated with Stroop task performance and nucleus accumbens (NAc) volume was associated with the internet addiction test (IAT) score in the IGD group. The increased volumes of the right caudate and NAc and their association with behavioral characteristics (i.e., cognitive control and severity) in IGD were detected in the present study. Our findings suggest that the striatum may be implicated in the underlying pathophysiology of IGD. PMID:25720356

  17. Characteristics of cognitive deficits and writing skills of Polish adults with developmental dyslexia.

    PubMed

    Bogdanowicz, Katarzyna Maria; Łockiewicz, Marta; Bogdanowicz, Marta; Pąchalska, Maria

    2014-07-01

    The present study was aimed at analysing cognitive deficits of dyslexic adults, and examining their written language skills in comparison with their peers. Our results confirm the presence of a certain profile of symptoms in adult dyslexics. We noticed deficits in: phonological (verbal) short-term memory, phonological awareness, rapid automatised naming (speed, self-corrections), visual perception and control, and visual-motor coordination. Moreover, the dyslexic participants, as compared with their nondyslexic peers, produced more word structure errors whilst writing an essay. However, there were no significant differences between the two groups in the length of the essay, the number of linguistic and punctuation errors, the number of adjectives, and stylistic devices. PMID:23524010

  18. Deficits of cognitive restructuring in major depressive disorder: Measured by textual micro-counseling dialogues.

    PubMed

    Jiang, Nengzhi; Yu, Fei; Zhang, Wencai; Zhang, Jianxin

    2016-04-30

    Cognitive restructuring is an important strategy in cognitive behavioral therapy (CBT). The present study aimed to observe cognitive restructuring in major depressive disorder (MDD) patients using textual micro-counseling dialogue situations. A set of textual micro-counseling dialogues was used to trigger cognitive restructuring in 25 MDD patients and 27 healthy adults. The participants read descriptions ("problems") and explanations ("solutions") for psychologically distressing situations. High-, low-, and zero-restructuring solutions were randomly matched to the problems. The participants evaluated the adaptability and emotional valence of the problems and the insightfulness, adaptability, novelty, and emotional valence of the solutions. Insightfulness ratings for high-restructuring solutions were significantly higher relative to those of low-restructuring solutions in healthy adults, while adaptability ratings for low-restructuring solutions were significantly higher relative to those of high-restructuring solutions in MDD patients. Insightfulness ratings for the solutions were significantly predicted by novelty and adaptability in healthy adults and emotional valence in MDD patients. Lower insightfulness in high-restructuring solutions and higher adaptability in low-restructuring solutions in MDD patients may reflect deficits in cognitive control. PMID:27086227

  19. Manganese exposure and cognitive deficits: A growing concern for manganese neurotoxicity⋆

    PubMed Central

    Roels, H.A.; Bowler, R.M.; Kim, Y.; Henn, B. Claus; Mergler, D.; Hoet, P.; Gocheva, V.V.; Bellinger, D.C.; Wright, R.O.; Harris, M.G.; Chang, Y.; Bouchard, M.F.; Riojas-Rodriguez, H.; Menezes-Filho, J.A.; Téllez-Rojo, Martha Maria

    2013-01-01

    This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children’s cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. PMID:22498092

  20. Manganese exposure and cognitive deficits: a growing concern for manganese neurotoxicity.

    PubMed

    Roels, H A; Bowler, R M; Kim, Y; Claus Henn, B; Mergler, D; Hoet, P; Gocheva, V V; Bellinger, D C; Wright, R O; Harris, M G; Chang, Y; Bouchard, M F; Riojas-Rodriguez, H; Menezes-Filho, J A; Téllez-Rojo, Martha Maria

    2012-08-01

    This symposium comprised five oral presentations dealing with recent findings on Mn-related cognitive and motor changes from epidemiological studies across the life span. The first contribution highlighted the usefulness of functional neuroimaging of the central nervous system (CNS) to evaluate cognitive as well as motor deficits in Mn-exposed welders. The second dealt with results of two prospective studies in Mn-exposed workers or welders showing that after decrease of Mn exposure the outcome of reversibility in adverse CNS effects may differ for motor and cognitive function and, in addition the issue of plasma Mn as a reliable biomarker for Mn exposure in welders has been addressed. The third presentation showed a brief overview of the results of an ongoing study assessing the relationship between environmental airborne Mn exposure and neurological or neuropsychological effects in adult Ohio residents living near a Mn point source. The fourth paper focused on the association between blood Mn and neurodevelopment in early childhood which seems to be sensitive to both low and high Mn concentrations. The fifth contribution gave an overview of six studies indicating a negative impact of excess environmental Mn exposure from air and drinking water on children's cognitive performance, with special attention to hair Mn as a potential biomarker of exposure. These studies highlight a series of questions about Mn neurotoxicity with respect to cognitive processes, forms and routes of exposure, adequate biomarkers of exposure, gender differences, susceptibility and exposure limits with regard to age. PMID:22498092

  1. Blocking leukotriene synthesis attenuates the pathophysiology of traumatic brain injury and associated cognitive deficits

    PubMed Central

    Corser-Jensen, Chelsea E.; Goodell, Dayton J.; Freund, Ronald K.; Serbedzija, Predrag; Murphy, Robert C.; Farias, Santiago E.; Dell'Acqua, Mark L.; Frey, Lauren C.; Serkova, Natalie; Heidenreich, Kim A.

    2014-01-01

    Neuroinflammation is a component of secondary injury following traumatic brain injury (TBI) that can persist beyond the acute phase. Leukotrienes are potent, pro-inflammatory lipid mediators generated from membrane phospholipids. In the absence of injury, leukotrienes are undetectable in brain, but after trauma they are rapidly synthesized by a transcellular event involving infiltrating neutrophils and endogenous brain cells. Here, we investigate the efficacy of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP), in blocking leukotriene synthesis, secondary brain damage, synaptic dysfunction, and cognitive impairments after TBI. Male Sprague Dawley rats (9-11 weeks) received either MK-886 or vehicle after they were subjected to unilateral moderate fluid percussion injury (FPI) to assess the potential clinical use of FLAP inhibitors for TBI. MK-886 was also administered before FPI to determine the preventative potential of FLAP inhibitors. MK-886 given before or after injury significantly blocked the production of leukotrienes, measured by reverse-phase liquid chromatography coupled to tandem mass spectrometry (RP LC-MS/MS), and brain edema, measured by T2-weighted magnetic resonance imaging (MRI). MK-886 significantly attenuated blood-brain barrier disruption in the CA1 hippocampal region and deficits in long-term potentiation (LTP) at CA1 hippocampal synapses. The prevention of FPI-induced synaptic dysfunction by MK-886 was accompanied by fewer deficits in post-injury spatial learning and memory performance in the radial arms water maze (RAWM). These results indicate that leukotrienes contribute significantly to secondary brain injury and subsequent cognitive deficits. FLAP inhibitors represent a novel anti-inflammatory approach for treating human TBI that is feasible for both intervention and prevention of brain injury and neurologic deficits. PMID:24681156

  2. Age-related decline of precision and binding in visual working memory.

    PubMed

    Peich, Muy-Cheng; Husain, Masud; Bays, Paul M

    2013-09-01

    Working memory declines with normal aging, but the nature of this impairment is debated. Studies based on detecting changes to arrays of visual objects have identified two possible components to age-related decline: a reduction in the number of items that can be stored, or a deficit in maintaining the associations (bindings) between individual object features. However, some investigations have reported intact binding with aging, and specific deficits arising only in Alzheimer's disease. Here, using a recently developed continuous measure of recall fidelity, we tested the precision with which adults of different ages could reproduce from memory the orientation and color of a probed array item. The results reveal a further component of cognitive decline: an age-related decrease in the resolution with which visual information can be maintained in working memory. This increase in recall variability with age was strongest under conditions of greater memory load. Moreover, analysis of the distribution of errors revealed that older participants were more likely to incorrectly report one of the unprobed items in memory, consistent with an age-related increase in misbinding. These results indicate a systematic decline with age in working memory resources that can be recruited to store visual information. The paradigm presented here provides a sensitive index of both memory resolution and feature binding, with the potential for assessing their modulation by interventions. The findings have implications for understanding the mechanisms underpinning working memory deficits in both health and disease. PMID:23978008

  3. Calpain inhibitor AK295 attenuates motor and cognitive deficits following experimental brain injury in the rat.

    PubMed Central

    Saatman, K E; Murai, H; Bartus, R T; Smith, D H; Hayward, N J; Perri, B R; McIntosh, T K

    1996-01-01

    Marked increases in intracellular calcium may play a role in mediating cellular dysfunction and death following central nervous system trauma, in part through the activation of the calcium-dependent neutral protease calpain. In this study, we evaluated the effect of the calpain inhibitor AK295 [Z-Leu-aminobutyric acid-CONH(CH2)3-morpholine] on cognitive and motor deficits following lateral fluid percussion brain injury in rats. Before injury, male Sprague-Dawley rats (350-425 g) were trained to perform a beam-walking task and to learn a cognitive test using a Morris water maze paradigm. Animals were subjected to fluid percussion injury (2.2-2.4 atm; 1 atm = 101.3 kPa) and, beginning at 15 min postinjury, received a continuous intraarterial infusion of AK295 (120-140 mg/kg, n = 15) or vehicle (n= 16) for 48 hr. Sham (uninjured) animals received either drug (n = 5) or vehicle (n = 10). Animals were evaluated for neurobehavioral motor function at 48 hr and 7 days postinjury and were tested in the Morris water maze to evaluate memory retention at 7 days postinjury. At 48 hr, both vehicle- and AK295-treated injured animals showed significant neuromotor deficits (P< 0.005). At 7 days, injured animals that received vehicle continued to exhibit significant motor dysfunction (P< 0.01). However, brain-injured, AK295-treated animals showed markedly improved motor scores (P<0.02), which were not significantly different from sham (uninjured) animals. Vehicle-treated, injured animals demonstrated a profound cognitive deficit (P< 0.001), which was significantly attenuated by AK295 treatment (P< 0.05). To our knowledge, this study is the first to use a calpain inhibitor following brain trauma and suggests that calpain plays a role in the posttraumatic events underlying memory and neuromotor dysfunction. PMID:8622952

  4. Focal cerebral hypoperfusion and selective cognitive deficit in dementia of the Alzheimer type.

    PubMed Central

    Celsis, P; Agniel, A; Puel, M; Rascol, A; Marc-Vergnes, J P

    1987-01-01

    Regional cerebral blood flow was investigated using single photon emission computed tomography and xenon-133 intravenous injection in six patients with dementia of the Alzheimer type (DAT) with atypical focal clinical presentation, and in 20 age-matched healthy volunteers. The patients had a progressive and preponderant cognitive deficit and a focal hypoperfusion that correlated with the neuropsychological findings, whereas the average flow did not significantly differ from that of controls. The assessment of concordant haemodynamic and neuropsychological focal abnormalities could be useful in the diagnosis of atypical cases of DAT. Images PMID:3501801

  5. Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic interneurons.

    PubMed

    Bissonette, Gregory B; Bae, Mihyun H; Suresh, Tejas; Jaffe, David E; Powell, Elizabeth M

    2014-02-01

    Alterations of inhibitory GABAergic neurons are implicated in multiple psychiatric and neurological disorders, including schizophrenia, autism and epilepsy. In particular, interneuron deficits in prefrontal areas, along with presumed decreased inhibition, have been reported in several human patients. The majority of forebrain GABAergic interneurons arise from a single subcortical source before migrating to their final regional destination. Factors that govern the interneuron populations have been identified, demonstrating that a single gene mutation may globally affect forebrain structures or a single area. In particular, mice lacking the urokinase plasminogen activator receptor (Plaur) gene have decreased GABAergic interneurons in frontal and parietal, but not caudal, cortical regions. Plaur assists in the activation of hepatocyte growth factor/scatter factor (HGF/SF), and several of the interneuron deficits are correlated with decreased levels of HGF/SF. In some cortical regions, the interneuron deficit can be remediated by endogenous overexpression of HGF/SF. In this study, we demonstrate decreased parvalbumin-expressing interneurons in the medial frontal cortex, but not in the hippocampus or basal lateral amygdala in the Plaur null mouse. The Plaur null mouse demonstrates impaired medial frontal cortical function in extinction of cued fear conditioning and the inability to form attentional sets. Endogenous HGF/SF overexpression increased the number of PV-expressing cells in medial frontal cortical areas to levels greater than found in wildtype mice, but did not remediate the behavioral deficits. These data suggest that proper medial frontal cortical function is dependent upon optimum levels of inhibition and that a deficit or excess of interneuron numbers impairs normal cognition. PMID:24211452

  6. Prefrontal cognitive deficits in mice with altered cerebral cortical GABAergic interneurons

    PubMed Central

    Bissonette, Gregory B.; Bae, Mihyun H.; Suresh, Tejas; Jaffe, David E.; Powell, Elizabeth M.

    2013-01-01

    Alterations of inhibitory GABAergic neurons are implicated in multiple psychiatric and neurological disorders, including schizophrenia, autism and epilepsy. In particular, interneuron deficits in prefrontal areas, along with presumed decreased inhibition, have been reported in several human patients. The majority of forebrain GABAergic interneurons arise from a single subcortical source before migrating to their final regional destination. Factors that govern the interneuron populations have been identified, demonstrating that a single gene mutation may globally affect forebrain structures or a single area. In particular, mice lacking the urokinase plasminogen activator receptor (Plaur) gene have decreased GABAergic interneurons in frontal and parietal, but not caudal, cortical regions. Plaur assists in the activation of hepatocyte growth factor/scatter factor (HGF/SF), and several of the interneuron deficits are correlated with decreased levels of HGF/SF. In some cortical regions, the interneuron deficit can be remediated by endogenous overexpression of HGF/SF. In this study, we demonstrate decreased parvalbumin-expressing interneurons in the medial frontal cortex, but not in the hippocampus or basal lateral amygdala in the Plaur null mouse. The Plaur null mouse demonstrates impaired medial frontal cortical function in extinction of cued fear conditioning and the inability to form attentional sets. Endogenous HGF/SF overexpression increased the number of PV-expressing cells in medial frontal cortical areas to levels greater than found in wildtype mice, but did not remediate the behavioral deficits. These data suggest that proper medial frontal cortical function is dependent upon optimum levels of inhibition and that a deficit or excess of interneuron numbers impairs normal cognition. PMID:24211452

  7. [The histaminergic system: a target for innovative treatments of cognitive deficits].

    PubMed

    Motawaj, Mouhammad; Burban, Aude; Davenas, Elisabeth; Gbahou, Florence; Faucard, Raphaël; Morisset, Séverine; Arrang, Jean-Michel

    2010-01-01

    The central effects of histamine are mediated by H(1), H(2) and H(3) receptors. The H(3) receptor inhibits histamine release in brain. Therefore, H(3) receptor inverse agonists, by suppressing this brake, enhance histamine neuron activity. The histaminergic system plays a major role in cognition and H(3) receptor inverse agonists are expected to be a potential therapeutics for cognitive deficits of Alzheimer's disease (AD). They are eagerly awaited inasmuch as other treatments of the disease, such as tacrine or memantine, also enhance, through different mechanisms, histaminergic neurotransmission. An important loss of histaminergic neurons has been observed in AD. In contrast, levels of the histamine metabolite in the CSF of AD patients show that their global activity is decreased by only 25%. This indicates that activating histamine neurons in AD can be envisaged. PMID:21144476

  8. Alzheimer's disease: role of size and location of white matter changes in determining cognitive deficits.

    PubMed

    Bracco, L; Piccini, C; Moretti, M; Mascalchi, M; Sforza, A; Nacmias, B; Cellini, E; Bagnoli, S; Sorbi, S

    2005-01-01

    This study investigated the contribution that white matter changes (WMCs) make to clinical and cognitive features in Alzheimer's disease (AD), independently of possible confounders such as cortical atrophy and the apolipoprotein E genotype as well as their relationship to vascular risk factors. We semiquantitatively assessed the degree and location of WMCs (global, periventricular and deep white matter), lacunes and global atrophy on brain MRI scans of 86 AD cases, extensively evaluated from a clinical and neuropsychological point of view. Multivariate logistic and linear regression analysis showed that age was the only significant predictor of all WMC measures and revealed a significant association of periventricular WMCs with performance on executive function tasks as well as of deep WMCs with history of mood depression. Our results underline the significance of WMC location over size in the occurrence of specific cognitive deficits in AD. PMID:16192726

  9. Blue-yellow colour vision impairment and cognitive deficits in occasional and dependent stimulant users.

    PubMed

    Hulka, Lea M; Wagner, Michael; Preller, Katrin H; Jenni, Daniela; Quednow, Boris B

    2013-04-01

    Specific blue-yellow colour vision impairment has been reported in dependent cocaine users and it was postulated that drug-induced changes in retinal dopamine neurotransmission are responsible. However, it is unclear whether these changes are confined to chronic cocaine users, whether they are specific for dopaminergic stimulants such as cocaine and amphetamine and whether they are related to cognitive functions such as working memory, encoding and consolidation. In 47 occasional and 29 dependent cocaine users, 23 MDMA (commonly known as 'ecstasy') users and 47 stimulant-naive controls, colour vision discrimination was measured with the Lanthony Desaturated Panel D-15 Test and memory performance with the Auditory Verbal Learning Test. Both occasional and dependent cocaine users showed higher colour confusion indices than controls. Users of the serotonergic stimulant MDMA (26%), occasional (30%) and dependent cocaine users (34%) exhibited more frequent blue-yellow colour vision disorders compared to controls (9%). Inferior performance of MDMA users was caused by a subgroup with high amphetamine co-use (55%), while MDMA use alone was not associated with decreased blue-yellow discrimination (0%). Cognitive performance was worse in cocaine users with colour vision disorder compared to users and controls with intact colour vision and both colour vision impairment and cognitive deficits were related to cocaine use. Occasional cocaine and amphetamine use might induce blue-yellow colour vision impairment, whereas the serotonergic stimulant MDMA does not impair colour vision. The association between colour vision impairment and cognitive deficits in cocaine users may reflect that retinal and cerebral dopamine alterations are linked to a certain degree. PMID:22704223

  10. Early detection of cognitive deficits in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Stover, Kurt R; Campbell, Mackenzie A; Van Winssen, Christine M; Brown, Richard E

    2015-08-01

    Which behavioral test is the most sensitive for detecting cognitive deficits in the 3xTg-AD at 6.5 months of age? The 3xTg-AD mouse model of Alzheimer's disease (AD) has three transgenes (APPswe, PS1M146V, and Tau P301L) which cause the development of amyloid beta plaques, neurofibrillary tangles, and cognitive deficits with age. In order to determine which task is the most sensitive in the early detection of cognitive deficits, we compared male and female 3xTg-AD and B6129SF2 wildtype mice at 6.5 months of age on a test battery including spontaneous alternation in the Y-Maze, novel object recognition, spatial memory in the Barnes maze, and cued and contextual fear conditioning. The 3xTg-AD mice had impaired learning and memory in the Barnes maze but performed better than B6129SF2 wildtype mice in the Y-Maze and in contextual fear conditioning. Neither genotype demonstrated a preference in the novel object recognition task nor was there a genotype difference in cued fear conditioning but females performed better than males. From our results we conclude that the 3xTg-AD mice have mild cognitive deficits in spatial learning and memory and that the Barnes maze was the most sensitive test for detecting these cognitive deficits in 6.5-month-old mice. PMID:25896362

  11. Canonical correlation analysis of synchronous neural interactions and cognitive deficits in Alzheimer's dementia

    NASA Astrophysics Data System (ADS)

    Karageorgiou, Elissaios; Lewis, Scott M.; Riley McCarten, J.; Leuthold, Arthur C.; Hemmy, Laura S.; McPherson, Susan E.; Rottunda, Susan J.; Rubins, David M.; Georgopoulos, Apostolos P.

    2012-10-01

    In previous work (Georgopoulos et al 2007 J. Neural Eng. 4 349-55) we reported on the use of magnetoencephalographic (MEG) synchronous neural interactions (SNI) as a functional biomarker in Alzheimer's dementia (AD) diagnosis. Here we report on the application of canonical correlation analysis to investigate the relations between SNI and cognitive neuropsychological (NP) domains in AD patients. First, we performed individual correlations between each SNI and each NP, which provided an initial link between SNI and specific cognitive tests. Next, we performed factor analysis on each set, followed by a canonical correlation analysis between the derived SNI and NP factors. This last analysis optimally associated the entire MEG signal with cognitive function. The results revealed that SNI as a whole were mostly associated with memory and language, and, slightly less, executive function, processing speed and visuospatial abilities, thus differentiating functions subserved by the frontoparietal and the temporal cortices. These findings provide a direct interpretation of the information carried by the SNI and set the basis for identifying specific neural disease phenotypes according to cognitive deficits.

  12. Stress acts cumulatively to precipitate Alzheimer's disease-like tau pathology and cognitive deficits.

    PubMed

    Sotiropoulos, Ioannis; Catania, Caterina; Pinto, Lucilia G; Silva, Rui; Pollerberg, G Elizabeth; Takashima, Akihiko; Sousa, Nuno; Almeida, Osborne F X

    2011-05-25

    Stressful life experiences are likely etiological factors in sporadic forms of Alzheimer's disease (AD). Many AD patients hypersecrete glucocorticoids (GCs), and their GC levels correlate with the rate of cognitive impairment and extent of neuronal atrophy. Severity of cognitive deficits in AD correlates strongly with levels of hyperphosphorylated forms of the cytoskeletal protein TAU, an essential mediator of the actions of amyloid β (Aβ), another molecule with a key pathogenic role in AD. Our objective was to investigate the sequential interrelationships between these various pathogenic elements, in particular with respect to the mechanisms through which stress might precipitate cognitive decline. We thus examined whether stress, through the mediation of GCs, influences TAU hyperphosphorylation, a critical and early event in the cascade of processes leading to AD pathology. Results from healthy, wild-type, middle-aged rats show that chronic stress and GC induce abnormal hyperphosphorylation of TAU in the hippocampus and prefrontal cortex (PFC), with contemporaneous impairments of hippocampus- and PFC-dependent behaviors. Exogenous GC potentiated the ability of centrally infused Aβ to induce hyperphosphorylation of TAU epitopes associated with AD and cytoplasmic accumulation of TAU, while previous exposure to stress aggravated the biochemical and behavioral effects of GC in Aβ-infused animals. Thus, lifetime stress/GC exposure may have a cumulative impact on the onset and progress of AD pathology, with TAU hyperphosphorylation serving to transduce the negative effects of stress and GC on cognition. PMID:21613497

  13. Inhibition of inflammation by astaxanthin alleviates cognition deficits in diabetic mice.

    PubMed

    Zhou, Xiaoyan; Zhang, Fang; Hu, Xiaotong; Chen, Jing; Wen, Xiangru; Sun, Ying; Liu, Yonghai; Tang, Renxian; Zheng, Kuiyang; Song, Yuanjian

    2015-11-01

    Neurons in the hippocampal and cortical functional regions are more susceptible to damage induced by hyperglycemia, which can result in severe spatial learning and memory impairment. Neuroprotection ameliorates cognitive impairment induced by hyperglycemia in diabetic encephalopathy (DE). Astaxanthin has been widely studied in diabetes mellitus and diabetic complications due to its hypoglycemic, antioxidant and anti-apoptotic effects. However, whether astaxanthin can alleviate cognition deficits induced by DE and its precise mechanisms remain undetermined. In this study, DE was induced by streptozotocin (STZ, 150 mg/kg) in ICR mice. We observed the effect of astaxanthin on cognition and investigated its potential mechanisms in DE mice. Results showed that astaxanthin treatment significantly decreased the latency and enhanced the distance and time spent in the target quadrant in the Morris water maze test. Furthermore, neuronal survival was significantly increased in the hippocampal CA3 region and the frontal cortex following treatment with astaxanthin. Meanwhile, immunoblotting was used to observe the nuclear translocation of nuclear factor-kappaB (NF-κB) p65 and the expression of tumor necrosis factor-α (TNF-α) in the hippocampus and frontal cortex. The results indicated that astaxanthin could inhibit NF-κB nuclear translocation and downregulate TNF-α expression in the hippocampus and frontal cortex. Overall, the present study implied that astaxanthin could improve cognition by protecting neurons against inflammation injury potentially through inhibiting the nuclear translocation of NF-κB and down-regulating TNF-α. PMID:26272354

  14. Cognitive heterogeneity in adult attention deficit/hyperactivity disorder: A systematic analysis of neuropsychological measurements.

    PubMed

    Mostert, Jeanette C; Onnink, A Marten H; Klein, Marieke; Dammers, Janneke; Harneit, Anais; Schulten, Theresa; van Hulzen, Kimm J E; Kan, Cornelis C; Slaats-Willemse, Dorine; Buitelaar, Jan K; Franke, Barbara; Hoogman, Martine

    2015-11-01

    Attention Deficit/Hyperactivity Disorder (ADHD) in childhood is associated with impaired functioning in multiple cognitive domains: executive functioning (EF), reward and timing. Similar impairments have been described for adults with persistent ADHD, but an extensive investigation of neuropsychological functioning in a large sample of adult patients is currently lacking. We systematically examined neuropsychological performance on tasks measuring EF, delay discounting, time estimation and response variability using univariate ANCOVA's comparing patients with persistent ADHD (N=133, 42% male, mean age 36) and healthy adults (N=132, 40% male, mean age 36). In addition, we tested which combination of variables provided the highest accuracy in predicting ADHD diagnosis. We also estimated for each individual the severity of neuropsychological dysfunctioning. Lastly, we investigated potential effects of stimulant medication and a history of comorbid major depressive disorder (MDD) on performance. Compared to healthy adults, patients with ADHD showed impaired EF, were more impulsive, and more variable in responding. However, effect sizes were small to moderate (range: 0.05-0.70) and 11% of patients did not show neuropsychological dysfunctioning. The best fitting model predicting ADHD included measures from distinct cognitive domains (82.1% specificity, 64.9% sensitivity). Furthermore, patients receiving stimulant medication or with a history of MDD were not distinctively impaired. To conclude, while adults with ADHD as a group are impaired on several cognitive domains, the results confirm that adult ADHD is neuropsychologically heterogeneous. This provides a starting point to investigate individual differences in terms of impaired cognitive pathways. PMID:26336867

  15. Cholesterol diet counteracts repeated anesthesia/infusion-induced cognitive deficits in male Brown Norway rats

    PubMed Central

    Hohsfield, Lindsay A.; Ehrlich, Daniela; Humpel, Christian

    2015-01-01

    A variety of cardiovascular and cerebrovascular diseases are associated with alterations in cholesterol levels and metabolism. Moreover, convincing evidence shows that high cholesterol diet can lead to learning and memory impairments. On the other hand, a significant body of research has also demonstrated that learning is improved by elevated dietary cholesterol. Despite these conflicting findings, it is clear that cholesterol plays an important role in these cognitive properties. However, it remains unclear how this blood-brain barrier (BBB)-impenetrable molecule affects the brain and under what circumstances it provides either detrimental or beneficial effects to learning and memory. The aim of this study was to characterize the effects of 5% cholesterol diet on six-month-old inbred Brown Norway rats. More important, we sought to examine the role that cholesterol can play when repeated anesthesia and intravenous infusion disrupts cognitive function. This present study supports previous work showing that enriched cholesterol diet leads to significant alterations in neuroinflammation and BBB disruption. Following repeated anesthesia and intravenous infusion of saline we observe that animals under normal diet conditions exhibit significant deficiencies in spatial learning and cholinergic neuron populations compared to animals under enriched cholesterol diet, which do not show such deficiencies. These findings indicate that cholesterol diet can protect against or counteract anesthesia/infusion-induced cognitive deficits. Ultimately, these results suggest that cholesterol homeostasis serves an important functional role in the brain and that altering this homeostasis can either exert positive or negative effects on cognitive properties. PMID:23973449

  16. Number Processing and Heterogeneity of Developmental Dyscalculia: Subtypes With Different Cognitive Profiles and Deficits.

    PubMed

    Skagerlund, Kenny; Träff, Ulf

    2016-01-01

    This study investigated if developmental dyscalculia (DD) in children with different profiles of mathematical deficits has the same or different cognitive origins. The defective approximate number system hypothesis and the access deficit hypothesis were tested using two different groups of children with DD (11-13 years old): a group with arithmetic fact dyscalculia (AFD) and a group with general dyscalculia (GD). Several different aspects of number magnitude processing were assessed in these two groups and compared with age-matched typically achieving children. The GD group displayed weaknesses with both symbolic and nonsymbolic number processing, whereas the AFD group displayed problems only with symbolic number processing. These findings provide evidence that the origins of DD in children with different profiles of mathematical problems diverge. Children with GD have impairment in the innate approximate number system, whereas children with AFD suffer from an access deficit. These findings have implications for researchers' selection procedures when studying dyscalculia, and also for practitioners in the educational setting. PMID:24598147

  17. Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin

    PubMed Central

    Ma, Ping; Liu, Xudong; Wu, Jiliang; Yan, Biao; Zhang, Yuchao; Lu, Yu; Wu, Yang; Liu, Chao; Guo, Junhui; Nanberg, Eewa; Bornehag, Carl-Gustaf; Yang, Xu

    2015-01-01

    Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-а] and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects. PMID:26424168

  18. Personality disturbances in amyotrophic lateral sclerosis: a case study demonstrating changes in personality without cognitive deficits.

    PubMed

    Waldron, Eric J; Barrash, Joseph; Swenson, Andrea; Tranel, Daniel

    2014-08-01

    Patients with amyotrophic lateral sclerosis (ALS) often show deficits on neuropsychological tests that tap functions related to the integrity of the prefrontal lobes. Various aspects of personality are also known to be mediated by prefrontal regions, particularly ventromedial prefrontal cortex (vmPFC). Other than apathy, personality changes have not been widely reported in patients with ALS, although clinical observations indicate such changes might be relatively common. Here, we report on a middle-aged woman with bulbar onset ALS (diagnosed 06/2011, examined in Spring, 2012) whose neuropsychological exam did not reveal cognitive deficits. She performed normally on tests of executive functioning. Self-report measures of mood and personality were unremarkable. However, significant personality changes subsequent to disease onset were reported by her husband and two daughters, and these changes were quantified with the Iowa Scales of Personality Change. Results show that personality disturbance may manifest in the absence of notable cognitive changes in ALS, and careful assessment of personality may be important for documenting early neurobehavioral changes in some ALS patients. Findings also show that patients with ALS may not have good insight into personality changes, underscoring the importance of acquiring collateral information. More generally, the results provide further evidence that ALS may compromise the integrity of ventromedial prefrontal regions. PMID:24854881

  19. Cognitive deficits and anxiety induced by diisononyl phthalate in mice and the neuroprotective effects of melatonin.

    PubMed

    Ma, Ping; Liu, Xudong; Wu, Jiliang; Yan, Biao; Zhang, Yuchao; Lu, Yu; Wu, Yang; Liu, Chao; Guo, Junhui; Nanberg, Eewa; Bornehag, Carl-Gustaf; Yang, Xu

    2015-01-01

    Diisononyl phthalate (DINP) is a plasticizer that is frequently used as a substitute for other plasticizers whose use is prohibited in certain products. In vivo studies on the neurotoxicity of DINP are however, limited. This work aims to investigate whether DINP causes neurobehavioral changes in mice and to provide useful advice on preventing the occurrence of these adverse effects. Behavioral analysis showed that oral administration of 20 or 200 mg/kg/day DINP led to mouse cognitive deficits and anxiety. Brain histopathological observations, immunohistochemistry assays (cysteine-aspartic acid protease 3 [caspase-3], glial fibrillary acidic protein [GFAP]), oxidative stress assessments (reactive oxygen species [ROS], glutathione [GSH], superoxide dismutase [SOD] activities, 8-hydroxy-2-deoxyguanosine [8-OH-dG] and DNA-protein crosslinks [DPC]), and assessment of inflammation (tumor necrosis factor alpha [TNF-а] and interleukin-1 beta [IL-1β]) of mouse brains showed that there were histopathological alterations in the brain and increased levels of oxidative stress, and inflammation for these same groups. However, some of these effects were blocked by administration of melatonin (50 mg/kg/day). Down-regulation of oxidative stress was proposed to explain the neuroprotective effects of melatonin. The data suggests that DINP could cause cognitive deficits and anxiety in mice, and that melatonin could be used to avoid these adverse effects. PMID:26424168

  20. Macular degeneration - age-related

    MedlinePlus

    Age-related macular degeneration (ARMD); AMD ... distorted and wavy. There may be a small dark spot in the center of your vision that ... leafy vegetables, may also decrease your risk of age-related macular degeneration. If you have wet AMD, ...

  1. Vitamin D3 attenuates oxidative stress and cognitive deficits in a model of toxic demyelination

    PubMed Central

    Tarbali, Sepideh; Khezri, Shiva

    2016-01-01

    Objective(s): Multiple sclerosis (MS) is a demyelinating disease. The prevalence of MS is highest where environmental supplies of vitamin D are low. Cognitive deficits have been observed in patients with MS. Oxidative damage may contribute to the formation of MS lesions. Considering the involvement of hippocampus in MS, an attempt is made in this study to investigate the effects of vitamin D3 on behavioral process and the oxidative status in the dorsal hippocampus (CA1 area) following the induction of experimental demyelination in rats. Materials and Methods: Animals were divided into six groups. Control group: animals received no surgery and treatment; saline group: animals received normal saline; sham group: animals received 150 μl sesame oil IP; vitamin D3 group: animals received 5 μg/kg vitamin D3 IP; lysophosphatidyl choline (LPC) group (toxic demyelination’s model): animals received LPC by stereotaxic intra-hippocampal injection of 2 μl LPC in CA1 area; Vitamin D3- treated group: animals were treated with vitamin D3 at doses of 5 μg/kg IP for 7 and 21 days post lesion. The spatial memory, biochemical parameters including catalase (CAT) activities and lipid peroxidation levels were investigated. Results: Animals in LPC group had more deficits in spatial memory than the control group in radial arm maze. Vitamin D3 significantly improved spatial memory compared to LPC group. Also, results indicated that vitamin D3 caused a decrease in lipid peroxidation levels and an increase in CAT activities. Conclusion: Current findings suggest that vitamin D3 may have a protective effect on cognitive deficits and oxidative stress in toxic demyelination’s model. PMID:27096068

  2. Chronic periadolescent alcohol consumption produces persistent cognitive deficits in rhesus macaques.

    PubMed

    Wright, M Jerry; Taffe, Michael A

    2014-11-01

    Although human alcoholics exhibit lasting cognitive deficits, it can be difficult to definitively rule out pre-alcohol performance differences. For example, individuals with a family history of alcoholism are at increased risk for alcoholism and are also behaviorally impaired. Animal models of controlled alcohol exposure permit balanced group assignment, thereby ruling out the effects of pre-existing differences. Periadolescent male rhesus macaques (N = 5) consumed alcohol during 200 drinking sessions (M-F) across a 10-month period (mean daily alcohol consumption: 1.38 g/kg/day). A control group (N = 5) consumed a fruit-flavored vehicle during the same period. Spatial working memory, visual discrimination learning and retention and response time behavioral domains were assessed with subtests of the Monkey CANTAB (CAmbridge Neuropsychological Test Automated Battery). Spatial working memory performance was impaired in the alcohol group after 120 drinking sessions (6 mo) in a manner that depended on retention interval. The chronic alcohol animals were also impaired in retaining a visual discrimination over 24 hrs when assessed 6-8 weeks after cessation of alcohol drinking. Finally, the presentation of distractors in the response time task impaired the response time and accuracy of the chronic alcohol group more than controls after 6 months of alcohol cessation. Chronic alcohol consumption over as little as 6 months produces cognitive deficits, with some domains still affected after acute (6-8 wks) and lasting (6 mo) discontinuation from drinking. Animals were matched on alcohol preference and behavioral performance prior to exposure, thus providing strong evidence for the causal role of chronic alcohol in these deficits. PMID:25018042

  3. Early deficits in motor coordination and cognitive dysfunction in a mouse model of the neurodegenerative lysosomal storage disorder, Sandhoff disease

    PubMed Central

    Gulinello, Maria; Chen, Fengying; Dobrenis, Kostantin

    2014-01-01

    Mouse models of lysosomal storage diseases, including Sandhoff disease, are frequently employed to test therapies directed at the central nervous system. We backbred such mice and conducted a behavioral test battery which included sensorimotor and cognitive assessments. This is the first report of short-term memory deficits in a murine model of Sandhoff disease. We also document early onset of motor deficits using the balance beam test. PMID:18611415

  4. Early Cognitive Deficits in Type 2 Diabetes: A Population-Based Study

    PubMed Central

    Marseglia, Anna; Fratiglioni, Laura; Laukka, Erika J.; Santoni, Giola; Pedersen, Nancy L.; Bäckman, Lars; Xu, Weili

    2016-01-01

    Evidence links type 2 diabetes to dementia risk. However, our knowledge on the initial cognitive deficits in diabetic individuals and the factors that might promote such deficits is still limited. This study aimed to identify the cognitive domains initially impaired by diabetes and the factors that play a role in this first stage. Within the population-based Swedish National Study on Aging and Care–Kungsholmen, 2305 cognitively intact participants aged ≥60 y were identified. Attention/working memory, perceptual speed, category fluency, letter fluency, semantic memory, and episodic memory were assessed. Diabetes (controlled and uncontrolled) and prediabetes were ascertained by clinicians, who also collected information on vascular disorders (hypertension, heart diseases, and stroke) and vascular risk factors (VRFs, including smoking and overweight/obesity). Data were analyzed with linear regression models. Overall, 196 participants (8.5%) had diabetes, of which 144 (73.5%) had elevated glycaemia (uncontrolled diabetes); 571 (24.8%) persons had prediabetes. In addition, diabetes, mainly uncontrolled, was related to lower performance in perceptual speed (β – 1.10 [95% CI – 1.98, – 0.23]), category fluency (β – 1.27 [95% CI – 2.52, – 0.03]), and digit span forward (β – 0.35 [95% CI – 0.54, – 0.17]). Critically, these associations were present only among APOE ɛ4 non–carriers. The associations of diabetes with perceptual speed and category fluency were present only among participants with VRFs or vascular disorders. Diabetes, especially uncontrolled diabetes, is associated with poorer performance in perceptual speed, category fluency, and attention/primary memory. VRFs, vascular disorders, and APOE status play a role in these associations. PMID:27314527

  5. Nobiletin treatment improves motor and cognitive deficits seen in MPTP-induced Parkinson model mice.

    PubMed

    Yabuki, Y; Ohizumi, Y; Yokosuka, A; Mimaki, Y; Fukunaga, K

    2014-02-14

    Nobiletin, a polymethoxylated flavonoid found in citrus fruit peel, reportedly improves memory impairment in rodent models. Here we report its effect on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced motor and cognitive deficits. Nobiletin administration (50mg/kg i.p.) for 2 consecutive weeks improved motor deficits seen in MPTP-induced Parkinson model mice by 2weeks, an effect that continued until 2weeks after drug withdrawal. Drug treatment promoted similar rescue of MPTP-induced cognitive impairment at equivalent time points. Nonetheless, nobiletin treatment did not block loss of dopaminergic neurons seen in the MPTP-treated mouse midbrain, nor did it rescue decreased tyrosine hydroxylase (TH) protein levels seen in the striatum or hippocampal CA1 region of these mice. Interestingly, nobiletin administration (50mg/kg i.p.) rescued reduced levels of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) autophosphorylation and phosphorylation at Thr-34 of dopamine- and cAMP-regulated phosphoprotein-32 (DARPP-32) in striatum and hippocampal CA1 to levels seen in sham-operated mice. Likewise, CaMKII- and cAMP kinase-dependent TH phosphorylation was significantly restored by nobiletin treatment. MPTP-induced reduction of dopamine contents in the striatum and hippocampal CA1 region was improved by nobiletin administration (50mg/kg i.p.). Acute intraperitoneal administration of nobiletin also enhanced dopamine release in striatum and hippocampal CA1, an effect partially inhibited by treatment with nifedipine (a L-type Ca(2+) channel inhibitor) or NNC 55-0396 (a T-type Ca(2+) channel inhibitor) and completely abolished by combined treatment with both. Overall, our study describes a novel nobiletin activity in brain and suggests that nobiletin rescues motor and cognitive dysfunction in MPTP-induced Parkinson model mice, in part by enhancing dopamine release. PMID:24316474

  6. Intra-regional and inter-regional abnormalities and cognitive control deficits in young adult smokers.

    PubMed

    Feng, Dan; Yuan, Kai; Li, Yangding; Cai, Chenxi; Yin, Junsen; Bi, Yanzhi; Cheng, Jiadong; Guan, Yanyan; Shi, Sha; Yu, Dahua; Jin, Chenwang; Lu, Xiaoqi; Qin, Wei; Tian, Jie

    2016-06-01

    Tobacco use during later adolescence and young adulthood may cause serious neurophysiological changes; rationally, it is extremely important to study the relationship between brain dysfunction and behavioral performances in young adult smokers. Previous resting state studies investigated the neural mechanisms in smokers. Unfortunately, few studies focused on spontaneous activity differences between young adult smokers and nonsmokers from both intra-regional and inter-regional levels, less is known about the association between resting state abnormalities and behavioral deficits. Therefore, we used fractional amplitude of low frequency fluctuation (fALFF) and resting state functional connectivity (RSFC) to investigate the resting state spontaneous activity differences between young adult smokers and nonsmokers. A correlation analysis was carried out to assess the relationship between neuroimaging findings and clinical information (pack-years, cigarette dependence, age of onset and craving score) as well as cognitive control deficits measured by the Stroop task. Consistent with previous addiction findings, our results revealed the resting state abnormalities within frontostriatal circuits, i.e., enhanced spontaneous activity of the caudate and reduced functional strength between the caudate and anterior cingulate cortex (ACC) in young adult smokers. Moreover, the fALFF values of the caudate were correlated with craving and RSFC strength between the caudate and ACC was associated with the cognitive control impairments in young adult smokers. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in young smokers by providing regional and brain circuit spontaneous neuronal activity properties as well as their association with cognitive control impairments. PMID:26164168

  7. Virtual environment navigation tasks and the assessment of cognitive deficits in individuals with brain injury.

    PubMed

    Livingstone, Sharon A; Skelton, Ronald W

    2007-12-11

    Navigation in real environments is often impaired by traumatic brain injury (TBI). These deficits in wayfinding appear to be due to disruption of cognitive processes underlying navigation and may in turn be due to damage to the hippocampus and frontal lobes. These wayfinding problems after TBI were investigated using a virtual simulation of a Morris Water Maze (MWM), a standard test of hippocampal function in laboratory animals. The virtual environment consisted of a large virtual arena in a very large virtual room whose walls provided views of a naturalistic landscape. Eleven community-dwelling TBI survivors and 12 comparison participants, matched for gender, age and education were tested to see if they could find a location in the arena marked by one of the following: (a) a visible platform, (b) a single proximal object, (c) a single proximal object among seven other distracter objects, or (d) distal features inside and outside the room. The proximal objects allowed participants to use egocentric (body-centered) navigational strategies that rely on relatively simple stimulus-response associations. The absence of proximal cues forced the participants to rely on distal features of the environment (room walls, landscape elements) and tested their ability to use allocentric (world-based) navigational strategies requiring cognitive mapping. Results indicated that the navigation of TBI survivors was not impaired when the proximal cues were present but was impaired when proximal cues were absent. These results provide more evidence that the navigational deficit after TBI is due to an inability to form, remember or use cognitive maps. PMID:17727970

  8. Cognitive Deficits in Long-Term Anabolic-Androgenic Steroid Users

    PubMed Central

    Kanayama, Gen; Kean, Joseph; Hudson, James I.; Pope, Harrison G.

    2012-01-01

    Background Millions of individuals worldwide have used anabolic-androgenic steroids (AAS) to gain muscle or improve athletic performance. Recently, in vitro investigations have suggested that supraphysiologic AAS doses cause apoptosis of neuronal cells. These findings raise the possibility, apparently still untested, that humans using high-dose AAS might eventually develop cognitive deficits. Methods We administered five cognitive tests from the computerized CANTAB battery (Pattern Recognition Memory, Verbal Recognition Memory, Paired Associates Learning, Choice Reaction Time, and Rapid Visual Information Processing) to 31 male AAS users and 13 non-AAS-using weightlifters age 29-55, recruited and studied in May 2012 in Middlesbrough, UK. Testers were blinded to participants’ AAS status and other historical data. Results Long-term AAS users showed no significant differences from nonusers on measures of response speed, sustained attention, and verbal memory. On visuospatial memory, however, AAS users performed significantly more poorly than nonusers, and within the user group, visuospatial performance showed a significant negative correlation with total lifetime AAS dose. These were large effects: on Pattern Recognition Memory, long-term AAS users underperformed nonusers by almost one standard deviation, based on normative population scores (adjusted mean difference in z-scores = 0.89; p = 0.036), and performance on this test declined markedly with increasing lifetime AAS dose (adjusted change in z-score = −0.13 per 100g of lifetime AAS dose; p = 0.002). These results remained stable in sensitivity analyses addressing potential confounding factors. Conclusions These preliminary findings raise the ominous possibility that long-term high-dose AAS exposure may cause cognitive deficits, notably in visuospatial memory. PMID:23253252

  9. Attention-deficit hyperactivity disorder (ADHD) stimulant medications as cognitive enhancers.

    PubMed

    Advokat, Claire; Scheithauer, Mindy

    2013-01-01

    Recent increases in attention deficit hyperactivity disorder (ADHD) diagnoses, and the escalation of stimulant prescriptions, has raised concern about diversion and abuse of stimulants, as well as the ethics of using these drugs as "cognitive enhancers."Such concern appears misplaced in the face of substantial evidence that stimulant drugs do not improve the academic performance of ADHD-diagnosed students. Moreover, numerous studies have found little or no benefit of stimulants on neuropsychological tests of ADHD-diagnosed as well as normal, individuals. This paper examines the apparent paradox: why don't drugs that improve "attention," produce better academic outcomes in ADHD-diagnosed students? We found that stimulant drugs significantly improved impairment of episodic memory in ADHD-diagnosed undergraduate students. Nevertheless, we also found consistent academic deficits between ADHD students and their non-ADHD counterparts, regardless of whether or not they used stimulant medications. We reviewed the current literature on the behavioral effects of stimulants, to try to find an explanation for these conflicting phenomena. Across a variety of behavioral tasks, stimulants have been shown to reduce emotional reactions to frustration, improve the ability to detect errors, and increase effortful behavior. However, all of these effects would presumably enhance academic performance. On the other hand, the drugs were also found to promote "risky behavior" and to increase susceptibility to environmental distraction. Such negative effects, including the use of drugs to promote wakefulness for last minute study, might explain the lack of academic benefit in the "real world," despite their cognitive potential. Like many drugs, stimulants influence behavior in multiple ways, depending on the environmental contingencies. Depending on the circumstances, stimulants may, or may not, enhance cognition. PMID:23754970

  10. Cognitive Training at a Young Age Attenuates Deficits in the zQ175 Mouse Model of HD.

    PubMed

    Curtin, Paul C P; Farrar, Andrew M; Oakeshott, Stephen; Sutphen, Jane; Berger, Jason; Mazzella, Matthew; Cox, Kimberly; He, Dansha; Alosio, William; Park, Larry C; Howland, David; Brunner, Daniela

    2015-01-01

    Huntington's Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32-33 weeks age), while deficits in zQ175 mice trained from 6-7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7-8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28-29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6-9 weeks of age, while deficits in naive mice exposed to training at 28-29 weeks were severe. Re-testing mice at 28-29 weeks age, were previously trained starting at 6-9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males zQ175 exhibiting

  11. Cognitive Training at a Young Age Attenuates Deficits in the zQ175 Mouse Model of HD

    PubMed Central

    Curtin, Paul C. P.; Farrar, Andrew M.; Oakeshott, Stephen; Sutphen, Jane; Berger, Jason; Mazzella, Matthew; Cox, Kimberly; He, Dansha; Alosio, William; Park, Larry C.; Howland, David; Brunner, Daniela

    2016-01-01

    Huntington's Disease (HD) is a progressive neurodegenerative disorder that causes motor, cognitive, and psychiatric symptoms. In these experiments, we tested if operant training at an early age affected adult cognitive deficits in the zQ175 KI Het (zQ175) mouse model of HD. In Experiment 1 we trained zQ175 mice in a fixed-ratio/progressive ratio (FR/PR) task to assay learning and motivational deficits. We found pronounced deficits in response rates and task engagement in naïve adult zQ175 mice (32–33 weeks age), while deficits in zQ175 mice trained from 6–7 weeks age were either absent or less severe. When those mice were re-tested as adults, FR/PR performance deficits were absent or otherwise less severe than deficits observed in naïve adult zQ175 relative to wild type (WT) mice. In Experiment 2, we used a Go/No-go operant task to assess the effects of early cognitive testing on response inhibition deficits in zQ175 mice. We found that zQ175 mice that began testing at 7–8 weeks did not exhibit deficits in Go/No-go testing, but when re-tested at 28–29 weeks age exhibited an initial impairment that diminished with training. These transient deficits were nonetheless mild relative to deficits observed among adult zQ175 mice without prior testing experience. In Experiment 3 we trained mice in a two-choice visual discrimination test to evaluate cognitive flexibility. As in prior experiments, we found performance deficits were mild or absent in mice that started training at 6–9 weeks of age, while deficits in naive mice exposed to training at 28–29 weeks were severe. Re-testing mice at 28–29 weeks age, were previously trained starting at 6–9 weeks, revealed that deficits in learning and cognitive flexibility were absent or reduced relative to effects observed in naive adults. In Experiment 4, we tested working memory deficits with a delayed non-match to position (DNMTP) test. Mice with prior experience exhibited mild working memory deficits, with males

  12. Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen

    PubMed Central

    Porrino, Linda J.; Hampson, Robert E.; Opris, Ioan; Deadwyler, Samuel A.

    2013-01-01

    Rationale Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment. Objective Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates. Methods Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [18F]-fluorodeoxyglucose. Results Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine. Conclusions The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure. PMID:22836369

  13. Time may not fully attenuate solvent-associated cognitive deficits in highly exposed workers

    PubMed Central

    Gutierrez, Laure-Anne; Okechukwu, Cassandra A.; Singh-Manoux, Archana; Amieva, Hélène; Goldberg, Marcel; Zins, Marie; Berr, Claudine

    2014-01-01

    Objective: To test the effects of lifetime occupational solvent exposure, as measured by dose and timing, on performance on multiple cognitive tests among retired French utility workers. Methods: A total of 2,143 retirees in the GAZEL cohort underwent cognitive testing in 2010. Lifetime exposure to chlorinated solvents, petroleum solvents, and benzene was assessed using a job exposure matrix. We modeled effects of lifetime solvent dose, timing of last exposure, and a combination of these metrics on risk for cognitive impairment. Results: Thirty-three percent of participants were exposed to chlorinated solvents, 26% to benzene, and 25% to petroleum solvents. High exposure to solvents was significantly associated with poor cognition; for example, those highly exposed to chlorinated solvents were at risk of impairment on the Mini-Mental State Examination (risk ratio 1.18; 95% confidence interval 1.06, 1.31), the Digit Symbol Substitution Test (1.54; 1.31, 1.82), semantic fluency test (1.33; 1.14, 1.55), and the Trail Making Test B (1.49; 1.25, 1.77). Retirees at greatest risk for deficits had both high lifetime exposure to solvents and were last exposed 12 to 30 years before testing. Risk was somewhat elevated among those with high lifetime exposure who were last exposed 31 to 50 years before testing. Those with high, recent exposure exhibited impairment in almost all domains, including those not typically associated with solvent exposure. Conclusions: While risk of cognitive impairment among moderately exposed workers may attenuate with time, this may not be fully true for those with higher exposure. This has implications for physicians working with formerly solvent-exposed patients as well as for workplace exposure limit policies. PMID:24821933

  14. Smaller than expected cognitive deficits in schizophrenia patients from the population-representative ABC catchment cohort.

    PubMed

    Lennertz, Leonhard; An der Heiden, Wolfram; Kronacher, Regina; Schulze-Rauschenbach, Svenja; Maier, Wolfgang; Häfner, Heinz; Wagner, Michael

    2016-08-01

    Most neuropsychological studies on schizophrenia suffer from sample selection bias, with male and chronic patients being overrepresented. This probably leads to an overestimation of cognitive impairments. The present study aimed to provide a less biased estimate of cognitive functions in schizophrenia using a population-representative catchment area sample. Schizophrenia patients (N = 89) from the prospective Mannheim ABC cohort were assessed 14 years after disease onset and first diagnosis, using a comprehensive neuropsychological test battery. A healthy control group (N = 90) was carefully matched according to age, gender, and geographic region (city, rural surrounds). The present sample was representative for the initial ABC cohort. In the comprehensive neuropsychological assessment, the schizophrenia patients were only moderately impaired as compared to the healthy control group (d = 0.56 for a general cognitive index, d = 0.42 for verbal memory, d = 0.61 for executive functions, d = 0.69 for attention). Only 33 % of the schizophrenia patients scored one standard deviation unit below the healthy control group in the general cognitive index. Neuropsychological performance did not correlate with measures of the clinical course including age at onset, number of hospital admissions, and time in paid work. Thus, in this population-representative sample of schizophrenia patients, neuropsychological deficits were less pronounced than expected from meta-analyses. In agreement with other epidemiological studies, this suggests a less devastating picture of cognition in schizophrenia. PMID:26233432

  15. Pathologic and imaging correlates of cognitive deficits in multiple sclerosis: changing the paradigm of diagnosis and prognosis.

    PubMed

    Shi, Jiong; Baxter, Leslie C; Kuniyoshi, Sandra M

    2014-03-01

    From 1868, when Charcot first described the clinical features and the pathologic correlates, up till the present day, multiple sclerosis (MS) has commonly been characterized by the symptoms caused by inflammatory plaques in the white matter of the brain and spinal cord. Early use of magnetic resonance imaging (MRI) to diagnose MS focused on detecting these white matter lesions. By the 1990s, researchers recognized that many patients with MS have cognitive deficits that can cause severe disability, and also determined the associated pathology; these findings shed more light on both the pathogenesis and progression. Since 2004, several lines of evidence have shown that the extent of white matter plaques identified on MRI does not correlate well with cognitive deficits. High-resolution MRI and advances in immunohistochemical techniques have enabled detection of cortical demyelination early in the course, correlating with cognitive deficits. Late in the course, pathologic changes in normal-looking white and gray matter correlate more closely with progressive cognitive deficits than with visual, sensory, and motor symptoms. This finding implies the need to redefine the disease and its progression. In this review, we discuss the histopathologic studies of cortical plaques in MS and early indications about their role in disease definition and progression, describe the role of high-resolution MRI in staging and determining progression of cognitive symptoms, and discuss how advances in these areas are forcing us to rethink diagnosis and determination of progression. PMID:24674960

  16. 16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks

    PubMed Central

    Lewis, Freeman C.; Sarvi, Michael S.; Foley, Gillian M.; Crawley, Jacqueline N.

    2015-01-01

    Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/−) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/− mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/−, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/− mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey–Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/− mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/− failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/−. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/− mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome. PMID:26572653

  17. 16p11.2 Deletion mice display cognitive deficits in touchscreen learning and novelty recognition tasks.

    PubMed

    Yang, Mu; Lewis, Freeman C; Sarvi, Michael S; Foley, Gillian M; Crawley, Jacqueline N

    2015-12-01

    Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2+/- mice, confirming previous findings. A similarly robust deficit in object location memory was discovered in +/-, indicating impaired spatial novelty recognition. Generalizability of novelty recognition deficits in +/- mice extended to preference for social novelty. Robust learning deficits and cognitive inflexibility were detected using Bussey-Saksida touchscreen operant chambers. During acquisition of pairwise visual discrimination, +/- mice required significantly more training trials to reach criterion than wild-type littermates (+/+), and made more errors and correction errors than +/+. In the reversal phase, all +/+ reached criterion, whereas most +/- failed to reach criterion by the 30-d cutoff. Contextual and cued fear conditioning were normal in +/-. These cognitive phenotypes may be relevant to some aspects of cognitive impairments in humans with 16p11.2 deletion, and support the use of 16p11.2+/- mice as a model system for discovering treatments for cognitive impairments in 16p11.2 deletion syndrome. PMID:26572653

  18. The effects of sigma (σ1) receptor-selective ligands on muscarinic receptor antagonist-induced cognitive deficits in mice

    PubMed Central

    Malik, Maninder; Rangel-Barajas, Claudia; Sumien, Nathalie; Su, Chang; Singh, Meharvan; Chen, Zhenglan; Huang, Ren-Qi; Meunier, Johann; Maurice, Tangui; Mach, Robert H; Luedtke, Robert R

    2015-01-01

    Background and Purpose Cognitive deficits in patients with Alzheimer's disease, Parkinson's disease, traumatic brain injury and stroke often involve alterations in cholinergic signalling. Currently available therapeutic drugs provide only symptomatic relief. Therefore, novel therapeutic strategies are needed to retard and/or arrest the progressive loss of memory. Experimental Approach Scopolamine-induced memory impairment provides a rapid and reversible phenotypic screening paradigm for cognition enhancement drug discovery. Male C57BL/6J mice given scopolamine (1 mg·kg−1) were used to evaluate the ability of LS-1–137, a novel sigma (σ1) receptor-selective agonist, to improve the cognitive deficits associated with muscarinic antagonist administration. Key Results LS-1–137 is a high-affinity (Ki = 3.2 nM) σ1 receptor agonist that is 80-fold selective for σ1, compared with σ2 receptors. LS-1–137 binds with low affinity at D2-like (D2, D3 and D4) dopamine and muscarinic receptors. LS-1–137 was found to partially reverse the learning deficits associated with scopolamine administration using a water maze test and an active avoidance task. LS-1–137 treatment was also found to trigger the release of brain-derived neurotrophic factor from rat astrocytes. Conclusions and Implications The σ1 receptor-selective compound LS-1–137 may represent a novel candidate cognitive enhancer for the treatment of muscarinic receptor-dependent cognitive deficits. PMID:25573298

  19. The effects of human corticotrophin releasing factor on motor and cognitive deficits after impact acceleration injury.

    PubMed

    Beaumont, A; Marmarou, C; Marmarou, A

    2000-10-01

    Corticotrophin releasing factor has been shown in several models of tissue injury to be an effective treatment for edema. In a previous study we demonstrated this ability in two models of traumatic brain injury (TBI). The aim of this study was to assess whether human corticotrophin releasing factor (hCRF) could additionally improve motor and cognitive deficits. Adult male Sprague-Dawley rats were randomised into five groups and injured with the Impact Acceleration Model of TBI. Groups I and II received sham injury followed by treatment with either drug vehicle or 100 micrograms kg-1 hCRF respectively. Group III was injured with no treatment; Group IV animals were injured and treated with 50 micrograms kg-1 hCRF and Group V were injured and treated with 100 micrograms kg-1 hCRF. Animals were assessed both before and after injury with a battery of standardised neuropsychological tests including the Morris Water Maze, the Beam Walk Test, the Beam Balance Test and the Inclined Plane Test. Both 50 micrograms kg-1 and 100 micrograms kg-1 hCRF caused significant improvements in motor and cognitive functioning, confirming that in addition to edema-reducing properties, human corticotrophin releasing factor is also capable of improving motor and cognitive functioning. Given the beneficial experimental effects of this compound, hCRF may be a useful clinical treatment, which requires formal evaluation. PMID:11091970

  20. Cognitive deficits are associated with unemployment in adults with sickle cell anemia.

    PubMed

    Sanger, Maureen; Jordan, Lori; Pruthi, Sumit; Day, Matthew; Covert, Brittany; Merriweather, Brenda; Rodeghier, Mark; DeBaun, Michael; Kassim, Adetola

    2016-08-01

    An estimated 25-60% of adults with sickle cell disease (SCD) are unemployed. Factors contributing to the high unemployment rate in this population are not well studied. With the known risk of cognitive deficits associated with SCD, we tested the hypothesis that unemployment is related to decrements in intellectual functioning. We conducted a retrospective chart review of 50 adults with sickle cell anemia who completed cognitive testing, including the Wechsler Adult Intelligence Scale-IV, as part of standard care. Employment status was recorded at the time of testing. Medical variables examined as possible risk factors for unemployment included disease phenotype, cerebral infarction, and pain frequency. The mean age of the sample was 30.7 years (range = 19-59); 56% were women. Almost half of the cohort (44%) were unemployed. In a multivariate logistic regression model, lower IQ scores (odds ratio = 0.88; p = .002, 95% confidence interval, CI [0.82, 0.96]) and lower educational attainment (odds ratio = 0.13; p = .012, 95% CI [0.03, 0.65]) were associated with increasing odds of unemployment. The results suggest that cognitive impairment in adults with sickle cell anemia may contribute to the risk of unemployment. Helping these individuals access vocational rehabilitation services may be an important component of multidisciplinary care. PMID:27167865

  1. Cognitive deficits in first-degree relatives of bipolar patients: the use of homogeneous subgroups in the search of cognitive endophenotypes.

    PubMed

    Volkert, Julia; Haubner, J; Kazmaier, J; Glaser, F; Kopf, J; Kittel-Schneider, S; Reif, A

    2016-08-01

    Previous studies have demonstrated impairments in attention, memory and executive functions in euthymic bipolar patients (BP) as well as their unaffected first-degree relatives, albeit in an attenuated form. Subsequently, cognitive deficits are discussed as a possible endophenotype of bipolar disorder. However, recent studies showed that only a subgroup of BP shows cognitive impairments. The aim of the present study was to investigate cognitive functioning in relatives compared to BP, to find out if the differentiation in a cognitive deficit vs. non-deficit subgroup is valid for relatives of BP, too. Therefore, the performance of 27 unaffected relatives of BP, 27 euthymic BP and 27 HC were compared using a neuropsychological test battery. The results showed that BP exhibited a reduced psychomotor speed and deficits in working memory compared to relatives and HC. Relatives performed significantly slower (psychomotor speed) as compared to HC (p = 0.024); performance in the other test measures lie between BP and HC. Furthermore, a detailed evaluation of the data indicated that only subgroups of BP and relatives exhibited cognitive impairments in the implemented tests. However, the deficit and non-deficit groups did not differ in sociodemographic and clinical variables from each other, possibly due to the small sample size. In conclusion, our results suggest that reduced psychomotor speed could serve as a potential endophenotype for bipolar disorder which should be investigated along the developmental trajectory of this disorder, also to examine whether abnormalities therein precede onset of the first mood episode. Furthermore, the division of relatives into subgroups aids in the identification of stable trait markers and high-risk bipolar groups and could enable early prevention strategies. As to that more research using distinct and homogeneous subgroups is necessary. PMID:27273092

  2. Stimulation of 5-HT2C Receptors Improves Cognitive Deficits Induced by Human Tryptophan Hydroxylase 2 Loss of Function Mutation

    PubMed Central

    Del'Guidice, Thomas; Lemay, Francis; Lemasson, Morgane; Levasseur-Moreau, Jean; Manta, Stella; Etievant, Adeline; Escoffier, Guy; Doré, François Y; Roman, François S; Beaulieu, Jean-Martin

    2014-01-01

    Polymorphisms in the gene encoding the serotonin synthesis enzyme Tph2 have been identified in mental illnesses, including bipolar disorder, major depression, autism, schizophrenia, and ADHD. Deficits in cognitive flexibility and perseverative behaviors are shared common symptoms in these disorders. However, little is known about the impact of Tph2 gene variants on cognition. Mice expressing a human TPH2 variant (Tph2-KI) were used to investigate cognitive consequences of TPH2 loss of function and pharmacological treatments. We applied a recently developed behavioral assay, the automated H-maze, to study cognitive functions in Tph2-KI mice. This assay involves the consecutive discovery of three different rules: a delayed alternation task, a non-alternation task, and a delayed reversal task. Possible contribution of locomotion, reward, and sensory perception were also investigated. The expression of loss-of-function mutant Tph2 in mice was associated with impairments in reversal learning and cognitive flexibility, accompanied by perseverative behaviors similar to those observed in human clinical studies. Pharmacological restoration of 5-HT synthesis with 5-hydroxytryptophan or treatment with the 5-HT2C receptor agonist CP809.101 reduced cognitive deficits in Tph2-KI mice and abolished perseveration. In contrast, treatment with the psychostimulant methylphenidate exacerbated cognitive deficits in mutant mice. Results from this study suggest a contribution of TPH2 in the regulation of cognition. Furthermore, identification of a role for a 5-HT2 receptor agonist as a cognition-enhancing agent in mutant mice suggests a potential avenue to explore for the personalized treatment of cognitive symptoms in humans with reduced 5-HT synthesis and TPH2 polymorphisms. PMID:24196946

  3. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline.

    PubMed

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-08-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer's disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline. PMID:25866202

  4. Aging-associated formaldehyde-induced norepinephrine deficiency contributes to age-related memory decline

    PubMed Central

    Mei, Yufei; Jiang, Chun; Wan, You; Lv, Jihui; Jia, Jianping; Wang, Xiaomin; Yang, Xu; Tong, Zhiqian

    2015-01-01

    A norepinephrine (NE) deficiency has been observed in aged rats and in patients with Alzheimer’s disease and is thought to cause cognitive disorder. Which endogenous factor induces NE depletion, however, is largely unknown. In this study, we investigated the effects of aging-associated formaldehyde (FA) on the inactivation of NE in vitro and in vivo, and on memory behaviors in rodents. The results showed that age-related DNA demethylation led to hippocampal FA accumulation, and when this occurred, the hippocampal NE content was reduced in healthy male rats of different ages. Furthermore, biochemical analysis revealed that FA rapidly inactivated NE in vitro and that an intrahippocampal injection of FA markedly reduced hippocampal NE levels in healthy adult rats. Unexpectedly, an injection of FA (at a pathological level) or 6-hydroxydopamine (6-OHDA, a NE depletor) can mimic age-related NE deficiency, long-term potentiation (LTP) impairments, and spatial memory deficits in healthy adult rats. Conversely, an injection of NE reversed age-related deficits in both LTP and memory in aged rats. In agreement with the above results, the senescence-accelerated prone 8 (SAMP8) mice also exhibited a severe deficit in LTP and memory associated with a more severe NE deficiency and FA accumulation, when compared with the age-matched, senescence-resistant 1 (SAMR1) mice. Injection of resveratrol (a natural FA scavenger) or NE into SAMP8 mice reversed FA accumulation and NE deficiency and restored the magnitude of LTP and memory. Collectively, these findings suggest that accumulated FA is a critical endogenous factor for aging-associated NE depletion and cognitive decline. PMID:25866202

  5. Methylphenidate improves the behavioral and cognitive deficits of neurogranin knockout mice

    PubMed Central

    Huang, Freesia L.; Huang, Kuo-Ping

    2012-01-01

    Neurogranin (Ng), a brain-specific calmodulin-binding protein, is expressed highly in hippocampus, and is important for cognitive function. Deletion of the Ng gene from mice caused attenuation of signal reaction cascade in hippocampus, impairments in learning and memory and high frequency stimulation-induced long-term potentiation. Environmental enrichment alone failed to improve cognitive function. In the present study, behavioral testing revealed that Ng knockout mice were both hyperactive and socially withdrawn. Methylphenidate (MPH) was given to mice while they were also kept under an enrichment condition. MPH treatment reduced the hyperactivity of Ng knockout mice tested in both the open field and forced swim chamber. MPH improved their social abilities such that mice recognized and interacted better with novel subjects. The cognitive memories of MPH-treated mutants were improved in both water maze and contextual fear conditioning tests. High frequency stimulation-induced long-term potentiation of Ng knockout mice was also improved by MPH. The present treatment regimen, however, did not fully reverse the deficits of the mutant mice. In contrast, MPH exerted only a minimal effect on the wild type mice. At the cellular level, MPH increased the number of glial fibrillary acidic protein-positive cells in hippocampus, particularly within the dentate gyrus of Ng knockout mice. Therefore it will be of interest to determine the nature of MPH-mediated astrocyte activation and how it may modulate behavior in future studies. Taken together these Ng knockout mice may be useful for the development of better drug treatment to improve cognitive and behavioral impairments. PMID:22809330

  6. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease

    PubMed Central

    Xu, Jian; Chatterjee, Manavi; Baguley, Tyler D.; Brouillette, Jonathan; Kurup, Pradeep; Ghosh, Debolina; Kanyo, Jean; Zhang, Yang; Seyb, Kathleen; Ononenyi, Chimezie; Foscue, Ethan; Anderson, George M.; Gresack, Jodi; Cuny, Gregory D.; Glicksman, Marcie A.; Greengard, Paul; Lam, TuKiet T.; Tautz, Lutz; Nairn, Angus C.; Ellman, Jonathan A.; Lombroso, Paul J.

    2014-01-01

    STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD. AD mice lacking STEP have restored levels of glutamate receptors on synaptosomal membranes and improved cognitive function, results that suggest STEP as a novel therapeutic target for AD. Here we describe the first large-scale effort to identify and characterize small-molecule STEP inhibitors. We identified the benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) as an inhibitor of STEP with an IC50 of 24.6 nM. TC-2153 represents a novel class of PTP inhibitors based upon a cyclic polysulfide pharmacophore that forms a reversible covalent bond with the catalytic cysteine in STEP. In cell-based secondary assays, TC-2153 increased tyrosine phosphorylation of STEP substrates ERK1/2, Pyk2, and GluN2B, and exhibited no toxicity in cortical cultures. Validation and specificity experiments performed in wild-type (WT) and STEP knockout (KO) cortical cells and in vivo in WT and STEP KO mice suggest specificity of inhibitors towards STEP compared to highly homologous tyrosine phosphatases. Furthermore, TC-2153 improved cognitive function in several cognitive tasks in 6- and 12-mo-old triple transgenic AD (3xTg-AD) mice, with no change in beta amyloid and phospho-tau levels. PMID:25093460

  7. Inhibitor of the tyrosine phosphatase STEP reverses cognitive deficits in a mouse model of Alzheimer's disease.

    PubMed

    Xu, Jian; Chatterjee, Manavi; Baguley, Tyler D; Brouillette, Jonathan; Kurup, Pradeep; Ghosh, Debolina; Kanyo, Jean; Zhang, Yang; Seyb, Kathleen; Ononenyi, Chimezie; Foscue, Ethan; Anderson, George M; Gresack, Jodi; Cuny, Gregory D; Glicksman, Marcie A; Greengard, Paul; Lam, TuKiet T; Tautz, Lutz; Nairn, Angus C; Ellman, Jonathan A; Lombroso, Paul J

    2014-08-01

    STEP (STriatal-Enriched protein tyrosine Phosphatase) is a neuron-specific phosphatase that regulates N-methyl-D-aspartate receptor (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) trafficking, as well as ERK1/2, p38, Fyn, and Pyk2 activity. STEP is overactive in several neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease (AD). The increase in STEP activity likely disrupts synaptic function and contributes to the cognitive deficits in AD. AD mice lacking STEP have restored levels of glutamate receptors on synaptosomal membranes and improved cognitive function, results that suggest STEP as a novel therapeutic target for AD. Here we describe the first large-scale effort to identify and characterize small-molecule STEP inhibitors. We identified the benzopentathiepin 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (known as TC-2153) as an inhibitor of STEP with an IC50 of 24.6 nM. TC-2153 represents a novel class of PTP inhibitors based upon a cyclic polysulfide pharmacophore that forms a reversible covalent bond with the catalytic cysteine in STEP. In cell-based secondary assays, TC-2153 increased tyrosine phosphorylation of STEP substrates ERK1/2, Pyk2, and GluN2B, and exhibited no toxicity in cortical cultures. Validation and specificity experiments performed in wild-type (WT) and STEP knockout (KO) cortical cells and in vivo in WT and STEP KO mice suggest specificity of inhibitors towards STEP compared to highly homologous tyrosine phosphatases. Furthermore, TC-2153 improved cognitive function in several cognitive tasks in 6- and 12-mo-old triple transgenic AD (3xTg-AD) mice, with no change in beta amyloid and phospho-tau levels. PMID:25093460

  8. Gray and White Matter Contributions to Cognitive Frontostriatal Deficits in Non-Demented Parkinson's Disease

    PubMed Central

    Price, Catherine C.; Tanner, Jared; Nguyen, Peter T.; Schwab, Nadine A.; Mitchell, Sandra; Slonena, Elizabeth; Brumback, Babette; Okun, Michael S.; Mareci, Thomas H.; Bowers, Dawn

    2016-01-01

    Objective This prospective investigation examined: 1) processing speed and working memory relative to other cognitive domains in non-demented medically managed idiopathic Parkinson’s disease, and 2) the predictive role of cortical/subcortical gray thickness/volume and white matter fractional anisotropy on processing speed and working memory. Methods Participants completed a neuropsychological protocol, Unified Parkinson’s Disease Rating Scale, brain MRI, and fasting blood draw to rule out vascular contributors. Within group a priori anatomical contributors included bilateral frontal thickness, caudate nuclei volume, and prefrontal white matter fractional anisotropy. Results Idiopathic Parkinson’s disease (n = 40; Hoehn & Yahr stages 1–3) and non-Parkinson’s disease ‘control’ peers (n = 40) matched on demographics, general cognition, comorbidity, and imaging/blood vascular metrics. Cognitively, individuals with Parkinson’s disease were significantly more impaired than controls on tests of processing speed, secondary deficits on working memory, with subtle impairments in memory, abstract reasoning, and visuoperceptual/spatial abilities. Anatomically, Parkinson’s disease individuals were not statistically different in cortical gray thickness or subcortical gray volumes with the exception of the putamen. Tract Based Spatial Statistics showed reduced prefrontal fractional anisotropy for Parkinson’s disease relative to controls. Within Parkinson’s disease, prefrontal fractional anisotropy and caudate nucleus volume partially explained processing speed. For controls, only prefrontal white matter was a significant contributor to processing speed. There were no significant anatomical predictors of working memory for either group. Conclusions Caudate nuclei volume and prefrontal fractional anisotropy, not frontal gray matter thickness, showed unique and combined significance for processing speed in Parkinson’s disease. Findings underscore the

  9. Separation of cognitive impairments in attention deficit hyperactivity disorder into two familial factors

    PubMed Central

    Kuntsi, J.; Wood, A.C.; Rijsdijk, F.; Johnson, K.A.; Andreou, P.; Albrecht, B.; Arias-Vasquez, A.; Buitelaar, J.K.; Mcloughlin, G.; Rommelse, N.N.J.; Sergeant, J.A.; Sonuga-Barke, E.J.S.; Uebel, H.; van der Meere, J.J.; Banaschewski, T.; Gill, M.; Manor, I.; Miranda, A.; Mulas, F.; Oades, R.D.; Roeyers, H.; Rothenberger, A.; Steinhausen, H.C.; Faraone, S.V.; Asherson, P.

    2013-01-01

    Context Attention deficit hyperactivity disorder (ADHD) is associated with widespread cognitive impairments, but it is not known whether the apparent multiple impairments share etiological roots, or whether separate etiological pathways exist. A better understanding of the etiological pathways is important for the development of targeted interventions and for identification of suitable intermediate phenotypes for molecular genetic investigations. Objective To determine, using a multivariate familial factor analysis approach, whether one or more familial factors underlie the slow and variable reaction times (RTs), impaired response inhibition and choice impulsivity that are associated with ADHD. Design An ADHD and control sibling-pair design. Setting Belgium, Germany, Ireland, Israel, Spain, Switzerland and the United Kingdom. Participants The sample consisted of 1265 participants, aged 6 to 18 years: 464 probands with ADHD and 456 of their siblings (524 with ADHD combined subtype), and 345 control participants. Main Outcome Measures Performance on a four-choice RT task, a go/no-go inhibition task and a choice-delay task. Results The final model consisted of two familial factors. The larger factor, reflecting 85% of the familial variance of ADHD, captured 98-100% of the familial influences on mean RT and RT variability. The second smaller factor, reflecting 12.5% of the familial variance of ADHD, captured 62-82% of the familial influences on commission and omission errors on the go/no-go task. Choice impulsivity was excluded in the final model, due to poor fit. Conclusions The findings suggest the existence of two familial pathways to cognitive impairments in ADHD and indicate promising cognitive targets for future molecular genetic investigations. The familial distinction between the two cognitive impairments is consistent with recent theoretical models – a developmental model and an arousal-attention model – on two separable underlying processes in ADHD

  10. Current Status of Cognitive Behavioral Therapy for Adult Attention-Deficit Hyperactivity Disorder

    PubMed Central

    Knouse, Laura E.; Safren, Steven A.

    2010-01-01

    Synopsis Attention-deficit / hyperactivity disorder (ADHD) is a valid and impairing psychological disorder that persists into adulthood in a majority of cases and is associated with chronic functional impairment and increased rates of comorbidity. Cognitive-behavioral therapy (CBT) approaches for this disorder have emerged relatively recently, and available evidence from open and randomized controlled trials suggests that these approaches are promising in producing significant symptom reduction. A conceptual model of how CBT may work for ADHD is reviewed along with existing efficacy studies. A preliminary comparison of effect sizes across intervention packages suggests that targeted learning and practice of specific behavioral compensatory strategies may be a critical “active ingredient” in CBT for adult ADHD. The article concludes with a discussion of future directions and critical questions that must be addressed in this area of clinical research. PMID:20599129

  11. The neural architecture of age-related dual-task interferences

    PubMed Central

    Chmielewski, Witold X.; Yildiz, Ali; Beste, Christian

    2014-01-01

    In daily life elderly adults exhibit deficits when dual-tasking is involved. So far these deficits have been verified on a behavioral level in dual-tasking. Yet, the neuronal architecture of these deficits in aging still remains to be explored especially when late-middle aged individuals around 60 years of age are concerned. Neuroimaging studies in young participants concerning dual-tasking were, among others, related to activity in middle frontal (MFG) and superior frontal gyrus (SFG) and the anterior insula (AI). According to the frontal lobe hypothesis of aging, alterations in these frontal regions (i.e., SFG and MFG) might be responsible for cognitive deficits. We measured brain activity using fMRI, while examining age-dependent variations in dual-tasking by utilizing the PRP (psychological refractory period) test. Behavioral data showed an increasing PRP effect in late-middle aged adults. The results suggest the age-related deteriorated performance in dual-tasking, especially in conditions of risen complexity. These effects are related to changes in networks involving the AI, the SFG and the MFG. The results suggest that different cognitive subprocesses are affected that mediate the observed dual-tasking problems in late-middle aged individuals. PMID:25132818

  12. Riluzole rescues glutamate alterations, cognitive deficits, and tau pathology associated with P301L tau expression.

    PubMed

    Hunsberger, Holly C; Weitzner, Daniel S; Rudy, Carolyn C; Hickman, James E; Libell, Eric M; Speer, Rebecca R; Gerhardt, Greg A; Reed, Miranda N

    2015-10-01

    Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for amyotrophic lateral sclerosis that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved performance in the water radial arm maze and the Morris water maze, associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus, cornu ammonis 3 (CA3), and cornu ammonis 1 (CA1) regions of the hippocampus. Riluzole also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter 1, which packages glutamate into vesicles and influences glutamate release; and the TauP301L-mediated decrease in hippocampal glutamate transporter 1, the major transporter responsible for removing glutamate from the extracellular space. The TauP301L-mediated reduction in PSD-95 expression, a marker of excitatory synapses in the hippocampus, was also rescued by riluzole. Riluzole treatment reduced total levels of tau, as well as the pathological phosphorylation and conformational changes in tau associated with the P301L mutation. These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD. PMID:26146790

  13. Autism-Relevant Social Abnormalities and Cognitive Deficits in Engrailed-2 Knockout Mice

    PubMed Central

    Brielmaier, Jennifer; Matteson, Paul G.; Silverman, Jill L.; Senerth, Julia M.; Kelly, Samantha; Genestine, Matthieu; Millonig, James H.

    2012-01-01

    ENGRAILED 2 (En2), a homeobox transcription factor, functions as a patterning gene in the early development and connectivity of rodent hindbrain and cerebellum, and regulates neurogenesis and development of monoaminergic pathways. To further understand the neurobiological functions of En2, we conducted neuroanatomical expression profiling of En2 wildtype mice. RTQPCR assays demonstrated that En2 is expressed in adult brain structures including the somatosensory cortex, hippocampus, striatum, thalamus, hypothalamus and brainstem. Human genetic studies indicate that EN2 is associated with autism. To determine the consequences of En2 mutations on mouse behaviors, including outcomes potentially relevant to autism, we conducted comprehensive phenotyping of social, communication, repetitive, and cognitive behaviors. En2 null mutants exhibited robust deficits in reciprocal social interactions as juveniles and adults, and absence of sociability in adults, replicated in two independent cohorts. Fear conditioning and water maze learning were impaired in En2 null mutants. High immobility in the forced swim test, reduced prepulse inhibition, mild motor coordination impairments and reduced grip strength were detected in En2 null mutants. No genotype differences were found on measures of ultrasonic vocalizations in social contexts, and no stereotyped or repetitive behaviors were observed. Developmental milestones, general health, olfactory abilities, exploratory locomotor activity, anxiety-like behaviors and pain responses did not differ across genotypes, indicating that the behavioral abnormalities detected in En2 null mutants were not attributable to physical or procedural confounds. Our findings provide new insight into the role of En2 in complex behaviors and suggest that disturbances in En2 signaling may contribute to neuropsychiatric disorders marked by social and cognitive deficits, including autism spectrum disorders. PMID:22829897

  14. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease.

    PubMed

    Jankowsky, Joanna L; Melnikova, Tatiana; Fadale, Daniel J; Xu, Guilian M; Slunt, Hilda H; Gonzales, Victoria; Younkin, Linda H; Younkin, Steven G; Borchelt, David R; Savonenko, Alena V

    2005-05-25

    Epidemiological studies suggest that individuals with greater education or more cognitively demanding occupations have diminished risk of developing dementia. We wanted to test whether this effect could be recapitulated in rodents using environmental enrichment, a paradigm well documented to attenuate behavioral deficits induced by various pathological insults. Here, we demonstrate that learning and memory deficits observed in a transgenic mouse model of Alzheimer's disease can be ameliorated by enrichment. Female transgenic mice overexpressing amyloid precursor protein and/or presenilin-1 and nontransgenic controls were placed into enriched or standard cages at 2 months of age and tested for cognitive behavior after 6 months of differential housing. Enrichment significantly improved performance of all genotypes in the radial water maze and in the classic and repeated-reversal versions of the Morris water maze. However, enrichment did not benefit all genotypes equally. Mice overproducing amyloid-beta (Abeta), particularly those with amyloid deposits, showed weaker memory for the platform location in the classic Morris water maze and learned new platform positions in the repeated-reversals task less quickly than their nontransgenic cagemates. Nonetheless, enrichment normalized the performance of Abeta-overproducing mice to the level of standard-housed nontransgenic mice. Moreover, this functional preservation occurred despite increased neuritic plaque burden in the hippocampus of double-transgenic animals and elevated steady-state Abeta levels, because both endogenous and transgene-derived Abeta are increased in enriched animals. These results demonstrate that the generation of Abeta in vivo and its impact on the function of the nervous system can be strongly modulated by environmental factors. PMID:15917461

  15. Delta9-Tetrahydrocannabinol-induced cognitive deficits are reversed by olanzapine but not haloperidol in rats.

    PubMed

    Egashira, Nobuaki; Ishigami, Noriko; Mishima, Kenichi; Iwasaki, Katsunori; Oishi, Ryozo; Fujiwara, Michihiro

    2008-02-15

    Cannabis is the most widely used illicit substance. Delta9-Tetrahydrocannabinol (THC), the major psychoactive component of cannabis, is known to induce cognitive impairment that closely resembles the impairment observed in schizophrenic patients. THC has also been known to impair spatial memory in rats tested in the eight-arm radial maze. We previously reported that microinjection of THC (20 microg/side) into the rat dorsal hippocampus impaired spatial memory and that i.p. injection of THC (6 mg/kg) decreased the extracellular levels of acetylcholine (ACh) in the dorsal hippocampus. In the present study, we compared the effects of olanzapine, an atypical antipsychotic, with those of haloperidol, a typical neuroleptic, on the impairments of spatial memory and decreased ACh levels induced by THC (6 mg/kg, i.p.) in rats. We found that olanzapine (0.1 mg/kg, i.p.) reversed the THC-induced memory deficits and decrease in extracellular ACh levels, whereas haloperidol (0.03-0.3 mg, i.p.) had no effect. These results suggest that olanzapine may improve the THC-induced impairment of spatial memory, partly by enhancing ACh release in the dorsal hippocampus. Therefore, olanzapine could attenuate the acute short-term and working memory deficits induced by cannabis. PMID:18029074

  16. Critical Role of Acetylation in Tau-Mediated Neurodegeneration and Cognitive Deficits

    PubMed Central

    Min, Sang-Won; Chen, Xu; Tracy, Tara E; Li, Yaqiao; Zhou, Yungui; Wang, Chao; Shirakawa, Kotaro; Minami, S. Sakura; Defensor, Erwin; Mok, Sue Ann; Sohn, Peter Dongmin; Schilling, Birgit; Cong, Xin; Ellerby, Lisa; Gibson, Bradford W.; Johnson, Jeffrey; Krogan, Nevan; Shamloo, Mehrdad; Gestwicki, Jason; Masliah, Eliezer; Verdin, Eric; Gan, Li

    2015-01-01

    Tauopathies, including frontotemporal dementia (FTD) and Alzheimer’s disease (AD), are neurodegenerative diseases in which tau fibrils accumulate. Recent evidence supports soluble tau species as the major toxic species. How soluble tau accumulates and how it causes neurodegeneration remains unclear. Here we identified tau acetylation at K174 as an early change in AD brains and as a critical determinant in tau homeostasis and toxicity in mice. An acetyl-mimicking mutant (K174Q) slows down tau turnover and induces cognitive deficits in vivo. The acetyltransferase p300-induced tau acetylation is inhibited by a prescription drug salsalate/salicylate, which enhances tau turnover and reduces tau levels. In the PS19 transgenic mouse model of FTD, administering salsalate after disease onset inhibited p300 activity, lowered ac-K174 and total tau levels, rescued tau-induced memory deficits and prevented hippocampal atrophy. The tau-lowering and protective effects of salsalate/salicylate are diminished in neurons expressing K174Q tau. Targeting tau acetylation could be a new therapeutic strategy against human tauopathies. PMID:26390242

  17. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits.

    PubMed

    Min, Sang-Won; Chen, Xu; Tracy, Tara E; Li, Yaqiao; Zhou, Yungui; Wang, Chao; Shirakawa, Kotaro; Minami, S Sakura; Defensor, Erwin; Mok, Sue Ann; Sohn, Peter Dongmin; Schilling, Birgit; Cong, Xin; Ellerby, Lisa; Gibson, Bradford W; Johnson, Jeffrey; Krogan, Nevan; Shamloo, Mehrdad; Gestwicki, Jason; Masliah, Eliezer; Verdin, Eric; Gan, Li

    2015-10-01

    Tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD), are neurodegenerative diseases in which tau fibrils accumulate. Recent evidence supports soluble tau species as the major toxic species. How soluble tau accumulates and causes neurodegeneration remains unclear. Here we identify tau acetylation at Lys174 (K174) as an early change in AD brains and a critical determinant in tau homeostasis and toxicity in mice. The acetyl-mimicking mutant K174Q slows tau turnover and induces cognitive deficits in vivo. Acetyltransferase p300-induced tau acetylation is inhibited by salsalate and salicylate, which enhance tau turnover and reduce tau levels. In the PS19 transgenic mouse model of FTD, administration of salsalate after disease onset inhibited p300 activity, lowered levels of total tau and tau acetylated at K174, rescued tau-induced memory deficits and prevented hippocampal atrophy. The tau-lowering and protective effects of salsalate were diminished in neurons expressing K174Q tau. Targeting tau acetylation could be a new therapeutic strategy against human tauopathies. PMID:26390242

  18. High Suicide Risk after the Development of Cognitive and Working Memory Deficits Caused by Cannabis, Cocaine and Ecstasy Use

    ERIC Educational Resources Information Center

    Pompili, Maurizio; Lester, David; Girardi, Paolo; Tatarelli, Roberto

    2007-01-01

    We report the case of attempted suicide by a 30-year-old man who had significant cognitive deficits that developed after at least three years of polysubstance use with cannabis, methylenedioxymethamphetamine (MDMA, "ecstasy") and cocaine. The patient reported increasing difficulties in his professional and interpersonal life which may have been…

  19. The Relationship between Prenatal and Postnatal Exposure to Polychlorinated Biphenyls (PCBs) and Cognitive, Neuropsychological, and Behavioral Deficits: A Critical Appraisal

    ERIC Educational Resources Information Center

    Cicchetti, Domenic V.; Kaufman, Alan S.; Sparrow, Sara S.

    2004-01-01

    Our purpose in this report is to evaluate scientifically that body of literature relating the effects of prenatal and postnatal exposure to polychlorinated biphenyls (PCBs) upon neurobehavioral, health-related, and cognitive deficits in neonates, developing infants, children, and adults. The data derive from seven cohorts: six cohorts of mothers…

  20. Quantitative EEG Magnitudes in Children with and without Attention Deficit Disorder during Neurological Screening and Cognitive Tasks.

    ERIC Educational Resources Information Center

    Crawford, Helen J.; Barabasz, Marianne

    1996-01-01

    Quantitative EEG magnitude data were obtained from children with and without attention deficit disorder (ADD). The data suggest that the right fronto-centro-temporal region is not as "cognitively activated" relative to the left hemisphere in those children with ADD. Neurotherapy training of the right frontal and central regions in ADD children was…

  1. Spelling Difficulties in School-Aged Girls with Attention-Deficit/Hyperactivity Disorder: Behavioral, Psycholinguistic, Cognitive, and Graphomotor Correlates

    ERIC Educational Resources Information Center

    Åsberg Johnels, Jakob; Kopp, Svenny; Gillberg, Christopher

    2014-01-01

    Writing difficulties are common among children with attention-deficit/hyperactivity disorder (ADHD), but the nature of these difficulties has not been well studied. Here we relate behavioral, psycholinguistic, cognitive (memory/executive), and graphomotor measures to spelling skills in school-age girls with ADHD (n = 30) and an age-matched group…

  2. A Case Study of the Cognitive and Behavioral Deficits of Temporal Lobe Damage in Herpes Simplex Encephalitis.

    ERIC Educational Resources Information Center

    Greer, Margaret K.; And Others

    1989-01-01

    This case study illustrates the highly significant language difficulties, marked memory deficits, and propensity for physical aggression following temporal lobe damage brought about by herpes encephalitis, and presents the usefulness of a new diagnostic measure in delineating such a variable cognitive pattern. (Author)

  3. An Investigation of an Evaluation Method and Retraining Procedures for Emotionally Handicapped Children with Cognitive-Motor Deficits. Final Report.

    ERIC Educational Resources Information Center

    Rubin, Eli Z.; And Others

    To assess the effects of specialized retraining of cognitive, perceptual, and motor (CPM) deficits, a battery of tests was prepared and used with 200 behaviorally maladjusted and 200 problem-free children. The composite score indicated that 40% of the maladjusted group manifested major dysfunction whereas none of the problem-free group…

  4. Berry fruit can improve age-associated neuronal and cognitive deficits: from the laboratory to the clinic

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

  5. 16p11.2 Deletion Mice Display Cognitive Deficits in Touchscreen Learning and Novelty Recognition Tasks

    ERIC Educational Resources Information Center

    Yang, Mu; Lewis, Freeman C.; Sarvi, Michael S.; Foley, Gillian M.; Crawley, Jacqueline N.

    2015-01-01

    Chromosomal 16p11.2 deletion syndrome frequently presents with intellectual disabilities, speech delays, and autism. Here we investigated the Dolmetsch line of 16p11.2 heterozygous (+/-) mice on a range of cognitive tasks with different neuroanatomical substrates. Robust novel object recognition deficits were replicated in two cohorts of 16p11.2…

  6. Numerical and Arithmetical Cognition: A Longitudinal Study of Process and Concept Deficits in Children with Learning Disability.

    ERIC Educational Resources Information Center

    Geary, David C.; Hamson, Carmen O.; Hoard, Mary K.

    2000-01-01

    Compared performance of first and second graders with normal intelligence but with learning disabilities (LD) in mathematics, reading, or both and children with variable achievement test performance to that of academically normal peers on experimental and psychometric tasks. Found that LD groups showed specific cognitive deficit patterns; children…

  7. An Integrative, Cognitive-Behavioral, Systemic Approach to Working with Students Diagnosed with Attention Deficit Hyperactive Disorder

    ERIC Educational Resources Information Center

    Shillingford, Margaret Ann; Lambie, Glenn W.; Walter, Sara Meghan

    2007-01-01

    Attention deficit hyperactive disorder (ADHD) is a prevalent diagnostic disorder for many students, which correlates with negative academic, social, and personal consequences. This article presents an integrative, cognitive-behavioral, systemic approach that offers behaviorally based interventions for professional school counselors to support…

  8. A principal component model of medical health: implications for cognitive deficits and decline among adults in a population-based sample.

    PubMed

    Persson, Ninni; Viitanen, Matti; Almkvist, Ove; Wahlin, Åke

    2013-10-01

    Longitudinal blood- and cognitive data from 879 adults were analyzed to extract a multidimensional health structure for prediction of cognitive change. Six health components were identified and replicated at two waves. Following, cognitive outcomes were regressed on the health components. Large proportions of cognitive age related variations were accounted for by baseline health in both cross-sectional and prospective analyses. Less variation was accounted for when health change and cognitive change were contrasted. Cardiovascular health was particularly important for prediction of cognitive change. Our study underlines causal relations between health and cognitive functions, and suggests that some effects are long term. PMID:23180878

  9. Insulin-like growth factor 2 rescues aging-related memory loss in rats.

    PubMed

    Steinmetz, Adam B; Johnson, Sarah A; Iannitelli, Dylan E; Pollonini, Gabriella; Alberini, Cristina M

    2016-08-01

    Aging is accompanied by declines in memory performance, and particularly affects memories that rely on hippocampal-cortical systems, such as episodic and explicit. With aged populations significantly increasing, the need for preventing or rescuing memory deficits is pressing. However, effective treatments are lacking. Here, we show that the level of the mature form of insulin-like growth factor 2 (IGF-2), a peptide regulated in the hippocampus by learning, required for memory consolidation and a promoter of memory enhancement in young adult rodents, is significantly reduced in hippocampal synapses of aged rats. By contrast, the hippocampal level of the immature form proIGF-2 is increased, suggesting an aging-related deficit in IGF-2 processing. In agreement, aged compared to young adult rats are deficient in the activity of proprotein convertase 2, an enzyme that likely mediates IGF-2 posttranslational processing. Hippocampal administration of the recombinant, mature form of IGF-2 rescues hippocampal-dependent memory deficits and working memory impairment in aged rats. Thus, IGF-2 may represent a novel therapeutic avenue for preventing or reversing aging-related cognitive impairments. PMID:27318130

  10. Oligodendrocyte and Interneuron Density in Hippocampal Subfields in Schizophrenia and Association of Oligodendrocyte Number with Cognitive Deficits

    PubMed Central

    Falkai, Peter; Steiner, Johann; Malchow, Berend; Shariati, Jawid; Knaus, Andreas; Bernstein, Hans-Gert; Schneider-Axmann, Thomas; Kraus, Theo; Hasan, Alkomiet; Bogerts, Bernhard; Schmitt, Andrea

    2016-01-01

    In schizophrenia, previous stereological post-mortem investigations of anterior, posterior, and total hippocampal subfields showed no alterations in total neuron number but did show decreased oligodendrocyte numbers in CA4, an area that corresponds to the polymorph layer of the dentate gyrus (DG). However, these investigations identified oligodendrocytes only on the basis of morphological criteria in Nissl staining and did not assess alterations of interneurons with immunohistochemical markers. Moreover, the association of findings in the posterior hippocampus with cognitive deficits remains unknown. On the basis of the available clinical records, we compared patients with definite and possible cognitive dysfunction; nine patients had evidence in their records of either definite (n = 4) or possible (n = 5) cognitive dysfunction. Additionally, we assessed the density of two oligodendrocyte subpopulations immunostained by the oligodendrocyte transcription factors Olig1 and Olig2 and of interneurons immunolabeled by parvalbumin. We investigated posterior hippocampal subregions in the post-mortem brains of the same schizophrenia patients (SZ; n = 10) and healthy controls (n = 10) we examined in our previously published stereological studies. Our stereological studies found that patients with definite cognitive deficits had decreased total/Nissl-stained oligodendrocyte numbers in the left (p = 0.014) and right (p = 0.050) CA4, left CA2/3 (p = 0.050), left CA1 (p = 0.027), and left (p = 0.050) and right (p = 0.014) subiculum of the anterior part of the hippocampus compared to patients with possible cognitive deficits. In the present study, we found no significant influence of definite cognitive deficits in the posterior part of the hippocampus, whereas in the entire hippocampus SZ with definite cognitive deficits showed decreased oligodendrocyte numbers in the left (p = 0.050) and right (p = 0.050) DG and left CA2/3 (p = 0.050). We did not find significant differences in

  11. Methylene blue reduces Aβ levels and rescues early cognitive deficit by increasing proteasome activity

    PubMed Central

    Medina, David X.; Caccamo, Antonella; Oddo, Salvatore

    2010-01-01

    Promising results have emerged from a phase II clinical trial testing Methylene blue (MB) as a potential therapeutic for Alzheimer disease (AD), where improvements in cognitive functions of AD patients after 6 months of MB administration have been reported. Despite these reports, no preclinical testing of MB in mammals has been published, and thus its mechanism of action in relation to AD pathology remains unknown. In order to elucidate the effects of MB on AD pathology and to determine its mechanism of action, we used a mouse model (3xTg-AD) that develops age-dependent accumulation of Aβ and tau and cognitive decline. Here, we report that chronic dietary MB treatment reduces Aβ levels and improves learning and memory deficits in the 3xTg-AD mice. The mechanisms underlying the effects of MB on Aβ pathology appears to be mediated by an increase in Aβ clearance as we show that MB increases the chymotrypsin-and trypsin-like activities of the proteasome in the brain. To our knowledge, this is the first report showing that MB increases proteasome function and ameliorates AD-like pathology in vivo. Overall, the data presented here support the use of MB for the treatment of AD and offer a possible mechanism of action. PMID:20731659

  12. Effectiveness of nootropic drugs with cholinergic activity in treatment of cognitive deficit: a review

    PubMed Central

    Colucci, Luisa; Bosco, Massimiliano; Rosario Ziello, Antonio; Rea, Raffaele; Amenta, Francesco; Fasanaro, Angiola Maria

    2012-01-01

    Nootropics represent probably the first “smart drugs” used for the treatment of cognitive deficits. The aim of this paper is to verify, by a systematic analysis of the literature, the effectiveness of nootropics in this indication. The analysis was limited to nootropics with cholinergic activity, in view of the role played by acetylcholine in learning and memory. Acetylcholine was the first neurotransmitter identified in the history of neuroscience and is the main neurotransmitter of the peripheral, autonomic, and enteric nervous systems. We conducted a systematic review of the literature for the 5-year period 2006–2011. From the data reported in the literature, it emerges that nootropics may be an effective alternative for strengthening and enhancing cognitive performance in patients with a range of pathologies. Although nootropics, and specifically the cholinergic precursors, already have a long history behind them, according to recent renewal of interest, they still seem to have a significant therapeutic role. Drugs with regulatory indications for symptomatic treatment of Alzheimer’s disease, such as cholinesterase inhibitors and memantine, often have transient effects in dementia disorders. Nootropics with a cholinergic profile and documented clinical effectiveness in combination with cognate drugs such as cholinesterase inhibitors or alone in patients who are not suitable for these inhibitors should be taken into account and evaluated further.

  13. Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer's Disease.

    PubMed

    Yang, Eun-Jeong; Ahn, Sangzin; Ryu, Junghwa; Choi, Moon-Seok; Choi, Shinkyu; Chong, Young Hae; Hyun, Jin-Won; Chang, Moon-Jeong; Kim, Hye-Sun

    2015-01-01

    Alzheimer's disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5-trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1-42 (Aβ1-42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1-42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels. PMID:26284625

  14. Phloroglucinol Attenuates the Cognitive Deficits of the 5XFAD Mouse Model of Alzheimer’s Disease

    PubMed Central

    Ryu, Junghwa; Choi, Moon-Seok; Choi, Shinkyu; Chong, Young Hae; Hyun, Jin-Won; Chang, Moon-Jeong; Kim, Hye-Sun

    2015-01-01

    Alzheimer’s disease (AD) is the most common form of dementia among the elderly. Neuritic plaques whose primary component is amyloid beta peptide (Aβ) and neurofibrillary tangles which are composed of hyperphosphorylated tau, are known to be the neuropathological hallmarks of AD. In addition, impaired synaptic plasticity in neuronal networks is thought to be important mechanism underlying for the cognitive deficits observed in AD. Although various causative factors, including excitotoxicity, mitochondrial dysregulation and oxidative damage caused by Aβ, are involved in early onset of AD, fundamental therapeutics that can modify the progression of this disease are not currently available. In the present study, we investigated whether phloroglucinol (1, 3, 5—trihydroxybenzene), a component of phlorotannins, which are plentiful in Ecklonia cava, a marine brown alga species, displays therapeutic activities in AD. We found that phloroglucinol attenuates the increase in reactive oxygen species (ROS) accumulation induced by oligomeric Aβ1–42 (Aβ1–42) treatment in HT-22, hippocampal cell line. In addition, phloroglucinol was shown to ameliorate the reduction in dendritic spine density induced by Aβ1–42 treatment in rat primary hippocampal neuron cultures. We also found that the administration of phloroglucinol to the hippocampal region attenuated the impairments in cognitive dysfunction observed in 22-week-old 5XFAD (Tg6799) mice, which are used as an AD animal model. These results indicate that phloroglucinol displays therapeutic potential for AD by reducing the cellular ROS levels. PMID:26284625

  15. Facilitative effects of bi-hemispheric tDCS in cognitive deficits of Parkinson disease patients.

    PubMed

    Leite, Jorge; Gonçalves, Oscar F; Carvalho, Sandra

    2014-02-01

    Parkinson's disease (PD) is a progressive neurodegenerative disorder, primarily characterized by motor symptoms such as tremor, rigidity, bradykinesia, stiffness, slowness and impaired equilibrium. Although the motor symptoms have been the focus in PD, slight cognitive deficits are commonly found in non-demented and non-depressed PD patients, even in early stages of the disease, which have been linked to the subsequent development of pathological dementia. Thus, strongly reducing the quality of life (QoL). Both levodopa therapy and deep brain stimulation (DBS) have yield controversial results concerning the cognitive symptoms amelioration in PD patients. That does not seems to be the case with transcranial direct current stimulation (tDCS), although better stimulation parameters are needed. Therefore we hypothesize that simultaneously delivering cathodal tDCS (or ctDCS), over the right prefrontal cortex delivered with anodal tDCS (or atDCS) to left prefrontal cortex could be potentially beneficial for PD patients, either by mechanisms of homeostatic plasticity and by increases in the extracellular dopamine levels over the striatum. PMID:24332532

  16. Social cognitive and neurocognitive deficits in inpatients with unilateral thalamic lesions – pilot study

    PubMed Central

    Wilkos, Ewelina; Brown, Timothy JB; Slawinska, Ksenia; Kucharska, Katarzyna A

    2015-01-01

    worse performance on Reading the Mind in the Eyes Test, revised version II. Neuropsychological assessment demonstrated some statistically significant deficits in learning and remembering both verbal and visual material, long-term information storing, problem solving, and executive functions such as verbal fluency. Conclusion Patients at early stage of unilateral thalamic stroke showed both neurocognitive and social cognitive deficits. Further research is needed to increase understanding about diagnosis, early treatment, and prognosis of patients with thalamic lesions. PMID:25914535

  17. Differential profiles in auditory social cognition deficits between adults with autism and schizophrenia spectrum disorders: A preliminary analysis.

    PubMed

    Tobe, Russell H; Corcoran, Cheryl M; Breland, Melissa; MacKay-Brandt, Anna; Klim, Casimir; Colcombe, Stanley J; Leventhal, Bennett L; Javitt, Daniel C

    2016-08-01

    Impairment in social cognition, including emotion recognition, has been extensively studied in both Autism Spectrum Disorders (ASD) and Schizophrenia (SZ). However, the relative patterns of deficit between disorders have been studied to a lesser degree. Here, we applied a social cognition battery incorporating both auditory (AER) and visual (VER) emotion recognition measures to a group of 19 high-functioning individuals with ASD relative to 92 individuals with SZ, and 73 healthy control adult participants. We examined group differences and correlates of basic auditory processing and processing speed. Individuals with SZ were impaired in both AER and VER while ASD individuals were impaired in VER only. In contrast to SZ participants, those with ASD showed intact basic auditory function. Our finding of a dissociation between AER and VER deficits in ASD relative to Sz support modality-specific theories of emotion recognition dysfunction. Future studies should focus on visual system-specific contributions to social cognitive impairment in ASD. PMID:27131617

  18. [Age-related macular degeneration].

    PubMed

    Budzinskaia, M V

    2014-01-01

    The review provides an update on the pathogenesis and new treatment modalities for neovascular age-related macular degeneration (AMD). The impact of polymorphism in particular genes, including complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2/LOC387715), and serine peptidase (HTRA1), on AMD development is discussed. Clinical presentations of different forms of exudative AMD, that is classic, occult, or more often mixed choroidal neovascularization, retinal angiomatous proliferation, and choroidal polypoidal vasculopathy, are described. Particular attention is paid to the results of recent clinical trials and safety issues around the therapy. PMID:25715554

  19. Sex Differences in Adult Cognitive Deficits after Adolescent Nicotine Exposure in Rats

    PubMed Central

    Pickens, Laura R. G.; Rowan, James D.; Bevins, Rick A.; Fountain, Stephen B.

    2013-01-01

    This study was designed to determine whether deficits in adult serial pattern learning caused by adolescent nicotine exposure persist as impairments in asymptotic performance, whether adolescent nicotine exposure differentially retards learning about pattern elements that are inconsistent with “perfect” pattern structure, and whether there are sex differences in rats’ response to adolescent nicotine exposure as assessed by a serial multiple choice task. The current study replicated the results of our initial report (Fountain, Rowan, Kelley, Willey, & Nolley, 2008) using this task by showing that adolescent nicotine exposure (1.0 mg/kg/day nicotine for 35 days) produced a specific cognitive impairment in male rats that persisted into adulthood at least a month after adolescent nicotine exposure ended. In addition, sex differences were observed even in controls, with additional evidence that adolescent nicotine exposure significantly impaired learning relative to same-sex controls for chunk boundary elements in males and for violation elements in females. All nicotine-induced impairments were overcome by additional training so that groups did not differ at asymptote. An examination of the types of errors rats made indicated that adolescent nicotine exposure slowed learning without affecting rats’ cognitive strategy in the task. This data pattern suggests that exposure to nicotine in adolescence may have impaired different aspects of adult stimulus-response discrimination learning processes in males and females, but left abstract rule learning processes relatively spared in both sexes. These effects converge with other findings in the field and reinforce the concern that adolescent nicotine exposure poses an important threat to cognitive capacity in adulthood. PMID:23673345

  20. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  1. Salidroside ameliorates arthritis-induced brain cognition deficits by regulating Rho/ROCK/NF-κB pathway.

    PubMed

    Zhu, Lingpeng; Chen, Tong; Chang, Xiayun; Zhou, Rui; Luo, Fen; Liu, Jingyan; Zhang, Kai; Wang, Yue; Yang, Ying; Long, Hongyan; Liu, Yu; Yan, Tianhua; Ma, Chunhua

    2016-04-01

    The prevalence of cognitive impairment in rheumatoid arthritis (RA) patients was increasingly serious nowadays. The purpose of the current study was to explore whether salidroside (Sal) could alleviate arthritis-induced cognition deficits and examine the relationship between the impairment and Rho/ROCK/NF-κB pathway. Collagen-induced arthritis (CIA) was established by the injection of chicken type II collagen (CII), complete Freund's adjuvant (CFA) and incomplete Freund's adjuvant (IFA). Arthritic lesions of CIA rats were assessed by arthritis index score, swelling of paws and histological analysis. Cognitive deficits symptoms of CIA rats were monitored through Morris water maze test. The contents of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) in hippocampus and serum were significantly reduced with salidroside (20 mg/kg, 40 mg/kg) treatment compared with those in the CIA group. In parallel, we demonstrated that the expressions of RhoA, ROCK1, ROCK2, p-NF-κBp65, p-IκBα, p-IKKα and p-IKKβ were enhanced accompanying the investigation arthritis-induced cognition deficits, which were remarkably down-regulated by salidroside and confirmed by the results obtained from western blot and immunohistochemistry. LC-MS/MS results ascertained that Sal could enter into the blood and brain tissues to exhibit the protective effect on arthritis-induced cognitive dysfunction. Therefore, it was assumed that Sal might be a potential therapeutic candidate to treat arthritis-induced brain cognition deficits through the regulation of Rho/ROCK/NF-κB signaling. PMID:26690894

  2. Emotion Perception or Social Cognitive Complexity: What Drives Face Processing Deficits in Autism Spectrum Disorder?

    ERIC Educational Resources Information Center

    Walsh, Jennifer A.; Creighton, Sarah E.; Rutherford, M. D.

    2016-01-01

    Some, but not all, relevant studies have revealed face processing deficits among those with autism spectrum disorder (ASD). In particular, deficits are revealed in face processing tasks that involve emotion perception. The current study examined whether either deficits in processing emotional expression or deficits in processing social cognitive…

  3. Age-related hearing loss

    MedlinePlus

    ... is no known single cause of age-related hearing loss. Most commonly, it is caused by changes in the inner ear that occur as you grow older. Your genes and loud noise (from rock concerts or music headphones) may play a large role. The following ...

  4. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice

    PubMed Central

    Yildirim, Emre; Connor, David A.; Gould, Thomas J.

    2015-01-01

    Nicotine withdrawal produces cognitive deficits that can predict relapse. Amelioration of these cognitive deficits emerges as a target in current smoking cessation therapies. In rodents, withdrawal from chronic nicotine disrupts contextual fear conditioning (CFC), whereas acute nicotine enhances this hippocampus-specific learning and memory. These modifications are mediated by β2-subunit-containing (β2*) nicotinic acetylcholine receptors in the hippocampus. We aimed to test ABT-089, a partial agonist of α4β2*, and ABT-107, an α7 nicotinic acetylcholine receptor agonist, for amelioration of cognitive deficits induced by withdrawal from chronic nicotine in mice. Mice underwent chronic nicotine administration (12.6 mg/kg/day or saline for 12 days), followed by 24 h of withdrawal. At the end of withdrawal, mice received 0.3 or 0.6 mg/kg ABT-089 or 0.3 mg/kg ABT-107 (doses were determined through initial dose–response experiments and prior studies) and were trained and tested for CFC. Nicotine withdrawal produced deficits in CFC that were reversed by acute ABT-089, but not ABT-107. Cued conditioning was not affected. Taken together, our results suggest that modulation of hippocampal learning and memory using ABT-089 may be an effective component of novel therapeutic strategies for nicotine addiction. PMID:25426579

  5. Longitudinal characterization of motor and cognitive deficits in a model of penetrating ballistic-like brain injury.

    PubMed

    Shear, Deborah A; Lu, Xi-Chun May; Bombard, Matthew C; Pedersen, Rebecca; Chen, Zhiyong; Davis, Angela; Tortella, Frank C

    2010-10-01

    Traumatic brain injury (TBI) produces a wide range of motor and cognitive changes. While some neurological symptoms may respond to therapeutic intervention during the initial recovery period, others may persist for many years after the initial insult, and often have a devastating impact on quality of life for the TBI victim. The aim of the current study was to develop neurobehavioral testing parameters designed to provide a longitudinal assessment of neurofunctional deficits in a rodent model of penetrating ballistic-like brain injury (PBBI). We report here a series of experiments in which unilateral frontal PBBI was induced in rats, and motor/cognitive abilities were assessed using a battery of tests ranging from 30 min to 10 weeks post-injury. The results showed that PBBI produced consistent and significant (1) neurological deficits (neuroscore examination: 30 min to 10 weeks post-PBBI), (2) sensorimotor dysfunction in the contralateral forelimb (forelimb asymmetry task: 7 and 21 days), (3) motor dysfunction (balance beam task: 3-7 days; and fixed-speed rotarod task: 3-28 days), and (4) spatial learning deficits in the Morris water maze (MWM) task out to 10 weeks post-injury. Overall, the results of this study demonstrate that PBBI produces enduring motor and cognitive deficits, and identifies the optimal task and testing parameters for facilitating longitudinal screening of promising therapeutic interventions in this brain injury model. PMID:20684676

  6. Cluster analysis of cognitive deficits may mark heterogeneity in schizophrenia in terms of outcome and response to treatment

    PubMed Central

    Gilbert, Elsa; Mérette, Chantal; Jomphe, Valérie; Émond, Claudia; Rouleau, Nancie; Bouchard, Roch-Hugo; Roy, Marc-André; Paccalet, Thomas

    2016-01-01

    Cognitive impairments are central to schizophrenia, but their clinical utility for tagging heterogeneity in lifetime outcome and response to treatment is not conclusive. By exploiting four cognitive domains consistently showing large deficits in studies, we tested whether cluster analysis would define separate subsets of patients and then whether the disease heterogeneity marked by these clusters would be related to lifetime outcome and response to treatment. A total of 112 schizophrenia patients completed a neuropsychological evaluation. The PANSS, GAF-S and GAF-F were rated at the onset and endpoint of the illness trajectory. A blind judgment of the lifetime response to treatment was made. The first cluster presented near-normal cognitive performance. Two other clusters of severely impaired patients were identified: one generally impaired in the four cognitive domains and another selectively impaired in visual episodic memory and processing speed, each relating to a different lifetime evolution of disease and treatment response. Although the two impaired clusters were clinically indistinguishable in symptom severity and functioning at disease onset, patients with selective cognitive impairments demonstrated better improvement at outcome, whereas the generally impaired patients were more likely to be treatment refractory. The findings have implications for the management of patients and for clinical trials since particular combinations of cognitive deficits in patients would influence their treatment response. PMID:24173295

  7. Cognition and the compassion deficit: the social psychology of helping behaviour in nursing.

    PubMed

    Paley, John

    2014-10-01

    This paper discusses compassion failure and compassion deficits in health care, using two major reports by Robert Francis in the UK as a point of reference. Francis enquired into events at the Mid Staffordshire Hospital between 2005 and 2009, events that unequivocally warrant the description 'appalling care'. These events prompted an intense national debate, along with proposals for significant changes in the regulation of nursing and nurse education. The circumstances are specific to the UK, but the issues are international. I suggest that social psychology provides numerous hints about the mechanisms that might have been involved at Mid Staffs and about the reasons why outsiders are blind to these mechanisms. However, there have been few references to social psychology in the post-Francis debate (the Francis Report itself makes no reference to it at all). It is an enormously valuable resource, and it has been overlooked. Drawing on the social psychology literature, I express scepticism about the idea that there was a compassion deficit among the Mid Staff nurses - the assumption that the appalling care had something to do with the character, attitudes, and values of nurses - and argue that the Francis Report's emphasis on a 'culture of compassion and caring in nurse recruitment, training and education' is misconceived. It was not a 'failure of compassion' that led to the events in Mid Staffs but an interlocking set of contextual factors that are known to affect social cognition. These factors cannot be corrected or compensated for by teaching ethics, empathy, and compassion to student nurses. PMID:24447716

  8. Lack of association between mutation size and cognitive/behavior deficits in fragile X males: A brief report

    SciTech Connect

    Fisch, G.S.; Simensen, R.

    1996-08-09

    Previously, researchers reported molecular-neurobehavioral or molecular-cognitive associations in individuals with fra(X) (fragile X) mutation. However, not all investigators have noted molecular-behavioral relationships. Consequently, we examined prospectively 30 fra(X) males age 3-15 years from four testing sites to determine whether there was a relationship between mutation size and degree of either cognitive or adaptive behavior deficit. To measure cognitive abilities, all individuals were administered the Stanford-Binet (4th edition) IQ test. To evaluate adaptive behavior (DQ) skills, all individuals were assessed using the Vineland Adaptive Behavior Scale. To determine fra(X) status, genomic DNA from all individuals was extracted and digested with EcoRI and EagI restriction enzymes. Southern blots were prepared and hybridized with the pE5.1 probe. The Pearson correlation coefficient between full mutation size and composite IQ score revealed a non-significant, near-zero association (r = 0.06; P > .76). The Pearson coefficient between mutation size and DQ also showed a non-significant, near-zero association (r = 0.06; P >.73). We conclude that while fra(X) mutation produces cognitive and behavior deficits in males who inherit the defective gene, there is no relationship between mutation size and degree of deficit. 14 refs., 2 figs.

  9. Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice.

    PubMed

    Wu, Ruiyong; Shui, Li; Wang, Siyang; Song, Zhenzhen; Tai, Fadao

    2016-10-01

    Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful neuroprotection and stress-alleviating properties. However, whether BB exerts a positive effect on depression and cognitive deficit induced by chronic stress is not known. The present study was designed to investigate the influence of BB on depression and cognitive impairments induced by chronic unpredictable mild stress (CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We replicated the finding that CUMS induced depression-like behavior and cognitive deficits as the CUMS+vehicle (VEH) group showed a significant increase in immobility in the tail suspension test, a decrease in the discrimination index of the novel object recognition task, and increased latency to platform and decreased number of platform crossings in the Morris water maze compared with the control+VEH group. Chronic administration of BB effectively reversed these alterations. In addition, the CUMS+VEH group showed significantly higher levels of baseline serum corticosterone than those of the control+VEH group and BB dose-dependently inhibited this effect. Our results suggest that BB may be useful for inhibition of depression-like behavior and cognitive deficits, and this protective effect was possibly exerted partly through an action on the hypothalamic-pituitary-adrenal axis. PMID:27509313

  10. Lack of association between mutation size and cognitive/behavior deficits in fragile X males: a brief report.

    PubMed

    Fisch, G S; Carpenter, N; Howard-Peebles, P N; Maddalena, A; Simensen, R; Tarleton, J; Julien-Inalsingh, C; Chalifoux, M; Holden, J J

    1996-08-01

    Previously, researchers reported molecular-neurobehavioral or molecular-cognitive associations in individuals with fra(X) (fragile X) mutation. However, not all investigators have noted molecular-behavioral relationships. Consequently, we examined prospectively 30 fra(X) males age 3-15 years from four testing sites to determine whether there was a relationship between mutation size and degree of either cognitive or adaptive behavior deficit. To measure cognitive abilities, all individuals were administered the Stanford-Binet (4th edition) IQ test. To evaluate adaptive behavior (DQ) skills, all individuals were assessed using the Vineland Adaptive Behavior Scale. To determine fra(X) status, genomic DNA from all individuals was extracted and digested with EcoRI and EagI restriction enzymes. Southern blots were prepared and hybridized with the pE5.1 probe. The Pearson correlation coefficient between full mutation size and composite IQ score revealed a nonsignificant, near-zero association (r = 0.06; P > .76). The Pearson coefficient between mutation size and DQ also showed a nonsignificant, near-zero association (r = 0.06; P > .73). We conclude that while fra(X) mutation produces cognitive and behavior deficits in males who inherit the defective gene, there is no relationship between mutation size and degree of deficit. PMID:8844081

  11. Early treatment with high-dose interferon beta-1a reverses cognitive and cortical plasticity deficits in multiple sclerosis

    PubMed Central

    Mori, Francesco; Kusayanagi, Hajime; Buttari, Fabio; Centini, Barbara; Monteleone, Fabrizia; Nicoletti, Carolina Gabri; Bernardi, Giorgio; Di Cantogno, Elisabetta Verdun; Marciani, Maria Grazia; Centonze, Diego

    2012-01-01

    Summary Acute inflammation is associated with cognitive deficits and alterations of cortical plasticity in multiple sclerosis (MS). We tested whether early treatment with high-dose interferon (IFN) beta-1a, known to reduce inflammatory activity, improves cortical function and cognitive deficits in MS. Eighty treatment-naïve relapsing-remitting MS (RRMS) patients received IFN beta-1a (44 mcg) subcutaneously three times per week. Cognitive performance and cortical plasticity were measured through the paced auditory serial addition test (PASAT) and intermittent theta burst stimulation (iTBS) before and up to two years after IFN beta-1a initiation. Before treatment, patients with gadolinium-enhancing lesions (Gd+) on MRI performed worse on the PASAT, and showed lower iTBS-induced plasticity, compared with Gd− patients. Six months after treatment initiation both PASAT and iTBS-induced plasticity improved in Gd+ and remained stable in Gd− patients. These results suggest that cognitive and synaptic plasticity deficits may be rescued during high-dose IFN beta-1a treatment in newly-diagnosed RRMS patients with Gd+ lesions. PMID:23402677

  12. Sensation-to-Cognition Cortical Streams in Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X.; García-García, David; Lage-Castellanos, Agustín; Dijk, Koene R.A.Van; Navas-Sánchez, Francisco J.; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

    2015-01-01

    We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex—visual, auditory, and somatosensory—we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. PMID:25821110

  13. Sensation-to-cognition cortical streams in attention-deficit/hyperactivity disorder.

    PubMed

    Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X; García-García, David; Lage-Castellanos, Agustín; Van Dijk, Koene R A; Navas-Sánchez, Francisco J; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

    2015-07-01

    We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex-visual, auditory, and somatosensory-we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. PMID:25821110

  14. Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice.

    PubMed

    Huang, Pengcheng; Li, Cai; Fu, Tianli; Zhao, Dan; Yi, Zhen; Lu, Qing; Guo, Lianjun; Xu, Xulin

    2015-07-15

    Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways. PMID:25869780

  15. Hypercholesterolemic diet applied to rat dams protects their offspring against cognitive deficits. Simulated neonatal anoxia model.

    PubMed

    Bohr, Iwo

    2004-09-30

    There is accumulating data suggesting a neuroprotective activity of cholesterol, especially in stroke and Alzheimer's disease (AD). In the present study, a protective activity of this lipid in simulated neonatal anoxia was investigated. Rats were subjected to high cholesterol by feeding their dams with a diet enriched with cholesterol. Half of these rats were subjected to anoxia. One and a half months later, the rats were tested for their ability to acquire a spatial memory, one group on the linear maze and the other on the Morris water maze. After these assessments, the level of total plasma cholesterol was measured. Rats from dams subjected to neonatal anoxia on standard diet performed worse than control rats in both types of behavioral experiments, whereas anoxic rats from dams were housed on hypercholesterolemic diet performed as control animals. It suggests that dietetic cholesterol applied by their dams protected rats against cognitive deficits elicited by neonatal anoxia. Furthermore, offspring of anoxic rats housed on standard diet had elevated levels of blood cholesterol in relation to control animals. Generally, anoxia affected the concentration of this lipid much stronger than hypercholesterolemic diet of their dams. It might mean that the anoxia-related rise of cholesterol could be involved in physiological phenomenon being an adaptive response to neurotoxic processes. This concept is discussed in relation to pathological mechanisms in AD. PMID:15327920

  16. MDM2 inhibition rescues neurogenic and cognitive deficits in a mouse model of fragile X syndrome.

    PubMed

    Li, Yue; Stockton, Michael E; Bhuiyan, Ismat; Eisinger, Brian E; Gao, Yu; Miller, Jessica L; Bhattacharyya, Anita; Zhao, Xinyu

    2016-04-27

    Fragile X syndrome, the most common form of inherited intellectual disability, is caused by loss of the fragile X mental retardation protein (FMRP). However, the mechanism remains unclear, and effective treatment is lacking. We show that loss of FMRP leads to activation of adult mouse neural stem cells (NSCs) and a subsequent reduction in the production of neurons. We identified the ubiquitin ligase mouse double minute 2 homolog (MDM2) as a target of FMRP. FMRP regulates Mdm2 mRNA stability, and loss of FMRP resulted in elevated MDM2 mRNA and protein. Further, we found that increased MDM2 expression led to reduced P53 expression in adult mouse NSCs, leading to alterations in NSC proliferation and differentiation. Treatment with Nutlin-3, a small molecule undergoing clinical trials for treating cancer, specifically inhibited the interaction of MDM2 with P53, and rescued neurogenic and cognitive deficits in FMRP-deficient mice. Our data reveal a potential regulatory role for FMRP in the balance between adult NSC activation and quiescence, and identify a potential new treatment for fragile X syndrome. PMID:27122614

  17. Smart Soup, a Traditional Chinese Medicine Formula, Ameliorates Amyloid Pathology and Related Cognitive Deficits

    PubMed Central

    Li, Xiaohang; Cui, Jin; Ding, Jianqing; Wang, Ying; Zeng, Xianglu; Ling, Yun; Shen, Xiaoheng; Chen, Shengdi; Huang, Chenggang; Pei, Gang

    2014-01-01

    Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae (RP), is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease. PMID:25386946

  18. Inhibitory Interneuron Deficit Links Altered Network Activity and Cognitive Dysfunction in Alzheimer Model

    PubMed Central

    Verret, Laure; Mann, Edward O.; Hang, Giao B.; Barth, Albert M. I.; Cobos, Inma; Ho, Kaitlyn; Devidze, Nino; Masliah, Eliezer; Kreitzer, Anatol C.; Mody, Istvan; Mucke, Lennart; Palop, Jorge J.

    2012-01-01

    SUMMARY Alzheimer's disease (AD) results in cognitive decline and altered network activity, but the mechanisms are unknown. To identify such mechanisms, we studied human amyloid precursor protein (hAPP) transgenic mice, which simulate key aspects of AD. Electroencephalographic recordings in hAPP mice revealed spontaneous epileptiform discharges, indicating network hypersynchrony, primarily during reduced gamma oscillatory activity. Because this oscillatory rhythm is generated by inhibitory parvalbumin (PV) cells, network dysfunction in hAPP mice might arise from impaired PV cells. Supporting this hypothesis, hAPP mice and AD patients had decreased levels of the interneuron-specific and PV cell–predominant voltage-gated sodium channel subunit Nav1.1. Restoring Nav1.1 levels in hAPP mice by Nav1.1-BAC expression increased inhibitory synaptic activity and gamma oscillations and reduced hypersynchrony, memory deficits, and premature mortality. We conclude that reduced Nav1.1 levels and PV cell dysfunction critically contribute to abnormalities in oscillatory rhythms, network synchrony, and memory in hAPP mice and possibly in AD. PMID:22541439

  19. Thalamic damage in periventricular leukomalacia: novel pathologic observations relevant to cognitive deficits in survivors of prematurity.

    PubMed

    Ligam, Poonam; Haynes, Robin L; Folkerth, Rebecca D; Liu, Lena; Yang, May; Volpe, Joseph J; Kinney, Hannah C

    2009-05-01

    Despite major advances in the long-term survival of premature infants, cognitive deficits occur in 30-50% of very preterm (<32 gestational weeks) survivors. Impaired working memory and attention despite average global intelligence are central to the academic difficulties of the survivors. Periventricular leukomalacia (PVL), characterized by periventricular necrosis and diffuse gliosis in the cerebral white matter, is the major brain pathology in preterm infants. We tested the novel hypothesis that pathology in thalamic nuclei critical for working memory and attention, i.e. mediodorsal nucleus and reticular nucleus, respectively, occurs in PVL. In 22 PVL cases (gestational age 32.5 +/- 4.8 wk) and 16 non-PVL controls (36.7 +/- 5.2 wk) who died within infancy, the incidence of thalamic pathology was significantly higher in PVL cases (59%; 13/22) compared with controls (19%; 3/16) (p = 0.01), with substantial involvement of the mediodorsal, and reticular nuclei in PVL. The prevention of thalamic damage may be required for the eradication of defects in survivors with PVL. PMID:19127204

  20. Neuregulin 1 improves cognitive deficits and neuropathology in an Alzheimer’s disease model

    PubMed Central

    Xu, Jiqing; de Winter, Fred; Farrokhi, Catherine; Rockenstein, Edward; Mante, Michael; Adame, Anthony; Cook, Jonathan; Jin, Xin; Masliah, Eliezer; Lee, Kuo-Fen

    2016-01-01

    Several lines of evidence suggest that neuregulin 1 (NRG1) signaling may influence cognitive function and neuropathology in Alzheimer’s disease (AD). To test this possibility, full-length type I or type III NRG1 was overexpressed via lentiviral vectors in the hippocampus of line 41 AD mouse. Both type I and type III NRG1 improves deficits in the Morris water-maze behavioral task. Neuropathology was also significantly ameliorated. Decreased expression of the neuronal marker MAP2 and synaptic markers PSD95 and synaptophysin in AD mice was significantly reversed. Levels of Aβ peptides and plaques were markedly reduced. Furthermore, we showed that soluble ectodomains of both type I and type III NRG1 significantly increased expression of Aβ-degrading enzyme neprilysin (NEP) in primary neuronal cultures. Consistent with this finding, immunoreactivity of NEP was increased in the hippocampus of AD mice. These results suggest that NRG1 provides beneficial effects in candidate neuropathologic substrates of AD and, therefore, is a potential target for the treatment of AD. PMID:27558862

  1. Hippocampal Aβ expression, but not phosphorylated tau, predicts cognitive deficits following repeated peripheral poly I:C administration.

    PubMed

    White, J D; Eimerbrink, M J; Hayes, H B; Hardy, A; Van Enkevort, E A; Peterman, J L; Chumley, M J; Boehm, G W

    2016-10-15

    Alzheimer's disease is marked by the accumulation of the amyloid-beta (Aβ) peptide, and increases in phosphorylation of the microtubule associated protein, tau. Changes in these proteins are considered responsible, in part, for the progressive neuronal degeneration and cognitive deficits seen in AD. We examined the effect of repeated consecutive peripheral poly I:C injections on cognitive deficits, central Aβ, and phosphorylated tau accumulation, following three treatment durations: 7, 14, and 21 days. Forty-eight hours after the final injection, animals were trained in a contextual fear-conditioning paradigm, and tested 24h later. Immediately after testing, the hippocampus was collected to quantify Aβ and phosphorylated tau accumulation. Results showed that, although poly I:C-induced Aβ was significantly elevated at all time points examined, poly I:C only disrupted cognition after 14 and 21 days of administration. Moreover, elevations in phosphorylated tau were not seen until the 14-day time point. Interestingly, phosphorylated tau expression then declined at the 21-day time point. Finally, we demonstrated that Aβ levels are a stronger predictor of cognitive dysfunction, explaining 37% of the variance, whereas phosphorylated tau levels only accounted for 0.2%. Taken together, these results support the hypothesis that inflammation-induced elevation in Aβ disrupts cognition, independently of phosphorylated tau, and suggest that long-term administration of poly I:C may provide a model to investigate the contribution of long-term inflammation toward the development of Alzheimer's-like pathology. PMID:27449203

  2. Concussive Brain Trauma in the Mouse Results in Acute Cognitive Deficits and Sustained Impairment of Axonal Function

    PubMed Central

    Creed, Jennifer A.; DiLeonardi, Ann Mae; Fox, Douglas P.; Tessler, Alan R.

    2011-01-01

    Abstract Concussive brain injury (CBI) accounts for approximately 75% of all brain-injured people in the United States each year and is particularly prevalent in contact sports. Concussion is the mildest form of diffuse traumatic brain injury (TBI) and results in transient cognitive dysfunction, the neuropathologic basis for which is traumatic axonal injury (TAI). To evaluate the structural and functional changes associated with concussion-induced cognitive deficits, adult mice were subjected to an impact on the intact skull over the midline suture that resulted in a brief apneic period and loss of the righting reflex. Closed head injury also resulted in an increase in the wet weight:dry weight ratio in the cortex suggestive of edema in the first 24 h, and the appearance of Fluoro-Jade-B-labeled degenerating neurons in the cortex and dentate gyrus of the hippocampus within the first 3 days post-injury. Compared to sham-injured mice, brain-injured mice exhibited significant deficits in spatial acquisition and working memory as measured using the Morris water maze over the first 3 days (p<0.001), but not after the fourth day post-injury. At 1 and 3 days post-injury, intra-axonal accumulation of amyloid precursor protein in the corpus callosum and cingulum was accompanied by neurofilament dephosphorylation, impaired transport of Fluoro-Gold and synaptophysin, and deficits in axonal conductance. Importantly, deficits in retrograde transport and in action potential of myelinated axons continued to be observed until 14 days post-injury, at which time axonal degeneration was apparent. These data suggest that despite recovery from acute cognitive deficits, concussive brain trauma leads to axonal degeneration and a sustained perturbation of axonal function. PMID:21299360

  3. Fingolimod protects against neonatal white matter damage and long-term cognitive deficits caused by hyperoxia.

    PubMed

    Serdar, Meray; Herz, Josephine; Kempe, Karina; Lumpe, Katharina; Reinboth, Barbara S; Sizonenko, Stéphane V; Hou, Xinlin; Herrmann, Ralf; Hadamitzky, Martin; Heumann, Rolf; Hansen, Wiebke; Sifringer, Marco; van de Looij, Yohan; Felderhoff-Müser, Ursula; Bendix, Ivo

    2016-02-01

    Cerebral white matter injury is a leading cause of adverse neurodevelopmental outcome in prematurely born infants involving cognitive deficits in later life. Despite increasing knowledge about the pathophysiology of perinatal brain injury, therapeutic options are limited. In the adult demyelinating disease multiple sclerosis the sphingosine-1-phosphate (S1P) receptor modulating substance fingolimod (FTY720) has beneficial effects. Herein, we evaluated the neuroprotective potential of FTY720 in a neonatal model of oxygen-toxicity, which is associated with hypomyelination and impaired neuro-cognitive outcome. A single dose of FTY720 (1mg/kg) at the onset of neonatal hyperoxia (24h 80% oxygen on postnatal day 6) resulted in improvement of neuro-cognitive development persisting into adulthood. This was associated with reduced microstructural white matter abnormalities 4 months after the insult. In search of the underlying mechanisms potential non-classical (i.e. lymphocyte-independent) pathways were analysed shortly after the insult, comprising modulation of oxidative stress and local inflammatory responses as well as myelination, oligodendrocyte degeneration and maturation. Treatment with FTY720 reduced hyperoxia-induced oxidative stress, microglia activation and associated pro-inflammatory cytokine expression. In vivo and in vitro analyses further revealed that oxygen-induced hypomyelination is restored to control levels, which was accompanied by reduced oligodendrocyte degeneration and enhanced maturation. Furthermore, hyperoxia-induced elevation of S1P receptor 1 (S1P1) protein expression on in vitro cultured oligodendrocyte precursor cells was reduced by activated FTY720 and protection from degeneration is abrogated after selective S1P1 blockade. Finally, FTY720s' classical mode of action (i.e. retention of immune cells within peripheral lymphoid organs) was analysed demonstrating that FTY720 diminished circulating lymphocyte counts independent from hyperoxia

  4. Enriched endogenous n-3 polyunsaturated fatty acids alleviate cognitive and behavioral deficits in a mice model of Alzheimer's disease.

    PubMed

    Wu, Kefeng; Gao, Xiang; Shi, Baoyan; Chen, Shiyu; Zhou, Xin; Li, Zhidong; Gan, Yuhong; Cui, Liao; Kang, Jing Xuan; Li, Wende; Huang, Ren

    2016-10-01

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accompanied by memory deficits and neuropsychiatric dysfunction. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have seemly therapeutic potential in AD, but the benefit of n-3 PUFAs is still in debates. Here, we employed a transgenic mice carry fat-1 gene to encode n-3 desaturase from Caenorhabditis elegans, which increase endogenous n-3 PUFAs by converting n-6 PUFAs to n-3 PUFAs crossed with amyloid precursor protein (APP) Tg mice to evaluate the protective effects of endogenous n-3 PUFAs on cognitive and behavioral deficits of APP Tg mice. We fed APP, APP/fat-1 and fat-1 mice with n-6 PUFAs rich diet. Brain tissues were collected at 3, 9 and 12 months for fatty acid and gene expression analysis, histology and protein assays. Morris Water Maze Test, open field test and elevated plus maze test were performed to measure the behavior capability. From the results, the expression of fat-1 transgene increased cortical n-3: n-6 PUFAs ratio and n-3 PUFAs concentrations, and sensorimotor dysfunction and cognitive deficits in AD were significantly less severe in APP/fat-1 mice with endogenous n-3 PUFAs than in APP mice controls. The protection against disturbance of spontaneous motor activity and cognitive deficits in AD was strongly correlated with increased n-3: n-6 PUFAs ratio and endogenous n-3 PUFAs, reduced APP generation, inhibited amyloid β peptide aggregation, suppressed nuclear factor-kappa B and astroglia activation, and reduced death of neurons in the cortex of APP/fat-1 mice compared with APP mice controls. In conclusion, our study demonstrates that an available medication with the maintenance of enriched n-3 PUFAs in the brain could slow down cognitive decline and prevent neuropsychological disorder in AD. PMID:27474225

  5. Cognitive deficits caused by a disease-mutation in the α3 Na(+)/K(+)-ATPase isoform.

    PubMed

    Holm, Thomas Hellesøe; Isaksen, Toke Jost; Glerup, Simon; Heuck, Anders; Bøttger, Pernille; Füchtbauer, Ernst-Martin; Nedergaard, Steen; Nyengaard, Jens Randel; Andreasen, Mogens; Nissen, Poul; Lykke-Hartmann, Karin

    2016-01-01

    The Na(+)/K(+)-ATPases maintain Na(+) and K(+) electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na(+)/K(+)-ATPase α3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the α3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (α3(+/D801Y)) was generated. The α3(+/D801Y) mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the α3(+/D801Y) mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na(+)/K(+)-ATPase α3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission. PMID:27549929

  6. Cognitive deficits caused by a disease-mutation in the α3 Na+/K+-ATPase isoform

    PubMed Central

    Holm, Thomas Hellesøe; Isaksen, Toke Jost; Glerup, Simon; Heuck, Anders; Bøttger, Pernille; Füchtbauer, Ernst-Martin; Nedergaard, Steen; Nyengaard, Jens Randel; Andreasen, Mogens; Nissen, Poul; Lykke-Hartmann, Karin

    2016-01-01

    The Na+/K+-ATPases maintain Na+ and K+ electrochemical gradients across the plasma membrane, a prerequisite for electrical excitability and secondary transport in neurons. Autosomal dominant mutations in the human ATP1A3 gene encoding the neuron-specific Na+/K+-ATPase α3 isoform cause different neurological diseases, including rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) with overlapping symptoms, including hemiplegia, dystonia, ataxia, hyperactivity, epileptic seizures, and cognitive deficits. Position D801 in the α3 isoform is a mutational hotspot, with the D801N, D801E and D801V mutations causing AHC and the D801Y mutation causing RDP or mild AHC. Despite intensive research, mechanisms underlying these disorders remain largely unknown. To study the genotype-to-phenotype relationship, a heterozygous knock-in mouse harboring the D801Y mutation (α3+/D801Y) was generated. The α3+/D801Y mice displayed hyperactivity, increased sensitivity to chemically induced epileptic seizures and cognitive deficits. Interestingly, no change in the excitability of CA1 pyramidal neurons in the α3+/D801Y mice was observed. The cognitive deficits were rescued by administration of the benzodiazepine, clonazepam, a GABA positive allosteric modulator. Our findings reveal the functional significance of the Na+/K+-ATPase α3 isoform in the control of spatial learning and memory and suggest a link to GABA transmission. PMID:27549929

  7. Allicin improves endoplasmic reticulum stress-related cognitive deficits via PERK/Nrf2 antioxidative signaling pathway.

    PubMed

    Zhu, Yao-Feng; Li, Xian-Hui; Yuan, Zhi-Peng; Li, Chun-Yan; Tian, Rong-Bo; Jia, Wei; Xiao, Zhu-Ping

    2015-09-01

    Endoplasmic reticulum (ER) stress is involved in neurodegenerative diseases including Alzheimer's disease (AD), in which dysregulation of double-stranded RNA-dependent protein kinase (PKR)-like ER-resident kinase (PERK) is considered to play a critical role. Allicin, a garlic extract, has been demonstrated a protective role in AD model. The present study was designed to investigate the possible protective effect of allicin on ER stress-induced cognitive deficits and underlying mechanisms in rats. In this study, 72h of lateral ventricular infusion of tunicamycin (TM), an ER stress stimulator, induced significant cognitive deficits. TM increased tau phosphorylation, Aβ42 deposit, and oxidative stress, and reduced antioxidative enzymes activity in the hippocampus. TM moderately elevated the expression of PERK and its downstream substrate nuclear factor erythroid-derived 2-like 2 (Nrf2) in the hippocampus. All these impaired changes by TM were significantly improved by allicin pretreatment. Allicin markedly increased PERK and Nrf2 expression in the hippocampus. Thus, our data demonstrate the protective role of allicin in ER stress-related cognitive deficits, and suggest that PERK/Nrf2 antioxidative signaling pathway underlies the action mechanism. PMID:26049013

  8. Rosemary extract improves cognitive deficits in a rats model of repetitive mild traumatic brain injury associated with reduction of astrocytosis and neuronal degeneration in hippocampus.

    PubMed

    Song, Hai; Xu, Lincheng; Zhang, Rongping; Cao, Zhenzhen; Zhang, Huan; Yang, Li; Guo, Zeyun; Qu, Yongqiang; Yu, Jianyun

    2016-05-27

    In this study, we investigated whether Rosemary extract (RE) improved cognitive deficits in repetitive mild Traumatic brain injury (rmTBI) rats and its potential mechanisms. The present results showed that rmTBI caused cognitive deficits, such as increased latency to find platform and decreased time spent in target quadrant in Morris water maze (MWM). These behavioral alterations were accompanying with the increased neuronal degeneration and glial fibrillary acidic protein (GFAP)-positive cells, increased Reactive oxygen species (ROS) generation, decreased activity of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT), elevated protein level of IL-1β, IL-6 and TNF-α in hippocampus. Treatment with RE prevented these changes above. Our findings confirmed the effect of rosemary extract on improvement of cognitive deficits and suggested its mechanisms might be mediated by anti-oxidative and anti-inflammatory. Therefore, rosemary extract may be a potential treatment to improve cognitive deficits in rmTBI patients. PMID:27113205

  9. The effect of erythropoietin on cognition in affective disorders - Associations with baseline deficits and change in subjective cognitive complaints.

    PubMed

    Ott, Caroline Vintergaard; Vinberg, Maj; Kessing, Lars V; Miskowiak, Kamilla W

    2016-08-01

    This is a secondary data analysis from our erythropoietin (EPO) trials. We examine (I) whether EPO improves speed of complex cognitive processing across bipolar and unipolar disorder, (II) if objective and subjective baseline cognitive impairment increases patients׳ chances of treatment-efficacy and (III) if cognitive improvement correlates with better subjective cognitive function, quality of life and socio-occupational capacity. Patients with unipolar or bipolar disorder were randomized to eight weekly EPO (N=40) or saline (N=39) infusions. Cognition, mood, quality of life and socio-occupational capacity were assessed at baseline (week 1), after treatment completion (week 9) and at follow-up (week 14). We used repeated measures analysis of covariance to investigate the effect of EPO on speed of complex cognitive processing. With logistic regression, we examined whether baseline cognitive impairment predicted treatment-efficacy. Pearson correlations were used to assess associations between objective and subjective cognition, quality of life and socio-occupational capacity. EPO improved speed of complex cognitive processing across affective disorders at weeks 9 and 14 (p≤0.05). In EPO-treated patients, baseline cognitive impairment increased the odds of treatment-efficacy on cognition at weeks 9 and 14 by a factor 9.7 (95% CI:1.2-81.1) and 9.9 (95% CI:1.1-88.4), respectively (p≤0.04). Subjective cognitive complaints did not affect chances of treatment-efficacy (p≥0.45). EPO-associated cognitive improvement correlated with reduced cognitive complaints but not with quality of life or socio-occupational function. As the analyses were performed post-hoc, findings are only hypothesis-generating. In conclusion, pro-cognitive effects of EPO occurred across affective disorders. Neuropsychological screening for cognitive dysfunction may be warranted in future cognition trials. PMID:27349944

  10. Advantages of the multiple case series approach to the study of cognitive deficits in autism spectrum disorder

    PubMed Central

    Towgood, Karren J.; Meuwese, Julia D.I.; Gilbert, Sam J.; Turner, Martha S.; Burgess, Paul W.

    2009-01-01

    In the neuropsychological case series approach, tasks are administered that tap different cognitive domains, and differences within rather than across individuals are the basis for theorising; each individual is effectively their own control. This approach is a mainstay of cognitive neuropsychology, and is particularly suited to the study of populations with heterogeneous deficits. However it has very rarely been applied to the study of cognitive differences in autism spectrum disorder (ASD). Here, we investigate whether this approach can yield information beyond that given by the typical group study method, when applied to an ASD population. Twenty-one high-functioning adult ASD participants and 22 IQ, age, and gender-matched control participants were administered a large battery of neuropsychological tests that would represent a typical neuropsychological assessment for neurological patients in the United Kingdom. The data were analysed using both group and single-case study methods. The group analysis revealed a limited number of deficits, principally on tests with a large executive function component, with no impairment in more routine abilities such as basic attending, language and perception. Single-case study analysis proved more fruitful revealing evidence of considerable variation in abilities both between and within ASD participants. Both sub-normal and supra-normal performance were observed, with the most defining feature of the ASD group being this variability. We conclude that the use of group-level analysis alone in the study of cognitive deficits in ASD risks missing cognitive characteristics that may be vitally important both theoretically and clinically, and even may be misleading because of averaging artifact. PMID:19580821

  11. Advantages of the multiple case series approach to the study of cognitive deficits in autism spectrum disorder.

    PubMed

    Towgood, Karren J; Meuwese, Julia D I; Gilbert, Sam J; Turner, Martha S; Burgess, Paul W

    2009-11-01

    In the neuropsychological case series approach, tasks are administered that tap different cognitive domains, and differences within rather than across individuals are the basis for theorising; each individual is effectively their own control. This approach is a mainstay of cognitive neuropsychology, and is particularly suited to the study of populations with heterogeneous deficits. However it has very rarely been applied to the study of cognitive differences in autism spectrum disorder (ASD). Here, we investigate whether this approach can yield information beyond that given by the typical group study method, when applied to an ASD population. Twenty-one high-functioning adult ASD participants and 22 IQ, age, and gender-matched control participants were administered a large battery of neuropsychological tests that would represent a typical neuropsychological assessment for neurological patients in the United Kingdom. The data were analysed using both group and single-case study methods. The group analysis revealed a limited number of deficits, principally on tests with a large executive function component, with no impairment in more routine abilities such as basic attending, language and perception. Single-case study analysis proved more fruitful revealing evidence of considerable variation in abilities both between and within ASD participants. Both sub-normal and supra-normal performance were observed, with the most defining feature of the ASD group being this variability. We conclude that the use of group-level analysis alone in the study of cognitive deficits in ASD risks missing cognitive characteristics that may be vitally important both theoretically and clinically, and even may be misleading because of averaging artifact. PMID:19580821

  12. [Age-related macular degeneration].

    PubMed

    Garcia Layana, A

    1998-01-01

    Age-related macular degeneration (ARMD) is the leading cause of blindness in the occidental world. Patients suffering this process have an important reduction on their quality of life being handicapped to read, to write, to recognise faces of their friends, or even to watch the television. One of the main problems of that disease is the absence of an effective treatment able to revert the process. Laser treatment is only useful in a limited number of patients, and even in these cases recurrent lesions are frequent. These facts and the progressive ageing of our society establish the ARMD as one of the biggest aim of medical investigations for the next century, and currently is focus of attention in the most industrialised countries. One of the most promising pieces of research is focused in the investigation of the risk factors associated with the age-related macular degeneration, in order to achieve a prophylactic treatment avoiding its appearance. Diet elements such as fat ingestion or reduced antioxidant intakes are being investigated as some of these factors, what open a new possibility for a prophylactic treatment. Finally, research is looking for new therapeutic modalities such as selective radiotherapy in order to improve or maintain the vision of these patients. PMID:10420956

  13. Training of attentional control in mild cognitive impairment with executive deficits: results from a double-blind randomised controlled study.

    PubMed

    Gagnon, Lyssa G; Belleville, Sylvie

    2012-01-01

    This study evaluated the efficacy of a cognitive intervention for attentional control in older adults with mild cognitive impairment (MCI) with an executive deficit. It also sought to verify if the benefits of training generalised to primary and secondary outcome measures. Participants (n = 24) were randomly assigned to a training programme or active control condition. The experimental group completed a computer-based training programme involving Variable Priority (VP) coordination of both components of a dual task, to which was added a self-regulatory strategy designed to augment meta-cognition. The active control group performed Fixed Priority (FP) training: rote practice of the same dual task involving a visual detection task combined with an alpha-arithmetic task. Six one-hour training sessions were held three times a week for two weeks. Participants were tested pre- and post-training to detect improvement and transfer effects. Both groups improved on the visual detection and alpha-arithmetic tasks completed in focused attention, but only participants receiving VP training significantly improved their dual-task cost in accuracy for the visual detection task. As for transfer effects, both FP and VP training produced improvements on select outcome measures: focused attention, speed of processing, and switching abilities. No reliable advantage for generalisability of VP over FP training was found. Overall, these findings indicate that cognitive intervention may improve attentional control in persons with MCI and an executive deficit. PMID:22712452

  14. Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

    PubMed Central

    Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

    2015-01-01

    Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities. PMID:25945108

  15. Prenatal exposure to vapors of gasoline-ethanol blends causes few cognitive deficits in adult rats.

    PubMed

    Oshiro, W M; Beasley, T E; McDaniel, K L; Evansky, P A; Martin, S A; Moser, V C; Gilbert, M E; Bushnell, P J

    2015-01-01

    any choice reaction time measure. Finally, no response inhibition deficit was observed in a differential reinforcement of low rate (DRL) response schedule in males or females in the E15 or E85 experiments. In summary, prenatal exposure to these fuel blends produced few deficits in adult offspring on these cognitive tests. Significant effects found during a water maze probe trial and choice reaction time tests were observed at vapor concentrations of 6000 ppm or higher, a concentration that is 4-6 orders of magnitude higher than those associated with normal automotive fueling operations and garages. Similar effects were not consistently observed in a previous study of inhaled ethanol, and thus these effects cannot be attributed to the concentration of ethanol in the mixture. PMID:25876165

  16. Chronic behavioral and cognitive deficits in a rat survival model of paraoxon toxicity

    PubMed Central

    Deshpande, Laxmikant S.; Phillips, Kristin; Huang, Beverly; DeLorenzo, Robert J.

    2014-01-01

    Organophosphate (OP) compounds, including paraoxon (POX), are similar to nerve agents such as sarin. There is a growing concern that OP agents could be weaponized to cause mass civilian causalities. We have developed a rodent survival model of POX toxicity that is being used to evaluate chronic morbidity and to screen for medical countermeasures against severe OP exposure. It is well known that the survivors of nerve gas and chronic OP exposure exhibit neurobehavioral deficits such as mood changes, depression, and memory impairments. In this study we investigated whether animals surviving severe POX exposure exhibited long-term neurological impairments. POX exposure produced overt signs of cholinergic toxicity. Rats were rescued using an optimized atropine, 2-PAM and diazepam therapy. Surviving rats were studied using established behavioral assays for identifying symptoms of depression and memory impairment 3-months after POX exposure. In the forced swim test, POX rats exhibited increased immobility time indicative of a despair-like state. In the sucrose preference test, POX rats consumed significantly less sucrose water indicating anhedonia-like condition. POX rats also displayed increased anxiety as characterized by significantly lower performance in the open arm of the elevated plus maze. Further, when tested with a novel object recognition paradigm, POX rats exhibited a negative discrimination ratio indicative of impaired recognition memory. The results indicate that this model of survival from severe POX exposure can be employed to study some of the molecular bases for OP-induced chronic behavioral and cognitive comorbidities and develop therapies for their treatment. PMID:25172410

  17. Down syndrome: genes, model systems, and progress towards pharmacotherapies and clinical trials for cognitive deficits.

    PubMed

    Busciglio, J; Capone, G; O'Bryan, J; O'Byran, J P; Gardiner, K J

    2013-01-01

    Down syndrome (DS) is caused by an extra copy of all or part of the long arm of human chromosome 21 (HSA21). While the complete phenotype is both complex, involving most organs and organ systems, and variable in severity among individuals, intellectual disability (ID) is seen in all people with DS and may have the most significant impact on quality of life. Because the worldwide incidence of DS remains at approximately 1 in 1,000 live births, DS is the most common genetic cause of ID. In recent years, there have been important advances in our understanding of the functions of genes encoded by HSA21 and in the number and utility of in vitro and in vivo systems for modeling DS. Of particular importance, several pharmacological treatments have been shown to rescue learning and memory deficits in one mouse model of DS, the Ts65Dn. Because adult mice were used in the majority of these experiments, there is considerable interest in extending the studies to human clinical trials, and a number of trials have been completed, are in progress or are being planned. A recent conference brought together researchers with a diverse array of expertise and interests to discuss (1) the functions of HSA21 genes with relevance to ID in DS, (2) the utility of model systems including Caenorhabditis elegans, zebrafish and mouse, as well as human neural stem cells and induced pluripotent stems cells, for studies relevant to ID in DS, (3) outcome measures used in pharmacological treatment of mouse models of DS and (4) outcome measures suitable for clinical trials for cognition in adults and children with DS. PMID:24008277

  18. Prefrontal cortex cognitive deficits in children treated early and continuously for PKU.

    PubMed

    Diamond, A; Prevor, M B; Callender, G; Druin, D P

    1997-01-01

    To begin to study the importance of dopamine for executive function abilities dependent on prefrontal cortex during early childhood, the present investigation studied children in whom we predicted reduced dopamine in prefrontal cortex but otherwise normal brains. These are children treated early and continuously for the metabolic disorder phenylketonuria (PKU). Untreated PKU is the most common biochemical cause of mental retardation. The root problem is an inability to convert one amino acid, phenylalanine (Phe), into another, tyrosine (Tyr), the precursor of dopamine. Phe levels in the bloodstream soar; Tyr levels fall. Treatment with a diet low in Phe reduces the Phe:Tyr imbalance but cannot eliminate it. We hypothesized that the resultant modest elevation in the ratio of Phe to Tyr in the blood, which results in slightly less Tyr reaching the brain, uniquely affects the cognitive functions dependent on prefrontal cortex because of the special sensitivity of prefrontally projecting dopamine neurons to small decreases in Tyr. In a 4-year longitudinal study, we found that PKU children whose plasma Phe levels were three to five times normal (6-10 mg/dl) performed worse than other PKU children with lower Phe levels, matched controls, their own siblings, and children from the general population on tasks that required the working memory and inhibitory control abilities dependent on dorsolateral prefrontal cortex. The impairment was as evident in our oldest age range (3 1/2-7 years) as it was in the youngest (6-12 months). The higher a child's Phe level, the worse that child's performance. Girls were more adversely affected than boys. The deficit appears to be selective, affecting principally one neural system, since even PKU children with Phe levels three to five times normal performed well on the 13 control tasks. Clinical implications for the treatment of PKU and other neurodevelopmental disorders are discussed. PMID:9421921

  19. Identification of a strategic brain network underlying processing speed deficits in vascular cognitive impairment.

    PubMed

    Duering, Marco; Gonik, Mariya; Malik, Rainer; Zieren, Nikola; Reyes, Sonia; Jouvent, Eric; Hervé, Dominique; Gschwendtner, Andreas; Opherk, Christian; Chabriat, Hugues; Dichgans, Martin

    2013-02-01

    Patients with vascular cognitive impairment (VCI) commonly exhibit deficits in processing speed. This has been attributed to a disruption of frontal-subcortical neuronal circuits by ischemic lesions, but the exact mechanisms and underlying anatomical structures are poorly understood. We set out to identify a strategic brain network for processing speed by applying graph-based data-mining techniques to MRI lesion maps from patients with small vessel disease. We studied 235 patients with CADASIL, a genetic small vessel disease causing pure VCI. Using a probabilistic atlas in standard space we first determined the regional volumes of white matter hyperintensities (WMH) and lacunar lesions (LL) within major white matter tracts. Conditional dependencies between the regional lesion volumes and processing speed were then examined using Bayesian network analysis. Exploratory analysis identified a network of five imaging variables as the best determinant of processing speed. The network included LL in the left anterior thalamic radiation and the left cingulum as well as WMH in the left forceps minor, the left parahippocampal white matter and the left corticospinal tract. Together these variables explained 34% of the total variance in the processing speed score. Structural equation modeling confirmed the findings obtained from the Bayesian models. In summary, using graph-based models we identified a strategic brain network having the highest predictive value for processing speed in our cohort of patients with pure small vessel disease. Our findings confirm and extend previous results showing a role of frontal-subcortical neuronal circuits, in particular dorsolateral prefrontal and cingulate circuits, in VCI. PMID:23153965

  20. Emotional face recognition deficit in amnestic patients with mild cognitive impairment: behavioral and electrophysiological evidence

    PubMed Central

    Yang, Linlin; Zhao, Xiaochuan; Wang, Lan; Yu, Lulu; Song, Mei; Wang, Xueyi

    2015-01-01

    Amnestic mild cognitive impairment (MCI) has been conceptualized as a transitional stage between healthy aging and Alzheimer’s disease. Thus, understanding emotional face recognition deficit in patients with amnestic MCI could be useful in determining progression of amnestic MCI. The purpose of this study was to investigate the features of emotional face processing in amnestic MCI by using event-related potentials (ERPs). Patients with amnestic MCI and healthy controls performed a face recognition task, giving old/new responses to previously studied and novel faces with different emotional messages as the stimulus material. Using the learning-recognition paradigm, the experiments were divided into two steps, ie, a learning phase and a test phase. ERPs were analyzed on electroencephalographic recordings. The behavior data indicated high emotion classification accuracy for patients with amnestic MCI and for healthy controls. The mean percentage of correct classifications was 81.19% for patients with amnestic MCI and 96.46% for controls. Our ERP data suggest that patients with amnestic MCI were still be able to undertake personalizing processing for negative faces, but not for neutral or positive faces, in the early frontal processing stage. In the early time window, no differences in frontal old/new effect were found between patients with amnestic MCI and normal controls. However, in the late time window, the three types of stimuli did not elicit any old/new parietal effects in patients with amnestic MCI, suggesting their recollection was impaired. This impairment may be closely associated with amnestic MCI disease. We conclude from our data that face recognition processing and emotional memory is impaired in patients with amnestic MCI. Such damage mainly occurred in the early coding stages. In addition, we found that patients with amnestic MCI had difficulty in post-processing of positive and neutral facial emotions. PMID:26347065

  1. Effects of cariprazine, a novel antipsychotic, on cognitive deficit and negative symptoms in a rodent model of schizophrenia symptomatology.

    PubMed

    Neill, Jo C; Grayson, Ben; Kiss, Béla; Gyertyán, István; Ferguson, Paul; Adham, Nika

    2016-01-01

    Negative symptoms and cognitive impairment associated with schizophrenia are strongly associated with poor functional outcome and reduced quality of life and remain an unmet clinical need. Cariprazine is a dopamine D3/D2 receptor partial agonist with preferential binding to D3 receptors, recently approved by the FDA for the treatment of schizophrenia and manic or mixed episodes associated with bipolar I disorder. The aim of this study is to evaluate effects of cariprazine in an animal model of cognitive deficit and negative symptoms of schizophrenia. Following sub-chronic PCP administration (2mg/kg, IP for 7 days followed by 7 days drug-free), female Lister Hooded rats were administered cariprazine (0.05, 0.1, or 0.25mg/kg, PO) or risperidone (0.16 or 0.1mg/kg, IP) before testing in novel object recognition (NOR), reversal learning (RL), and social interaction (SI) paradigms. As we have consistently demonstrated, sub-chronic PCP significantly impaired behavior in these tests. Deficits were significantly improved by cariprazine, in a dose dependent manner in the operant RL test with efficacy at lower doses in the NOR and SI tests. Locomotor activity was reduced at the highest doses of 0.1mg/kg and 0.25mg/kg in NOR and SI. Risperidone also reversed the PCP-induced deficit in all tests. In conclusion, cariprazine was effective to overcome PCP-induced deficits in cognition and social behavior in a thoroughly validated rat model in tests representing specific symptom domains in schizophrenia patients. These findings support very recent results showing efficacy of cariprazine in the treatment of negative symptoms in schizophrenia patients. PMID:26655189

  2. Long-term oral galactose treatment prevents cognitive deficits in male Wistar rats treated intracerebroventricularly with streptozotocin.

    PubMed

    Salkovic-Petrisic, Melita; Osmanovic-Barilar, Jelena; Knezovic, Ana; Hoyer, Siegfried; Mosetter, Kurt; Reutter, Werner

    2014-02-01

    Basic and clinical research has demonstrated that dementia of sporadic Alzheimer's disease (sAD) type is associated with dysfunction of the insulin-receptor (IR) system followed by decreased glucose transport via glucose transporter GLUT4 and decreased glucose metabolism in brain cells. An alternative source of energy is d-galactose (the C-4-epimer of d-glucose) which is transported into the brain by insulin-independent GLUT3 transporter where it might be metabolized to glucose via the Leloir pathway. Exclusively parenteral daily injections of galactose induce memory deterioration in rodents and are used to generate animal aging model, but the effects of oral galactose treatment on cognitive functions have never been tested. We have investigated the effects of continuous daily oral galactose (200 mg/kg/day) treatment on cognitive deficits in streptozotocin-induced (STZ-icv) rat model of sAD, tested by Morris Water Maze and Passive Avoidance test, respectively. One month of oral galactose treatment initiated immediately after the STZ-icv administration, successfully prevented development of the STZ-icv-induced cognitive deficits. Beneficial effect of oral galactose was independent of the rat age and of the galactose dose ranging from 100 to 300 mg/kg/day. Additionally, oral galactose administration led to the appearance of galactose in the blood. The increase of galactose concentration in the cerebrospinal fluid was several times lower after oral than after parenteral administration of the same galactose dose. Oral galactose exposure might have beneficial effects on learning and memory ability and could be worth investigating for improvement of cognitive deficits associated with glucose hypometabolism in AD. PMID:24055495

  3. Calorie Restriction Alleviates Age-Related Decrease in Neural Progenitor Cell Division in the Aging Brain

    PubMed Central

    Park, June-Hee; Glass, Zachary; Sayed, Kasim; Michurina, Tatyana V.; Lazutkin, Alexander; Mineyeva, Olga; Velmeshev, Dmitry; Ward, Walter F.; Richardson, Arlan; Enikolopov, Grigori

    2013-01-01

    Production of new neurons from stem cells is important for cognitive function, and the reduction of neurogenesis in the aging brain may contribute to the accumulation of age-related cognitive deficits. Restriction of calorie intake and prolonged treatment with rapamycin have been shown to extend the lifespan of animals and delay the onset of age-related decline in tissue and organ function. Using a reporter line in which neural stem and progenitor cells are marked by the expression of GFP, we examined the effect of prolonged exposure to calorie restriction (CR) or rapamycin on hippocampal neural stem and progenitor cell proliferation in aging mice. We show that CR increases the number of dividing cells in the dentate gyrus (DG) of female mice. The majority of these cells corresponded to Nestin-GFP-expressing neural stem or progenitor cells; however, this increased proliferative activity of stem and progenitor cells did not result in a significant increase in the number of doublecortin-positive newborn neurons. Our results suggest that restricted calorie intake may increase the number of divisions that neural stem and progenitor cells undergo in the aging brain of females. PMID:23773068

  4. Age-related changes in Egr1 transcription and DNA methylation within the hippocampus.

    PubMed

    Penner, M R; Parrish, R R; Hoang, L T; Roth, T L; Lubin, F D; Barnes, C A

    2016-08-01

    Aged animals show functional alterations in hippocampal neurons that lead to deficits in synaptic plasticity and changes in cognitive function. Transcription of immediate-early genes (IEGs), including Egr1, is necessary for processes such as long-term potentiation and memory consolidation. Here, we show an age-related reduction in the transcription of Egr1 in the dentate gyrus following spatial behavior, whereas in the area CA1, Egr1 is reduced at rest, but its transcription can be effectively driven by spatial behavior to levels equivalent to those observed in adult animals. One mechanism possibly contributing to these aging-related changes is an age-associated, CpG site-specific change in methylation in DNA associated with the promoter region of the Egr1 gene. Our results add to a growing body of work demonstrating that complex transcriptional and epigenetic changes in the hippocampus significantly contribute to brain and cognitive aging. © 2016 Wiley Periodicals, Inc. PMID:26972614

  5. Activated Microglia-Induced Deficits in Excitatory Synapses Through IL-1β: Implications for Cognitive Impairment in Sepsis.

    PubMed

    Moraes, Carolina A; Santos, Gabriel; de Sampaio e Spohr, Tania Cristina Leite; D'Avila, Joana C; Lima, Flávia Regina Souza; Benjamim, Claudia Farias; Bozza, Fernando A; Gomes, Flávia Carvalho Alcantara

    2015-08-01

    Recent clinical studies have shown that sepsis survivors may develop long-term cognitive impairments. The cellular and molecular mechanisms involved in these events are not well understood. This study investigated synaptic deficits in sepsis and the involvement of glial cells in this process. Septic animals showed memory impairment and reduced numbers of hippocampal and cortical excitatory synapses, identified by synaptophysin/PSD-95 co-localization, 9 days after disease onset. The behavioral deficits and synaptophysin/PSD-95 co-localization were rescued to normal levels within 30 days post-sepsis. Septic mice presented activation of microglia and reactive astrogliosis, which are hallmarks of brain injury and could be involved in the associated synaptic deficits. We treated neuronal cultures with conditioned medium derived from cultured astrocytes (ACM) and microglia (MCM) that were either non-stimulated or stimulated with lipopolysaccharide (LPS) to investigate the molecular mechanisms underlying synaptic deficits in sepsis. ACM and MCM increased the number of synapses between cortical neurons in vitro, and these effects were antagonized by LPS stimulation. LPS-MCM reduced the number of synapses by 50%, but LPS-ACM increased the number of synapses by 500%. Analysis of the composition of these conditioned media revealed increased levels of IL-1β in LPS-MCM. Furthermore, inhibition of IL-1β signaling through the addition of a soluble IL-1β receptor antagonist (IL-1 Ra) fully prevented the synaptic deficit induced by LPS-MCM. These results suggest that sepsis induces a transient synaptic deficit associated with memory impairments mediated by IL-1β secreted by activated microglia. PMID:25257696

  6. Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

    PubMed Central

    Robbins, T W; James, M; Owen, A M; Lange, K W; Lees, A J; Leigh, P N; Marsden, C D; Quinn, N P; Summers, B A

    1994-01-01

    Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways. The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage. On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task. On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit. The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage. It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another. PMID:8301310

  7. Sleep Disturbance and Cognitive Deficits in Bipolar Disorder: Toward An Integrated Examination of Disorder Maintenance and Functional Impairment

    PubMed Central

    Boland, Elaine M.; Alloy, Lauren B.

    2012-01-01

    Bipolar disorder is frequently associated with a number of poor outcomes including, but not limited to, a significant impairment in the ability to return to premorbid levels of occupational and psychosocial functioning, often despite the remission of mood symptoms. Sleep disturbance is an oft-reported residual symptom of manic and depressive episodes that has likewise been associated with the onset of manic episodes. Also present during affective episodes as well as the inter-episode periods are reports of deficits in cognitive functioning, which many reports have shown to play an important role in this persistent disability. Despite the presence of deficits in these two domains of functioning during affective episodes as well as the inter-episode phase, there has been no evaluation of the degree to which these systems may interact to maintain such high rates of functional disability. The aim of this review is to examine evidence for the study of the relationship between sleep disturbance and cognitive impairments in bipolar disorder as well as the ways in which deficits in these domains may work together to maintain functional impairment. PMID:23123569

  8. The Neural Substrates of Cognitive Control Deficits in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Solomon, Marjorie; Ozonoff, Sally J.; Ursu, Stefan; Ravizza, Susan; Cummings, Neil; Ly, Stanford; Carter, Cameron S.

    2009-01-01

    Executive function deficits are among the most frequently reported symptoms of autism spectrum disorders (ASDs), however, there have been few functional magnetic resonance imaging (fMRI) studies that investigate the neural substrates of executive function deficits in ASDs, and only one in adolescents. The current study examined cognitive…

  9. The Cognitive Deficits Responsible for Developmental Dyslexia: Review of Evidence for a Selective Visual Attentional Disorder

    ERIC Educational Resources Information Center

    Valdois, Sylviane; Bosse, Marie-Line; Tainturier, Marie-Josephe

    2004-01-01

    There is strong converging evidence suggesting that developmental dyslexia stems from a phonological processing deficit. However, this hypothesis has been challenged by the widely admitted heterogeneity of the dyslexic population, and by several reports of dyslexic individuals with no apparent phonological deficit. In this paper, we discuss the…

  10. Parallels in Cognitive-Perceptual Deficit between Alcoholics and Antisocial Psychiatric Patients.

    ERIC Educational Resources Information Center

    Gorenstein, Ethan E.

    Theorists have hypothesized that alcoholism, antisocial behavior, and childhood hyperactivity are part of a spectrum of disorders that have a common etiologic component, i.e., neuropsychological deficits to the structures (limbic system, frontal lobes) which regulate impulses. To examine the similarities in neuropsychological deficits between…

  11. Comparison of the Recovery Patterns of Language and Cognitive Functions in Patients with Post-Traumatic Language Processing Deficits and in Patients with Aphasia Following a Stroke

    ERIC Educational Resources Information Center

    Vukovic, Mile; Vuksanovic, Jasmina; Vukovic, Irena

    2008-01-01

    In this study we investigated the recovery patterns of language and cognitive functions in patients with post-traumatic language processing deficits and in patients with aphasia following a stroke. The correlation of specific language functions and cognitive functions was analyzed in the acute phase and 6 months later. Significant recovery of the…

  12. Induction of cognitive deficits by immunization with cholinergic cell bodies: the influence of age and integrity of the blood-brain barrier.

    PubMed

    Alroy, G; Chapman, J; Feldon, J; Michaelson, D M

    1991-01-01

    We have recently shown that prolonged immunization of young rats for one year with cholinergic cell bodies (perikarya, PK) purified from Torpedo electric lobe results in the accumulation of IgG in specific brain areas such as the hippocampus and induces behavioral deficits in spatial orientation and short term memory /1, 7/. We presently studied the rate of development of the cognitive deficit in older (12 months old) Sprague Dawley rats which were immunized for periods of up to one year with either Torpedo cholinergic PK or adjuvant (controls). T-maze alternation and Morris swim maze tests revealed a small deficit in the performance of the PK immunized rats after 6 months whereas significant deficits were observed after 12 months of immunization. These results suggest that the duration of immunization is a more significant factor than the age of the animals in the development of the behavioral deficit. In order to examine whether permeability of the blood-brain barrier to IgG influences the rate of development of the cognitive deficit, we disrupted the blood-brain barrier of PK immunized rats by hypercapnia. This treatment repeated weekly for 2 months was found not to accelerate the rate of appearance of deficits in performance of the rats in the T-maze alternation and Morris swim test. These results suggest that penetration of IgG via the blood-brain barrier does not determine the rate of appearance of the cognitive deficits. PMID:1797094

  13. Experimental ‘Jet Lag’ Inhibits Adult Neurogenesis and Produces Long-Term Cognitive Deficits in Female Hamsters

    PubMed Central

    Gibson, Erin M.; Wang, Connie; Tjho, Stephanie; Khattar, Neera; Kriegsfeld, Lance J.

    2010-01-01

    Background Circadian disruptions through frequent transmeridian travel, rotating shift work, and poor sleep hygiene are associated with an array of physical and mental health maladies, including marked deficits in human cognitive function. Despite anecdotal and correlational reports suggesting a negative impact of circadian disruptions on brain function, this possibility has not been experimentally examined. Methodology/Principal Findings In the present study, we investigated whether experimental ‘jet lag’ (i.e., phase advances of the light∶dark cycle) negatively impacts learning and memory and whether any deficits observed are associated with reductions in hippocampal cell proliferation and neurogenesis. Because insults to circadian timing alter circulating glucocorticoid and sex steroid concentrations, both of which influence neurogenesis and learning/memory, we assessed the contribution of these endocrine factors to any observed alterations. Circadian disruption resulted in pronounced deficits in learning and memory paralleled by marked reductions in hippocampal cell proliferation and neurogenesis. Significantly, deficits in hippocampal-dependent learning and memory were not only seen during the period of the circadian disruption, but also persisted well after the cessation of jet lag, suggesting long-lasting negative consequences on brain function. Conclusions/Significance Together, these findings support the view that circadian disruptions suppress hippocampal neurogenesis via a glucocorticoid-independent mechanism, imposing pronounced and persistent impairments on learning and memory. PMID:21152025

  14. Age-Related Factors in Second Language Acquisition.

    ERIC Educational Resources Information Center

    Twyford, Charles William

    The convergence of several lines of psycholinguistic and sociolinguistic research suggests possible explanations for age-related influences on language acquisition. These factors, which include cognitive development, sociocultural context, affective factors, and language input, can be helpful to language educators. By being alert to the cognitive…

  15. Soluble Aβ levels correlate with cognitive deficits in the 12-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease.

    PubMed

    Zhang, Wei; Hao, Jian; Liu, Rui; Zhang, Zhuo; Lei, Gesheng; Su, Changjun; Miao, Jianting; Li, Zhuyi

    2011-09-23

    Amyloid-beta peptide (Aβ) is believed to be central in the pathogenesis of Alzheimer's disease (AD) characterized by cognitive deficits. However, it remains uncertain which form(s) of Aβ pathology is responsible for the cognitive deficits in AD. In the present study, the cognitive deficits and the profiles of Aβ pathology were characterized in the 12-month-old APPswe/PS1dE9 double transgenic mice, and their correlations were examined. Compared with non-transgenic littermates, the middle-aged APPswe/PS1dE9 mice exhibited spatial learning and memory deficits in the water maze test and long-term contextual memory deficits in the step-down passive avoidance test. Among the middle-aged APPswe/PS1dE9 mice, hippocampal soluble Aβ1-40 and Aβ1-42 levels were highly correlated with spatial learning deficits and long-term contextual memory deficits, as well as cortical and hippocampal soluble Aβ1-40 and Aβ1-42 levels were strongly correlated with spatial memory deficits. By contrast, no significant correlations were observed between three measures of cognitive functions and amyloid plaque burden (total Aβ plaque load and fibrillar Aβ plaque load), total Aβ levels (Aβ1-40 and Aβ1-42), as well as insoluble Aβ levels (Aβ1-40 and Aβ1-42). Stepwise multiple regression analysis identified hippocampal soluble Aβ1-40 and Aβ1-42 levels as independent factors for predicting the spatial learning deficits and the long-term contextual memory deficits, as well as hippocampal and cortical soluble Aβ1-40 and Aβ1-42 levels as independent factors for predicting the spatial memory deficits in transgenic mice. These results demonstrate that cognitive deficits are highly related to the levels of soluble Aβ in middle-aged APPswe/PS1dE9 mice, in which soluble Aβ levels are only a tiny fraction of the amount of total Aβ levels. Consequently, our findings provide further evidence that soluble Aβ might primarily contribute to cognitive deficits in AD, suggesting that reducing

  16. Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Aβ23-35-Induced Alzheimer's Disease Rat Model.

    PubMed

    Qu, Mei-Hua; Yang, Xiaoyun; Wang, Yuming; Tang, Qingjuan; Han, Hailin; Wang, Jia; Wang, Guo-Du; Xue, Changhu; Gao, Zhiqin

    2016-01-01

    Both Docosahexaenoic acid (DHA) and Phosphatidylcholine (PC) have been shown to halt the pathogenesis of Alzheimer disease (AD) and vascular dementia. This study aimed to investigate the role of DHA-containing PC (DHA-PC) in the improvement of Aβ25-35-induced cognitive deficits in rats. Aβ25-35-induced AD rats were treated for 30 days with DHA-PC, which was extracted from Sthenoteuthis oualaniensis spawns. Cognitive improvement of the AD rats was detected using the Morris water maze (MWM). The results demonstrated that DHA-PC could improve the learning and memory abilities of AD rats in a dose-dependent pattern. Further analyses showed that expression of phosphorylated tau decreased, and the neuronal morphology recovered in brains of DHA-PC-treated AD rats, as compared with mock-treated AD rats. In addition, DHAPC treatment increased the activity of GSH-Px and SOD in the cortex and hippocampus of AD rats. Taken together, these data suggest that DHA-PC is able to improve the cognitive deficits in AD rats, probably through decreasing the phosphorylation of tau in the cortex and hippocampus CA1 area, and increasing the GSH-Px and SOD activities in the brain of AD rats. PMID:26268328

  17. Auditory and cognitive deficits associated with acquired amusia after stroke: a magnetoencephalography and neuropsychological follow-up study.

    PubMed

    Särkämö, Teppo; Tervaniemi, Mari; Soinila, Seppo; Autti, Taina; Silvennoinen, Heli M; Laine, Matti; Hietanen, Marja; Pihko, Elina

    2010-01-01

    Acquired amusia is a common disorder after damage to the middle cerebral artery (MCA) territory. However, its neurocognitive mechanisms, especially the relative contribution of perceptual and cognitive factors, are still unclear. We studied cognitive and auditory processing in the amusic brain by performing neuropsychological testing as well as magnetoencephalography (MEG) measurements of frequency and duration discrimination using magnetic mismatch negativity (MMNm) recordings. Fifty-three patients with a left (n = 24) or right (n = 29) hemisphere MCA stroke (MRI verified) were investigated 1 week, 3 months, and 6 months after the stroke. Amusia was evaluated using the Montreal Battery of Evaluation of Amusia (MBEA). We found that amusia caused by right hemisphere damage (RHD), especially to temporal and frontal areas, was more severe than amusia caused by left hemisphere damage (LHD). Furthermore, the severity of amusia was found to correlate with weaker frequency MMNm responses only in amusic RHD patients. Additionally, within the RHD subgroup, the amusic patients who had damage to the auditory cortex (AC) showed worse recovery on the MBEA as well as weaker MMNm responses throughout the 6-month follow-up than the non-amusic patients or the amusic patients without AC damage. Furthermore, the amusic patients both with and without AC damage performed worse than the non-amusic patients on tests of working memory, attention, and cognitive flexibility. These findings suggest domain-general cognitive deficits to be the primary mechanism underlying amusia without AC damage whereas amusia with AC damage is associated with both auditory and cognitive deficits. PMID:21152040

  18. Amyloid β Protein Aggravates Neuronal Senescence and Cognitive Deficits in 5XFAD Mouse Model of Alzheimer's Disease

    PubMed Central

    Wei, Zhen; Chen, Xiao-Chun; Song, Yue; Pan, Xiao-Dong; Dai, Xiao-Man; Zhang, Jing; Cui, Xiao-Li; Wu, Xi-Lin; Zhu, Yuan-Gui

    2016-01-01

    Background: Amyloid β (Aβ) has been established as a key factor for the pathological changes in the brains of patients with Alzheimer's disease (AD), and cellular senescence is closely associated with aging and cognitive impairment. However, it remains blurred whether, in the AD brains, Aβ accelerates the neuronal senescence and whether this senescence, in turn, impairs the cognitive function. This study aimed to explore the expression of senescence-associated genes in the hippocampal tissue from young to aged 5XFAD mice and their age-matched wild type (WT) mice to determine whether senescent neurons are present in the transgenic AD mouse model. Methods: The 5XFAD mice and age-matched wild type mice, both raised from 1 to 18 months, were enrolled in the study. The senescence-associated genes in the hippocampus were analyzed and differentially expressed genes (DEGs) were screened by quantitative real-time polymerase chain reaction. Cognitive performance of the mice was evaluated by Y-maze and Morris water maze tests. Oligomeric Aβ (oAβ) (1–42) was applied to culture primary neurons to simulate the in vivo manifestation. Aging-related proteins were detected by Western blotting analysis and immunofluorescence. Results: In 5XFAD mice, of all the DEGs, the senescence-associated marker p16 was most significantly increased, even at the early age. It was mainly localized in neurons, with a marginal expression in astrocytes (labeled as glutamine synthetase), nil expression in activated microglia (labeled as Iba1), and negatively correlated with the spatial cognitive impairments of 5XFAD mice. oAβ (1–42) induced the production of senescence-related protein p16, but not p53 in vitro, which was in line with the in vivo manifestation. Conclusions: oAβ-accelerated neuronal senescence may be associated with the cognitive impairment in 5XFAD mice. Senescence-associated marker p16 can serve as an indicator to estimate the cognitive prognosis for AD population. PMID

  19. Remission of Cognitive Deficits in Parkinson's Disease: Recovery from a Nonamnestic Mild Cognitive Impairment or Psychiatric Symptoms Remission?

    PubMed Central

    de Paula, Jonas Jardim; Cintra, Marco Túlio Gualberto; Miranda, Débora Marques; Bicalho, Maria Aparecida Camargos; Moares, Edgar Nunes; Malloy-Diniz, Leandro Fernandes

    2012-01-01

    Mild cognitive impairment is a clinical condition more frequent in patients with Parkinson's disease than in general population. The nonamnestic presentations, usually characterized by executive dysfunction, are most prevalent. We present a case report of a Parkinson's disease patient diagnosed with nonamnestic mild cognitive impairment that showed complete remission of cognitive symptoms after one year. We discuss the possible causes for the remission, focusing on the treatment of medical conditions such as a major depressive episode and vitamin B12 deficiency, in addition to the change of pharmacological treatment. In a third assessment, cognitive performance remained normal. The case report highlights the importance of controlling clinical comorbidities on the assessment and followup of mild cognitive impairment, especially on Parkinson's disease. PMID:23193494

  20. Attention-deficit/hyperactivity disorder and sluggish cognitive tempo dimensions in relation to executive functioning in adolescents with ADHD.

    PubMed

    Becker, Stephen P; Langberg, Joshua M

    2014-02-01

    Previous research has failed to find a consistent relation between Sluggish Cognitive Tempo (SCT) and executive function (EF) in youth with Attention-Deficit/Hyperactivity Disorder (ADHD) when laboratory-based neuropsychological tasks of EF are used, whereas recent research with youth and adults suggests a significant relation between SCT and ratings of EF. The purpose of this study was to examine ADHD dimensions and SCT symptoms in relation to ratings of EF in adolescents with ADHD. Fifty-two adolescents (ages 12-16; 70 % male) participated in this study. Parents and teachers completed validated measures of SCT, ADHD symptoms, and EF in daily life. Adolescents' intelligence and academic achievement were also assessed. ADHD and SCT symptoms were significantly correlated with ratings of EF. Regression analyses demonstrated that, as hypothesized, ADHD hyperactive-impulsive symptoms were strongly associated with behavioral regulation EF deficits, with ADHD inattentive and SCT symptoms unrelated to behavioral regulation EF when hyperactive-impulsivity symptoms were included in the model. The parent-reported SCT Slow scale measuring motivation, initiative, and apathy predicted both parent- and teacher-reported metacognitive EF deficits above and beyond youth characteristics and ADHD symptoms. In contrast, teacher-reported ADHD inattention was most clearly associated with teacher-reported metacognitive EF deficits. This study provides preliminary evidence for the importance of SCT symptoms in relation to metacognitive EF deficits among adolescents with ADHD and the need to further investigate the overlap and distinctiveness of SCT/ADHD. Further research is needed to replicate and extend these findings. PMID:23443466

  1. Recovery of functional and structural age-related changes in the rat primary auditory cortex with operant training

    PubMed Central

    de Villers-Sidani, Etienne; Alzghoul, Loai; Zhou, Xiaoming; Simpson, Kimberly L.; Lin, Rick C. S.; Merzenich, Michael M.

    2010-01-01

    Cognitive decline is a virtually universal aspect of the aging process. However, its neurophysiological basis remains poorly understood. We describe here more than 20 age-related cortical processing deficits in the primary auditory cortex of aging versus young rats that appear to be strongly contributed to by altered cortical inhibition. Consistent with these changes, we recorded in old rats a decrease in parvalbumin-labeled inhibitory cortical neurons. Furthermore, old rats were slower to master a simple behavior, with learning progressions marked by more false-positive responses. We then examined the effect of intensive auditory training on the primary auditory cortex in these aged rats by using an oddball discrimination task. Following training, we found a nearly complete reversal of the majority of previously observed functional and structural cortical impairments. These findings suggest that age-related cognitive decline is a tightly regulated plastic process, and demonstrate that most of these age-related changes are, by their fundamental nature, reversible. PMID:20643928

  2. Mechanisms underlying cognitive enhancement and reversal of cognitive deficits in nonhuman primates by the ampakine CX717

    PubMed Central

    Hampson, R. E.; España, R. A.; Rogers, G. A.; Porrino, L. J.; Deadwyler, S. A.

    2011-01-01

    Rationale Performance of cognitive tasks in nonhuman primates (NHPs) requires specific brain regions to make decisions under different degrees of difficulty or “cognitive load.” Objective Local cerebral metabolic activity ([18F]FDG PET imaging) in dorsolateral prefrontal cortex (DLPFC), medial temporal lobe (MTL), and dorsal striatum (DStr) is examined in NHPs performing a delayed-match-to-sample (DMS) task with variable degrees of cognitive load. Materials and methods Correlations between cognitive load and degree of brain metabolic activity were obtained with respect to the influence of the ampakine CX717 (Cortex Pharmaceuticals), using brain imaging and recordings of neuronal activity in NHPs and measures of intracellular calcium release in rat hippocampal slices. Results Activation of DLPFC, MTL, and DStr reflected changes in performance related to cognitive load within the DMS task and were engaged primarily on high load trials. Similar increased activation patterns and improved performance were also observed following administration of CX717. Sleep deprivation in NHPs produced impaired performance and reductions in brain activation which was reversed by CX717. One potential basis for this facilitation of cognition by CX717 was increased firing of task-specific hippocampal cells. Synaptic mechanisms affected by CX717 were examined in rat hippocampal slices which showed that N-methyl-d-aspartic acid-mediated release of intracellular calcium was reduced in slices from sleep-deprived rats and reversed by application of CX717 to the bathing medium. Conclusions The findings provide insight into how cognition is enhanced by CX717 in terms of brain, and underlying neural, processes that are activated on high vs. low cognitive load trials. PMID:18985324

  3. BDNF pathway is involved in the protective effects of SS-31 on isoflurane-induced cognitive deficits in aging mice.

    PubMed

    Wu, Jing; Zhang, Mingqiang; Li, Huihui; Sun, Xiaoru; Hao, Shuangying; Ji, Muhuo; Yang, Jianjun; Li, Kuanyu

    2016-05-15

    Mitochondrial dysfunction has been linked to the earliest pathogenesis of isoflurane-induced cognitive impairments in developing or aging mammalian brain. However, its molecular mechanism is poorly understood and a pharmacologic treatment to rapidly reverse mitochondrial dysfunction is lacking. Fifteen-month-old male C57BL/6 mice were exposed to isoflurane for two hours following intraperitoneal administration of mitochondrion-targeted peptide SS-31 or vehicle with 30min interval. The hippocampus was immediately removed for biochemical assays and mitochondria isolation after inhalation. Behavioral tests were evaluated by the open field test and fear conditioning test 24h after the experiment. We showed that cognitive deficits induced by exposure of the aging mice to isoflurane were accompanied by mitochondrial dysfunction in hippocampus due to loss of the enzymatic activity of complex I. This loss resulted in the increase of reactive oxygen species production, decrease of ATP production and mitochondrial membrane potential, and opening of mitochondrial permeability transition pore. Further, we provided evidence that the BDNF signaling pathway was involved in this process to regulate synaptic plasticity-related proteins, for instance, downregulation of synapsin 1, PSD-95 and p-CREB, and upregulation of NR2A, NR2B, CaMKIIα and CaMKIIβ. Of note, the isoflurane-induced cognitive deficits were rescued by SS-31 through reversal of mitochondrial dysfunction, which facilitated the regulation of BDNF signaling including the expression reversal of aforementioned important synaptic-signaling proteins in aging mice. Our data demonstrate that reversing mitochondrial dysfunction by SS-31 enhances BDNF signaling pathway and synaptic plasticity, and provides protective effects on cognitive function, thereby support the notion that SS-31 may have therapeutic benefits for elderly humans undertaking anesthesia. PMID:26944333

  4. Neuroimaging explanations of age-related differences in task performance

    PubMed Central

    Steffener, Jason; Barulli, Daniel; Habeck, Christian; Stern, Yaakov

    2014-01-01

    Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower) task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance. PMID:24672481

  5. Molecular Mechanism for Age-Related Memory Loss: The Histone-Binding Protein RbAp48

    PubMed Central

    Pavlopoulos, Elias; Jones, Sidonie; Kosmidis, Stylianos; Close, Maggie; Kim, Carla; Kovalerchik, Olga; Small, Scott A.; Kandel, Eric R.

    2016-01-01

    To distinguish age-related memory loss more explicitly from Alzheimer’s disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention. PMID:23986399

  6. Molecular mechanism for age-related memory loss: the histone-binding protein RbAp48.

    PubMed

    Pavlopoulos, Elias; Jones, Sidonie; Kosmidis, Stylianos; Close, Maggie; Kim, Carla; Kovalerchik, Olga; Small, Scott A; Kandel, Eric R

    2013-08-28

    To distinguish age-related memory loss more explicitly from Alzheimer's disease (AD), we have explored its molecular underpinning in the dentate gyrus (DG), a subregion of the hippocampal formation thought to be targeted by aging. We carried out a gene expression study in human postmortem tissue harvested from both DG and entorhinal cortex (EC), a neighboring subregion unaffected by aging and known to be the site of onset of AD. Using expression in the EC for normalization, we identified 17 genes that manifested reliable age-related changes in the DG. The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. To test whether the RbAp48 decline could be responsible for age-related memory loss, we turned to mice and found that, consistent with humans, RbAp48 was less abundant in the DG of old than in young mice. We next generated a transgenic mouse that expressed a dominant-negative inhibitor of RbAp48 in the adult forebrain. Inhibition of RbAp48 in young mice caused hippocampus-dependent memory deficits similar to those associated with aging, as measured by novel object recognition and Morris water maze tests. Functional magnetic resonance imaging studies showed that within the hippocampal formation, dysfunction was selectively observed in the DG, and this corresponded to a regionally selective decrease in histone acetylation. Up-regulation of RbAp48 in the DG of aged wild-type mice ameliorated age-related hippocampus-based memory loss and age-related abnormalities in histone acetylation. Together, these findings show that the DG is a hippocampal subregion targeted by aging, and identify molecular mechanisms of cognitive aging that could serve as valid targets for therapeutic intervention. PMID:23986399

  7. Effects of Pycnogenol and vitamin E on cognitive deficits and oxidative damage induced by intracerebroventricular streptozotocin in rats.

    PubMed

    Ishrat, Tauheed; Parveen, Kehkashan; Hoda, Md Nasrul; Khan, Mohammad Badruzzaman; Yousuf, Seema; Ansari, Mubeen Ahmad; Saleem, Sofiyan; Islam, Fakhrul

    2009-10-01

    Oxidative stress plays a crucial role in the progression of cognitive decline in Alzheimer's disease (AD). Considerable attention has been focused on increasing the internal antioxidant defenses in response to AD. This study was designed to examine and compare the pretreatment effects of Pycnogenol (PYC) and vitamin E (Vit E) on cognitive deficits and oxidative damage in the hippocampus and cerebral cortex of intracerebroventricular streptozotocin (ICV-STZ)-infused rats. Rats pretreated with PYC (10 mg/kg), Vit E (100 mg/kg), and vehicle (intraperitoneal; once daily for 3 weeks) were bilaterally injected with ICV-STZ (3 mg/kg), whereas sham rats received the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using passive avoidance and water maze tasks, and then killed for biochemical assays. ICV-STZ induced significant declines in cognitive performance and choline acetyltransferase activity in the hippocampus, which were significantly attenuated with PYC and Vit E. Pretreatment with PYC and Vit E produced a significantly enhanced glutathione level and Na+/K+-ATPase activity and decreased thiobarbituric acid reactive substances and protein carbonyl. These findings suggest that PYC and Vit E may provide a promising approach for the treatment of oxidative stress-related neurodegeneration in conditions such as AD. PMID:19654508

  8. A functional magnetic resonance imaging study of cognitive control and neurosensory deficits in mild traumatic brain injury.

    PubMed

    Mayer, Andrew R; Hanlon, Faith M; Dodd, Andrew B; Ling, Josef M; Klimaj, Stefan D; Meier, Timothy B

    2015-11-01

    Mild traumatic brain injury patients (mTBI) frequently report symptoms of increased distractability and sensory disturbances during mutisensory stimulation. These common post-concussive symptoms could putatively result from dysfunction within the cognitive control network (CCN; top-down) or from unisensory cortex (bottom-up) itself. Functional magnetic resonance imaging (fMRI) and high-resolution structural data were therefore prospectively collected during a multisensory (audio-visual) cognitive control task from 46 mTBI patients within 3 weeks of injury and 46 matched healthy controls (HC), with a subset of participants returning at 4 months. Multisensory stimuli were presented at two frequencies to manipulate cognitive and perceptual load. Patients self-reported more cognitive, emotional, somatic, vestibular and visual symptoms relative to HC, which improved, but did not entirely resolve, over the 4 month follow-up period. There were no group differences in behavior or functional activation during cognitive control (incongruent--congruent trials). In contrast, patients exhibited abnormal activation within different regions of visual cortex that depended on whether attention was focused on auditory or visual information streams. Patients also exhibited increased activation within bilateral inferior parietal lobules during higher cognitive/perceptual loads, suggesting a compensatory mechanism to achieve similar levels of behavioral performance. Functional abnormalities within the visual cortex and inferior parietal lobules were only partially resolved at 4 months post-injury, suggesting that neural abnormalities may take longer to resolve than behavioral measures used in most clinical settings. In summary, current results indicate that abnormalities within unisensory cortex (particularly visual areas) following mTBI, which likely contribute to deficits commonly reported during multisensory stimulation. PMID:26493161

  9. Metacognition-augmented cognitive remediation training reduces jumping to conclusions and overconfidence but not neurocognitive deficits in psychosis

    PubMed Central

    Moritz, Steffen; Thoering, Teresa; Kühn, Simone; Willenborg, Bastian; Westermann, Stefan; Nagel, Matthias

    2015-01-01

    The majority of patients with schizophrenia display neurocognitive deficits (e.g., memory impairment) as well as inflated cognitive biases (e.g., jumping to conclusions). Both cognitive domains are implicated in the pathogenesis of the disorder and are known to compromise functional outcome. At present, there is a dearth of effective treatment options. A total of 90 patients with schizophrenia were recruited online (a diagnosis of schizophrenia had been confirmed in a large subgroup during a previous hospital admission). Subsequent to a baseline assessment encompassing psychopathology, self-reported cognition as well as objective memory and reasoning tests, patients were randomized to one of three conditions: standard cognitive remediation (mybraintraining), metacognition-augmented cognition remediation (CR) condition (variant of mybraintraining which encouraged patients to reduce speed of decision-making and attenuate response confidence when participants made high-confidence judgements and hasty incorrect decisions) and a waitlist control group. Patients were retested after 6 weeks and again 3 months after the second assessment. Groups did not differ on psychopathology and neurocognitive parameters at any timepoint. However, at follow-up the metacognitive-augmented CR group displayed a significant reduction on jumping to conclusions and overconfidence. Treatment adherence correlated with a reduction of depression; gains in the training exercises from the standard mybraintraining condition were correlated with improved objective memory performance. The study suggests that metacognition-augmented CR may ameliorate cognitive biases but not neurocognition. The study ties in well with prior research showing that neurocognitive dysfunctions are rather resistant to change; the failure to detect significant improvement of CR or metacognition-augmented CR on psychopathology and neurocognition over time may partly be attributed to a number of methodological limitations of

  10. Age-related forgetting in locomotor adaptation

    PubMed Central

    Malone, Laura A.; Bastian, Amy J.

    2016-01-01

    The healthy aging process affects the ability to learn and remember new facts and tasks. Prior work has shown that motor learning can be adversely affected by non-motor deficits, such as time. Here we investigated how age, and a dual task influence the learning and forgetting of a new walking pattern. We studied healthy younger (<30 yo) and older adults (>50 yo) as they alternated between 5-minute bouts of split-belt treadmill walking and resting. Older subjects learned a new walking pattern at the same rate as younger subjects, but forgot some of the new pattern during the rest breaks. We tested if forgetting was due to reliance on a cognitive strategy that was not fully engaged after rest breaks. When older subjects performed a dual cognitive task to reduce strategic control of split-belt walking, their adaptation rate slowed, but they still forgot much of the new pattern during the rest breaks. Our results demonstrate that the healthy aging process weakens motor memories during rest breaks and that this phenomenon cannot be explained solely by reliance on a conscious strategy in older adults. PMID:26589520

  11. Odor identification deficit in mild cognitive impairment and Alzheimer's disease is associated with hippocampal and deep gray matter atrophy.

    PubMed

    Hagemeier, Jesper; Woodward, Matthew R; Rafique, Usama A; Amrutkar, Chaitanya V; Bergsland, Niels; Dwyer, Michael G; Benedict, Ralph; Zivadinov, Robert; Szigeti, Kinga

    2016-09-30

    Even in early stages, Alzheimer's disease (AD) is associated with olfactory deficit. We assess the association of volumetric differences in subcortical deep gray matter (DGM) structures and odor identification deficit (OID) in subjects with amnestic mild cognitive impairment (aMCI), AD and normal controls (NCs), and relate findings to the current gold standard right sided memory measure, visual reproduction. Eighty subjects (19 aMCI; 42 CE; 19 NC) were included in this study. We obtained olfactory testing and normalized structural brain volumes from 3T T1 MRI scans. Associations between MRI, olfactory- and memory impairment were studied using Pearson- and partial-correlation adjusted for age. AD patients had significantly higher olfactory deficits, lower visual reproduction scores, and reduced brain volumes (p<0.05). Within aMCI, OID was associated with lower right hippocampal- and left amygdala volume (p<0.05). In AD, OID was associated with bilaterally lower hippocampus and left amygdala volumes. In contrast, visual reproduction was associated with bilateral volume loss regardless of study group. OID is a more specific marker of early pathological right mesial-temporal involvement than the currently regarded gold standard of right sided-memory (visual reproduction). OID may be valuable in the longitudinal evaluation of disease modifying treatments in early disease course. PMID:27567325

  12. Designing websites for persons with cognitive deficits: Design and usability of a psychoeducational intervention for persons with severe mental illness.

    PubMed Central

    Rotondi, Armando J.; Sinkule, Jennifer; Haas, Gretchen L.; Spring, Michael B.; Litschge, Christine M.; Newhill, Christina E.; Ganguli, Rohan; Anderson, Carol M.

    2013-01-01

    The purpose of this study was to develop an understanding of the design elements that influence the ability of persons with severe mental illness (SMI) and cognitive deficits to use a website, and to use this knowledge to design a web-based telehealth application to deliver a psychoeducation program to persons with schizophrenia and their families. Usability testing was conducted with 98 persons with SMI. First, individual website design elements were tested. Based on these results, theoretical website design models were used to create several alternative websites. These designs were tested for their ability to facilitate use by persons with SMI. The final website design is presented. The results indicate that commonly prescribed design models and guidelines produce websites that are poorly suited and confusing to persons with SMI. Our findings suggest an alternative model that should be considered when designing websites and other telehealth interventions for this population. Implications for future studies addressing the characteristics of accessible designs for persons with SMI and cognitive deficits are discussed. PMID:26321884

  13. Cognitive deficits and decreased locomotor activity induced by single-walled carbon nanotubes and neuroprotective effects of ascorbic acid.

    PubMed

    Liu, Xudong; Zhang, Yuchao; Li, Jinquan; Wang, Dong; Wu, Yang; Li, Yan; Lu, Zhisong; Yu, Samuel C T; Li, Rui; Yang, Xu

    2014-01-01

    Single-walled carbon nanotubes (SWCNTs) have shown increasing promise in the field of biomedicine, especially in applications related to the nervous system. However, there are limited studies available on the neurotoxicity of SWCNTs used in vivo. In this study, neurobehavioral changes caused by SWCNTs in mice and oxidative stress were investigated. The results of ethological analysis (Morris water maze and open-field test), brain histopathological examination, and assessments of oxidative stress (reactive oxygen species [ROS], malondialdehyde [MDA], and glutathione [GSH]), inflammation (nuclear factor κB, tumor necrosis factor α, interleukin-1β), and apoptosis (cysteine-aspartic acid protease 3) in brains showed that 6.25 and 12.50 mg/kg/day SWCNTs in mice could induce cognitive deficits and decreased locomotor activity, brain histopathological alterations, and increased levels of oxidative stress, inflammation, and apoptosis in mouse brains; however, 3.125 mg/kg/day SWCNTs had zero or minor adverse effects in mice, and these effects were blocked by concurrent administration of ascorbic acid. Down-regulation of oxidative stress, inflammation, and apoptosis were proposed to explain the neuroprotective effects of ascorbic acid. This work suggests SWCNTs could induce cognitive deficits and decreased locomotor activity, and provides a strategy to avoid the adverse effects. PMID:24596461

  14. Distinguishing between autism spectrum disorder and attention deficit hyperactivity disorder by using behavioral checklists, cognitive assessments, and neuropsychological test battery.

    PubMed

    Matsuura, Naomi; Ishitobi, Makoto; Arai, Sumiyoshi; Kawamura, Kaori; Asano, Mizuki; Inohara, Keisuke; Narimoto, Tadamasa; Wada, Yuji; Hiratani, Michio; Kosaka, Hirotaka

    2014-12-01

    Children with attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share many common symptoms, including attention deficit, behavioral problems, and difficulties with social skills. The aim of this study was to distinguish between ASD and ADHD by identifying the characteristic features of both the disorders, by using multidimensional assessments, including screening behavioral checklists, cognitive assessments, and comprehensive neurological battery. After screening for comorbid disorders, we carefully selected age-, sex-, IQ-, and socio-economic status-matched children with typical development (TD). In the Wechsler Intelligence Scale for children, a lower score was observed for the ASD group than for the TD group in Picture concept, which is a subscale of perceptual reasoning. A lower score was shown by the ADHD group than by the TD group in the spatial working memory test in the Cambridge Neuropsychological Test Automated Battery (CANTAB(®)). Although ASD and ADHD have many similar symptoms, they can be differentiated by focusing on the behavioral and cognitive characteristics of executive function. PMID:25440561

  15. Effectiveness of cognitive-functional (Cog-Fun) intervention with children with attention deficit hyperactivity disorder: a pilot study.

    PubMed

    Hahn-Markowitz, Jeri; Manor, Iris; Maeir, Adina

    2011-01-01

    The executive function (EF) deficits of children with attention deficit hyperactivity disorder (ADHD) hinder their performance of complex daily functions. Despite the existing evidence-based pharmacological interventions for ADHD symptoms, no intervention has yet been found that deals directly with EFs in daily tasks. Fourteen children and their parents participated in the Cognitive-Functional (Cog-Fun) program in occupational therapy, which is tailored to the executive dysfunction of ADHD and focuses on enabling cognitive strategies for occupational performance. The study included initial assessment of EFs (Behavior Rating Inventory of Executive Functions; Tower of London(DX)), occupational performance (Canadian Occupational Performance Measure), 10 sessions of Cog-Fun intervention with each child-parent dyad, and postintervention and 3-month follow-up assessments. We found significant improvements with medium to large effects on outcome measures after intervention, and most effects were maintained at follow-up. The findings warrant controlled studies examining the effectiveness of this intervention for children with ADHD. PMID:21834453

  16. Autologous transplantation of intestine-isolated glia cells improves neuropathology and restores cognitive deficits in β amyloid-induced neurodegeneration

    PubMed Central

    Esposito, Giuseppe; Sarnelli, Giovanni; Capoccia, Elena; Cirillo, Carla; Pesce, Marcella; Lu, Jie; Calì, Gaetano; Cuomo, Rosario; Steardo, Luca

    2016-01-01

    Alzheimer’s disease (AD) is characterized by chronic deposition of β-amyloid (Aβ) in the brain, progressive neurodegeneration and consequent cognitive and behavioral deficits that typify the disease. Astrocytes are pivotal in this process because they are activated in the attempt to digest Aβ which starts a neuroinflammatory response that further contributes to neurodegeneration. The intestine is a good source of astrocytes-like cells-referred to as enteric glial cells (EGCs). Here we show that the autologous transplantation of EGCs into the brain of Aβ-injected rats arrested the development of the disease after their engraftment. Transplanted EGCs showed anti-amyloidogenic activity, embanked Aβ-induced neuroinflammation and neurodegeneration, and released neutrophic factors. The overall result was the amelioration of the pathological hallmarks and the cognitive and behavioral deficits typical of Aβ-associated disease. Our data indicate that autologous EGCs transplantation may provide an efficient alternative for applications in cell-replacement therapies to treat neurodegeneration in AD. PMID:26940982

  17. Cognitive Training for Attention-Deficit/Hyperactivity Disorder: Meta-Analysis of Clinical and Neuropsychological Outcomes From Randomized Controlled Trials

    PubMed Central

    Cortese, Samuele; Ferrin, Maite; Brandeis, Daniel; Buitelaar, Jan; Daley, David; Dittmann, Ralf W.; Holtmann, Martin; Santosh, Paramala; Stevenson, Jim; Stringaris, Argyris; Zuddas, Alessandro; Sonuga-Barke, Edmund J.S.

    2015-01-01

    Objective The authors performed meta-analyses of randomized controlled trials to examine the effects of cognitive training on attention-deficit/hyperactivity disorder (ADHD) symptoms, neuropsychological deficits, and academic skills in children/adolescents with ADHD. Method The authors searched Pubmed, Ovid, Web of Science, ERIC, and CINAHAL databases through May 18, 2014. Data were aggregated using random-effects models. Studies were evaluated with the Cochrane risk of bias tool. Results Sixteen of 695 nonduplicate records were analyzed (759 children with ADHD). When all types of training were considered together, there were significant effects on total ADHD (standardized mean difference [SMD] = 0.37, 95% CI = 0.09–0.66) and inattentive symptoms (SMD = 0.47, 95% CI = 0.14–0.80) for reports by raters most proximal to the treatment setting (i.e., typically unblinded). These figures decreased substantially when the outcomes were provided by probably blinded raters (ADHD total: SMD = 0.20, 95% CI = 0.01–0.40; inattention: SMD = 0.32, 95% CI = −0.01 to 0.66). Effects on hyperactivity/impulsivity symptoms were not significant. There were significant effects on laboratory tests of working memory (verbal: SMD = 0.52, 95% CI = 0.24–0.80; visual: SMD = 0.47, 95% CI = 0.23–0.70) and parent ratings of executive function (SMD = 0.35, 95% CI = 0.08–0.61). Effects on academic performance were not statistically significant. There were no effects of working memory training, specifically on ADHD symptoms. Interventions targeting multiple neuropsychological deficits had large effects on ADHD symptoms rated by most proximal assessors (SMD = 0.79, 95% CI = 0.46–1.12). Conclusion Despite improving working memory performance, cognitive training had limited effects on ADHD symptoms according to assessments based on blinded measures. Approaches targeting multiple neuropsychological processes may optimize the transfer of effects from cognitive deficits to

  18. [Prognosis of cognitive deficit progression in aged patients with mild cognitive impairment under prolonged therapy (a three year observation)].

    PubMed

    Gavrilova, S I; Kolykhalov, I V; Fedorova, Ia B; Kalyn, Ia B; Selezneva, N D; Samorodov, A V; Miasoedov, S N; Boksha, I S

    2013-01-01

    The aim of the study was to predict treatment efficacy in patients with mild cognitive impairment (MCI) and to find the most reliable clinical tests for the prediction of dementia. Patients with amnestic MCI (n=53) were treated with cerebrolysin for three years and underwent regularly neurocognitive and clinical psychiatric tests. The data were analyzed using non-parametric statistics, cluster analysis, and linear discriminate analysis. The combination of statistical methods has enabled to predict the degree of cognitive impairment as well as the development of dementia. A "dementia risk group" with fast cognitive decline (i.e. the low efficacy of the treatment) was identified. The tests are ranked according to their predictive values. PMID:23612410

  19. ELEVATED LEVELS OF KYNURENIC ACID DURING GESTATION PRODUCE NEUROCHEMICAL, MORPHOLOGICAL, AND COGNITIVE DEFICITS IN ADULTHOOD: IMPLICATIONS FOR SCHIZOPHRENIA

    PubMed Central

    Pershing, Michelle L.; Bortz, David M.; Pocivavsek, Ana; Fredericks, Peter J.; Jørgensen, Christinna V.; Vunck, Sarah A.; Leuner, Benedetta; Schwarcz, Robert; Bruno, John P.

    2016-01-01

    The levels of kynurenic acid (KYNA), an endogenous negative modulator of alpha 7 nicotinic acetylcholine receptors (α7nAChRs), are elevated in the brains of patients with schizophrenia (SZ). We reported that increases of brain KYNA in rats, through dietary exposure to its precursor kynurenine from embryonic day (ED)15 to postnatal day (PD) 21, result in neurochemical and cognitive deficits in adulthood. The present experiments focused on the effects of prenatal exposure to elevated kynurenine on measures of prefrontal excitability known to be impaired in SZ. Pregnant dams were fed a mash containing kynurenine (100 mg/day; progeny = EKYNs) from ED15 until ED22. Controls were fed an unadulterated mash (progeny = ECONs). The dietary loading procedure elevated maternal and fetal plasma kynurenine (2223% and 693% above controls, respectively) and increased fetal KYNA (forebrain; 500% above controls) on ED21. Elevations in forebrain KYNA disappeared after termination of the loading (PD2), but KYNA levels in the prefrontal cortex (PFC) were unexpectedly increased again when measured in adults (PD56-80; 75% above controls). We also observed changes in several markers of prefrontal excitability, including expression of the α7nAChR (22% and 17% reductions at PD2 and PD56-80), expression of mGluR2 (31% and 24% reductions at ED21 and PD56-80), dendritic spine density (11–14% decrease at PD56-80), subsensitive mesolimbic stimulation of glutamate release in PFC, and reversal/extra-dimensional shift deficits in the prefrontally-mediated set-shifting task. These results highlight the deleterious impact of elevated KYNA levels during sensitive periods of early development, which model the pathophysiological and cognitive deficits seen in SZ. PMID:25446576

  20. Nut consumption and age-related disease.

    PubMed

    Grosso, G; Estruch, R

    2016-02-01

    Current knowledge on the effects of nut consumption on human health has rapidly increased in recent years and it now appears that nuts may play a role in the prevention of chronic age-related diseases. Frequent nut consumption has been associated with better metabolic status, decreased body weight as well as lower body weight gain over time and thus reduce the risk of obesity. The effect of nuts on glucose metabolism, blood lipids, and blood pressure is still controversial. However, significant decreased cardiovascular risk has been reported in a number of observational and clinical intervention studies. Thus, findings from cohort studies show that increased nut consumption is associated with a reduced risk of cardiovascular disease and mortality (especially that due to cardiovascular-related causes). Similarly, nut consumption has been also associated with reduced risk of certain cancers, such as colorectal, endometrial, and pancreatic neoplasms. Evidence regarding nut consumption and neurological or psychiatric disorders is scarce, but a number of studies suggest significant protective effects against depression, mild cognitive disorders and Alzheimer's disease. The underlying mechanisms appear to include antioxidant and anti-inflammatory actions, particularly related to their mono- and polyunsaturated fatty acids (MUFA and PUFA, as well as vitamin and polyphenol content). MUFA have been demonstrated to improve pancreatic beta-cell function and regulation of postprandial glycemia and insulin sensitivity. PUFA may act on the central nervous system protecting neuronal and cell-signaling function and maintenance. The fiber and mineral content of nuts may also confer health benefits. Nuts therefore show promise as useful adjuvants to prevent, delay or ameliorate a number of chronic conditions in older people. Their association with decreased mortality suggests a potential in reducing disease burden, including cardiovascular disease, cancer, and cognitive impairments

  1. Long-Term Cognitive Deficits in Chimpanzees Associated with Early Impoverished Rearing

    ERIC Educational Resources Information Center

    Davenport, Richard K.; And Others

    1973-01-01

    According to transfer index testing, chimpanzees who had been reared in restricted laboratory environments for the first two years of life were inferior in cognitive skills to wild born control subjects. Findings are discussed in terms of the role of early experience in cognitive development. (DP)

  2. Genetic Markers in Biological Fluids for Aging-Related Major Neurocognitive Disorder

    PubMed Central

    Castro-Chavira, S.A.; Fernández, T.; Nicolini, H.; Diaz-Cintra, S.; Prado-Alcalá, R.A.

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer’s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  3. Genetic markers in biological fluids for aging-related major neurocognitive disorder.

    PubMed

    Castro-Chavira, S A; Fernandez, T; Nicolini, H; Diaz-Cintra, S; Prado-Alcala, R A

    2015-01-01

    Aging-related major neurocognitive disorder (NCD), formerly named dementia, comprises of the different acquired diseases whose primary deficit is impairment in cognitive functions such as complex attention, executive function, learning and memory, language, perceptual/motor skills, and social cognition, and that are related to specific brain regions and/or networks. According to its etiology, the most common subtypes of major NCDs are due to Alzheimer' s disease (AD), vascular disease (VaD), Lewy body disease (LBD), and frontotemporal lobar degeneration (FTLD). These pathologies are frequently present in mixed forms, i.e., AD plus VaD or AD plus LBD, thus diagnosed as due to multiple etiologies. In this paper, the definitions, criteria, pathologies, subtypes and genetic markers for the most common age-related major NCD subtypes are summarized. The current diagnostic criteria consider cognitive decline leading to major NCD or dementia as a progressive degenerative process with an underlying neuropathology that begins before the manifestation of symptoms. Biomarkers associated with this asymptomatic phase are being developed as accurate risk factor and biomarker assessments are fundamental to provide timely treatment since no treatments to prevent or cure NCD yet exist. Biological fluid assessment represents a safer, cheaper and less invasive method compared to contrast imaging studies to predict NCD appearance. Genetic factors particularly have a key role not only in predicting development of the disease but also the age of onset as well as the presentation of comorbidities that may contribute to the disease pathology and trigger synergistic mechanisms which may, in turn, accelerate the neurodegenerative process and its resultant behavioral and functional disorders. PMID:25731625

  4. Age-related changes of adaptive and neuropsychological features in persons with Down Syndrome.

    PubMed

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

  5. Age-Related Changes of Adaptive and Neuropsychological Features in Persons with Down Syndrome

    PubMed Central

    Ghezzo, Alessandro; Salvioli, Stefano; Solimando, Maria Caterina; Palmieri, Alice; Chiostergi, Chiara; Scurti, Maria; Lomartire, Laura; Bedetti, Federica; Cocchi, Guido; Follo, Daniela; Pipitone, Emanuela; Rovatti, Paolo; Zamberletti, Jessica; Gomiero, Tiziano; Castellani, Gastone; Franceschi, Claudio

    2014-01-01

    Down Syndrome (DS) is characterised by premature aging and an accelerated decline of cognitive functions in the vast majority of cases. As the life expectancy of DS persons is rapidly increasing, this decline is becoming a dramatic health problem. The aim of this study was to thoroughly evaluate a group of 67 non-demented persons with DS of different ages (11 to 66 years), from a neuropsychological, neuropsychiatric and psychomotor point of view in order to evaluate in a cross-sectional study the age-related adaptive and neuropsychological features, and to possibly identify early signs predictive of cognitive decline. The main finding of this study is that both neuropsychological functions and adaptive skills are lower in adult DS persons over 40 years old, compared to younger ones. In particular, language and short memory skills, frontal lobe functions, visuo-spatial abilities and adaptive behaviour appear to be the more affected domains. A growing deficit in verbal comprehension, along with social isolation, loss of interest and greater fatigue in daily tasks, are the main features found in older, non demented DS persons evaluated in our study. It is proposed that these signs can be alarm bells for incipient dementia, and that neuro-cognitive rehabilitation and psycho-pharmacological interventions must start as soon as the fourth decade (or even earlier) in DS persons, i.e. at an age where interventions can have the greatest efficacy. PMID:25419980

  6. Epigenetic modifications by inhibiting histone deacetylases reverse memory impairment in insulin resistance induced cognitive deficit in mice.

    PubMed

    Sharma, Sorabh; Taliyan, Rajeev

    2016-06-01

    Insulin resistance has been reported as a strong risk factor for Alzheimer's disease. However the molecular mechanisms of association between these still remain elusive. Various studies have highlighted the involvement of histone deacetylases (HDACs) in insulin resistance and cognitive deficits. Thus, the present study was designed to investigate the possible neuroprotective role of HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA) in insulin resistance induced cognitive impairment in mice. Mice were subjected to either normal pellet diet (NPD) or high fat diet (HFD) for 8 weeks. HFD fed mice were treated with SAHA at 25 and 50 mg/kg i.p. once daily for 2 weeks. Serum insulin, glucose, triglycerides, total cholesterol and HDL-cholesterol levels were measured. A battery of behavioral parameters was performed to assess cognitive functions. Level of tumour necrosis factor (TNF-α) was measured in hippocampus to assess neuroinflammation. To further explore the molecular mechanisms we measured the histone H3 acetylation and brain derived neurotrophic factor (BDNF) level. HFD fed mice exhibit characteristic features of insulin resistance. These mice also showed a severe deficit in learning and memory along with reduced histone H3 acetylation and BDNF levels. In contrast, the mice treated with SAHA showed significant and dose dependent improvement in insulin resistant condition. These mice also showed improved learning and memory performance. SAHA treatment ameliorates the HFD induced reduction in histone H3 acetylation and BDNF levels. Based upon these results, it could be suggested that HDAC inhibitors exert neuroprotective effects by increasing H3 acetylation and subsequently BDNF level. PMID:26805421

  7. Behavioral, Cognitive, and Motor Preparation Deficits in a Visual Cued Spatial Attention Task in Autism Spectrum Disorder.

    PubMed

    Sokhadze, Estate M; Tasman, Allan; Sokhadze, Guela E; El-Baz, Ayman S; Casanova, Manuel F

    2016-03-01

    Abnormalities in motor skills have been regarded as part of the symptomatology characterizing autism spectrum disorder (ASD). It has been estimated that 80 % of subjects with autism display "motor dyspraxia" or clumsiness that are not readily identified in a routine neurological examination. In this study we used behavioral measures, event-related potentials (ERP), and lateralized readiness potential (LRP) to study cognitive and motor preparation deficits contributing to the dyspraxia of autism. A modified Posner cueing task was used to analyze motor preparation abnormalities in children with autism and in typically developing children (N = 30/per group). In this task, subjects engage in preparing motor response based on a visual cue, and then execute a motor movement based on the subsequent imperative stimulus. The experimental conditions, such as the validity of the cue and the spatial location of the target stimuli were manipulated to influence motor response selection, preparation, and execution. Reaction time and accuracy benefited from validly cued targets in both groups, while main effects of target spatial position were more obvious in the autism group. The main ERP findings were prolonged and more negative early frontal potentials in the ASD in incongruent trials in both types of spatial location. The LRP amplitude was larger in incongruent trials and had stronger effect in the children with ASD. These effects were better expressed at the earlier stages of LRP, specifically those related to response selection, and showed difficulties at the cognitive phase of stimulus processing rather that at the motor execution stage. The LRP measures at different stages reflect the chronology of cognitive aspects of movement preparation and are sensitive to manipulations of cue correctness, thus representing very useful biomarker in autism dyspraxia research. Future studies may use more advance and diverse manipulations of movement preparation demands in testing more

  8. Do Social and Cognitive Deficits Curtail Musical Understanding? Evidence from Autism and Down Syndrome

    ERIC Educational Resources Information Center

    Heaton, Pamela; Allen, Rory; Williams, Kerry; Cummins, Omar; Happe, Francesca

    2008-01-01

    Children with autism experience difficulties in understanding social affective cues, and it has been suggested that such deficits will generalize to music. In order to investigate this proposal, typically developing individuals and children with autism and Down syndrome were compared on tasks measuring perception of affective and movement states…

  9. Cognitive Behavior Therapy for College Students with Attention-Deficit/Hyperactivity Disorder

    ERIC Educational Resources Information Center

    Ramsay, J. Russell; Rostain, Anthony L.

    2006-01-01

    Attention-Deficit/Hyperactivity Disorder (ADHD) is a developmental syndrome that persists into adulthood for the majority of children with ADHD. Other individuals may not experience the full negative effects of undiagnosed ADHD until they face the demands of adult life. College counseling centers in particular are seeing a rise in the number of…

  10. Systematic review of the relationship between amyloid-β levels and measures of transgenic mouse cognitive deficit in Alzheimer's disease.

    PubMed

    Foley, Avery M; Ammar, Zeena M; Lee, Robert H; Mitchell, Cassie S

    2015-01-01

    Amyloid-β (Aβ) is believed to directly affect memory and learning in Alzheimer's disease (AD). It is widely suggested that there is a relationship between Aβ40 and Aβ42 levels and cognitive performance. In order to explore the validity of this relationship, we performed a meta-analysis of 40 peer-reviewed, published AD transgenic mouse studies that quantitatively measured Aβ levels in brain tissue after assessing cognitive performance. We examined the relationship between Aβ levels (Aβ40, Aβ42, or the ratio of Aβ42 to Aβ40) and cognitive function as measured by escape latency times in the Morris water maze or exploratory preference percentage in the novel object recognition test. Our systematic review examined five mouse models (Tg2576, APP, PS1, 3xTg, APP(OSK)-Tg), gender, and age. The overall result revealed no statistically significant correlation between quantified Aβ levels and experimental measures of cognitive function. However, enough of the trends were of the same sign to suggest that there probably is a very weak qualitative trend visible only across many orders of magnitude. In summary, the results of the systematic review revealed that mice bred to show elevated levels of Aβ do not perform significantly worse in cognitive tests than mice that do not have elevated Aβ levels. Our results suggest two lines of inquiry: 1) Aβ is a biochemical "side effect" of the AD pathology; or 2) learning and memory deficits in AD are tied to the presence of qualitatively "high" levels of Aβ but are not quantitatively sensitive to the levels themselves. PMID:25362040

  11. Childhood abuse and neglect may induce deficits in cognitive precursors of psychosis in high-risk children

    PubMed Central

    Berthelot, Nicolas; Paccalet, Thomas; Gilbert, Elsa; Moreau, Isabel; Mérette, Chantal; Gingras, Nathalie; Rouleau, Nancie; Maziade, Michel

    2015-01-01

    Background Millions of children are born to parents affected by major psychoses. Cognitive dysfunctions seen in patients are already detectable in these children. In parallel, childhood maltreatment increases the risk of adult psychoses through unknown mechanisms. We investigated whether high-risk offspring exposed to abuse/neglect displayed more cognitive precursors of adult psychoses in childhood and adolescence than nonexposed offspring. Methods We used a stepwise selection strategy from a 25-year follow-up of 48 densely affected kindreds including 1500 adults (405 patients with schizophrenia or bipolar disorder) to select high-risk offspring aged 6–22 years for inclusion in our study. All offspring were assessed for childhood trauma from direct interviews with the offspring, parents and relatives and from the review of lifetime medical records of parents and children and administered a neuropsychological battery including IQ and 4 of the most impaired neuropsychological domains in psychoses. Results Our study included 66 high-risk offspring. Those who were exposed to abuse/neglect had significantly lower IQ (effect size [ES] = 0.61) than nonexposed offspring and displayed poorer cognitive performance in visual episodic memory (ES = 0.67) and in executive functions of initiation (ES = 1.01). Moreover, exposed offspring presented more combinations of cognitive deficits that were associated with lower Global Assessment of Functioning scores. Limitations Exposure to abuse/neglect was not assessed in the control group, thus the study could not test whether the effect of childhood maltreatment occured only in a high-risk setting and not in the general population. Conclusion In high-risk youths, maltreatment in childhood/adolescence may negatively impact cognitive domains known to be impaired in adults with psychoses, suggesting an early mediating effect in the association between abuse/neglect and adult psychoses. This finding provides a target for future

  12. The heterogeneity of attention-deficit/hyperactivity disorder symptoms and conduct problems: Cognitive inhibition, emotion regulation, emotionality, and disorganized attachment.

    PubMed

    Forslund, Tommie; Brocki, Karin C; Bohlin, Gunilla; Granqvist, Pehr; Eninger, Lilianne

    2016-09-01

    This study examined the contributions of several important domains of functioning to attention-deficit/hyperactivity disorder (ADHD) symptoms and conduct problems. Specifically, we investigated whether cognitive inhibition, emotion regulation, emotionality, and disorganized attachment made independent and specific contributions to these externalizing behaviour problems from a multiple pathways perspective. The study included laboratory measures of cognitive inhibition and disorganized attachment in 184 typically developing children (M age = 6 years, 10 months, SD = 1.7). Parental ratings provided measures of emotion regulation, emotionality, and externalizing behaviour problems. Results revealed that cognitive inhibition, regulation of positive emotion, and positive emotionality were independently and specifically related to ADHD symptoms. Disorganized attachment and negative emotionality formed independent and specific relations to conduct problems. Our findings support the multiple pathways perspective on ADHD, with poor regulation of positive emotion and high positive emotionality making distinct contributions to ADHD symptoms. More specifically, our results support the proposal of a temperamentally based pathway to ADHD symptoms. The findings also indicate that disorganized attachment and negative emotionality constitute pathways specific to conduct problems rather than to ADHD symptoms. PMID:26895773

  13. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits

    PubMed Central

    Aungst, Stephanie L; Kabadi, Shruti V; Thompson, Scott M; Stoica, Bogdan A; Faden, Alan I

    2014-01-01

    Repeated mild traumatic brain injury (mTBI) can cause sustained cognitive and psychiatric changes, as well as neurodegeneration, but the underlying mechanisms remain unclear. We examined histologic, neurophysiological, and cognitive changes after single or repeated (three injuries) mTBI using the rat lateral fluid percussion (LFP) model. Repeated mTBI caused substantial neuronal cell loss and significantly increased numbers of activated microglia in both ipsilateral and contralateral hippocampus on post-injury day (PID) 28. Long-term potentiation (LTP) could not be induced on PID 28 after repeated mTBI in ex vivo hippocampal slices from either hemisphere. N-Methyl-D-aspartate (NMDA) receptor-mediated responses were significantly attenuated after repeated mTBI, with no significant changes in α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated responses. Long-term potentiation was elicited in slices after single mTBI, with potentiation significantly increased in ipsilateral versus contralateral hippocampus. After repeated mTBI, rats displayed cognitive impairments in the Morris water maze (MWM) and novel object recognition (NOR) tests. Thus, repeated mTBI causes deficits in the hippocampal function and changes in excitatory synaptic neurotransmission, which are associated with chronic neuroinflammation and neurodegeneration. PMID:24756076

  14. Increased hippocampal NgR1 signaling machinery in aged rats with deficits of spatial cognition

    PubMed Central

    VanGuilder Starkey, Heather D.; Sonntag, William E.; Freeman, Willard M.

    2013-01-01

    Myelin-associated inhibitor/NgR1 signaling has important roles in modulation of synaptic plasticity, with demonstrated effects on cognitive function. We have previously demonstrated that NgR1 and its ligands are upregulated in the hippocampus of aged rats with impaired spatial learning and memory, but it is unknown whether increased expression of these proteins indicates a potential increase in pathway signaling because NgR1 requires co-receptors for signal transduction through RhoA. Two co-receptor complexes have been identified to date, comprised of NgR1 and LINGO-1, and either p75 or TROY. In this study, we assessed the expression of LINGO-1, p75 and TROY, and the downstream effector RhoA in mature adult (12 months) and aged (26 months) male Fischer 344/Brown Norway hybrid rats classified as cognitively impaired or cognitively intact by Morris water maze testing. The hippocampal distribution of NgR1 and its co-receptors was assessed to determine whether receptor/co-receptor interaction, and therefore signaling through this pathway, is possible. Protein expression of LINGO-1, p75, TROY, and RhoA was significantly elevated in cognitively impaired, but not intact, aged rats compared to mature adults, and expression levels correlated significantly with water maze performance. Co-localization of NgR1 with LINGO-1, p75 and TROY was observed in hippocampal neurons of aged, cognitively impaired rats. Further, expression profiles of NgR1 pathway components were demonstrated to classify rats as cognitively intact or cognitively impaired with high accuracy. Together, this suggests that hippocampal induction of this pathway is a conserved phenomenon in cognitive decline that may impair learning and memory by suppressing neuronal plasticity. PMID:23438185

  15. Gender differences in cognitive deficits in schizophrenia with and without diabetes.

    PubMed

    Zhang, Bao Hua; Han, Mei; Zhang, Xiang Yang; Hui, Li; Jiang, Shu Rong; Yang, Fu De; Tan, Yun Long; Wang, Zhi Ren; Li, Juan; Huang, Xu Feng

    2015-11-01

    This study investigated gender differences in cognition in schizophrenia with and without diabetes. Cognition was assessed in 263 individuals with schizophrenia with age range (40-68): 67 males and 34 females with schizophrenia with diabetes; and 125 males and 37 females with schizophrenia without diabetes according to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Fasting glucose, hemoglobin A1c (HbA1c) and lipid levels were measured. Results showed that male individuals performed worse on most cognitive tasks, especially attention, in schizophrenia with than without diabetes. This result was not observed in female individuals. Also, individuals of both genders showed higher fasting glucose and HbA1c in schizophrenia with than without diabetes. In schizophrenia with diabetes, males had significantly worse cognition than females in all cognitive domains. Higher HbA1c, lower high-density lipoprotein, and an earlier age of onset of schizophrenia were found in males compared with female individuals. HbA1c was negatively associated with attention and the RBANS total score for males but not for females. In schizophrenia without diabetes, males showed worse performance in immediate and delayed memory than females. This study support cognition was worse for males with schizophrenia irrespective of whether they have diabetes. However, diabetes exemplified the gender differences, especially in attention. PMID:26555485

  16. Developing treatments for cognitive deficits in schizophrenia: the challenge of translation.

    PubMed

    Young, J W; Geyer, M A

    2015-02-01

    Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. While antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult, however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition. PMID:25516372

  17. Developing treatments for cognitive deficits in schizophrenia: The challenge of translation

    PubMed Central

    Young, J.W.; Geyer, M.A.

    2015-01-01

    Schizophrenia is a life-long debilitating mental disorder affecting tens of millions of people worldwide. The serendipitous discovery of antipsychotics focused pharmaceutical research on developing a better antipsychotic. Our understanding of the disorder has advanced however, with the knowledge that cognitive enhancers are required for patients in order to improve their everyday lives. Whilst antipsychotics treat psychosis, they do not enhance cognition and hence are not antischizophrenics. Developing pro-cognitive therapeutics has been extremely difficult however, especially when no approved treatment exists. In lieu of stumbling on an efficacious treatment, developing targeted compounds can be facilitated by understanding the neural mechanisms underlying altered cognitive functioning in patients. Equally importantly, these cognitive domains will need to be measured similarly in animals and humans so that novel targets can be tested prior to conducting expensive clinical trials. To date, the limited similarity of testing across species has resulted in a translational bottleneck. In this review, we emphasize that schizophrenia is a disorder characterized by abnormal cognitive behavior. Quantifying these abnormalities using tasks having cross-species validity would enable the quantification of comparable processes in rodents. This approach would increase the likelihood that the neural substrates underlying relevant behaviors will be conserved across species. Hence, we detail cross-species tasks which can be used to test the effects of manipulations relevant to schizophrenia and putative therapeutics. Such tasks offer the hope of providing a bridge between non-clinical and clinical testing that will eventually lead to treatments developed specifically for patients with deficient cognition. PMID:25516372

  18. Assessing Social-Cognitive Deficits in Schizophrenia With the Mayer-Salovey-Caruso Emotional Intelligence Test

    PubMed Central

    Eack, Shaun M.; Greeno, Catherine G.; Pogue-Geile, Michael F.; Newhill, Christina E.; Hogarty, Gerard E.

    2010-01-01

    The emotion management subscale of the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT) has recently been recommended by the National Institute of Mental Health Measurement and Treatment Research to Improve Cognition in Schizophrenia committee as the sole measure of social cognition for trials of cognitive enhancement in schizophrenia, yet the psychometric properties of this subscale and the larger instrument in schizophrenia patients have not been thoroughly examined. This research presents a psychometric investigation of the MSCEIT in a sample of 64 early course outpatients with schizophrenia, schizoaffective, or schizophreniform disorder. Results demonstrated that the MSCEIT possesses adequate internal consistency reliability among its branch and total scales and that patients’ branch and overall test performance was significantly below normative levels. Estimates of discriminant and concurrent validity indicated that the MSCEIT diverged from measures of neurocognitive functioning and psychopathology, but was only modestly related with objective measures of functional outcome. Convergent validity estimates suggested that, contrary to expectations, the MSCEIT did not correlate with a behavioral measure of social cognition. Finally, exploratory factor analyses suggested the possibility of a shift in the latent structure of emotional intelligence in schizophrenia, compared with studies with healthy individuals. These findings support the use of the MSCEIT as a reliable and potentially valid method of assessing the emotional components of social cognition in schizophrenia, but also point to a need for additional measurement development efforts to assess broader social-cognitive domains that may exhibit stronger relations with functional outcome. Further investigation is warranted to examine the instrument's latent factor structure and convergence with other measures of social cognition. PMID:18648021

  19. Deregulated semantic cognition contributes to object-use deficits in Alzheimer's disease: A comparison with semantic aphasia and semantic dementia.

    PubMed

    Corbett, Faye; Jefferies, Elizabeth; Burns, Alistair; Lambon Ralph, Matthew A

    2015-09-01

    Executive control is impaired from the early stages of Alzheimer's Disease (AD) and this produces deregulated semantic cognition (Corbett, Jefferies, Burns, & Lambon Ralph, ; Perry, Watson, & Hodges, ). While control deficits should affect semantic retrieval across all modalities, previous studies have typically focused on verbal semantic tasks. Even when non-verbal semantic tasks have been used, these have typically employed simple picture-matching tasks, which may be influenced by abnormalities in covert naming. Therefore, in the present study, we examined 10 patients with AD on a battery of object-use tasks, in order to advance our understanding of the origins of non-verbal semantic deficits in this population. The AD patients' deficits were contrasted with previously published performance on the same tasks within two additional groups of patients, displaying either semantic degradation (semantic dementia) or deregulation of semantic retrieval (semantic aphasia; Corbett, Jefferies, Ehsan, & Lambon Ralph, ). While overall accuracy was comparable to the scores in both other groups, the AD patients' object-use impairment most closely resembled that observed in SA; they exhibited poorer performance on comprehension tasks that placed strong demands on executive control. A similar pattern was observed in the expressive domain: the AD and SA groups were relatively good at straightforward object use compared to executively demanding, mechanical puzzles. Error types also differed: while all patients omitted essential actions, the SA and AD groups' demonstrations also featured unrelated intrusions. An association between AD patients' object use and their scores on standard executive measures suggested that control deficits contributed to their non-verbal semantic deficits. Moreover, in a task specifically designed to manipulate executive demand, patients with AD (and SA) exhibited difficulty in thinking flexibly about the non-canonical uses of everyday objects, especially

  20. Biochemical, Biomedical and Metabolic Aspects of Imidazole-Containing Dipeptides with the Inherent Complexity to Neurodegenerative Diseases and Various States of Mental Well-Being: A Challenging Correction and Neurotherapeutic Pharmaceutical Biotechnology for Treating Cognitive Deficits, Depression and Intellectual Disabilities.

    PubMed

    Babizhayev, Mark A

    2014-01-01

    The activities of carnosine (β-alanyl-L-histidine), carnosine imidazole containing dipeptide based derivatives (N-acetylcarnosine, carcinine, homocarnosine) and a carnosine degrading enzyme (serum carnosinase (EC 3.4.13.20); [human tissue carnosinase (EC 3.4.13.3), CN2 (CNDP2)] ) activities have been discrepantly linked to neuropathophysiological processes. Approximately 82% of the U.S. population will experience normal age-related cognitive decline, as compared to the precipitous losses that are associated with dementing disorders. Interventions designed to promote health and function through everyday activity and specific pharmaco-nutritional therapeutic treatments may enhance brain plasticity in key regions that support executive function. Cognitive health is multidimensional cascade of functions. It encompasses an array of functions, including general intellectual ability, memory, language, allowing a person to interact effectively and appropriately with the environment. The risk factors for reduced physical and cognitive functions in elderly people, as identified in longitudinal studies, relate to comorbidities, critical care situations, physical and psychosocial health, environmental conditions, social circumstances, nutrition, and lifestyle. Depression and dementia are both common in older adults; cognitive functioning declines slightly with normal aging; depression itself can be associated with cognitive impairment and dementia. In this study the role of carnosine and related neuron specific naturally-occurring endogenous imidazole-containing dipeptide pharmacoperones (N-acetylcarnosine, carcinine) is revealed presently in a surprisingly large amounts in long-lived human tissues to correct conformational abnormalities leading to distinct neurodegeneration and age-related disease states, treating cognitive deficits, depression and intellectual disabilities. Carnosine serves as a physiological buffering agent and a metal ion (e.g., zinc and copper) chelator

  1. Assessing Specific Cognitive Deficits Associated with Dementia in Older Adults with Down Syndrome: Use and Validity of the Arizona Cognitive Test Battery (ACTB)

    PubMed Central

    Sinai, Amanda; Hassiotis, Angela; Rantell, Khadija; Strydom, Andre

    2016-01-01

    Background Down syndrome is associated with specific cognitive deficits. Alongside this, older adults with Down syndrome are a high risk group for dementia. The Arizona Cognitive Test Battery (ACTB), a cognitive assessment battery specifically developed for use with individuals with Down syndrome, has been proposed for use as outcome measures for clinical trials in this population. It has not been validated in older adults with Down syndrome. This study aims to assess the use and validity of the ACTB in older adults with Down syndrome. Methods Participants with Down syndrome aged 45 and over were assessed using the ACTB, standard tabletop tests and informant ratings. Results Assessment outcomes of 49 participants were analysed. Of these, 19 (39%) had a diagnosis of dementia or possible dementia. Most participants were able to attempt most of the tasks, although some tasks had high floor effects (including CANTAB Intra-Extra Dimensional shift stages completed and Modified Dots Task). Of the ACTB tasks, statistically significant differences were observed between the dementia and no dementia groups on CANTAB Simple Reaction Time median latency, NEPSY Visuomotor Precision—Car and Motorbike and CANTAB Paired Associates Learning stages completed. No significant differences were observed for CANTAB Intra-Extra Dimensional Shift, Modified Dots Task, Finger Sequencing, NEPSY Visuomotor precision—Train and Car and CANTAB Paired Associates Learning first trial memory score. Several of the tasks in the ACTB can be used in older adults with Down syndrome and have mild to moderate concurrent validity when compared to tabletop tests and informant ratings, although this varies on a test by test basis. Conclusions Overall, scores for a number of tests in the ACTB were similar when comparing dementia and no dementia groups of older adults with Down syndrome, suggesting that it would not be an appropriate outcome measure of cognitive function for clinical trials of dementia

  2. Acai fruit improves motor and cognitive function in aged rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aged rats show impaired performance on motor and cognitive tasks that require the use of spatial learning and memory. In previous studies, we have shown the beneficial effects of various berry fruits (blueberries, strawberries, and blackberries) in reversing age-related deficits in behavioral and ne...

  3. Naringin ameliorates cognitive deficits via oxidative stress, proinflammatory factors and the PPARγ signaling pathway in a type 2 diabetic rat model.

    PubMed

    Qi, Zhonghua; Xu, Yinghui; Liang, Zhanhua; Li, Sheng; Wang, Jie; Wei, Yi; Dong, Bin

    2015-11-01

    Naringenin is a flavonoid polyphenolic compound, which facilitates the removal of free radicals, oxidative stress and inflammation. The present study aimed to obtain a better understanding of the effects of curcumin on the regulation of diabetes‑associated cognitive decline, and its underlying mechanisms. An experimental diabetes mellitus (DM) rat model was induced by streptozoticin (50 mg/kg). Following treatment with naringin (100 and 200 mg/kg) for 16 weeks, the body weight and blood glucose levels of the DM rats were measured. A morris water maze test was used to analyze the effects of naringin on the cognitive deficit of the DM rats. The levels of oxidative stress, proinflammatory factors, caspase‑3 and caspase‑9, and the protein expression of peroxisome proliferator‑activated receptor γ (PPARγ) were quantified in the DM rats using a commercially‑available kit and western blot assay, respectively. In addition, a GW9662 PPARγ inhibitor (0.3 mg/kg) was administered to the DM rats to determine whether PPARγ affected the effects of naringin on the cognitive deficit of the DM rats. The results demonstrated that naringin increased the body weight, blood glucose levels, and cognitive deficits of the DM rats. The levels of oxidative stress and proinflammatory factors in the naringin‑treated rats were significantly lower, compared with those of the DM rats. In addition, naringin activated the protein expression of PPARγ, and administration of the PPARγ inhibitor decreased the protein expression of PPARγ, and attenuated the effects of naringin on cognitive