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Sample records for age-related memory impairments

  1. Activation of NO-cGMP Signaling Rescues Age-Related Memory Impairment in Crickets

    PubMed Central

    Matsumoto, Yukihisa; Matsumoto, Chihiro S.; Takahashi, Toshihumi; Mizunami, Makoto

    2016-01-01

    Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes. PMID:27616985

  2. Activation of NO-cGMP Signaling Rescues Age-Related Memory Impairment in Crickets.

    PubMed

    Matsumoto, Yukihisa; Matsumoto, Chihiro S; Takahashi, Toshihumi; Mizunami, Makoto

    2016-01-01

    Age-related memory impairment (AMI) is a common feature and a debilitating phenotype of brain aging in many animals. However, the molecular mechanisms underlying AMI are still largely unknown. The cricket Gryllus bimaculatus is a useful experimental animal for studying age-related changes in learning and memory capability; because the cricket has relatively short life-cycle and a high capability of olfactory learning and memory. Moreover, the molecular mechanisms underlying memory formation in crickets have been examined in detail. In the present study, we trained male crickets of different ages by multiple-trial olfactory conditioning to determine whether AMI occurs in crickets. Crickets 3 weeks after the final molt (3-week-old crickets) exhibited levels of retention similar to those of 1-week-old crickets at 30 min or 2 h after training; however they showed significantly decreased levels of 1-day retention, indicating AMI in long-term memory (LTM) but not in anesthesia-resistant memory (ARM) in olfactory learning of crickets. Furthermore, 3-week-old crickets injected with a nitric oxide (NO) donor, a cyclic GMP (cGMP) analog or a cyclic AMP (cAMP) analog into the hemolymph before conditioning exhibited a normal level of LTM, the same level as that in 1-week-old crickets. The rescue effect by NO donor or cGMP analog injection was absent when the crickets were injected after the conditioning. For the first time, an NO donor and a cGMP analog were found to antagonize the age-related impairment of LTM formation, suggesting that deterioration of NO synthase (NOS) or molecules upstream of NOS activation is involved in brain-aging processes. PMID:27616985

  3. Moringa oleifera mitigates memory impairment and neurodegeneration in animal model of age-related dementia.

    PubMed

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180-220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988

  4. Moringa oleifera Mitigates Memory Impairment and Neurodegeneration in Animal Model of Age-Related Dementia

    PubMed Central

    Sutalangka, Chatchada; Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-mee, Wipawee

    2013-01-01

    To date, the preventive strategy against dementia is still essential due to the rapid growth of its prevalence and the limited therapeutic efficacy. Based on the crucial role of oxidative stress in age-related dementia and the antioxidant and nootropic activities of Moringa oleifera, the enhancement of spatial memory and neuroprotection of M. oleifera leaves extract in animal model of age-related dementia was determined. The possible underlying mechanism was also investigated. Male Wistar rats, weighing 180–220 g, were orally given M. oleifera leaves extract at doses of 100, 200, and 400 mg/kg at a period of 7 days before and 7 days after the intracerebroventricular administration of AF64A bilaterally. Then, they were assessed memory, neuron density, MDA level, and the activities of SOD, CAT, GSH-Px, and AChE in hippocampus. The results showed that the extract improved spatial memory and neurodegeneration in CA1, CA2, CA3, and dentate gyrus of hippocampus together with the decreased MDA level and AChE activity but increased SOD and CAT activities. Therefore, our data suggest that M. oleifera leaves extract is the potential cognitive enhancer and neuroprotectant. The possible mechanism might occur partly via the decreased oxidative stress and the enhanced cholinergic function. However, further explorations concerning active ingredient(s) are still required. PMID:24454988

  5. Exercise Counteracts Aging-Related Memory Impairment: A Potential Role for the Astrocytic Metabolic Shuttle

    PubMed Central

    Tsai, Sheng-Feng; Chen, Pei-Chun; Calkins, Marcus J.; Wu, Shih-Ying; Kuo, Yu-Min

    2016-01-01

    Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. PMID:27047373

  6. Exercise Counteracts Aging-Related Memory Impairment: A Potential Role for the Astrocytic Metabolic Shuttle.

    PubMed

    Tsai, Sheng-Feng; Chen, Pei-Chun; Calkins, Marcus J; Wu, Shih-Ying; Kuo, Yu-Min

    2016-01-01

    Age-related cognitive impairment has become one of the most common health threats in many countries. The biological substrate of cognition is the interconnection of neurons to form complex information processing networks. Experience-based alterations in the activities of these information processing networks lead to neuroadaptation, which is physically represented at the cellular level as synaptic plasticity. Although synaptic plasticity is known to be affected by aging, the underlying molecular mechanisms are not well described. Astrocytes, a glial cell type that is infrequently investigated in cognitive science, have emerged as energy suppliers which are necessary for meeting the abundant energy demand resulting from glutamatergic synaptic activity. Moreover, the concerted action of an astrocyte-neuron metabolic shuttle is essential for cognitive function; whereas, energetic incoordination between astrocytes and neurons may contribute to cognitive impairment. Whether altered function of the astrocyte-neuron metabolic shuttle links aging to reduced synaptic plasticity is unexplored. However, accumulated evidence documents significant beneficial effects of long-term, regular exercise on cognition and synaptic plasticity. Furthermore, exercise increases the effectiveness of astrocyte-neuron metabolic shuttle by upregulation of astrocytic lactate transporter levels. This review summarizes previous findings related to the neuronal activity-dependent astrocyte-neuron metabolic shuttle. Moreover, we discuss how aging and exercise may shape the astrocyte-neuron metabolic shuttle in cognition-associated brain areas. PMID:27047373

  7. Age-related impairment of visual recognition memory correlates with impaired synaptic distribution of GluA2 and protein kinase Mζ in the dentate gyrus.

    PubMed

    Aicardi, Giorgio

    2012-10-01

    Age-related functional alterations in the perforant path projection from the entorhinal cortex to the dentate gyrus (DG) of the hippocampus play a major role in age-related memory impairments, but little is known about the molecular mechanisms responsible for these changes. In a recent study, young and aged monkeys were tested on the visual recognition memory test "delayed nonmatching-to-sample"; then, electron microscopic immunocytochemistry was performed in the hippocampal DG to determine the subcellular localization of the GluA2 subunit of the glutamate α-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid receptor (AMPAR) and protein kinase Mζ (PKMζ), which promotes memory storage by regulating GluA2-containing AMPAR trafficking. The results obtained suggest that age-related deficits in visual recognition memory are coupled with impairment in PKMζ-dependent maintenance of GluA2 at the synapse. Together with previous evidences of the critical role of PKMζ in memory consolidation, these data render this enzyme an attractive potential therapeutic target for treating age-related memory decline, and support the view that the pharmacological manipulation of AMPAR trafficking in the synapses may provide new insights in the search of memory enhancers for aged individuals, including those affected by Alzheimer disease. PMID:22985047

  8. 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

  9. Isoflurane Exposure during Mid-Adulthood Attenuates Age-Related Spatial Memory Impairment in APP/PS1 Transgenic Mice

    PubMed Central

    Xu, Huan; Wang, Beilei; Chen, Xuemei; Chen, Jie; Wang, Xiangrui

    2012-01-01

    Many in vitro findings suggest that isoflurane exposure might accelerate the process of Alzheimer Disease (AD); however, no behavioral evidence exists to support this theory. In the present study, we hypothesized that exposure of APP/PS1 transgenic mice to isoflurane during mid-adulthood, which is the pre-symptomatic phase of amyloid beta (Abeta) deposition, would alter the progression of AD. Seven-month-old Tg(APPswe,PSEN1dE9)85Dbo/J transgenic mice and their wild-type littermates were exposed to 1.1% isoflurane for 2 hours per day for 5 days. Learning and memory ability was tested 48 hours and 5 months following isoflurane exposure using the Morris Water Maze and Y maze, respectively. Abeta deposition and oligomers in the hippocampus were measured by immunohistochemistry or Elisa 5 months following isoflurane exposure. We found that the performance of both the transgenic and wild-type mice in the Morris Water Maze significantly improved 48 hours following isoflurane exposure. The transgenic mice made significantly fewer discrimination errors in the Y maze following isoflurane exposure, and no differences were found between wild-type littermates 5 months following isoflurane exposure. For the transgenic mice, the Abeta plaque and oligomers in the hippocampus was significantly decreased in the 5 months following isoflurane exposure. In summary, repeated isoflurane exposure during the pre-symptomatic phase not only improved spatial memory in both the APP/PS1 transgenic and wild-type mice shortly after the exposure but also prevented age-related decline in learning and memory and attenuated the Abeta plaque and oligomers in the hippocampus of transgenic mice. PMID:23185565

  10. 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

  11. Age-related increase in amyloid plaque burden is associated with impairment in conditioned fear memory in CRND8 mouse model of amyloidosis

    PubMed Central

    2012-01-01

    Introduction The current pathological confirmation of the diagnosis of Alzheimer's disease (AD) is still based on postmortem identification of parenchymal amyloid beta (Aβ) plaques, intra-neuronal neurofibrillary tangles, and neuronal loss. The memory deficits that are present in the early stages of AD are linked to the dysfunction of structures in the entorhinal cortex and limbic system, especially the hippocampus and amygdala. Using the CRND8 transgenic mouse model of amyloidosis, which over-expresses a mutant human amyloid precursor protein (APP) gene, we evaluated hippocampus-dependent contextual and amygdala-dependent tone fear conditioned (FC) memory, and investigated the relationship between the fear memory indices and Aβ plaque burden. Methods Mice were tested at three, six, and 12 months of age, which corresponds to early, mild, and severe Aβ plaque deposition, following a cross-sectional experimental design. We used a delay version of the fear conditioning paradigm in which tone stimulus was co-terminated with foot-shocks during exploration of the training chamber. The Aβ plaque burden was evaluated at each age after the completion of the behavioral tests. Results CRDN8 mice showed context fear memory comparable to control mice at three and six months, but were significantly impaired at 12 months of age. In contrast, the tone fear memory was significantly impaired in the model at each age of testing. The Aβ plaque burden significantly increased with age, and was correlated with the overall impairment in context and tone fear memory in the CRND8 mice within the studied age. Conclusions Our data extend previous studies showing that other APP mouse models exhibit impairment in fear conditioned memory, by demonstrating that this impairment is progressive and correlates well with an overall increase in Aβ burden. Also, the demonstrated greater sensitivity of the tone conditioning test in the identification of age dependent differences between CRND8 and

  12. Alzheimer's disease and age-related memory decline (preclinical).

    PubMed

    Terry, Alvin V; Callahan, Patrick M; Hall, Brandon; Webster, Scott J

    2011-08-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  13. Association of Age Related Macular Degeneration and Age Related Hearing Impairment

    PubMed Central

    Ghasemi, Hassan; Pourakbari, Malihe Shahidi; Entezari, Morteza; Yarmohammadi, Mohammad Ebrahim

    2016-01-01

    Purpose: To evaluate the association between age-related macular degeneration (ARMD) and sensory neural hearing impairment (SHI). Methods: In this case-control study, hearing status of 46 consecutive patients with ARMD were compared with 46 age-matched cases without clinical ARMD as a control group. In all patients, retinal involvements were confirmed by clinical examination, fluorescein angiography (FA) and optical coherence tomography (OCT). All participants were examined with an otoscope and underwent audiological tests including pure tone audiometry (PTA), speech reception threshold (SRT), speech discrimination score (SDS), tympanometry, reflex tests and auditory brainstem response (ABR). Results: A significant (P = 0.009) association was present between ARMD, especially with exudative and choroidal neovascularization (CNV) components, and age-related hearing impairment primarily involving high frequencies. Patients had higher SRT and lower SDS against anticipated presbycusis than control subjects. Similar results were detected in exudative, CNV and scar patterns supporting an association between late ARMD with SRT and SDS abnormalities. ABR showed significantly prolonged wave I and IV latency times in ARMD (P = 0.034 and 0.022, respectively). Average latency periods for wave I in geographic atrophy (GA) and CNV, and that for wave IV in drusen patterns of ARMD were significantly higher than controls (P = 0.030, 0.007 and 0.050, respectively). Conclusion: The association between ARMD and age-related SHI may be attributed to common anatomical components such as melanin in these two sensory organs. PMID:27195086

  14. Soybean β-Conglycinin Prevents Age-Related Hearing Impairment

    PubMed Central

    Tanigawa, Tohru; Shibata, Rei; Kondo, Kazuhisa; Katahira, Nobuyuki; Kambara, Takahiro; Inoue, Yoko; Nonoyama, Hiroshi; Horibe, Yuichiro; Ueda, Hiromi; Murohara, Toyoaki

    2015-01-01

    Obesity-related complications are associated with the development of age-related hearing impairment. β-Conglycinin (β-CG), one of the main storage proteins in soy, offers multiple health benefits, including anti-obesity and anti-atherosclerotic effects. Here, to elucidate the potential therapeutic application of β-CG, we investigated the effect of β-CG on age-related hearing impairment. Male wild-type mice (age 6 months) were randomly divided into β-CG-fed and control groups. Six months later, the body weight was significantly lower in β-CG-fed mice than in the controls. Consumption of β-CG rescued the hearing impairment observed in control mice. Cochlear blood flow also increased in β-CG-fed mice, as did the expression of eNOS in the stria vascularis (SV), which protects vasculature. β-CG consumption also ameliorated oxidative status as assessed by 4-HNE staining. In the SV, lipofuscin granules of marginal cells and vacuolar degeneration of microvascular pericytes were decreased in β-CG-fed mice, as shown by transmission electron microscopy. β-CG consumption prevented loss of spiral ganglion cells and reduced the frequencies of lipofuscin granules, nuclear invaginations, and myelin vacuolation. Our observations indicate that β-CG ameliorates age-related hearing impairment by preserving cochlear blood flow and suppressing oxidative stress. PMID:26348726

  15. 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

  16. Ageing-related stereotypes in memory: When the beliefs come true.

    PubMed

    Bouazzaoui, Badiâa; Follenfant, Alice; Ric, François; Fay, Séverine; Croizet, Jean-Claude; Atzeni, Thierry; Taconnat, Laurence

    2016-05-01

    Age-related stereotype concerns culturally shared beliefs about the inevitable decline of memory with age. In this study, stereotype priming and stereotype threat manipulations were used to explore the impact of age-related stereotype on metamemory beliefs and episodic memory performance. Ninety-two older participants who reported the same perceived memory functioning were divided into two groups: a threatened group and a non-threatened group (control). First, the threatened group was primed with an ageing stereotype questionnaire. Then, both groups were administered memory complaints and memory self-efficacy questionnaires to measure metamemory beliefs. Finally, both groups were administered the Logical Memory task to measure episodic memory, for the threatened group the instructions were manipulated to enhance the stereotype threat. Results indicated that the threatened individuals reported more memory complaints and less memory efficacy, and had lower scores than the control group on the logical memory task. A multiple mediation analysis revealed that the stereotype threat effect on the episodic memory performance was mediated by both memory complaints and memory self-efficacy. This study revealed that stereotype threat impacts belief in one's own memory functioning, which in turn impairs episodic memory performance. PMID:26057336

  17. 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

  18. Aging-related episodic memory decline: are emotions the key?

    PubMed Central

    Kinugawa, Kiyoka; Schumm, Sophie; Pollina, Monica; Depre, Marion; Jungbluth, Carolin; Doulazmi, Mohamed; Sebban, Claude; Zlomuzica, Armin; Pietrowsky, Reinhard; Pause, Bettina; Mariani, Jean; Dere, Ekrem

    2013-01-01

    Episodic memory refers to the recollection of personal experiences that contain information on what has happened and also where and when these events took place. Episodic memory function is extremely sensitive to cerebral aging and neurodegerative diseases. We examined episodic memory performance with a novel test in young (N = 17, age: 21–45), middle-aged (N = 16, age: 48–62) and aged but otherwise healthy participants (N = 8, age: 71–83) along with measurements of trait and state anxiety. As expected we found significantly impaired episodic memory performance in the aged group as compared to the young group. The aged group also showed impaired working memory performance as well as significantly decreased levels of trait anxiety. No significant correlation between the total episodic memory and trait or state anxiety scores was found. The present results show an age-dependent episodic memory decline along with lower trait anxiety in the aged group. Yet, it still remains to be determined whether this difference in anxiety is related to the impaired episodic memory performance in the aged group. PMID:23378831

  19. Age-related differences in memory and in the memory effects of nootropic drugs.

    PubMed

    Petkov, V D; Mosharrof, A H; Petkov, V V; Kehayov, R A

    1990-01-01

    In experiments of 2-, 5-, 10- and 22-month old rats, using active avoidance with punishment reinforcement (maze and shuttle-box) and passive avoidance (step-down), we found that acquisition and retention in aged rats were impaired significantly or only as a trend. The nootropics adafenoxate, meclofenoxate, citicholine, aniracetam and the standardized ginseng extract administered orally for 7 to 10 days usually facilitated learning and improved memory in the rats of all ages. By some of the indices used the drugs gave more pronounced favourable effects in old rats, while by others better effects were observed in young or adult rats. The results demonstrate significant age-related differences in learning and memory in rats and in the effects of nootropic drugs on these processes. PMID:2281798

  20. 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

  1. 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

  2. Age-related differences in working memory updating components.

    PubMed

    Linares, Rocío; Bajo, M Teresa; Pelegrina, Santiago

    2016-07-01

    The aim of this study was to investigate possible age-related changes throughout childhood and adolescence in different component processes of working memory updating (WMU): retrieval, transformation, and substitution. A set of numerical WMU tasks was administered to four age groups (8-, 11-, 14-, and 21-year-olds). To isolate the effect of each of the WMU components, participants performed different versions of a task that included different combinations of the WMU components. The results showed an expected overall decrease in response times and an increase in accuracy performance with age. Most important, specific age-related changes in the retrieval component were found, demonstrating that the effect of retrieval on accuracy was larger in children than in adolescents or young adults. These findings indicate that the availability of representations from outside the focus of attention may change with age. Thus, the retrieval component of updating could contribute to the age-related changes observed in the performance of many updating tasks. PMID:26985577

  3. I owe you: age-related similarities and differences in associative memory for gains and losses.

    PubMed

    Castel, Alan D; Friedman, Michael C; McGillivray, Shannon; Flores, Cynthia C; Murayama, Kou; Kerr, Tyson; Drolet, Aimee

    2016-09-01

    Older adults often experience associative memory impairments but can sometimes remember important information. The current experiments investigate potential age-related similarities and differences associate memory for gains and losses. Younger and older participants were presented with faces and associated dollar amounts, which indicated how much money the person "owed" the participant, and were later given a cued recall test for the dollar amount. Experiment 1 examined face-dollar amount pairs while Experiment 2 included negative dollar amounts to examine both gains and losses. While younger adults recalled more information relative to older adults, both groups were more accurate in recalling the correct value associated with high-value faces compared to lower-value faces and remembered gist-information about the values. However, negative values (losses) did not have a strong impact on recall among older adults versus younger adults, illustrating important associative memory differences between younger and older adults. PMID:26847137

  4. 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

  5. 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

  6. 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

  7. 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

  8. Aging accelerates memory extinction and impairs memory restoration in Drosophila.

    PubMed

    Chen, Nannan; Guo, Aike; Li, Yan

    2015-05-15

    Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. PMID:25842205

  9. DRYAD and ADH: Further comments on explaining age-related differences in memory.

    PubMed

    Naveh-Benjamin, Moshe; Smyth, Andrea C

    2016-02-01

    Recently, Smyth and Naveh-Benjamin (2016) questioned some of the main assumptions/hypotheses of DRYAD (or density of representations yields age-related deficits), a global-deficit model of aging and memory judgments (Benjamin, 2010; Benjamin et al., 2012). Smyth and Naveh-Benjamin (2016) provided empirical evidence that seems incompatible with DRYAD, but that fits the associative deficit hypothesis (ADH; Naveh-Benjamin, 2000), 1 specific-deficit theoretical view. In response, Aaron Benjamin (2016) offered a discussion of the complementary strengths and weaknesses of the DRYAD and the ADH, and the potential ways they might work together. We agree with many of his comments, but are not convinced that DRYAD is able to explain basic replicable empirical evidence of the type mentioned in Smyth and Naveh-Benjamin (2016). We discuss the reasons why we are not fully convinced by the demonstration of DRYAD's simulation of results presented in Benjamin (2016) and then present an implementation of ADH in a computationally based age-related impaired neuromodulation approach that was shown to simulate the basic empirical results of age-related associative memory deficits. We also discuss the issues of parsimony of theories and the appropriate type of representation, in the context of global versus specific deficits theoretical views. Finally, we show that the ADH's take on the distinction between items and associations has been adopted by some global computational models of memory. We believe that considerations of the above issues and others raised by Benjamin (2016) can lead to fruitful discussions that will benefit both theory development and existing knowledge of aging and memory. PMID:26866588

  10. 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

  11. 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

  12. Resveratrol Prevents Age-Related Memory and Mood Dysfunction with Increased Hippocampal Neurogenesis and Microvasculature, and Reduced Glial Activation

    PubMed Central

    Kodali, Maheedhar; Parihar, Vipan K.; Hattiangady, Bharathi; Mishra, Vikas; Shuai, Bing; Shetty, Ashok K.

    2015-01-01

    Greatly waned neurogenesis, diminished microvasculature, astrocyte hypertrophy and activated microglia are among the most conspicuous structural changes in the aged hippocampus. Because these alterations can contribute to age-related memory and mood impairments, strategies efficacious for mitigating these changes may preserve cognitive and mood function in old age. Resveratrol, a phytoalexin found in the skin of red grapes having angiogenic and antiinflammatory properties, appears ideal for easing these age-related changes. Hence, we examined the efficacy of resveratrol for counteracting age-related memory and mood impairments and the associated detrimental changes in the hippocampus. Two groups of male F344 rats in late middle-age having similar learning and memory abilities were chosen and treated with resveratrol or vehicle for four weeks. Analyses at ~25 months of age uncovered improved learning, memory and mood function in resveratrol-treated animals but impairments in vehicle-treated animals. Resveratrol-treated animals also displayed increased net neurogenesis and microvasculature, and diminished astrocyte hypertrophy and microglial activation in the hippocampus. These results provide novel evidence that resveratrol treatment in late middle age is efficacious for improving memory and mood function in old age. Modulation of the hippocampus plasticity and suppression of chronic low-level inflammation appear to underlie the functional benefits mediated by resveratrol. PMID:25627672

  13. Understanding age-related reductions in visual working memory capacity: Examining the stages of change detection

    PubMed Central

    Duda, Bryant; Hussey, Erin; Mason, Emily; Molitor, Robert J.; Woodman, Geoffrey F.; Ally, Brandon A.

    2014-01-01

    Visual working memory (VWM) capacity is reduced in older adults. Research has shown age-related impairments to VWM encoding, but aging is likely to affect multiple stages of VWM. In the present study, we recorded the event-related potentials (ERPs) of younger and older adults during VWM maintenance and retrieval. We measured encoding-stage processing with the P1 component, maintenance-stage processing with the contralateral delay activity (CDA), and retrieval-stage processing by comparing the activity for old and new items (old–new effect). Older adults showed lower behavioral capacity estimates (K) than did younger adults, but surprisingly, their P1 components and CDAs were comparable to those of younger adults. This remarkable dissociation between neural activity and behavior in the older adults indicated that the P1 and CDA did not accurately assess their VWM capacity. However, the neural activity evoked during VWM retrieval yielded results that helped clarify the age-related differences. During retrieval, younger adults showed early old–new effects in frontal and occipital areas and a late central–parietal old–new effect, whereas older adults showed a late right-lateralized parietal old–new effect. The younger adults’ early old–new effects strongly resembled an index of perceptual fluency, suggesting that perceptual implicit memory was activated. The activation of implicit memory could have facilitated the younger adults’ behavior, and the lack of these early effects in older adults may suggest that they have much lower-resolution memory than do younger adults. From these data, we speculated that younger and older adults store the same number of items in VWM, but that younger adults store a higher-resolution representation than do older adults. PMID:24420648

  14. Maternal inflammation linearly exacerbates offspring age-related changes of spatial learning and memory, and neurobiology until senectitude.

    PubMed

    Li, Xue-Wei; Cao, Lei; Wang, Fang; Yang, Qi-Gang; Tong, Jing-Jing; Li, Xue-Yan; Chen, Gui-Hai

    2016-06-01

    Maternal inflammation during pregnancy can elevate the risk of neurodegenerative disorders in offspring. However, how it affects age-related impairments of spatial learning and memory and changes in the neurobiological indictors in the offspring in later adulthood is still elusive. In this study, the CD-1 mice with maternal gestational inflammation due to receiving lipopolysaccharide (LPS, i.p. 50 or 25μg/kg) were divided into 3-, 12-, 18-, and 22-month-old groups. The spatial learning and memory were evaluated using a six-radial arm water maze and the levels of presynaptic proteins (synaptotagmin-1 and syntaxin-1) and histone acetylation (H3K9ac and H4K8ac) in the dorsal hippocampus were detected using the immunohistochemical method. The results indicated that there were significant age-related impairments of spatial learning and memory, decreased levels of H4K8ac, H3K9ac, and syntaxin-1, and increased levels of synaptotagmin-1 in the offspring mice from 12 months old to 22 months old compared to the same-age controls. Maternal LPS treatment significantly exacerbated the offspring impairments of spatial learning and memory, the reduction of H3K9ac, H4K8ac, and syntaxin-1, and the increment of synaptotagmin-1 from 12 months old to 22 months old compared to the same-age control groups. The changes in the neurobiological indicators significantly correlated with the impairments of spatial learning and memory. Furthermore, this correlation, besides the age and LPS-treatment effects, also showed a dose-dependent effect. Our results suggest that maternal inflammation during pregnancy could exacerbate age-related impairments of spatial learning and memory, and neurobiochemical indicators in the offspring CD-1 mice from midlife to senectitude. PMID:26992827

  15. Repetition Priming in Adults with Williams Syndrome: Age-Related Dissociation between Implicit and Explicit Memory

    ERIC Educational Resources Information Center

    Krinsky-McHale, Sharon J.; Kittler, Phyllis; Brown, W. Ted; Jenkins, Edmund C.; Devenny, Darlynne A.

    2005-01-01

    We examined implicit and explicit memory in adults with Williams syndrome. An age-related dissociation was found; repetition priming (reflecting implicit memory) did not show change with age, but free recall (reflecting explicit memory) was markedly reduced. We also compared the performance of adults with Williams syndrome to adults with Down…

  16. Alzheimer’s Disease and Age-Related Memory Decline (Preclinical)

    PubMed Central

    Terry, Alvin V.; Callahan, Patrick M.; Hall, Brandon; Webster, Scott J.

    2011-01-01

    An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer’s disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as “Mild Cognitive Impairment” (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD, MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy, adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory

  17. Age-related reduction of the confidence-accuracy relationship in episodic memory: effects of recollection quality and retrieval monitoring.

    PubMed

    Wong, Jessica T; Cramer, Stefanie J; Gallo, David A

    2012-12-01

    We investigated age-related reductions in episodic metamemory accuracy. Participants studied pictures and words in different colors and then took forced-choice recollection tests. These tests required recollection of the earlier presentation color, holding familiarity of the response options constant. Metamemory accuracy was assessed for each participant by comparing recollection test accuracy with corresponding confidence judgments. We found that recollection test accuracy was greater in younger than older adults and also for pictures than font color. Metamemory accuracy tracked each of these recollection differences, as well as individual differences in recollection test accuracy within each age group, suggesting that recollection ability affects metamemory accuracy. Critically, the age-related impairment in metamemory accuracy persisted even when the groups were matched on recollection test accuracy, suggesting that metamemory declines were not entirely due to differences in recollection frequency or quantity, but that differences in recollection quality and/or monitoring also played a role. We also found that age-related impairments in recollection and metamemory accuracy were equivalent for pictures and font colors. This result contrasted with previous false recognition findings, which predicted that older adults would be differentially impaired when monitoring memory for less distinctive memories. These and other results suggest that age-related reductions in metamemory accuracy are not entirely attributable to false recognition effects, but also depend heavily on deficient recollection and/or monitoring of specific details associated with studied stimuli. PMID:22449027

  18. The Prevalence of Age-Related Eye Diseases and Visual Impairment in Aging: Current Estimates

    PubMed Central

    Klein, Ronald; Klein, Barbara E. K.

    2013-01-01

    Purpose. To examine prevalence of five age-related eye conditions (age-related cataract, AMD, open-angle glaucoma, diabetic retinopathy [DR], and visual impairment) in the United States. Methods. Review of published scientific articles and unpublished research findings. Results. Cataract, AMD, open-angle glaucoma, DR, and visual impairment prevalences are high in four different studies of these conditions, especially in people over 75 years of age. There are disparities among racial/ethnic groups with higher age-specific prevalence of DR, open-angle glaucoma, and visual impairment in Hispanics and blacks compared with whites, higher prevalence of age-related cataract in whites compared with blacks, and higher prevalence of late AMD in whites compared with Hispanics and blacks. The estimates are based on old data and do not reflect recent changes in the distribution of age and race/ethnicity in the United States population. There are no epidemiologic estimates of prevalence for many visually-impairing conditions. Conclusions. Ongoing prevalence surveys designed to provide reliable estimates of visual impairment, AMD, age-related cataract, open-angle glaucoma, and DR are needed. It is important to collect objective data on these and other conditions that affect vision and quality of life in order to plan for health care needs and identify areas for further research. PMID:24335069

  19. Who, When, and Where? Age-Related Differences on a New Memory Test

    ERIC Educational Resources Information Center

    Sumida, Catherine A.; Holden, Heather M.; Van Etten, Emily J.; Wagner, Gabrielle M.; Hileman, Jacob D.; Gilbert, Paul E.

    2016-01-01

    Our study examined age-related differences on a new memory test assessing memory for "who," "when," and "where," and associations among these elements. Participants were required to remember a sequence of pictures of different faces paired with different places. Older adults remembered significantly fewer correct…

  20. Mechanisms of Age-Related Decline in Memory Search across the Adult Life Span

    ERIC Educational Resources Information Center

    Hills, Thomas T.; Mata, Rui; Wilke, Andreas; Samanez-Larkin, Gregory R.

    2013-01-01

    Three alternative mechanisms for age-related decline in memory search have been proposed, which result from either reduced processing speed (global slowing hypothesis), overpersistence on categories (cluster-switching hypothesis), or the inability to maintain focus on local cues related to a decline in working memory (cue-maintenance hypothesis).…

  1. Young and Older Adults’ Beliefs about Effective Ways to Mitigate Age-Related Memory Decline

    PubMed Central

    Horhota, Michelle; Lineweaver, Tara; Ositelu, Monique; Summers, Kristi; Hertzog, Christopher

    2013-01-01

    This study investigated whether young and older adults vary in their beliefs about the impact of various mitigating factors on age-related memory decline. Eighty young (ages 18–23) and eighty older (ages 60–82) participants reported their beliefs about their own memory abilities and the strategies that they use in their everyday lives to attempt to control their memory. Participants also reported their beliefs about memory change with age for hypothetical target individuals who were described as using (or not using) various means to mitigate memory decline. There were no age differences in personal beliefs about control over current or future memory ability. However, the two age groups differed in the types of strategies they used in their everyday life to control their memory. Young adults were more likely to use internal memory strategies, whereas older adults were more likely to focus on cognitive exercise and maintaining physical health as ways to optimize their memory ability. There were no age differences in rated memory change across the life span in hypothetical individuals. Both young and older adults perceived strategies related to improving physical and cognitive health as effective means of mitigating memory loss with age, whereas internal memory strategies were perceived as less effective means for controlling age-related memory decline. PMID:22082012

  2. Destination memory impairment in older people.

    PubMed

    Gopie, Nigel; Craik, Fergus I M; Hasher, Lynn

    2010-12-01

    Older adults are assumed to have poor destination memory-knowing to whom they tell particular information-and anecdotes about them repeating stories to the same people are cited as informal evidence for this claim. Experiment 1 assessed young and older adults' destination memory by having participants tell facts (e.g., "A dime has 118 ridges around its edge") to pictures of famous people (e.g., Oprah Winfrey). Surprise recognition memory tests, which also assessed confidence, revealed that older adults, compared to young adults, were disproportionately impaired on destination memory relative to spared memory for the individual components (i.e., facts, faces) of the episode. Older adults also were more confident that they had not told a fact to a particular person when they actually had (i.e., a miss); this presumably causes them to repeat information more often than young adults. When the direction of information transfer was reversed in Experiment 2, such that the famous people shared information with the participants (i.e., a source memory experiment), age-related memory differences disappeared. In contrast to the destination memory experiment, older adults in the source memory experiment were more confident than young adults that someone had shared a fact with them when a different person actually had shared the fact (i.e., a false alarm). Overall, accuracy and confidence jointly influence age-related changes to destination memory, a fundamental component of successful communication. PMID:20718537

  3. Stress Constellations and Coping Styles of Older Adults with Age-Related Visual Impairment

    ERIC Educational Resources Information Center

    Lee, Kyoung Othelia; Brennan, Mark

    2006-01-01

    Narrative data from two earlier studies of adaptation to age-related visual impairment were examined for constellations of stressors and coping styles. In the course of previous qualitative analyses, the researchers identified stress and coping codes according to behavioral, psychological, and social domains using a grounded theory approach. In…

  4. 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…

  5. Controlled processes account for age-related decrease in episodic memory.

    PubMed

    Vanderaspoilden, Valérie; Adam, Stéphane; der Linden, Martial Van; Morais, José

    2007-05-01

    A decrease in controlled processes has been proposed to be responsible for age-related episodic memory decline. We used the Process Dissociation Procedure, a method that attempts to estimate the contribution of controlled and automatic processes to cognitive performance, and entered both estimates in regression analyses. Results indicate that only controlled processes explained a great part of the age-related variance in a word recall task, especially when little environmental support was offered. PMID:16860766

  6. Destination Memory Impairment in Older People

    PubMed Central

    Gopie, Nigel; Craik, Fergus I. M.; Hasher, Lynn

    2012-01-01

    Older adults are assumed to have poor destination memory— knowing to whom they tell particular information—and anecdotes about them repeating stories to the same people are cited as informal evidence for this claim. Experiment 1 assessed young and older adults’ destination memory by having participants tell facts (e.g., “A dime has 118 ridges around its edge”) to pictures of famous people (e.g., Oprah Winfrey). Surprise recognition memory tests, which also assessed confidence, revealed that older adults, compared to young adults, were disproportionately impaired on destination memory relative to spared memory for the individual components (i.e., facts, faces) of the episode. Older adults also were more confident that they had not told a fact to a particular person when they actually had (i.e., a miss); this presumably causes them to repeat information more often than young adults. When the direction of information transfer was reversed in Experiment 2, such that the famous people shared information with the participants (i.e., a source memory experiment), age-related memory differences disappeared. In contrast to the destination memory experiment, older adults in the source memory experiment were more confident than young adults that someone had shared a fact with them when a different person actually had shared the fact (i.e., a false alarm). Overall, accuracy and confidence jointly influence age-related changes to destination memory, a fundamental component of successful communication. PMID:20718537

  7. Positivity effect specific to older adults with subclinical memory impairment.

    PubMed

    Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A

    2016-08-01

    Numerous studies have suggested that older adults preferentially remember positive information ("positivity effect"), however others have reported mixed results. One potential source of conflict is that aging is not a unitary phenomenon and individual differences exist. We modified a standard neuropsychological test to vary emotional content and tested memory at three time points (immediate/20 min/1 wk). Cognitively normal older adults were stratified into those with and without subclinical memory impairment. We found that the positivity effect was limited to those with subclinical memory impairment, suggesting that consideration of subclinical memory impairment is necessary for understanding age-related emotional memory alterations. PMID:27421893

  8. Age-related changes in rostral basal forebrain cholinergic and GABAergic projection neurons: Relationship with spatial impairment

    PubMed Central

    Bañuelos, C.; LaSarge, C. L.; McQuail, J. A.; Hartman, J. J.; Gilbert, R. J.; Ormerod, B. K.; Bizon, J. L.

    2013-01-01

    Both cholinergic and GABAergic projections from the rostral basal forebrain have been implicated in hippocampal function and mnemonic abilities. While dysfunction of cholinergic neurons has been heavily implicated in age-related memory decline, significantly less is known regarding how age-related changes in co-distributed GABAergic projection neurons contribute to a decline in hippocampal-dependent spatial learning. In the current study, confocal stereology was used to quantify cholinergic (choline acetyltransferase (ChAT) immunopositive) neurons, GABAergic projection (glutamic decarboxylase 67 (GAD67) immunopositive) neurons, and total (NeuN immunopositive) neurons in the rostral basal forebrain of young and aged rats that were first characterized on a spatial learning task. ChAT immunopositive neurons were significantly but modestly reduced in aged rats. Although ChAT immunopositive neuron number was strongly correlated with spatial learning abilities among young rats, the reduction of ChAT immunopositive neurons was not associated with impaired spatial learning in aged rats. In contrast, the number of GAD67 immunopositive neurons was robustly and selectively elevated in aged rats that exhibited impaired spatial learning. Interestingly, the total number of rostral basal forebrain neurons was comparable in young and aged rats, regardless of their cognitive status. These data demonstrate differential effects of age on phenotypically distinct rostral basal forebrain projection neurons, and implicate dysregulated cholinergic and GABAergic septohippocampal circuitry in age-related mnemonic decline. PMID:22817834

  9. Memory Impairment in Children with Language Impairment

    ERIC Educational Resources Information Center

    Baird, Gillian; Dworzynski, Katharina; Slonims, Vicky; Simonoff, Emily

    2010-01-01

    Aim: The aim of this study was to assess whether any memory impairment co-occurring with language impairment is global, affecting both verbal and visual domains, or domain specific. Method: Visual and verbal memory, learning, and processing speed were assessed in children aged 6 years to 16 years 11 months (mean 9y 9m, SD 2y 6mo) with current,…

  10. The Role of Hippocampal Iron Concentration and Hippocampal Volume in Age-Related Differences in Memory

    PubMed Central

    Rodrigue, Karen M.; Daugherty, Ana M.; Haacke, E. Mark; Raz, Naftali

    2013-01-01

    The goal of this study was to examine the relationships between 2 age-sensitive indices of brain integrity—volume and iron concentration—and the associated age differences in memory performance. In 113 healthy adults (age 19–83 years), we measured the volume and estimated iron concentration in the hippocampus (HC), caudate nucleus (Cd), and primary visual cortex (VC) in vivo with T2* relaxation times, and assessed memory performance with multiple tests. We applied structural equation modeling to evaluate the contribution of individual differences in 2 indices of integrity, volume and T2*, to age-related memory variance. The results show that in healthy adults, age differences in memory can be explained in part by individual differences in HC volume that in turn are associated with differences in HC iron concentration. Lower memory scores were linked to smaller HC and higher HC iron concentration. No such associations were noted for Cd and VC. We conclude that the association between age-related declines in memory and reduced hippocampal volume may reflect the impact of oxidative stress related to increase in free iron concentration. Longitudinal follow-up is needed to test whether altered iron homeostasis in the HC is an early marker for age-related cognitive decline. PMID:22645251

  11. 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

  12. Age-Related Changes in Duration Reproduction: Involvement of Working Memory Processes

    ERIC Educational Resources Information Center

    Baudouin, Alexia; Vanneste, Sandrine; Pouthas, Viviane; Isingrini, Michel

    2006-01-01

    The aim of the present research was to study age-related changes in duration reproduction by differentiating the working memory processes underlying this time estimation task. We compared performances of young and elderly adults in a duration reproduction task performed in simple and concurrent task conditions. Participants were also administered…

  13. 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

  14. 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

  15. Age-related hearing impairment and the triad of acquired hearing loss

    PubMed Central

    Yang, Chao-Hui; Schrepfer, Thomas; Schacht, Jochen

    2015-01-01

    Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise. PMID:26283913

  16. Gulliver meets Descartes: early modern concepts of age-related memory loss.

    PubMed

    Schäfer, Daniel

    2003-03-01

    Age-related memory loss was a marginal issue in medical discussions during early modern times and until well into the second half of the 17th century. There are many possible explanations: the lack of similar traditions in antiquity and in the Middle Ages, insufficient physiological and morphological knowledge of the brain, and the underlying conflict between idealistic and materialistic perspectives on the functions of the soul and the conditions of these in old age. After these boundaries had been pushed back by the influence of Cartesianism and Iatromechanism, the problem of age-related memory loss was increasingly regarded as a physical illness and began to receive more attention. This trend first occurred in medicine, before spreading to the literary world, where the novel "Gulliver's Travels" is one clear and famous example. PMID:12785108

  17. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline.

    PubMed

    Müller, Nils C J; Genzel, Lisa; Konrad, Boris N; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel; Dresler, Martin

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience-in our case piano skills-increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

  18. Motor Skills Enhance Procedural Memory Formation and Protect against Age-Related Decline

    PubMed Central

    Müller, Nils C. J.; Genzel, Lisa; Konrad, Boris N.; Pawlowski, Marcel; Neville, David; Fernández, Guillén; Steiger, Axel

    2016-01-01

    The ability to consolidate procedural memories declines with increasing age. Prior knowledge enhances learning and memory consolidation of novel but related information in various domains. Here, we present evidence that prior motor experience–in our case piano skills–increases procedural learning and has a protective effect against age-related decline for the consolidation of novel but related manual movements. In our main experiment, we tested 128 participants with a sequential finger-tapping motor task during two sessions 24 hours apart. We observed enhanced online learning speed and offline memory consolidation for piano players. Enhanced memory consolidation was driven by a strong effect in older participants, whereas younger participants did not benefit significantly from prior piano experience. In a follow up independent control experiment, this compensatory effect of piano experience was not visible after a brief offline period of 30 minutes, hence requiring an extended consolidation window potentially involving sleep. Through a further control experiment, we rejected the possibility that the decreased effect in younger participants was caused by training saturation. We discuss our results in the context of the neurobiological schema approach and suggest that prior experience has the potential to rescue memory consolidation from age-related cognitive decline. PMID:27333186

  19. Treatment of age-related memory complaints with Ginkgo biloba extract: a randomized double blind placebo-controlled study.

    PubMed

    Brautigam, M R; Blommaert, F A; Verleye, G; Castermans, J; Jansen Steur, E N; Kleijnen, J

    1998-12-01

    A growing number of people is subject to age-related cognitive impairment due to the proportional increase of the ageing population. Therefore, there is a growing interest in cognition-enhancing substances. The efficacy of an alcohol/water extract of Ginkgo biloba in elderly individuals with memory- and/or concentration complaints was tested in a randomized, double-blind, placebo-controlled study by using both subjective and objective parameters. After a wash-out period of 4 weeks 241 non-institutionalised patients in the age range 55-86 years were randomly allocated to receive either Ginkgo biloba alcohol/water extract in a high dose (HD), a low dose (LD) or a placebo (PL) for 24 weeks. Patients were assessed using a psychometric testbattery in the following order: Expended Mental Control Test (EMCT) measuring attention and concentration, Benton Test of Visual Retention-Revised (measures short term visual memory), Rey Test part 1 (measures short term memory and learning curve), Beck Depressive Inventory (BDI) measuring the presence and severeness of a depression in order to exclude depressive patients and Rey Test part 2 (measures long term memory: recognition). Furthermore, subjective perception of memory and concentration was measured. 197 patients completed the study (mean MMSE score: 26.29). In the subjective test, the EMCT, the Rey 1 and Rey 2 no significant differences in improvement in time between the groups were observed. In the Benton test increases of 18%, 26% and 11% (expressed as percentage of baseline scores) were observed in the HD, LD and PL respectively (MANOVA; p = 0.0076). No substantial correlation was observed between subjective perception of the severeness of memory complaints and the objective test results. No differences in the number of (gastrointestinal) side effects were observed between placebo and verum groups. These results indicate that the use of Ginkgo extracts in elderly individuals with cognitive impairment might be promising

  20. Progress and Prospects in Human Genetic Research into Age-Related Hearing Impairment

    PubMed Central

    Sugiura, Saiko; Ueda, Hiromi; Nakashima, Tsutomu

    2014-01-01

    Age-related hearing impairment (ARHI) is a complex, multifactorial disorder that is attributable to confounding intrinsic and extrinsic factors. The degree of impairment shows substantial variation between individuals, as is also observed in the senescence of other functions. This individual variation would seem to refute the stereotypical view that hearing deterioration with age is inevitable and may indicate that there is ample scope for preventive intervention. Genetic predisposition could account for a sizable proportion of interindividual variation. Over the past decade or so, tremendous progress has been made through research into the genetics of various forms of hearing impairment, including ARHI and our knowledge of the complex mechanisms of auditory function has increased substantially. Here, we give an overview of recent investigations aimed at identifying the genetic risk factors involved in ARHI and of what we currently know about its pathophysiology. This review is divided into the following sections: (i) genes causing monogenic hearing impairment with phenotypic similarities to ARHI; (ii) genes involved in oxidative stress, biologic stress responses, and mitochondrial dysfunction; and (iii) candidate genes for senescence, other geriatric diseases, and neurodegeneration. Progress and prospects in genetic research are discussed. PMID:25140308

  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. A four-component model of age-related memory change.

    PubMed

    Healey, M Karl; Kahana, Michael J

    2016-01-01

    We develop a novel, computationally explicit, theory of age-related memory change within the framework of the context maintenance and retrieval (CMR2) model of memory search. We introduce a set of benchmark findings from the free recall and recognition tasks that include aspects of memory performance that show both age-related stability and decline. We test aging theories by lesioning the corresponding mechanisms in a model fit to younger adult free recall data. When effects are considered in isolation, many theories provide an adequate account, but when all effects are considered simultaneously, the existing theories fail. We develop a novel theory by fitting the full model (i.e., allowing all parameters to vary) to individual participants and comparing the distributions of parameter values for older and younger adults. This theory implicates 4 components: (a) the ability to sustain attention across an encoding episode, (b) the ability to retrieve contextual representations for use as retrieval cues, (c) the ability to monitor retrievals and reject intrusions, and (d) the level of noise in retrieval competitions. We extend CMR2 to simulate a recognition memory task using the same mechanisms the free recall model uses to reject intrusions. Without fitting any additional parameters, the 4-component theory that accounts for age differences in free recall predicts the magnitude of age differences in recognition memory accuracy. Confirming a prediction of the model, free recall intrusion rates correlate positively with recognition false alarm rates. Thus, we provide a 4-component theory of a complex pattern of age differences across 2 key laboratory tasks. PMID:26501233

  3. Cellular and molecular mechanisms of age-related macular degeneration: from impaired autophagy to neovascularization.

    PubMed

    Klettner, Alexa; Kauppinen, Anu; Blasiak, Janusz; Roider, Johan; Salminen, Antero; Kaarniranta, Kai

    2013-07-01

    Age-related macular degeneration (AMD) is a complex, degenerative and progressive disease involving multiple genetic and environmental factors. It can result in severe visual loss e.g. AMD is the leading cause of blindness in the elderly in the western countries. Although age, genetics, diet, smoking, and many cardiovascular factors are known to be linked with this disease there is increasing evidence that long-term oxidative stress, impaired autophagy clearance and inflammasome mediated inflammation are involved in the pathogenesis. Under certain conditions these may trigger detrimental processes e.g. release of vascular endothelial growth factor (VEGF), causing choroidal neovascularization e.g. in wet AMD. This review ties together these crucial pathological threads in AMD. PMID:23603148

  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 changes in overcoming proactive interference in associative memory: The role of PFC-mediated executive control processes at retrieval.

    PubMed

    Dulas, Michael R; Duarte, Audrey

    2016-05-15

    Behavioral evidence has shown age-related impairments in overcoming proactive interference in memory, but it is unclear what underlies this deficit. Imaging studies in the young suggest overcoming interference may require several executive control processes supported by the ventrolateral prefrontal cortex (VLPFC) and dorsolateral PFC (DLPFC). The present functional magnetic resonance imaging (fMRI) study investigated whether age-related changes in dissociable executive control processes underlie deficits in overcoming proactive interference in associative memory during retrieval. Participants were tasked with remembering which associate (face or scene) objects were paired with most recently during study, under conditions of high or low proactive interference. Behavioral results demonstrated that, as interference increased, memory performance decreased similarly across groups, with slight associative memory deficits in older adults. Imaging results demonstrated that, across groups, left mid-VLPFC showed increasing activity with increasing interference, though activity did not distinguish correct from incorrect associative memory responses, suggesting this region may not directly serve in successful resolution of proactive interference, per se. Under conditions of high interference, older adults showed reduced associative memory accuracy effects in the DLPFC and anterior PFC. These results suggest that age-related PFC dysfunction may not be ubiquitous. Executive processes supported by ventral regions that detect mnemonic interference may be less affected than processes supported by dorsal and anterior regions that directly resolve interference. PMID:26879623

  6. Neurophysiological correlates of age-related changes in working memory capacity.

    PubMed

    Mattay, Venkata S; Fera, Francesco; Tessitore, Alessandro; Hariri, Ahmad R; Berman, Karen F; Das, Saumitra; Meyer-Lindenberg, Andreas; Goldberg, Terry E; Callicott, Joseph H; Weinberger, Daniel R

    2006-01-01

    Cognitive abilities such as working memory (WM) capacity decrease with age. To determine the neurophysiological correlates of age-related reduction in working memory capacity, we studied 10 young subjects (<35 years of age; mean age=29) and twelve older subjects (>55 years of age; mean age=59) with whole brain blood oxygenation-level dependent (BOLD) fMRI on a 1.5 T GE MR scanner using a SPIRAL FLASH pulse sequence (TE=24 ms, TR=56 ms, FA=60 degrees , voxel dimensions=3.75 mm(3)). Subjects performed a modified version of the "n" back working memory task at different levels of increasing working memory load (1-Back, 2-Back and 3-Back). Older subjects performed as well as the younger subjects at 1-Back (p=0.4), but performed worse than the younger subjects at 2-Back (p<0.01) and 3-Back (p=0.06). Older subjects had significantly longer reaction time (RT) than younger subjects (p<0.04) at all levels of task difficulty. Image analysis using SPM 99 revealed a similar distribution of cortical activity between younger and older subjects at all task levels. However, an analysis of variance revealed a significant group x task interaction in the prefrontal cortex bilaterally; within working memory capacity, as in 1-Back when the older subjects performed as well as the younger subjects, they showed greater prefrontal cortical (BA 9) activity bilaterally. At higher working memory loads, however, when they performed worse then the younger subjects, the older subjects showed relatively reduced activity in these prefrontal regions. These data suggest that, within capacity, compensatory mechanisms such as additional prefrontal cortical activity are called upon to maintain proficiency in task performance. As cognitive demand increases, however, they are pushed past a threshold beyond which physiological compensation cannot be made and, a decline in performance occurs. PMID:16213083

  7. Age-Related Impairment in Choroidal Blood Flow Compensation for Arterial Blood Pressure Fluctuation in Pigeons

    PubMed Central

    Del Mar, Nobel; Zagvazdin, Yuri; Li, Chunyan; Fitzgerald, Malinda E. C.

    2011-01-01

    Purpose. Choroidal vessels compensate for changes in systemic blood pressure (BP) so that choroidal blood flow (ChBF) remains stable over a BP range of approximately 40 mm Hg above and below basal. Because of the presumed importance of ChBF regulation for maintenance of retinal health, we investigated if ChBF compensation for BP fluctuation in pigeons fails with age. Methods. Transcleral laser Doppler flowmetry was used to measure ChBF during spontaneous BP fluctuation in anesthetized pigeons ranging in age from 0.5 to 17 years (pigeons can live approximately 20 years in captivity). Results. ChBF in <8-year-old pigeons remained near 100% of basal ChBF at BPs ranging 40 mm Hg above and below basal BP (95 mm Hg). Baroregulation failed below approximately 50 mm Hg BP. In ≥8-year-old pigeons, ChBF compensation was absent at >90 mm Hg BP, with ChBF linearly following BP. Over the 60 to 90 mm Hg range, ChBF in ≥8-year-old pigeons was maintained at 60–70% of young basal ChBF. Below approximately 55 mm Hg, baroregulation again followed BP linearly. Conclusions. Age-related ChBF baroregulatory impairment occurs in pigeons, with ChBF linear with above-basal BP, and ChBF failing to adequately maintain ChBF during below-basal BP. Defective autonomic sympathetic and parasympathetic neurogenic control, or defective myogenic control, may cause these baroregulatory defects. In either case, overperfusion during high BP may cause oxidative injury to the outer retina, whereas underperfusion during low BP may result in deficient nutrient supply and waste removal, with both abnormalities contributing to age-related retinal pathology and vision loss. PMID:21828151

  8. 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

  9. Misaligned feeding impairs memories

    PubMed Central

    Loh, Dawn H; Jami, Shekib A; Flores, Richard E; Truong, Danny; Ghiani, Cristina A; O’Dell, Thomas J; Colwell, Christopher S

    2015-01-01

    Robust sleep/wake rhythms are important for health and cognitive function. Unfortunately, many people are living in an environment where their circadian system is challenged by inappropriate meal- or work-times. Here we scheduled food access to the sleep time and examined the impact on learning and memory in mice. Under these conditions, we demonstrate that the molecular clock in the master pacemaker, the suprachiasmatic nucleus (SCN), is unaltered while the molecular clock in the hippocampus is synchronized by the timing of food availability. This chronic circadian misalignment causes reduced hippocampal long term potentiation and total CREB expression. Importantly this mis-timed feeding resulted in dramatic deficits in hippocampal-dependent learning and memory. Our findings suggest that the timing of meals have far-reaching effects on hippocampal physiology and learned behaviour. DOI: http://dx.doi.org/10.7554/eLife.09460.001 PMID:26652002

  10. Age-related prefrontal impairments implicate deficient prediction of future reward in older adults.

    PubMed

    Eppinger, Ben; Heekeren, Hauke R; Li, Shu-Chen

    2015-08-01

    Foresighted decision-making depends on the ability to learn the value of future outcomes and the sequential choices necessary to achieve them. Using a 3-stage Markov decision task and functional magnetic resonance imaging, we investigated age differences in the ability to extract state transition structures while learning to predict future reward. In younger adults learning was associated with enhanced activity in the prefrontal cortex (PFC). In older adults (OA) we found no evidence for PFC recruitment. However, high-performing OA showed enhanced striatal activity, suggesting that they may engage in a model-free (experience-based) learning strategy. Change point analyses revealed that in younger adults learning was characterized by distinct and abrupt shifts in PFC activity, which were predictive of behavioral change points. In OA PFC activity was less pronounced and not predictive of behavior. Our findings suggest that age-related impairments in learning future reward value can be attributed to a deficit in extracting sequential state transition structures. This deficit may lead to myopic decisions in OA if contextual information has to be temporally integrated. PMID:26004018

  11. Episodic future thinking: the role of working memory and inhibition on age-related differences.

    PubMed

    Zavagnin, Michela; De Beni, Rossana; Borella, Erika; Carretti, Barbara

    2016-02-01

    The ability to remember past events and imagine future events (episodic future thinking-EFT) has been shown to decline with aging. However, only few studies have analyzed the cognitive mechanisms involved in EFT in both young and older adults. The present study examined the role of working memory and inhibition on age-related differences between young and older adults in EFT, in response to short sentences reflecting common events, some of which were repeated in both conditions (past and future). Thirty-seven young and 36 older adults completed an adapted version of the autobiographical interview, in which sentences were presented. Results showed that processing resources explained a significant part of the variance in the amount of details; in particular, inhibition explained the amount of external details produced in the future condition. In addition, using sentences, the older group did not differ from the young adults in terms of the proportion of internal details recalled in the past condition, whereas they produced a lower proportion of internal details in the future condition. The effect of using structured material was reinforced by repeating some sentences in the past. Further, only older adults rated the remembered episodes as more emotionally salient and relevant than the imagined ones. Age-related differences between young and older adults in EFT appear to depend on the type of material used, on basic mechanisms of cognition, and are characterized by both quantitative and qualitative differences. PMID:25963665

  12. Age-related effects on perceptual and semantic encoding in memory.

    PubMed

    Kuo, M C C; Liu, K P Y; Ting, K H; Chan, C C H

    2014-03-01

    This study examined the age-related subsequent memory effect (SME) in perceptual and semantic encoding using event-related potentials (ERPs). Seventeen younger adults and 17 older adults studied a series of Chinese characters either perceptually (by inspecting orthographic components) or semantically (by determining whether the depicted object makes sounds). The two tasks had similar levels of difficulty. The participants made studied or unstudied judgments during the recognition phase. Younger adults performed better in both conditions, with significant SMEs detected in the time windows of P2, N3, P550, and late positive component (LPC). In the older group, SMEs were observed in the P2 and N3 latencies in both conditions but were only detected in the P550 in the semantic condition. Between-group analyses showed larger frontal and central SMEs in the younger sample in the LPC latency regardless of encoding type. Aging effect appears to be stronger on influencing perceptual than semantic encoding processes. The effects seem to be associated with a decline in updating and maintaining representations during perceptual encoding. The age-related decline in the encoding function may be due in part to changes in frontal lobe function. PMID:24374080

  13. Age-Related Impairments in Object-Place Associations Are Not Due to Hippocampal Dysfunction

    PubMed Central

    Hernandez, Abigail R.; Maurer, Andrew P.; Reasor, Jordan E.; Turner, Sean M.; Barthle, Sarah E.; Johnson, Sarah A.; Burke, Sara N.

    2016-01-01

    Age-associated cognitive decline can reduce an individual’s quality of life. As no single neurobiological deficit can account for the wide spectrum of behavioral impairments observed in old age, it is critical to develop an understanding of how interactions between different brain regions change over the life span. The performance of young and aged animals on behaviors that require the hippocampus and cortical regions to interact, however, has not been well characterized. Specifically, the ability to link a spatial location with specific features of a stimulus, such as object identity, relies on the hippocampus, perirhinal and prefrontal cortices. Although aging is associated with dysfunction in each of these brain regions, behavioral measures of functional change within the hippocampus, perirhinal and prefrontal cortices in individual animals are often not correlated. Thus, how dysfunction of a single brain region within this circuit, such as the hippocampus, impacts behaviors that require communication with the perirhinal and prefrontal cortices remains unknown. To address this question, young and aged rats were tested on the interregion dependent object-place paired association task, as well as a hippocampal-dependent test of spatial reference memory. This particular cohort of aged rats did not show deficits on the hippocampal-dependent task, but were significantly impaired at acquiring object-place associations relative to young. These data suggest that behaviors requiring functional connectivity across different regions of the memory network may be particularly sensitive to aging, and can be used to develop models that will clarify the impact of systems-level dysfunction in the elderly. PMID:26413723

  14. Age-Related Declines in Early Sensory Memory: Identification of Rapid Auditory and Visual Stimulus Sequences

    PubMed Central

    Fogerty, Daniel; Humes, Larry E.; Busey, Thomas A.

    2016-01-01

    Age-related temporal-processing declines of rapidly presented sequences may involve contributions of sensory memory. This study investigated recall for rapidly presented auditory (vowel) and visual (letter) sequences presented at six different stimulus onset asynchronies (SOA) that spanned threshold SOAs for sequence identification. Younger, middle-aged, and older adults participated in all tasks. Results were investigated at both equivalent performance levels (i.e., SOA threshold) and at identical physical stimulus values (i.e., SOAs). For four-item sequences, results demonstrated best performance for the first and last items in the auditory sequences, but only the first item for visual sequences. For two-item sequences, adults identified the second vowel or letter significantly better than the first. Overall, when temporal-order performance was equated for each individual by testing at SOA thresholds, recall accuracy for each position across the age groups was highly similar. These results suggest that modality-specific processing declines of older adults primarily determine temporal-order performance for rapid sequences. However, there is some evidence for a second amodal processing decline in older adults related to early sensory memory for final items in a sequence. This selective deficit was observed particularly for longer sequence lengths and was not accounted for by temporal masking. PMID:27199737

  15. VISION PROBLEMS IN THE U.S.-PREVALENCE OF ADULT VISION IMPAIRMENT AND AGE-RELATED EYE DISEASES IN AMERICA

    EPA Science Inventory

    Leading causes of vision impairment and blindness in the United States. Diabetic retinopathy? Age-related macular degeneration (AMD)? Cataract? Glaucoma? The Vision Problems in the U.S. study was the result of a 2001 consensus meeting, convened by the National Eye Institute and ...

  16. Sleep, Torpor and Memory Impairment

    NASA Astrophysics Data System (ADS)

    Palchykova, S.; Tobler, I.

    It is now well known that daily torpor induces a sleep deficit. Djungarian hamsters emerging from this hypometabolic state spend most of the time in sleep. This sleep is characterized by high initial values of EEG slow-wave activity (SWA) that monotonically decline during recovery sleep. These features resemble the changes seen in numerous species during recovery after prolonged wakefulness or sleep deprivation (SD). When hamsters are totally or partially sleep deprived immediately after emerging from torpor, an additional increase in SWA can be induced. It has been therefore postulated, that these slow- waves are homeostatically regulated, as predicted by the two-process model of sleep regulation, and that during daily torpor a sleep deficit is accumulated as it is during prolonged waking. The predominance of SWA in the frontal EEG observed both after SD and daily torpor provides further evidence for the similarity of these conditions. It has been shown in several animal and human studies that sleep can enhance memory consolidation, and that SD leads to memory impairment. Preliminary data obtained in the Djungarian hamster showed that both SD and daily torpor result in object recognition deficits. Thus, animals subjected to SD immediately after learning, or if they underwent an episode of daily torpor between learning and retention, displayed impaired recognition memory for complex object scenes. The investigation of daily torpor can reveal mechanisms that could have important implications for hypometabolic state induction in other mammalian species, including humans.

  17. Age-Related Impairment in the 250-Millisecond Delay Eyeblink Classical Conditioning Procedure in C57BL/6 Mice

    PubMed Central

    Vogel, Richard W.; Ewers, Michael; Ross, Charlene; Gould, Thomas J.; Woodruff-Pak, Diana S.

    2002-01-01

    In this study we tested 4-, 9-, 12-, and 18-month-old C57BL/6 mice in the 250-msec delay eyeblink classical conditioning procedure to study age-related changes in a form of associative learning. The short life expectancy of mice, complete knowledge about the mouse genome, and the availability of transgenic and knock-out mouse models of age-related impairments make the mouse an excellent species for expanding knowledge on the neurobiologically and behaviorally well-characterized eyeblink classical conditioning paradigm. Based on previous research with delay eyeblink conditioning in rabbits and humans, we predicted that mice would be impaired on this cerebellar-dependent associative learning task in middle-age, at ∼9 months. To fully examine age differences in behavior in mice, we used a battery of additional behavioral measures with which to compare young and older mice. These behaviors included the acoustic startle response, prepulse inhibition, rotorod, and the Morris water maze. Mice began to show impairment in cerebellar-dependent tasks such as rotorod and eyeblink conditioning at 9 to 12 months of age. Performance in hippocampally dependent tasks was not impaired in any group, including 18-month-old mice. These results in mice support results in other species, indicating that cerebellar-dependent tasks show age-related deficits earlier in adulthood than do hippocampally dependent tasks. PMID:12359840

  18. 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

  19. ESTROGENS AND AGE-RELATED MEMORY DECLINE IN RODENTS: WHAT HAVE WE LEARNED AND WHERE DO WE GO FROM HERE?

    PubMed Central

    Frick, Karyn M.

    2009-01-01

    The question of whether ovarian hormone therapy can prevent or reduce age-related memory decline in menopausal women has been the subject of much recent debate. Although numerous studies have demonstrated a beneficial effect of estrogen and/or progestin therapy for certain types of memory in menopausal women, recent clinical trials suggest that such therapy actually increases the risk of cognitive decline and dementia. Because rodent models have been frequently used to examine the effects of age and/or ovarian hormone deficiency on mnemonic function, rodent models of age-related hormone and memory decline may be useful in helping to resolve this issue. This review will focus on evidence suggesting that estradiol modulates memory, particularly hippocampal-dependent memory, in young and aging female rats and mice. Various factors affecting the mnemonic response to estradiol in aging females will be highlighted to illustrate the complications inherent to studies of estrogen therapy in aging females. Avenues for future development of estradiol-based therapies will also be discussed, and it is argued that an approach to drug development based on identifying the molecular mechanisms underlying estrogenic modulation of memory may lead to promising future treatments for reducing age-related mnemonic decline. PMID:18835561

  20. Verbal memory impairments in dyslexia.

    PubMed

    Kramer, J H; Knee, K; Delis, D C

    2000-01-01

    Although verbal memory deficits are frequently reported in reading disabled children, the specific mechanisms underlying these impairments have yet to be clearly defined. The present study used the California Verbal Learning Test-Children's Version (CVLT-C) to assess verbal learning in 57 dyslexic children and 114 controls matched for gender, age, and WISC-R Vocabulary score. Three areas of verbal memory were investigated: Recall and recognition, use of learning strategies, and interference effects. The dyslexic group learned the list items more slowly, recalled fewer words on the last learning trial and the delayed trials, and performed less well on the recognition condition. Dyslexics and controls displayed similar vulnerability to interference, but group differences were evident in serial position effects. Taken together, our data suggest that dyslexics have less efficient rehearsal and encoding mechanisms, resulting in deficient encoding of new information, but normal retention and retrieval. PMID:14590570

  1. 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…

  2. Age-Related Effects of Study Time Allocation on Memory Performance in a Verbal and a Spatial Task

    ERIC Educational Resources Information Center

    Krueger, Lacy E.

    2012-01-01

    Past studies have suggested that study time allocation partially mediates age relations on memory performance in a verbal task. To identify whether this applied to a different material modality, participants ages 20-87 completed a spatial task in addition to a traditional verbal task. In both the verbal and the spatial task, increased age was…

  3. 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

  4. 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

  5. Memory Loss, Dementia, and Stroke: Implications for Rehabilitation of Older Adults with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Warren, Mary

    2008-01-01

    Older adults with age-related macular degeneration (AMD) are not immune to the other diseases of aging. Although AMD is the leading cause of low vision in older Americans, stroke is the leading cause of disability, and dementias affect another 2.5 million older Americans. Each condition alone can significantly impair a person's ability to…

  6. Long-term caloric restriction in mice may prevent age-related learning impairment via suppression of apoptosis.

    PubMed

    Ma, Lina; Wang, Rong; Dong, Wen; Li, Yun; Xu, Baolei; Zhang, Jingshuang; Zhao, Zhiwei

    2016-12-15

    Caloric restriction (CR) is the most reliable intervention to extend lifespan and prevent age-related disorders in various species from yeast to rodents. However, the underlying mechanisms have not yet been clearly defined. Therefore, we aimed to identify the underlying mechanisms of long-term CR on age-related learning impairment in C57/BL mice. Thirty six-week-old male C57/BL mice were randomly divided into three groups: normal control group (NC group, n=10), high energy group (HE group, n=10), and CR group (n=10). After 10 months, the Morris water maze test was performed to monitor learning abilities. Western blotting, immunohistochemistry and real-time polymerase chain reaction were used to monitor changes in protein and mRNA levels associated with apoptosis-related proteins in the hippocampus. The average escape latency was lower in the CR group compared with the NC group, and the average time taken to first cross the platform in the CR group was significantly shorter than the HE group. Both Bcl-2 protein and mRNA expression levels in the CR group were significantly higher than those of the NC group and HE group. The expression of Bax, Caspase-3 and PARP protein in the CR group was significantly lower than the NC group. Our findings demonstrate that long-term CR may prevent age-related learning impairments via suppressing apoptosis in mice. PMID:27452805

  7. Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

    PubMed

    Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

    2014-11-15

    Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease. PMID:25143549

  8. Age-related fragmentation of the motor endplate is not associated with impaired neuromuscular transmission in the mouse diaphragm

    PubMed Central

    Willadt, Silvia; Nash, Mark; Slater, Clarke R.

    2016-01-01

    As mammals age, their neuromuscular junctions (NMJs) gradually change their form, acquiring an increasingly fragmented appearance consisting of numerous isolated regions of synaptic differentiation. It has been suggested that this remodelling is associated with impairment of neuromuscular transmission, and that this contributes to age-related muscle weakness in mammals, including humans. The underlying hypothesis, that increasing NMJ fragmentation is associated with impaired transmission, has never been directly tested. Here, by comparing the structure and function of individual NMJs, we show that neuromuscular transmission at the most highly fragmented NMJs in the diaphragms of old (26–28 months) mice is, if anything, stronger than in middle-aged (12–14 months) mice. We suggest that NMJ fragmentation per se is not a reliable indicator of impaired neuromuscular transmission. PMID:27094316

  9. 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

  10. 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

  11. Stereotype threat can both enhance and impair older adults' memory.

    PubMed

    Barber, Sarah J; Mather, Mara

    2013-12-01

    Negative stereotypes about aging can impair older adults' memory via stereotype threat; however, the mechanisms underlying this phenomenon are unclear. In two experiments, we tested competing predictions derived from two theoretical accounts of stereotype threat: executive-control interference and regulatory fit. Older adults completed a working memory test either under stereotype threat about age-related memory declines or not under such threat. Monetary incentives were manipulated such that recall led to gains or forgetting led to losses. The executive-control-interference account predicts that stereotype threat decreases the availability of executive-control resources and hence should impair working memory performance. The regulatory-fit account predicts that threat induces a prevention focus, which should impair performance when gains are emphasized but improve performance when losses are emphasized. Results were consistent only with the regulatory-fit account. Although stereotype threat significantly impaired older adults' working memory performance when remembering led to gains, it significantly improved performance when forgetting led to losses. PMID:24150969

  12. Acute ozone (O3) -induced impairment of glucose regulation: Age-related and temporal changes

    EPA Science Inventory

    O3 is associated with adverse cardiopulmonary health effects in humans and is thought to produce metabolic effects, such as insulin resistance. Recently, we showed that episodic O3 exposure increased insulin levels in aged rats. We hypothesized that O3 exposure could impair gluc...

  13. Negative reinforcement impairs overnight memory consolidation.

    PubMed

    Stamm, Andrew W; Nguyen, Nam D; Seicol, Benjamin J; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J

    2014-11-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into dreaming. Contrary to our hypothesis, we found that the addition of reward impaired overnight consolidation of spatial memory. Our findings seemingly contradict prior reports that enhancing the reward value of learned information augments sleep-dependent memory processing. Given that the reward followed a negative reinforcement paradigm, consolidation may have been impaired via a stress-related mechanism. PMID:25320351

  14. Age-related improvements in auditory temporal resolution in reading-impaired children.

    PubMed

    Hautus, Michael J; Setchell, Gregory J; Waldie, Karen E; Kirk, Ian J

    2003-02-01

    Individuals with developmental dyslexia show impairments in processing that require precise timing of sensory events. Here, we show that in a test of auditory temporal acuity (a gap-detection task) children ages 6-9 years with dyslexia exhibited a significant deficit relative to age-matched controls. In contrast, this deficit was not observed in groups of older reading-impaired individuals (ages 10-11 years; 12-13 years) or in adults (ages 23-25 years). It appears, therefore, that early temporal resolution deficits in those with reading impairments may significantly ameliorate over time. However, the occurrence of an early deficit in temporal acuity may be antecedent to other language-related perceptual problems (particularly those related to phonological processing) that persist after the primary deficit has resolved. This result suggests that if remedial interventions targeted at temporal resolution deficits are to be effective, the early detection of the deficit and early application of the remedial programme is especially critical. PMID:12625375

  15. 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

  16. 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

  17. Age-related Changes in the Sleep-dependent Reorganization of Declarative Memories.

    PubMed

    Baran, Bengi; Mantua, Janna; Spencer, Rebecca M C

    2016-06-01

    Consolidation of declarative memories has been associated with slow wave sleep in young adults. Previous work suggests that, in spite of changes in sleep, sleep-dependent consolidation of declarative memories may be preserved with aging, although reduced relative to young adults. Previous work on young adults shows that, with consolidation, retrieval of declarative memories gradually becomes independent of the hippocampus. To investigate whether memories are similarly reorganized over sleep at the neural level, we compared functional brain activation associated with word pair recall following a nap and equivalent wake in young and older adults. SWS during the nap predicted better subsequent memory recall and was negatively associated with retrieval-related hippocampal activation in young adults. In contrast, in older adults there was no relationship between sleep and memory performance or with retrieval-related hippocampal activation. Furthermore, compared with young adults, postnap memory retrieval in older adults required strong functional connectivity of the hippocampus with the PFC, whereas there were no differences between young and older adults in the functional connectivity of the hippocampus following wakefulness. These results suggest that, although neural reorganization takes place over sleep in older adults, the shift is unique from that seen in young adults, perhaps reflecting memories at an earlier stage of stabilization. PMID:26918588

  18. Early Age-Related Macular Degeneration Impairs Tolerance To Stimulus Degradation

    PubMed Central

    Liu, Lei; White, Janis

    2010-01-01

    Purpose Pathologic changes of retinal photoreceptors associated with early age-related macular degeneration (AMD) have been well established, but the disease is usually asymptomatic at the early stage and traditional suprathreshold clinical tests often fail to reveal functional deficiencies. The aim of this study is to demonstrate subtle changes of one suprathreshold visual function in early AMD eyes. Methods The quality of pre-attentively discriminable texture stimuli was systematically degraded through random deletion of texture checks. The subjects’ task was to make a forced-choice decision on whether two equally degraded patches contained samples of the same or different types of textures. Tolerance to texture stimulus degradation was measured in young and elderly normal controls and in patients with early AMD. Results Subjects were trained to perform the texture discrimination task until they made few errors in discriminating intact textures. Texture discrimination deteriorated with increasing stimulus degradation in all subjects. There was no significant difference between performance of young and elderly normal controls. Early AMD eyes showed significantly less tolerance to stimulus degradation than age-similar normal controls at a range of degradation levels. After controlling for visual acuity, normal subjects still performed significantly better than early AMD eyes around 22% check deletion. There was no significant difference between better eyes of early AMD patients and fellow eyes of late AMD eyes. Performance on the degraded texture task was not correlated with visual acuity. A mild blur of the stimulus had little effect on discrimination of degraded textures. Conclusions Early AMD may not directly affect suprathreshold visual functions when the stimuli are intact and contain redundant information, but may manifest itself as a reduction of tolerance to stimulus degradation in the form of localized information loss. The performance of patients with

  19. 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

  20. 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

  1. 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

  2. Verbal declarative memory impairments in specific language impairment are related to working memory deficits

    PubMed Central

    Lum, Jarrad A.G.; Ullman, Michael T.; Conti-Ramsden, Gina

    2015-01-01

    This study examined verbal declarative memory functioning in SLI and its relationship to working memory. Encoding, recall, and recognition of verbal information was examined in children with SLI who had below average working memory (SLILow WM), children with SLI who had average working memory (SLIAvg. WM) and, a group of non-language impaired children with average working memory (TDAvg. WM). The SLILow WM group was significantly worse than both the SLIAvg. WM and TDAvg. WM groups at encoding verbal information and at retrieving verbal information following a delay. In contrast, the SLIAvg. WM group showed no verbal declarative memory deficits. The study demonstrates that verbal declarative memory deficits in SLI only occur when verbal working memory is impaired. Thus SLI declarative memory is largely intact and deficits are likely to be related to working memory impairments. PMID:25660053

  3. Age-related differences in time-based prospective memory: The role of time estimation in the clock monitoring strategy.

    PubMed

    Vanneste, Sandrine; Baudouin, Alexia; Bouazzaoui, Badiâa; Taconnat, Laurence

    2016-07-01

    Time-based prospective memory (TBPM) is required when it is necessary to remember to perform an action at a specific future point in time. This type of memory has been found to be particularly sensitive to ageing, probably because it requires a self-initiated response at a specific time. In this study, we sought to examine the involvement of temporal processes in the time monitoring strategy, which has been demonstrated to be a decisive factor in TBPM efficiency. We compared the performance of young and older adults in a TBPM task in which they had to press a response button every minute while categorising words. The design allowed participants to monitor time by checking a clock whenever they decided. Participants also completed a classic time-production task and several executive tasks assessing inhibition, updating and shifting processes. Our results confirm an age-related lack of accuracy in prospective memory performance, which seems to be related to a deficient strategic use of time monitoring. This could in turn be partially explained by age-related temporal deficits, as evidenced in the duration production task. These findings suggest that studies designed to investigate the age effect in TBPM tasks should consider the contribution of temporal mechanisms. PMID:26247302

  4. Age-related changes in working memory and the ability to ignore distraction.

    PubMed

    McNab, Fiona; Zeidman, Peter; Rutledge, Robb B; Smittenaar, Peter; Brown, Harriet R; Adams, Rick A; Dolan, Raymond J

    2015-05-19

    A weakened ability to effectively resist distraction is a potential basis for reduced working memory capacity (WMC) associated with healthy aging. Exploiting data from 29,631 users of a smartphone game, we show that, as age increases, working memory (WM) performance is compromised more by distractors presented during WM maintenance than distractors presented during encoding. However, with increasing age, the ability to exclude distraction at encoding is a better predictor of WMC in the absence of distraction. A significantly greater contribution of distractor filtering at encoding represents a potential compensation for reduced WMC in older age. PMID:25941369

  5. Age-Related Differences on Cognitive Overload in an Audio-Visual Memory Task

    ERIC Educational Resources Information Center

    Murray, Jennifer; Thomson, Mary E.

    2011-01-01

    The present study aimed to provide evidence outlining whether the type of stimuli used in teaching would provoke differing levels of recall across three different academic age groups. One hundred and twenty-one participants, aged 11-25 years, were given a language-based memory task in the form of a wordlist consisting of 15 concrete and 15…

  6. Age-Related Differences in the Temporal Dynamics of Prospective Memory Retrieval: A Lifespan Approach

    ERIC Educational Resources Information Center

    Mattli, Florentina; Zollig, Jacqueline; West, Robert

    2011-01-01

    The efficiency of prospective memory (PM) typically increases from childhood to young adulthood and then decreases in later adulthood. The current study used event-related brain potentials (ERPs) to examine the development of the neural correlates of processes associated with the detection of a PM cue, switching from the ongoing activity to the…

  7. 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

  8. Memory Impairments Underlying Language Difficulties in Dementia.

    ERIC Educational Resources Information Center

    Azuma, Tamiko; Bayles, Kathryn A.

    1997-01-01

    The memory deficits associated with the dementia syndromes of Alzheimer's, Parkinson's, and Lewy body disease are outlined and related to the language impairments that have been observed in patients with these disorders. Assessment techniques are described, including commonly used individual tests and test batteries that assess memory and…

  9. The significance of caudate volume for age-related associative memory decline.

    PubMed

    Bauer, E; Toepper, M; Gebhardt, H; Gallhofer, B; Sammer, G

    2015-10-01

    Aging comes along with reduced gray matter (GM) volume in several cerebral areas and with cognitive performance decline in different cognitive domains. Moreover, regional GM volume is linked to specific cognitive sub processes in older adults. However, it remains unclear which regional changes in older individuals are directly associated with decreased cognitive performance. Moreover, most of the studies on this topic focused on hippocampal and prefrontal brain regions and their relation to memory and executive functioning. Interestingly, there are only a few studies that reported an association between striatal brain volume and cognitive performance. This is insofar surprising that striatal structures are (1) highly affected by age and (2) involved in different neural circuits that serve intact cognition. To address these issues, voxel-based morphometry (VBM) was used to analyze GM volume in 18 younger and 18 older adults. Moreover, several neuropsychological tests from different neuropsychological test batteries were applied to assess a broad range of cognitive domains. Older adults showed less GM volume than younger adults within frontal, striatal, and cerebellar brain regions. In the group of older adults, significant correlations were found between striatal GM volume and memory performance and between prefrontal/temporal GM volume and executive functioning. The only direct overlap between brain regions associated with regional atrophy and cognitive performance in older adults was found for the right caudate: older adults showed reduced caudate volume relative to younger adults. Moreover, caudate volume was positively correlated with associative memory accuracy in older adults and older adults showed poorer performances than younger adults in the respective associative memory task. Taken together, the current findings indicate the relevance of the caudate for associative memory decline in the aging brain. PMID:26119913

  10. Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway.

    PubMed

    Sebastián, David; Sorianello, Eleonora; Segalés, Jessica; Irazoki, Andrea; Ruiz-Bonilla, Vanessa; Sala, David; Planet, Evarist; Berenguer-Llergo, Antoni; Muñoz, Juan Pablo; Sánchez-Feutrie, Manuela; Plana, Natàlia; Hernández-Álvarez, María Isabel; Serrano, Antonio L; Palacín, Manuel; Zorzano, Antonio

    2016-08-01

    Mitochondrial dysfunction and accumulation of damaged mitochondria are considered major contributors to aging. However, the molecular mechanisms responsible for these mitochondrial alterations remain unknown. Here, we demonstrate that mitofusin 2 (Mfn2) plays a key role in the control of muscle mitochondrial damage. We show that aging is characterized by a progressive reduction in Mfn2 in mouse skeletal muscle and that skeletal muscle Mfn2 ablation in mice generates a gene signature linked to aging. Furthermore, analysis of muscle Mfn2-deficient mice revealed that aging-induced Mfn2 decrease underlies the age-related alterations in metabolic homeostasis and sarcopenia. Mfn2 deficiency reduced autophagy and impaired mitochondrial quality, which contributed to an exacerbated age-related mitochondrial dysfunction. Interestingly, aging-induced Mfn2 deficiency triggers a ROS-dependent adaptive signaling pathway through induction of HIF1α transcription factor and BNIP3. This pathway compensates for the loss of mitochondrial autophagy and minimizes mitochondrial damage. Our findings reveal that Mfn2 repression in muscle during aging is a determinant for the inhibition of mitophagy and accumulation of damaged mitochondria and triggers the induction of a mitochondrial quality control pathway. PMID:27334614

  11. Evidence for age-related changes to temporal attention and memory from the choice time production task

    PubMed Central

    Gooch, Cynthia M.; Stern, Yaakov; Rakitin, Brian C.

    2009-01-01

    The effect of aging on interval timing was examined using a choice time production task, which required participants to choose a key response based on the location of the stimulus, but to delay responding until after a learned time interval. Experiment 1 varied attentional demands of the response choice portion of the task by varying difficulty of stimulus-response mapping. Choice difficulty affected temporal accuracy equally in both age groups, but older participants’ response latencies were more variable under more difficult response choice conditions. Experiment 2 tested the contribution of long-term memory to differences in choice time production between age groups over 3 days of testing. Direction of errors in time production between the two age groups diverged over the 3 sessions, but variability did not differ. Results from each experiment separately show age-related changes to attention and memory in temporal processing using different measures and manipulations in the same task. PMID:19132578

  12. Age-related slowing of memory retrieval: Contributions of perceptual speed and cerebral white matter integrity

    PubMed Central

    Bucur, Barbara; Madden, David J.; Spaniol, Julia; Provenzale, James M.; Cabeza, Roberto; White, Leonard E.; Huettel, Scott A.

    2007-01-01

    Previous research suggests that, in reaction time (RT) measures of episodic memory retrieval, the unique effects of adult age are relatively small compared to the effects aging shares with more elementary abilities such as perceptual speed. Little is known, however, regarding the mechanisms of perceptual speed. We used diffusion tensor imaging (DTI) to test the hypothesis that white matter integrity, as indexed by fractional anisotropy (FA), serves as one mechanism of perceptual slowing in episodic memory retrieval. Results indicated that declines in FA in the pericallosal frontal region and in the genu of the corpus callosum, but not in other regions, mediated the relationship between perceptual speed and episodic retrieval RT. This relation held, though to a different degree, for both hits and correct rejections. These findings suggest that white matter integrity in prefrontal regions is one mechanism underlying the relation between individual differences in perceptual speed and episodic retrieval. PMID:17383774

  13. A Calendar Savant with Episodic Memory Impairments

    PubMed Central

    Olson, Ingrid R.; Berryhill, Marian E.; Drowos, David B.; Brown, Lawrence; Chatterjee, Anjan

    2010-01-01

    Patients with memory disorders have severely restricted learning and memory. For instance, patients with anterograde amnesia can learn motor procedures as well as retaining some restricted ability to learn new words and factual information. However, such learning is inflexible and frequently inaccessible to conscious awareness. Here we present a case of patient AC596, a 25-year old male with severe episodic memory impairments, presumably due to anoxia during a preterm birth. In contrast to his poor episodic memory, he exhibits savant-like memory for calendar information that can be flexibly accessed by day, month, and year cues. He also has the ability to recollect the exact date of a wide range of personal experiences over the past 20 years. The patient appears to supplement his generally poor episodic memory by using memorized calendar information as a retrieval cue for autobiographical events. These findings indicate that islands of preserved memory functioning, such as a highly developed semantic memory system, can exist in individuals with severely impaired episodic memory systems. In this particular case, our patient’s memory for dates far outstripped that of normal individuals and served as a keen retrieval cue, allowing him to access information that was otherwise unavailable. PMID:20104390

  14. Compensatory effects of pointing and predictive cueing on age-related declines in visuospatial working memory.

    PubMed

    Ouwehand, Kim; van Gog, Tamara; Paas, Fred

    2016-08-01

    In this study, we investigated whether the visuospatial working memory performance of young and older adults would improve if they used a multimodal as compared with a unimodal encoding strategy, and whether or not visual cues would add to this effect. In Experiment 1, participants were presented with trials consisting of an array of squares and an array of circles. They were instructed to point at one type of figure (multimodal encoding strategy) and only to observe the other (unimodal encoding strategy). After each trial, an immediate location recognition test of one of the two arrays followed. In Experiment 2, the same task was used, but a cue was provided, either before or after the encoding phase, indicating which of the two arrays would be tested. Our results showed that a multimodal, as compared with a unimodal, encoding strategy improved visuospatial working memory performance in both young and older adults (Exp. 1), and that adding visual cues to the multimodal but not to the unimodal encoding strategy improved older adults' performance up to the level of young adults (Exp. 2). In both age groups, cueing after encoding led to higher performance in the multimodal than in the unimodal condition when the second array was tested. However, cueing before encoding led to higher performance in the multimodal than in the unimodal condition when the first array of the figure sequence was tested. These results suggest that pointing together with predictive cueing can have beneficial effects on visuospatial working memory, which is especially important for older adults. PMID:27126873

  15. Astrocytes Underlie Neuroinflammatory Memory Impairment.

    PubMed

    Osso, Lindsay A; Chan, Jonah R

    2015-12-17

    Neuroinflammation is being increasingly recognized as a potential mediator of cognitive impairments in various neurological conditions. Habbas et al. demonstrate that the pro-inflammatory cytokine tumor necrosis factor alpha signals through astrocytes to alter synaptic transmission and impair cognition in a mouse model of multiple sclerosis. PMID:26687350

  16. Early age-related changes in episodic memory retrieval as revealed by event-related potentials.

    PubMed

    Guillaume, Cécile; Clochon, Patrice; Denise, Pierre; Rauchs, Géraldine; Guillery-Girard, Bérengère; Eustache, Francis; Desgranges, Béatrice

    2009-01-28

    Familiarity is better preserved than recollection in ageing. The age at which changes first occur and the slope of the subsequent decline, however, remain unclear. In this study, we investigated changes in episodic memory, by using event-related potentials (ERPs) in young (m=24), middle-aged (m=58) and older (m=70) adults. Although behavioural performance did not change before the age of 65 years, changes in ERP correlates were already present in the middle-aged adults. The ERP correlates of recollection and monitoring processes were the first to be affected by ageing, with a linear decrease as age increased. Conversely, the ERP correlate of familiarity remained unchanged, at least up to the age of 65 years. These results suggest a differential time course for the age effects on episodic retrieval. PMID:19104457

  17. 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

  18. 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

  19. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance.

    PubMed

    Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura

    2015-08-01

    The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic's endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749

  20. Aging-related anatomical and biochemical changes in lymphatic collectors impair lymph transport, fluid homeostasis, and pathogen clearance

    PubMed Central

    Zolla, Valerio; Nizamutdinova, Irina Tsoy; Scharf, Brian; Clement, Cristina C; Maejima, Daisuke; Akl, Tony; Nagai, Takashi; Luciani, Paola; Leroux, Jean-Christophe; Halin, Cornelia; Stukes, Sabriya; Tiwari, Sangeeta; Casadevall, Arturo; Jacobs, William R; Entenberg, David; Zawieja, David C; Condeelis, John; Fooksman, David R; Gashev, Anatoliy A; Santambrogio, Laura

    2015-01-01

    The role of lymphatic vessels is to transport fluid, soluble molecules, and immune cells to the draining lymph nodes. Here, we analyze how the aging process affects the functionality of the lymphatic collectors and the dynamics of lymph flow. Ultrastructural, biochemical, and proteomic analysis indicates a loss of matrix proteins, and smooth muscle cells in aged collectors resulting in a decrease in contraction frequency, systolic lymph flow velocity, and pumping activity, as measured in vivo in lymphatic collectors. Functionally, this impairment also translated into a reduced ability for in vivo bacterial transport as determined by time-lapse microscopy. Ultrastructural and proteomic analysis also indicates a decrease in the thickness of the endothelial cell glycocalyx and loss of gap junction proteins in aged lymph collectors. Redox proteomic analysis mapped an aging-related increase in the glycation and carboxylation of lymphatic’s endothelial cell and matrix proteins. Functionally, these modifications translate into apparent hyperpermeability of the lymphatics with pathogen escaping from the collectors into the surrounding tissue and a decreased ability to control tissue fluid homeostasis. Altogether, our data provide a mechanistic analysis of how the anatomical and biochemical changes, occurring in aged lymphatic vessels, compromise lymph flow, tissue fluid homeostasis, and pathogen transport. PMID:25982749

  1. Dissecting the age-related decline on spatial learning and memory tasks in rodent models: N-methyl-D-aspartate receptors and voltage-dependent Ca2+ channels in senescent synaptic plasticity

    PubMed Central

    Foster, Thomas C.

    2012-01-01

    In humans, heterogeneity in the decline of hippocampal-dependent episodic memory is observed during aging. Rodents have been employed as models of age-related cognitive decline and the spatial water maze has been used to show variability in the emergence and extent of impaired hippocampal-dependent memory. Impairment in the consolidation of intermediate-term memory for rapidly acquired and flexible spatial information emerges early, in middle-age. As aging proceeds, deficits may broaden to include impaired incremental learning of a spatial reference memory. The extent and time course of impairment has been be linked to senescence of calcium (Ca2+) regulation and Ca2+-dependent synaptic plasticity mechanisms in region CA1. Specifically, aging is associated with altered function of N-methyl-D-aspartate receptors (NMDARs), voltage-dependent Ca2+ channels (VDCCs), and ryanodine receptors (RyRs) linked to intracellular Ca2+ stores (ICS). In young animals, NMDAR activation induces long-term potentiation of synaptic transmission (NMDAR-LTP), which is thought to mediate the rapid consolidation of intermediate-term memory. Oxidative stress, starting in middle-age, reduces NMDAR function. In addition, VDCCs and ICS can actively inhibit NMDAR-dependent LTP and oxidative stress enhances the role of VDCC and RyR-ICS in regulating synaptic plasticity. Blockade of L-type VDCCs promotes NMDAR-LTP and memory in older animals. Interestingly, pharmacological or genetic manipulations to reduce hippocampal NMDAR function readily impair memory consolidation or rapid learning, generally leaving incremental learning intact. Finally, evidence is mounting to indicate a role for VDCC-dependent synaptic plasticity in associative learning and the consolidation of remote memories. Thus, VDCC-dependent synaptic plasticity and extrahippocampal systems may contribute to incremental learning deficits observed with advanced aging. PMID:22307057

  2. Age-related differences in affective responses to and memory for emotions conveyed by music: a cross-sectional study.

    PubMed

    Vieillard, Sandrine; Gilet, Anne-Laure

    2013-01-01

    There is mounting evidence that aging is associated with the maintenance of positive affect and the decrease of negative affect to ensure emotion regulation goals. Previous empirical studies have primarily focused on a visual or autobiographical form of emotion communication. To date, little investigation has been done on musical emotions. The few studies that have addressed aging and emotions in music were mainly interested in emotion recognition, thus leaving unexplored the question of how aging may influence emotional responses to and memory for emotions conveyed by music. In the present study, eighteen older (60-84 years) and eighteen younger (19-24 years) listeners were asked to evaluate the strength of their experienced emotion on happy, peaceful, sad, and scary musical excerpts (Vieillard et al., 2008) while facial muscle activity was recorded. Participants then performed an incidental recognition task followed by a task in which they judged to what extent they experienced happiness, peacefulness, sadness, and fear when listening to music. Compared to younger adults, older adults (a) reported a stronger emotional reactivity for happiness than other emotion categories, (b) showed an increased zygomatic activity for scary stimuli, (c) were more likely to falsely recognize happy music, and (d) showed a decrease in their responsiveness to sad and scary music. These results are in line with previous findings and extend them to emotion experience and memory recognition, corroborating the view of age-related changes in emotional responses to music in a positive direction away from negativity. PMID:24137141

  3. Memory for sequences of events impaired in typical aging.

    PubMed

    Allen, Timothy A; Morris, Andrea M; Stark, Shauna M; Fortin, Norbert J; Stark, Craig E L

    2015-03-01

    Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to remember sequences of events, an important feature of episodic memory. Unlike existing paradigms, this task is nonspatial, nonverbal, and can be used to isolate different cognitive processes that may be differentially affected in aging. Here, we used this task to make a comprehensive comparison of sequence memory performance between younger (18-22 yr) and older adults (62-86 yr). Specifically, participants viewed repeated sequences of six colored, fractal images and indicated whether each item was presented "in sequence" or "out of sequence." Several out of sequence probe trials were used to provide a detailed assessment of sequence memory, including: (i) repeating an item from earlier in the sequence ("Repeats"; e.g., AB A: DEF), (ii) skipping ahead in the sequence ("Skips"; e.g., AB D: DEF), and (iii) inserting an item from a different sequence into the same ordinal position ("Ordinal Transfers"; e.g., AB 3: DEF). We found that older adults performed as well as younger controls when tested on well-known and predictable sequences, but were severely impaired when tested using novel sequences. Importantly, overall sequence memory performance in older adults steadily declined with age, a decline not detected with other measures (RAVLT or BPS-O). We further characterized this deficit by showing that performance of older adults was severely impaired on specific probe trials that required detailed knowledge of the sequence (Skips and Ordinal Transfers), and was associated with a shift in their underlying mnemonic representation of the sequences. Collectively, these findings provide unambiguous evidence that the capacity to remember

  4. Impaired allocentric spatial memory underlying topographical disorientation.

    PubMed

    Burgess, Neil; Trinkler, Iris; King, John; Kennedy, Angus; Cipolotti, Lisa

    2006-01-01

    The cognitive processes supporting spatial navigation are considered in the context of a patient (CF) with possible very early Alzheimer's disease who presents with topographical disorientation. Her verbal memory and her recognition memory for unknown buildings, landmarks and outdoor scenes was intact, although she showed an impairment in face processing. By contrast, her navigational ability, quantitatively assessed within a small virtual reality (VR) town, was significantly impaired. Interestingly, she showed a selective impairment in a VR object-location memory test whenever her viewpoint was shifted between presentation and test, but not when tested from the same viewpoint. We suggest that a specific impairment in locating objects relative to the environment rather than relative to the perceived viewpoint (i.e. allocentric rather than egocentric spatial memory) underlies her topographical disorientation. We discuss the likely neural bases of this deficit in the light of related studies in humans and animals, focusing on the hippocampus and related areas. The specificity of our test indicates a new way of assessing topographical disorientation, with possible application to the assessment of progressive dementias such as Alzheimer's disease. PMID:16703955

  5. Age-Related Differences in Cortical Activity during a Visuo-Spatial Working Memory Task with Facial Stimuli

    PubMed Central

    Belham, Flávia Schechtman; Satler, Corina; Garcia, Ana; Tomaz, Carlos; Gasbarri, Antonella; Rego, Artur; Tavares, Maria Clotilde H.

    2013-01-01

    Emotion, importantly displayed by facial expressions, is one of the most significant memory modulators. The interaction between memory and the different emotional valences change across lifespan, while young adults (YA) are expected to better recall negative events (Negativity Bias Hypothesis), older adults (OA) tend to focus on positive stimuli (Positivity Effect Hypothesis). This research work aims at verifying whether cortical electrical activity of these two age groups would also be differently influenced by emotional valences in a visuo-spatial working memory task. 27 YA (13 males) and 25 OA (14 males), all healthy volunteers, underwent electroencephalographic recordings (21 scalp electrodes montage), while performing the Spatial Delayed Recognition Span Task using a touch screen with different stimuli categories: neutral, positive and negative faces and geometric pictures. YA obtained higher scores than OA, and showed higher activation of theta and alpha bands in the frontal and midline regions, besides a more evident right-hemispheric asymmetry on alpha band when compared to OA. For both age groups, performance in the task was worse for positive faces than to negative and to neutral faces. Facial stimuli induced a better performance and higher alpha activation on the pre-frontal region for YA, and on the midline, occipital and left temporal regions for OA when compared to geometric figures. The superior performance of YA was expected due to the natural cognitive deficits connected to ageing, as was a better performance with facial stimuli due to the evolutionary importance of faces. These results were related to cortical activity on areas of importance for action-planning, decision making and sustained attention. Taken together, they are in accordance with the Negativity Bias but do not support the Positivity Effect. The methodology used was able to identify age-related differences in cortical activity during emotional mnemonic processing and may be

  6. FDG-PET Contributions to the Pathophysiology of Memory Impairment.

    PubMed

    Segobin, Shailendra; La Joie, Renaud; Ritz, Ludivine; Beaunieux, Hélène; Desgranges, Béatrice; Chételat, Gaël; Pitel, Anne Lise; Eustache, Francis

    2015-09-01

    Measurement of synaptic activity by Positron Emission Tomography (PET) and its relation to cognitive functions such as episodic memory, working memory and executive functions in healthy humans and patients with neurocognitive disorders have been well documented. In this review, we introduce the concept of PET imaging that allows the observation of a particular biological process in vivo through the use of radio-labelled compounds, its general use to the medical world and its contributions to the understanding of memory systems. We then focus on [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG-PET), the radiotracer that is used to measure local cerebral metabolic rate of glucose that is indicative of synaptic activity in the brain. FDG-PET at rest has been at the forefront of functional neuroimaging over the past 3 decades, contributing to the understanding of cognitive functions in healthy humans and how these functional patterns change with cognitive alterations. We discuss methodological considerations that are important for optimizing FDG-PET imaging data prior to analysis. We then highlight the contribution of FDG-PET to the understanding of the patterns of functional differences in non-degenerative pathologies, normal ageing, and age-related neurodegenerative disorders. Through reasonable temporal and spatial resolution, its ability to measure synaptic activity in the whole brain, independently of any specific network and disease, makes it ideal to observe regional functional changes associated with memory impairment. PMID:26319237

  7. Effects of Grape Skin Extract on Age-Related Mitochondrial Dysfunction, Memory and Life Span in C57BL/6J Mice.

    PubMed

    Asseburg, Heike; Schäfer, Carmina; Müller, Madeleine; Hagl, Stephanie; Pohland, Maximilian; Berressem, Dirk; Borchiellini, Marta; Plank, Christina; Eckert, Gunter P

    2016-09-01

    Dementia contributes substantially to the burden of disability experienced at old age, and mitochondrial dysfunction (MD) was identified as common final pathway in brain aging and Alzheimer's disease. Due to its early appearance, MD is a promising target for nutritional prevention strategies and polyphenols as potential neurohormetic inducers may be strong neuroprotective candidates. This study aimed to investigate the effects of a polyphenol-rich grape skin extract (PGE) on age-related dysfunctions of brain mitochondria, memory, life span and potential hormetic pathways in C57BL/6J mice. PGE was administered at a dose of 200 mg/kg body weight/d in a 3-week short-term, 6-month long-term and life-long study. MD in the brains of aged mice (19-22 months old) compared to young mice (3 months old) was demonstrated by lower ATP levels and by impaired mitochondrial respiratory complex activity (except for mice treated with antioxidant-depleted food pellets). Long-term PGE feeding partly enhanced brain mitochondrial respiration with only minor beneficial effect on brain ATP levels and memory of aged mice. Life-long PGE feeding led to a transient but significant shift of survival curve toward higher survival rates but without effect on the overall survival. The moderate effects of PGE were associated with elevated SIRT1 but not SIRT3 mRNA expressions in brain and liver tissue. The beneficial effects of the grape extract may have been influenced by the profile of bioavailable polyphenols and the starting point of interventions. PMID:27455862

  8. 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

  9. Simulating Memory Impairment for Child Sexual Abuse.

    PubMed

    Newton, Jeremy W; Hobbs, Sue D

    2015-08-01

    The current study investigated effects of simulated memory impairment on recall of child sexual abuse (CSA) information. A total of 144 adults were tested for memory of a written CSA scenario in which they role-played as the victim. There were four experimental groups and two testing sessions. During Session 1, participants read a CSA story and recalled it truthfully (Genuine group), omitted CSA information (Omission group), exaggerated CSA information (Commission group), or did not recall the story at all (No Rehearsal group). One week later, at Session 2, all participants were told to recount the scenario truthfully, and their memory was then tested using free recall and cued recall questions. The Session 1 manipulation affected memory accuracy during Session 2. Specifically, compared with the Genuine group's performance, the Omission, Commission, or No Rehearsal groups' performance was characterized by increased omission and commission errors and decreased reporting of correct details. Victim blame ratings (i.e., victim responsibility and provocativeness) and participant gender predicted increased error and decreased accuracy, whereas perpetrator blame ratings predicted decreased error and increased accuracy. Findings are discussed in relation to factors that may affect memory for CSA information. PMID:26294381

  10. The limits of arousal's memory impairing effects on nearby information

    PubMed Central

    Mather, Mara; Gorlick, Marissa; Nesmith, Kathryn

    2009-01-01

    Showing an arousing central stimulus in a scene often leads to enhanced memory for the arousing central information and impaired memory for peripheral details. However, it is not clear from previous work whether arousing stimuli impair memory for all non-arousing nearby information or just background information. In several experiments, we tested how emotionally arousing pictures affect memory for nearby pictures and for background information. We found that when two pictures were presented together, having one of the pictures be arousing did not affect item and location memory for the other picture. In contrast, an arousing picture impaired memory for a background pattern. These findings suggest that arousal impairs memory for information that is the target of perceptual suppression, such as background information when there is a figure-ground distinction, but does not impair memory for other foreground information. PMID:19827704

  11. Psychosocial Adaptation to Visual Impairment and Its Relationship to Depressive Affect in Older Adults with Age-Related Macular Degeneration

    ERIC Educational Resources Information Center

    Tolman, Jennifer; Hill, Robert D.; Kleinschmidt, Julia J.; Gregg, Charles H.

    2005-01-01

    Purpose: In this study we examined psychosocial adaptation to vision loss and its relationship to depressive symptomatology in legally blind older adults with age-related macular degeneration (ARMD). Design and Methods: The 144 study participants were outpatients of a large regional vision clinic that specializes in the diagnosis and treatment of…

  12. Impaired Odor Recognition Memory in Patients with Hippocampal Lesions

    ERIC Educational Resources Information Center

    Levy, Daniel A.; Squire, Larry R.; Hopkins, Ramona O.

    2004-01-01

    In humans, impaired recognition memory following lesions thought to be limited to the hippocampal region has been demonstrated for a wide variety of tasks. However, the importance of the human hippocampus for olfactory recognition memory has scarcely been explored. We evaluated the ability of memory-impaired patients with damage thought to be…

  13. 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

  14. 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

  15. Non-Alzheimer's disease—related memory impairment and dementia

    PubMed Central

    Arlt, Sönke

    2013-01-01

    Although Alzheimer's disease (AD) is a common cause of memory impairment and dementia in the elderly disturbed memory function is a widespread subjective and/or objective symptom in a variety of medical conditions. The early detection and correct distinction of AD from non-AD memory impairment is critically important to detect possibly treatable and reversible underlying causes. In the context of clinical research, it is crucial to correctly distinguish between AD or non-AD memory impairment in order to build homogenous study populations for the assessment of new therapeutic possibilities. The distinction of AD from non-AD memory impairment may be difficult, especially in mildly affected patients, due to an overlap of clinical symptoms and biomarker alterations between AD and certain non-AD conditions. This review aims to describe recent aspects of the differential diagnosis of AD and non-AD related memory impairment and how these may be considered in the presence of memory deficits. PMID:24459413

  16. Memory for Sequences of Events Impaired in Typical Aging

    ERIC Educational Resources Information Center

    Allen, Timothy A.; Morris, Andrea M.; Stark, Shauna M.; Fortin, Norbert J.; Stark, Craig E. L.

    2015-01-01

    Typical aging is associated with diminished episodic memory performance. To improve our understanding of the fundamental mechanisms underlying this age-related memory deficit, we previously developed an integrated, cross-species approach to link converging evidence from human and animal research. This novel approach focuses on the ability to…

  17. Extinction memory is impaired in schizophrenia

    PubMed Central

    Holt, Daphne. J.; Lebron-Milad, Kelimer; Milad, Mohammed R.; Rauch, Scott L.; Pitman, Roger K.; Orr, Scott P.; Cassidy, Brittany S.; Walsh, Jared P.; Goff, Donald C.

    2013-01-01

    Background Schizophrenia is associated with abnormalities in emotional processing and social cognition, which may result from disruption of the underlying neural mechanism(s) governing emotional learning and memory. To investigate this possibility, we measured the acquisition and extinction of conditioned fear responses and delayed recall of extinction in schizophrenia and control subjects. Methods 28 schizophrenia and 18 demographically-matched control subjects underwent a two-day fear conditioning, extinction learning and extinction recall procedure, in which skin conductance response (SCR) magnitude was used as the index of conditioned responses. Results During fear acquisition, 83% of the controls and 57% of the patients showed autonomic responsivity (‘responders’), and the patients showed larger SCRs to the stimulus that was not paired with the unconditioned stimulus (CS−) than the controls. Within the responder group, there was no difference between the patients and controls in levels of extinction learning; however, the schizophrenia patients showed significant impairment, relative to the controls, in context-dependent recall of the extinction memory. In addition, delusion severity in the patients correlated with baseline skin conductance levels. Conclusions These data are consistent with prior evidence for a heightened neural response to innocuous stimuli in schizophrenia and elevated arousal levels in psychosis. The finding of deficient extinction recall in schizophrenia patients who showed intact extinction learning suggests that schizophrenia is associated with a disturbance in the neural processes supporting emotional memory. PMID:18986648

  18. Recognition Memory Is Impaired in Children after Prolonged Febrile Seizures

    ERIC Educational Resources Information Center

    Martinos, Marina M.; Yoong, Michael; Patil, Shekhar; Chin, Richard F. M.; Neville, Brian G.; Scott, Rod C.; de Haan, Michelle

    2012-01-01

    Children with a history of a prolonged febrile seizure show signs of acute hippocampal injury on magnetic resonance imaging. In addition, animal studies have shown that adult rats who suffered febrile seizures during development reveal memory impairments. Together, these lines of evidence suggest that memory impairments related to hippocampal…

  19. Neuroinflammatory TNFα Impairs Memory via Astrocyte Signaling.

    PubMed

    Habbas, Samia; Santello, Mirko; Becker, Denise; Stubbe, Hiltrud; Zappia, Giovanna; Liaudet, Nicolas; Klaus, Federica R; Kollias, George; Fontana, Adriano; Pryce, Christopher R; Suter, Tobias; Volterra, Andrea

    2015-12-17

    The occurrence of cognitive disturbances upon CNS inflammation or infection has been correlated with increased levels of the cytokine tumor necrosis factor-α (TNFα). To date, however, no specific mechanism via which this cytokine could alter cognitive circuits has been demonstrated. Here, we show that local increase of TNFα in the hippocampal dentate gyrus activates astrocyte TNF receptor type 1 (TNFR1), which in turn triggers an astrocyte-neuron signaling cascade that results in persistent functional modification of hippocampal excitatory synapses. Astrocytic TNFR1 signaling is necessary for the hippocampal synaptic alteration and contextual learning-memory impairment observed in experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis (MS). This process may contribute to the pathogenesis of cognitive disturbances in MS, as well as in other CNS conditions accompanied by inflammatory states or infections. PMID:26686654

  20. Age-Related Visual and Kinesthetic Encoding Effects on Spatial Memory of a Maze-Like Floor Plan.

    ERIC Educational Resources Information Center

    Sinnott, Jan D.; And Others

    As part of an experimental research program on lifespan naturalistic and laboratory memory for spatial representation, investigators examined interactions between the effects of visual and kinesthetic encoding and age on memory for space using a modification of the Sinnott (1987) human maze paradigm. It was hypothesized that an age effect favoring…

  1. Rethinking the Connection between Working Memory and Language Impairment

    ERIC Educational Resources Information Center

    Archibald, Lisa M. D.; Harder Griebeling, Katherine

    2016-01-01

    Background: Working memory deficits have been found for children with specific language impairment (SLI) on tasks imposing increasing short-term memory load with or without additional, consistent (and simple) processing load. Aims: To examine the processing function of working memory in children with low language (LL) by employing tasks imposing…

  2. 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

  3. Long-term dietary extra-virgin olive oil rich in polyphenols reverses age-related dysfunctions in motor coordination and contextual memory in mice: role of oxidative stress.

    PubMed

    Pitozzi, Vanessa; Jacomelli, Michela; Catelan, Dolores; Servili, Maurizio; Taticchi, Agnese; Biggeri, Annibale; Dolara, Piero; Giovannelli, Lisa

    2012-12-01

    The aim of this study was to evaluate the effects of olive oil phenols on brain aging in mice and to verify whether the antioxidant and antiinflammatory activities of these polyphenols were involved. C57Bl/6J mice were fed from middle age to senescence with extra-virgin olive oil (10% wt/wt dry diet) rich in phenols (total polyphenol dose/day, 6 mg/kg). Behavioral tests were employed to assess cognitive, motor, and emotional behavior after 6 or 12 months of treatment. Parameters of oxidative status and inflammation were measured in different brain areas at the same times and evaluated for correlation with behavioral changes. The treatment with olive oil phenols improved contextual memory in the step-down test to levels similar to young animals and prevented the age-related impairment in motor coordination in the rotarod test. This motor effect was correlated with reduced lipid peroxidation in the cerebellum (p<0.05), whereas the memory effect did not correlate with oxidation or inflammation parameters. In conclusion, this work points out that natural polyphenols contained in extra-virgin olive oil can improve some age-related dysfunctions by differentially affecting different brain areas. Such a modulation can be obtained with an olive oil intake that is normal in the Mediterranean area, provided that the oil has a sufficiently high content of polyphenols. PMID:22950431

  4. Age-related and intelligence-related differences in implicit memory: effects of generation on a word-fragment completion test.

    PubMed

    Komatsu, S; Naito, M; Fuke, T

    1996-07-01

    In two experiments, subjects either read a bracketed word in a sentence or generated a word in response to its definition. A word-fragment completion test was then carried out. In Experiment 1, children's priming under the generate condition was substantial, as compared with baseline performance, but was significantly lower than that under the read condition, whereas there was no difference in adults' priming between these two conditions. Furthermore, prior generation induced an age-related increase in priming despite no age difference under the read condition. In Experiment 2, mentally retarded persons exhibited a profile similar to that of children. These results suggests that there are two different components in implicit memory, one that shows no developmental difference and heavily relies on perceptual processing and the other that shows an age-related or intelligence-related increase and heavily relies on conceptual processing. PMID:8683186

  5. At What Level of Heat Load Are Age-Related Impairments in the Ability to Dissipate Heat Evident in Females?

    PubMed Central

    Stapleton, Jill M.; Poirier, Martin P.; Flouris, Andreas D.; Boulay, Pierre; Sigal, Ronald J.; Malcolm, Janine; Kenny, Glen P.

    2015-01-01

    Studies have reported that older females have impaired heat loss responses during work in the heat compared to young females. However, it remains unclear at what level of heat stress these differences occur. Therefore, we examined whole-body heat loss [evaporative (HE) and dry heat loss, via direct calorimetry] and changes in body heat storage (∆Hb, via direct and indirect calorimetry) in 10 young (23±4 years) and 10 older (58±5 years) females matched for body surface area and aerobic fitness (VO2peak) during three 30-min exercise bouts performed at incremental rates of metabolic heat production of 250 (Ex1), 325 (Ex2) and 400 (Ex3) W in the heat (40°C, 15% relative humidity). Exercise bouts were separated by 15 min of recovery. Since dry heat gain was similar between young and older females during exercise (p=0.52) and recovery (p=0.42), differences in whole-body heat loss were solely due to HE. Our results show that older females had a significantly lower HE at the end of Ex2 (young: 383±34 W; older: 343±39 W, p=0.04) and Ex3 (young: 437±36 W; older: 389±29 W, p=0.008), however no difference was measured at the end of Ex1 (p=0.24). Also, the magnitude of difference in the maximal level of HE achieved between the young and older females became greater with increasing heat loads (Ex1=10.2%, Ex2=11.6% and Ex3=12.4%). Furthermore, a significantly greater ∆Hb was measured for all heat loads for the older females (Ex1: 178±44 kJ; Ex2: 151±38 kJ; Ex3: 216±25 kJ, p=0.002) relative to the younger females (Ex1: 127±35 kJ; Ex2: 96±45 kJ; Ex3: 146±46 kJ). In contrast, no differences in HE or ∆Hb were observed during recovery (p>0.05). We show that older habitually active females have an impaired capacity to dissipate heat compared to young females during exercise-induced heat loads of ≥325 W when performed in the heat. PMID:25790024

  6. EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats

    PubMed Central

    Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge

    2016-01-01

    Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging. PMID:27242514

  7. EPA/DHA and Vitamin A Supplementation Improves Spatial Memory and Alleviates the Age-related Decrease in Hippocampal RXRγ and Kinase Expression in Rats.

    PubMed

    Létondor, Anne; Buaud, Benjamin; Vaysse, Carole; Richard, Emmanuel; Layé, Sophie; Pallet, Véronique; Alfos, Serge

    2016-01-01

    Studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and vitamin A are critical to delay aged-related cognitive decline. These nutrients regulate gene expression in the brain by binding to nuclear receptors such as the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Moreover, EPA/DHA and retinoids activate notably kinase signaling pathways such as AKT or MAPK, which includes ERK1/2. This suggests that these nutrients may modulate brain function in a similar way. Therefore, we investigated in middle-aged rats the behavioral and molecular effects of supplementations with EPA/DHA and vitamin A alone or combined. 18-month-old rats exhibited reference and working memory deficits in the Morris water maze, associated with a decrease in serum vitamin A and hippocampal EPA/DHA contents. RARα, RXRβ, and RXRγ mRNA expression and CAMKII, AKT, ERK1/2 expression were decreased in the hippocampus of middle-aged rats. A combined EPA/DHA and vitamin A supplementation had a beneficial additive effect on reference memory but not in working memory in middle-aged rats, associated with an alleviation of the age-related decrease in RXRγ, CAMKII, AKT, and ERK1 expression in the hippocampus. This study provides a new combined nutritional strategy to delay brain aging. PMID:27242514

  8. Impaired Transcriptional Activity of Nrf2 in Age-Related Myocardial Oxidative Stress Is Reversible by Moderate Exercise Training

    PubMed Central

    Gounder, Sellamuthu S.; Kannan, Sankaranarayanan; Devadoss, Dinesh; Miller, Corey J.; Whitehead, Kevin S.; Odelberg, Shannon J.; Firpo, Matthew A.; Paine, Robert; Hoidal, John R.; Abel, E. Dale; Rajasekaran, Namakkal S.

    2012-01-01

    Aging promotes accumulation of reactive oxygen/nitrogen species (ROS/RNS) in cardiomyocytes, which leads to contractile dysfunction and cardiac abnormalities. These changes may contribute to increased cardiovascular disease in the elderly. Inducible antioxidant pathways are regulated by nuclear erythroid 2 p45-related factor 2 (Nrf2) through antioxidant response cis-elements (AREs) and are impaired in the aging heart. Whereas acute exercise stress (AES) activates Nrf2 signaling and promotes myocardial antioxidant function in young mice (∼2 months), aging mouse (>23 months) hearts exhibit significant oxidative stress as compared to those of the young. The purpose of this study was to investigate age-dependent regulation of Nrf2-antioxidant mechanisms and redox homeostasis in mouse hearts and the impact of exercise. Old mice were highly susceptible to oxidative stress following high endurance exercise stress (EES), but demonstrated increased adaptive redox homeostasis after moderate exercise training (MET; 10m/min, for 45 min/day) for ∼6 weeks. Following EES, transcription and protein levels for most of the ARE-antioxidants were increased in young mice but their induction was blunted in aging mice. In contrast, 6-weeks of chronic MET promoted nuclear levels of Nrf2 along with its target antioxidants in the aging heart to near normal levels as seen in young mice. These observations suggest that enhancing Nrf2 function and endogenous cytoprotective mechanisms by MET, may combat age-induced ROS/RNS and protect the myocardium from oxidative stress diseases. PMID:23029187

  9. Positive emotion can protect against source memory impairment.

    PubMed

    MacKenzie, Graham; Powell, Tim F; Donaldson, David I

    2015-01-01

    Despite widespread belief that memory is enhanced by emotion, evidence also suggests that emotion can impair memory. Here we test predictions inspired by object-based binding theory, which states that memory enhancement or impairment depends on the nature of the information to be retrieved. We investigated emotional memory in the context of source retrieval, using images of scenes that were negative, neutral or positive in valence. At study each scene was paired with a colour and during retrieval participants reported the source colour for recognised scenes. Critically, we isolated effects of valence by equating stimulus arousal across conditions. In Experiment 1 colour borders surrounded scenes at study: memory impairment was found for both negative and positive scenes. Experiment 2 used colours superimposed over scenes at study: valence affected source retrieval, with memory impairment for negative scenes only. These findings challenge current theories of emotional memory by showing that emotion can impair memory for both intrinsic and extrinsic source information, even when arousal is equated between emotional and neutral stimuli, and by dissociating the effects of positive and negative emotion on episodic memory retrieval. PMID:24784151

  10. 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

  11. Glucocorticoids can induce PTSD-like memory impairments in mice.

    PubMed

    Kaouane, Nadia; Porte, Yves; Vallée, Monique; Brayda-Bruno, Laurent; Mons, Nicole; Calandreau, Ludovic; Marighetto, Aline; Piazza, Pier Vincenzo; Desmedt, Aline

    2012-03-23

    Posttraumatic stress disorder (PTSD) is characterized by a hypermnesia of the trauma and by a memory impairment that decreases the ability to restrict fear to the appropriate context. Infusion of glucocorticoids in the hippocampus after fear conditioning induces PTSD-like memory impairments and an altered pattern of neural activation in the hippocampal-amygdalar circuit. Mice become unable to identify the context as the correct predictor of the threat and show fear responses to a discrete cue not predicting the threat in normal conditions. These data demonstrate PTSD-like memory impairments in rodents and identify a potential pathophysiological mechanism of this condition. PMID:22362879

  12. Children's and Adults' Memory for Emotional Pictures: Examining Age-Related Patterns Using the Developmental Affective Photo System

    ERIC Educational Resources Information Center

    Cordon, Ingrid M.; Melinder, Annika M. D.; Goodman, Gail S.; Edelstein, Robin S.

    2013-01-01

    Two studies were conducted to examine theoretical questions about children's and adults' memory for emotional visual stimuli. In Study 1, 7- to 9-year-olds and adults (N = 172) participated in the initial creation of the Developmental Affective Photo System (DAPS). Ratings of emotional valence, arousal, and complexity were obtained. In Study 2,…

  13. The Canine Sand Maze: An Appetitive Spatial Memory Paradigm Sensitive to Age-Related Change in Dogs

    ERIC Educational Resources Information Center

    Salvin, Hannah E.; McGreevy, Paul D.; Sachdev, Perminder S.; Valenzuela, Michael J.

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter…

  14. Antiamnesic Effects of Walnuts Consumption on Scopolamine-Induced Memory Impairments in Rats

    PubMed Central

    Harandi, Shaahin; Golchin, Leila; Ansari, Mehdi; Moradi, Alireza; Shabani, Mohammad; Sheibani, Vahid

    2015-01-01

    Introduction: Alzheimer’s disease (AD) is an age-related neurodegenerative disease, which impairs memory and cognitive function. Walnuts are a dietary source of polyphenols, antioxidants and other compounds with health beneficial effects. These characteristic of walnuts make them perfect candidates for evaluation of their possible effects on neurodegenerative diseases. Therefore the present study was designed to investigate the effects of walnuts consumption (2%, 6% and 9% walnut diets) on memory enhancement and acetylcholinesterase (AChE) activity of brain in scopolamine-induced amnesic rats. Methods: Learning, memory and locomotor activity parameters were evaluated using Morris water maze (MWM), passive avoidance and rotarod tests. Results: Our results showed that consumption of walnuts at doses of 6% and 9% significantly restored the scopolamine-induced memory impairments in the MWM and passive avoidance tests. Moreover, the potential of walnuts to prevent scopolamine neurotoxicity was also reflected by the decreased AChE activity in the whole brain in comparison with the scopolamine group. Discussion: These results suggest that walnuts may be useful against memory impairment and it may exert these anti-amnesic activities via inhibition of AChE activity in the brain. It would be worthwhile to explore the potential of this nut and its active components in the management of the AD. PMID:27307953

  15. Age-Related Hearing Impairment (ARHI) Associated with GJB2 Single Mutation IVS1+1G>A in the Yakut Population Isolate in Eastern Siberia

    PubMed Central

    Pshennikova, Vera G.; Solovyev, Aisen V.; Klarov, Leonid A.; Solovyeva, Natalya A.; Kozhevnikov, Andrei A.; Vasilyeva, Lena M.; Fedotova, Elvira E.; Pak, Maria V.; Lekhanova, Sargylana N.; Zakharova, Elena V.; Savvinova, Kyunney E.; Gotovtsev, Nyurgun N.; Rafailo, Adyum M.; Luginov, Nikolay V.; Alexeev, Anatoliy N.; Posukh, Olga L.; Dzhemileva, Lilya U.; Khusnutdinova, Elza K.; Fedorova, Sardana A.

    2014-01-01

    Age-Related Hearing Impairment (ARHI) is one of the frequent sensory disorders registered in 50% of individuals over 80 years. ARHI is a multifactorial disorder due to environmental and poor-known genetic components. In this study, we present the data on age-related hearing impairment of 48 heterozygous carriers of mutation IVS1+1G>A (GJB2 gene) and 97 subjects with GJB2 genotype wt/wt in the Republic of Sakha/Yakutia (Eastern Siberia, Russia). This subarctic territory was found as the region with the most extensive accumulation of mutation IVS1+1G>A in the world as a result of founder effect in the unique Yakut population isolate. The GJB2 gene resequencing and detailed audiological analysis in the frequency range 0.25, 0.5, 1.0, 2.0, 4.0, 8.0 kHz were performed in all examined subjects that allowed to investigate genotype-phenotype correlations between the presence of single mutation IVS1+1G>A and hearing of subjects from examined groups. We revealed the linear correlation between increase of average hearing thresholds at speech frequencies (PTA0.5,1.0,2.0,4.0 kHz) and age of individuals with GJB2 genotype IVS1+1G>A/wt (rs = 0.499, p = 0.006860 for males and rs = 0.427, p = 0.000277 for females). Moreover, the average hearing thresholds on high frequency (8.0 kHz) in individuals with genotype IVS1+1G>A/wt (both sexes) were significantly worse than in individuals with genotype wt/wt (p<0.05). Age of hearing loss manifestation in individuals with genotype IVS1+1G>A/wt was estimated to be ∼40 years (rs = 0.504, p = 0.003). These findings demonstrate that the single IVS1+1G>A mutation (GJB2) is associated with age-related hearing impairment (ARHI) of the IVS1+1G>A carriers in the Yakuts. PMID:24959830

  16. 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

  17. 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

  18. Does Fatigue Complaint Reflect Memory Impairment in Multiple Sclerosis?

    PubMed Central

    Jougleux-Vie, Caroline; Duhin, Emeline; Deken, Valerie; Outteryck, Olivier; Vermersch, Patrick; Zéphir, Hélène

    2014-01-01

    Background and Purpose. Fatigue and memory impairment are common symptoms in multiple sclerosis (MS) and both may interact with cognition. This can contribute to making a complaint misrepresentative of the objective disorder. We sought to determine whether fatigue complaint in MS reflects memory impairment and investigated whether patients' subjective fatigue is associated with memory complaint. Methods. Fifty MS patients complaining of fatigue underwent subjective assessment of fatigue and memory complaint measured using self-assessment scales. Cognitive functions were assessed using a battery of neuropsychological tests, including a test of verbal episodic memory, the selective reminding test (SRT). Correlations were studied between subjective fatigue, memory complaint, and performance in verbal episodic memory. Results. Depression score, psychotropic and/or antiepileptic drug use, Expanded Disability Status Scale (EDSS) score, and MS form were confounding factors. After adjusting for these confounding factors, neither fatigue complaint nor memory complaint was correlated with SRT performance. Subjective fatigue was significantly associated with memory complaint. Conclusion. Although complaint of fatigue in MS was correlated with memory complaint, subjective fatigue was not the expression of memory impairment. PMID:24724029

  19. That's a good one! Belief in efficacy of mnemonic strategies contributes to age-related increase in associative memory.

    PubMed

    Daugherty, Ana M; Ofen, Noa

    2015-08-01

    The development of associative memory during childhood may be influenced by metacognitive factors. Here, one aspect of metamemory function--belief in strategy efficacy-was tested for a role in the effective use of encoding strategies. A sample of 61 children and adults (8-25 years of age) completed an associative recognition memory test and were assessed on belief in the efficacy of encoding strategies. Independent of age, belief ratings identified two factors: "deep" and "shallow" encoding strategies. Although the strategy factor structure was stable across age, adolescents and adults were more likely to prefer using a deep encoding strategy, whereas children were equally likely to prefer a shallow strategy. Belief ratings of deep encoding strategies increased with age and, critically, accounted for better associative recognition. PMID:25854595

  20. Age-related changes in neural activity during source memory encoding in young, middle-aged and elderly adults.

    PubMed

    Cansino, Selene; Trejo-Morales, Patricia; Hernández-Ramos, Evelia

    2010-07-01

    Source memory, the ability to remember contextual information present at the moment an event occurs, declines gradually during normal aging. The present study addressed whether source memory decline is related to changes in neural activity during encoding across age. Event-related potentials (ERPs) were recorded in three groups of 14 subjects each: young (21-26 years), middle-aged (50-55 years) and older adults (70-77 years). ERPs were recorded while the subjects performed a natural/artificial judgment on images of common objects that were presented randomly in one of the quadrants of the screen (encoding phase). At retrieval, old images mixed with new ones were presented at the center of the screen and the subjects judged whether each image was new or old and, if old, were asked to indicate at which position of the screen the image was presented in the encoding session. The neurophysiological activity recorded during encoding was segregated for the study items according to whether their context was correctly retrieved or not, so as to search for subsequent memory effects (SME). These effects, which consisted of larger amplitude for items subsequently attracting a correct source judgment than an incorrect one, were observed in the three groups, but their onset was delayed across the age groups. The amplitude of the SME was similar across age groups at the frontal and central electrode sites, but was manifested more at the posterior sites in middle-aged and older adults, suggesting that source memory decline may be related to less efficient encoding mechanisms. PMID:20441775

  1. 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

  2. Effects of green tea and physical exercise on memory impairments associated with aging.

    PubMed

    Flôres, Maíra F; Martins, Alexandre; Schimidt, Helen L; Santos, Francielli W; Izquierdo, Iván; Mello-Carpes, Pâmela B; Carpes, Felipe P

    2014-12-01

    We investigated the effects of physical exercise and green tea supplementation (associated or not) on biochemical and behavioral parameters in the time course of normal aging. Male Wistar rats aged 9 months were divided into groups: control, physical exercise (treadmill running), and supplemented with green tea while either performing physical exercise or not. A young control group was also studied. Physical exercise and green tea supplementation lasted 3 months. Afterwards, behavioral and biochemical tests were performed. Biochemical measurements revealed differences in antioxidant and oxidant responses in hippocampus, prefrontal cortex and striatum. Behavioral testing showed age-related memory impairments reversed by physical exercise. The association of green tea supplementation and physical exercise did not provide aged rats with additional improvements in memory or brain oxidative markers. Green tea per se significantly decreased reactive oxygen species levels and improved antioxidant defenses although it did not reverse memory deficits associated with normal aging. PMID:25195719

  3. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults' performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064

  4. Are age-related differences between young and older adults in an affective working memory test sensitive to the music effects?

    PubMed Central

    Borella, Erika; Carretti, Barbara; Grassi, Massimo; Nucci, Massimo; Sciore, Roberta

    2014-01-01

    There are evidences showing that music can affect cognitive performance by improving our emotional state. The aim of the current study was to analyze whether age-related differences between young and older adults in a Working Memory (WM) Span test in which the stimuli to be recalled have a different valence (i.e., neutral, positive, or negative words), are sensitive to exposure to music. Because some previous studies showed that emotional words can sustain older adults’ performance in WM, we examined whether listening to music could enhance the benefit of emotional material, with respect to neutral words, on WM performance decreasing the age-related difference between younger and older adults. In particular, the effect of two types of music (Mozart vs. Albinoni), which differ in tempo, arousal and mood induction, on age-related differences in an affective version of the Operation WM Span task was analyzed. Results showed no effect of music on the WM test regardless of the emotional content of the music (Mozart vs. Albinoni). However, a valence effect for the words in the WM task was found with a higher number of negative words recalled with respect to positive and neutral ones in both younger and older adults. When individual differences in terms of accuracy in the processing phase of the Operation Span task were considered, only younger low-performing participants were affected by the type music, with the Albinoni condition that lowered their performance with respect to the Mozart condition. Such a result suggests that individual differences in WM performance, at least when young adults are considered, could be affected by the type of music. Altogether, these findings suggest that complex span tasks, such as WM tasks, along with age-related differences are not sensitive to music effects. PMID:25426064

  5. Negative Reinforcement Impairs Overnight Memory Consolidation

    ERIC Educational Resources Information Center

    Stamm, Andrew W.; Nguyen, Nam D.; Seicol, Benjamin J.; Fagan, Abigail; Oh, Angela; Drumm, Michael; Lundt, Maureen; Stickgold, Robert; Wamsley, Erin J.

    2014-01-01

    Post-learning sleep is beneficial for human memory. However, it may be that not all memories benefit equally from sleep. Here, we manipulated a spatial learning task using monetary reward and performance feedback, asking whether enhancing the salience of the task would augment overnight memory consolidation and alter its incorporation into…

  6. "Everyday Memory" Impairments in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Jones, Catherine R. G.; Happe, Francesca; Pickles, Andrew; Marsden, Anita J. S.; Tregay, Jenifer; Baird, Gillian; Simonoff, Emily; Charman, Tony

    2011-01-01

    "Everyday memory" is conceptualised as memory within the context of day-to-day life and, despite its functional relevance, has been little studied in individuals with autism spectrum disorders (ASDs). In the first study of its kind, 94 adolescents with an ASD and 55 without an ASD completed measures of everyday memory from the Rivermead…

  7. Memory Impairment at Initial Clinical Presentation in Posterior Cortical Atrophy.

    PubMed

    Ahmed, Samrah; Baker, Ian; Husain, Masud; Thompson, Sian; Kipps, Christopher; Hornberger, Michael; Hodges, John R; Butler, Christopher R

    2016-04-23

    Posterior cortical atrophy (PCA) is characterized by core visuospatial and visuoperceptual deficits, and predominant atrophy in the parieto-occipital cortex. The most common underlying pathology is Alzheimer's disease (AD). Existing diagnostic criteria suggest that episodic memory is relatively preserved. The aim of this study was to examine memory performance at initial clinical presentation in PCA, compared to early-onset AD patients (EOAD). 15 PCA patients and 32 EOAD patients, and 34 healthy controls were entered into the study. Patients were tested on the Addenbrooke's Cognitive Examination (ACE-R), consisting of subscales in memory and visuospatial skills. PCA and EOAD patients were significantly impaired compared to controls on the ACE total score (p < 0.001), visuospatial skills (p < 0.001), and memory (p < 0.001). Consistent with the salient diagnostic deficits, PCA patients were significantly more impaired on visuospatial skills compared to EOAD patients (p < 0.001). However, there was no significant difference between patient groups in memory. Further analysis of learning, recall, and recognition components of the memory subscale showed that EOAD and PCA patients were significantly impaired compared to controls on all three components (p < 0.001), however, there was no significant difference between EOAD and PCA patients. The results of this study show that memory is impaired in the majority of PCA patients at clinical presentation. The findings suggest that memory impairment must be considered in assessment and management of PCA. Further study into memory in PCA is warranted, since the ACE-R is a brief screening tool and is likely to underestimate the presence of memory impairment. PMID:27128371

  8. Next-day memory impairment with triazolam use.

    PubMed

    Bixler, E O; Kales, A; Manfredi, R L; Vgontzas, A N; Tyson, K L; Kales, J D

    1991-04-01

    The prevalence, rate, and degree of memory impairment for next-day activities during a short, intermittent course of bedtime doses of triazolam, temazepam, and placebo were assessed in a double-blind parallel-group study. 5 of the 6 subjects in the triazolam group reported at least one episode of next-day memory impairment/amnesia, with a total of 12 episodes being reported for the 30 subject-drug nights (a rate of 40%). In the temazepam group there were no such episodes of memory impairment. Immediate and delayed recall were also tested and related to whether active drug or placebo had been taken the night before. Impairment of delayed recall was significantly and several times greater than that in the temazepam or placebo groups. Next-day memory impairment/amnesia after a bedtime dose of triazolam tended to increase with continued or intermittent drug use. Cognitive impairments associated with triazolam probably represent a spectrum of organic brain dysfunction, with memory impairment/amnesia and confusion being the commonest, and milder manifestations and hallucinations and delusions the more severe and less common, features. PMID:1672921

  9. Negative Affect Impairs Associative Memory but Not Item Memory

    ERIC Educational Resources Information Center

    Bisby, James A.; Burgess, Neil

    2014-01-01

    The formation of associations between items and their context has been proposed to rely on mechanisms distinct from those supporting memory for a single item. Although emotional experiences can profoundly affect memory, our understanding of how it interacts with different aspects of memory remains unclear. We performed three experiments to examine…

  10. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment.

    PubMed

    Westerberg, Carmen E; Mander, Bryce A; Florczak, Susan M; Weintraub, Sandra; Mesulam, M-Marsel; Zee, Phyllis C; Paller, Ken A

    2012-05-01

    Whereas patients with Alzheimer's disease (AD) experience difficulties forming and retrieving memories, their memory impairments may also partially reflect an unrecognized dysfunction in sleep-dependent consolidation that normally stabilizes declarative memory storage across cortical areas. Patients with amnestic mild cognitive impairment (aMCI) exhibit circumscribed declarative memory deficits, and many eventually progress to an AD diagnosis. Whether sleep is disrupted in aMCI and whether sleep disruptions contribute to memory impairment is unknown. We measured sleep physiology and memory for two nights and found that aMCI patients had fewer stage-2 spindles than age-matched healthy adults. Furthermore, aMCI patients spent less time in slow-wave sleep and showed lower delta and theta power during sleep compared to controls. Slow-wave and theta activity during sleep appear to reflect important aspects of memory processing, as evening-to-morning change in declarative memory correlated with delta and theta power during intervening sleep in both groups. These results suggest that sleep changes in aMCI patients contribute to memory impairments by interfering with sleep-dependent memory consolidation. PMID:22300710

  11. Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment.

    PubMed

    Falah, Masoumeh; Najafi, Mohammad; Houshmand, Massoud; Farhadi, Mohammad

    2016-01-01

    Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apoptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. PMID:27555755

  12. 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

  13. 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

  14. Expression levels of the BAK1 and BCL2 genes highlight the role of apoptosis in age-related hearing impairment

    PubMed Central

    Falah, Masoumeh; Najafi, Mohammad; Houshmand, Massoud; Farhadi, Mohammad

    2016-01-01

    Age-related hearing impairment (ARHI) is a progressive and a common sensory disorder in the elderly and will become an increasingly important clinical problem given the growing elderly population. Apoptosis of cochlear cells is an important factor in animal models of ARHI. As these cells cannot regenerate, their loss leads to irreversible hearing impairment. Identification of molecular mechanisms can facilitate disease prevention and effective treatment. In this study, we compared the expression of the genes BAK1 and BCL2 as two arms of the intrinsic apoptosis pathway between patients with ARHI and healthy subjects. ARHI and healthy subjects were selected after an ear nose throat examination, otoscopic investigation, and pure tone audiometry. RNA was extracted from peripheral blood samples, and relative gene expression levels were measured using quantitative real-time polymerase chain reaction. BAK1 and the BAK1/BCL2 ratio were statistically significantly upregulated in the ARHI subjects. The BAK1/BCL2 ratio was positively correlated with the results of the audiometric tests. Our results indicate that BAK-mediated apoptosis may be a core mechanism in the progression of ARHI in humans, similar to finding in animal models. Moreover, the gene expression changes in peripheral blood samples could be used as a rapid and simple biomarker for early detection of ARHI. PMID:27555755

  15. Age-related changes in feature-based object memory retrieval as measured by event-related potentials

    PubMed Central

    Chiang, Hsueh-Sheng; Mudar, Raksha A.; Spence, Jeffrey S.; Pudhiyidath, Athula; Eroh, Justin; DeLaRosa, Bambi; Kraut, Michael A.; Hart, John

    2014-01-01

    To investigate neural mechanisms that support semantic functions in aging, we recorded scalp EEG during an object retrieval task in 22 younger and 22 older adults. The task required determining if a particular object could be retrieved when two visual words representing object features were presented. Both age groups had comparable accuracy although response times were longer in older adults. In both groups a left fronto-temporal negative potential occurred at around 750 msec during object retrieval, consistent with previous findings (Brier et al., 2008). Only in older adults a later positive frontal potential was found peaking between 800 and 1000 msec during no retrieval. These findings suggest younger and older adults employ comparable neural mechanisms when features clearly facilitate retrieval of an object memory, but when features yield no retrieval, older adults use additional neural resources to engage in a more effortful and exhaustive search prior to making a decision. PMID:24911552

  16. The canine sand maze: an appetitive spatial memory paradigm sensitive to age-related change in dogs.

    PubMed

    Salvin, Hannah E; McGreevy, Paul D; Sachdev, Perminder S; Valenzuela, Michael J

    2011-01-01

    Aged dogs exhibit a spectrum of cognitive abilities including a syndrome similar to Alzheimer's disease. A major impediment to research so far has been the lack of a quick and accurate test of visuospatial memory appropriate for community-based animals. We therefore report on the development and validation of the Canine Sand Maze. A 4.5-m-diameter circular pool was filled with a sand and powdered food reward mix to a depth of 10 cm. Dogs were given 4 habituation and 16 learning trials which alternated a food reward being half (control trials) or fully-buried (acquisition trials) in a fixed location. After a 90-min break, a probe trial was conducted. Cognitively normal, aged (> 8 years, n  =  11) and young (1-4 years, n  =  11), breed-matched dogs were compared. After correction for differences in control trials, average probe times were 2.97 and 10.81 s for young and aged dogs, respectively. In the probe trial, both groups spent significantly more time in the target quadrant but there was a trend for young dogs to cross a 1 m(2) annulus zone around the buried reward more frequently (2.6 times) than aged dogs (1.5 times). Test-retest reliability in a subset of young dogs (n  =  5) was high. On the basis of these findings, the Canine Sand Maze is presented as a quick, sensitive and nonaversive tool for assessing spatial learning and reference memory in dogs. PMID:21541168

  17. Impaired short-term memory for pitch in congenital amusia.

    PubMed

    Tillmann, Barbara; Lévêque, Yohana; Fornoni, Lesly; Albouy, Philippe; Caclin, Anne

    2016-06-01

    Congenital amusia is a neuro-developmental disorder of music perception and production. The hypothesis is that the musical deficits arise from altered pitch processing, with impairments in pitch discrimination (i.e., pitch change detection, pitch direction discrimination and identification) and short-term memory. The present review article focuses on the deficit of short-term memory for pitch. Overall, the data discussed here suggest impairments at each level of processing in short-term memory tasks; starting with the encoding of the pitch information and the creation of the adequate memory trace, the retention of the pitch traces over time as well as the recollection and comparison of the stored information with newly incoming information. These impairments have been related to altered brain responses in a distributed fronto-temporal network, associated with decreased connectivity between these structures, as well as in abnormalities in the connectivity between the two auditory cortices. In contrast, amusic participants׳ short-term memory abilities for verbal material are preserved. These findings show that short-term memory deficits in congenital amusia are specific to pitch, suggesting a pitch-memory system that is, at least partly, separated from verbal memory. This article is part of a Special Issue entitled SI: Auditory working memory. PMID:26505915

  18. Age-related impairments in skeletal muscle PDH phosphorylation and plasma lactate are indicative of metabolic inflexibility and the effects of exercise training.

    PubMed

    Consitt, Leslie A; Saxena, Gunjan; Saneda, Alicson; Houmard, Joseph A

    2016-07-01

    The purpose of this study was to determine whether plasma lactate and skeletal muscle glucose regulatory pathways, specifically PDH dephosphorylation, are impaired during hyperinsulinemic conditions in middle- to older-aged individuals and determine whether exercise training could improve key variables responsible for skeletal muscle PDH regulation. Eighteen young (19-29 yr; n = 9 males and 9 females) and 20 middle- to older-aged (57-82 yr; n = 10 males and 10 females) individuals underwent a 2-h euglycemic hyperinsulinemic clamp. Plasma samples were obtained at baseline and at 30, 50, 90, and 120 min for analysis of lactate, and skeletal muscle biopsies were performed at 60 min for analysis of protein associated with glucose metabolism. In response to insulin, plasma lactate was elevated in aged individuals when normalized to insulin action. Insulin-stimulated phosphorylation of skeletal muscle PDH on serine sites 232, 293, and 300 decreased in young individuals only. Changes in insulin-stimulated PDH phosphorylation were positively related to changes in plasma lactate. No age-related differences were observed in skeletal muscle phosphorylation of LDH, GSK-3α, or GSK-3β in response to insulin or PDP1, PDP2, PDK2, PDK4, or MPC1 total protein. Twelve weeks of endurance- or strength-oriented exercise training improved insulin-stimulated PDH dephosphorylation, which was related to a reduced lactate response. These findings suggest that impairments in insulin-induced PDH regulation in a sedentary aging population contribute to impaired glucose metabolism and that exercise training is an effective intervention for treating metabolic inflexibility. PMID:27221120

  19. Toxin-Induced Experimental Models of Learning and Memory Impairment.

    PubMed

    More, Sandeep Vasant; Kumar, Hemant; Cho, Duk-Yeon; Yun, Yo-Sep; Choi, Dong-Kug

    2016-01-01

    Animal models for learning and memory have significantly contributed to novel strategies for drug development and hence are an imperative part in the assessment of therapeutics. Learning and memory involve different stages including acquisition, consolidation, and retrieval and each stage can be characterized using specific toxin. Recent studies have postulated the molecular basis of these processes and have also demonstrated many signaling molecules that are involved in several stages of memory. Most insights into learning and memory impairment and to develop a novel compound stems from the investigations performed in experimental models, especially those produced by neurotoxins models. Several toxins have been utilized based on their mechanism of action for learning and memory impairment such as scopolamine, streptozotocin, quinolinic acid, and domoic acid. Further, some toxins like 6-hydroxy dopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and amyloid-β are known to cause specific learning and memory impairment which imitate the disease pathology of Parkinson's disease dementia and Alzheimer's disease dementia. Apart from these toxins, several other toxins come under a miscellaneous category like an environmental pollutant, snake venoms, botulinum, and lipopolysaccharide. This review will focus on the various classes of neurotoxin models for learning and memory impairment with their specific mechanism of action that could assist the process of drug discovery and development for dementia and cognitive disorders. PMID:27598124

  20. Memory activation enhances EEG abnormality in mild cognitive impairment.

    PubMed

    van der Hiele, K; Vein, A A; Kramer, C G S; Reijntjes, R H A M; van Buchem, M A; Westendorp, R G J; Bollen, E L E M; van Dijk, J G; Middelkoop, H A M

    2007-01-01

    This exploratory study investigated EEG power changes during memory activation in patients with amnestic mild cognitive impairment (MCI). Twelve MCI patients and 16 age-matched controls underwent EEG registration during two conventional EEG conditions ('eyes closed' and 'eyes open') and three memory conditions ('word memory', 'picture memory' and 'animal fluency'). For all conditions, EEG power in the theta (4-8 Hz), lower alpha (8-10.5 Hz) and upper alpha (10.5-13 Hz) bands were expressed as percentile changes compared to 'eyes closed'. MCI patients showed significantly less decrease in the lower alpha band than controls (p=0.04) during picture memory activation. The word memory task showed a trend towards a similar effect (p=0.09). This study suggests that memory activation reveals EEG differences between MCI patients and controls while conventional EEG conditions do not. PMID:16406153

  1. 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

  2. Age-associated memory impairment. Assessing the role of nitric oxide.

    PubMed

    Meyer, R C; Spangler, E L; Kametani, H; Ingram, D K

    1998-11-20

    Several neurotransmitter systems have been investigated to assess hypothesized mechanisms underlying the decline in recent memory abilities in normal aging and in Alzheimer's disease. Examining the performance of F344 rats in a 14-unit T-maze (Stone maze), we have focused on the muscarinic cholinergic (mACh) and the N-methyl-D-aspartate (NMDA) glutamate (Glu) systems and their interactions. Maze learning is impaired by antagonists to mACh or NMDA receptors. We have also shown that stimulation of mACh receptors can overcome a maze learning deficit induced by NMDA blockade, and stimulation of the NMDA receptor can overcome a similar blockade of mACh receptors. No consistent evidence in rats has been produced from our laboratory to reveal significant age-related declines in mACh or NMDA receptor binding in the hippocampus (HC), a brain region that is greatly involved in processing of recent memory. Thus, we have directed attention to the possibility of a common signal transduction pathway, the nitric oxide (NO) system. Activated by calcium influx through the NMDA receptor, NO is hypothesized to be a retrograde messenger that enhances presynaptic Glu release. Maze learning can be impaired by inhibiting the synthetic enzyme for NO, nitric oxide synthase (NOS), or enhanced by stimulating NO release. However, we have found no age-related loss of NOS-containing HC neurons or fibers in rats. Additionally, other laboratories have reported no evidence of an age-related loss of HC NOS activity. In a microdialysis study we have found preliminary evidence of reduced NO production following NMDA stimulation. We are currently working to identify the parameters of this phenomenon as well as testing various strategies for safely stimulating the NO system to improve memory function in aged rats. PMID:9928439

  3. Impaired insulin signaling and mechanisms of memory loss.

    PubMed

    Bloemer, Jenna; Bhattacharya, Subhrajit; Amin, Rajesh; Suppiramaniam, Vishnu

    2014-01-01

    Insulin is secreted from the β-cells of the pancreas and helps maintain glucose homeostasis. Although secreted peripherally, insulin also plays a profound role in cognitive function. Increasing evidence suggests that insulin signaling in the brain is necessary to maintain health of neuronal cells, promote learning and memory, decrease oxidative stress, and ultimately increase neuronal survival. This chapter summarizes the different facets of insulin signaling necessary for learning and memory and additionally explores the association between cognitive impairment and central insulin resistance. The role of impaired insulin signaling in the advancement of cognitive dysfunction is relevant to the current debate of whether the shared pathophysiological mechanisms between diabetes and cognitive impairment implicate a direct relationship. Here, we summarize a vast amount of literature that suggests a strong association between impaired brain insulin signaling and cognitive impairment. PMID:24373245

  4. Impaired memory for pitch in congenital amusia.

    PubMed

    Gosselin, Nathalie; Jolicoeur, Pierre; Peretz, Isabelle

    2009-07-01

    We examined memory for pitch in congenital amusia in two tasks. In one task, we varied the pitch distance between the target and comparison tone from 4 to 9 semitones and inserted either a silence or 6 interpolated tones between the tones to be compared. In a second task, we manipulated the number of pitches to be retained in sequences of length 1, 3, or 5. Amusics' sensitivity to pitch distance was exacerbated by the presence of interpolated tones, and amusics' performance was more strongly affected by the number of pitches to maintain in memory than controls. A pitch perception deficit could not account for the pitch memory deficit of amusics. PMID:19673791

  5. Tempol prevents chronic sleep-deprivation induced memory impairment.

    PubMed

    Alzoubi, Karem H; Khabour, Omar F; Albawaana, Amal S; Alhashimi, Farah H; Athamneh, Rabaa Y

    2016-01-01

    Sleep deprivation is associated with oxidative stress that causes learning and memory impairment. Tempol is a nitroxide compound that promotes the metabolism of many reactive oxygen species (ROS) and has antioxidant and neuroprotective effect. The current study investigated whether chronic administration of tempol can overcome oxidative stress and prevent learning and memory impairment induced by sleep deprivation. Sleep deprivation was induced in rats using multiple platform model. Tempol was administered to rats via oral gavages. Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze. The hippocampus was dissected; antioxidant biomarkers (GSH, GSSG, GSH/GSSG ratio, GPx, SOD, and catalase) were assessed. The result of this project revealed that chronic sleep deprivation impaired both short and long term memory (P<0.05), while tempol treatment prevented such effect. Furthermore, tempol normalized chronic sleep deprivation induced reduction in the hippocampus activity of catalase, GPx, and SOD (P<0.05). Tempol also enhanced the ratio of GSH/GSSG in chronically sleep deprived rats treated with tempol as compared with only sleep deprived rats (P<0.05). In conclusion chronic sleep deprivation induced memory impairment, and treatment with tempol prevented this impairment probably through normalizing antioxidant mechanisms in the hippocampus. PMID:26616531

  6. Does stress enhance or impair memory consolidation?

    PubMed

    Trammell, Janet P; Clore, Gerald L

    2014-01-01

    Three experiments examined the hypothesis that stress-induced arousal enhances long-term memory for experiences associated with arousing events. Contrary to expectations, in each experiment exposure to a stressor (arm immersion in ice water) interfered with, rather than enhanced, long-term memory for associated material. Despite varying the stimuli (words, pictures), their emotional value (positive, negative, neutral), the time between learning and stress inductions (0 to 1 minute), and opportunities for post-learning rehearsal, each experiment produced a significant reversal of the hypothesised effect. That is, in each experiment, exposure to a stressor interfered with, rather than enhanced, long-term memory for associated material. We conclude that the relationship between stress and memory consolidation is more bounded than previously believed. PMID:23895111

  7. Does Stress Enhance or Impair Memory Consolidation?

    PubMed Central

    Trammell, Janet P.; Clore, Gerald L.

    2014-01-01

    Three experiments examined the hypothesis that stress-induced arousal enhances long term memory for experiences associated with an arousing events. Contrary to expectations, in each experiment exposure to a stressor (arm immersion in ice water) interfered with, rather than enhanced, long term memory for associated material. Despite varying the stimuli (words, pictures), their emotional value (positive, negative, neutral), the time between learning and stress inductions (0 to 1 minute), and opportunities for post-learning rehearsal, each experiment produced a significant reversal of the hypothesized effect. That is, in each experiment, exposure to a stressor interfered with, rather than enhanced, long term memory for associated material. We conclude that the relationship between stress and memory consolidation is more bounded than previously believed. PMID:23895111

  8. Working memory and reward association learning impairments in obesity

    PubMed Central

    Coppin, Géraldine; Nolan-Poupart, Sarah; Jones-Gotman, Marilyn; Small, Dana M.

    2014-01-01

    Obesity has been associated with impaired executive functions including working memory. Less explored is the influence of obesity on learning and memory. In the current study we assessed stimulus reward association learning, explicit learning and memory and working memory in healthy weight, overweight and obese individuals. Explicit learning and memory did not differ as a function of group. In contrast, working memory was significantly and similarly impaired in both overweight and obese individuals compared to the healthy weight group. In the first reward association learning task the obese, but not healthy weight or overweight participants consistently formed paradoxical preferences for a pattern associated with a negative outcome (fewer food rewards). To determine if the deficit was specific to food reward a second experiment was conducted using money. Consistent with experiment 1, obese individuals selected the pattern associated with a negative outcome (fewer monetary rewards) more frequently than healthy weight individuals and thus failed to develop a significant preference for the most rewarded patterns as was observed in the healthy weight group. Finally, on a probabilistic learning task, obese compared to healthy weight individuals showed deficits in negative, but not positive outcome learning. Taken together, our results demonstrate deficits in working memory and stimulus reward learning in obesity and suggest that obese individuals are impaired in learning to avoid negative outcomes. PMID:25447070

  9. Impairment of aversive memory reconsolidation by localized intracranial electrical stimulation.

    PubMed

    Stehberg, Jimmy; Levy, Dino; Zangen, Abraham

    2009-03-01

    Reconsolidation of long-term memory is blocked in animal models by macromolecular synthesis inhibitors, resulting in item-specific post-retrieval amnesia. The induction of such amnesia could ameliorate traumatic memories and phobias. However, this pharmacological approach is of limited value in humans because of toxicity. Here we report that reconsolidation of conditioned taste aversion in the rat is impaired by localized intracranial electrical stimulation. Lasting impairment was obtained only when stimulation was applied during memory reactivation and only to the dysgranular insular cortex bilaterally, which subserves the memory, but not to adjacent brain sites. The ability to learn a new association was not affected. The same method blocked new memory consolidation, but produced anterograde amnesia, reminiscent of the known effect of non-localized electroconvulsive therapy. Our results suggest that localized electrical microstimulation, such as produced by deep-brain stimulation or deep transcranial magnetic stimulation, could be used to impair long-term memory if applied during memory reactivation, and could lead to the development of a novel treatment for intractable post-traumatic stress disorder. PMID:19200060

  10. Cue-independent memory impairment by reactivation-coupled interference in human declarative memory.

    PubMed

    Zhu, Zijian; Wang, Yingying; Cao, Zhijun; Chen, Biqing; Cai, Huaqian; Wu, Yanhong; Rao, Yi

    2016-10-01

    Memory is a dynamic process. While memory becomes increasingly resistant to interference after consolidation, a brief reactivation renders it unstable again. Previous studies have shown that interference, when applied upon reactivation, impairs the consolidated memory, presumably by disrupting the reconsolidation of the memory. However, attempts have failed in disrupting human declarative memory, raising a question about whether declarative memory becomes unstable upon reactivation. Here, we used a double-cue/one-target paradigm, which associated the same target with two different cues in initial memory formation. Only one cue/target association was later reactivated and treated with behavioral interference. Our results showed, for the first time, that reactivation-coupled interference caused cue-independent memory impairment that generalized to other cues associated with the memory. Critically, such memory impairment appeared immediately after interference, before the reconsolidation process was completed, suggesting that common manipulations of reactivation-coupled interference procedures might disrupt other processes in addition to the reconsolidation process in human declarative memory. PMID:27389345

  11. The European GWAS-identified risk SNP rs457717 within IQGAP2 is not associated with age-related hearing impairment in Han male Chinese population.

    PubMed

    Luo, Huajie; Wu, Hao; Shen, Hailian; Chen, Haifeng; Yang, Tao; Huang, Zhiwu; Jin, Xiaojie; Pang, Xiuhong; Li, Lei; Hu, Xianting; Jiang, Xuemei; Fan, Zhuping; Li, Jiping

    2016-07-01

    This study aimed to test the association between the European GWAS-identified risk IQGAP2 SNP rs457717 (A>G) and age-related hearing impairment (ARHI) in a Han male Chinese (HMC) population. A total of 2420 HMC subjects were divided into two groups [group 70+: >70 years (n = 1306), and group 70-: ≤70 years (n = 1114)]. The participants were categorised into case and control groups according to Z high scores for group 70- and the severity of hearing loss and different audiogram shapes identified by K-means cluster analysis for group 70+. The IQGAP2 tagSNP rs457717 was genotyped in accordance with the different ARHI phenotypes. The genotype distributions of IQGAP2 (AA/AG/GG) were not significantly different between the case and control groups (P = 0.613 for group 70-; P = 0.602 for group 70+). Compared with genotype AA, the ORs of genotypes AG and GG for ARHI were not significantly different following adjustment for other environmental risk factors. We demonstrated that the IQGAP2 TagSNP rs457717 (A/G) was not associated with ARHI in HMC individuals. PMID:26187738

  12. Lost Forever or Temporarily Misplaced? The Long Debate about the Nature of Memory Impairment

    ERIC Educational Resources Information Center

    Squire, Larry R.

    2006-01-01

    Studies of memory impairment in humans and experimental animals have been fundamental to learning about the organization of memory and its cellular and molecular substrates. When memory impairment occurs, especially after perturbations of the nervous system, the question inevitably arises whether the impairment reflects impaired information…

  13. Impairing existing declarative memory in humans by disrupting reconsolidation

    PubMed Central

    Chan, Jason C. K.; LaPaglia, Jessica A.

    2013-01-01

    During the past decade, a large body of research has shown that memory traces can become labile upon retrieval and must be restabilized. Critically, interrupting this reconsolidation process can abolish a previously stable memory. Although a large number of studies have demonstrated this reconsolidation associated amnesia in nonhuman animals, the evidence for its occurrence in humans is far less compelling, especially with regard to declarative memory. In fact, reactivating a declarative memory often makes it more robust and less susceptible to subsequent disruptions. Here we show that existing declarative memories can be selectively impaired by using a noninvasive retrieval–relearning technique. In six experiments, we show that this reconsolidation-associated amnesia can be achieved 48 h after formation of the original memory, but only if relearning occurred soon after retrieval. Furthermore, the amnesic effect persists for at least 24 h, cannot be attributed solely to source confusion and is attainable only when relearning targets specific existing memories for impairment. These results demonstrate that human declarative memory can be selectively rewritten during reconsolidation. PMID:23690586

  14. Impairing existing declarative memory in humans by disrupting reconsolidation.

    PubMed

    Chan, Jason C K; LaPaglia, Jessica A

    2013-06-01

    During the past decade, a large body of research has shown that memory traces can become labile upon retrieval and must be restabilized. Critically, interrupting this reconsolidation process can abolish a previously stable memory. Although a large number of studies have demonstrated this reconsolidation associated amnesia in nonhuman animals, the evidence for its occurrence in humans is far less compelling, especially with regard to declarative memory. In fact, reactivating a declarative memory often makes it more robust and less susceptible to subsequent disruptions. Here we show that existing declarative memories can be selectively impaired by using a noninvasive retrieval-relearning technique. In six experiments, we show that this reconsolidation-associated amnesia can be achieved 48 h after formation of the original memory, but only if relearning occurred soon after retrieval. Furthermore, the amnesic effect persists for at least 24 h, cannot be attributed solely to source confusion and is attainable only when relearning targets specific existing memories for impairment. These results demonstrate that human declarative memory can be selectively rewritten during reconsolidation. PMID:23690586

  15. Visuospatial deficits in schizophrenia: central executive and memory subsystems impairments.

    PubMed

    Leiderman, Eduardo A; Strejilevich, Sergio A

    2004-06-01

    Object and spatial visual working memory are impaired in schizophrenic patients. It is not clear if the impairments reside in each memory subsystem alone or also in the central executive component that coordinates these processes. In order to elucidate which memory component is impaired, we developed a paradigm with single spatial and object working memory tasks and dual ones with two different delays (5 and 30 s). Fifteen schizophrenic patients and 14 control subjects performed these tests. Schizophrenic patients had a poorer performance compared to normal controls in all tasks and in all time delays. Both schizophrenics and controls performed significantly worse in the object task than in the spatial task. The performance was even worse in the dual task compared to the singles ones in schizophrenic patients but not in controls. These data suggest that visuospatial performance deficits in schizophrenia are due to both visuospatial memory subsystems impairments and central executive ones. The pattern of deficits observed points to a codification or evocation deficit and not to a maintenance one. PMID:15099604

  16. Verbal Memory Impairment in Polydrug Ecstasy Users: A Clinical Perspective

    PubMed Central

    Kuypers, Kim P. C.; Theunissen, Eef L.; van Wel, Janelle H. P.; de Sousa Fernandes Perna, Elizabeth B.; Linssen, Anke; Sambeth, Anke; Schultz, Benjamin G.; Ramaekers, Johannes G.

    2016-01-01

    Background Ecstasy use has been associated with short-term and long-term memory deficits on a standard Word Learning Task (WLT). The clinical relevance of this has been debated and is currently unknown. The present study aimed at evaluating the clinical relevance of verbal memory impairment in Ecstasy users. To that end, clinical memory impairment was defined as decrement in memory performance that exceeded the cut-off value of 1.5 times the standard deviation of the average score in the healthy control sample. The primary question was whether being an Ecstasy user (E-user) was predictive of having clinically deficient memory performance compared to a healthy control group. Methods WLT data were pooled from four experimental MDMA studies that compared memory performance during placebo and MDMA intoxication. Control data were taken from healthy volunteers with no drug use history who completed the WLT as part of a placebo-controlled clinical trial. This resulted in a sample size of 65 E-users and 65 age- and gender-matched healthy drug-naïve controls. All participants were recruited by similar means and were tested at the same testing facilities using identical standard operating procedures. Data were analyzed using linear mixed-effects models, Bayes factor, and logistic regressions. Results Findings were that verbal memory performance of placebo-treated E-users did not differ from that of controls, and there was substantial evidence in favor of the null hypothesis. History of use was not predictive of memory impairment. During MDMA intoxication of E-users, verbal memory was impaired. Conclusion The combination of the acute and long-term findings demonstrates that, while clinically relevant memory impairment is present during intoxication, it is absent during abstinence. This suggests that use of Ecstasy/MDMA does not lead to clinically deficient memory performance in the long term. Additionally, it has to be investigated whether the current findings apply to more

  17. Brain aging, memory impairment and oxidative stress: a study in Drosophila melanogaster.

    PubMed

    Haddadi, Mohammad; Jahromi, Samaneh Reiszadeh; Sagar, B K Chandrasekhar; Patil, Rajashekhar K; Shivanandappa, T; Ramesh, S R

    2014-02-01

    Memory impairment during aging is believed to be a consequence of decline in neuronal function and increase in neurodegeneration. Accumulation of oxidative damage and reduction of antioxidant defense system play a key role in organismal aging and functional senescence. In our study, we examined the age-related memory impairment (AMI) in relation to oxidative stress using Drosophila model. We observed a decline in cognitive function in old flies with respect to both short-lived and consolidated forms of olfactory memory. Light and electron microscopy of mushroom bodies revealed a reduction in the number of synapses and discernible architectural defects in mitochondria. An increase in neuronal apoptosis in Kenyon cells was also evident in aged flies. Biochemical investigations revealed a comparable age-associated decrease in the activity of antioxidant enzymes such as catalase and superoxide dismutase as well as the GSH level, accompanied by an increase in the level of lipid peroxidation and generation of reactive oxygen species in the brain. There was no significant difference in the activity level of AChE and BChE enzymes between different age groups while immunohistochemical studies showed a significant decrease in the level of ChAT in 50-day-old flies. RNAi-mediated silencing of cat and sod1 genes caused severe memory impairment in 15-day-old flies, whereas, over-expression of cat gene could partially rescue the memory loss in the old flies. We demonstrated that a Drosophila long-lived strain, possessing enhanced activity of antioxidant enzymes and higher rate of resistance to oxidative stress, shows lower extent of AMI compared to normal lifespan strain. Present study provides evidence for involvement of oxidative stress in AMI in Drosophila. PMID:24183945

  18. Rumination and autobiographical memory impairment in patients with schizophrenia.

    PubMed

    Ricarte, J J; Hernández, J V; Latorre, J M; Danion, J M; Berna, F

    2014-12-01

    Although patients with schizophrenia exhibit autobiographical memory impairment, which is considered to be a limiting factor in their daily life, the mechanisms underlying such impairment have been rarely studied. In the current study, we investigate whether rumination and, in particular, brooding, which is a form of maladaptive repetitive thinking, may be linked to the difficulty that patients with schizophrenia experience when attempting to access specific autobiographical memories. Our results indicate that patients reported less specific autobiographical memories compared to control participants. Patients also displayed a higher level of brooding and had more depressive symptoms. According to the CaR-FA-X model (Williams et al., 2007), depression and brooding were associated with memory specificity in control participants. In contrast, neither depression nor brooding was correlated with memory specificity in patients. These results suggest that depression and rumination may not be directly related to patients' difficulty to recall specific memories and that other factors, such as metacognitive deficits, must first be considered when seeking interventions aimed to improve autobiographical memory in patients with schizophrenia. PMID:25464919

  19. Ascent to moderate altitude impairs overnight memory improvements.

    PubMed

    Tesler, Noemi; Latshang, Tsogyal D; Lo Cascio, Christian M; Stadelmann, Katrin; Stoewhas, Anne-Christin; Kohler, Malcolm; Bloch, Konrad E; Achermann, Peter; Huber, Reto

    2015-02-01

    Several studies showed beneficial effects of sleep on memory performance. Slow waves, the electroencephalographic characteristic of deep sleep, reflected on the neuronal level by synchronous slow oscillations, seem crucial for these benefits. Traveling to moderate altitudes decreases deep sleep. In a randomized cross-over design healthy male subjects performed a visuo-motor learning task in Zurich (490 m) and at Davos Jakobshorn (2590 m) in random order. Memory performance was assessed immediately after learning, before sleep, and in the morning after a night of sleep. Sleep EEG recordings were performed during the nights. Our findings show an altitude induced reduction of sleep dependent memory performance. Moreover, this impaired sleep dependent memory performance was associated with reduced slow wave derived measures of neuronal synchronization. Our results are consistent with a critical role of slow waves for the beneficial effects of sleep on memory that is susceptible to natural environmental influences. PMID:25449393

  20. NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries

    PubMed Central

    Trott, Daniel W.; Seawright, John W.; Luttrell, Meredith J.

    2011-01-01

    We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O2−) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H2O2), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H2O2 scavenger altered flow-induced dilation, whereas both H2O2 scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H2O2 and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA. PMID:21233343

  1. NAD(P)H oxidase-derived reactive oxygen species contribute to age-related impairments of endothelium-dependent dilation in rat soleus feed arteries.

    PubMed

    Trott, Daniel W; Seawright, John W; Luttrell, Meredith J; Woodman, Christopher R

    2011-05-01

    We tested the hypothesis that age-related endothelial dysfunction in rat soleus muscle feed arteries (SFA) is mediated in part by NAD(P)H oxidase-derived reactive oxygen species (ROS). SFA from young (4 mo) and old (24 mo) Fischer 344 rats were isolated and cannulated for examination of vasodilator responses to flow and acetylcholine (ACh) in the absence or presence of a superoxide anion (O(2)(-)) scavenger (Tempol; 100 μM) or an NAD(P)H oxidase inhibitor (apocynin; 100 μM). In the absence of inhibitors, flow- and ACh-induced dilations were attenuated in SFA from old rats compared with young rats. Tempol and apocynin improved flow- and ACh-induced dilation in SFA from old rats. In SFA from young rats, Tempol and apocynin had no effect on flow-induced dilation, and apocynin attenuated ACh-induced dilation. To determine the role of hydrogen peroxide (H(2)O(2)), dilator responses were assessed in the absence and presence of catalase (100 U/ml) or PEG-catalase (200 U/ml). Neither H(2)O(2) scavenger altered flow-induced dilation, whereas both H(2)O(2) scavengers blunted ACh-induced dilation in SFA from young rats. In old SFA, catalase improved flow-induced dilation whereas PEG-catalase improved ACh-induced dilation. Compared with young SFA, in response to exogenous H(2)O(2) and NADPH, old rats exhibited blunted dilation and constriction, respectively. Immunoblot analysis revealed that the NAD(P)H oxidase subunit gp91phox protein content was greater in old SFA compared with young. These results suggest that NAD(P)H oxidase-derived reactive oxygen species contribute to impaired endothelium-dependent dilation in old SFA. PMID:21233343

  2. Speed of Processing, Working Memory, and Language Impairment in Children

    ERIC Educational Resources Information Center

    Leonard, Laurence B.; Weismer, Susan Ellis; Miller, Carol A.; Francis, David J.; Tomblin, J. Bruce; Kail, Robert V.

    2007-01-01

    Purpose: Children with language impairment (LI) often perform below the level of typically developing peers on measures of both processing speed and working memory. This study examined the relationship between these 2 types of measures and attempted to determine whether such measures can account for the LI itself. Method: Fourteen-year-old…

  3. Infliximab ameliorates AD-associated object recognition memory impairment.

    PubMed

    Kim, Dong Hyun; Choi, Seong-Min; Jho, Jihoon; Park, Man-Seok; Kang, Jisu; Park, Se Jin; Ryu, Jong Hoon; Jo, Jihoon; Kim, Hyun Hee; Kim, Byeong C

    2016-09-15

    Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Aβ oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Aβ oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-α, visual recognition memory impaired by pre-administered Aβ oligomers dramatically improved and the detrimental Aβ effect on mAChR-LTD was annulled. Taken together, these findings suggest that Aβ-induced inflammation is mediated through TNF-α signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits. PMID:27265784

  4. Age-Related Differences in Memory and Executive Functions in Healthy APOE ε4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

    PubMed Central

    Bender, Andrew R.; Raz, Naftali

    2012-01-01

    Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially, the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of perceptual processing. Presence of a known genetic risk factor for cognitive decline and vascular disease, the ε4 allele of the apolipoprotein E (APOE) gene, accounts for some share of those declines; however, the extent of the joint contribution of genetic and physiological vascular risk factors on the aging brain and cognition is unclear. In a sample of healthy adults (age 19–77), we examined the effects of a vascular risk indicator (systolic blood pressure, SBP) and volumes of hippocampus (HC), lateral prefrontal cortex (lPFC), and prefrontal white matter (pFWM) on processing speed, working memory (WM), and recognition memory. Using path analyses, we modeled indirect effects of age, SBP, and brain volumes on processing speed, WM, and memory and compared the patterns of structural relations among those variables in APOE ε4 carriers and ε3 homozygotes. Among ε4 carriers, age differences in WM were explained by increase in SBP, reduced FWM volume, and slower processing. In contrast, lPFC and FWM volumes, but not BP, explained a share of age differnces in WM among ε3 homozygotes. Thus, even in healthy older carriers of the APOE ε4 allele, clinically unremarkable increase in vascular risk may be associated with reduced frontal volumes and impaired cognitive functions. PMID:22245009

  5. Age-Related Changes in the Functional Network Underlying Specific and General Autobiographical Memory Retrieval: A Pivotal Role for the Anterior Cingulate Cortex

    PubMed Central

    Martinelli, Pénélope; Sperduti, Marco; Devauchelle, Anne-Dominique; Kalenzaga, Sandrine; Gallarda, Thierry; Lion, Stéphanie; Delhommeau, Marion; Anssens, Adèle; Amado, Isabelle; Meder, Jean François; Krebs, Marie-Odile; Oppenheim, Catherine; Piolino, Pascale

    2013-01-01

    Age-related changes in autobiographical memory (AM) recall are characterized by a decline in episodic details, while semantic aspects are spared. This deleterious effect is supposed to be mediated by an inefficient recruitment of executive processes during AM retrieval. To date, contrasting evidence has been reported on the neural underpinning of this decline, and none of the previous studies has directly compared the episodic and semantic aspects of AM in elderly. We asked 20 young and 17 older participants to recall specific and general autobiographical events (i.e., episodic and semantic AM) elicited by personalized cues while recording their brain activity by means of fMRI. At the behavioral level, we confirmed that the richness of episodic AM retrieval is specifically impoverished in aging and that this decline is related to the reduction of executive functions. At the neural level, in both age groups, we showed the recruitment of a large network during episodic AM retrieval encompassing prefrontal, cortical midline and posterior regions, and medial temporal structures, including the hippocampus. This network was very similar, but less extended, during semantic AM retrieval. Nevertheless, a greater activity was evidenced in the dorsal anterior cingulate cortex (dACC) during episodic, compared to semantic AM retrieval in young participants, and a reversed pattern in the elderly. Moreover, activity in dACC during episodic AM retrieval was correlated with inhibition and richness of memories in both groups. Our findings shed light on the direct link between episodic AM retrieval, executive control, and their decline in aging, proposing a possible neuronal signature. They also suggest that increased activity in dACC during semantic AM retrieval in the elderly could be seen as a compensatory mechanism underpinning successful AM performance observed in aging. These results are discussed in the framework of recently proposed models of neural reorganization in aging

  6. A stroke patient with impairment of auditory sensory (echoic) memory.

    PubMed

    Kojima, T; Karino, S; Yumoto, M; Funayama, M

    2014-04-01

    A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM. PMID:23173635

  7. Declarative and Procedural Memory in Danish Speaking Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Bleses, Dorthe

    2012-01-01

    It has been proposed that the language problems in specific language impairment (SLI) arise from basal ganglia abnormalities that lead to impairments with procedural and working memory but not declarative memory. In SLI, this profile of memory functioning has been hypothesized to underlie grammatical impairment but leave lexical knowledge…

  8. Memantine prevents reference and working memory impairment caused by sleep deprivation in both young and aged Octodon degus.

    PubMed

    Tarragon, Ernesto; Lopez, Dolores; Estrada, Cristina; Gonzalez-Cuello, Ana; Ros, Carmen Ma; Lamberty, Yves; Pifferi, Fabien; Cella, Massimo; Canovi, Mara; Guiso, Giovanna; Gobbi, Marco; Fernández-Villalba, Emiliano; Blin, Olivier; Bordet, Regis; Richardson, Jill C; Herrero, María Trinidad

    2014-10-01

    Memory loss is one of the key features of cognitive impairment in either aging, Mild Cognitive Impairment (MCI) or dementia. Pharmacological treatments for memory loss are today focused on addressing symptomatology. One of these approved compounds is memantine, a partial NMDA receptor antagonist that has proved its beneficial effects in cognition. The Octodon degus (O. degus) has been recently proposed as a potential model relevant for neurodegenerative diseases. However, there are no previous studies investigating the effect of pharmacological treatments for age-related cognitive impairment in this rodent. In this work we aimed to evaluate the effect of memantine on sleep deprivation (SD)-induced memory impairment in young and old O. degus. Young and old animals were trained in different behavioral paradigms validated for memory evaluation, and randomly assigned to a control (CTL, n=14) or an SD (n=14) condition, and treated with vehicle or memantine (10-mg/Kg i.p.) before the SD started. We demonstrate that SD impairs memory in both young and old animals, although the effect in the old group was significantly more severe (P<0.05). Memantine pretreatment was able to prevent the cognitive impairment caused by SD in both age groups, while it had no negative effect on CTL animals. The positive effect of memantine in counteracting the negative effect of SD on the retrieval process even in the aged O. degus further supports the translational potential of both the challenge and the species, and will enable a better understanding of the behavioral features of memantine effects, especially related with reference and working memories. PMID:24878242

  9. Working memory contributions to reinforcement learning impairments in schizophrenia.

    PubMed

    Collins, Anne G E; Brown, Jaime K; Gold, James M; Waltz, James A; Frank, Michael J

    2014-10-01

    Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia. PMID:25297101

  10. Procedural and Declarative Memory in Children with and without Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Gelgic, Celin; Conti-Ramsden, Gina

    2010-01-01

    Background: Much evidence has accumulated to indicate memory deficits in children with specific language impairment. However, most research has focused on working memory impairments in these children. Less is known about the functioning of other memory systems in this population. Aims: This study examined procedural and declarative memory in young…

  11. Adaptive memory: Animacy enhances free recall but impairs cued recall.

    PubMed

    Popp, Earl Y; Serra, Michael J

    2016-02-01

    Recent research suggests that human memory systems evolved to remember animate things better than inanimate things. In the present experiments, we examined whether these effects occur for both free recall and cued recall. In Experiment 1, we directly compared the effect of animacy on free recall and cued recall. Participants studied lists of objects and lists of animals for free-recall tests, and studied sets of animal-animal pairs and object-object pairs for cued-recall tests. In Experiment 2, we compared participants' cued recall for English-English, Swahili-English, and English-Swahili word pairs involving either animal or object English words. In Experiment 3, we compared participants' cued recall for animal-animal, object-object, animal-object, and object-animal pairs. Although we were able to replicate past effects of animacy aiding free recall, animacy typically impaired cued recall in the present experiments. More importantly, given the interactions found in the present experiments, we conclude that some factor associated with animacy (e.g., attention capture or mental arousal) is responsible for the present patterns of results. This factor seems to moderate the relationship between animacy and memory, producing a memory advantage for animate stimuli in scenarios where the moderator leads to enhanced target retrievability but a memory disadvantage for animate stimuli in scenarios where the moderator leads to impaired association memory. PMID:26375781

  12. Tenuigenin ameliorates learning and memory impairments induced by ovariectomy.

    PubMed

    Cai, Zhao-Lin; Wang, Chun-Yang; Gu, Xing-Yang; Wang, Na-Jie; Wang, Jin-Jing; Liu, Wen-Xiao; Xiao, Peng; Li, Chu-Hua

    2013-06-13

    Estrogen deficiency is associated with cognitive impairment. Hormone replacement therapy (HRT) has proven to be effective in preventing and reversing the memory and learning deficiencies. However, conventional estrogenic treatment could increase the risks of breast cancer and venous thromboembolism. Tenuigenin (TEN) is putatively believed as the active component extracted from a Chinese herb Polygala tenuifolia root. Although TEN has been shown to enhance learning and memory in healthy mice, it remains unknown whether or not TEN could ameliorate learning and memory impairments. In the present study, mice were divided into four groups: sham-operated (sham), ovariectomized (OVX), OVX+estradiol benzoate (EB) and OVX+TEN groups. Step-through passive avoidance and Y-maze tests were used to assess learning and memory abilities, and the number of nitric oxide synthase (NOS) positive neurons and the synaptic measurement of hippocampal CA1 area were examined. The results showed that TEN was given orally to OVX mice, leading to the improvement of learning and memory in step-through passive avoidance and Y-maze tests. TEN could reduce the loss of NOS positive neurons and prevent the synaptic morphological changes induced by ovariectomy. Our results suggest that TEN may exert a potential therapeutic value for menopause cognitive dysfunction. PMID:23688946

  13. Revised associative inference paradigm confirms relational memory impairment in schizophrenia

    PubMed Central

    Armstrong, Kristan; Williams, Lisa E.; Heckers, Stephan

    2013-01-01

    Objective Patients with schizophrenia have widespread cognitive impairments, with selective deficits in relational memory. We previously reported a differential relational memory deficit in schizophrenia using the Associative Inference Paradigm (AIP), a task suggested by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative to examine relational memory. However, the AIP had limited feasibility for testing in schizophrenia due to high attrition of schizophrenia patients during training. Here we developed and tested a revised version of the AIP to improve feasibility. Method 30 healthy control and 37 schizophrenia subjects received 3 study-test sessions on 3 sets of paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), and F3-F4 (two novel faces). After training, subjects were tested on the trained, non-inferential Face-Face pairs (F3-F4) and novel, inferential Face-Face pairs (F1-F2), constructed from the faces of the trained House-Face pairs. Results Schizophrenia patients were significantly more impaired on the inferential F1-F2 pairs than the non-inferential F3-F4 pairs, providing evidence for a differential relational memory deficit. Only 8 percent of schizophrenia patients were excluded from testing due to poor training performance. Conclusions The revised AIP confirmed the previous finding of a relational memory deficit in a larger and more representative sample of schizophrenia patients. PMID:22612578

  14. Memory impairment in the weapon focus effect.

    PubMed

    Saunders, Jo

    2009-04-01

    Two experiments are reported in which postevent source of misinformation was manipulated within weapon-present and weapon-absent scenarios. Participants viewed slides depicting either a weapon or a newspaper event and then received either incomplete questioning or a narrative. Both postevent sources contained misleading information about a central and peripheral detail concerning either the weapon or the newspaper scenario. With a modified test in Experiment 1, questioning was found to increase misinformation effects concerning the central item, as compared with a narrative, and more misinformation effects were found for the weapon-peripheral than for the newspaper-peripheral item. In Experiment 2, the participants were more likely to claim to have seen contradictory and additive misinformation about the central item in the slides following questioning, and more contradictory and additive misinformation effects occurred for the weapon-peripheral than for the newspaper-peripheral item. The findings are considered in terms of the effects of both postevent and encoding factors on memory. PMID:19246347

  15. Decreased Npas4 and Arc mRNA Levels in the Hippocampus of Aged Memory-Impaired Wild-Type But Not Memory Preserved 11β-HSD1 Deficient Mice.

    PubMed

    Qiu, J; Dunbar, D R; Noble, J; Cairns, C; Carter, R; Kelly, V; Chapman, K E; Seckl, J R; Yau, J L W

    2016-01-01

    Mice deficient in the glucocorticoid-regenerating enzyme 11β-HSD1 resist age-related spatial memory impairment. To investigate the mechanisms and pathways involved, we used microarrays to identify differentially expressed hippocampal genes that associate with cognitive ageing and 11β-HSD1. Aged wild-type mice were separated into memory-impaired and unimpaired relative to young controls according to their performance in the Y-maze. All individual aged 11β-HSD1-deficient mice showed intact spatial memory. The majority of differentially expressed hippocampal genes were increased with ageing (e.g. immune/inflammatory response genes) with no genotype differences. However, the neuronal-specific transcription factor, Npas4, and immediate early gene, Arc, were reduced (relative to young) in the hippocampus of memory-impaired but not unimpaired aged wild-type or aged 11β-HSD1-deficient mice. A quantitative reverse transcriptase-polymerase chain reaction and in situ hybridisation confirmed reduced Npas4 and Arc mRNA expression in memory-impaired aged wild-type mice. These findings suggest that 11β-HSD1 may contribute to the decline in Npas4 and Arc mRNA levels associated with memory impairment during ageing, and that decreased activity of synaptic plasticity pathways involving Npas4 and Arc may, in part, underlie the memory deficits seen in cognitively-impaired aged wild-type mice. PMID:26563879

  16. When two is too many: Collaborative encoding impairs memory.

    PubMed

    Barber, Sarah J; Rajaram, Suparna; Aron, Arthur

    2010-04-01

    Humans routinely encode and retrieve experiences in interactive, collaborative contexts. Yet much of what we know about human memory comes from research on individuals working in isolation. Some recent research has examined collaboration during retrieval, but not much is known about how collaboration during encoding affects memory. We examined this issue. Participants created episodes by elaborating on study materials alone or collaboratively, and they later performed a cued-recall task alone, with the study partner, or with a different partner (Experiment 1). Collaborative encoding impaired recall. This counterintuitive outcome was found for both individual and group recall, even when the same partners collaborated across encoding and retrieval. This impairment was significantly reduced, but persisted, when the encoding instructions encouraged free-flowing collaboration (Experiment 2). Thus, the collaborative-encoding deficit is robust in nature and likely occurs because collaborative encoding produces less effective cues for later retrieval. PMID:20234016

  17. Hippocampal formation lesions produce memory impairment in the rhesus monkey.

    PubMed

    Beason-Held, L L; Rosene, D L; Killiany, R J; Moss, M B

    1999-01-01

    There is much debate over the role of temporal lobe structures in the ability to learn and retain new information. To further assess the contributions of the hippocampal formation (HF), five rhesus monkeys received stereotactically placed ibotenic acid lesions of this region without involvement of surrounding ventromedial temporal cortices. After surgery, the animals were trained on two recognition memory tasks: the Delayed Non-Match to Sample (DNMS) task, which tests the ability to remember specific trial unique stimuli, and the Delayed Recognition Span Task (DRST), which tests the ability to remember an increasing array of stimuli. Relative to normal control monkeys, those with HF lesions demonstrated significant impairments in both learning and memory stages of the DNMS task. Additionally, the HF group was significantly impaired on spatial, color, and object versions of the DRST. Contrary to suggestions that damage to the entorhinal and parahippocampal cortices is required to produce significant behavioral deficits in the monkey, these results demonstrate that selective damage to the HF is sufficient to produce impairments on tasks involving delayed recognition and memory load. This finding illustrates the importance of the HF in the acquisition and retention of new information. PMID:10560927

  18. Brain Injury Impairs Working Memory and Prefrontal Circuit Function

    PubMed Central

    Smith, Colin J.; Xiong, Guoxiang; Elkind, Jaclynn A.; Putnam, Brendan; Cohen, Akiva S.

    2015-01-01

    More than 2.5 million Americans suffer a traumatic brain injury (TBI) each year. Even mild to moderate TBI causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI), the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice, while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI. PMID:26617569

  19. Impaired drawing from memory in a visual agnosic patient.

    PubMed

    Trojano, L; Grossi, D

    1992-11-01

    A case is reported of an associative visual agnosic patient who could not draw from memory objects he could recognize, even though he could copy drawings flawlessly. His ability to generate mental visual images was found to be spared, as was his ability to operate upon mental images. These data suggest that the patient could generate mental images but could not draw from memory because he did not have access to stored knowledge about pictorial attributes of objects. A similar functional impairment can be found in some other visual agnosic patients and in patients affected by optic aphasia. The present case allows a discussion of relationships among drawing from memory, imagery, and copying procedures. PMID:1449762

  20. Curcumin alleviates cisplatin-induced learning and memory impairments.

    PubMed

    Oz, Mehmet; Nurullahoglu Atalik, K Esra; Yerlikaya, F Humeyra; Demir, Enver Ahmet

    2015-09-01

    The present study has been designed to investigate the role of curcumin on cisplatin-inducedcognitive impairment and to reveal mechanisms of cisplatin's detrimental actions on cognition in rats. Animals were treated with cisplatin (5mg/kg/week) and/or curcumin (300mg/kg/day) for 5weeks. Morris water maze test was used to assess spatial learning and memory. Enzymatic activities of acetylcholinesterase (AChE) and superoxide dismutase (SOD) were evaluated from hippocampus and plasma samples, and malondialdehyde (MDA), which is the end-product of lipid peroxidation, was determined by a colorimetric method. Our results showed that cisplatin (5mg/kg/week, 5weeks) caused learning and memory deficits, elevated MDA content, decreased SOD activity in the hippocampus and plasma, and AChE activity in the hippocampus. Curcumin improved learning and memory in rats with administration of cisplatin. In addition, curcumin significantly reduced the level of MDA and increased the activities of SOD and AChE. Taken together, our findings indicate that curcumin ameliorates cisplatin-induced spatial learning and memory impairment, possibly through restored cholinergic function and enhanced oxidative status. PMID:25982942

  1. [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

  2. The Societal Impact of Age-Related Macular Degeneration: Use of Social Support Resources Differs by the Severity of the Impairment

    ERIC Educational Resources Information Center

    Brennan, Mark; Horowitz, Amy; Reinhardt, Joann P.; Stuen, Cynthia; Rubio, Roman; Oestreicher, Nina

    2011-01-01

    Age-related macular degeneration (AMD) is the leading cause of legal blindness among persons aged 50 years and older and is most prevalent among individuals of European descent aged 65 and older (Friedman et al., 2004; Rosenthal & Thompson, 2003). By affecting central vision, AMD interferes with such tasks as reading, driving, and activities of…

  3. Awareness of memory task impairment versus everyday memory difficulties in dementia.

    PubMed

    Morris, Robin G; Nelis, Sharon M; Martyr, Anthony; Markova, Ivana; Roth, Ilona; Woods, Robert T; Whitaker, Christopher J; Clare, Linda

    2016-03-01

    The study investigated different types of awareness of memory dysfunction in dementia, specifically judgements concerning memory task performance or appraisal of everyday memory functioning and also exploring the neuropsychological correlates of such awareness. This was investigated in 76 people with dementia, comprising 46 patients with Alzheimer's disease (AD) and 30 patients with vascular dementia (VaD). The Memory Awareness Rating Scale (Clare et al., 2002, Neuropsychol Rehabil, 12, 341-362) was used, which includes an Objective-Judgement Discrepancy (OJD) technique involving comparison of subjective evaluation of performance on specific memory tasks with actual performance, and a Subjective Rating Discrepancy (SRD) technique, which compares self versus informant judgement of everyday memory function. The AD and VaD groups showed lower awareness than a normal control group for both types of measures, the AD group showing less awareness than the VaD group on the OJD measure. Regression analyses supported associations for both groups between memory impairment and the OJD measure and between naming impairment and the SRD measure. The findings are discussed in terms of neurocognitive theories accounting for loss of awareness in dementia. PMID:25488044

  4. Preserved memory monitoring but impaired memory control during episodic encoding in patients with schizophrenia.

    PubMed

    Bacon, Elisabeth; Izaute, Marie; Danion, Jean-Marie

    2007-03-01

    Metamemory awareness refers to the ability to monitor and control how well information is processed depending on the loads and needs of the task at hand. There is some evidence that metamemory functions are impaired in schizophrenia at the time of memory retrieval. This study investigated whether patients with schizophrenia exhibit metamemory abnormalities during the encoding of new information. The frequency of item presentation was varied. Both memory control and memory monitoring were assessed using study-time allocation and Judgments of Learning (JOL), respectively. Repeated items were recalled better by both groups, but memory performance was lower in patients than controls. Patients' behavior patterns were abnormal in terms of the study-time allocated for each item according to presentation frequency. Patients' JOLs were lower than those of controls but remained sensitive to item repetition. Patients' predictive values on memory accuracy were no different to those measured in controls. In addition, none of the patients reported using efficient strategies to help memorize target items. The results show a dissociation between memory control, which was impaired, and memory monitoring, which was spared, in patients with schizophrenia during encoding of new information. PMID:17286879

  5. Verbal memory impairments in schizophrenia associated with cortical thinning

    PubMed Central

    Guimond, S.; Chakravarty, M.M.; Bergeron-Gagnon, L.; Patel, R.; Lepage, M.

    2015-01-01

    Verbal memory (VM) represents one of the most affected cognitive domains in schizophrenia. Multiple studies have shown that schizophrenia is associated with cortical abnormalities, but it remains unclear whether these are related to VM impairments. Considering the vast literature demonstrating the role of the frontal cortex, the parahippocampal cortex, and the hippocampus in VM, we examined the cortical thickness/volume of these regions. We used a categorical approach whereby 27 schizophrenia patients with ‘moderate to severe’ VM impairments were compared to 23 patients with ‘low to mild’ VM impairments and 23 healthy controls. A series of between-group vertex-wise GLM on cortical thickness were performed for specific regions of interest defining the parahippocampal gyrus and the frontal cortex. When compared to healthy controls, patients with ‘moderate to severe’ VM impairments revealed significantly thinner cortex in the left frontal lobe, and the parahippocampal gyri. When compared to patients with ‘low to mild’ VM impairments, patients with ‘moderate to severe’ VM impairments showed a trend of thinner cortex in similar regions. Virtually no differences were observed in the frontal area of patients with ‘low to mild’ VM impairments relative to controls. No significant group differences were observed in the hippocampus. Our results indicate that patients with greater VM impairments demonstrate significant cortical thinning in regions known to be important in VM performance. Treating VM deficits in schizophrenia could have a positive effect on the brain; thus, subgroups of patients with more severe VM deficits should be a prioritized target in the development of new cognitive treatments. PMID:26909322

  6. Dietary ketosis enhances memory in mild cognitive impairment

    PubMed Central

    Krikorian, Robert; Shidler, Marcelle D; Dangelo, Krista; Couch, Sarah C; Benoit, Stephen C; Clegg, Deborah J

    2010-01-01

    We randomly assigned 23 older adults with Mild Cognitive Impairment to either a high carbohydrate or very low carbohydrate diet. Following the six-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p < 0.0001), fasting glucose (p = 0.009), and fasting insulin (p = 0.005). Level of depressive symptoms was not affected. Change in calorie intake, insulin level, and weight were not correlated with memory performance for the entire sample, although a trend toward a moderate relationship between insulin and memory was observed within the low carbohydrate group. Ketone levels were positively correlated with memory performance (p = 0.04). These findings indicate that very low carbohydrate consumption, even in the short-term, can improve memory function in older adults with increased risk for Alzheimer’s disease. While this effect may be attributable in part to correction of hyperinsulinemia, other mechanisms associated with ketosis such as reduced inflammation and enhanced energy metabolism also may have contributed to improved neurocognitive function. Further investigation of this intervention is warranted to evaluate its preventive potential and mechanisms of action in the context of early neurodegeneration. PMID:21130529

  7. Changes in Patterns of Age-Related Visual Impairment in the Netherlands: A Comparison of Two Cohorts of Patients Referred to Rehabilitation Programs 10 Years Apart

    ERIC Educational Resources Information Center

    van Rens, Ger H. M. B.; Lens, Judith A.; de Boer, Michael R.

    2006-01-01

    Most of the studies of the causes of visual impairment have been population-based studies. These population-based studies provide important information on the incidence and prevalence of "theoretical" eye problems in a community. However, not all those who are visually impaired, from a theoretical point of view, consider themselves as such and…

  8. Intellectual impairment, memory impairment, suggestibility and voir dire proceedings: a case study.

    PubMed

    Howells, K; Ward, M

    1994-04-01

    The psychology and psychiatry of interrogation, confession and testimony have recently become the subjects of considerable theoretical analysis, research and professional interest (Gudjonsson, 1992). A case study is reported involving a defendant whose testimony under police interrogation incriminated himself and 13 other defendants in a murder trial. Issues of intellectual impairment, memory impairment, confabulation and suggestibility were addressed in voir dire proceedings, and are described in this paper. The case also demonstrates the importance of psychological tests being administered by suitably qualified personnel. PMID:8028495

  9. The limits of arousal's memory-impairing effects on nearby information.

    PubMed

    Mather, Mara; Gorlick, Marissa A; Nesmith, Kathryn

    2009-01-01

    Showing an arousing central stimulus in a scene often leads to enhanced memory for the arousing central information and impaired memory for peripheral details. However, it is not clear from previous work whether arousing stimuli impair memory for all nonarousing nearby information or just background information. In several experiments, we tested how emotionally arousing pictures affect memory for nearby pictures and for background information. We found that when 2 pictures were presented together, an arousing picture did not affect item and location memory for the other picture. In contrast, an arousing picture impaired memory for a background pattern. These findings suggest that arousal impairs memory for information that is the target of perceptual suppression, such as background information when there is a figure-ground distinction, but does not impair memory for other foreground information. PMID:19827704

  10. Domain-Specific Treatment Effects in Children with Language and/or Working Memory Impairments: A Pilot Study

    ERIC Educational Resources Information Center

    Wener, Sarah E; Archibald, Lisa MD

    2011-01-01

    This pilot study with an n-of-1 design examined whether children with a specific language impairment without working memory impairment (SLI), a specific working memory impairment without language impairment (SWMI), or mixed language and working memory impairments (L&WMI) may respond differently to treatment targeting verbal or visuospatial…

  11. Mild Memory Impairment in Healthy Older Adults Is Distinct from Normal Aging

    ERIC Educational Resources Information Center

    Cargin, J. Weaver; Maruff, P.; Collie, A.; Masters, C.

    2006-01-01

    Mild memory impairment was detected in 28% of a sample of healthy community-dwelling older adults using the delayed recall trial of a word list learning task. Statistical analysis revealed that individuals with memory impairment also demonstrated relative deficits on other measures of memory, and tests of executive function, processing speed and…

  12. Postnatal TLR2 activation impairs learning and memory in adulthood.

    PubMed

    Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

    2015-08-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. PMID:26021559

  13. Postnatal TLR2 activation impairs learning and memory in adulthood

    PubMed Central

    Madar, Ravit; Rotter, Aviva; Ben-Asher, Hiba Waldman; Mughal, Mohamed R.; Arumugam, Thiruma V.; Wood, WH; Becker, KG; Mattson, Mark P.; Okun, Eitan

    2015-01-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. PMID:26021559

  14. A high fructose diet impairs spatial memory in male rats.

    PubMed

    Ross, A P; Bartness, T J; Mielke, J G; Parent, M B

    2009-10-01

    Over the past three decades there has been a substantial increase in the amount of fructose consumed by North Americans. Recent evidence from rodents indicates that hippocampal insulin signaling facilitates memory and excessive fructose consumption produces hippocampal insulin resistance. Based on this evidence, the present study tested the hypothesis that a high fructose diet would impair hippocampal-dependent memory. Adult male Sprague-Dawley rats (postnatal day 61) were fed either a control (0% fructose) or high fructose diet (60% of calories). Food intake and body mass were measured regularly. After 19 weeks, the rats were given 3 days of training (8 trials/day) in a spatial version of the water maze task, and retention performance was probed 48 h later. The high fructose diet did not affect acquisition of the task, but did impair performance on the retention test. Specifically, rats fed a high fructose diet displayed significantly longer latencies to reach the area where the platform had been located, made significantly fewer approaches to that area, and spent significantly less time in the target quadrant than did control diet rats. There was no difference in swim speed between the two groups. The retention deficits correlated significantly with fructose-induced elevations of plasma triglyceride concentrations. Consequently, the impaired spatial water maze retention performance seen with the high fructose diet may have been attributable, at least in part, to fructose-induced increases in plasma triglycerides. PMID:19500683

  15. Serotonin transporter deficiency in rats contributes to impaired object memory.

    PubMed

    Olivier, J D A; Jans, L A W; Blokland, A; Broers, N J; Homberg, J R; Ellenbroek, B A; Cools, A R

    2009-11-01

    Serotonin is well known for its role in affection, but less known for its role in cognition. The serotonin transporter (SERT) has an essential role in serotonergic neurotransmission as it determines the magnitude and duration of the serotonin signal in the synaptic cleft. There is evidence to suggest that homozygous SERT knockout rats (SERT(-/-)), as well as humans with the short SERT allele, show stronger cognitive effects than wild-type control rats (SERT(+/+)) and humans with the long SERT allele after acute tryptophan depletion. In rats, SERT genotype is known to affect brain serotonin levels, with SERT(-/-) rats having lower intracellular basal serotonin levels than wild-type rats in several brain areas. In the present study, it was investigated whether SERT genotype affects memory performance in an object recognition task with different inter-trial intervals. SERT(-/-), heterozygous SERT knockout (SERT(+/-)) and SERT(+/+) rats were tested in an object recognition test applying an inter-trial interval of 2, 4 and 8 h. SERT(-/-) and SERT(+/-) rats showed impaired object memory with an 8 h inter-trial interval, whereas SERT(+/+) rats showed intact object memory with this inter-trial interval. Although brain serotonin levels cannot fully explain the SERT genotype effect on object memory in rats, these results do indicate that serotonin is an important player in object memory in rats, and that lower intracellular serotonin levels lead to enhanced memory loss. Given its resemblance with the human SERT-linked polymorphic region and propensity to develop depression-like symptoms, our findings may contribute to further understanding of mechanisms underlying cognitive deficits in depression. PMID:19740092

  16. The role of hepatic & splenic macrophages in E. coli-induced memory impairments in aged rats

    PubMed Central

    Barrientos, Ruth M.; Thompson, Vanessa M.; Arnold, T. Hayes; Frank, Matthew G.; Watkins, Linda R.; Maier, Steven F.

    2014-01-01

    Bi-directional communication between the peripheral and central nervous systems has been extensively demonstrated. Aged rats exhibit a prolonged proinflammatory response in the hippocampus region of the brain following a peripheral bacterial infection, and this response in turn causes robust memory declines. Here we aimed to determine whether hepatic or splenic macrophages play a role in the maintenance of this central response. Proinflammatory cytokines measured in liver and spleen four days following an E. coli infection revealed a potentiated proinflammatory response in liver, and to a lesser extent in spleen, in aged relative to young rats. To determine whether this potentiated response was caused by impaired bacterial clearance in these organs, E. coli colony forming units in liver and spleen were measured 4 days after infection, and there were no difference between young and aged rats in either organ. No E. coli was detected in the hippocampus, eliminating the possibility that the aged blood brain barrier allowed E. coli to enter the brain. Depletion of hepatic and splenic macrophages with clodronate-encapsulated liposomes effectively eliminated the proinflammatory response to E. coli at four days in both organs. However, this treatment failed to reduce the proinflammatory response in the hippocampus. Moreover, depletion of peripheral macrophages from liver and spleen did not prevent E. coli-induced memory impairment. These data strongly suggest that hepatic and splenic macrophages do not play a major role in the long-lasting maintenance of the proinflammatory response in the hippocampus of aged rats following a bacterial infection, or the memory declines that this response produces. PMID:25043992

  17. Improved effect of Pycnogenol on impaired spatial memory function in partial androgen deficiency rat model.

    PubMed

    Hasegawa, Noboru; Mochizuki, Miyako

    2009-06-01

    The improved effect of Pycnogenol on impaired spatial memory function was studied in orchidectomized rats. Endogenous testosterone levels were decreased by approximately one-half for 3 months after castration. In the radial arm maze, castration significantly impaired working and reference memory function without lowering motor function. Pycnogenol increased the NGF content in the hippocampus and cortex, and improved the spatial memory impairment. These observations confirmed that diagnostic accuracy can be improved by Pycnogenol in androgen-deficient rats. PMID:19142987

  18. 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…

  19. Memory for Items and Relationships among Items Embedded in Realistic Scenes: Disproportionate Relational Memory Impairments in Amnesia

    PubMed Central

    Hannula, Deborah E.; Tranel, Daniel; Allen, John S.; Kirchhoff, Brenda A.; Nickel, Allison E.; Cohen, Neal J.

    2014-01-01

    Objective The objective of this study was to examine the dependence of item memory and relational memory on medial temporal lobe (MTL) structures. Patients with amnesia, who either had extensive MTL damage or damage that was relatively restricted to the hippocampus, were tested, as was a matched comparison group. Disproportionate relational memory impairments were predicted for both patient groups, and those with extensive MTL damage were also expected to have impaired item memory. Method Participants studied scenes, and were tested with interleaved two-alternative forced-choice probe trials. Probe trials were either presented immediately after the corresponding study trial (lag 1), five trials later (lag 5), or nine trials later (lag 9) and consisted of the studied scene along with a manipulated version of that scene in which one item was replaced with a different exemplar (item memory test) or was moved to a new location (relational memory test). Participants were to identify the exact match of the studied scene. Results As predicted, patients were disproportionately impaired on the test of relational memory. Item memory performance was marginally poorer among patients with extensive MTL damage, but both groups were impaired relative to matched comparison participants. Impaired performance was evident at all lags, including the shortest possible lag (lag 1). Conclusions The results are consistent with the proposed role of the hippocampus in relational memory binding and representation, even at short delays, and suggest that the hippocampus may also contribute to successful item memory when items are embedded in complex scenes. PMID:25068665

  20. Memory impairment is not sufficient for choice blindness to occur

    PubMed Central

    Sagana, Anna; Sauerland, Melanie; Merckelbach, Harald

    2014-01-01

    Choice blindness refers to the phenomenon that people can be easily misled about the choices they made in the recent past. The aim of this study was to explore the cognitive mechanisms underlying choice blindness. Specifically, we tested whether memory impairment may account for choice blindness. A total of N = 88 participants provided sympathy ratings on 10-point scales for 20 female faces. Subsequently, participants motivated some of their ratings. However, on three trials, they were presented with sympathy ratings that deviated from their original ratings by three full scale points. On nearly 41% of the trials, participants failed to detect (i.e., were blind) the manipulation. After a short interval, participants were informed that some trials had been manipulated and were asked to recall their original ratings. Participants adopted the manipulated outcome in only 3% of the trials. Furthermore, the extent to which the original ratings were accurately remembered was not higher for detected as compared with non-detected trials. From a theoretical point of view our findings indicate that memory impairment does not fully account for blindness phenomena. PMID:24904467

  1. Memory impairment in aged primates is associated with region-specific network dysfunction.

    PubMed

    Thomé, A; Gray, D T; Erickson, C A; Lipa, P; Barnes, C A

    2016-09-01

    Age-related deficits in episodic memory result, in part, from declines in the integrity of medial temporal lobe structures, such as the hippocampus, but are not thought to be due to widespread loss of principal neurons. Studies in rodents suggest, however, that inhibitory interneurons may be particularly vulnerable in advanced age. Optimal encoding and retrieval of information depend on a balance of excitatory and inhibitory transmission. It is not known whether a disruption of this balance is observed in aging non-human primates, and whether such changes affect network function and behavior. To examine this question, we combine large-scale electrophysiological recordings with cell-type-specific imaging in the medial temporal lobe of cognitively assessed, aged rhesus macaques. We found that neuron excitability in the hippocampal region CA3 is negatively correlated with the density of somatostatin-expressing inhibitory interneurons in the vicinity of the recording electrodes in the stratum oriens. By contrast, no hyperexcitability or interneuron loss was observed in the perirhinal cortex of these aged, memory-impaired monkeys. These data provide a link, for the first time, between selective increases in principal cell excitability and declines in a molecularly defined population of interneurons that regulate network inhibition. PMID:26503764

  2. Memory impairment in aged primates is associated with region-specific network dysfunction

    PubMed Central

    Thomé, Alexander; Gray, Daniel T.; Erickson, Cynthia A.; Lipa, Peter; Barnes, Carol A.

    2015-01-01

    Age-related deficits in episodic memory result, in part, from declines in the integrity of medial temporal lobe structures, such as the hippocampus, but are not thought to be due to widespread loss of principal neurons. Studies in rodents suggest, however, that inhibitory interneurons may be particularly vulnerable in advanced age. Optimal encoding and retrieval of information depend on a balance of excitatory and inhibitory transmission. It is not known whether a disruption of this balance is observed in aging nonhuman primates, and whether such changes affect network function and behavior. To examine this question we combine large scale electrophysiological recordings with cell type-specific imaging in the medial temporal lobe of cognitively-assessed, aged rhesus macaques. We found that neuron excitability in hippocampal region CA3 is negatively correlated with the density of the somatostatin-expressing inhibitory interneurons in the vicinity of the recording electrodes in stratum oriens. By contrast, no hyperexcitability or interneuron loss was observed in the perirhinal cortex of these aged, memory-impaired monkeys. These data provide a link, for the first time, between selective increases in principal cell excitability and declines in a molecularly-defined population of interneurons that regulate network inhibition. PMID:26503764

  3. Age-related impairment of humoral response to influenza is associated with changes in antigen specific T follicular helper cell responses.

    PubMed

    Lefebvre, Julie S; Masters, April R; Hopkins, Jacob W; Haynes, Laura

    2016-01-01

    T follicular helper (TFH) cell responses are essential for generation of protective humoral immunity during influenza infection. Aging has a profound impact on CD4(+) T cell function and humoral immunity, yet the impact of aging on antigen specific TFH responses remains unclear. Influenza specific TFH cells are generated in similar numbers in young and aged animals during infection, but TFH cells from aged mice exhibit significant differences, including reduced expression of ICOS and elevated production of IL-10 and IFNγ, which potentially impairs interaction with cognate B cells. Also, more influenza specific T cells in aged mice have a regulatory phenotype, which could contribute to the impaired TFH function. Adoptive transfer studies with young T cells demonstrated that TGF-β1 in the aged environment can drive increased regulatory T cell accumulation. Aging and the aged environment thus impact antigen specific TFH cell function and formation, which contribute to reduced protective humoral responses. PMID:27109638

  4. Age-related impairment of humoral response to influenza is associated with changes in antigen specific T follicular helper cell responses

    PubMed Central

    Lefebvre, Julie S; Masters, April R; Hopkins, Jacob W; Haynes, Laura

    2016-01-01

    T follicular helper (TFH) cell responses are essential for generation of protective humoral immunity during influenza infection. Aging has a profound impact on CD4+ T cell function and humoral immunity, yet the impact of aging on antigen specific TFH responses remains unclear. Influenza specific TFH cells are generated in similar numbers in young and aged animals during infection, but TFH cells from aged mice exhibit significant differences, including reduced expression of ICOS and elevated production of IL-10 and IFNγ, which potentially impairs interaction with cognate B cells. Also, more influenza specific T cells in aged mice have a regulatory phenotype, which could contribute to the impaired TFH function. Adoptive transfer studies with young T cells demonstrated that TGF-β1 in the aged environment can drive increased regulatory T cell accumulation. Aging and the aged environment thus impact antigen specific TFH cell function and formation, which contribute to reduced protective humoral responses. PMID:27109638

  5. Age-Related Macular Degeneration-Associated Silent Polymorphisms in HtrA1 Impair Its Ability To Antagonize Insulin-Like Growth Factor 1

    PubMed Central

    Jacobo, Sarah Melissa P.; DeAngelis, Margaret M.; Kim, Ivana K.

    2013-01-01

    Synonymous single nucleotide polymorphisms (SNPs) within a transcript's coding region produce no change in the amino acid sequence of the protein product and are therefore intuitively assumed to have a neutral effect on protein function. We report that two common variants of high-temperature requirement A1 (HTRA1) that increase the inherited risk of neovascular age-related macular degeneration (NvAMD) harbor synonymous SNPs within exon 1 of HTRA1 that convert common codons for Ala34 and Gly36 to less frequently used codons. The frequent-to-rare codon conversion reduced the mRNA translation rate and appeared to compromise HtrA1's conformation and function. The protein product generated from the SNP-containing cDNA displayed enhanced susceptibility to proteolysis and a reduced affinity for an anti-HtrA1 antibody. The NvAMD-associated synonymous polymorphisms lie within HtrA1's putative insulin-like growth factor 1 (IGF-1) binding domain. They reduced HtrA1's abilities to associate with IGF-1 and to ameliorate IGF-1-stimulated signaling events and cellular responses. These observations highlight the relevance of synonymous codon usage to protein function and implicate homeostatic protein quality control mechanisms that may go awry in NvAMD. PMID:23478260

  6. Age-related impairment of bones' adaptive response to loading in mice is associated with sex-related deficiencies in osteoblasts but no change in osteocytes.

    PubMed

    Meakin, Lee B; Galea, Gabriel L; Sugiyama, Toshihiro; Lanyon, Lance E; Price, Joanna S

    2014-08-01

    Bones adjust their mass and architecture to be sufficiently robust to withstand functional loading by adapting to their strain environment. This mechanism appears less effective with age, resulting in low bone mass. In male and female young adult (17-week-old) and old (19-month-old) mice, we investigated the effect of age in vivo on bones' adaptive response to loading and in vitro in primary cultures of osteoblast-like cells derived from bone cortices. Right tibias were axially loaded on alternate days for 2 weeks. Left tibias were non-loaded controls. In a separate group, the number of sclerostin-positive osteocytes and the number of periosteal osteoblasts were analyzed 24 hours after a single loading episode. The responses to strain of the primary osteoblast-like cells derived from these mice were assessed by EGR2 expression, change in cell number and Ki67 immunofluorescence. In young male and female mice, loading increased trabecular thickness and the number of trabecular connections. Increase in the number of trabecular connections was impaired with age but trabecular thickness was not. In old mice, the loading-related increase in periosteal apposition of the cortex was less than in young ones. Age was associated with a lesser loading-related increase in osteoblast number on the periosteal surface but had no effect on loading-related reduction in the number of sclerostin-positive osteocytes. In vitro, strain-related proliferation of osteoblast-like cells was lower in cells from old than young mice. Cells from aged female mice demonstrated normal entry into the cell cycle but subsequently arrested in G2 phase, reducing strain-related increases in cell number. Thus, in both male and female mice, loading-related adaptive responses are impaired with age. This impairment is different in females and males. The deficit appears to occur in osteoblasts' proliferative responses to strain rather than earlier strain-related responses in the osteocytes. PMID:24644060

  7. The Cognitive and Neural Expression of Semantic Memory Impairment in Mild Cognitive Impairment and Early Alzheimer's Disease

    ERIC Educational Resources Information Center

    Joubert, Sven; Brambati, Simona M.; Ansado, Jennyfer; Barbeau, Emmanuel J.; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Celine; Kergoat, Marie-Jeanne

    2010-01-01

    Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to…

  8. Is Body Mass Index Associated With the Development of Age-Related Hearing Impairment in Koreans? The Korean National Health and Nutrition Examination Survey 2009–2012

    PubMed Central

    Jung, Da Jung; Jang, Jeong Hun; Lee, Kyu-Yup

    2016-01-01

    Objectives The aim of this study was to evaluate whether body mass index (BMI) is associated with age-related hearing loss (ARHL) in the Asian elderly population. Methods Data from the Korean National Health and Nutrition Examination Survey 2009–2012 were used for the analyses. The pure tones at 0.5 and 1 kHz of both ears of each subject were averaged to obtain the low-frequency, those at 2 and 3 kHz were averaged to obtain the mid-frequency, and those at 4 and 6 kHz were averaged to obtain the high-frequency. The average hearing threshold (AHT) was calculated as pure tone average at 4 frequencies in the better ear. ARHL was defined as the AHT >25 dB. Results Univariate analyses revealed an increase in the BMI tertile in men was associated with a decreased low-frequency threshold, while an increase in the BMI tertile in women was associated with decreased mid- and high-frequency thresholds. Multivariate analyses adjusted for confounders show no significant differences in low-, mid-, or high-frequency. There was no significant difference in the prevalence of ARHL by BMI tertiles. Linear regression analyses show no association between BMI and low-, mid-, and high-frequency or AHTs. The area under the receiver operating characteristic curve values for AHT was 0.515 in men and 0.522 in women. The logistic regression analyses showed no association between BMI and ARHL in either sex. Conclusion BMI is not advantageous for the prediction of ARHL. In future epidemiological studies, BMI as a covariate of obesity may be replaced by other active metabolic parameters that have better predictive ability of ARHL than BMI. PMID:27090278

  9. 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

  10. Working Memory and Learning in Children with Developmental Coordination Disorder and Specific Language Impairment

    ERIC Educational Resources Information Center

    Alloway, Tracy Packiam; Archibald, Lisa

    2008-01-01

    The authors compared 6- to 11-year-olds with developmental coordination disorder (DCD) and those with specific language impairment (SLI) on measures of memory (verbal and visuospatial short-term and working memory) and learning (reading and mathematics). Children with DCD with typical language skills were impaired in all four areas of memory…

  11. Age-Related Impairment of Bones' Adaptive Response to Loading in Mice Is Associated With Sex-Related Deficiencies in Osteoblasts but No Change in Osteocytes†

    PubMed Central

    Meakin, Lee B; Galea, Gabriel L; Sugiyama, Toshihiro; Lanyon, Lance E; Price, Joanna S

    2014-01-01

    Bones adjust their mass and architecture to be sufficiently robust to withstand functional loading by adapting to their strain environment. This mechanism appears less effective with age, resulting in low bone mass. In male and female young adult (17-week-old) and old (19-month-old) mice, we investigated the effect of age in vivo on bones' adaptive response to loading and in vitro in primary cultures of osteoblast-like cells derived from bone cortices. Right tibias were axially loaded on alternate days for 2 weeks. Left tibias were non-loaded controls. In a separate group, the number of sclerostin-positive osteocytes and the number of periosteal osteoblasts were analyzed 24 hours after a single loading episode. The responses to strain of the primary osteoblast-like cells derived from these mice were assessed by EGR2 expression, change in cell number and Ki67 immunofluorescence. In young male and female mice, loading increased trabecular thickness and the number of trabecular connections. Increase in the number of trabecular connections was impaired with age but trabecular thickness was not. In old mice, the loading-related increase in periosteal apposition of the cortex was less than in young ones. Age was associated with a lesser loading-related increase in osteoblast number on the periosteal surface but had no effect on loading-related reduction in the number of sclerostin-positive osteocytes. In vitro, strain-related proliferation of osteoblast-like cells was lower in cells from old than young mice. Cells from aged female mice demonstrated normal entry into the cell cycle but subsequently arrested in G2 phase, reducing strain-related increases in cell number. Thus, in both male and female mice, loading-related adaptive responses are impaired with age. This impairment is different in females and males. The deficit appears to occur in osteoblasts' proliferative responses to strain rather than earlier strain-related responses in the osteocytes. © 2014 The Authors

  12. The 12-item Buschke memory test: appropriate for use across levels of impairment.

    PubMed

    O'Connell, Megan E; Tuokko, Holly

    2002-01-01

    Monitoring cognitive functions as older adults move from independent to assisted living is of utmost importance with respect to care planning. To this end, we examined the utility of a 12- item, free and cued recall, selective reminding, memory task for assessing persons across levels of functioning. Using cross-sectional data from the Canadian Study of Health and Aging, it was observed that the 12-item Buschke memory test was well tolerated by participants regardless of their level of impairment. Further, various measures from the memory task differentiated among participants with different levels of impairment: Individuals living in the community performed better than those in institutions; individuals with no or mild functional impairment performed better than individuals with moderate or severe functional impairments; individuals with mild dementia performed better than those with moderate to severe dementia. Normative data are provided for this easily administered and well-tolerated memory measure. Key words: cognitive assessment, memory test, dementia, levels of impairment PMID:12584076

  13. Verbal memory impairment in subcortical ischemic vascular disease: a descriptive analysis in CADASIL.

    PubMed

    Epelbaum, S; Benisty, S; Reyes, S; O'Sullivan, M; Jouvent, E; Düring, M; Hervé, D; Opherk, C; Hernandez, K; Kurtz, A; Viswanathan, A; Bousser, M G; Dichgans, M; Chabriat, H

    2011-12-01

    In the elderly, the high prevalence of Alzheimer's disease neuropathology presents a major challenge to the investigation of memory decline in common diseases such as small vessel disease. CADASIL represents a unique clinical model to determine the spectrum of memory impairment in subcortical ischemic vascular dementia (SIVD). One hundred and forty CADASIL patients underwent detailed clinical, neuropsychological and imaging analyses. The Free and Cued Selective Reminding Test was used as a measure of verbal memory. Forty-four out of 140 CADASIL patients (31.4%) presented with memory impairment according to this test. Eight out of 44 (18.2%) subjects with memory impairment matched the definition of the amnestic syndrome of hippocampal type. While alterations in spontaneous recall were related to the severity of subcortical ischemic lesions, the profile of memory impairment, particularly the sensitivity to cueing was found related to other factors such as hippocampal atrophy. PMID:20149485

  14. Impairment of fear memory consolidation and expression by antihistamines.

    PubMed

    Nonaka, Ayako; Masuda, Fumitaka; Nomura, Hiroshi; Matsuki, Norio

    2013-02-01

    Antihistamines are widely used to treat allergy symptoms. First-generation antihistamines have adverse effects on the central nervous system (CNS), such as hypnotic and amnesic effects, whereas second-generation antihistamines have poor brain penetration, and therefore, have fewer CNS-related adverse effects. Memory consists of several phases, including acquisition, consolidation, expression, and extinction. It remains unclear whether these phases are affected by antihistamines. We investigated the effects of diphenhydramine, a first-generation antihistamine, and levocetirizine and olopatadine, second-generation antihistamines, on memory phases. Mice were subjected to fear conditioning on day 1 and tested on day 2. Antihistamines were administered before conditioning, immediately after conditioning, or before the test session. Diphenhydramine (30mg/kg) decreased freezing time when administered immediately after conditioning or before the test session. These effects were not attributable to a change in locomotor activity. Levocetirizine (0.1, 1, 10mg/kg) and olopatadine (1, 10, 20mg/kg) had no effects on conditioned fear. We also examined the effect of diphenhydramine and levocetirizine on the expression of an activity-dependent gene associated with the test session. Diphenhydramine, but not levocetirizine, increased Arc transcription in the central nucleus of the amygdala. These data indicate that diphenhydramine, but not levocetirizine or olopatadine, impairs the consolidation and expression of conditioned fear. PMID:23178698

  15. Cortical thinning in individuals with subjective memory impairment.

    PubMed

    Meiberth, Dix; Scheef, Lukas; Wolfsgruber, Steffen; Boecker, Henning; Block, Wolfgang; Träber, Frank; Erk, Susanne; Heneka, Michael T; Jacobi, Heike; Spottke, Annika; Walter, Henrik; Wagner, Michael; Hu, Xiaochen; Jessen, Frank

    2015-01-01

    Elderly individuals with subjective memory impairment (SMI) report memory decline, but perform within the age-, gender-, and education- adjusted normal range on neuropsychological tests. Longitudinal studies indicate SMI as a risk factor or early sign of Alzheimer's disease (AD). There is increasing evidence from neuroimaging that at the group level, subjects with SMI display evidence of AD related pathology. This study aimed to determine differences in cortical thickness between individuals with SMI and healthy control subjects (CO) using the FreeSurfer environment. 110 participants (41 SMI/69 CO) underwent structural 3D-T1 MR imaging. Cortical thickness values were compared between groups in predefined AD-related brain regions of the medial temporal lobe, namely the bilateral entorhinal cortex and bilateral parahippocampal cortex. Cortical thickness reduction was observed in the SMI group compared to controls in the left entorhinal cortex (p = 0.003). We interpret our findings as evidence of early AD-related brain changes in persons with SMI. PMID:25471190

  16. Acute and chronic tramadol administration impair spatial memory in rat

    PubMed Central

    Hosseini-Sharifabad, Ali; Rabbani, Mohammad; Sharifzadeh, Mohammad; Bagheri, Narges

    2016-01-01

    Tramadol hydrochloride, a synthetic opioid, acts via a multiple mechanism of action. Tramadol can potentially change the behavioral phenomena. The present study evaluates the effect of tramadol after single or multiple dose/s on the spatial memory of rat using object recognition task (ORT). Tramadol, 20 mg/kg, was injected intraperitoneally (i.p) as a single dose or once a day for 21 successive days considered as acute or chronic treatment respectively. After treatment, animals underwent two trials in the ORT. In the first trial (T1), animals encountered with two identical objects for exploration in a five-minute period. After 1 h, in the T2 trial, the animals were exposed to a familiar and a nonfamiliar object. The exploration times and frequency of the exploration for any objects were recorded. The results showed that tramadol decreased the exploration times for the nonfamiliar object in the T2 trial when administered either as a single dose (P<0.001) or as the multiple dose (P<0.05) compared to the respective control groups. Both acute and chronic tramadol administration eliminated the different frequency of exploration between the familiar and nonfamiliar objects. Our findings revealed that tramadol impaired memory when administered acutely or chronically. Single dose administration of tramadol showed more destructive effect than multiple doses of tramadol on the memory. The observed data can be explained by the inhibitory effects of tramadol on the wide range of neurotransmitters and receptors including muscarinic, N-methyl D-aspartate, AMPA as well as some second messenger like cAMP and cGMP or its stimulatory effect on the opioid, gama amino butyric acid, dopamine or serotonin in the brain. PMID:27051432

  17. Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.

    PubMed

    Atsak, Piray; Guenzel, Friederike M; Kantar-Gok, Deniz; Zalachoras, Ioannis; Yargicoglu, Piraye; Meijer, Onno C; Quirarte, Gina L; Wolf, Oliver T; Schwabe, Lars; Roozendaal, Benno

    2016-05-01

    Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress

  18. Genetic Disruption of the Core Circadian Clock Impairs Hippocampus-Dependent Memory

    ERIC Educational Resources Information Center

    Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao; Storm, Daniel R.

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1[superscript -/-] mice, which are arrhythmic…

  19. Working Memory Functioning in Children with Learning Disorders and Specific Language Impairment

    ERIC Educational Resources Information Center

    Schuchardt, Kirsten; Bockmann, Ann-Katrin; Bornemann, Galina; Maehler, Claudia

    2013-01-01

    Purpose: On the basis of Baddeley's working memory model (1986), we examined working memory functioning in children with learning disorders with and without specific language impairment (SLI). We pursued the question whether children with learning disorders exhibit similar working memory deficits as children with additional SLI. Method: In…

  20. Intra-Amygdala Injections of CREB Antisense Impair Inhibitory Avoidance Memory: Role of Norepinephrine and Acetylcholine

    ERIC Educational Resources Information Center

    Canal, Clinton E.; Chang, Qing; Gold, Paul E.

    2008-01-01

    Infusions of CREB antisense into the amygdala prior to training impair memory for aversive tasks, suggesting that the antisense may interfere with CRE-mediated gene transcription and protein synthesis important for the formation of new memories within the amygdala. However, the amygdala also appears to modulate memory formation in distributed…

  1. Age-Related Differences in Memory and Executive Functions in Healthy "APOE"[epsilon]4 Carriers: The Contribution of Individual Differences in Prefrontal Volumes and Systolic Blood Pressure

    ERIC Educational Resources Information Center

    Bender, Andrew R.; Raz, Naftali

    2012-01-01

    Advanced age and vascular risk are associated with declines in the volumes of multiple brain regions, especially the prefrontal cortex, and the hippocampus. Older adults, even unencumbered by declining health, perform less well than their younger counterparts in multiple cognitive domains, such as episodic memory, executive functions, and speed of…

  2. 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 ...

  3. Examining factors involved in stress-related working memory impairments: Independent or conditional effects?

    PubMed

    Banks, Jonathan B; Tartar, Jaime L; Tamayo, Brittney A

    2015-12-01

    A large and growing body of research demonstrates the impact of psychological stress on working memory. However, the typical study approach tests the effects of a single biological or psychological factor on changes in working memory. The current study attempted to move beyond the standard single-factor assessment by examining the impact of 2 possible factors in stress-related working memory impairments. To this end, 60 participants completed a working memory task before and after either a psychological stressor writing task or a control writing task and completed measures of both cortisol and mind wandering. We also included a measure of state anxiety to examine the direct and indirect effect on working memory. We found that mind wandering mediated the relationship between state anxiety and working memory at the baseline measurement. This indirect relationship was moderated by cortisol, such that the impact of mind wandering on working memory increased as cortisol levels increased. No overall working memory impairment was observed following the stress manipulation, but increases in state anxiety and mind wandering were observed. State anxiety and mind wandering independently mediated the relationship between change in working memory and threat perception. The indirect paths resulted in opposing effects on working memory. Combined, the findings from this study suggest that cortisol enhances the impact of mind wandering on working memory, that state anxiety may not always result in stress-related working memory impairments, and that high working memory performance can protect against mind wandering. PMID:26098727

  4. Flashbulb Memories and Posttraumatic Stress Reactions Across the Life-Span: Age-related effects of the German Occupation of Denmark during WWII

    PubMed Central

    Berntsen, Dorthe; Rubin, David C.

    2014-01-01

    A representative sample of older Danes were interviewed about experiences from the German occupation of Denmark in WWII. The number of participants with flashbulb memories for the German invasion (1940) and capitulation (1945) increased with participants’ age at the time of the events up to age 8. Among participants under 8 years at the time of their most traumatic event, age at the time correlated positively with current level of posttraumatic stress reactions, vividness of stressful memories and their centrality to life-story and identity. These findings were replicated in Study 2 for self-nominated stressful events sampled from the entire life span using a representative sample of Danes born after 1945. The results are discussed in relation to Posttraumatic Stress Disorder (PTSD) and childhood amnesia. PMID:16594798

  5. Flashbulb memories and posttraumatic stress reactions across the life span: age-related effects of the German occupation of Denmark during World War II.

    PubMed

    Berntsen, Dorthe; Rubin, David C

    2006-03-01

    A representative sample of older Danes were interviewed about experiences from the German occupation of Denmark in World War II. The number of participants with flashbulb memories for the German invasion (1940) and capitulation (1945) increased with participants' age at the time of the events up to age 8. Among participants under 8 years at the time of their most traumatic event, age at the time correlated positively with the current level of posttraumatic stress reactions and the vividness of stressful memories and their centrality to life story and identity. These findings were replicated in Study 2 for self-nominated stressful events sampled from the entire life span using a representative sample of Danes born after 1945. The results are discussed in relation to posttraumatic stress disorder and childhood amnesia. PMID:16594798

  6. Prevalence and incidence of blindness and other degrees of sight impairment in patients treated for neovascular age-related macular degeneration in a well-defined region of the United Kingdom

    PubMed Central

    Buckle, M; Lee, A; Mohamed, Q; Fletcher, E; Sallam, A; Healy, R; Stratton, I; Tufail, A; Johnston, R L

    2015-01-01

    Aims This study aimed to evaluate the incidence and prevalence of blindness, sight impairment, and other visual acuity (VA) states in patients receiving ranibizumab for neovascular age-related macular degeneration (nAMD) in Gloucestershire. Methods Serial VA and injection data for all treatment-naive patients receiving their first intravitreal injections of ranibizumab for nAMD in the Gloucestershire National Health Service Ophthalmology department between 2008 and 2010 were extracted from an electronic medical record system. Results The prevalence of blindness (VA in the better-seeing eye ≤25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters) at the time of first intravitreal injection was 0.8%, increasing to 3.5% after 3 years. The prevalence of sight impairment (VA in the better-seeing eye 26–39 ETDRS letters) increased from 4.1% at baseline to 5.5% after 3 years. The incidence of initiating ranibizumab treatment for nAMD in people aged ≥50 years in Gloucestershire was 111 people per 100 000 population in 2009, and 97 people in 2010. The incidence of patients meeting the visual criteria for blindness and sight impairment registration from treated nAMD in people aged ≥50 years in Gloucestershire was 3.5 and 9.7 people, respectively per 100 000 population in 2010. Conclusion This is the first real-world study on the incidence and prevalence of eligibility for blindness and sight impairment registration in treated nAMD in the UK based on VA data. The incidence and prevalence of eligibility for certification of blindness or sight impairment in patients treated with ranibizumab for nAMD is low in Gloucestershire, with only 3.6% of the incident population progressing to blindness in 2010. PMID:25592123

  7. Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype.

    PubMed

    Reger, M A; Watson, G S; Frey, W H; Baker, L D; Cholerton, B; Keeling, M L; Belongia, D A; Fishel, M A; Plymate, S R; Schellenberg, G D; Cherrier, M M; Craft, S

    2006-03-01

    Raising insulin acutely in the periphery and in brain improves verbal memory. Intranasal insulin administration, which raises insulin acutely in the CNS without raising plasma insulin levels, provides an opportunity to determine whether these effects are mediated by central insulin or peripheral processes. Based on prior research with intravenous insulin, we predicted that the treatment response would differ between subjects with (epsilon4+) and without (epsilon4-) the APOE-epsilon4 allele. On separate mornings, 26 memory-impaired subjects (13 with early Alzheimer's disease and 13 with amnestic mild cognitive impairment) and 35 normal controls each underwent three intranasal treatment conditions consisting of saline (placebo) or insulin (20 or 40 IU). Cognition was tested 15 min post-treatment, and blood was acquired at baseline and 45 min after treatment. Intranasal insulin treatment did not change plasma insulin or glucose levels. Insulin treatment facilitated recall on two measures of verbal memory in memory-impaired epsilon4- adults. These effects were stronger for memory-impaired epsilon4- subjects than for memory-impaired epsilon4+ subjects and normal adults. Unexpectedly, memory-impaired epsilon4+ subjects showed poorer recall following insulin administration on one test of memory. These findings suggest that intranasal insulin administration may have therapeutic benefit without the risk of peripheral hypoglycemia and provide further evidence for apolipoprotein E (APOE) related differences in insulin metabolism. PMID:15964100

  8. Visual and Visuospatial Short-Term Memory in Mild Cognitive Impairment and Alzheimer Disease: Role of Attention

    ERIC Educational Resources Information Center

    Alescio-Lautier, B.; Michel, B. F.; Herrera, C.; Elahmadi, A.; Chambon, C.; Touzet, C.; Paban, V.

    2007-01-01

    It has been proposed that visual recognition memory and certain attentional mechanisms are impaired early in Alzheimer disease (AD). Little is known about visuospatial recognition memory in AD. The crucial role of the hippocampus on spatial memory and its damage in AD suggest that visuospatial recognition memory may also be impaired early. The aim…

  9. Acute stress impairs the retrieval of extinction memory in humans

    PubMed Central

    Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.

    2014-01-01

    Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less

  10. Specific marker of feigned memory impairment: The activation of left superior frontal gyrus.

    PubMed

    Chen, Zi-Xiang; Xue, Li; Liang, Chun-Yu; Wang, Li-Li; Mei, Wei; Zhang, Qiang; Zhao, Hu

    2015-11-01

    Faking memory impairment means normal people complain lots of memory problems without organic damage in forensic assessments. Using alternative forced-choice paradigm, containing digital or autobiographical information, previous neuroimaging studies have indicated that faking memory impairment could cause the activation in the prefrontal and parietal regions, and might involve a fronto-parietal-subcortical circuit. However, it is still unclear whether different memory types have influence on faking or not. Since different memory types, such as long-term memory (LTM) and short-term memory (STM), were found supported by different brain areas, we hypothesized that feigned STM or LTM impairment had distinct neural activation mapping. Besides that, some common neural correlates may act as the general characteristic of feigned memory impairment. To verify this hypothesis, the functional magnetic resonance imaging (fMRI) combined with an alternative word forced-choice paradigm were used in this study. A total of 10 right-handed participants, in this study, had to perform both STW and LTM tasks respectively under answering correctly, answering randomly and feigned memory impairment conditions. Our results indicated that the activation of the left superior frontal gyrus and the left medial frontal gyrus was associated with feigned LTM impairment, whereas the left superior frontal gyrus, the left precuneus and the right anterior cingulate cortex (ACC) were highly activated while feigning STM impairment. Furthermore, an overlapping was found in the left superior frontal gyrus, and it suggested that the activity of the left superior frontal gyrus might be acting as a specific marker of feigned memory impairment. PMID:26479324

  11. Structural MRI Correlates of Episodic Memory Processes in Parkinson’s Disease Without Mild Cognitive Impairment

    PubMed Central

    Pirogovsky-Turk, Eva; Filoteo, J. Vincent; Litvan, Irene; Harrington, Deborah L.

    2016-01-01

    Background Changes in episodic memory are common early in Parkinson’s disease (PD) and may be a risk factor for future cognitive decline. Although medial temporal lobe (MTL) memory and frontostriatal (FS) executive systems are thought to play different roles in distinct components of episodic memory impairment in PD, no study has investigated whether different aspects of memory functioning are differentially associated with MTL and FS volumes in nondemented patients without mild cognitive impairment (PD-woMCI). Objectives The present study investigated MRI markers of different facets of memory functioning in 48 PD-woMCI patients and 42 controls. Methods Regional volumes were measured in structures comprising the MTL and FS systems and then correlated with key indices of memory from the California Verbal Learning Test. Results In PD-woMCI patients, memory was impaired only for verbal learning, which was not associated with executive, attention/working memory, or visuospatial functioning. Despite an absence of cortical atrophy, smaller right MTL volumes in patients were associated with poorer verbal learning, long delayed free recall, long delayed cued recall, and recognition memory hits and false positives. Smaller right pars triangularis (inferior frontal) volumes were also associated with poorer long delayed cued recall and recognition memory hits. These relationships were not found in controls. Conclusions The findings indicate that MTL volumes are sensitive to subtle changes in almost all facets of memory in PD-woMCI, whereas FS volumes are sensitive only to memory performances in cued-testing formats. PMID:26577652

  12. Enhanced resting-state functional connectivity between core memory-task activation peaks is associated with memory impairment in MCI.

    PubMed

    Zhang, Yifei; Simon-Vermot, Lee; Araque Caballero, Miguel Á; Gesierich, Benno; Taylor, Alexander N W; Duering, Marco; Dichgans, Martin; Ewers, Michael

    2016-09-01

    Resting-state functional connectivity (FC) is altered in Alzheimer's disease (AD) but its predictive value for episodic memory impairment is debated. Here, we aimed to assess whether resting-state FC in core brain regions activated during memory-task functional magnetic resonance imaging is altered and predictive of memory performance in AD and amnestic mild cognitive impairment (aMCI). Twenty-three elderly cognitively healthy controls (HC), 76 aMCI subjects, and 19 AD dementia patients were included. We computed resting-state FC between 18 meta-analytically determined peak coordinates of brain activation during successful memory retrieval. Higher FC between the parahippocampus, parietal cortex, and the middle frontal gyrus was observed in both AD and mild cognitive impairment compared to HC (false-discovery rate-corrected p < 0.05). The increase in FC between the parahippocampus and middle frontal gyrus was associated with reduced episodic memory in aMCI, independent of amyloid-beta positron emission tomography binding and apolipoprotein E ε4-carrier status. In conclusion, increased parahippocampal-prefrontal FC is predictive of impaired episodic memory in aMCI and may reflect a dysfunctional change within the episodic memory-related neural network. PMID:27459924

  13. 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

  14. Phonological working memory impairments in children with specific language impairment: where does the problem lie?

    PubMed Central

    Alt, Mary

    2010-01-01

    Purpose The purpose of this study was to determine which factors contribute to the lexical learning deficits of children with Specific Language Impairment (SLI). Method Participants included 40 7-8-year old participants, half of whom were diagnosed with SLI and half of whom had normal language skills. We tested hypotheses about the contributions to word learning of the initial encoding of phonological information and the link to long-term memory. Children took part in a computer-based fast-mapping task which manipulated word length and phonotactic probability to address the hypotheses. The task had a recognition and a production component. Data were analyzed using mixed ANOVAs with post-hoc testing. Results Results indicate that the main problem for children with SLI is with initial encoding, with implications for limited capacity. There was not strong evidence for specific deficits in the link to long term memory. Conclusions We were able to ascertain which aspects of lexical learning are most problematic for children with SLI in terms of fast-mapping. These findings may allow clinicians to focus intervention on known areas of weakness. Future directions include extending these findings to slow mapping scenarios. PMID:20943232

  15. Auditory Association Cortex Lesions Impair Auditory Short-Term Memory in Monkeys

    NASA Astrophysics Data System (ADS)

    Colombo, Michael; D'Amato, Michael R.; Rodman, Hillary R.; Gross, Charles G.

    1990-01-01

    Monkeys that were trained to perform auditory and visual short-term memory tasks (delayed matching-to-sample) received lesions of the auditory association cortex in the superior temporal gyrus. Although visual memory was completely unaffected by the lesions, auditory memory was severely impaired. Despite this impairment, all monkeys could discriminate sounds closer in frequency than those used in the auditory memory task. This result suggests that the superior temporal cortex plays a role in auditory processing and retention similar to the role the inferior temporal cortex plays in visual processing and retention.

  16. IMPAIRED CATEGORY FLUENCY IN MEDIAL TEMPORAL LOBE AMNESIA: THE ROLE OF EPISODIC MEMORY

    PubMed Central

    Greenberg, Daniel L.; Keane, Margaret M.; Ryan, Lee; Verfaellie, Mieke

    2009-01-01

    Memory tasks are often classified as semantic or episodic, but recent research shows that these types of memory are highly interactive. Category fluency, for example, is generally considered to reflect retrieval from semantic memory, but behavioral evidence suggests that episodic memory is also involved: Participants frequently draw on autobiographical experiences while generating exemplars of certain categories. Neuroimaging studies accordingly have reported increased medial temporal lobe (MTL) activation during exemplar generation. Studies of fluency in MTL amnesics have yielded mixed results but were not designed to determine the precise contributions of episodic memory. We addressed this issue by asking MTL amnesics and controls to generate exemplars of three types of categories. One type tended to elicit autobiographical and spatial retrieval strategies (AS). Another type elicited strategies that were autobiographical but nonspatial (AN). The third type elicited neither autobiographical nor spatial strategies (N). Amnesic patients and control participants generated exemplars for 8 categories of each type. Patients were impaired on all category types but were more impaired on AS and AN categories. After covarying for phonemic fluency (total FAS score), the N category impairment was not significant, but the impairment on AS and AN categories remained. The same results were obtained for patients with lesions restricted to the MTL and those with more extensive lesions. We conclude that patients’ episodic memory impairment hindered their performance on this putatively semantic task. This interaction between episodic and semantic memory might partially account for fluency deficits seen in aging, mild cognitive impairment, and Alzheimer’s disease. PMID:19726648

  17. Free recall behaviour in children with and without spelling impairment: the impact of working memory subcapacities.

    PubMed

    Malstädt, Nadine; Hasselhorn, Marcus; Lehmann, Martin

    2012-11-01

    This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with spelling deficits. Video analyses revealed that recall behaviour was similar in impaired and unimpaired children, indicating that both groups applied similar learning activities. Group differences in number of recalled items were attributed to differences in working memory subcapacities between children with and without spelling impairment, especially with regard to central executive and phonological loop functioning. PMID:23059749

  18. Delayed Environmental Enrichment Reverses Sevoflurane-Induced Memory Impairment in Rats

    PubMed Central

    Shih, Jennifer; May, Laura d.V.; Gonzalez, Heidi E.; Lee, Elaine W.; Alvi, Rehan S.; Sall, Jeffrey W.; Rau, Vinuta; Bickler, Philip E.; Lalchandani, Gopal R.; Ysupova, Marianna; Woodward, Elliott; Kang, Heejae; Wilk, Alan J.; Carlston, Colleen M.; Mendoza, Mortay V.; Guggenheim, Jeremy N.; Schaefer, Maximilian; Rowe, Allison M.; Stratmann, Greg

    2014-01-01

    Background Anesthesia given to immature rodents causes cognitive decline raising the possibility that the same might be true for millions of children undergoing surgical procedures under general anesthesia each year. We tested the hypothesis that anesthesia-induced cognitive decline in rats is treatable. We also tested if anesthesia-induced cognitive decline is aggravated by tissue injury. Methods 7-day old rats underwent sevoflurane anesthesia (1 MAC, 4 hours) with or without tail clamping. At 4 weeks, rats were randomized to environmental enrichment or normal housing. At 8 weeks rats underwent neurocognitive testing, which consisted of fear conditioning, spatial reference memory and water maze-based memory consolidation tests, that interrogated working memory, short term memory and early long term memory. Results Sevoflurane-treated rats had a greater escape latency when the delay between memory acquisition and memory retrieval was increased from 1 minute to 1 hour, indicating that short term memory was impaired. Delayed environmental enrichment reversed the effects of sevoflurane on short term memory and generally improved many tested aspects of cognitive function, both in sevoflurane-treated and control animals. The performance of tail clamped rats did not differ from those rats receiving anesthesia alone. Conclusion Sevoflurane-induced cognitive decline in rats is treatable. Delayed environmental enrichment rescued the sevoflurane-induced impairment in short-term memory. Tissue injury did not worsen the anesthesia-induced memory impairment. These findings may have relevance to neonatal and pediatric anesthesia. PMID:22354242

  19. Dissociation of working memory impairments and attention-deficit/hyperactivity disorder in the brain

    PubMed Central

    Mattfeld, Aaron T.; Whitfield-Gabrieli, Susan; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Fried, Ronna; Gabrieli, John D.E.

    2015-01-01

    Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity. PMID:26900567

  20. Developmental dyscalculia is related to visuo-spatial memory and inhibition impairment.

    PubMed

    Szucs, Denes; Devine, Amy; Soltesz, Fruzsina; Nobes, Alison; Gabriel, Florence

    2013-01-01

    Developmental dyscalculia is thought to be a specific impairment of mathematics ability. Currently dominant cognitive neuroscience theories of developmental dyscalculia suggest that it originates from the impairment of the magnitude representation of the human brain, residing in the intraparietal sulcus, or from impaired connections between number symbols and the magnitude representation. However, behavioral research offers several alternative theories for developmental dyscalculia and neuro-imaging also suggests that impairments in developmental dyscalculia may be linked to disruptions of other functions of the intraparietal sulcus than the magnitude representation. Strikingly, the magnitude representation theory has never been explicitly contrasted with a range of alternatives in a systematic fashion. Here we have filled this gap by directly contrasting five alternative theories (magnitude representation, working memory, inhibition, attention and spatial processing) of developmental dyscalculia in 9-10-year-old primary school children. Participants were selected from a pool of 1004 children and took part in 16 tests and nine experiments. The dominant features of developmental dyscalculia are visuo-spatial working memory, visuo-spatial short-term memory and inhibitory function (interference suppression) impairment. We hypothesize that inhibition impairment is related to the disruption of central executive memory function. Potential problems of visuo-spatial processing and attentional function in developmental dyscalculia probably depend on short-term memory/working memory and inhibition impairments. The magnitude representation theory of developmental dyscalculia was not supported. PMID:23890692

  1. Chronic Cold-Water-Induced Hypothermia Impairs Memory Retrieval and Nepeta menthoides as a Traditional "Hot" Herb Reverses the Impairment.

    PubMed

    Ahmadian-Attar, Mohammad Mahdi; Ahmadiani, Abolhassan; Kamalinejad, Mohammad; Dargahi, Leila; Mosaddegh, Mahmoud

    2014-01-01

    Iranian Traditional Medicine (ITM) describes a kind of dementia with similar signs and symptoms of Alzheimer's disease (AD). It explains the pathology of dementia with cold intemperament of the brain, which means that the brain is colder than its healthy form. ITM strategy for treatment of dementia is to heat the brain up by medical "hot" herbs. Nepeta menthoides (NM) is one of these "hot" herbs. To evaluate the veracity of ITM concept about dementia and its treatment, we first try to examine if coldness of brain can make memory impairment. If so, can NM reverse memory impairment? Rats in cold-water-induced hypothermic (CWH) groups were immersed up to the neck in 3.5 °C water, for 5 min during 14 consecutive days. As a control, rats were forced to swim in warm water at the same conditions. To eliminate the impact of forced swimming stress, a group of intact rats was also added. After last swimming in day 14, some groups received drug (100 or 500 mg/ Kg aqueous extract of NM) or vehicle via i.p. injection. Learning and memory were assessed by Morris water maze, and tau hyperphosphorylation was measured by western blotting. The results showed that CWH impairs learning and memory and induces tau hyperphosphorylation. 100 mg/Kg of NM reversed memory impairment as well as tau hyperphosphorylation. ITM theory about the relationship between brain hypothermia and dementia is in accordance with our findings. PMID:24711845

  2. Memory and executive function impairments after frontal or posterior cortex lesions.

    PubMed

    Daum, Irene; Mayes, Andrew R.

    2000-01-01

    Free recall and recognition, memory for temporal order, spatial memory and prospective memory were assessed in patients with frontal lobe lesions, patients with posterior cortex lesions and control subjects. Both patient groups showed equivalent memory deficits relative to control subjects on a range of free recall and recognition tasks, on memory for temporal order and on a prospective memory task. The patient groups also performed equivalently on the spatial memory task although only patients with frontal lobe lesions were significantly impaired. However, the patients with frontal lobe lesions showed an increased false alarm rate and made more intrusion errors relative not only to the control subjects, but also to the patients with poster or cortex lesions. These memory problems are discussed in relation to deficits in executive function and basic memory processes. PMID:11568428

  3. Memory Impairment in Korsakoff's Psychosis: A Correlation with Brain Noradrenergic Activity.

    ERIC Educational Resources Information Center

    McEntee, William J.; Mair, Robert G.

    1978-01-01

    The concentration of the primary brain metabolite of norepinephrine is diminished in the lumbar spinal fluid of patients with Korsakoff's syndrome. The extent of its reduction is correlated with measures of memory impairment. (BB)

  4. Gummed-up memory: chewing gum impairs short-term recall.

    PubMed

    Kozlov, Michail D; Hughes, Robert W; Jones, Dylan M

    2012-01-01

    Several studies have suggested that short-term memory is generally improved by chewing gum. However, we report the first studies to show that chewing gum impairs short-term memory for both item order and item identity. Experiment 1 showed that chewing gum reduces serial recall of letter lists. Experiment 2 indicated that chewing does not simply disrupt vocal-articulatory planning required for order retention: Chewing equally impairs a matched task that required retention of list item identity. Experiment 3 demonstrated that manual tapping produces a similar pattern of impairment to that of chewing gum. These results clearly qualify the assertion that chewing gum improves short-term memory. They also pose a problem for short-term memory theories asserting that forgetting is based on domain-specific interference given that chewing does not interfere with verbal memory any more than tapping. It is suggested that tapping and chewing reduce the general capacity to process sequences. PMID:22150606

  5. Effects of selegiline alone or with donepezil on memory impairment in rats.

    PubMed

    Takahata, Kazue; Minami, Akiko; Kusumoto, Haruko; Shimazu, Seiichiro; Yoneda, Fumio

    2005-08-22

    Selegiline, a monoamine oxidase-B inhibitor, is reported to improve memory and learning in dementia of Alzheimer's type. However, only a few studies have reported its use in animal models. Here, we evaluated the effects of selegiline only or its combined use with donepezil, a selective acetylcholinesterase inhibitor on memory impairment, using a Morris water maze. Selegiline dose-dependently attenuated ethylcholine aziridinium ion-induced memory impairment. Co-administration of selegiline and donepezil, at doses that do not exert efficacy individually, significantly ameliorated scopolamine+p-chlorophenylalanine-induced memory deficits. These results suggest that selegiline improves memory impairment mediated by the cholinergic system, and provide evidence of the usefulness of co-treatment with selegiline and donepezil for treating spatial deficits in dementia. PMID:16061218

  6. Topographic amnesia: spatial memory disorder, perceptual dysfunction, or category specific semantic memory impairment?

    PubMed Central

    McCarthy, R A; Evans, J J; Hodges, J R

    1996-01-01

    A 60 year old patient, SE, who presented with a severe difficulty in finding his way around previously familiar environments and a mild prosopagnosia is described. SE had herpes simplex encephalitis resulting in selective right temporal lobe damage. He showed normal spatial learning, but was severely imparied in his ability to recognise pictures of buildings and landmarks. The disorder was not confined to the visual modality, but rather involved a loss of knowledge about famous buildings and landmarks when tested from their spoken name. SE was contrasted with a more severely prosopagnosic patient, PHD, who showed normal ability to recognise buildings and landmarks, indicating that recognition of people dissociates from recognition of buildings/landmarks. It is concluded that SE's failure of place knowledge represents a category specific supramodal semantic memory impairment. Images PMID:8609511

  7. Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

    PubMed

    Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

    2016-08-30

    Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders. PMID:27528659

  8. Working Memory Limitations in Children with Severe Language Impairment

    ERIC Educational Resources Information Center

    van Daal, John; Verhoeven, Ludo; van Leeuwe, Jan; van Balkom, Hans

    2008-01-01

    In the present study, the relations of various aspects of working memory to various aspects of language problems in a clinical sample of 97 Dutch speaking 5-year-old children with severe language problems were studied. The working memory and language abilities of the children were examined using an extensive battery of tests. Working memory was…

  9. Memory and Language Impairment in Children and Adults: New Perspectives.

    ERIC Educational Resources Information Center

    Gillam, Ronald B.

    This book contains articles from two issues of "Topics in Language Disorders" that focus on recent developments in the understanding of short-term memory, working memory, and long-term memory systems and their relationship to language comprehension, lexical development, early academic development, later academic development, and communication…

  10. 1'-Acetoxychavicol acetate ameliorates age-related spatial memory deterioration by increasing serum ketone body production as a complementary energy source for neuronal cells.

    PubMed

    Kojima-Yuasa, Akiko; Yamamoto, Tomiya; Yaku, Keisuke; Hirota, Shiori; Takenaka, Shigeo; Kawabe, Kouichi; Matsui-Yuasa, Isao

    2016-09-25

    1'-Acetoxychavicol acetate (ACA) is naturally obtained from the rhizomes and seeds of Alpinia galangal. Here, we examined the effect of ACA on learning and memory in senescence-accelerated mice prone 8 (SAMP8). In mice that were fed a control diet containing 0.02% ACA for 25 weeks, the learning ability in the Morris water maze test was significantly enhanced in comparison with mice that were fed the control diet alone. In the Y-maze test, SAMP8 mice showed decreased spontaneous alterations in comparison with senescence-accelerated resistant/1 (SAMR1) mice, a homologous control, which was improved by ACA pretreatment. Serum metabolite profiles were obtained by GC-MS analysis, and each metabolic profile was plotted on a 3D score plot. Based upon the diagram, it can be seen that the distribution areas for the three groups were completely separate. Furthermore, the contents of β-hydroxybutyric acid and palmitic acid in the serum of SAMP8-ACA mice were higher than those of SAMP8-control mice and SAMR1-control mice. We also found that SAMR1 mice did not show histological abnormalities, whereas histological damage in the CA1 region of the hippocampus in SAMP8-control mice was observed. However, SAMP8-ACA mice were observed in a similar manner as SAMR1 mice. These findings confirm that ACA increases the serum concentrations of β-hydroxybutyric acid and palmitic acid levels and thus these fuels might contribute to the maintenance of the cognitive performance of SAMP8 mice. PMID:27481192

  11. Early immature neuronal death is partially involved in memory impairment induced by cerebral ischemia.

    PubMed

    Yi, Jee Hyun; Cho, So Yeon; Jeon, Se Jin; Jung, Ji Wook; Park, Man Seok; Kim, Dong Hyun; Ryu, Jong Hoon

    2016-07-15

    Memory impairment is a common after an ischemic stroke. While delayed neuronal death in the CA1 region is usually linked to cerebral ischemia-induced memory impairment, the role of early immature neuronal death within the DG region in the memory state of an ischemic stroke model has rarely been studied. Here, we show a partial role of immature neuronal death in memory impairment in a global ischemia model. We found early immature neuronal death, which was determined by DCX and NeuN-double-staining. Injection of z-DEVD-fmk, a caspase-3 inhibitor, into the DG region rescued cells from immature neuronal death in the DG region without affecting delayed neuronal death in the CA1 region of an ischemic brain. Moreover, z-DEVD-fmk treatment partially rescued ischemia-induced spatial memory impairment. We also found that ischemia-induced LTP impairment in the perforant pathway was restored by z-DEVD-fmk treatment. These results suggest that early immature neuronal death is partially involved in ischemia-induced spatial memory impairment. PMID:27085588

  12. Verbal and Visual Memory Impairments in Bipolar I and II Disorder

    PubMed Central

    Ha, Tae Hyon; Kim, Ji Sun; Chang, Jae Seung; Oh, Sung Hee; Her, Ju Young; Cho, Hyun Sang; Park, Tae Sung; Shin, Soon Young

    2012-01-01

    Objective To compare verbal and visual memory performances between patients with bipolar I disorder (BD I) and patients with bipolar II disorder (BD II) and to determine whether memory deficits were mediated by impaired organizational strategies. Methods Performances on the Korean-California Verbal Learning Test (K-CVLT) and the Rey-Osterrieth Complex Figure Test (ROCF) in 37 patients with BD I, 46 patients with BD II and 42 healthy subjects were compared. Mediating effects of impaired organization strategies on poor delayed recall was tested by comparing direct and mediated models using multiple regression analysis. Results Both patients groups recalled fewer words and figure components and showed lower Semantic Clustering compared to controls. Verbal memory impairment was partly mediated by difficulties in Semantic Clustering in both subtypes, whereas the mediating effect of Organization deficit on the visual memory impairment was present only in BD I. In all mediated models, group differences in delayed recall remained significant. Conclusion Our findings suggest that memory impairment may be one of the fundamental cognitive deficits in bipolar disorders and that executive dysfunctions can exert an additional influence on memory impairments. PMID:23251197

  13. Impairment in Emotional Modulation of Attention and Memory in Schizophrenia

    PubMed Central

    Walsh-Messinger, Julie; Ramirez, Paul Michael; Wong, Philip; Antonius, Daniel; Aujero, Nicole; McMahon, Kevin; Opler, Lewis A.; Malaspina, Dolores

    2014-01-01

    Emotion plays a critical role in cognition and goal-directed behavior via complex interconnections between the emotional and motivational systems. It has been hypothesized that the impairment in goal-directed behavior widely noted in schizophrenia may result from defects in the interaction between the neural (ventral) emotional system and (rostral) cortical processes. The present study examined the impact of emotion on attention and memory in schizophrenia. Twenty-five individuals with schizophrenia related psychosis and 25 healthy control subjects were administered a computerized task in which they were asked to search for target images during a rapid serial visual presentation of pictures. Target stimuli were either positive, negative, or neutral images presented at either 200ms or 700ms lag. Additionally, a visual hedonics task was used to assess differences between the schizophrenia group and controls on ratings of valence and arousal from the picture stimuli. Compared to controls, individuals with schizophrenia detected fewer emotional images under both the 200ms and 700ms lag conditions. Multivariate analyses showed that the schizophrenia group also detected fewer positive images under the 700 lag condition and fewer negative images under the 200 lag condition. Individuals with schizophrenia reported higher pleasantness and unpleasantness ratings than controls in response to neutral stimuli, while controls reported higher arousal ratings for neutral and positive stimuli compared to the schizophrenia group. These results highlight dysfunction in the neural modulation of emotion, attention, and cortical processing in schizophrenia, adding to the growing but mixed body of literature on emotion processing in the disorder. PMID:24910446

  14. Impaired declarative memory for emotional material following bilateral amygdala damage in humans.

    PubMed

    Adolphs, R; Cahill, L; Schul, R; Babinsky, R

    1997-01-01

    Everyday experience suggests that highly emotional events are often the most memorable, an observation supported by psychological and pharmacological studies in humans. Although studies in animals have shown that nondeclarative emotional memory (behaviors associated with emotional situations) may be impaired by lesions of the amygdala, little is known about the neural underpinnings of emotional memory in humans, especially in regard to declarative memory (memory for facts that can be assessed verbally). We investigated the declarative memory of two rare patients with selective bilateral amygdala damage. Both subjects showed impairments in long-term declarative memory for emotionally arousing material. The data support the hypothesis that the human amygdala normally enhances acquisition of declarative knowledge regarding emotionally arousing stimuli. PMID:10456070

  15. 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 ...

  16. Children with Specific Language Impairment and Resolved Late Talkers: Working Memory Profiles at 5 Years

    ERIC Educational Resources Information Center

    Petruccelli, Nadia; Bavin, Edith L.; Bretherton, Lesley

    2012-01-01

    Purpose: The evidence of a deficit in working memory in specific language impairment (SLI) is of sufficient magnitude to suggest a primary role in developmental language disorder. However, little research has investigated memory in late talkers who recover from their early delay. Drawing on a longitudinal, community sample, this study compared the…

  17. Are Errors Differentiable from Deceptive Responses when Feigning Memory Impairment? An fMRI Study

    ERIC Educational Resources Information Center

    Lee, Tatia M. C.; Au, Ricky K. C.; Liu, Ho-Ling; Ting, K. H.; Huang, Chih-Mao; Chan, Chetwyn C. H.

    2009-01-01

    Previous neuroimaging studies have suggested that the neural activity associated with truthful recall, with false memory, and with feigned memory impairment are different from one another. Here, we report a functional magnetic resonance imaging (fMRI) study that addressed an important but yet unanswered question: Is the neural activity associated…

  18. Dietary CDP-Choline Supplementation Prevents Memory Impairment Caused by Impoverished Environmental Conditions in Rats

    ERIC Educational Resources Information Center

    Teather, Lisa A.; Wurtman, Richard J.

    2005-01-01

    The authors previously showed that dietary cytidine (5')-diphosphocholine (CDP-choline) supplementation could protect against the development of memory deficits in aging rats. In the present study, younger rats exposed to impoverished environmental conditions and manifesting hippocampal-dependent memory impairments similar to those observed in the…

  19. Impaired Memory Retrieval Correlates with Individual Differences in Cortisol Response but Not Autonomic Response

    ERIC Educational Resources Information Center

    Tranel, Daniel; Adolphs, Ralph; Buchanan, Tony W.

    2006-01-01

    Stress can enhance or impair memory performance. Both cortisol release and sympathetic nervous system responses have been implicated in these differential effects. Here we investigated how memory retrieval might be affected by stress-induced cortisol release, independently of sympathetic nervous system stress responses. Thirty-two healthy…

  20. Spatial but Not Object Memory Impairments in Children with Fetal Alcohol Syndrome.

    ERIC Educational Resources Information Center

    Nadel, Lynn; Uecker, Anne

    1998-01-01

    Thirty Native American children (mean age=10.3 years), 15 identified with fetal alcohol syndrome (FAS) and 15 controls, were asked to recall places and objects in a task previously shown to be sensitive to memory skills in individuals with and without mental retardation. Children with FAS demonstrated a spatial but not an object memory impairment.…

  1. Does Physical Activity Influence Semantic Memory Activation in Amnestic Mild Cognitive Impairment?

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Verber, Matthew D.; Durgerian, Sally; Antuono, Piero; Butts, Alissa M.; Hantke, Nathan C.; Lancaster, Melissa A.; Rao, Stephen M.

    2011-01-01

    The effect of physical activity (PA) on functional brain activation for semantic memory in amnestic mild cognitive impairment (aMCI) was examined using event-related fMRI during fame discrimination. Greater semantic memory activation occurred in the left caudate of High- versus Low-PA patients (P = 0.03), suggesting PA may enhance memory-related caudate activation in aMCI. PMID:21601432

  2. Psychological Characteristics of Children with Visual Impairments: Learning, Memory and Imagery

    ERIC Educational Resources Information Center

    Pring, Linda

    2008-01-01

    The performance of children (and sometimes adults) with visual impairments (VI) on a range of tasks that reflect learning, memory and mental imagery is considered in this article. Sometimes the evidence suggests that there are impairments in performance in comparison with typically developing children with vision, and sometimes some advantages…

  3. Specific Language or Working Memory Impairments: A Small Scale Observational Study

    ERIC Educational Resources Information Center

    Archibald, Lisa M. D.; Joanisse, Marc; Edmunds, Alan

    2011-01-01

    Study of the developmental relationship between language and working memory skills has only just begun, despite the prominent role of their interdependency in some theoretical accounts of developmental language impairments. Recently, Archibald and Joanisse (2009) identified children with specific language impairment (SLI), or specific working…

  4. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    ERIC Educational Resources Information Center

    Wong, Ling M.; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. The authors examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with…

  5. Free Recall Behaviour in Children with and without Spelling Impairment: The Impact of Working Memory Subcapacities

    ERIC Educational Resources Information Center

    Malstadt, Nadine; Hasselhorn, Marcus; Lehmann, Martin

    2012-01-01

    This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with…

  6. 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

  7. Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition.

    PubMed

    Yamashita, Naoya; Takahashi, Aoi; Takao, Keizo; Yamamoto, Toshifumi; Kolattukudy, Pappachan; Miyakawa, Tsuyoshi; Goshima, Yoshio

    2013-01-01

    Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1 (-/-) mice exhibited behavioral abnormalities related to schizophrenia. The crmp1 (-/-) mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1 (-/-) mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1 (-/-) mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1 (-/-) mouse may model endophenotypes present in this neuropsychiatric disorder. PMID:24409129

  8. Depletion of Serotonin Selectively Impairs Short-Term Memory without Affecting Long-Term Memory in Odor Learning in the Terrestrial Slug "Limax Valentianus"

    ERIC Educational Resources Information Center

    Santa, Tomofumi; Kirino, Yutaka; Watanabe, Satoshi; Shirahata, Takaaki; Tsunoda, Makoto

    2006-01-01

    The terrestrial slug "Limax" is able to acquire short-term and long-term memories during aversive odor-taste associative learning. We investigated the effect of the selective serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) on memory. Behavioral studies indicated that 5,7-DHT impaired short-term memory but not long-term memory. HPLC…

  9. Effect of glatiramer acetate on short-term memory impairment induced by lipopolysaccharide in male mice.

    PubMed

    Mohammadi, Fatemeh; Rahimian, Reza; Fakhraei, Nahid; Rezayat, Seyed Mahdi; Javadi-Paydar, Mehrak; Dehpour, Ahmad R; Afshari, Khashayar; Ejtemaei Mehr, Shahram

    2016-08-01

    Glatiramer acetate (GA) demonstrates neuroprotective, neurogenesis, and anti-inflammatory properties. This study examines the probable protective effect of acute GA on lipopolysaccharide (LPS)-induced memory impairment in male mice and further explores which routes of administration [subcutaneous (s.c.) or intracerebroventricular (i.c.v.)] exert optimum effect. Memory performance was evaluated in two-trial recognition Y-maze and passive-avoidance tasks evaluating special recognition memory and fear memory, respectively. Memory impairment was induced by LPS [100 μg/kg, intraperitoneally (i.p.)], 4 h before training. In Y-maze, GA (10, 2.5, 0.625, 0.153, and 0.03 mg/kg, s.c.; 250 μg/mouse; i.c.v.) was administered 10 min following LPS, and special memory was assayed in Y-maze apparatus. In passive avoidance, LPS (100, 250 μg/kg; i.p.) was injected 4 h before receiving foot shock, and GA (10, 2.5; s.c.) or (250 μg/mouse; i.c.v.) was administered 4 h before the shock. Following 24 h, the fear memory was evaluated. Memory impaired significantly following LPS (100, 250 μg/kg; i.p.) in Y-maze and passive-avoidance tasks, P < 0.001 and P < 0.05, respectively. The data revealed that GA (250 μg/mouse, i.c.v.) and GA (10, 2.5 mg/kg; s.c.) in Y-maze reversed memory impairment (LPS 100 μg/kg, i.p.) (P < 0.01). In passive-avoidance task, GA (2.5, 10 mg/kg; s.c.) reversed LPS-induced impairment and the mice showed significantly longer latency times during the retention trial (P < 0.01). GA improved memory impairment both centrally and systemically. It improved spatial recognition memory increasing the average time in the novel arm and improved fear memory increasing latency time. GA administration improved memory impairment profoundly through both systemic and central routs. PMID:27129444

  10. Practitioner Review: Short-Term and Working Memory Impairments in Neurodevelopmental Disorders--Diagnosis and Remedial Support

    ERIC Educational Resources Information Center

    Gathercole, Susan E.; Alloway, Tracy Packiam

    2006-01-01

    Background: This article provides an introduction to current models of working and short-term memory, their links with learning, and diagnosis of impairments. The memory impairments associated with a range of neurodevelopmental disorders (Down's syndrome, Williams syndrome, Specific Language Impairment, and attentional deficits) are discussed.…

  11. 2-Phenylethynyl-butyltellurium enhances learning and memory impaired by scopolamine in mice.

    PubMed

    Souza, Ana Cristina G; Bruning, César A; Acker, Carmine I; Neto, José S S; Nogueira, Cristina W

    2013-08-01

    Taking into account the memory-enhancing properties of 2-phenylethynyl-butyltellurium (PEBT) and the constant search for drugs that improve cognitive performance, the present study was designed to investigate the effect of PEBT on cognitive impairment induced by scopolamine in mice. PEBT (10 mg/kg, gavage) was administered to mice 1 h before the probe trial in the Morris water maze task. Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneally) 30 min before the probe trial. PEBT significantly ameliorated the scopolamine-induced impairment of long-term memory, as indicated by a decrease in escape latency and an increase in the number of crossings of the platform location when compared with the amnesic mice. To evaluate the effect of PEBT on different phases of memory (acquisition, consolidation, and retrieval) impaired by scopolamine, the step-down inhibitory avoidance task was used. Scopolamine was administered 30 min before training (acquisition), test (retrieval), or immediately after training (consolidation). PEBT, administered 30 min before scopolamine, increased step-down latency in memory-impaired mice, improving the consolidation and retrieval stages, but not acquisition. No significant alterations in locomotor or exploratory behaviors were found in animals treated with PEBT and/or scopolamine. PEBT improved memory deficits during consolidation and retrieval induced by scopolamine. PMID:23751517

  12. Chronic Melatonin Treatment Prevents Memory Impairment Induced by Chronic Sleep Deprivation.

    PubMed

    Alzoubi, Karem H; Mayyas, Fadia A; Khabour, Omar F; Bani Salama, Fatima M; Alhashimi, Farah H; Mhaidat, Nizar M

    2016-07-01

    Sleep deprivation (SD) has been associated with memory impairment through induction of oxidative stress. Melatonin, which promotes the metabolism of many reactive oxygen species (ROS), has antioxidant and neuroprotective properties. In this study, the effect of melatonin on memory impairment induced by 4 weeks of SD was investigated using rat animal model. Animals were sleep deprived using modified multiple platform model. Melatonin was administered via oral gavage (100 mg/kg/day). Spatial learning and memory were assessed using the radial arm water maze (RAWM). Changes in oxidative stress biomarkers in the hippocampus following treatments were measured using ELISA procedure. The result revealed that SD impaired both short- and long-term memory (P < 0.05). Use of melatonin prevented memory impairment induced by SD. Furthermore, melatonin normalized SD-induced reduction in the hippocampus activity of catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, melatonin enhanced the ratio of reduced to oxidized glutathione GSH/GSSG in sleep-deprived rats (P < 0.05) without affecting thiobarbituric acid reactive substance (TBARS) levels (P > 0.05). In conclusion, SD induced memory impairment, which was prevented by melatonin. This was correlated with normalizing hippocampus antioxidant mechanisms during chronic SD. PMID:26084441

  13. Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila.

    PubMed

    Drago, Ilaria; Davis, Ronald L

    2016-09-01

    The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism. PMID:27568554

  14. 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

  15. Spatial discrimination deficits as a function of mnemonic interference in aged adults with and without memory impairment.

    PubMed

    Reagh, Zachariah M; Roberts, Jared M; Ly, Maria; DiProspero, Natalie; Murray, Elizabeth; Yassa, Michael A

    2014-03-01

    It is well established that aging is associated with declines in episodic memory. In recent years, an emphasis has emerged on the development of behavioral tasks and the identification of biomarkers that are predictive of cognitive decline in healthy as well as pathological aging. Here, we describe a memory task designed to assess the accuracy of discrimination ability for the locations of objects. Object locations were initially encoded incidentally, and appeared in a single space against a 5 × 7 grid. During retrieval, subjects viewed repeated object-location pairings, displacements of 1, 2, 3, or 4 grid spaces, and maximal corner-to-opposite-corner displacements. Subjects were tasked with judging objects in this second viewing as having retained their original location, or having moved. Performance on a task such as this is thought to rely on the capacity of the individual to perform hippocampus-mediated pattern separation. We report a performance deficit associated with a physically healthy aged group compared to young adults specific to trials with low mnemonic interference. Additionally, for aged adults, performance on the task was correlated with performance on the delayed recall portion of the Rey Auditory Verbal Learning Test (RAVLT), a neuropsychological test sensitive to hippocampal dysfunction. In line with prior work, dividing the aged group into unimpaired and impaired subgroups based on RAVLT Delayed Recall scores yielded clearly distinguishable patterns of performance, with the former subgroup performing comparably to young adults, and the latter subgroup showing generally impaired memory performance even with minimal interference. This study builds on existing tasks used in the field, and contributes a novel paradigm for differentiation of healthy from possible pathological aging, and may thus provide an avenue for early detection of age-related cognitive decline. PMID:24167060

  16. Gestures make memories, but what kind? Patients with impaired procedural memory display disruptions in gesture production and comprehension

    PubMed Central

    Klooster, Nathaniel B.; Cook, Susan W.; Uc, Ergun Y.; Duff, Melissa C.

    2015-01-01

    Hand gesture, a ubiquitous feature of human interaction, facilitates communication. Gesture also facilitates new learning, benefiting speakers and listeners alike. Thus, gestures must impact cognition beyond simply supporting the expression of already-formed ideas. However, the cognitive and neural mechanisms supporting the effects of gesture on learning and memory are largely unknown. We hypothesized that gesture's ability to drive new learning is supported by procedural memory and that procedural memory deficits will disrupt gesture production and comprehension. We tested this proposal in patients with intact declarative memory, but impaired procedural memory as a consequence of Parkinson's disease (PD), and healthy comparison participants with intact declarative and procedural memory. In separate experiments, we manipulated the gestures participants saw and produced in a Tower of Hanoi (TOH) paradigm. In the first experiment, participants solved the task either on a physical board, requiring high arching movements to manipulate the discs from peg to peg, or on a computer, requiring only flat, sideways movements of the mouse. When explaining the task, healthy participants with intact procedural memory displayed evidence of their previous experience in their gestures, producing higher, more arching hand gestures after solving on a physical board, and smaller, flatter gestures after solving on a computer. In the second experiment, healthy participants who saw high arching hand gestures in an explanation prior to solving the task subsequently moved the mouse with significantly higher curvature than those who saw smaller, flatter gestures prior to solving the task. These patterns were absent in both gesture production and comprehension experiments in patients with procedural memory impairment. These findings suggest that the procedural memory system supports the ability of gesture to drive new learning. PMID:25628556

  17. Ameliorating Effects of Ethanol Extract of Fructus mume on Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Kim, Min-Soo; Jeon, Won Kyung; Lee, Kye Wan; Park, Yu Hwa; Han, Jung-Soo

    2015-01-01

    We previously reported that Fructus mume (F. mume) extract shows protective effects on memory impairments and anti-inflammatory effects induced by chronic cerebral hypoperfusion. Neurodegeneration of basal cholinergic neurons is also observed in the brain with chronic cerebral hypoperfusion. Therefore, the present study was conducted to examine whether F. mume extracts enhance cognitive function via the action of cholinergic neuron using a scopolamine-induced animal model of memory impairments. F. mume (50, 100, or 200 mg/kg) was administered to C57BL/6 mice for 14 days (days 1–14) and memory impairment was induced by scopolamine (1 mg/kg), a muscarinic receptor antagonist for 7 days (days 8–14). Spatial memory was assessed using Morris water maze and hippocampal level of acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) was examined by ELISA and immunoblotting. Mice that received scopolamine alone showed impairments in acquisition and retention in Morris water maze task and increased activity of AChE in the hippocampus. Mice that received F. mume and scopolamine showed no scopolamine-induced memory impairment and increased activity of AChE. In addition, treatments of F. mume increased ChAT expression in the hippocampus. These results indicated that F. mume might enhance cognitive function via action of cholinergic neurons. PMID:25705233

  18. Isoflurane-Induced Spatial Memory Impairment in Mice is Prevented by the Acetylcholinesterase Inhibitor Donepezil

    PubMed Central

    Wang, Beilei; Xu, Huan; Li, Wen; Chen, Jie; Wang, Xiangrui

    2011-01-01

    Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. PMID:22114680

  19. Isoflurane-induced spatial memory impairment in mice is prevented by the acetylcholinesterase inhibitor donepezil.

    PubMed

    Su, Diansan; Zhao, Yanxing; Wang, Beilei; Xu, Huan; Li, Wen; Chen, Jie; Wang, Xiangrui

    2011-01-01

    Although many studies have shown that isoflurane exposure impairs spatial memory in aged animals, there are no clinical treatments available to prevent this memory deficit. The anticholinergic properties of volatile anesthetics are a biologically plausible cause of cognitive dysfunction in elderly subjects. We hypothesized that pretreatment with the acetylcholinesterase inhibitor donepezil, which has been approved by the Food and Drug Administration (FDA) for the treatment of Alzheimer's disease, prevents isoflurane-induced spatial memory impairment in aged mice. In present study, eighteen-month-old mice were administered donepezil (5 mg/kg) or an equal volume of saline by oral gavage with a feeding needle for four weeks. Then the mice were exposed to isoflurane (1.2%) for six hours. Two weeks later, mice were subjected to the Morris water maze to examine the impairment of spatial memory after exposure to isoflurane. After the behavioral test, the mice were sacrificed, and the protein expression level of acetylcholinesterase (AChE), choline acetylase (ChAT) and α7 nicotinic receptor (α7-nAChR) were measured in the brain. Each group consisted of 12 mice. We found that isoflurane exposure for six hours impaired the spatial memory of the mice. Compared with the control group, isoflurane exposure dramatically decreased the protein level of ChAT, but not AChE or α7-nAChR. Donepezil prevented isoflurane-induced spatial memory impairments and increased ChAT levels, which were downregulated by isoflurane. In conclusions, pretreatment with the AChE inhibitor donepezil prevented isoflurane-induced spatial memory impairment in aged mice. The mechanism was associated with the upregulation of ChAT, which was decreased by isoflurane. PMID:22114680

  20. Serum perfluoroalkyl acids concentrations and memory impairment in a large cross-sectional study

    PubMed Central

    Gallo, Valentina; Leonardi, Giovanni; Brayne, Carol; Armstrong, Ben; Fletcher, Tony

    2013-01-01

    Objectives To examine the cross-sectional association between serum perfluorooctanate (PFOA), perfuorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) concentrations with self-reported memory impairment in adults and the interaction of these associations with diabetes status. Design Cross-sectional study. Setting Population-based in Mid-Ohio Valley, West Virginia following contamination by a chemical plant. Participants The C8 Health Project collected data and measured the serum level of perfluoroalkyl acids (PFAAs) of 21 024 adults aged 50+ years. Primary outcome measure Self-reported memory impairment as defined by the question ‘have experienced short-term memory loss?’ Results A total of 4057 participants self-reported short-term memory impairment. Inverse associations between PFOS and PFOA and memory impairment were highly statistically significant with fully adjusted OR=0.93 (95% CI 0.90 to 0.96) for doubling PFOS and OR=0.96 (95% CI 0.94 to 0.98) for doubling PFOA concentrations. Comparable inverse associations with PFNA and PFHxS were of borderline statistical significance. Inverse associations of PFAAs with memory impairment were weaker or non-existent in patients with diabetes than overall in patients without diabetes. Conclusions An inverse association between PFAA serum levels and self-reported memory impairment has been observed in this large population-based, cross-sectional study that is stronger and more statistically significant for PFOA and PFOS. The associations can be potentially explained by a preventive anti-inflammatory effect exerted by a peroxisome proliferator-activated receptor agonist effect of these PFAAs, but confounding or even reverse causation cannot be excluded as an alternative explanation. PMID:23794579

  1. The contribution of executive functions deficits to impaired episodic memory in individuals with alcoholism.

    PubMed

    Noël, Xavier; Van der Linden, Martial; Brevers, Damien; Campanella, Salvatore; Hanak, Catherine; Kornreich, Charles; Verbanck, Paul

    2012-06-30

    Individuals with alcoholism commonly exhibit impaired performance on episodic memory tasks. However, the contribution of their impaired executive functioning to poor episodic memory remains to be clarified. Thirty-six recently detoxified and sober asymptomatic alcoholic men and 36 matched non-alcoholic participants were tested for processing speed, prepotent response inhibition, mental flexibility, coordination of dual-task and a verbal episodic memory task. Compared with non-alcoholic individuals, the alcoholic patients showed impaired executive functions combined with below normal performance on both free and delayed recall. In contrast, processing speed, cued recall and recognition were preserved. Regression analyses revealed that 47% of alcoholics' episodic memory's free recall performance was predicted by mental flexibility and that 49% of their delayed recall performance was predicted by mental flexibility, manipulation of dual-task and prepotent response inhibition. Regarding participants' executive predictors of episodic memory performance, the slopes of β coefficients were significantly different between the two groups, with alcoholics requiring more their executive system than non-alcoholics. Once detoxified, alcoholic patients showed episodic memory deficits mainly characterized by impaired effortful (executive) processes. Compared with controls, patients used effortful learning strategies, which are nonetheless less efficient. PMID:22377577

  2. Mutation of Dcdc2 in mice leads to impairments in auditory processing and memory ability.

    PubMed

    Truong, D T; Che, A; Rendall, A R; Szalkowski, C E; LoTurco, J J; Galaburda, A M; Holly Fitch, R

    2014-11-01

    Dyslexia is a complex neurodevelopmental disorder characterized by impaired reading ability despite normal intellect, and is associated with specific difficulties in phonological and rapid auditory processing (RAP), visual attention and working memory. Genetic variants in Doublecortin domain-containing protein 2 (DCDC2) have been associated with dyslexia, impairments in phonological processing and in short-term/working memory. The purpose of this study was to determine whether sensory and behavioral impairments can result directly from mutation of the Dcdc2 gene in mice. Several behavioral tasks, including a modified pre-pulse inhibition paradigm (to examine auditory processing), a 4/8 radial arm maze (to assess/dissociate working vs. reference memory) and rotarod (to examine sensorimotor ability and motor learning), were used to assess the effects of Dcdc2 mutation. Behavioral results revealed deficits in RAP, working memory and reference memory in Dcdc2(del2/del2) mice when compared with matched wild types. Current findings parallel clinical research linking genetic variants of DCDC2 with specific impairments of phonological processing and memory ability. PMID:25130614

  3. Protective effect of tetrahydropalmatine against d-galactose induced memory impairment in rat.

    PubMed

    Qu, Zhuo; Zhang, Jingze; Yang, Honggai; Huo, Liqin; Gao, Jing; Chen, Hong; Gao, Wenyuan

    2016-02-01

    Aging is associated with Alzheimer's disease (AD), cardiovascular disease and cancer. Oxidative stress is considered as a major factor that accelerates the aging process. d-galactose (d-gal), a reducing sugar, induces oxidative stress resulting in alteration in mitochondrial dynamics and apoptosis of neurons. To understand the ability of tetrahydropalmatine (THP) to ameliorate memory impairment caused by aging, we investigated the effect of THP on d-gal induced memory impairment in rats. Subcutaneous injection of d-gal (100mg/kg/d) for 8weeks caused memory loss as detected by the Morris water maze and morphologic abnormalities of neurons in the hippocampus regions and cortex of rat brain. THP treatment ameliorated d-gal induced memory impairment associated with the decrease of malondialdehyde (MDA) and nitric oxide (NO) contents, as well as the increase of glutathione (GSH) levels, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities. THP treatment was also found to reverse the abnormality of acetylcholine (ACh) levels and acetylcholinesterase (AChE) activities. In addition, treatment with THP could decrease the expression of nuclear factor κ (NF-κB) and glial fibrillary acidic protein (GFAP) which prevented the neuroinflammation and memory impairment in the d-gal treated rats. Taken together, these results clearly demonstrated that subcutaneous injection of d-gal produced memory deficits, meanwhile THP could protect neuron from d-gal insults and improve cognition. This study provided an experimental basis for clinical application of THP in AD therapy. PMID:26592138

  4. Impaired Contingent Attentional Capture Predicts Reduced Working Memory Capacity in Schizophrenia

    PubMed Central

    Mayer, Jutta S.; Fukuda, Keisuke; Vogel, Edward K.; Park, Sohee

    2012-01-01

    Although impairments in working memory (WM) are well documented in schizophrenia, the specific factors that cause these deficits are poorly understood. In this study, we hypothesized that a heightened susceptibility to attentional capture at an early stage of visual processing would result in working memory encoding problems. 30 patients with schizophrenia and 28 demographically matched healthy participants were presented with a search array and asked to report the orientation of the target stimulus. In some of the trials, a flanker stimulus preceded the search array that either matched the color of the target (relevant-flanker capture) or appeared in a different color (irrelevant-flanker capture). Working memory capacity was determined in each individual using the visual change detection paradigm. Patients needed considerably more time to find the target in the no-flanker condition. After adjusting the individual exposure time, both groups showed equivalent capture costs in the irrelevant-flanker condition. However, in the relevant-flanker condition, capture costs were increased in patients compared to controls when the stimulus onset asynchrony between the flanker and the search array was high. Moreover, the increase in relevant capture costs correlated negatively with working memory capacity. This study demonstrates preserved stimulus-driven attentional capture but impaired contingent attentional capture associated with low working memory capacity in schizophrenia. These findings suggest a selective impairment of top-down attentional control in schizophrenia, which may impair working memory encoding. PMID:23152783

  5. Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

    PubMed Central

    Wardlaw, Sarah M.; Phan, Trongha X.; Saraf, Amit; Chen, Xuanmao

    2014-01-01

    Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1−/− mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1−/− mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1−/− mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1. PMID:25034823

  6. Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.

    PubMed

    Nedaei, Seyed Ershad; Rezayof, Ameneh; Pourmotabbed, Ali; Nasehi, Mohammad; Zarrindast, Mohammad-Reza

    2016-09-15

    The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats. The animals were bilaterally implanted with the cannulas in the BLA and submitted to a step-through type passive avoidance task to measure the memory formation. The results showed that intraperitoneal (i.p.) administration of different doses of scopolamine (0.5-1.5mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 1-4ng/rat), into the BLA significantly improved scopolamine-induced memory consolidation impairment. On the other hand, co-administration of AM251, a cannabinoid CB1 receptor antagonist (0.25-1ng/rat, intra-BLA), with an ineffective dose of scopolamine (0.5mg/kg, i.p.), significantly impaired memory consolidation and mimicked the response of a higher dose of scopolamine. It is important to note that post-training intra-BLA microinjections of the same doses of ACPA or AM251 alone had no effect on memory consolidation. Moreover, the blockade of the BLA CB1 receptors by 0.3ng/rat of AM251 prevented ACPA-induced improvement of the scopolamine response. In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment. Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation. PMID:27230394

  7. Comparison of explicit and incidental learning strategies in memory-impaired patients

    PubMed Central

    Smith, Christine N.; Urgolites, Zhisen J.; Hopkins, Ramona O.; Squire, Larry R.

    2014-01-01

    Declarative memory for rapidly learned, novel associations is thought to depend on structures in the medial temporal lobe (MTL), whereas associations learned more gradually can sometimes be supported by nondeclarative memory and by structures outside the MTL. A recent study suggested that even rapidly learned associations can be supported by structures outside the MTL when an incidental encoding procedure termed “fast mapping” (FM) is used. We tested six memory-impaired patients with bilateral damage to hippocampus and one patient with large bilateral lesions of the MTL. Participants saw photographs and names of animals, plants, and foods that were previously unfamiliar (e.g., mangosteen). Instead of asking participants to study name–object pairings for a later memory test (as with traditional memory instructions), participants answered questions that allowed them to infer which object corresponded to a particular name. In a second condition, participants learned name–object associations of unfamiliar items by using standard, explicit encoding instructions (e.g., remember the mangosteen). In FM and explicit encoding conditions, patients were impaired (and performed no better than a group that was given the same tests but had not previously studied the material). The same results were obtained in a second experiment that used the same procedures with modifications to allow for more robust learning and more reliable measures of performance. Thus, our results with the FM procedure and memory-impaired patients yielded the same deficits in learning and memory that have been obtained by using other more traditional paradigms. PMID:24367093

  8. The nature of impairments of memory in patients with end-stage renal disease (ESRD).

    PubMed

    Jones, Daniel J W; Harris, John P; Vaux, Emma; Hadid, Rebecca; Kean, Rebecca; Butler, Laurie T

    2015-08-01

    Possible impairments of memory in end-stage renal disease (ESRD) were investigated in two experiments. In Experiment 1, in which stimulus words were presented visually, participants were tested on conceptual or perceptual memory tasks, with retrieval being either explicit or implicit. Compared with healthy controls, ESRD patients were impaired when memory required conceptual but not when it required perceptual processing, regardless of whether retrieval was explicit or implicit. An impairment of conceptual implicit memory (priming) in the ESRD group represented a previously unreported deficit compared to healthy aging. There were no significant differences between pre- and immediate post-dialysis memory performance in ESRD patients on any of the tasks. In Experiment 2, in which presentation was auditory, patients again performed worse than controls on an explicit conceptual memory task. We conclude that the type of processing required by the task (conceptual vs. perceptual) is more important than the type of retrieval (explicit vs. implicit) in memory failures in ESRD patients, perhaps because temporal brain regions are more susceptible to the effects of the illness than are posterior regions. PMID:25980628

  9. Age-related differences in the neural correlates of remembering time-based intentions.

    PubMed

    Cona, Giorgia; Arcara, Giorgio; Tarantino, Vincenza; Bisiacchi, Patrizia Silvia

    2012-09-01

    The present study used event-related potentials (ERPs) to explore the effect of age on the neural correlates of monitoring processes involved in time-based prospective memory. In both younger and older adults, the addition of a time-based prospective memory task to an ongoing task led to a sustained ERP activity broadly distributed over the scalp. Older adults, however, did not exhibit the slow wave activity observed in younger adults over prefrontal regions, which is considered to be associated with retrieval mode. This finding indicates that age-related decline in intention maintenance might be one source of the impaired prospective memory performance displayed by older adults. An 'anterior shift' in scalp distribution of the P3 was observed in older adults, and was related to lower levels of accuracy in prospective memory performance. This relationship suggests that possible factors responsible for age-related decline in prospective memory performance include the decreased efficiency of executive/frontal functions as well as the reduced amount of resources available for the prospective memory task. PMID:22841994

  10. Children with Chromosome 22q11.2 Deletion Syndrome Exhibit Impaired Spatial Working Memory

    PubMed Central

    Wong, Ling M; Riggins, Tracy; Harvey, Danielle; Cabaral, Margarita; Simon, Tony J.

    2014-01-01

    Individuals with chromosome 22q11.2 deletion syndrome (22q11.2DS) have been shown to have impairments in processing spatiotemporal information. We examined whether children with 22q11.2DS exhibit impairments in spatial working memory performance due to these weaknesses, even when controlling for maintenance of attention. Children with 22q11.2DS (n = 47) and typically developing controls (n = 49) ages 6–15 years saw images within a grid and after a delay, then indicated the positions of the images in the correct temporal order. Children with 22q11.2DS made more spatial and temporal errors than controls. Females with 22q11.2DS made more spatial and temporal errors than males. These results extend findings of impaired spatiotemporal processing into the memory domain in 22q11.2DS by documenting their influence on working memory performance. PMID:24679349

  11. Netrin-1 improves spatial memory and synaptic plasticity impairment following global ischemia in the rat.

    PubMed

    Bayat, Mahnaz; Baluchnejadmojarad, Tourandokht; Roghani, Mehrdad; Goshadrou, Fatemeh; Ronaghi, Abdolaziz; Mehdizadeh, Mehdi

    2012-05-01

    Cerebral ischemia, which is the second and most common cause of mortality, affects millions of individuals worldwide. The present study was performed to investigate whether intrahippocampal administration of netrin-1 could improve spatial memory impairment in radial arm maze task and restore long-term potentiation (LTP) in 4-vessel occlusion model of global ischemia. The results showed that intrahippocampal infusion of nerin-1 24 h after ischemia (at both doses of 400 and 800 ng) significantly ameliorated spatial memory impairment and at a dose of 800 ng was capable to improve synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP through enhancement of excitability and normalization of paired pulse response. Taken together, the present study shows that netrin-1 dose-dependently ameliorates spatial memory impairment and improves synaptic dysfunction as observed by recovery of population spike component of basal evoked potential and LTP in rats with global ischemia. PMID:22459051

  12. 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, ...

  13. Alzheimer's disease, amnestic mild cognitive impairment, and age-associated memory impairment: current understanding and progress toward integrative prevention.

    PubMed

    Kidd, Parris M

    2008-06-01

    Alzheimer's disease, AD, is the most common form of dementia. AD initially targets memory and progressively destroys the mind. The brain atrophies as the neocortex suffers neuronal, synaptic, and dendritic losses, and the hallmark amyloid plaques and neurofibrillary tangles proliferate. Pharmacological management, at best, is palliative and transiently effective, with marked adverse effects. Certain nutrients intrinsic to human biochemistry (orthomolecules) match or exceed pharmacological drug benefits in double-blind, randomized, controlled trials, with superior safety. Early intervention is feasible because its heritability is typically minimal and pathological deterioration is detectable years prior to diagnosis. The syndrome amnestic mild cognitive impairment exhibits AD pathology and to date has frustrated attempts at intervention. The condition age-associated memory impairment is a nonpathological extreme of normal brain aging, but with less severe cognitive impairment than amnestic mild cognitive impairment. Age-associated memory impairment is a feasible target for early intervention against AD, beginning with the modifiable AD risk factors - smoking, hypertension, homocysteine, type 2 diabetes, insulin resistance, and obesity. Stress reduction, avoidance of toxins, and mental and physical exercise are important aspects of prevention. The diet should emphasize omega-3 fatty acids docosahexaenoic acid and eicosapentaenoic acid; flavonoids and other antioxidant nutrients; and B vitamins, especially folate, B6 and B12. Dietary supplementation is best focused on those proven from randomized, controlled trials: the phospholipids phosphatidylserine and glycerophosphocholine, the energy nutrient acetyl-L-carnitine, vitamins C and E, and other antioxidants. A comprehensive integrative strategy initiated early in cognitive decline is the most pragmatic approach to controlling progression to Alzheimer's disease. PMID:18590347

  14. PPARγ activation prevents impairments in spatial memory and neurogenesis following transient illness

    PubMed Central

    Ormerod, Brandi K.; Hanft, Simon J.; Asokan, Aditya; Haditsch, Ursula; Lee, Star W.; Palmer, Theo D.

    2012-01-01

    The detrimental effects of illness on cognition are familiar to virtually everyone. Some effects resolve quickly while others may linger after the illness resolves. We found that a transient immune response stimulated by lipopolysaccharide (LPS) compromised hippocampal neurogenesis and impaired hippocampus-dependent spatial memory. The immune event caused a 50% reduction in the number of neurons generated during the illness and the onset of the memory impairment was delayed and coincided with the time when neurons generated during the illness would have become functional within the hippocampus. Broad spectrum non-steroidal anti-inflammatory drugs attenuated these effects but selective Cox-2 inhibition was ineffective while PPARγ activation was surprisingly effective at protecting both neurogenesis and memory from the effects of LPS-produced transient illness. These data may highlight novel mechanisms behind chronic inflammatory and neuroinflammatory episodes that are known to compromise hippocampus-dependent forms of learning and memory. PMID:23108061

  15. The heterogeneity and natural history of mild cognitive impairment of visual memory predominant type.

    PubMed

    Ye, Byoung Seok; Chin, Juhee; Kim, Seong Yoon; Lee, Jung-Sun; Kim, Eun-Joo; Lee, Yunhwan; Hong, Chang Hyung; Choi, Seong Hye; Park, Kyung Won; Ku, Bon D; Moon, So Young; Kim, SangYun; Han, Seol-Hee; Lee, Jae-Hong; Cheong, Hae-Kwan; Park, Sun Ah; Jeong, Jee Hyang; Na, Duk L; Seo, Sang Won

    2015-01-01

    We evaluate the longitudinal outcomes of amnestic mild cognitive impairment (aMCI) according to the modality of memory impairment involved. We recruited 788 aMCI patients and followed them up. aMCI patients were categorized into three groups according to the modality of memory impairment: Visual-aMCI, only visual memory impaired; Verbal-aMCI, only verbal memory impaired; and Both-aMCI, both visual and verbal memory impaired. Each aMCI group was further categorized according to the presence or absence of recognition failure. Risk of progression to dementia was compared with pooled logistic regression analyses while controlling for age, gender, education, and interval from baseline. Of the sample, 219 (27.8%) aMCI patients progressed to dementia. Compared to the Visual-aMCI group, Verbal-aMCI (OR = 1.98, 95% CI = 1.19-3.28, p = 0.009) and Both-aMCI (OR = 3.05, 95% CI = 1.97-4.71, p < 0.001) groups exhibited higher risks of progression to dementia. Memory recognition failure was associated with increased risk of progression to dementia only in the Visual-aMCI group, but not in the Verbal-aMCI and Both-aMCI groups. The Visual-aMCI without recognition failure group were subcategorized into aMCI with depression, small vessel disease, or accelerated aging, and these subgroups showed a variety of progression rates. Our findings underlined the importance of heterogeneous longitudinal outcomes of aMCI, especially Visual-aMCI, for designing and interpreting future treatment trials in aMCI. PMID:25079794

  16. Salience Network and Parahippocampal Dopamine Dysfunction in Memory-Impaired Parkinson Disease

    PubMed Central

    Christopher, Leigh; Duff-Canning, Sarah; Koshimori, Yuko; Segura, Barbara; Boileau, Isabelle; Chen, Robert; Lang, Anthony E.; Houle, Sylvain; Rusjan, Pablo; Strafella, Antonio P.

    2016-01-01

    Objective Patients with Parkinson disease (PD) and mild cognitive impairment (MCI) are vulnerable to dementia and frequently experience memory deficits. This could be the result of dopamine dysfunction in corticostriatal networks (salience, central executive networks, and striatum) and/or the medial temporal lobe. Our aim was to investigate whether dopamine dysfunction in these regions contributes to memory impairment in PD. Methods We used positron emission tomography imaging to compare D2 receptor availability in the cortex and striatal (limbic and associative) dopamine neuron integrity in 4 groups: memory-impaired PD (amnestic MCI; n=9), PD with nonamnestic MCI (n=10), PD without MCI (n=11), and healthy controls (n=14). Subjects were administered a full neuropsychological test battery for cognitive performance. Results Memory-impaired patients demonstrated more significant reductions in D2 receptor binding in the salience network (insular cortex and anterior cingulate cortex [ACC] and the right parahippocampal gyrus [PHG]) compared to healthy controls and patients with no MCI. They also presented reductions in the right insula and right ACC compared to nonamnestic MCI patients. D2 levels were correlated with memory performance in the right PHG and left insula of amnestic patients and with executive performance in the bilateral insula and left ACC of all MCI patients. Associative striatal dopamine denervation was significant in all PD patients. Interpretation Dopaminergic differences in the salience network and the medial temporal lobe contribute to memory impairment in PD. Furthermore, these findings indicate the vulnerability of the salience network in PD and its potential role in memory and executive dysfunction. PMID:25448687

  17. Lead-Induced Impairments in the Neural Processes Related to Working Memory Function

    PubMed Central

    Jin, Seong-Uk; Park, Jang Woo; Kim, Yang-Tae; Ryeom, Hun-Kyu; Lee, Jongmin; Suh, Kyung Jin; Kim, Suk Hwan; Park, Sin-Jae; Jeong, Kyoung Sook; Ham, Jung-O; Kim, Yangho; Chang, Yongmin

    2014-01-01

    Background It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls. Methodology/Principal Findings Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between-group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex. Conclusions/Significance Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects. PMID:25141213

  18. Neuroanatomical Correlates of Malingered Memory Impairment: Event-related fMRI of Deception on a Recognition Memory Task

    PubMed Central

    Browndyke, Jeffrey N.; Paskavitz, James; Sweet, Lawrence H.; Cohen, Ronald A.; Tucker, Karen A.; Welsh-Bohmer, Kathleen A.; Burke, James R.; Schmechel, Donald E.

    2010-01-01

    Primary objective Event-related, functional magnetic resonance imaging (fMRI) data were acquired in healthy participants during purposefully malingered and normal recognition memory performances to evaluate the neural substrates of feigned memory impairment. Methods and procedures Pairwise, between-condition contrasts of neural activity associated with discrete recognition memory responses were conducted to isolate dissociable neural activity between normal and malingered responding while simultaneously controlling for shared stimulus familiarity and novelty effects. Response timing characteristics were also examined for any association with observed between-condition activity differences. Outcomes and results Malingered recognition memory errors, regardless of type, were associated with inferior parietal and superior temporal activity relative to normal performance, while feigned recognition target misses produced additional dorsomedial frontal activation and feigned foil false alarms activated bilateral ventrolateral frontal regions. Malingered response times were associated with activity in the dorsomedial frontal, temporal, and inferior parietal regions. Normal memory responses were associated with greater inferior occipitotemporal and dorsomedial parietal activity, suggesting greater reliance upon visual/attentional networks for proper task performance. Conclusions The neural substrates subserving feigned recognition memory deficits are influenced by response demand and error type, producing differential activation of cortical regions important to complex visual processing, executive control, response planning, and working memory processes. PMID:18465389

  19. CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory

    PubMed Central

    Li, Yong; Kim, Jimok

    2016-01-01

    Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids. CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function. Behavioral assays revealed that hippocampus-dependent, long-term contextual fear memory was impaired whereas hippocampus-independent, cued fear memory was normal in CB2 receptor knockout mice. These mice also displayed enhanced spatial working memory when tested in a Y-maze. Motor activity and anxiety of CB2 receptor knockout mice were intact when assessed in an open field arena and an elevated zero maze. In contrast to the knockout of CB2 receptors, acute blockade of CB2 receptors by AM603 in C57BL/6J mice had no effect on memory, motor activity, or anxiety. Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas. PMID:26819779

  20. The heterogeneity of verbal short-term memory impairment in aphasia.

    PubMed

    Majerus, Steve; Attout, Lucie; Artielle, Marie-Amélie; Van der Kaa, Marie-Anne

    2015-10-01

    Verbal short-term memory (STM) impairment represents a frequent and long-lasting deficit in aphasia, and it will prevent patients from recovering fully functional language abilities. The aim of this study was to obtain a more precise understanding of the nature of verbal STM impairment in aphasia, by determining whether verbal STM impairment is merely a consequence of underlying language impairment, as suggested by linguistic accounts of verbal STM, or whether verbal STM impairment reflects an additional, specific deficit. We investigated this question by contrasting item-based STM measures, supposed to depend strongly upon language activation, and order-based STM measures, supposed to reflect the operation of specific, serial order maintenance mechanisms, in a sample of patients with single-word processing deficits at the phonological and/or lexical level. A group-level analysis showed robust impairment for both item and serial order STM aspects in the aphasic group relative to an age-matched control group. An analysis of individual profiles revealed an important heterogeneity of verbal STM profiles, with patients presenting either selective item STM deficits, selective order STM deficits, generalized item and serial order STM deficits or no significant STM impairment. Item but not serial order STM impairment correlated with the severity of phonological impairment. These results disconfirm a strong version of the linguistic account of verbal STM impairment in aphasia, by showing variable impairment to both item and serial order processing aspects of verbal STM. PMID:26275964

  1. Semantic impairment disrupts perception, memory, and naming of secondary but not primary colours.

    PubMed Central

    Rogers, Timothy T.; Graham, Kim S.; Patterson, Karalyn

    2015-01-01

    To investigate how basic aspects of perception are shaped by acquired knowledge about the world, we assessed colour perception and cognition in patients with semantic dementia (SD), a disorder that progressively erodes conceptual knowledge. We observed a previously undocumented pattern of impairment to colour perception and cognition characterized by: (i) a normal ability to discriminate between only subtly different colours but an impaired ability to group different colours into categories, (ii) normal perception and memory for the colours red, green, and blue but impaired perception and memory for colours lying between these regions of a fully-saturated and luminant spectrum, and (iii) normal naming of polar colours in the opponent-process colour system (red, green, blue, yellow, white, and black) but impaired naming of other basic colours (brown, gray, pink, and orange). The results suggest that fundamental aspects of perception can be shaped by acquired knowledge about the world, but only within limits. PMID:25637227

  2. Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

    NASA Astrophysics Data System (ADS)

    Birnbaum, S. G.; Yuan, P. X.; Wang, M.; Vijayraghavan, S.; Bloom, A. K.; Davis, D. J.; Gobeske, K. T.; Sweatt, J. D.; Manji, H. K.; Arnsten, A. F. T.

    2004-10-01

    The prefrontal cortex is a higher brain region that regulates thought, behavior, and emotion using representational knowledge, operations often referred to as working memory. We tested the influence of protein kinase C (PKC) intracellular signaling on prefrontal cortical cognitive function and showed that high levels of PKC activity in prefrontal cortex, as seen for example during stress exposure, markedly impair behavioral and electrophysiological measures of working memory. These data suggest that excessive PKC activation can disrupt prefrontal cortical regulation of behavior and thought, possibly contributing to signs of prefrontal cortical dysfunction such as distractibility, impaired judgment, impulsivity, and thought disorder.

  3. The Chemokine MIP-1α/CCL3 impairs mouse hippocampal synaptic transmission, plasticity and memory

    PubMed Central

    Marciniak, Elodie; Faivre, Emilie; Dutar, Patrick; Alves Pires, Claire; Demeyer, Dominique; Caillierez, Raphaëlle; Laloux, Charlotte; Buée, Luc; Blum, David; Humez, Sandrine

    2015-01-01

    Chemokines are signaling molecules playing an important role in immune regulations. They are also thought to regulate brain development, neurogenesis and neuroendocrine functions. While chemokine upsurge has been associated with conditions characterized with cognitive impairments, their ability to modulate synaptic plasticity remains ill-defined. In the present study, we specifically evaluated the effects of MIP1-α/CCL3 towards hippocampal synaptic transmission, plasticity and spatial memory. We found that CCL3 (50 ng/ml) significantly reduced basal synaptic transmission at the Schaffer collateral-CA1 synapse without affecting NMDAR-mediated field potentials. This effect was ascribed to post-synaptic regulations, as CCL3 did not impact paired-pulse facilitation. While CCL3 did not modulate long-term depression (LTD), it significantly impaired long-term potentiation (LTP), an effect abolished by Maraviroc, a CCR5 specific antagonist. In addition, sub-chronic intracerebroventricular (icv) injections of CCL3 also impair LTP. In accordance with these electrophysiological findings, we demonstrated that the icv injection of CCL3 in mouse significantly impaired spatial memory abilities and long-term memory measured using the two-step Y-maze and passive avoidance tasks. These effects of CCL3 on memory were inhibited by Maraviroc. Altogether, these data suggest that the chemokine CCL3 is an hippocampal neuromodulator able to regulate synaptic plasticity mechanisms involved in learning and memory functions. PMID:26511387

  4. Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats.

    PubMed

    Sonkusare, Swapnil; Srinivasan, Krishnamoorthy; Kaul, Chamanlal; Ramarao, Poduri

    2005-05-20

    Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism in brain and synthesis of acetyl CoA. However, no reports are available regarding the cholinesterase inhibitors in this model. In aging brain, reduced energy metabolism increases glutamate release, which is blocked by L-type calcium channel blockers. These calcium channel blockers have shown beneficial effects on learning and memory in various models of cognitive impairment. The present study was designed to investigate the influence of chronic administration of donepezil (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ injected rats developed a severe deficit in learning and memory indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to control rats. Cholinesterase activity in brain was significantly increased in ICV STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity and improved performance in memory tests at both the doses. Lercanidipine (0.3 mg/kg) showed significant improvement in memory. When administered together, the effect of combination of these two drugs on memory and cholinesterase activity was higher than that obtained with either of the drugs when used alone. PMID:15848214

  5. Ameliorative effect of Noni fruit extract on streptozotocin-induced memory impairment in mice.

    PubMed

    Pachauri, Shakti D; Verma, Priya Ranjan P; Dwivedi, Anil K; Tota, Santoshkumar; Khandelwal, Kiran; Saxena, Jitendra K; Nath, Chandishwar

    2013-08-01

    This study evaluated the effects of a standardized ethyl acetate extract of Morinda citrifolia L. (Noni) fruit on impairment of memory, brain energy metabolism, and cholinergic function in intracerebral streptozotocin (STZ)-treated mice. STZ (0.5 mg/kg) was administered twice at an interval of 48 h. Noni (50 and 100 mg/kg, postoperatively) was administered for 21 days following STZ administration. Memory function was evaluated using Morris Water Maze and passive avoidance tests, and brain levels of cholinergic function, oxidative stress, energy metabolism, and brain-derived neurotrophic factor (BDNF) were estimated. STZ caused memory impairment in Morris Water Maze and passive avoidance tests along with reduced brain levels of ATP, BDNF, and acetylcholine and increased acetylcholinesterase activity and oxidative stress. Treatment with Noni extract (100 mg/kg) prevented the STZ-induced memory impairment in both behavioral tests along with reduced oxidative stress and acetylcholinesterase activity, and increased brain levels of BDNF, acetylcholine, and ATP level. The study shows the beneficial effects of Noni fruit against STZ-induced memory impairment, which may be attributed to improved brain energy metabolism, cholinergic neurotransmission, BDNF, and antioxidative action. PMID:23838966

  6. Amyloid β Enhances Typical Rodent Behavior While It Impairs Contextual Memory Consolidation

    PubMed Central

    Salgado-Puga, Karla; Prado-Alcalá, Roberto A.; Peña-Ortega, Fernando

    2015-01-01

    Alzheimer's disease (AD) is associated with an early hippocampal dysfunction, which is likely induced by an increase in soluble amyloid beta peptide (Aβ). This hippocampal failure contributes to the initial memory deficits observed both in patients and in AD animal models and possibly to the deterioration in activities of daily living (ADL). One typical rodent behavior that has been proposed as a hippocampus-dependent assessment model of ADL in mice and rats is burrowing. Despite the fact that AD transgenic mice show some evidence of reduced burrowing, it has not been yet determined whether or not Aβ can affect this typical rodent behavior and whether this alteration correlates with the well-known Aβ-induced memory impairment. Thus, the purpose of this study was to test whether or not Aβ affects burrowing while inducing hippocampus-dependent memory impairment. Surprisingly, our results show that intrahippocampal application of Aβ increases burrowing while inducing memory impairment. We consider that this Aβ-induced increase in burrowing might be associated with a mild anxiety state, which was revealed by increased freezing behavior in the open field, and conclude that Aβ-induced hippocampal dysfunction is reflected in the impairment of ADL and memory, through mechanisms yet to be determined. PMID:26229236

  7. Hippocampal Volume Reduction in Humans Predicts Impaired Allocentric Spatial Memory in Virtual-Reality Navigation

    PubMed Central

    Dzieciol, Anna M.; Gadian, David G.; Jentschke, Sebastian; Doeller, Christian F.; Burgess, Neil; Mishkin, Mortimer

    2015-01-01

    The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with “moderate” hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on

  8. Prevalence of Impaired Memory in Hospitalized Adults and Associations with In-Hospital Sleep Loss

    PubMed Central

    Calev, Hila; Spampinato, Lisa M; Press, Valerie G; Meltzer, David O; Arora, Vineet M

    2015-01-01

    Background Effective inpatient teaching requires intact patient memory, but studies suggest hospitalized adults may have memory deficits. Sleep loss among inpatients could contribute to memory impairment. Objective To assess memory in older hospitalized adults, and to test the association between sleep quantity, sleep quality and memory, in order to identify a possible contributor to memory deficits in these patients. Design Prospective cohort study Setting General medicine and hematology/oncology inpatient wards Patients 59 hospitalized adults at least 50 years of age with no diagnosed sleep disorder. Measurements Immediate memory and memory after a 24-hour delay were assessed using a word recall and word recognition task from the University of Southern California Repeatable Episodic Memory Test (USC-REMT). A vignette-based memory task was piloted as an alternative test more closely resembling discharge instructions. Sleep duration and efficiency overnight in the hospital were measured using actigraphy. Results Mean immediate recall was 3.8 words out of 15 (SD=2.1). Forty-nine percent of subjects had poor memory, defined as immediate recall score of 3 or lower. Median immediate recognition was 11 words out of 15 (IQR=9, 13). Median delayed recall score was 1 word and median delayed recognition was 10 words (IQR= 8–12). In-hospital sleep duration and efficiency were not significantly associated with memory. The medical vignette score was correlated with immediate recall (r=0.49, p<0.01) Conclusions About half of inpatients studied had poor memory while in the hospital, signaling that hospitalization might not be an ideal teachable moment. In-hospital sleep was not associated with memory scores. PMID:25872763

  9. The GABAA antagonist bicuculline attenuates progesterone-induced memory impairments in middle-aged ovariectomized rats

    PubMed Central

    Braden, B. Blair; Kingston, Melissa L.; Koenig, Elizabeth N.; Lavery, Courtney N.; Tsang, Candy W. S.; Bimonte-Nelson, Heather A.

    2015-01-01

    In women, high levels of natural progesterone have been associated with detrimental cognitive effects via the “maternal amnesia” phenomenon as well as in controlled experiments. In aged ovariectomized (Ovx) rats, progesterone has been shown to impair cognition and impact the GABAergic system in cognitive brain regions. Here, we tested whether the GABAergic system is a mechanism of progesterone’s detrimental cognitive effects in the Ovx rat by attempting to reverse progesterone-induced impairments via concomitant treatment with the GABAA antagonist, bicuculline. Thirteen month old rats received Ovx plus daily vehicle, progesterone, bicuculline, or progesterone+bicuculline injections beginning 2 weeks prior to testing. The water radial-arm maze was used to evaluate spatial working and reference memory. During learning, rats administered progesterone made more working memory errors than those administered vehicle, and this impairment was reversed by the addition of bicuculline. The progesterone impairment was transient and all animals performed similarly by the end of regular testing. On the last day of testing, a 6 hour delay was administered to evaluate memory retention. Progesterone-treated rats were the only group to increase working memory errors with the delay relative to baseline performance; again, the addition of bicuculline prevented the progesterone-induced impairment. The vehicle, bicuculline, and progesterone+bicuculline groups were not impaired by the delay. The current rodent findings corroborate prior research reporting progesterone-induced detriments on cognition in women and in the aging Ovx rat. Moreover, the data suggest that the progesterone-induced cognitive impairment is, in part, related to the GABAergic system. Given that progesterone is included in numerous clinically-prescribed hormone therapies and contraceptives (e.g., micronized), and as synthetic analogs, further research is warranted to better understand the parameters and

  10. Neurotoxicity induced by alkyl nitrites: Impairment in learning/memory and motor coordination.

    PubMed

    Cha, Hye Jin; Kim, Yun Ji; Jeon, Seo Young; Kim, Young-Hoon; Shin, Jisoon; Yun, Jaesuk; Han, Kyoungmoon; Park, Hye-Kyung; Kim, Hyung Soo

    2016-04-21

    Although alkyl nitrites are used as recreational drugs, there is only little research data regarding their effects on the central nervous system including their neurotoxicity. This study investigated the neurotoxicity of three representative alkyl nitrites (isobutyl nitrite, isoamyl nitrite, and butyl nitrite), and whether it affected learning/memory function and motor coordination in rodents. Morris water maze test was performed in mice after administrating the mice with varying doses of the substances in two different injection schedules of memory acquisition and memory retention. A rota-rod test was then performed in rats. All tested alkyl nitrites lowered the rodents' capacity for learning and memory, as assessed by both the acquisition and retention tests. The results of the rota-rod test showed that isobutyl nitrite in particular impaired motor coordination in chronically treated rats. The mice chronically injected with isoamyl nitrite also showed impaired function, while butyl nitrite had no significant effect. The results of the water maze test suggest that alkyl nitrites may impair learning and memory. Additionally, isoamyl nitrite affected the rodents' motor coordination ability. Collectively, our findings suggest that alkyl nitrites may induce neurotoxicity, especially on the aspect of learning and memory function. PMID:26971703

  11. A combined electrophysiological and morphological examination of episodic memory decline in amnestic mild cognitive impairment

    PubMed Central

    Hoppstädter, Michael; King, Andrea Victoria; Frölich, Lutz; Wessa, Michèle; Flor, Herta; Meyer, Patric

    2013-01-01

    Early stages of Alzheimer’s disease (AD) are characterized by neuropathological changes within the medial temporal lobe cortex (MTLC), which lead to characteristic impairments in episodic memory, i.e., amnestic mild cognitive impairment (aMCI). Here, we tested the neural correlates of this memory impairment using event-related potentials (ERPs) and voxel-based morphometry. Twenty-four participants were instructed to encode lists of words and were tested in a yes/no recognition memory task. The dual-process model of recognition memory dissociates between acontextual familiarity and recollection of contextual details. The early frontal ERP old/new effect, which is thought to represent a neural correlate of familiarity-based memory, was absent in aMCI, whereas the control group showed a significant early old/new effect at frontal electrodes. This effect was positively correlated with behavioral episodic memory performance. Analyses of brain morphology revealed a focused gray matter loss in the inferior and medial temporal lobes in aMCI versus healthy controls. Moreover, the positive correlation between gray matter volume in the MTLC and the familiarity-related early frontal old/new effect supports the notion that this effect relies upon the integrity of the MTLC. Thus, the present findings might provide a further functional marker for prodromal AD. PMID:24065918

  12. Negative Emotional Arousal Impairs Associative Memory Performance for Emotionally Neutral Content in Healthy Participants.

    PubMed

    Guez, Jonathan; Saar-Ashkenazy, Rotem; Mualem, Liran; Efrati, Matan; Keha, Eldad

    2015-01-01

    The effect of emotional arousal on memory presents a complex pattern with previous studies reporting conflicting results of both improved and reduced memory performance following arousal manipulations. In this study we further tested the effect of negative emotional arousal (NEA) on individual-item recognition and associative recognition of neutral stimuli in healthy participants, and hypothesized that NEA will particularly impair associative memory performance. The current study consists of two experiments; in both, participants studied a list of word-pairs and were then tested for items (items recognition test), and for associations (associative recognition test). In the first experiment, the arousal manipulation was induced by flashing emotionally-negative or neutral pictures between study-pairs while in the second experiment arousal was induced by presenting emotionally-negative or neutral pictures between lists. The results of the two experiments converged and supported an associative memory deficit observed under NEA conditions. We suggest that NEA is associated with an altered ability to bind one stimulus to another as a result of impaired recollection, resulting in poorer associative memory performance. The current study findings may contribute to the understanding of the mechanism underlying memory impairments reported in disorders associated with traumatic stress. PMID:26186001

  13. Negative Emotional Arousal Impairs Associative Memory Performance for Emotionally Neutral Content in Healthy Participants

    PubMed Central

    Guez, Jonathan; Saar-Ashkenazy, Rotem; Mualem, Liran; Efrati, Matan; Keha, Eldad

    2015-01-01

    The effect of emotional arousal on memory presents a complex pattern with previous studies reporting conflicting results of both improved and reduced memory performance following arousal manipulations. In this study we further tested the effect of negative emotional arousal (NEA) on individual-item recognition and associative recognition of neutral stimuli in healthy participants, and hypothesized that NEA will particularly impair associative memory performance. The current study consists of two experiments; in both, participants studied a list of word-pairs and were then tested for items (items recognition test), and for associations (associative recognition test). In the first experiment, the arousal manipulation was induced by flashing emotionally-negative or neutral pictures between study-pairs while in the second experiment arousal was induced by presenting emotionally-negative or neutral pictures between lists. The results of the two experiments converged and supported an associative memory deficit observed under NEA conditions. We suggest that NEA is associated with an altered ability to bind one stimulus to another as a result of impaired recollection, resulting in poorer associative memory performance. The current study findings may contribute to the understanding of the mechanism underlying memory impairments reported in disorders associated with traumatic stress. PMID:26186001

  14. The cognitive and neural expression of semantic memory impairment in mild cognitive impairment and early Alzheimer's disease.

    PubMed

    Joubert, Sven; Brambati, Simona M; Ansado, Jennyfer; Barbeau, Emmanuel J; Felician, Olivier; Didic, Mira; Lacombe, Jacinthe; Goldstein, Rachel; Chayer, Céline; Kergoat, Marie-Jeanne

    2010-03-01

    Semantic deficits in Alzheimer's disease have been widely documented, but little is known about the integrity of semantic memory in the prodromal stage of the illness. The aims of the present study were to: (i) investigate naming abilities and semantic memory in amnestic mild cognitive impairment (aMCI), early Alzheimer's disease (AD) compared to healthy older subjects; (ii) investigate the association between naming and semantic knowledge in aMCI and AD; (iii) examine if the semantic impairment was present in different modalities; and (iv) study the relationship between semantic performance and grey matter volume using voxel-based morphometry. Results indicate that both naming and semantic knowledge of objects and famous people were impaired in aMCI and early AD groups, when compared to healthy age- and education-matched controls. Item-by-item analyses showed that anomia in aMCI and early AD was significantly associated with underlying semantic knowledge of famous people but not with semantic knowledge of objects. Moreover, semantic knowledge of the same concepts was impaired in both the visual and the verbal modalities. Finally, voxel-based morphometry analyses revealed that semantic impairment in aMCI and AD was associated with cortical atrophy in the anterior temporal lobe (ATL) region as well as in the inferior prefrontal cortex (IPC), some of the key regions of the semantic cognition network. These findings suggest that the semantic impairment in aMCI may result from a breakdown of semantic knowledge of famous people and objects, combined with difficulties in the selection, manipulation and retrieval of this knowledge. PMID:19954747

  15. Long-Term Memory: A Review and Meta-Analysis of Studies of Declarative and Procedural Memory in Specific Language Impairment

    ERIC Educational Resources Information Center

    Lum, Jarrad A. G.; Conti-Ramsden, Gina

    2013-01-01

    This review examined the status of long-term memory systems in specific language impairment (SLI)--declarative memory and aspects of procedural memory in particular. Studies included in the review were identified following a systematic search of the literature and findings combined using meta-analysis. This review showed that individuals with SLI…

  16. Lateral and Anterior Thalamic Lesions Impair Independent Memory Systems

    ERIC Educational Resources Information Center

    Mitchell, Anna S.; Dalrymple-Alford, John C.

    2006-01-01

    Damage to the medial region of the thalamus, both in clinical cases (e.g., patients with infarcts or the Korsakoff's syndrome) and animal lesion models, is associated with variable amnesic deficits. Some studies suggest that many of these memory deficits rely on the presence of lateral thalamic lesions (LT) that include the intralaminar nuclei,…

  17. Adaptive Memory: Animacy Enhances Free Recall but Impairs Cued Recall

    ERIC Educational Resources Information Center

    Popp, Earl Y.; Serra, Michael J.

    2016-01-01

    Recent research suggests that human memory systems evolved to remember animate things better than inanimate things. In the present experiments, we examined whether these effects occur for both free recall and cued recall. In Experiment 1, we directly compared the effect of animacy on free recall and cued recall. Participants studied lists of…

  18. CANTAB Explicit Memory Is Less Impaired in Addicted Schizophrenia Patients

    ERIC Educational Resources Information Center

    Potvin, Stephane; Briand, Catherine; Prouteau, Antoinette; Bouchard, Roch-Hugo; Lipp, Olivier; Lalonde, Pierre; Nicole, Luc; Lesage, Alain; Stip, Emmanuel

    2005-01-01

    It has been suggested that in order to sustain the lifestyle of substance abuse, addicted schizophrenia patients would have less negative symptoms, better social skills, and less cognitive impairments. Mounting evidence supports the first two assumptions, but data lack regarding cognition in dual diagnosis schizophrenia. Seventy-six schizophrenia…

  19. Short-Term and Working Memory in Specific Language Impairment

    ERIC Educational Resources Information Center

    Archibald, Lisa M. D.; Gathercole, Susan E.

    2006-01-01

    Background: Investigations of the cognitive processes underlying specific language impairment (SLI) have implicated deficits in the storage and processing of phonological information, but to date these abilities have not been studied in the same group of children with SLI. Aims: To examine the extent to which deficits in immediate verbal…

  20. Free and cued recall memory in Parkinson's disease associated with amnestic mild cognitive impairment.

    PubMed

    Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A

    2014-01-01

    The hypothesis has been advanced that memory disorders in individuals with Parkinson's disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients' performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning. PMID:24465977

  1. Free and Cued Recall Memory in Parkinson’s Disease Associated with Amnestic Mild Cognitive Impairment

    PubMed Central

    Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A.

    2014-01-01

    The hypothesis has been advanced that memory disorders in individuals with Parkinson’s disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients’ performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning. PMID:24465977

  2. Role of Glia in Stress-Induced Enhancement and Impairment of Memory

    PubMed Central

    Pearson-Leary, Jiah; Osborne, Danielle Maria; McNay, Ewan C.

    2016-01-01

    Both acute and chronic stress profoundly affect hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesia. Often overlooked in consideration of the impact of stress on cognitive processes, and specifically memory, is the important contribution of glia as a target for stress-induced changes. Astrocytes, microglia, and oligodendrocytes all have unique contributions to learning and memory. Furthermore, these three types of glia express receptors for both norepinephrine and glucocorticoids and are hence immediate targets of stress hormone actions. It is becoming increasingly clear that inflammatory cytokines and immunomodulatory molecules released by glia during stress may promote many of the behavioral effects of acute and chronic stress. In this review, the role of traditional genomic and rapid hormonal mechanisms working in concert with glia to affect stress-induced learning and memory will be emphasized. PMID:26793072

  3. WORKING MEMORY IMPAIRMENT AS AN ENDOPHENOTYPIC MARKER OF A SCHIZOPHRENIA DIATHESIS

    PubMed Central

    Park, Sohee; Gooding, Diane C.

    2014-01-01

    This chapter focuses on the viability of working memory impairment as an endophenotypic marker of a schizophrenia diathesis. It begins with an introduction of the construct of working memory. It follows with a review of the operational criteria for defining an endophenotype. Research findings regarding the working memory performance of schizophrenia and schizophrenia-spectrum patients, first-degree relatives of schizophrenia patients and healthy controls, are reviewed in terms of the criteria for being considered an endophenotypic marker. Special attention is paid to specific components of the working memory deficit (namely, encoding, maintenance, and manipulation), in terms of which aspects are likely to be the best candidates for endophenotypes. We consider the extant literature regarding working memory performance in bipolar disorder and major depression in order to address the issue of relative specificity to schizophrenia. Despite some unresolved issues, it appears that working memory impairment is a very promising candidate for an endophenotypic marker of a schizophrenia diathesis but not for mood disorders. Throughout this chapter, we identify future directions for research in this exciting and dynamic area of research and evaluate the contribution of working memory research to our understanding of schizophrenia. PMID:25414816

  4. Long-Term Heavy Ketamine Use is Associated with Spatial Memory Impairment and Altered Hippocampal Activation

    PubMed Central

    Morgan, Celia J. A.; Dodds, Chris M.; Furby, Hannah; Pepper, Fiona; Fam, Johnson; Freeman, Tom P.; Hughes, Emer; Doeller, Christian; King, John; Howes, Oliver; Stone, James M.

    2014-01-01

    Ketamine, a non-competitive N-methyl-d-aspartate receptor antagonist, is rising in popularity as a drug of abuse. Preliminary evidence suggests that chronic, heavy ketamine use may have profound effects on spatial memory but the mechanism of these deficits is as yet unclear. This study aimed to examine the neural mechanism by which heavy ketamine use impairs spatial memory processing. In a sample of 11 frequent ketamine users and 15 poly-drug controls, matched for IQ, age, years in education. We used fMRI utilizing an ROI approach to examine the neural activity of three regions known to support successful navigation; the hippocampus, parahippocampal gyrus, and the caudate nucleus during a virtual reality task of spatial memory. Frequent ketamine users displayed spatial memory deficits, accompanied by and related to, reduced activation in both the right hippocampus and left parahippocampal gyrus during navigation from memory, and in the left caudate during memory updating, compared to controls. Ketamine users also exhibited schizotypal and dissociative symptoms that were related to hippocampal activation. Impairments in spatial memory observed in ketamine users are related to changes in medial temporal lobe activation. Disrupted medial temporal lobe function may be a consequence of chronic ketamine abuse and may relate to schizophrenia-like symptomatology observed in ketamine users. PMID:25538631

  5. The relation between receptive grammar and procedural, declarative, and working memory in specific language impairment

    PubMed Central

    Conti-Ramsden, Gina; Ullman, Michael T.; Lum, Jarrad A. G.

    2015-01-01

    What memory systems underlie grammar in children, and do these differ between typically developing (TD) children and children with specific language impairment (SLI)? Whilst there is substantial evidence linking certain memory deficits to the language problems in children with SLI, few studies have investigated multiple memory systems simultaneously, examining not only possible memory deficits but also memory abilities that may play a compensatory role. This study examined the extent to which procedural, declarative, and working memory abilities predict receptive grammar in 45 primary school aged children with SLI (30 males, 15 females) and 46 TD children (30 males, 16 females), both on average 9;10 years of age. Regression analyses probed measures of all three memory systems simultaneously as potential predictors of receptive grammar. The model was significant, explaining 51.6% of the variance. There was a significant main effect of learning in procedural memory and a significant group × procedural learning interaction. Further investigation of the interaction revealed that procedural learning predicted grammar in TD but not in children with SLI. Indeed, procedural learning was the only predictor of grammar in TD. In contrast, only learning in declarative memory significantly predicted grammar in SLI. Thus, different memory systems are associated with receptive grammar abilities in children with SLI and their TD peers. This study is, to our knowledge, the first to demonstrate a significant group by memory system interaction in predicting grammar in children with SLI and their TD peers. In line with Ullman’s Declarative/Procedural model of language and procedural deficit hypothesis of SLI, variability in understanding sentences of varying grammatical complexity appears to be associated with variability in procedural memory abilities in TD children, but with declarative memory, as an apparent compensatory mechanism, in children with SLI. PMID:26284013

  6. Preserved memory-based orienting of attention with impaired explicit memory in healthy ageing

    PubMed Central

    Salvato, Gerardo; Patai, Eva Z.; Nobre, Anna C.

    2016-01-01

    It is increasingly recognised that spatial contextual long-term memory (LTM) prepares neural activity for guiding visuo-spatial attention in a proactive manner. In the current study, we investigated whether the decline in explicit memory observed in healthy ageing would compromise this mechanism. We compared the behavioural performance of younger and older participants on learning new contextual memories, on orienting visual attention based on these learnt contextual associations, and on explicit recall of contextual memories. We found a striking dissociation between older versus younger participants in the relationship between the ability to retrieve contextual memories versus the ability to use these to guide attention to enhance performance on a target-detection task. Older participants showed significant deficits in the explicit retrieval task, but their behavioural benefits from memory-based orienting of attention were equivalent to those in young participants. Furthermore, memory-based orienting correlated significantly with explicit contextual LTM in younger adults but not in older adults. These results suggest that explicit memory deficits in ageing might not compromise initial perception and encoding of events. Importantly, the results also shed light on the mechanisms of memory-guided attention, suggesting that explicit contextual memories are not necessary. PMID:26649914

  7. Aspects of procedural memory are differentially impaired in Huntington's disease.

    PubMed

    Bylsma, F W; Brandt, J; Strauss, M E

    1990-01-01

    Procedural memory encompasses several phenomena, including motor and perceptual learning, cognitive rule learning and priming. These subclasses are differentially affected by differing neuropathologies, suggesting their functional independence and reliance upon different neural substrates. To test this hypothesis, performance on a maze learning task was compared in 15 Huntington's disease (HD) patients and 15 normal controls (NC) to assess specific route learning, cognitive skill learning and the effects of route predictability on performance. Results revealed that the HD group: (1) showed normal learning curves for a specific maze route; (2) are deficient in generalizing the cognitive skills across mazes; and, (3) fail to improve performance on a maze with a predictable route relative to mazes with unpredictable routes. These results are interpreted as supporting the independence of procedural memory subclasses. The basal ganglia are suggested as important structures in mediating the ability to generalize skills and appreciate patterned organization in to-be-acted-upon stimuli. PMID:14589688

  8. Distractor-relevance determines whether task-switching enhances or impairs distractor memory.

    PubMed

    Chiu, Yu-Chin; Egner, Tobias

    2016-01-01

    Richter and Yeung (2012) recently documented a novel task-switching effect, a switch-induced reduction in "memory selectivity," characterized by relatively enhanced memory for distractor stimuli and impaired memory for target stimuli encountered on switch trials compared with repeat trials. One interpretation of this finding argues that task-switching involves opening a "gate" to working memory, which promotes updating of the task-set, but at the same time allows for increased distraction from task-irrelevant information. However, in that study, the distractor category on a switch trial also represented the task-relevant target category from the previous trial. Thus, distractors were only intermittently task-irrelevant, such that switch-enhanced distractor memory could alternatively be because of remnant attention to the previously relevant stimuli, or "task-set inertia." Here we adjudicated between the open-gate and the task-set inertia accounts of switch-enhanced distractor memory by assessing incidental memory for distractors that were either intermittently or always task-irrelevant. While we replicated switch-enhanced distractor memory in the intermittently irrelevant distractor condition, this effect was reversed in the always-irrelevant distractor condition. These results speak against the open-gate account, and instead indicate that switch-enhanced distractor memory arises from task-set inertia, and will not be observed for truly task-irrelevant stimuli presented during switching. PMID:26594883

  9. Is sleep-related verbal memory consolidation impaired in sleepwalkers?

    PubMed

    Uguccioni, Ginevra; Pallanca, Olivier; Golmard, Jean-Louis; Leu-Semenescu, Smaranda; Arnulf, Isabelle

    2015-04-01

    In order to evaluate verbal memory consolidation during sleep in subjects experiencing sleepwalking or sleep terror, 19 patients experiencing sleepwalking/sleep terror and 19 controls performed two verbal memory tasks (16-word list from the Free and Cued Selective Reminding Test, and a 220- and 263-word modified story recall test) in the evening, followed by nocturnal video polysomnography (n = 29) and morning recall (night-time consolidation after 14 h, n = 38). The following morning, they were given a daytime learning task using the modified story recall test in reverse order, followed by an evening recall test after 9 h of wakefulness (daytime consolidation, n = 38). The patients experiencing sleepwalking/sleep terror exhibited more frequent awakenings during slow-wave sleep and longer wakefulness after sleep onset than the controls. Despite this reduction in sleep quality among sleepwalking/sleep terror patients, they improved their scores on the verbal tests the morning after sleep compared with the previous evening (+16 ± 33%) equally well as the controls (+2 ± 13%). The performance of both groups worsened during the daytime in the absence of sleep (-16 ± 15% for the sleepwalking/sleep terror group and -14 ± 11% for the control group). There was no significant correlation between the rate of memory consolidation and any of the sleep measures. Seven patients experiencing sleepwalking also sleep-talked during slow-wave sleep, but their sentences were unrelated to the tests or the list of words learned during the evening. In conclusion, the alteration of slow-wave sleep during sleepwalking/sleep terror does not noticeably impact on sleep-related verbal memory consolidation. PMID:25212397

  10. Sleep deprivation during a specific 3-hour time window post-training impairs hippocampal synaptic plasticity and memory

    PubMed Central

    Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer; Havekes, Robbert; Aton, Sara; Abel, Ted

    2014-01-01

    Sleep deprivation disrupts hippocampal function and plasticity. In particular, long-term memory consolidation is impaired by sleep deprivation, suggesting that a specific critical period exists following learning during which sleep is necessary. To elucidate the impact of sleep deprivation on long-term memory consolidation and synaptic plasticity, long-term memory was assessed when mice were sleep deprived following training in the hippocampus-dependent object place recognition task. We found that 3 hours of sleep deprivation significantly impaired memory when deprivation began 1 hour after training. In contrast, 3 hours of deprivation beginning immediately post-training did not impair spatial memory. Furthermore, a 3-hour sleep deprivation beginning 1 hour after training impaired hippocampal long-term potentiation (LTP), whereas sleep deprivation immediately after training did not affect LTP. Together, our findings define a specific 3-hour critical period, extending from 1 to 4 hours after training, during which sleep deprivation impairs hippocampal function. PMID:24380868

  11. Working Memory Impairment in People with Williams Syndrome: Effects of Delay, Task and Stimuli

    ERIC Educational Resources Information Center

    O'Hearn, Kirsten; Courtney, Susan; Street, Whitney; Landau, Barbara

    2009-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder associated with impaired visuospatial representations subserved by the dorsal stream and relatively strong object recognition abilities subserved by the ventral stream. There is conflicting evidence on whether this uneven pattern in WS extends to working memory (WM). The present studies…

  12. More than Memory Impairment in Voltage-Gated Potassium Channel Complex Encephalopathy

    PubMed Central

    Bettcher, Brianne M.; Gelfand, Jeffrey M.; Irani, Sarosh R.; Neuhaus, John; Forner, Sven; Hess, Christopher P.; Geschwind, Michael D.

    2014-01-01

    Objective Autoimmune encephalopathies (AE) are a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly endorsed, few reports of AE inclusively assess all cognitive domains in detail. Our aim was to perform an unbiased cognitive evaluation of AE patients with voltage-gated potassium channel complex antibodies (VGKCC-Abs) in order to delineate cognitive strengths and weaknesses. Methods We assessed serial VGKCC-Abs AE subjects (n=12) with a comprehensive evaluation of memory, executive functions, visuospatial skills, and language. Clinical MRI (n=10/12) was evaluated. Five subjects had serial cognitive testing available, permitting descriptive analysis of change. Results Subjects demonstrated mild to moderate impairment in memory (mean Z=−1.9) and executive functions (mean Z=−1.5), with variable impairments in language and sparing of visuospatial skills. MRI findings showed T2 hyperintensities in medial temporal lobe (10/10) and basal ganglia (2/10). Serial cognitive examination revealed heterogeneity in cognitive function; whereas most patients improved in one or more domains, residual impairments were observed in some patients. Conclusions This study augments prior neuropsychological analyses in VGKCC-Ab AE by identifying not only memory and executive function deficits, but also language impairments, with preservation of visuospatial functioning. This study further highlights the importance of domain-specific testing to parse out the complex cognitive phenotypes of VGKCC-Ab AE. PMID:24981998

  13. Cognitive-Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice.

    PubMed

    Lee, Hyeon Yong; Weon, Jin Bae; Jung, Youn Sik; Kim, Nam Young; Kim, Myong Ki; Ma, Choong Je

    2016-01-01

    Aronia melanocarpa (A. melanocarpa) berries are a fruit with a marked antioxidant effect. The objective of this study was to confirm the effect of A. melanocarpa berries extract against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance test. Moreover, we determined a possible mechanism of the cognitive-enhancing effect involving AChE activity and BDNF and p-CREB expression in the hippocampus of mice. A. melanocarpa berries extract attenuated the learning and memory impairment induced by scopolamine in the Morris water maze (79.3 ± 0.8 s of 200 mg/kg and 64.4 ± 10.7 s of 400 mg/kg on day 4) and passive avoidance tests (46.0 ± 41.1 s of 200 mg/kg and 25.6 ± 18.7 s of 400 mg/kg). A. melanocarpa berries extract reduced the acetylcholinesterase level in the hippocampus of scopolamine-injected mice and increased BDNF and p-CREB expression in the hippocampus. The major compound, cyanidin-3-O-galactoside, also reversed memory impairment. These results showed that A. melanocarpa berries extract improved memory impairment by inhibiting AChE and increasing BDNF and p-CREB expression, and cyanidin-3-O-galactoside may be responsible for the effect of A. melanocarpa berries extract. PMID:27239211

  14. Cognitive-Enhancing Effect of Aronia melanocarpa Extract against Memory Impairment Induced by Scopolamine in Mice

    PubMed Central

    Lee, Hyeon Yong; Weon, Jin Bae; Jung, Youn Sik; Kim, Nam Young; Kim, Myong Ki; Ma, Choong Je

    2016-01-01

    Aronia melanocarpa (A. melanocarpa) berries are a fruit with a marked antioxidant effect. The objective of this study was to confirm the effect of A. melanocarpa berries extract against scopolamine-induced memory impairment in mice using the Morris water maze and passive avoidance test. Moreover, we determined a possible mechanism of the cognitive-enhancing effect involving AChE activity and BDNF and p-CREB expression in the hippocampus of mice. A. melanocarpa berries extract attenuated the learning and memory impairment induced by scopolamine in the Morris water maze (79.3 ± 0.8 s of 200 mg/kg and 64.4 ± 10.7 s of 400 mg/kg on day 4) and passive avoidance tests (46.0 ± 41.1 s of 200 mg/kg and 25.6 ± 18.7 s of 400 mg/kg). A. melanocarpa berries extract reduced the acetylcholinesterase level in the hippocampus of scopolamine-injected mice and increased BDNF and p-CREB expression in the hippocampus. The major compound, cyanidin-3-O-galactoside, also reversed memory impairment. These results showed that A. melanocarpa berries extract improved memory impairment by inhibiting AChE and increasing BDNF and p-CREB expression, and cyanidin-3-O-galactoside may be responsible for the effect of A. melanocarpa berries extract. PMID:27239211

  15. Working Memory as a Predictor of Reading Achievement in Orally Educated Hearing-Impaired Children.

    ERIC Educational Resources Information Center

    Daneman, Meredyth; And Others

    1995-01-01

    This study found that three measures of working memory capacity (processing and storage capacity, reading and listening span, and visual shape span) were good predictors of reading achievement in 30 orally educated children (ages 5 to 14) with hearing impairments as well as in an age-matched hearing control group. Degree of hearing loss did not…

  16. Extensive Lesions of Cholinergic Basal Forebrain Neurons Do Not Impair Spatial Working Memory

    ERIC Educational Resources Information Center

    Vuckovich, Joseph A.; Semel, Mara E.; Baxter, Mark G.

    2004-01-01

    A recent study suggests that lesions to all major areas of the cholinergic basal forebrain in the rat (medial septum, horizontal limb of the diagonal band of Broca, and nucleus basalis magnocellularis) impair a spatial working memory task. However, this experiment used a surgical technique that may have damaged cerebellar Purkinje cells. The…

  17. Neuropsychological functioning in youth with obsessive compulsive disorder: an examination of executive function and memory impairment.

    PubMed

    Lewin, Adam B; Larson, Michael J; Park, Jennifer M; McGuire, Joseph F; Murphy, Tanya K; Storch, Eric A

    2014-04-30

    Preliminary research suggests neuropsychological deficits in youth with obsessive-compulsive disorder (OCD) similar to those in adults; however, small samples and methodological confounds limit interpretation. We aimed to examine the rates and clinical correlates of cognitive sequelae in youth with OCD, focusing on executive functioning and memory abilities. Youth ages 7-17 years with OCD (N=96) completed a hypothesis-driven neuropsychological battery (including the Rey-Osterreith Complex Figure, California Verbal Learning Test, and subtests of the Delis-Kaplan Executive Function System and Wide Range Assessment of Memory and Learning) that primarily assessed executive functioning, memory and processing speed. Cognitive sequelae were identified in 65% of youth (37% using a more stringent definition of impairment). Magnitude of cognitive sequelae was not associated with OCD severity or age; however, greater neuropsychological impairments were found amongst youth prescribed atypical neuroleptics and those diagnosed with comorbid tic disorders. Comorbidity burden was associated with presence of neuropsychological impairment, but was not specific to any single test. Findings suggest that the presence of cognitive sequelae is prevalent amongst treatment-seeking youth with OCD. Deficits were found in executive functioning and non-verbal memory performance but these impairments were not associated with OCD severity. PMID:24508366

  18. Effects of Increasing Task Load on Memory Impairment in Adults with Down Syndrome

    ERIC Educational Resources Information Center

    Oliver, Chris; Holland, Tony; Hall, Scott; Crayton, Lissa

    2005-01-01

    The effect of increasing the number of stimuli to be recalled was investigated to evaluate whether sensitivity for memory impairment was enhanced in adults with Down syndrome when using higher task load. Three levels of load were compared across three groups of adults: those with cognitive deterioration, no cognitive deterioration over age 40, and…

  19. Motor Control and Nonword Repetition in Specific Working Memory Impairment and SLI

    ERIC Educational Resources Information Center

    Archibald, Lisa M. D.; Joanisse, Marc F.; Munson, Benjamin

    2013-01-01

    Purpose: Debate around the underlying cognitive factors leading to poor performance in the repetition of nonwords by children with developmental impairments in language has centered around phonological short-term memory, lexical knowledge, and other factors. This study examines the impact of motor control demands on nonword repetition in groups of…

  20. Impaired Pitch Perception and Memory in Congenital Amusia: The Deficit Starts in the Auditory Cortex

    ERIC Educational Resources Information Center

    Albouy, Philippe; Mattout, Jeremie; Bouet, Romain; Maby, Emmanuel; Sanchez, Gaetan; Aguera, Pierre-Emmanuel; Daligault, Sebastien; Delpuech, Claude; Bertrand, Olivier; Caclin, Anne; Tillmann, Barbara

    2013-01-01

    Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a…

  1. Confirming feedback following a mistaken identification impairs memory for the culprit.

    PubMed

    Smalarz, Laura; Wells, Gary L

    2014-06-01

    This research examined whether confirming postidentification feedback following a mistaken identification impairs eyewitness memory for the original culprit. We also examined whether the degree of similarity between a mistakenly identified individual and the actual culprit plays a role in memory impairment. Participant-witnesses (N = 145) made mistaken identifications from a "similar" or a "dissimilar" culprit-absent photo lineup. The similar lineup contained individuals who were similar in appearance to the actual culprit and the dissimilar lineup contained individuals who were dissimilar in appearance to the actual culprit. After their identifications, witnesses were given confirming feedback ("Good job! You identified the suspect.") or no feedback. The experimenter then feigned having accidentally given the witnesses the wrong photo lineup. After telling witnesses to disregard whatever they saw in the first lineup, the experimenter gave witnesses the "correct" (culprit-present) lineup and told the witnesses to do their best to identify the culprit. Identifying a dissimilar individual and receiving confirming feedback after a misidentification had independent impairing effects on memory for the original culprit. Results extend the traditional conceptualization of the postidentification feedback effect by showing that confirming feedback not only distorts witnesses' retrospective self-reports, but it also impairs recognition memory for the culprit. PMID:24707912

  2. A Functional Magnetic Resonance Imaging Investigation of Verbal Working Memory in Adolescents with Specific Language Impairment

    ERIC Educational Resources Information Center

    Weismer, Susan Ellis; Plante, Elena; Jones, Maura; Tomblin, Bruce J.

    2005-01-01

    This study used neuroimaging and behavioral techniques to examine the claim that processing capacity limitations underlie specific language impairment (SLI). Functional magnetic resonance imaging (fMRI) was used to investigate verbal working memory in adolescents with SLI and normal language (NL) controls. The experimental task involved a modified…

  3. Mothers' Autobiographical Memory and Book Narratives with Children with Specific Language Impairment

    ERIC Educational Resources Information Center

    Tompkins, Virginia; Farrar, M. Jeffrey

    2011-01-01

    This study examined the role that mothers' scaffolding plays in the autobiographical memory (AM) and storybook narratives of children with specific language impairment (SLI). Seven 4-5-year-old children and their mothers co-constructed narratives in both contexts. We also compared children's narratives with mothers to their narratives with an…

  4. 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

  5. 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

  6. Memory for Public Events in Mild Cognitive Impairment and Alzheimer's Disease: The Importance of Rehearsal.

    PubMed

    Langlois, Roxane; Joubert, Sven; Benoit, Sophie; Dostie, Valérie; Rouleau, Isabelle

    2016-01-22

    Ribot's law refers to the better preservation of remote memories compared with recent ones that presumably characterizes retrograde amnesia. Even if Ribot-type temporal gradient has been extensively studied in retrograde amnesia, particularly in Alzheimer's disease (AD), this pattern has not been consistently found. One explanation for these results may be that rehearsal frequency rather than remoteness accounts for the better preservation of these memories. Thus, the aim of present study was to address this question by studying retrograde semantic memory in subjects with amnestic mild cognitive impairment (aMCI) (n = 20), mild AD (n = 20) and in healthy older controls (HC; n = 19). In order to evaluate the impact of repetition as well as the impact of remoteness, we used a test assessing memory for enduring and transient public events that occurred in the recent and remote past. Results show no clear temporal gradient across time periods (1960-1975; 1976-1990; 1991-2005; 2006-2011), but a better performance was observed in all three groups for enduring compared with transient events. Moreover, although deficits were globally found in both patients groups compared with HC, more specific analyses revealed that aMCI patients were only impaired on transient events while AD patients were impaired on both transient and enduring events. Exploratory analyses also revealed a tendency suggesting preservation of remote transient events in aMCI. These findings are discussed with regards to memory consolidation models. PMID:26836162

  7. Acute stress does not affect the impairing effect of chronic stress on memory retrieval

    PubMed Central

    Ozbaki, Jamile; Goudarzi, Iran; Salmani, Mahmoud Elahdadi; Rashidy-Pour, Ali

    2016-01-01

    Objective(s): Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress.

  8. Short-term memory for order but not for item information is impaired in developmental dyslexia.

    PubMed

    Hachmann, Wibke M; Bogaerts, Louisa; Szmalec, Arnaud; Woumans, Evy; Duyck, Wouter; Job, Remo

    2014-07-01

    Recent findings suggest that people with dyslexia experience difficulties with the learning of serial order information during the transition from short- to long-term memory (Szmalec et al. Journal of Experimental Psychology: Learning, Memory, & Cognition 37(5): 1270-1279, 2011). At the same time, models of short-term memory increasingly incorporate a distinction of order and item processing (Majerus et al. Cognition 107: 395-419, 2008). The current study is aimed to investigate whether serial order processing deficiencies in dyslexia can be traced back to a selective impairment of short-term memory for serial order and whether this impairment also affects processing beyond the verbal domain. A sample of 26 adults with dyslexia and a group of age and IQ-matched controls participated in a 2 × 2 × 2 experiment in which we assessed short-term recognition performance for order and item information, using both verbal and nonverbal material. Our findings indicate that, irrespective of the type of material, participants with dyslexia recalled the individual items with the same accuracy as the matched control group, whereas the ability to recognize the serial order in which those items were presented appeared to be affected in the dyslexia group. We conclude that dyslexia is characterized by a selective impairment of short-term memory for serial order, but not for item information, and discuss the integration of these findings into current theoretical views on dyslexia and its associated dysfunctions. PMID:24488229

  9. Reentrainment Impairs Spatial Working Memory until Both Activity Onset and Offset Reentrain.

    PubMed

    Ruby, Norman F; Patton, Danica F; Bane, Shalmali; Looi, David; Heller, H Craig

    2015-10-01

    Compression of the active phase (α) during reentrainment to phase-shifted light-dark (LD) cycles is a common feature of circadian systems, but its functional consequences have not been investigated. This study tested whether α compression in Siberian hamsters (Phodopus sungorus) impaired their spatial working memory as assessed by spontaneous alternation (SA) behavior in a T-maze. Animals were exposed to a 1- or 3-h phase delay of the LD cycle (16 h light/8 h dark). SA behavior was tested at 4 multiday intervals after the phase shift, and α was quantified for those days. All animals failed at the SA task while α was decompressing but recovered spatial memory ability once α returned to baseline levels. A second experiment exposed hamsters to a 2-h light pulse either early or late at night to compress α without phase-shifting the LD cycle. SA behavior was impaired until α decompressed to baseline levels. In a third experiment, α was compressed by changing photoperiod (LD 16:8, 18:6, 20:4) to see if absolute differences in α were related to spatial memory ability. Animals performed the SA task successfully in all 3 photoperiods. These data show that the dynamic process of α compression and decompression impairs spatial working memory and suggests that α modulation is a potential biomarker for assessing the impact of transmeridian flight or shift work on memory. PMID:26224657

  10. Mice lacking collapsin response mediator protein 1 manifest hyperactivity, impaired learning and memory, and impaired prepulse inhibition

    PubMed Central

    Yamashita, Naoya; Takahashi, Aoi; Takao, Keizo; Yamamoto, Toshifumi; Kolattukudy, Pappachan; Miyakawa, Tsuyoshi; Goshima, Yoshio

    2013-01-01

    Collapsin response mediator protein 1 (CRMP1) is one of the CRMP family members that are involved in various aspects of neuronal development such as axonal guidance and neuronal migration. Here we provide evidence that crmp1−/− mice exhibited behavioral abnormalities related to schizophrenia. The crmp1−/− mice exhibited hyperactivity and/or impaired emotional behavioral phenotype. These mice also exhibited impaired context-dependent memory and long-term memory retention. Furthermore, crmp1−/− mice exhibited decreased prepulse inhibition, and this phenotype was rescued by administration of chlorpromazine, a typical antipsychotic drug. In addition, in vivo microdialysis revealed that the methamphetamine-induced release of dopamine in prefrontal cortex was exaggerated in crmp1−/− mice, suggesting that enhanced mesocortical dopaminergic transmission contributes to their hyperactivity phenotype. These observations suggest that impairment of CRMP1 function may be involved in the pathogenesis of schizophrenia. We propose that crmp1−/− mouse may model endophenotypes present in this neuropsychiatric disorder. PMID:24409129

  11. Histone Acetylation Regulation in Sleep Deprivation-Induced Spatial Memory Impairment.

    PubMed

    Duan, Ruifeng; Liu, Xiaohua; Wang, Tianhui; Wu, Lei; Gao, Xiujie; Zhang, Zhiqing

    2016-09-01

    Sleep disorders negatively affect cognition and health. Recent evidence has indicated that chromatin remodeling via histone acetylation regulates cognitive function. This study aimed to investigate the possible roles of histone acetylation in sleep deprivation (SD)-induced cognitive impairment. Results of the Morris water maze test showed that 3 days of SD can cause spatial memory impairment in Wistar rats. SD can also decrease histone acetylation levels, increase histone deacetylase 2 (HDAC2) expression, and decrease histone acetyltransferase (CBP) expression. Furthermore, SD can reduce H3 and H4 acetylation levels in the promoters of the brain-derived neurotrophic factor (Bdnf) gene and thus significantly downregulate BDNF expression and impair the activity of key BDNF signaling pathways (pCaMKII, pErk2, and pCREB). However, treatment with the HDAC inhibitor trichostatin A attenuated all the negative effects induced by SD. Therefore, BDNF and its histone acetylation regulation may play important roles in SD-induced spatial memory impairment, whereas HDAC inhibition possibly confers protection against SD-induced impairment in spatial memory and hippocampal functions. PMID:27161370

  12. Ameliorating effect of luteolin on memory impairment in an Alzheimer's disease model

    PubMed Central

    WANG, HUIMIN; WANG, HUILING; CHENG, HUIXIN; CHE, ZHENYONG

    2016-01-01

    Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorder. It is characterized by the formation of amyloid plaques and neurofibrillary tangles in the brain, the degeneration of cholinergic neurons and neuronal cell death. The present study aimed to investigate the effect of luteolin, a flavonoid compound, on memory impairment in a streptozotocin (STZ)-induced Alzheimer's rat model. Morris water maze and probe tests were performed to examine the effect of luteolin treatment on cognition and memory. The effect of luteolin on CA1 pyramidal layer thickness was also examined. The results demonstrated that luteolin significantly ameliorated the spatial learning and memory impairment induced by STZ treatment. STZ significantly reduced the thickness of CA1 pyramidal layer and treatment of luteolin completely abolished the inhibitory effect of STZ. Our results suggest that luteolin has a potentially protective effect on learning defects and hippocampal structures in AD. PMID:27035793

  13. Electroacupuncture restores learning and memory impairment induced by both diabetes mellitus and cerebral ischemia in rats.

    PubMed

    Jing, Xiang-Hong; Chen, Shu-Li; Shi, Hong; Cai, Hong; Jin, Zhi-Gao

    2008-10-10

    Previous investigations have demonstrated that electroacupunctural stimulation can ameliorate primary and secondary symptoms such as peripheral neuropathy and diabetic encephalopathy in diabetic rats. In this study, we investigated whether electroacupuncture could improve learning and memory which was typically impaired in diabetic rats with cerebral ischemia. Furthermore, we investigated the mechanisms underlying its effects using passive avoidance test, active avoidance test, Morris water maze and electrophysiology. Electroacupuncture increased the step-down latency in passive avoidance test and accurate rate in active avoidance test, decreased the escape latency in Morris water maze. After electroacupuncture treatment, the long-term potentiation (LTP) impaired by both diabetes and cerebral ischemia was restored significantly. These results suggest that electroacupuncture can ameliorate learning and memory capacity impaired by hyperglycemia and ischemia. LTP plays a very important role in this beneficial effect. PMID:18692547

  14. Greater memory impairment in dementing females than males relative to sex-matched healthy controls.

    PubMed

    Gale, Shawn D; Baxter, Leslie; Thompson, Juliann

    2016-01-01

    Previously we demonstrated sex differences in episodic memory in healthy elderly and suggested that normative data be separated by sex. The present study extended the exploration of sex differences on memory measures into two clinical populations, mild cognitive impairment (MCI) and Alzheimer's disease (AD). Seventy-six subjects with MCI and 101 subjects with AD diagnosed by a multidisciplinary team were included. These two groups were also compared to a group of 177 healthy elderly control participants. Sex differences on the Rey Auditory Verbal Learning Test (RAVLT; total and delayed recall) raw scores and Brief Visuospatial Memory Test-Revised (BVMT-R) were demonstrated within the healthy but not the MCI or AD groups. Calculating z scores by sex for both dementing groups based on the healthy controls suggested a larger performance gap between healthy and dementing women than between healthy and dementing men. MCI females were on average 0.48 standard deviations lower for total verbal learning compared to healthy female controls than were MCI males when compared to healthy male controls. For verbal delayed recall the gap was even larger (SD = 1.09). Similarly, on the BVMT-R, a measure of visual memory, the difference was 0.60 standard deviations for total visual learning and 0.99 standard deviations for delayed recall. This same sex difference, with females showing greater impairment compared to the controls group than did the males, was also present within the AD group. The greater memory impairment in dementing females rather than males when compared to sex-matched healthy controls was unlikely to be due to more severe illness since females performed equivalently to males on the Clinical Dementia Rating Scale, Mini-Mental Status Examination, and Dementia Rating Scale, and were also similar for age, education, and apolipoprotein status. The present study suggested relatively greater memory impairment in females with MCI or AD than in controls. PMID:26735615

  15. Stress and memory retrieval in women: no strong impairing effect during the luteal phase.

    PubMed

    Schoofs, Daniela; Wolf, Oliver T

    2009-06-01

    Stress has been shown to impair delayed memory retrieval, but so far no study has been conducted solely with naturally cycling women. In a crossover design, 36 women (all in the luteal phase) participated in two experimental conditions (stress vs. control). Delayed memory retrieval of a wordlist learned 24 hours earlier was tested after stress or control treatment. Although stressed subjects showed a strong cortisol increase following stress, no influence on memory retrieval occurred. In an additional data analysis, subjects were split up into a cortisol responder and a cortisol nonresponder group. However, again no evidence for a stress-induced retrieval impairment became apparent. Similarly, no correlation was observed between the stress-induced cortisol increase and memory. This study failed to find an influence of stress on memory retrieval in women tested in the luteal phase. The findings are in contrast to our previous results obtained with men. Evidence is discussed that the luteal phase, which is characterized by elevated gonadal steroids, is associated with reduced glucocorticoid sensitivity. This might underlie the missing impact of stress on memory. PMID:19485561

  16. Excitotoxic lesion of the perirhinal cortex impairs spatial working memory in a delayed-alternation task.

    PubMed

    Maioli, Silvia; Gangarossa, Giuseppe; Locchi, Federica; Andrioli, Anna; Bertini, Giuseppe; Rimondini, Roberto

    2012-05-01

    The perirhinal cortex (PRh) is strategically located between the neocortex and memory-related structures such as the entorhinal cortex and the hippocampal formation. The pattern of strong reciprocal connections between these areas, together with experimental evidence that PRh damage induces specific memory deficits, has placed this cortical region at the center of a growing interest for its role in learning and memory mechanisms. The aim of the present study is to clarify the involvement of PRh in learning and retention in a novel experimental model of spatial working memory, the water T-maze. The data show that pre-acquisition neurotoxic PRh lesions caused task-learning deficits. This impairment was observed during the acquisition phase as well as the retrieval phase. On the other hand, a post-acquisition PRh neurotoxic lesion failed to impair the acquisition and the retrieval of the water T-maze task performed 32 day after lesion. These results suggest a possible key role of PRh in the acquisition but not in the retention of a working memory task. Furthermore, these results show that the water T-maze may be a suitable learning paradigm to study different components of learning and memory. PMID:22391121

  17. Associative memory and underlying brain correlates in older adults with mild cognitive impairment.

    PubMed

    Chen, Pei-Ching; Chang, Yu-Ling

    2016-05-01

    This study investigated associative recognition memory by using unique features of the Chinese language and the underlying neuroanatomical correlates. The study participants were 22 Chinese speakers with mild cognitive impairment (MCI) and 25 cognitively normal (CN) Chinese speakers. The results revealed that the MCI group demonstrated impaired associative memory performance, despite exhibiting item memory performance comparable with that of the CN group, and that associative memory performance in older adults was associated with gray matter integrity in the medial temporal regions as well as executive function. An abnormal elevation was also observed in false-positive errors related to features unique to Chinese characters, namely orthographical errors, in addition to rearranged and semantic errors in the MCI group relative to the CN group, and the three error subtypes were differentially associated with gray matter integrity in the hippocampus or lateral prefrontal regions. Overall, these results demonstrate the value of evaluating associative memory in people with prodromal Alzheimer's disease (AD), and further elucidate the underlying neural substrates related to associative recognition memory in older adults. PMID:27033742

  18. Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence.

    PubMed

    Cooper, Janine M; Gadian, David G; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-06-01

    Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. PMID:24343890

  19. Cholinergic hypofunction impairs memory acquisition possibly through hippocampal Arc and BDNF downregulation.

    PubMed

    Gil-Bea, Francisco J; Solas, Maite; Mateos, Laura; Winblad, Bengt; Ramírez, María J; Cedazo-Mínguez, Angel

    2011-09-01

    Recent evidence suggests that activity-regulated cytoskeleton associated protein (Arc) and brain-derived neurotrophic factor (BDNF) are key players in the cellular mechanisms that trigger synaptic changes and memory consolidation. Cholinergic deafferentiation of hippocampus has been largely shown to induce memory impairments in different behavioral tasks. However, the mechanisms underlying cholinergic-induced memory formation remain unclear. The role of hippocampal cholinergic denervation on synaptic consolidation and further acquisition of spatial memory was hereby examined by analyzing Arc and BDNF in standard environment and after behavioral training in Morris water maze (MWM). In standard environment, a cholinergic hypofunction induced by the toxin (192) IgG-saporin led to significant decreases in Arc protein and mRNA as well as in BDNF. Lesioned rats subjected to MWM showed a worse acquisition performance that was reversed after galantamine treatment. Recovery of memory acquisition was accompanied by normalization of Arc and BDNF levels in hippocampus. Stimulation of muscarinic, but not nicotinic receptors, in hippocampal primary neurons caused a rapid induction of Arc production. These data suggest that cholinergic denervation of hippocampus leads to deficits in muscarinic-dependent induction of Arc and a subsequent impairment of spatial memory acquisition. PMID:20865740

  20. Neonatal Hypoxia, Hippocampal Atrophy, and Memory Impairment: Evidence of a Causal Sequence

    PubMed Central

    Cooper, Janine M.; Gadian, David G.; Jentschke, Sebastian; Goldman, Allan; Munoz, Monica; Pitts, Georgia; Banks, Tina; Chong, W. Kling; Hoskote, Aparna; Deanfield, John; Baldeweg, Torsten; de Haan, Michelle; Mishkin, Mortimer; Vargha-Khadem, Faraneh

    2015-01-01

    Neonates treated for acute respiratory failure experience episodes of hypoxia. The hippocampus, a structure essential for memory, is particularly vulnerable to such insults. Hence, some neonates undergoing treatment for acute respiratory failure might sustain bilateral hippocampal pathology early in life and memory problems later in childhood. We investigated this possibility in a cohort of 40 children who had been treated neonatally for acute respiratory failure but were free of overt neurological impairment. The cohort had mean hippocampal volumes (HVs) significantly below normal control values, memory scores significantly below the standard population means, and memory quotients significantly below those predicted by their full scale IQs. Brain white matter volume also fell below the volume of the controls, but brain gray matter volumes and scores on nonmnemonic neuropsychological tests were within the normal range. Stepwise linear regression models revealed that the cohort's HVs were predictive of degree of memory impairment, and gestational age at treatment was predictive of HVs: the younger the age, the greater the atrophy. We conclude that many neonates treated for acute respiratory failure sustain significant hippocampal atrophy as a result of the associated hypoxia and, consequently, show deficient memory later in life. PMID:24343890

  1. Antioxidant administration prevents memory impairment in an animal model of maple syrup urine disease.

    PubMed

    Scaini, Giselli; Teodorak, Brena P; Jeremias, Isabela C; Morais, Meline O; Mina, Francielle; Dominguini, Diogo; Pescador, Bruna; Comim, Clarissa M; Schuck, Patrícia F; Ferreira, Gustavo C; Quevedo, João; Streck, Emilio L

    2012-05-16

    Maple syrup urine disease (MSUD) is an autosomal recessive metabolic disorder resulting from deficiency of branched-chain α-keto acid dehydrogenase complex leading to branched chain amino acids (BCAA) leucine, isoleucine, and valine accumulation as well as their corresponding transaminated branched-chain α-keto acids. MSUD patients present neurological dysfunction and cognitive impairment. Here, we investigated whether acute and chronic administration of a BCAA pool causes impairment of acquisition and retention of avoidance memory in young rats. We have used two administration protocols. Acute administration consisted of three subcutaneous administrations of the BCAA pool (15.8 μL/g body weight at 1-h intervals) containing 190 mmol/L leucine, 59 mmol/L isoleucine, and 69 mmol/L valine or saline solution (0.85% NaCl; control group) in 30 days old Wistar rats. Chronic administration consisted of two subcutaneous administrations of BCAA pool for 21 days in 7 days old Wistar rats. N-acetylcysteine (NAC; 20 mg/kg) and deferoxamine (DFX; 20 mg/kg) co administration influence on behavioral parameters after chronic BCAA administration was also investigated. BCAA administration induced long-term memory impairment in the inhibitory avoidance and CMIA (continuous multiple-trials step-down inhibitory avoidance) tasks whereas with no alterations in CMIA retention memory. Inhibitory avoidance alterations were prevented by NAC and DFX. BCAA administration did not impair the neuropsychiatric state, muscle tone and strength, and autonomous function evaluated with the SHIRPA (SmithKline/Harwell/ImperialCollege/RoyalHospital/Phenotype Assessment) protocol. Taken together, our results indicate that alterations of motor activity or emotionality probably did not contribute to memory impairment after BCAA administration and NAC and DFX effects suggest that cognition impairment after BCAA administration may be caused by oxidative brain damage. PMID:22433584

  2. The effects of Anethum graveolens essence on scopolamine-induced memory impairment in mice.

    PubMed

    Mesripour, Azadeh; Rafieian-Kopaei, Mahmoud; Bahrami, Bahareh

    2016-01-01

    Since Anethum graveolens (Dill) has phytoestrogenic compounds and it is proven that estrogens exert beneficial effects on cognition; the aim of this study was to understand if this plant can improve memory performance. Male Balb/c mice weighing 25-30 g were used in this study and memory was assessed by the novel object recognition task. In this method, the difference in the exploration time between a familiar object and a novel object is taken as an index of memory performance (recognition index, RI). Scopolamine significantly reduced memory index (RI = -15.5% ± 3.0). Dill essence (100 mg/kg, ip) prevented the harmful effects of scopolamine on memory (RI = 40% ± 5.5), thus RI did not differ with control animals (RI = 50% ± 5.8). In addition, 17-β estradiol also prevented memory impairment in animals (0.2 mg/kg, ip; RI = 35.8% ± 6.5). Nevertheless, the beneficial effects of dill essence were antagonized by prior injection of tamoxifen (1 mg/kg, ip; RI = -30% ± 7.8). Although phytoesrogens are not steroids, the beneficial effect of dill on memory, at least in part, may have been achieved by estrogenic receptors present in the brain. Thus dill essence could be promising in improving memory and cognition, mainly in postmenopausal women. PMID:27168754

  3. Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice.

    PubMed

    Tuscher, Jennifer J; Szinte, Julia S; Starrett, Joseph R; Krentzel, Amanda A; Fortress, Ashley M; Remage-Healey, Luke; Frick, Karyn M

    2016-07-01

    The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in the dorsal hippocampus observed 30min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. PMID:27178577

  4. The effects of Anethum graveolens essence on scopolamine-induced memory impairment in mice

    PubMed Central

    Mesripour, Azadeh; Rafieian-Kopaei, Mahmoud; Bahrami, Bahareh

    2016-01-01

    Since Anethum graveolens (Dill) has phytoestrogenic compounds and it is proven that estrogens exert beneficial effects on cognition; the aim of this study was to understand if this plant can improve memory performance. Male Balb/c mice weighing 25-30 g were used in this study and memory was assessed by the novel object recognition task. In this method, the difference in the exploration time between a familiar object and a novel object is taken as an index of memory performance (recognition index, RI). Scopolamine significantly reduced memory index (RI = -15.5% ± 3.0). Dill essence (100 mg/kg, ip) prevented the harmful effects of scopolamine on memory (RI = 40% ± 5.5), thus RI did not differ with control animals (RI = 50% ± 5.8). In addition, 17-β estradiol also prevented memory impairment in animals (0.2 mg/kg, ip; RI = 35.8% ± 6.5). Nevertheless, the beneficial effects of dill essence were antagonized by prior injection of tamoxifen (1 mg/kg, ip; RI = -30% ± 7.8). Although phytoesrogens are not steroids, the beneficial effect of dill on memory, at least in part, may have been achieved by estrogenic receptors present in the brain. Thus dill essence could be promising in improving memory and cognition, mainly in postmenopausal women. PMID:27168754

  5. Olfactory dysfunction and cognitive impairment in age-related neurodegeneration: prevalence related to patient selection, diagnostic criteria and therapeutic treatment of aged clients receiving clinical neurology and community-based care.

    PubMed

    Babizhayev, Mark A; Deyev, Anatoliy I; Yegorov, Yegor E

    2011-11-01

    A decrease in olfactory function with age has been attributed to a variety of factors including normal anatomical and physiological changes in aging, surgery, trauma, environmental factors, medications and disease. Olfactory impairment has also been associated with neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Deficits in these chemical senses cannot only reduce the pleasure and comfort from food, but represent risk factors for nutritional and immune deficiencies as well as adherence to specific dietary regimens. Therapy is limited, but one should be aware of the existing medical and surgical treatment modalities. Reactive oxygen and nitrogen species, copper and zinc ions, glycating agents and reactive aldehydes, protein cross-linking and proteolytic dysfunction may all contribute to neurodegeneration, olfactory dysfunction, AD. Carnosine (beta-alanyl- L-histidine) is a naturally-occurring, pluripotent, homeostatic transglycating agent. The olfactory lobe is normally enriched in carnosine and zinc. Loss of olfactory function and oxidative damage to olfactory tissue are early symptoms of AD. Protein and lipid oxidation and glycation are integral components of the AD pathophysiology. Carnosine can suppress amyloidbeta peptide toxicity, inhibit production of oxygen free-radicals, scavenge hydroxyl radicals and reactive aldehydes, and suppresses protein glycation. The observations suggest that patented non-hydrolyzed carnosine lubricant drug delivery or perfume toilet water formulations combined with related moiety amino acid structures, such as beta-alanine, should be explored for therapeutic potential towards olfactory dysfunction, AD and other neurodegenerative disorders. "The olfactory system, anatomically, is right in the middle of the part of the brain that's very important for memory. There are strong neural connections between the two." ~ Donald Wilson. PMID:22082323

  6. Syntactic comprehension and working memory in children with Specific Language Impairment, Autism or Down Syndrome

    PubMed Central

    Fortunato-Tavares, Talita; Andrade, Claudia R. F.; Befi-Lopes, Debora; Limongi, Suelly O.; Fernandes, Fernanda D. M.; Schwartz, Richard G.

    2016-01-01

    This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA), and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerized picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA, and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA, and DS differ from children with TLD in their comprehension of predicate and reflexive structures where knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance. PMID:25901467

  7. Syntactic comprehension and working memory in children with specific language impairment, autism or Down syndrome.

    PubMed

    Fortunato-Tavares, Talita; Andrade, Claudia R F; Befi-Lopes, Debora; Limongi, Suelly O; Fernandes, Fernanda D M; Schwartz, Richard G

    2015-07-01

    This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance. PMID:25901467

  8. Visual neglect: is there a relationship between impaired spatial working memory and re-cancellation?

    PubMed

    Wansard, Murielle; Meulemans, Thierry; Gillet, Sophie; Segovia, Fermin; Bastin, Christine; Toba, Monica N; Bartolomeo, Paolo

    2014-10-01

    In visual search tasks, neglect patients tend to explore and repeatedly re-cancel stimuli on the ipsilesional side, as if they did not realize that they had previously examined the rightward locations favoured by their lateral bias. The aim of this study was to explore the hypothesis that a spatial working memory deficit explains these ipsilesional re-cancellation errors in neglect patients. For the first time, we evaluated spatial working memory and re-cancellation through separate and independent tasks in a group of patients with right hemisphere damage and a diagnosis of left neglect. Results showed impaired spatial working memory in neglect patients. Compared to the control group, neglect patients cancelled fewer targets and made more re-cancellations both on the left side and on the right side. The spatial working memory deficit appears to be related to re-cancellations, but only for some neglect patients. Alternative interpretations of re-exploration of space are discussed. PMID:24989636

  9. Transfer and maintenance effects of online working-memory training in normal ageing and mild cognitive impairment.

    PubMed

    Vermeij, Anouk; Claassen, Jurgen A H R; Dautzenberg, Paul L J; Kessels, Roy P C

    2016-10-01

    Working memory (WM) is one of the cognitive functions that is susceptible to ageing-related decline. Interventions that are able to improve WM functioning at older age are thus highly relevant. In this pilot study, we explored the transfer effects of core WM training on the WM domain and other cognitive domains in 23 healthy older adults and 18 patients with amnestic mild cognitive impairment (MCI). Performance on neuropsychological tests was assessed before and after completion of the online five-week adaptive WM training, and after a three-month follow-up period. After training, both groups improved on the Digit Span and Spatial Span, gains that were maintained at follow-up. At an individual level, a limited number of participants showed reliable training gain. Healthy older adults, and to a lesser extent MCI patients, additionally improved on figural fluency at group level, but not at individual level. Results furthermore showed that global brain atrophy and hippocampal atrophy, as assessed by MRI, may negatively affect training outcome. Our study examined core WM training, showing gains on trained and untrained tasks within the WM domain, but no broad generalisation to other cognitive domains. More research is needed to evaluate the clinical relevance of these findings and to identify participant characteristics that are predictive of training gain. PMID:26010573

  10. [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

  11. Intermittent fasting attenuates lipopolysaccharide-induced neuroinflammation and memory impairment

    PubMed Central

    2014-01-01

    Background Systemic bacterial infections often result in enduring cognitive impairment and are a risk factor for dementia. There are currently no effective treatments for infection-induced cognitive impairment. Previous studies have shown that intermittent fasting (IF) can increase the resistance of neurons to injury and disease by stimulating adaptive cellular stress responses. However, the impact of IF on the cognitive sequelae of systemic and brain inflammation is unknown. Methods Rats on IF for 30 days received 1 mg/kg of lipopolysaccharide (LPS) or saline intravenously. Half of the rats were subjected to behavioral tests and the other half were euthanized two hours after LPS administration and the hippocampus was dissected and frozen for analyses. Results Here, we report that IF ameliorates cognitive deficits in a rat model of sepsis by a mechanism involving NF-κB activation, suppression of the expression of pro-inflammatory cytokines, and enhancement of neurotrophic support. Treatment of rats with LPS resulted in deficits in cognitive performance in the Barnes maze and inhibitory avoidance tests, without changing locomotor activity, that were ameliorated in rats that had been maintained on the IF diet. IF also resulted in reduced levels of mRNAs encoding the LPS receptor TLR4 and inducible nitric oxide synthase (iNOS) in the hippocampus. Moreover, IF prevented LPS-induced elevation of IL-1α, IL-1β and TNF-α levels, and prevented the LPS-induced reduction of BDNF levels in the hippocampus. IF also significantly attenuated LPS-induced elevations of serum IL-1β, IFN-γ, RANTES, TNF-α and IL-6 levels. Conclusions Taken together, our results suggest that IF induces adaptive responses in the brain and periphery that can suppress inflammation and preserve cognitive function in an animal model of systemic bacterial infection. PMID:24886300

  12. Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory

    PubMed Central

    Fá, M.; Puzzo, D.; Piacentini, R.; Staniszewski, A.; Zhang, H.; Baltrons, M. A.; Li Puma, D. D.; Chatterjee, I.; Li, J.; Saeed, F.; Berman, H. L.; Ripoli, C.; Gulisano, W.; Gonzalez, J.; Tian, H.; Costa, J. A.; Lopez, P.; Davidowitz, E.; Yu, W. H.; Haroutunian, V.; Brown, L. M.; Palmeri, A.; Sigurdsson, E. M.; Duff, K. E.; Teich, A. F.; Honig, L. S.; Sierks, M.; Moe, J. G.; D’Adamio, L.; Grassi, C.; Kanaan, N. M.; Fraser, P. E.; Arancio, O.

    2016-01-01

    Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer’s disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology. PMID:26786552

  13. Ovariectomy ameliorates dextromethorphan--induced memory impairment in young female rats.

    PubMed

    Jahng, Jeong Won; Cho, Hee Jeong; Kim, Jae Goo; Kim, Nam Youl; Lee, Seoul; Lee, Yil Seob

    2006-01-01

    We have previously found that dextromethorphan (DM), over-the-counter cough suppressant, impairs memory retention in water maze task, when it is repeatedly administrated to adolescent female rats at high doses. In this study we examined first if ovariectomy ameliorates the DM-induced memory impairment in female rats, and then whether or not the DM effect is revived by estrogen replacement in ovariectomized female rats. Female rat pups received bilateral ovariectomy or sham operation on postnatal day (PND) 21, and then intraperitoneal DM (40 mg/kg) daily during PND 28-37. Rats were subjected to the Morris water maze task from PND 38, approximately 24 h after the last DM injection. In probe trial, goal quadrant dwell time was significantly reduced by DM in the sham operated group, however, the reduction by DM did not occur in the ovariectomy group. When 17beta-estradiol was supplied to ovariectomized females during DM treatment, the goal quadrant dwell time was significantly decreased, compared to the vehicle control group. Furthermore, a major effect of estrogen replacement was found in the escape latency during the last 3 days of initial learning trials. These results suggest that ovariectomy may ameliorate the adverse effect of DM treatment on memory retention in young female rats, and that estrogen replacement may revive it, i.e. estrogen may take a major role in DM-induced memory impairment in female rats. PMID:16563229

  14. Treadmill exercise prevents learning and memory impairment in Alzheimer's disease-like pathology.

    PubMed

    Dao, An T; Zagaar, Munder A; Levine, Amber T; Salim, Samina; Eriksen, Jason L; Alkadhi, Karim A

    2013-06-01

    Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive memory loss. In contrast, accumulating evidence suggests a neuroprotective role of regular exercise in aging associated memory impairment. In this study, we investigated the ability of regular exercise to prevent impairments of short-term memory (STM) and early long-term potentiation (E-LTP) in area CA1 of the hippocampus in a rat model of AD (i.c.v. infusion of 250 pmol/day Aβ1-42 peptides). We utilized behavioral assessment, in vivo electrophysiological recording, and immunoblotting in 4 groups of adult Wistar rats: control, treadmill exercise (Ex), β-amyloid-infused (Aβ), and amyloid-infused/treadmill exercised (Ex/Aβ). Our findings indicated that Aβ rats made significantly more errors in the radial arm water maze (RAWM) compared to all other groups and exhibited suppressed E-LTP in area CA1, which correlated with deleterious alterations in the levels of memory and E-LTP-related signaling molecules including calcineurin (PP2B), brain derivedneurotrophic factor (BDNF) and phosphorylated CaMKII (p-CaMKII). Compared to controls, Ex and Ex/Aβ rats showed a similar behavioral performance and a normal E-LTP with no detrimental changes in the levels of PP2B, BDNF, and p- CaMKII. We conclude that treadmill exercise maybe able to prevent cognitive impairment associated with AD pathology. PMID:23627709

  15. Puerarin attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice.

    PubMed

    Zhao, Shan-shan; Yang, Wei-na; Jin, Hui; Ma, Kai-ge; Feng, Gai-feng

    2015-12-01

    Puerarin (PUE), an isoflavone purified from the root of Pueraria lobata (Chinese herb), has been reported to attenuate learning and memory impairments in the transgenic mouse model of Alzheimer's disease (AD). In the present study, we tested PUE in a sporadic AD (SAD) mouse model which was induced by the intracerebroventricular injection of streptozotocin (STZ). The mice were administrated PUE (25, 50, or 100mg/kg/d) for 28 days. Learning and memory abilities were assessed by the Morris water maze test. After behavioral test, the biochemical parameters of oxidative stress (glutathione peroxidase (GSH-Px), superoxide dismutases (SOD), and malondialdehyde (MDA)) were measured in the cerebral cortex and hippocampus. The SAD mice exhibited significantly decreased learning and memory ability, while PUE attenuated these impairments. The activities of GSH-Px and SOD were decreased while MDA was increased in the SAD animals. After PUE treatment, the activities of GSH-Px and SOD were elevated, and the level of MDA was decreased. The middle dose PUE was more effective than others. These results indicate that PUE attenuates learning and memory impairments and inhibits oxidative stress in STZ-induced SAD mice. PUE may be a promising therapeutic agent for SAD. PMID:26511841

  16. Visuospatial working memory is severely impaired in Bálint syndrome patients.

    PubMed

    Funayama, Michitaka; Nakagawa, Yoshitaka; Sunagawa, Kosaku

    2015-08-01

    Although it has been proposed that visuospatial working memory may be impaired in Bálint syndrome patients, neither a systematic study concerning this proposal nor a comparison with patients having right-parietal damage has been made. Visuospatial working memory was assessed for six Bálint syndrome patients and members of two control groups-one composed of individuals with right-parietal damage (n = 15) and a second of age- and gender-matched healthy individuals (n = 26). We placed special emphasis on patients with a mild form of Bálint syndrome who can judge positional relationships between two objects. First, the participants were subjected to delayed visuospatial matching tasks. Next, their visuospatial-temporal integration abilities were assessed using a shape-from-moving-dots task. Visuospatial working memory was impaired for Bálint syndrome patients compared with controls according to the results of the tests. The differences between the Bálint syndrome and control subjects remained when only data for patients with the mild form of Bálint syndrome were included. We conclude that visuospatial working memory may be severely impaired in Bálint syndrome patients and, therefore, might influence their inability to properly execute movements and behaviours associated with daily living. PMID:26117797

  17. Extracellular Tau Oligomers Produce An Immediate Impairment of LTP and Memory.

    PubMed

    Fá, M; Puzzo, D; Piacentini, R; Staniszewski, A; Zhang, H; Baltrons, M A; Li Puma, D D; Chatterjee, I; Li, J; Saeed, F; Berman, H L; Ripoli, C; Gulisano, W; Gonzalez, J; Tian, H; Costa, J A; Lopez, P; Davidowitz, E; Yu, W H; Haroutunian, V; Brown, L M; Palmeri, A; Sigurdsson, E M; Duff, K E; Teich, A F; Honig, L S; Sierks, M; Moe, J G; D'Adamio, L; Grassi, C; Kanaan, N M; Fraser, P E; Arancio, O

    2016-01-01

    Non-fibrillar soluble oligomeric forms of amyloid-β peptide (oAβ) and tau proteins are likely to play a major role in Alzheimer's disease (AD). The prevailing hypothesis on the disease etiopathogenesis is that oAβ initiates tau pathology that slowly spreads throughout the medial temporal cortex and neocortices independently of Aβ, eventually leading to memory loss. Here we show that a brief exposure to extracellular recombinant human tau oligomers (oTau), but not monomers, produces an impairment of long-term potentiation (LTP) and memory, independent of the presence of high oAβ levels. The impairment is immediate as it raises as soon as 20 min after exposure to the oligomers. These effects are reproduced either by oTau extracted from AD human specimens, or naturally produced in mice overexpressing human tau. Finally, we found that oTau could also act in combination with oAβ to produce these effects, as sub-toxic doses of the two peptides combined lead to LTP and memory impairment. These findings provide a novel view of the effects of tau and Aβ on memory loss, offering new therapeutic opportunities in the therapy of AD and other neurodegenerative diseases associated with Aβ and tau pathology. PMID:26786552

  18. Memory Impairment and Reduced Exploratory Behavior in Mice after Administration of Systemic Morphine

    PubMed Central

    Kitanaka, Junichi; Kitanaka, Nobue; Hall, F Scott; Fujii, Mei; Goto, Akiko; Kanda, Yusuke; Koizumi, Akira; Kuroiwa, Hirotoshi; Mibayashi, Satoko; Muranishi, Yumi; Otaki, Soichiro; Sumikawa, Minako; Tanaka, Koh-ichi; Nishiyama, Nobuyoshi; Uhl, George R; Takemura, Motohiko

    2015-01-01

    In the present study, the effects of morphine were examined on tests of spatial memory, object exploration, locomotion, and anxiety in male ICR mice. Administration of morphine (15 or 30 mg/kg, intraperitoneally (i.p.)) induced a significant decrease in Y-maze alternations compared to saline vehicle-treated mice. The reduced Y-maze alternations induced by morphine were completely blocked by naloxone (15 mg/kg) or β-funaltrexamine (5 mg/kg) but not by norbinaltorphimine (5 mg/kg) or naltrindole (5 mg/kg), suggesting that the morphine-induced spatial memory impairment was mediated predominantly by μ-opioid receptors (MOPs). Significant spatial memory retrieval impairments were observed in the Morris water maze (MWM) in mice treated with morphine (15 mg/kg) or scopolamine (1 mg/kg), but not with naloxone or morphine plus naloxone. Reduced exploratory time was observed in mice after administration of morphine (15 mg/kg), in a novel-object exploration test, without any changes in locomotor activity. No anxiolytic-like behavior was observed in morphine-treated mice in the elevated plus maze. A significant reduction in buried marbles was observed in morphine-treated mice measured in the marble-burying test, which was blocked by naloxone. These observations suggest that morphine induces impairments in spatial short-term memory and retrieval, and reduces exploratory behavior, but that these effects are not because of overall changes in locomotion or anxiety. PMID:25987850

  19. Phonological Working Memory Impairments in Children with Specific Language Impairment: Where Does the Problem Lie?

    ERIC Educational Resources Information Center

    Alt, Mary

    2011-01-01

    Purpose: The purpose of this study was to determine which factors contribute to the lexical learning deficits of children with specific language impairment (SLI). Method: Participants included 40 7-8-year old participants, half of whom were diagnosed with SLI and half of whom had normal language skills. We tested hypotheses about the contributions…

  20. Speech Perception and Phonological Short-Term Memory Capacity in Language Impairment: Preliminary Evidence from Adolescents with Specific Language Impairment (SLI) and Autism Spectrum Disorders (ASD)

    ERIC Educational Resources Information Center

    Loucas, Tom; Riches, Nick Greatorex; Charman, Tony; Pickles, Andrew; Simonoff, Emily; Chandler, Susie; Baird, Gillian

    2010-01-01

    Background: The cognitive bases of language impairment in specific language impairment (SLI) and autism spectrum disorders (ASD) were investigated in a novel non-word comparison task which manipulated phonological short-term memory (PSTM) and speech perception, both implicated in poor non-word repetition. Aims: This study aimed to investigate the…

  1. Prospective Memory Impairment and Executive Dysfunction in Prefrontal Lobe Damaged Patients: Is There a Causal Relationship?

    PubMed Central

    Carlesimo, Giovanni A.; di Paola, Margherita; Fadda, Lucia; Caltagirone, Carlo; Costa, Alberto

    2014-01-01

    Background. The prospective memory (PM) construct is aimed at capturing cognitive operations involved in the successful accomplishment of delayed intentions. It is generally agreed that PM impairment occurs in patients with prefrontal lobes damage. Objective. To evaluate if there is a causal role of a deficit of executive abilities (failures of planning, set-shifting, selective attention, or working memory) over the PM impairment. Methods. We report a detailed investigation of PM and executive abilities in two patients with posttraumatic damage to prefrontal lobes who complained from a reduced compliance with appointments and daily routines. Results. Laboratory tests confirmed a difficulty in fulfilling delayed intentions in response to the occurrence of critical events and elapsed time. In one patient, PM impairment was associated with poor performance on tests investigating planning, working memory, and mental shifting. The other patient performed in the normal range on all executive tests. Conclusions. Despite the frequent claim of a dependence of PM deficits from executive dysfunction, the reported cases demonstrate that this is not necessarily the case. The results are discussed in the light of current hypotheses relating PM impairment to other deficits that commonly occur as a result of damage to the prefrontal lobes. PMID:24825947

  2. Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment.

    PubMed

    Delpech, Jean-Christophe; Thomazeau, Aurore; Madore, Charlotte; Bosch-Bouju, Clementine; Larrieu, Thomas; Lacabanne, Chloe; Remus-Borel, Julie; Aubert, Agnès; Joffre, Corinne; Nadjar, Agnès; Layé, Sophie

    2015-11-01

    Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment. PMID:25948102

  3. Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment

    PubMed Central

    Murphy, Kelly J.; Troyer, Angela K.; Levine, Brian; Moscovitch, Morris

    2008-01-01

    Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66–84 years) and 17 aMCI (age 66–84 years) participants described a personal event from each of five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial-temporal-lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact. PMID:18675285

  4. Learning and memory impairments in children and adolescents with attention-deficit/hyperactivity disorder.

    PubMed

    Andersen, Per N; Egeland, Jens; Øie, Merete

    2013-01-01

    There are relatively few studies on learning and delayed memory with attention-deficit/hyperactivity disorder (ADHD). The objective of the present study was to examine acquisition, free delayed memory, and recognition skills in medication naive children and adolescents aged 8-16 years with ADHD combined subtype (36 participants) and inattentive subtype (45) compared to 50 healthy controls (HC) aged 8-17 years. Learning and delayed memory were assessed with the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised, which have compatible methods of administration, test format, and score ranges. The results showed that children with both ADHD subtypes scored significantly below HC in acquisition, free delayed memory, and recognition, even when controlling for the effect of IQ. Comparing phases in the learning process showed an initial deficit in acquisition but no increase in effect size in subsequent testing of free delayed memory or recognition. The study indicates that learning and delayed memory processes are impaired in both combined and inattentive subtypes of ADHD and that the deficits are not merely an artifact of IQ. The study indicates that emphasis must be put on the acquisition phase and how students with ADHD organize and encode new information. PMID:22392892

  5. Disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

    PubMed

    Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

    2013-07-01

    It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. PMID:23567106

  6. Reprint of: disrupting Jagged1-Notch signaling impairs spatial memory formation in adult mice.

    PubMed

    Sargin, Derya; Botly, Leigh C P; Higgs, Gemma; Marsolais, Alexander; Frankland, Paul W; Egan, Sean E; Josselyn, Sheena A

    2013-10-01

    It is well-known that Notch signaling plays a critical role in brain development and growing evidence implicates this signaling pathway in adult synaptic plasticity and memory formation. The Notch1 receptor is activated by two subclasses of ligands, Delta-like (including Dll1 and Dll4) and Jagged (including Jag1 and Jag2). Ligand-induced Notch1 receptor signaling is modulated by a family of Fringe proteins, including Lunatic fringe (Lfng). Although Dll1, Jag1 and Lfng are critical regulators of Notch signaling, their relative contribution to memory formation in the adult brain is unknown. To investigate the roles of these important components of Notch signaling in memory formation, we examined spatial and fear memory formation in adult mice with reduced expression of Dll1, Jag1, Lfng and Dll1 plus Lfng. We also examined motor activity, anxiety-like behavior and sensorimotor gating using the acoustic startle response in these mice. Of the lines of mutant mice tested, we found that only mice with reduced Jag1 expression (mice heterozygous for a null mutation in Jag1, Jag1(+/-)) showed a selective impairment in spatial memory formation. Importantly, all other behavior including open field activity, conditioned fear memory (both context and discrete cue), acoustic startle response and prepulse inhibition, was normal in this line of mice. These results provide the first in vivo evidence that Jag1-Notch signaling is critical for memory formation in the adult brain. PMID:23850596

  7. Preferential loss of dorsal-hippocampus synapses underlies memory impairments provoked by short, multimodal stress

    PubMed Central

    Maras, P M; Molet, J; Chen, Y; Rice, C; Ji, S G; Solodkin, A; Baram, T Z

    2014-01-01

    The cognitive effects of stress are profound, yet it is unknown if the consequences of concurrent multiple stresses on learning and memory differ from those of a single stress of equal intensity and duration. We compared the effects on hippocampus-dependent memory of concurrent, hours-long light, loud noise, jostling and restraint (multimodal stress) with those of restraint or of loud noise alone. We then examined if differences in memory impairment following these two stress types might derive from their differential impact on hippocampal synapses, distinguishing dorsal and ventral hippocampus. Mice exposed to hours-long restraint or loud noise were modestly or minimally impaired in novel object recognition, whereas similar-duration multimodal stress provoked severe deficits. Differences in memory were not explained by differences in plasma corticosterone levels or numbers of Fos-labeled neurons in stress-sensitive hypothalamic neurons. However, although synapses in hippocampal CA3 were impacted by both restraint and multimodal stress, multimodal stress alone reduced synapse numbers severely in dorsal CA1, a region crucial for hippocampus-dependent memory. Ventral CA1 synapses were not significantly affected by either stress modality. Probing the basis of the preferential loss of dorsal synapses after multimodal stress, we found differential patterns of neuronal activation by the two stress types. Cross-correlation matrices, reflecting functional connectivity among activated regions, demonstrated that multimodal stress reduced hippocampal correlations with septum and thalamus and increased correlations with amygdala and BST. Thus, despite similar effects on plasma corticosterone and on hypothalamic stress-sensitive cells, multimodal and restraint stress differ in their activation of brain networks and in their impact on hippocampal synapses. Both of these processes might contribute to amplified memory impairments following short, multimodal stress. PMID:24589888

  8. Sustained increase in α5GABAA receptor function impairs memory after anesthesia

    PubMed Central

    Zurek, Agnieszka A.; Yu, Jieying; Wang, Dian-Shi; Haffey, Sean C.; Bridgwater, Erica M.; Penna, Antonello; Lecker, Irene; Lei, Gang; Chang, Tom; Salter, Eric W.R.; Orser, Beverley A.

    2014-01-01

    Many patients who undergo general anesthesia and surgery experience cognitive dysfunction, particularly memory deficits that can persist for days to months. The mechanisms underlying this postoperative cognitive dysfunction in the adult brain remain poorly understood. Depression of brain function during anesthesia is attributed primarily to increased activity of γ-aminobutyric acid type A receptors (GABAARs), and it is assumed that once the anesthetic drug is eliminated, the activity of GABAARs rapidly returns to baseline and these receptors no longer impair memory. Here, using a murine model, we found that a single in vivo treatment with the injectable anesthetic etomidate increased a tonic inhibitory current generated by α5 subunit–containing GABAARs (α5GABAARs) and cell-surface expression of α5GABAARs for at least 1 week. The sustained increase in α5GABAAR activity impaired memory performance and synaptic plasticity in the hippocampus. Inhibition of α5GABAARs completely reversed the memory deficits after anesthesia. Similarly, the inhaled anesthetic isoflurane triggered a persistent increase in tonic current and cell-surface expression of α5GABAARs. Thus, α5GABAAR function does not return to baseline after the anesthetic is eliminated, suggesting a mechanism to account for persistent memory deficits after general anesthesia. PMID:25365226

  9. Learning and serial effects on verbal memory in mild cognitive impairment.

    PubMed

    Campos-Magdaleno, María; Díaz-Bóveda, Rosalía; Juncos-Rabadán, Onésimo; Facal, David; Pereiro, Arturo X

    2016-01-01

    The objective of this study was to examine different patterns of learning and episodic memory in 3 mild cognitive impairment (MCI) groups and a control group by administering the California Verbal Learning Test (CVLT) and using serial position effect as a principal variable. The study sample included 3 groups of patients with MCI (n = 90) divided into single-domain amnestic, multiple-domain amnestic, and multiple-domain nonamnestic MCI and a group of healthy controls (n = 60). We compared the performance of each group on several CVLT measures used in previous research, and we included a new measure that provides specific information about the serial effect. Data showed a similar pattern of learning and memory impairment in both amnestic MCI groups (i.e., no differences between the multiple-domain and single-domain subtypes); the recency effect was significantly higher in both amnestic MCI groups than in all other groups, and the primacy effect was only lower in the multiple-domain amnestic MCI subtype. Verbal learning and memory profiles of patients with amnestic MCI were very similar, independent of the presence of deficits in cognitive domains other than episodic memory. Results are discussed in light of the unitary-store model of memory. PMID:26569625

  10. SPATIAL MEMORY IMPAIRMENT AND HIPPOCAMPAL CELL LOSS INDUCED BY OKADAIC ACID (EXPERIMENTAL STUDY).

    PubMed

    Chighladze, M; Dashniani, M; Beselia, G; Kruashvili, L; Naneishvili, T

    2016-01-01

    In the present study, we evaluated and compared effect of intracerebroventricular (ICV) and intrahippocampal bilateral microinjection of okadaic acid (OA) on spatial memory function assessed in one day water maze paradigm and hippocampal structure in rats. Rats were divided in following groups: Control(icv) - rats injected with ICV and aCSF; Control(hipp) - rats injected intrahippocampally with aCSF; OAicv - rats injected with ICV and OA; OAhipp - rats injected intrahippocampally with OA. Nissl staining of hippocampal sections showed that the pyramidal cell loss in OAhipp group is significantly higher than that in the OAicv. The results of behavioral experiments showed that ICV or intrahippocampal bilateral microinjection of OA did not affect learning process and short-term spatial memory but induced impairment in spatial long-term memory assessed in probe test performance 24 h after training. OA-induced spatial memory impairment may be attributed to the hippocampal cell death. Based on these results OA induced memory deficit and hippocampal cell loss in rat may be considered as a potential animal model for preclinical evaluation of antidementic drug activity. PMID:26870981

  11. High dose zinc supplementation induces hippocampal zinc deficiency and memory impairment with inhibition of BDNF signaling.

    PubMed

    Yang, Yang; Jing, Xiao-Peng; Zhang, Shou-Peng; Gu, Run-Xia; Tang, Fang-Xu; Wang, Xiu-Lian; Xiong, Yan; Qiu, Mei; Sun, Xu-Ying; Ke, Dan; Wang, Jian-Zhi; Liu, Rong

    2013-01-01

    Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit. PMID:23383172

  12. The memory-enhancing effect of erucic acid on scopolamine-induced cognitive impairment in mice.

    PubMed

    Kim, Eunji; Ko, Hae Ju; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Ha Neul; Woo, Eun-Rhan; Ryu, Jong Hoon

    2016-03-01

    Erucic acid is a monounsaturated omega-9 fatty acid isolated from the seed of Raphanus sativus L. that is known to normalize the accumulation of very long chain fatty acids in the brains of patients suffering from X-linked adrenoleukodystrophy. Here, we investigated whether erucic acid enhanced cognitive function or ameliorated scopolamine-induced memory impairment using the passive avoidance, Y-maze and Morris water maze tasks. Erucic acid (3mg/kg, p.o.) enhanced memory performance in normal naïve mice. In addition, erucic acid (3mg/kg, p.o.) ameliorated scopolamine-induced memory impairment, as assessed via the behavioral tasks. We then investigated the underlying mechanism of the memory-enhancing effect of erucic acid. The administration of erucic acid increased the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K), protein kinase C zeta (PKCζ), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and additional protein kinase B (Akt) in the hippocampus. These results suggest that erucic acid has an ameliorative effect in mice with scopolamine-induced memory deficits and that the effect of erucic acid is partially due to the activation of PI3K-PKCζ-ERK-CREB signaling as well as an increase in phosphorylated Akt in the hippocampus. Therefore, erucic acid may be a novel therapeutic agent for diseases associated with cognitive deficits, such as Alzheimer's disease. PMID:26780350

  13. Exploratory, anxiety and spatial memory impairments are dissociated in mice lacking the LPA1 receptor

    PubMed Central

    Castilla-Ortega, Estela; Sánchez-López, Jorge; Hoyo-Becerra, Carolina; Matas-Rico, Elisa; Zambrana-Infantes, Emma; Chun, Jerold; Fonseca, Fernando Rodríguez De; Pedraza, Carmen; Estivill-Torrús, Guillermo; Santin, Luis J.

    2013-01-01

    Lysophosphatidic acid (LPA) is a new, intercellular signalling molecule in the brain that has an important role in adult hippocampal plasticity. Mice lacking the LPA1 receptor exhibit motor, emotional and cognitive alterations. However, the potential relationship among these concomitant impairments was unclear. Wild-type and maLPA1-null mice were tested on the hole-board for habituation and spatial learning. MaLPA1-null mice exhibited reduced exploration in a novel context and a defective intersession habituation that also revealed increased anxiety-like behaviour throughout the hole-board testing. In regard to spatial memory, maLPA1 nulls failed to reach the controls’ performance at the end of the reference memory task. Moreover, their defective working memory on the first training day suggested a delayed acquisition of the task’s working memory rule, which is also a long term memory component. The temporal interval between trials and the task’s difficulty may explain some of the deficits found in these mice. Principal components analysis revealed that alterations found in each behavioural dimension were independent. Therefore, exploratory and emotional impairments did not account for the cognitive deficits that may be attributed to maLPA1 nulls’ hippocampal malfunction. PMID:20388543

  14. Central Auditory Dysfunction in Older People with Memory Impairment or Alzheimer's Dementia

    PubMed Central

    Gates, George A.; Anderson, Melissa L.; Feeney, M. Patrick; McCurry, Susan M.; Larson, Eric B.

    2009-01-01

    Central auditory function is commonly compromised in people with a diagnosis of Alzheimer's disease (AD) and may precede the onset of clinical dementia by several years. Given that screening for AD in its earliest stages might someday be useful for emerging therapies aimed at limiting progression, we inquired whether central auditory testing might be suitable for identifying people at risk for dementia. To address this question, we performed a battery of behavioral central auditory tests in a cohort of 313 older people enrolled in a dementia surveillance research program. The cohort consisted of three groups: controls without memory loss (N=232), targets with mild memory impairment but without dementia (N=64), and targets with a dementia diagnosis (N=17). The auditory tests were the Synthetic Sentence Identification with Ipsilateral Competing Message (SSI), the Dichotic Sentence Identification test (DSI), the Dichotic Digits Test (DDT), and the Pitch Pattern Sequence (PPS) test. Additional control was provided by electrophysiologic testing to assess the integrity of the primary auditory pathways. The mean score on each central auditory test worsened significantly across the three memory groups even after adjusting for age and peripheral hearing status, being poorest in the pAD group and moderately reduced in the memory-impaired group compared to the mean scores in the control group. Heterogeneity of results was noted in all three groups. The electrophysiologic tests did not differ across the three groups. Central auditory function was affected by mild memory impairment. The Dichotic Sentence Identification in the free report mode appears to be the central auditory test most sensitive to the presence of memory impairment. Although central auditory testing requires specialized equipment and training, the objectivity of these tests is appealing. We recommend that comprehensive auditory testing be considered and further evaluated for its potential value as a baseline

  15. 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 ...

  16. Verbal memory impairments in children after cerebellar tumor resection

    PubMed Central

    Kirschen, Matthew P.; Davis-Ratner, Mathew S.; Milner, Marnee W.; Annabel Chen, S.H.; Schraedley-Desmond, Pam; Fisher, Paul G.; Desmond, John E.

    2009-01-01

    This study was designed to investigate cerebellar lobular contributions to specific cognitive deficits observed after cerebellar tumor resection. Verbal working memory (VWM) tasks were administered to children following surgical resection of cerebellar pilocytic astrocytomas and age-matched controls. Anatomical MRI scans were used to quantify the extent of cerebellar lobular damage from each patient’s resection. Patients exhibited significantly reduced digit span for auditory but not visual stimuli, relative to controls, and damage to left hemispheral lobule VIII was significantly correlated with this deficit. Patients also showed reduced effects of articulatory suppression and this was correlated with damage to the vermis and hemispheral lobule IV/V bilaterally. Phonological similarity and recency effects did not differ overall between patients and controls, but outlier patients with abnormal phonological similarity effects to either auditory or visual stimuli were found to have damage to hemispheral lobule VIII/VIIB on the left and right, respectively. We postulate that damage to left hemispheral lobule VIII may interfere with encoding of auditory stimuli into the phonological store. These data corroborate neuroimaging studies showing focal cerebellar activation during VWM paradigms, and thereby allow us to predict with greater accuracy which specific neurocognitive processes will be affected by a cerebellar tumor resection. PMID:19491473

  17. CMIP and ATP2C2 Modulate Phonological Short-Term Memory in Language Impairment

    PubMed Central

    Newbury, Dianne F.; Winchester, Laura; Addis, Laura; Paracchini, Silvia; Buckingham, Lyn-Louise; Clark, Ann; Cohen, Wendy; Cowie, Hilary; Dworzynski, Katharina; Everitt, Andrea; Goodyer, Ian M.; Hennessy, Elizabeth; Kindley, A. David; Miller, Laura L.; Nasir, Jamal; O'Hare, Anne; Shaw, Duncan; Simkin, Zoe; Simonoff, Emily; Slonims, Vicky; Watson, Jocelynne; Ragoussis, Jiannis; Fisher, Simon E.; Seckl, Jonathon R.; Helms, Peter J.; Bolton, Patrick F.; Pickles, Andrew; Conti-Ramsden, Gina; Baird, Gillian; Bishop, Dorothy V.M.; Monaco, Anthony P.

    2009-01-01

    Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 × 10−7 at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 × 10−5 at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition. PMID:19646677

  18. An expanded role for neuroimaging in the evaluation of memory impairment

    PubMed Central

    Desikan, Rahul S.; Rafii, Michael S.; Brewer, James B.; Hess, Christopher P.

    2014-01-01

    Alzheimer’s disease (AD) affects millions of people worldwide. The neuropathologic process underlying AD begins years, if not decades, before the onset of memory decline. Recent advances in neuroimaging suggest that it is now possible to detect AD-associated neuropathological changes well before dementia onset. Here, we evaluate the role of recently developed in vivo biomarkers in the clinical evaluation of AD. We discuss how assessment strategies might incorporate neuroimaging markers to better inform patients, families and clinicians when memory impairment prompts a search for diagnosis and management options. PMID:23764728

  19. Algal toxin impairs sea lion memory and hippocampal connectivity, with implications for strandings.

    PubMed

    Cook, Peter F; Reichmuth, Colleen; Rouse, Andrew A; Libby, Laura A; Dennison, Sophie E; Carmichael, Owen T; Kruse-Elliott, Kris T; Bloom, Josh; Singh, Baljeet; Fravel, Vanessa A; Barbosa, Lorraine; Stuppino, Jim J; Van Bonn, William G; Gulland, Frances M D; Ranganath, Charan

    2015-12-18

    Domoic acid (DA) is a naturally occurring neurotoxin known to harm marine animals. DA-producing algal blooms are increasing in size and frequency. Although chronic exposure is known to produce brain lesions, the influence of DA toxicosis on behavior in wild animals is unknown. We showed, in a large sample of wild sea lions, that spatial memory deficits are predicted by the extent of right dorsal hippocampal lesions related to natural exposure to DA and that exposure also disrupts hippocampal-thalamic brain networks. Because sea lions are dynamic foragers that rely on flexible navigation, impaired spatial memory may affect survival in the wild. PMID:26668068

  20. Synthetic amyloid-beta oligomers impair long-term memory independently of cellular prion protein.

    PubMed

    Balducci, Claudia; Beeg, Marten; Stravalaci, Matteo; Bastone, Antonio; Sclip, Alessandra; Biasini, Emiliano; Tapella, Laura; Colombo, Laura; Manzoni, Claudia; Borsello, Tiziana; Chiesa, Roberto; Gobbi, Marco; Salmona, Mario; Forloni, Gianluigi

    2010-02-01

    Inability to form new memories is an early clinical sign of Alzheimer's disease (AD). There is ample evidence that the amyloid-beta (Abeta) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Abeta are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Abeta-mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Abeta(1-42) oligomers impaired consolidation of the long-term recognition memory, whereas mature Abeta(1-42) fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Abeta antibody. It has been suggested that the cellular prion protein (PrP(C)) mediates the impairment of synaptic plasticity induced by Abeta. We confirmed that Abeta(1-42) oligomers interact with PrP(C), with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Abeta(1-42) oligomers are responsible for cognitive impairment in AD and that PrP(C) is not required. PMID:20133875

  1. Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein

    PubMed Central

    Balducci, Claudia; Beeg, Marten; Stravalaci, Matteo; Bastone, Antonio; Sclip, Alessandra; Biasini, Emiliano; Tapella, Laura; Colombo, Laura; Manzoni, Claudia; Borsello, Tiziana; Chiesa, Roberto; Gobbi, Marco; Salmona, Mario; Forloni, Gianluigi

    2010-01-01

    Inability to form new memories is an early clinical sign of Alzheimer’s disease (AD). There is ample evidence that the amyloid-β (Aβ) peptide plays a key role in the pathogenesis of this disorder. Soluble, bio-derived oligomers of Aβ are proposed as the key mediators of synaptic and cognitive dysfunction, but more tractable models of Aβ−mediated cognitive impairment are needed. Here we report that, in mice, acute intracerebroventricular injections of synthetic Aβ1–42 oligomers impaired consolidation of the long-term recognition memory, whereas mature Aβ1–42 fibrils and freshly dissolved peptide did not. The deficit induced by oligomers was reversible and was prevented by an anti-Aβ antibody. It has been suggested that the cellular prion protein (PrPC) mediates the impairment of synaptic plasticity induced by Aβ. We confirmed that Aβ1–42 oligomers interact with PrPC, with nanomolar affinity. However, PrP-expressing and PrP knock-out mice were equally susceptible to this impairment. These data suggest that Aβ1–42 oligomers are responsible for cognitive impairment in AD and that PrPC is not required. PMID:20133875

  2. Evidence of an amnesia-like cued-recall memory impairment in nondementing idiopathic Parkinson's disease.

    PubMed

    Edelstyn, Nicola M J; John, Christopher M; Shepherd, Thomas A; Drakeford, Justine L; Clark-Carter, David; Ellis, Simon J; Mayes, Andrew R

    2015-10-01

    Medicated, non-dementing mild-to-moderate Parkinson's disease (PD) patients usually show recall/recollection impairments but have only occasionally shown familiarity impairments. We aimed to assess two explanations of this pattern of impairment. Recollection typically improves when effortful planning of encoding and retrieval processing is engaged. This depends on prefrontally-dependent executive processes, which are often disrupted in PD. Relative to an unguided encoding and retrieval of words condition (C1), giving suitable guidance at encoding alone (C2) or at encoding and retrieval (C3) should, if executive processes are disrupted, improve PD recollection more than control recollection and perhaps raise it to normal levels. Familiarity, being a relatively automatic kind of memory, whether impaired or intact, should be unaffected by guidance. According to the second explanation, PD deficits are amnesia-like and caused by medial temporal lobe dysfunction and although poorer recollection, which is caused by hippocampal disruption, may be improved by guidance, it should not improve more than control recollection. Familiarity impairment will also occur if the perirhinal cortex is disrupted, but will be unimproved by guidance. Without guidance, recollection/recall was impaired in thirty PD patients relative to twenty-two healthy controls and remained relatively equally impaired when full guidance was provided (C1 vs C3), both groups improving to broadly the same extent. Although impaired, and markedly less so than recollection, familiarity was not improved by guidance in both groups. The patients showed elevated rates of subclinical depressive symptoms, which weakly correlated with recall/recollection in all three conditions. PD executive function was also deficient and correlated with unguided/C1 recollection only. Our results are consistent with a major cause of the patients' recall/recollection impairments being hippocampal disruption, probably exacerbated by

  3. Transcription inhibitors prevent amnesia induced by NMDA antagonist-mediated impairment of memory reconsolidation.

    PubMed

    Nikitin, Vladimir P; Solntseva, Svetlana V; Shevelkin, Alexey V

    2016-09-01

    Recent studies report that long-term memory retrieval can induce memory reconsolidation, and impairment of this reconsolidation might lead to amnesia. Previously, we found that reconsolidation of a conditioned food aversion memory could be disrupted by translation inhibitors for up to 3 h following a reconsolidation event, thus inducing amnesia. We examined the role of transcription processes in the induction of amnesia in the land snail, Helix lucorum. It received N-methyl-D-aspartate (NMDA) glutamate receptor antagonist and transcription inhibitor 2 days after learning in a neutral context environment; it was then transferred to the learning context followed by reminder with conditioned food stimulus. NMDA receptor blockade, followed by a reminder session, impaired reconsolidation of an aversive memory. Simultaneous administration of an NMDA receptor antagonist and a transcription inhibitor prior to reminder of an aversive event prevented amnesia induction. In contrast, when a transcription inhibitor alone was injected prior to a reminder session, the blockade had no effect on memory. We found that transcription inhibition 0-6 h after amnesia induction suppressed memory loss, but this suppression was lost when inhibitors were administered 9 h after amnesia. Thus, amnesia is likely dependent on transcription processes within a 9-h time window. We can hypothesize that amnesia induction initiates synthesis of specific mRNAs and proteins; furthermore, these events occur within specific time-dependent windows. Our findings could prove useful for the analysis of amnesia formation and for the development of possible ways to prevent memory loss associated with various diseases and injuries in animals and humans. PMID:26742927

  4. Inactivation of Primate Prefrontal Cortex Impairs Auditory and Audiovisual Working Memory

    PubMed Central

    Hwang, Jaewon; Romanski, Lizabeth M.

    2015-01-01

    The prefrontal cortex is associated with cognitive functions that include planning, reasoning, decision-making, working memory, and communication. Neurophysiology and neuropsychology studies have established that dorsolateral prefrontal cortex is essential in spatial working memory while the ventral frontal lobe processes language and communication signals. Single-unit recordings in nonhuman primates has shown that ventral prefrontal (VLPFC) neurons integrate face and vocal information and are active during audiovisual working memory. However, whether VLPFC is essential in remembering face and voice information is unknown. We therefore trained nonhuman primates in an audiovisual working memory paradigm using naturalistic face-vocalization movies as memoranda. We inactivated VLPFC, with reversible cortical cooling, and examined performance when faces, vocalizations or both faces and vocalization had to be remembered. We found that VLPFC inactivation impaired subjects' performance in audiovisual and auditory-alone versions of the task. In contrast, VLPFC inactivation did not disrupt visual working memory. Our studies demonstrate the importance of VLPFC in auditory and audiovisual working memory for social stimuli but suggest a different role for VLPFC in unimodal visual processing. SIGNIFICANCE STATEMENT The ventral frontal lobe, or inferior frontal gyrus, plays an important role in audiovisual communication in the human brain. Studies with nonhuman primates have found that neurons within ventral prefrontal cortex (VLPFC) encode both faces and vocalizations and that VLPFC is active when animals need to remember these social stimuli. In the present study, we temporarily inactivated VLPFC by cooling the cortex while nonhuman primates performed a working memory task. This impaired the ability of subjects to remember a face and vocalization pair or just the vocalization alone. Our work highlights the importance of the primate VLPFC in the processing of faces and

  5. Age-related eye disease and gender.

    PubMed

    Zetterberg, Madeleine

    2016-01-01

    Worldwide, the prevalence of moderate to severe visual impairment and blindness is 285 millions, with 65% of visually impaired and 82% of all blind people being 50 years and older. Meta-analyses have shown that two out of three blind people are women, a gender discrepancy that holds true for both developed and developing countries. Cataract accounts for more than half of all blindness globally and gender inequity in access to cataract surgery is the major cause of the higher prevalence of blindness in women. In addition to gender differences in cataract surgical coverage, population-based studies on the prevalence of lens opacities indicate that women have a higher risk of developing cataract. Laboratory as well as epidemiologic studies suggest that estrogen may confer antioxidative protection against cataractogenesis, but the withdrawal effect of estrogen in menopause leads to increased risk of cataract in women. For the other major age-related eye diseases; glaucoma, age-related macular degeneration (AMD) and diabetic retinopathy, data are inconclusive. Due to anatomic factors, angle closure glaucoma is more common in women, whereas the dominating glaucoma type; primary open-angle glaucoma (POAG), is more prevalent in men. Diabetic retinopathy also has a male predominance and vascular/circulatory factors have been implied both in diabetic retinopathy and in POAG. For AMD, data on gender differences are conflicting although some studies indicate increased prevalence of drusen and neovascular AMD in women. To conclude, both biologic and socioeconomic factors must be considered when investigating causes of gender differences in the prevalence of age-related eye disease. PMID:26508081

  6. Inhibition of Rac1 Activity in the Hippocampus Impairs the Forgetting of Contextual Fear Memory.

    PubMed

    Jiang, Lizhu; Mao, Rongrong; Zhou, Qixin; Yang, Yuexiong; Cao, Jun; Ding, Yuqiang; Yang, Yuan; Zhang, Xia; Li, Lingjiang; Xu, Lin

    2016-03-01

    Fear is crucial for survival, whereas hypermnesia of fear can be detrimental. Inhibition of the Rac GTPase is recently reported to impair the forgetting of initially acquired memory in Drosophila. Here, we investigated whether inhibition of Rac1 activity in rat hippocampus could contribute to the hypermnesia of contextual fear. We found that spaced but not massed training of contextual fear conditioning caused inhibition of Rac1 activity in the hippocampus and heightened contextual fear. Furthermore, intrahippocampal injection of the Rac1 inhibitor NSC23766 heightened contextual fear in massed training, while Rac1 activator CN04-A weakened contextual fear in spaced training rats. Our study firstly demonstrates that contextual fear memory in rats is actively regulated by Rac1 activity in the hippocampus, which suggests that the forgetting impairment of traumatic events in posttraumatic stress disorder may be contributed to the pathological inhibition of Rac1 activity in the hippocampus. PMID:25613020

  7. Activation of the dorsal hippocampal nicotinic acetylcholine receptors improves tamoxifen-induced memory retrieval impairment in adult female rats.

    PubMed

    Tajik, Azam; Rezayof, Ameneh; Ghasemzadeh, Zahra; Sardari, Maryam

    2016-07-01

    Tamoxifen (TAM), a selective estrogen receptor modulator, has frequently been used in the treatment of breast cancer. In view of the fact that cognitive deficits in women who receive adjuvant chemotherapy for breast cancer is a common health problem, using female animal models for investigating the cognitive effects of TAM administration may improve our knowledge of TAM therapy. Therefore, the present study assessed the role of dorsal hippocampal cholinergic nicotinic receptors (nAChRs) in the effect of TAM administration on memory retrieval in ovariectomized (OVX) and non-OVX female rats using a passive avoidance learning task. Our results showed that pre-test administration of TAM (2-6mg/kg) impaired memory retrieval. Pre-test intra-CA1 microinjection of nicotine (0.3-0.5μg/rat) reversed TAM-induced memory impairment. Pre-test intra-CA1 microinjection of mecamylamine (0.1-0.3μg/rat) plus 2mg/kg (an ineffective dose) of TAM impaired memory retrieval. Pre-test intra-CA1 microinjection of the same doses of nicotine and mecamylamine by themselves had no effect on memory retrieval. In OVX rats, the administration of TAM (6mg/kg) produced memory impairment but pre-test intra-CA1 microinjection of nicotine (0.5μg/rat) had no effect on TAM response. Moreover, the administration of an ineffective dose of TAM (2mg/kg) had no effect on memory retrieval in OVX rats, while pre-test intra-CA1 microinjection of mecamylamine (0.3μg/rat) impaired memory retrieval. Taken together, it can be concluded that the impairing effect of TAM on memory formation may be modulated by nAChRs of the CA1 regions. It seems that memory impairment may be considered as an important side effect of TAM. PMID:27072849

  8. The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment.

    PubMed

    Jorissen, B L; Brouns, F; Van Boxtel, M P; Ponds, R W; Verhey, F R; Jolles, J; Riedel, W J

    2001-01-01

    Phosphatidylserine (PS) is a phospholipid widely sold as a nutritional supplement. PS has been claimed to enhance neuronal membrane function and hence cognitive function, especially in the elderly. We report the results of a clinical trial of soybean-derived PS (S-PS) in aging subjects with memory complaints. Subjects were 120 elderly (> 57 years) of both sexes who fulfilled the more stringent criteria for age-associated memory impairment (AAMI); some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300mg S-PS daily, or 600mg S-PS daily. Assessments were carried out at baseline, after 6 and 12 weeks of treatment, and after a wash-out period of 3 weeks. Tests of learning and memory, choice reaction time, planning and attentional functions were administered at each assessment. Delayed recall and recognition of a previously learned word list comprised the primary outcome measures. No significant differences were found in any of the outcome variables between the treatment groups. There were also no significant interactions between treatment and 'severity of memory complaints'. In conclusion, a daily supplement of S-PS does not affect memory or other cognitive functions in older individuals with memory complaints. PMID:11842880

  9. Examining the mechanisms of overgeneral autobiographical memory: capture and rumination, and impaired executive control.

    PubMed

    Sumner, Jennifer A; Griffith, James W; Mineka, Susan

    2011-02-01

    Overgeneral autobiographical memory (OGM) is an important cognitive phenomenon in depression, but questions remain regarding the underlying mechanisms. The CaR-FA-X model (Williams et al., 2007) proposes three mechanisms that may contribute to OGM, but little work has examined the possible additive and/or interactive effects among them. We examined two mechanisms of CaR-FA-X: capture and rumination, and impaired executive control. We analysed data from undergraduates (N=109) scoring high or low on rumination who were presented with cues of high and low self-relevance on the Autobiographical Memory Test (AMT). Executive control was operationalised as performance on both the Stroop Colour-Word Task and the Controlled Oral Word Association Test (COWAT). Hierarchical generalised linear modelling was used to predict whether participants would generate a specific memory on a trial of the AMT. Higher COWAT scores, lower rumination, and greater cue self-relevance predicted a higher probability of a specific memory. There was also a rumination×cue self-relevance interaction: Higher (vs lower) rumination was associated with a lower probability of a specific memory primarily for low self-relevant cues. We found no evidence of interactions between these mechanisms. Findings are interpreted with respect to current autobiographical memory models. Future directions for OGM mechanism research are discussed. PMID:21294036

  10. Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees

    PubMed Central

    Williamson, Sally M.; Wright, Geraldine A.

    2013-01-01

    SUMMARY Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes. PMID:23393272

  11. The effect of ghrelin on MK-801 induced memory impairment in rats.

    PubMed

    Goshadrou, Fatemeh; Kermani, Mojtaba; Ronaghi, Abdolaziz; Sajjadi, Samad

    2013-06-01

    Accumulating evidence indicates that the brain-gut peptide ghrelin which is expressed in hippocampus improves memory and learning processes. The MK-801, a noncompetitive NMDA receptor antagonist, has also shown amnesic properties in animal model. The current study was to find out whether intracerebroventricular administration of ghrelin can prevent amnesia induced by MK-801 in rats. A week after the surgery, during which cannuals were implanted in the lateral ventricular, the animals were trained and tested in a step-through type passive avoidance task. Memory retrieval was measured by step-through latency (STL) and total time in dark compartments (TDC). In the first series of experiments, we established a dose-response relationship for ghrelin on the passive avoidance paradigm. In the second set of experiments, animals were divided to two groups. In the first group, MK-801 (0.075, 0.15 and 0.3mg/kg) was injected intraperitoneally (i.p.) immediately after the acquisition session and in the second group MK-801 (same doses) was injected (i.p.) 30 min before the retention session. Analysis of data showed that in both groups, MK-801 impaired learning and memory. In the third set of experiments, administration of ghrelin (200 ng/rat) right after the acquisition session (i.e. before MK-801 injection) improved the MK-801 induced memory impairment, but administration of ghrelin before retrieval session did not affect the MK-801 induced memory impairment. These results show an interaction between ghrelin and glutamatergic system. A novel finding in this study is that ghrelin can prevent amnesia produced by NMDA antagonist in rats when injected in post-training phase. PMID:23538209

  12. Honokiol improves learning and memory impairments induced by scopolamine in mice.

    PubMed

    Xian, Yan-Fang; Ip, Siu-Po; Mao, Qing-Qiu; Su, Zi-Ren; Chen, Jian-Nan; Lai, Xiao-Ping; Lin, Zhi-Xiu

    2015-08-01

    Honokiol, a lignan isolated from the bark of Magnolia officinalis, has been reported to ameliorate the learning and memory impairments in senesed (SAMP8) mice. However, whether honokiol could improve scopolamine (SCOP)-induced learning and memory deficits in mice is still unknown. In this study, we aimed to investigate whether honokiol could reverse the SCOP-induced learning and memory impairments in mice and to elucidate its underlying mechanisms of action. Mice were given daily intraperitoneal injection of honokiol (10 and 20mg/kg) for 21 consecutive days. The results showed that honokiol significantly improved spatial learning and memory function (as assessed by the Morris water maze test) in the SCOP-treated mice. In addition, treatment with honokiol significantly decreased the protein and mRNA levels of interleukin (IL)-1β and the activity of acetylcholinesterase (AChE), while significantly increased the protein and mRNA levels of IL-10, and the level of acetylcholine (Ach) in the brain of the SCOP-treated mice. Moreover, honokiol also significantly suppressed the production of prostaglandin E 2 (PGE2) and mRNA expression of cyclooxygenase-2 (COX-2) in the brain of the SCOP-treated mice. Mechanistic investigations revealed that honokiol could markedly reverse the amount of phosphorylated Akt and extracellular regulated kinases 1/2 (ERK1/2) changes in the brain of the SCOP-treated mice. These results amply demonstrated that honokiol could improve learning and memory impairments induced by SCOP in mice, and the protective action may be mediated, at least in part, by inhibition of AChE activity, and amelioration of the neuroinflammatory processes in the SCOP-treated mice. PMID:25912802

  13. Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees.

    PubMed

    Williamson, Sally M; Wright, Geraldine A

    2013-05-15

    Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes. PMID:23393272

  14. Deer Bone Extract Prevents Against Scopolamine-Induced Memory Impairment in Mice

    PubMed Central

    Du, Chun Nan; Min, A Young; Kim, Hyun Jeong; Shin, Suk Kyung; Yu, Ha Ni; Sohn, Eun Jeong; Ahn, Chang-Won; Jung, Sung Ug; Park, Soo-Hyun

    2015-01-01

    Abstract Deer bone has been used as a health-enhancing food as well as an antiaging agent in traditional Oriental medicine. Recently, the water extract of deer bone (DBE) showed a neuroprotective action against glutamate or Aβ1–42-induced cell death of mouse hippocampal cells by exerting antioxidant activity through the suppression of MAP kinases. The present study is to examine whether DBE improves memory impairment induced by scopolamine. DBE (50, 100 or 200 mg/kg) was administered orally to mice for 14 days, and then scopolamine (2 mg/kg, i.p.) was administered together with DBE for another 7 days. Memory performance was evaluated in the Morris water maze (MWM) test and passive avoidance test. Also, brain acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activity, biomarkers of oxidative stress and the loss of neuronal cells in the hippocampus, was evaluated by histological examinations. Administration of DBE significantly restored memory impairments induced by scopolamine in the MWM test (escape latency and number of crossing platform area), and in the passive avoidance test. Treatment with DBE inhibited the AChE activity and increased the ChAT activity in the brain of memory-impaired mice induced by scopolamine. Additionally, the administration of DBE significantly prevented the increase of lipid peroxidation and the decrease of glutathione level in the brain of mice treated with scopolamine. Also, the DBE treatment restored the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and glutathione reductase to control the level. Furthermore, scopolamine-induced oxidative damage of neurons in hippocampal CA1 and CA3 regions were prevented by DBE treatment. It is suggested that DBE may be useful for memory improvement through the regulation of cholinergic marker enzyme activities and the suppression of oxidative damage of neurons in the brain of mice treated with scopolamine. PMID:25546299

  15. The Ameliorating Effect of Myrrh on Scopolamine-Induced Memory Impairments in Mice

    PubMed Central

    Baral, Samrat; Cho, Du-Hyong; Pariyar, Ramesh; Yoon, Chi-Su; Chang, Bo-yoon; Kim, Dae-Sung; Cho, Hyoung-Kwon; Kim, Sung Yeon; Oh, Hyuncheol; Kim, Youn-Chul; Kim, Jaehyo; Seo, Jungwon

    2015-01-01

    Myrrh has been used since ancient times for the treatment of various diseases such as inflammatory diseases, gynecological diseases, and hemiplegia. In the present study, we investigated the effects of aqueous extracts of myrrh resin (AEM) on scopolamine-induced memory impairments in mice. AEM was estimated with (2E,5E)-6-hydroxy-2,6-dimethylhepta-2,4-dienal as a representative constituent by HPLC. The oral administration of AEM for 7 days significantly reversed scopolamine-induced reduction of spontaneous alternation in the Y-maze test. In the passive avoidance task, AEM also restored the decreased latency time of the retention trial by scopolamine treatment. In addition, Western blot analysis and Immunohistochemistry revealed that AEM reversed scopolamine-decreased phosphorylation of Akt and extracellular signal-regulated kinase (ERK). Our study demonstrates for the first time that AEM ameliorates the scopolamine-induced memory impairments in mice and increases the phosphorylation of Akt and ERK in the hippocampus of mice brain. These results suggest that AEM has the therapeutic potential in memory impairments. PMID:26635888

  16. Global hypoxia induced impairment in learning and spatial memory is associated with precocious hippocampal aging.

    PubMed

    Biswal, Suryanarayan; Sharma, Deepti; Kumar, Kushal; Nag, Tapas Chandra; Barhwal, Kalpana; Hota, Sunil Kumar; Kumar, Bhuvnesh

    2016-09-01

    Both chronological aging and chronic hypoxia stress have been reported to cause degeneration of hippocampal CA3 neurons and spatial memory impairment through independent pathways. However, the possible occurrence of precocious biological aging on exposure to single episode of global hypoxia resulting in impairment of learning and memory remains to be established. The present study thus aimed at bridging this gap in existing literature on hypoxia induced biological aging. Male Sprague Dawley rats were exposed to simulated hypobaric hypoxia (25,000ft) for different durations and were compared with aged rats. Behavioral studies in Morris Water Maze showed decline in learning abilities of both chronologically aged as well as hypoxic rats as evident from increased latency and pathlength to reach target platform. These behavioral changes in rats exposed to global hypoxia were associated with deposition of lipofuscin and ultrastructural changes in the mitochondria of hippocampal neurons that serve as hallmarks of aging. A single episode of chronic hypobaric hypoxia exposure also resulted in the up-regulation of pro-aging protein, S100A9 and down regulation of Tau, SNAP25, APOE and Sod2 in the hippocampus similar to that in aged rats indicating hypoxia induced accelerated aging. The present study therefore provides evidence for role of biological aging of hippocampal neurons in hypoxia induced impairment of learning and memory. PMID:27246251

  17. Differential Effects of Olanzapine and Haloperidol on MK-801-induced Memory Impairment in Mice

    PubMed Central

    Song, Jae Chun; Seo, Mi Kyoung; Park, Sung Woo; Lee, Jung Goo; Kim, Young Hoon

    2016-01-01

    Objective We investigated the differential effects of the antipsychotic drugs olanzapine and haloperidol on MK-801-induced memory impairment and neurogenesis in mice. Methods MK-801 (0.1 mg/kg) was administered 20 minutes prior to behavioral testing over 9 days. Beginning on the sixth day of MK-801 treatment, either olanzapine (0.05 mg/kg) or haloperidol (0.05 mg/kg) was administered 40 minutes prior to MK-801 for the final 4 days. Spatial memory performance was measured using a Morris water maze (MWM) test for 9 days (four trials/day). Immunohistochemistry with bromodeoxyuridine (BrdU) was used to identify newborn cells labeled in tissue sections from the dentate gyrus of the hippocampus. Results MK-801 administration over 9 days significantly impaired memory performance in the MWM test compared to untreated controls (p<0.05) and these deficits were blocked by treatment with olanzapine (p<0.05) but not haloperidol. The administration of MK-801 also resulted in a decrease in the number of BrdU-labeled cells in the dentate gyrus (28.6%; p<0.01), which was prevented by treatment with olanzapine (p<0.05) but not haloperidol. Conclusion These results suggest that olanzapine has a protective effect against cognitive impairments induced by MK-801 in mice via the stimulating effects of neurogenesis. PMID:27489382

  18. Increasing stimulus duration improves attention and memory performance in elderly with cognitive impairment

    PubMed Central

    Lavner, Yizhar; Rabinowitz, Israel

    2015-01-01

    Objectives: In this study, we investigated whether increasing stimulus duration could improve performance on a test of attention and short-term memory in cognitively impaired individuals. Methods: A computer-generated forward digit span test was administered to 65 patients with mild cognitive impairment or dementia (28 intervention and 37 controls). After point of failure, testing in the intervention group was continued at the same rate, but with an average 150% digit lengthening to 800 ms. Testing of controls was continued using the standard digit span test. Results: In the intervention group, 13/28 (46.4%) improved their digit span test performance, compared to 2/37 (5.4%) in the control group (p = 0.00005). Conclusion: Cognitively impaired elderly participants improved performance on a test of attention and short-term memory, when stimulus duration was increased in proportion to elongation of the finger tap touch-phase previously found in a similar cohort. A possible mechanism for the effect of increased stimulus duration on attention and short-term memory is discussed. PMID:27081485

  19. Reconciling findings of emotion-induced memory enhancement and impairment of preceding items

    PubMed Central

    Knight, Marisa; Mather, Mara

    2009-01-01

    A large body of work reveals that people remember emotionally arousing information better than neutral information. However, previous research reveals contradictory effects of emotional events on memory for neutral events that precede or follow them: in some studies emotionally arousing items impair memory for immediately preceding or following items and in others arousing items enhance memory for preceding items. By demonstrating both emotion-induced enhancement and impairment, Experiments 1 and 2 clarified the conditions under which these effects are likely to occur. The results suggest that emotion-induced enhancement is most likely to occur for neutral items that: (1) precede (and so are poised to predict the onset of) emotionally arousing items, (2) have high attentional weights at encoding, and (3) are tested after a delay period of a week rather than within the same experiment session. In contrast, emotion-induced impairment is most likely to occur for neutral items near the onset of emotional arousal that are overshadowed by highly activated competing items during encoding. PMID:20001121

  20. Memory impairment induced by amphetamine derivatives in laboratory animals and in humans: a review.

    PubMed

    Camarasa, Jordi; Rodrigo, Teresa; Pubill, David; Escubedo, Elena

    2012-02-01

    Abstract The 20th century brought with it the so-called club drugs (the most notorious being amphetamine derivatives), which are used by young adults at all-night dance parties. Methamphet-amine and 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) are synthetic drugs with stimulant and psychoactive properties that belong to the amphetamine family. Here, we have reviewed the literature about the cognitive impairment induced by these two amphetamine derivatives and the preclinical and clinical outcomes. Although there is controversial evidence about the effect of methamphetamine and MDMA on learning and memory in laboratory animals, results from published papers demonstrate that amphetamines cause long-term impairment of cognitive functions. A large number of pharmacological receptors have been studied and screened as targets of amphetamine-induced cognitive dysfunction, and extensive research efforts have been invested to provide evidence about the molecular mechanisms behind these cognitive deficits. In humans, there is a considerable body of evidence indicating that methamphetamine and MDMA seriously disrupt memory and learning processes. Although an association between the impairments of memory performance and a history of recreational amphetamine ingestion has also been corroborated, a number of methodological difficulties continue to hamper research in this field, the most important being the concomitant use of other illicit drugs. PMID:25436520

  1. Learning and memory impairment in albino rats after potassium ethylxanthogenate. Effects of nootropic agents.

    PubMed

    Genkova-Papasova, M; Lazarova-Bakarova, M

    1991-01-01

    The effects of the nootropic agents piracetam, aniracetam, meclofenoxate and fipexide on the cognitive functions impaired after potassium ethylxanthogenate, inhibitor of dopamine-beta-hydroxylase, were tested in experiments on albino rats. The changes in learning and memory were traced by the active conditioned avoidance method with negative reinforcement (shuttle-box) and the passive avoidance method (step-down). Potassium ethylxanthogenate, injected intraperitoneally in a dose of 100 mg/kg, markedly impaired learning and memory with both methods used. Piracetam (600 mg/kg), aniracetam (50 mg/kg), meclofenoxate (100 mg/kg) and fipexide (10 mg/kg), administered orally five days before and five days during shuttle-box training, as well as five days before step-down training, completely prevented the impairing effect of potassium ethylxanthogenate on the cognitive processes. The role of the noradrenergic neurotransmitter system and of other brain transmitter systems for memory disturbances caused by potassium ethylxanthogenate, as well as the protective effect of the nootropic drugs used, are discussed. PMID:1668136

  2. Select Overexpression of Homer1a in Dorsal Hippocampus Impairs Spatial Working Memory

    PubMed Central

    Celikel, Tansu; Zivkovic, Aleksandar; Resnik, Evgeny; Hasan, Mazahir T.; Licznerski, Pawel; Osten, Pavel; Rozov, Andrej; Seeburg, Peter H.; Schwarz, Martin K.

    2007-01-01

    Long Homer proteins forge assemblies of signaling components involved in glutamate receptor signaling in postsynaptic excitatory neurons, including those underlying synaptic transmission and plasticity. The short immediate-early gene (IEG) Homer1a can dynamically uncouple these physical associations by functional competition with long Homer isoforms. To examine the consequences of Homer1a-mediated “uncoupling” for synaptic plasticity and behavior, we generated forebrain-specific tetracycline (tet) controlled expression of Venus-tagged Homer1a (H1aV) in mice. We report that sustained overexpression of H1aV impaired spatial working but not reference memory. Most notably, a similar impairment was observed when H1aV expression was restricted to the dorsal hippocampus (HP), which identifies this structure as the principal cortical area for spatial working memory. Interestingly, H1aV overexpression also abolished maintenance of CA3-CA1 long-term potentiation (LTP). These impairments, generated by sustained high Homer1a levels, identify a requirement for long Homer forms in synaptic plasticity and temporal encoding of spatial memory. PMID:18982121

  3. Neuropsychological substrates and everyday functioning implications of prospective memory impairment in schizophrenia.

    PubMed

    Twamley, Elizabeth W; Woods, Steven Paul; Zurhellen, Cynthia H; Vertinski, Mary; Narvaez, Jenille M; Mausbach, Brent T; Patterson, Thomas L; Jeste, Dilip V

    2008-11-01

    Individuals with schizophrenia demonstrate impairment in prospective memory (ProM), which describes the multifaceted ability to execute a future intention. Despite its clear implications for everyday functioning, the neuropsychological substrates and functional correlates of ProM impairment in schizophrenia remain poorly understood. In this study, the Memory for Intentions Screening Test (MIST), a standardized measure of ProM, was administered to 72 outpatients with schizophrenia or schizoaffective disorder as part of a comprehensive neuropsychological and psychiatric research evaluation. Results showed that ProM was positively correlated with standard clinical tests of attention, working memory, processing speed, learning, and executive functioning, but not delayed recall. In the context of multiple neuropsychological predictors, learning ability was the only domain that independently contributed to ProM. Importantly, better ProM was predictive of higher functional capacity (as measured by the UCSD Performance-Based Skills Assessment-Brief Version), above and beyond the variability explained by demographic and disease factors. Analysis of component processes revealed that event-based ProM, as well as no response (i.e., omission) and task substitution errors were the strongest predictors of everyday functioning. Overall, these findings suggest that ProM impairment in schizophrenia is associated with multiple cognitive substrates, particularly episodic learning deficits, and plays an important role in everyday living skills. Studies regarding the potential effectiveness of ProM-based remediation strategies to improve functional outcomes in schizophrenia are indicated. PMID:18055178

  4. Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization

    PubMed Central

    Linsenbardt, David N.; Lapish, Christopher C.

    2015-01-01

    Rationale Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. Objectives The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. Methods Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. Results Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. Conclusions The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization. PMID:25572530

  5. Intrahippocampal glutamine administration inhibits mTORC1 signaling and impairs long-term memory

    PubMed Central

    Rozas, Natalia S.; Redell, John B.; Pita-Almenar, Juan D.; Mckenna, James; Moore, Anthony N.; Gambello, Michael J.

    2015-01-01

    The mechanistic Target of Rapamycin Complex 1 (mTORC1), a key regulator of protein synthesis and cellular growth, is also required for long-term memory formation. Stimulation of mTORC1 signaling is known to be dependent on the availability of energy and growth factors, as well as the presence of amino acids. In vitro studies using serum- and amino acid-starved cells have reported that glutamine addition can either stimulate or repress mTORC1 activity, depending on the particular experimental system that was used. However, these experiments do not directly address the effect of glutamine on mTORC1 activity under physiological conditions in nondeprived cells in vivo. We present experimental results indicating that intrahippocampal administration of glutamine to rats reduces mTORC1 activity. Moreover, post-training administration of glutamine impairs long-term spatial memory formation, while coadministration of glutamine with leucine had no influence on memory. Intracellular recordings in hippocampal slices showed that glutamine did not alter either excitatory or inhibitory synaptic activity, suggesting that the observed memory impairments may not result from conversion of glutamine to either glutamate or GABA. Taken together, these findings indicate that glutamine can decrease mTORC1 activity in the brain and may have implications for treatments of neurological diseases associated with high mTORC1 signaling. PMID:25878136

  6. Memory-enhancing treatments reverse the impairment of inhibitory avoidance retention in sepsis-surviving rats

    PubMed Central

    Tuon, Lisiane; Comim, Clarissa M; Petronilho, Fabrícia; Barichello, Tatiana; Izquierdo, Ivan; Quevedo, João; Dal-Pizzol, Felipe

    2008-01-01

    Introduction Survivors from sepsis have presented with long-term cognitive impairment, including alterations in memory, attention, concentration, and global loss of cognitive function. Thus, we evaluated the effects of memory enhancers in sepsis-surviving rats. Methods The rats underwent cecal ligation and perforation (CLP) (sepsis group) with 'basic support' (saline at 50 mL/kg immediately and 12 hours after CLP plus ceftriaxone at 30 mg/kg and clindamycin at 25 mg/kg 6, 12, and 18 hours after CLP) or sham-operated (control group). After 10 or 30 days, rats were submitted to an inhibitory avoidance task. After task training, animals received injections of saline, epinephrine, naloxone, dexamethasone, or glucose. Twenty-four hours afterwards, animals were submitted to the inhibitory avoidance test. Results We demonstrated that memory enhancers reversed impairment in the sepsis group 10 and 30 days after sepsis induction. This effect was of lower magnitude when compared with sham animals 10 days, but not 30 days, after sepsis. Conclusions Using different pharmacologic approaches, we conclude that the adrenergic memory formation pathways are responsive in sepsis-surviving animals. PMID:18957125

  7. Low dose dexamethasone reverses depressive-like parameters and memory impairment in rats submitted to sepsis.

    PubMed

    Cassol-Jr, Omar J; Comim, Clarissa M; Petronilho, Fabricia; Constantino, Larissa S; Streck, Emilio L; Quevedo, João; Dal-Pizzol, Felipe

    2010-04-01

    Sepsis is characterized by a systemic inflammatory response of the immune system against an infection, presenting with hypothalamic-pituitary-adrenal (HPA) axis dysfunction, behavior alterations, and high mortality. In this study, we aimed to evaluate the effects of dexamethasone on mortality, anhedonia, circulating corticosterone and adrenocorticotropin hormone (ACTH) levels, body and adrenal gland weight, and aversive memory in sepsis survivor rats. Male Wistar rats underwent sham operation or cecal ligation and perforation (CLP) procedure. Rats subjected to CLP were treated with "basic support" and dexamethasone (at 0.2 and 2mg/kg daily for 7 days after CLP, intraperitonially) or saline. After 10 days of sepsis procedure, it was evaluated aversive memory, sweet food consumption, and body and adrenal gland weight. Serum and plasma were also obtained. It was observed that low dose dexamethasone reverted anhedonia, normalized adrenal gland and body weight, corticosterone and ACTH levels, and decreased mortality and avoidance memory impairment, demonstrating that low doses of dexamethasone for moderate periods may be beneficial for sepsis treatment and its sequelae-depressive-like parameters and memory impairment. PMID:20184944

  8. Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis.

    PubMed

    Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia; Wimmer, Mathieu E; van Tilborg, Erik; Park, Alan J; Poplawski, Shane G; Chung, Caroline W; Havekes, Robbert; Huang, Jiayan; Gatti, Evelina; Pierre, Philippe; Abel, Ted

    2016-01-01

    Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss. These findings collectively demonstrate that 4EBP2-regulated protein synthesis is a critical mediator of the memory deficits caused by sleep deprivation. PMID:27117251

  9. Ketogenic diet attenuates spatial and item memory impairment in pentylenetetrazol-kindled rats.

    PubMed

    Jiang, Yan; Lu, Yuqiang; Jia, Mengmeng; Wang, Xiaohang; Zhang, Zhengxiang; Hou, Qun; Wang, Baohui

    2016-09-01

    The ketogenic diet (KD) controls seizure and improves cognition in patients with drug refractory epilepsy. However, few experimental models have shown this neuroprotective effect on cognition. In this study, we investigated the cognitive protective effects of KD in pentylenetetrazol (PTZ)-kindled rats. We used two relatively low-stress behavioral assessment methods, the novel object recognition (NOR) task and the novel placement recognition (NPR) task, to reveal impairment in item and spatial memory, respectively. We used the Morris water maze (MWM) test for comparisons amongst memory assessment methods. The KD group had a slower body weight gain and shorter bregma-lambda length than the control normal diet (ND) group. KD did not increase anxiety or decrease motor activities in an open-field test. KD attenuated the decrease in exploration ratio both in NOR and NPR tasks in kindled rats. Compared to the kindled ND rats, kindled KD rats stayed longer in target quarter during the probe trial testing of MWM. However, there were no differences in memory acquisition based on the MWM test results. In conclusion, KD attenuated the spatial and item memory impairment in PTZ-induced seizures. PMID:27343950

  10. Prefrontal-temporal disconnection impairs recognition memory but not familiarity discrimination

    PubMed Central

    Browning, Philip G.F.; Baxter, Mark G.; Gaffan, David

    2013-01-01

    Neural mechanisms in the temporal lobe are essential for recognition memory. Evidence from human functional imaging and neuropsychology and monkey neurophysiology and neuropsychology also suggests a role for prefrontal cortex in recognition memory. To examine the interaction of these cortical regions in support of recognition memory we tested rhesus monkeys with prefrontal-inferotemporal (PFC-IT) cortical disconnection on two recognition memory tasks, a ‘Constant Negative’ task and delayed nonmatching-to-sample (DNMS). In the Constant Negative task monkeys were presented with sets of 100 discrimination problems. In each problem one unrewarded object was presented once every day, and became familiar over the course of several days testing. The other, rewarded object was always novel. In this task monkeys learned to avoid the familiar ‘constant negatives’ and choose the novel objects, so performance on this task is guided by a sense of familiarity for the constant negatives. Following PFC-IT disconnection monkeys were severely impaired at reacquiring the rule (to avoid familiar items) but were subsequently unimpaired at acquiring new constant negative problems, thus displaying intact familiarity recognition. The same monkeys were impaired in the acquisition of the DNMS task, as well as memory for lists of objects. This dissociation between two tests of recognition memory is best explained in terms of our general hypothesis that PFC-IT interactions support the representation of temporally complex events, which is necessary in DNMS but not in Constant Negative. These findings, furthermore, indicate that stimulus familiarity can be represented in the temporal cortex without input from the prefrontal cortex. PMID:23739963

  11. Multicenter randomized clinical trial of donepezil for memory impairment in multiple sclerosis

    PubMed Central

    Christodoulou, C.; Melville, P.; Scherl, W.F.; Pai, L.-Y.; Muenz, L.R.; He, D.; Benedict, R.H.B.; Goodman, A.; Rizvi, S.; Schwid, S.R.; Weinstock-Guttman, B.; Westervelt, H.J.; Wishart, H.

    2011-01-01

    Objectives: The goal of this study was to determine if memory would be improved by donepezil as compared to placebo in a multicenter, double-blind, randomized clinical trial (RCT). Methods: Donepezil 10 mg daily was compared to placebo to treat memory impairment. Eligibility criteria included the following: age 18–59 years, clinically definite multiple sclerosis (MS), and performance ≤½ SD below published norms on the Rey Auditory Verbal Learning Test (RAVLT). Neuropsychological assessments were performed at baseline and 24 weeks. Primary outcomes were change on the Selective Reminding Test (SRT) of verbal memory and the participant's impression of memory change. Secondary outcomes included changes on other neuropsychological tests and the evaluating clinician's impression of memory change. Results: A total of 120 participants were enrolled and randomized to either donepezil or placebo. No significant treatment effects were found between groups on either primary outcome of memory or any secondary cognitive outcomes. A trend was noted for the clinician's impression of memory change in favor of donepezil (37.7%) vs placebo (23.7%) (p = 0.097). No serious or unanticipated adverse events attributed to study medication developed. Conclusions: Donepezil did not improve memory as compared to placebo on either of the primary outcomes in this study. Classification of evidence: This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average. PMID:21519001

  12. Chronic Stress During Adolescence Impairs and Improves Learning and Memory in Adulthood

    PubMed Central

    Chaby, Lauren E.; Cavigelli, Sonia A.; Hirrlinger, Amy M.; Lim, James; Warg, Kendall M.; Braithwaite, Victoria A.

    2015-01-01

    HIGHLIGHTS This study tested the effects of adolescent-stress on adult learning and memory.Adolescent-stressed rats had enhanced reversal learning compared to unstressed rats.Adolescent-stress exposure made working memory more vulnerable to disturbance.Adolescent-stress did not affect adult associative learning or reference memory. Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they age is not as well understood. We determined how chronic unpredictable stress during adolescence affects multiple learning and memory processes in adulthood. Using male Sprague Dawley rats, we measured learning (both associative and reversal) and memory (both reference and working) starting 110 days after completion of an adolescent-stress treatment. We found that adolescent-stress affected adult cognitive abilities in a context-dependent way. Compared to rats reared without stress, adolescent-stressed rats exhibited enhanced reversal learning, an indicator of behavioral flexibility, but showed no change in associative learning and reference memory abilities. Working memory, which in humans is thought to underpin reasoning, mathematical skills, and reading comprehension, may be enhanced by exposure to adolescent-stress. However, when adolescent-stressed animals were tested after a novel disturbance, they exhibited a 5-fold decrease in working memory performance while unstressed rats continued to exhibit a linear learning curve. These results emphasize the capacity for stress during adolescence to transform the cognitive abilities of adult animals, even after stress exposure has ceased and animals have resided in safe environments for the majority of their lifespans. PMID:26696849

  13. Developmental D-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.

    PubMed

    Williams, Michael T; Morford, LaRonda L; Wood, Sandra L; Wallace, Tanya L; Fukumura, Masao; Broening, Harry W; Vorhees, Charles V

    2003-06-01

    In previous studies, we have shown that P11-20 treatment with D-methamphetamine (MA) (10 mg/kg x 4/day at 2-h intervals) induces impairments in spatial learning and memory in the Morris water maze after the offspring reach adulthood. Using a split-litter, multiple dose, design (0, 5, 10, and 15 mg/kg MA administered s.c. 4/day at 2-h intervals), the spatial learning effect was further explored with a multiple shifted platform (reversal), reference memory-based procedure and a working memory procedure. Prior to spatial learning, animals were first tested for swimming ability (in a straight swimming channel), sequential learning (in the Cincinnati multiple-T water maze), and proximal cue learning (in the Morris water maze). Rats were then assessed in the hidden platform, reference memory-based spatial version of the Morris maze for acquisition and on five subsequent phases in which the platform was moved to new locations. After the reference memory-based, fixed platform position learning phases, animals were tested in the trial-dependent, matching-to-sample, working memory version of the Morris maze. No group differences were found in straight channel, sequential maze, or cued Morris maze performance. By contrast, all MA groups were impaired in spatial learning during acquisition, multiple shift, and shifted with a reduced platform phases of reference memory-based learning. In addition, MA animals were impaired on memory (probe) trials during the acquisition and shifted with a reduced platform phases of learning. No effects on trial-dependent, matching-to-sample, working memory were found. The findings demonstrate that neonatal treatment with MA induces a selective impairment of reference memory-based spatial learning while sparing sequential, cued, and working memory-based learning. PMID:12645039

  14. Impairment of visual memory for objects in natural scenes by simulated central scotomata.

    PubMed

    Geringswald, Franziska; Porracin, Eleonora; Pollmann, Stefan

    2016-01-01

    Because of the close link between foveal vision and the spatial deployment of attention, typically only objects that have been foveated during scene exploration may form detailed and persistent memory representations. In a recent study on patients suffering from age-related macular degeneration, however, we found surprisingly accurate visual long-term memory for objects in scenes. Normal exploration patterns that the patients had learned to rereference saccade targets to an extrafoveal retinal location. This rereferencing may allow use of an extrafoveal location as a focus of attention for efficient object encoding into long-term memory. Here, we tested this hypothesis in normal-sighted observers with gaze-contingent central scotoma simulations. As these observers were inexperienced in scene exploration with central vision loss and had not developed saccadic rereferencing, we expected deficits in long-term memory for objects. We used the same change detection task as in our patient study, probing sensitivity to object changes after a period of free scene exploration. Change detection performance was significantly reduced for two types of scotoma simulation diminishing foveal and parafoveal vision--a visible gray disc and a more subtle image warping--compared with unimpaired controls, confirming our hypothesis. The impact of a smaller scotoma covering specifically foveal vision was less distinct, leading to a marginally significant decrease of long-term memory performance compared with controls. We conclude that attentive encoding of objects is deficient when central vision is lost as long as successful saccadic rereferencing has not yet developed. PMID:27002551

  15. Working Memory Capacity and Its Relation to Stroop Interference and Facilitation Effects in Individuals with Mild Cognitive Impairment

    ERIC Educational Resources Information Center

    Sung, Jee Eun; Kim, Jin Hee; Jeong, Jee Hyang; Kang, Heejin

    2012-01-01

    Purpose: The purposes of the study were to investigate (a) the task-specific differences in short-term memory (STM) and working memory capacity (WMC) in individuals with mild cognitive impairment (MCI) and normal elderly adults (NEAs), (b) the Stroop interference and facilitation effects, and (c) the relationship of STM and WMC to the Stroop…

  16. Role of Auditory Non-Verbal Working Memory in Sentence Repetition for Bilingual Children with Primary Language Impairment

    ERIC Educational Resources Information Center

    Ebert, Kerry Danahy

    2014-01-01

    Background: Sentence repetition performance is attracting increasing interest as a valuable clinical marker for primary (or specific) language impairment (LI) in both monolingual and bilingual populations. Multiple aspects of memory appear to contribute to sentence repetition performance, but non-verbal memory has not yet been considered. Aims: To…

  17. The effects of L-arginine on spatial memory and synaptic plasticity impairments induced by lipopolysaccharide

    PubMed Central

    Anaeigoudari, Akbar; Shafei, Mohammad Naser; Soukhtanloo, Mohammad; Sadeghnia, Hamid Reza; Reisi, Parham; Nosratabadi, Reza; Behradnia, Sepehr; Hosseini, Mahmoud

    2015-01-01

    Background: An important role of nitric oxide (NO) in neuroinflammation has been suggested. It is also suggested that NO has a critical role in learning and memory. Neuro-inflammation induced by lipopolysaccharide (LPS) has been reported that deteriorates learning and memory. The effect of L-arginine (LA) as a precursor of NO on LPS-induced spatial learning and memory and neuronal plasticity impairment was evaluated. Materials and Methods: The animals were grouped into: (1) Control, (2) LPS, (3) LA-LPS, and (4) LA. The rats received intraperitoneally LPS (1 mg/kg) 2 h before experiments and LA (200 mg/kg) 30 min before LPS. The animals were examined in Morris water maze (MWM). Long-term potentiation (LTP) from CA1 area of the hippocampus was also assessed by 100 Hz stimulation in the ipsilateral Schaffer collateral pathway. Results: In MWM, time latency and traveled path were higher in LPS group than the control group (P < 0.001) whereas in LA-LPS group they were shorter than LPS group (P < 0.001). The amplitude and slope of field excitatory postsynaptic potential (fEPSP) decreased in LPS group compared to control group (P < 0.05 and P < 0.01) whereas, there was not any significant difference in these parameters between LPS and LA-LPS groups. Conclusion: Administration of LPS impaired spatial memory and synaptic plasticity. Although LA ameliorated deleterious effects of LPS on learning of spatial tasks, it could not restore LPS-induced LTP impairment. PMID:26601090

  18. Blast neurotrauma impairs working memory and disrupts prefrontal myo-inositol levels in rats.

    PubMed

    Sajja, Venkata Siva Sai Sujith; Perrine, Shane A; Ghoddoussi, Farhad; Hall, Christina S; Galloway, Matthew P; VandeVord, Pamela J

    2014-03-01

    Working memory, which is dependent on higher-order executive function in the prefrontal cortex, is often disrupted in patients exposed to blast overpressure. In this study, we evaluated working memory and medial prefrontal neurochemical status in a rat model of blast neurotrauma. Adult male Sprague-Dawley rats were anesthetized with 3% isoflurane and exposed to calibrated blast overpressure (17 psi, 117 kPa) while sham animals received only anesthesia. Early neurochemical effects in the prefrontal cortex included a significant decrease in betaine (trimethylglycine) and an increase in GABA at 24 h, and significant increases in glycerophosphorylcholine, phosphorylethanolamine, as well as glutamate/creatine and lactate/creatine ratios at 48 h. Seven days after blast, only myo-inositol levels were altered showing a 15% increase. Compared to controls, short-term memory in the novel object recognition task was significantly impaired in animals exposed to blast overpressure. Working memory in control animals was negatively correlated with myo-inositol levels (r=-.759, p<0.05), an association that was absent in blast exposed animals. Increased myo-inositol may represent tardive glial scarring in the prefrontal cortex, a notion supported by GFAP changes in this region after blast overexposure as well as clinical reports of increased myo-inositol in disorders of memory. PMID:24534010

  19. Enhanced Odor Discrimination and Impaired Olfactory Memory by Spatially Controlled Switch of AMPA Receptors

    PubMed Central

    2005-01-01

    Genetic perturbations of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca2+-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q), both leading to increased Ca2+ permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable (“mosaic”) among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities. PMID:16216087

  20. Methylphenidate prevents high-fat diet (HFD)-induced learning/memory impairment in juvenile mice.

    PubMed

    Kaczmarczyk, Melissa M; Machaj, Agnieszka S; Chiu, Gabriel S; Lawson, Marcus A; Gainey, Stephen J; York, Jason M; Meling, Daryl D; Martin, Stephen A; Kwakwa, Kristin A; Newman, Andrew F; Woods, Jeffrey A; Kelley, Keith W; Wang, Yanyan; Miller, Michael J; Freund, Gregory G

    2013-09-01

    The prevalence of childhood obesity has risen dramatically and coincident with this upsurge is a growth in adverse childhood psychological conditions including impulsivity, depression, anxiety and attention deficit/hyperactive disorder (ADHD). Due to confounds that exist when determining causality of childhood behavioral perturbations, controversy remains as to whether overnutrition and/or childhood obesity is important. Therefore, we examined juvenile mice to determine if biobehaviors were impacted by a short-term feeding (1-3wks) of a high-fat diet (HFD). After 1wk of a HFD feeding, mouse burrowing and spontaneous wheel running were increased while mouse exploration of the open quadrants of a zero maze, perfect alternations in a Y-maze and recognition of a novel object were impaired. Examination of mouse cortex, hippocampus and hypothalamus for dopamine and its metabolites demonstrated increased homovanillic acid (HVA) concentrations in the hippocampus and cortex that were associated with decreased cortical BDNF gene expression. In contrast, pro-inflammatory cytokine gene transcripts and serum IL-1α, IL-1β, TNF-α and IL-6 were unaffected by the short-term HFD feeding. Administration to mice of the psychostimulant methylphenidate prevented HFD-dependent impairment of learning/memory. HFD learning/memory impairment was not inhibited by the anti-depressants desipramine or reboxetine nor was it blocked in IDO or IL-1R1 knockout mice. In sum, a HFD rapidly impacts dopamine metabolism in the brain appearing to trigger anxiety-like behaviors and learning/memory impairments prior to the onset of weight gain and/or pre-diabetes. Thus, overnutrition due to fats may be central to childhood psychological perturbations such as anxiety and ADHD. PMID:23411461