Bidirectional Regulation of Amyloid Precursor Protein-Induced Memory Defects by Nebula/DSCR1: A Protein Upregulated in Alzheimer's Disease and Down Syndrome

PubMed Central

Shaw, Jillian L.; Zhang, Shixing

2015-01-01

Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. SIGNIFICANCE STATEMENT Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results suggest that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory loss in DS and AD and points to correcting calcineurin signaling as a means to improve memory during aging. PMID:26269644

Bidirectional Regulation of Amyloid Precursor Protein-Induced Memory Defects by Nebula/DSCR1: A Protein Upregulated in Alzheimer's Disease and Down Syndrome.

PubMed

Shaw, Jillian L; Zhang, Shixing; Chang, Karen T

2015-08-12

Aging individuals with Down syndrome (DS) have an increased risk of developing Alzheimer's disease (AD), a neurodegenerative disorder characterized by impaired memory. Memory problems in both DS and AD individuals usually develop slowly and progressively get worse with age, but the cause of this age-dependent memory impairment is not well understood. This study examines the functional interactions between Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. Using Drosophila as a model, we find that overexpression of nebula (fly homolog of DSCR1) initially protects against APP-induced memory defects by correcting calcineurin and cAMP signaling pathways but accelerates the rate of memory loss and exacerbates mitochondrial dysfunction in older animals. We report that transient upregulation of Nebula/DSCR1 or acute pharmacological inhibition of calcineurin in aged flies protected against APP-induced memory loss. Our data suggest that calcineurin dyshomeostasis underlies age-dependent memory impairments and further imply that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory impairments in AD in DS. Most Down syndrome (DS) individuals eventually develop Alzheimer's disease (AD)-like dementia, but mechanisms underlying this age-dependent memory impairment remain poorly understood. This study examines Nebula/Down syndrome critical region 1 (DSCR1) and amyloid-precursor protein (APP), proteins upregulated in both DS and AD, in regulating memory. We uncover a previously unidentified role for Nebula/DSCR1 in modulating APP-induced memory defects during aging. We show that upregulation of Nebula/DSCR1, an inhibitor of calcineurin, rescues APP-induced memory defects in young flies but enhances memory loss of older flies. Excitingly, transient Nebula/DSCR1 overexpression or calcineurin inhibition in aged flies ameliorates APP-mediated memory problems. These results suggest that chronic Nebula/DSCR1 upregulation may contribute to age-dependent memory loss in DS and AD and points to correcting calcineurin signaling as a means to improve memory during aging. Copyright © 2015 the authors 0270-6474/15/3511374-10$15.00/0.

Autobiographical memory and patterns of brain atrophy in frontotemporal lobar degeneration.

PubMed

McKinnon, Margaret C; Nica, Elena I; Sengdy, Pheth; Kovacevic, Natasa; Moscovitch, Morris; Freedman, Morris; Miller, Bruce L; Black, Sandra E; Levine, Brian

2008-10-01

Autobiographical memory paradigms have been increasingly used to study the behavioral and neuroanatomical correlates of human remote memory. Although there are numerous functional neuroimaging studies on this topic, relatively few studies of patient samples exist, with heterogeneity of results owing to methodological variability. In this study, fronto-temporal lobar degeneration (FTLD), a form of dementia affecting regions crucial to autobiographical memory, was used as a model of autobiographical memory loss. We emphasized the separation of episodic (recollection of specific event, perceptual, and mental state information) from semantic (factual information unspecific in time and place) autobiographical memory, derived from a reliable method for scoring transcribed autobiographical protocols, the Autobiographical Interview [Levine, B., Svoboda, E., Hay, J., Winocur, G., & Moscovitch, M. Aging and autobiographical memory: Dissociating episodic from semantic retrieval. Psychology and Aging, 17, 677-689, 2002]. Patients with the fronto-temporal dementia (FTD) and mixed fronto-temporal and semantic dementia (FTD/SD) variants of FTLD were impaired at reconstructing episodically rich autobiographical memories across the lifespan, with FTD/SD patients generating an excess of generic semantic autobiographical information. Patients with progressive nonfluent aphasia were mildly impaired for episodic autobiographical memory, but this impairment was eliminated with the provision of structured cueing, likely reflecting relatively intact medial-temporal lobe function, whereas the same cueing failed to bolster the FTD and FTD/SD patients' performance relative to that of matched comparison subjects. The pattern of episodic, but not semantic, autobiographical impairment was enhanced with disease progression on 1- to 2-year follow-up testing in a subset of patients, supplementing the cross-sectional evidence for specificity of episodic autobiographical impairment with longitudinal data. This behavioral pattern covaried with volume loss in a distributed left-lateralized posterior network centered on the temporal lobe, consistent with evidence from other patient and functional neuroimaging studies of autobiographical memory. Frontal lobe volumes, however, did not significantly contribute to this network, suggesting that frontal contributions to autobiographical episodic memory may be more complex than previously appreciated.

Memory T and memory B cells share a transcriptional program of self-renewal with long-term hematopoietic stem cells

PubMed Central

Luckey, Chance John; Bhattacharya, Deepta; Goldrath, Ananda W.; Weissman, Irving L.; Benoist, Christophe; Mathis, Diane

2006-01-01

The only cells of the hematopoietic system that undergo self-renewal for the lifetime of the organism are long-term hematopoietic stem cells and memory T and B cells. To determine whether there is a shared transcriptional program among these self-renewing populations, we first compared the gene-expression profiles of naïve, effector and memory CD8+ T cells with those of long-term hematopoietic stem cells, short-term hematopoietic stem cells, and lineage-committed progenitors. Transcripts augmented in memory CD8+ T cells relative to naïve and effector T cells were selectively enriched in long-term hematopoietic stem cells and were progressively lost in their short-term and lineage-committed counterparts. Furthermore, transcripts selectively decreased in memory CD8+ T cells were selectively down-regulated in long-term hematopoietic stem cells and progressively increased with differentiation. To confirm that this pattern was a general property of immunologic memory, we turned to independently generated gene expression profiles of memory, naïve, germinal center, and plasma B cells. Once again, memory-enriched and -depleted transcripts were also appropriately augmented and diminished in long-term hematopoietic stem cells, and their expression correlated with progressive loss of self-renewal function. Thus, there appears to be a common signature of both up- and down-regulated transcripts shared between memory T cells, memory B cells, and long-term hematopoietic stem cells. This signature was not consistently enriched in neural or embryonic stem cell populations and, therefore, appears to be restricted to the hematopoeitic system. These observations provide evidence that the shared phenotype of self-renewal in the hematopoietic system is linked at the molecular level. PMID:16492737

Rapid Forgetting Results From Competition Over Time Between Items in Visual Working Memory

PubMed Central

2016-01-01

Working memory is now established as a fundamental cognitive process across a range of species. Loss of information held in working memory has the potential to disrupt many aspects of cognitive function. However, despite its significance, the mechanisms underlying rapid forgetting remain unclear, with intense recent debate as to whether it is interference between stored items that leads to loss of information or simply temporal decay. Here we show that both factors are essential and interact in a highly specific manner. Although a single item can be maintained in memory with high fidelity, multiple items compete in working memory, progressively degrading each other’s representations as time passes. Specifically, interaction between items is associated with both worsening precision and increased reporting errors of object features over time. Importantly, during the period of maintenance, although items are no longer visible, maintenance resources can be selectively redeployed to protect the probability to recall the correct feature and the precision with which cued items can be recalled, as if it was the only item in memory. These findings reveal that the biased competition concept could be applied not only to perceptual processes but also to active maintenance of working memory representations over time. PMID:27668485

Treadmill exercise alleviates short-term memory impairment in 6-hydroxydopamine-induced Parkinson's rats.

PubMed

Cho, Han-Sam; Shin, Mal-Soon; Song, Wook; Jun, Tae-Won; Lim, Baek-Vin; Kim, Young-Pyo; Kim, Chang-Ju

2013-01-01

Progressive loss of dopaminergic neurons in substantia nigra is a key pathogenesis of Parkinson's disease. In the present study, we investigated the effects of treadmill exercise on short-term memory, apoptotic dopaminergic neuronal cell death and fiber loss in the nigrostriatum, and cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. Parkinson's rats were made by injection of 6-hydroxydopamine (6-OHDA) into the striatum using stereotaxic instrument. Four weeks after 6-OHDA injection, the rats in the 6-OHDA-injection group exhibited significant rotational asymmetry following apomorphine challenge. The rats in the exercise groups were put on the treadmill to run for 30 min once a day for 14 consecutive days starting 4 weeks after 6-OHDA injection. In the present results, extensive degeneration of the dopaminergic neurons in the substantia nigra with loss of dopaminergic fibers in the striatum were produced in the rats without treadmill running, which resulted in short-term memory impairment. However, the rats performing treadmill running for 2 weeks alleviated nigrostriatal dopaminergic cell loss and alleviated short-term memory impairment with increasing cell proliferation in the hippocampal dentate gyrus of Parkinson's rats. The present results show that treadmill exercise may provide therapeutic value for the Parkinson's disease.

Loss of memory B cells impairs maintenance of long-term serologic memory during HIV-1 infection.

PubMed

Titanji, Kehmia; De Milito, Angelo; Cagigi, Alberto; Thorstensson, Rigmor; Grützmeier, Sven; Atlas, Ann; Hejdeman, Bo; Kroon, Frank P; Lopalco, Lucia; Nilsson, Anna; Chiodi, Francesca

2006-09-01

Circulating memory B cells are severely reduced in the peripheral blood of HIV-1-infected patients. We investigated whether dysfunctional serologic memory to non-HIV antigens is related to disease progression by evaluating the frequency of memory B cells, plasma IgG, plasma levels of antibodies to measles, and Streptococcus pneumoniae, and enumerating measles-specific antibody-secreting cells in patients with primary, chronic, and long-term nonprogressive HIV-1 infection. We also evaluated the in vitro production of IgM and IgG antibodies against measles and S pneumoniae antigens following polyclonal activation of peripheral blood mononuclear cells (PBMCs) from patients. The percentage of memory B cells correlated with CD4+ T-cell counts in patients, thus representing a marker of disease progression. While patients with primary and chronic infection had severe defects in serologic memory, long-term nonprogressors had memory B-cell frequency and levels of antigen-specific antibodies comparable with controls. We also evaluated the effect of antiretroviral therapy on these serologic memory defects and found that antiretroviral therapy did not restore serologic memory in primary or in chronic infection. We suggest that HIV infection impairs maintenance of long-term serologic immunity to HIV-1-unrelated antigens and this defect is initiated early in infection. This may have important consequences for the response of HIV-infected patients to immunizations.

Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology

PubMed Central

Yang, Sujeong; Cacquevel, Matthias; Saksida, Lisa M.; Bussey, Timothy J.; Schneider, Bernard L.; Aebischer, Patrick; Melani, Riccardo; Pizzorusso, Tommaso; Fawcett, James W.; Spillantini, Maria Grazia

2015-01-01

Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau hyperphosphorylation, aggregation and neurodegeneration: a transgenic mouse model in which the mutant P301S tau is expressed in neurons (Tg P301S), and a model in which an adeno-associated virus expressing P301S tau (AAV-P301S) was injected in the perirhinal cortex, a region critical for object recognition (OR) memory. Both models show profound loss of OR memory despite only 15% neuronal loss in the Tg P301S and 26% in AAV-P301S-injected mice. Recordings from perirhinal cortex slices of 3 month-old P301S transgenic mice showed a diminution in synaptic transmission following temporal stimulation. Chondroitinase ABC (ChABC) can reactivate plasticity and affect memory through actions on perineuronal nets. ChABC was injected into the perirhinal cortex and animals were tested for OR memory 1 week later, demonstrating restoration of OR memory to normal levels. Synaptic transmission indicated by fEPSP amplitude was restored to control levels following ChABC treatment. ChABC did not affect the progression of neurodegenerative tauopathy. These findings suggest that increasing plasticity by manipulation of perineuronal nets offers a novel therapeutic approach to the treatment of memory loss in neurodegenerative disorders. PMID:25483398

Memory loss in Alzheimer's disease: implications for development of therapeutics

PubMed Central

Gold, Carl A; Budson, Andrew E

2009-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by a constellation of cognitive disturbances, the earliest and most prominent being impaired episodic memory. Episodic memory refers to the memory system that allows an individual to consciously retrieve a previously experienced item or episode of life. Many recent studies have focused on characterizing how AD pathology impacts particular aspects of episodic memory and underlying mental and neural processes. This review summarizes the findings of those studies and discusses the effects of current and promising treatments for AD on episodic memory. The goal of this review is to raise awareness of the strides that cognitive neuroscientists have made in understanding intact and dysfunctional memory. Knowledge of the specific memorial processes that are impaired in AD may be of great value to basic scientists developing novel therapies and to clinical researchers assessing the efficacy of those therapies. PMID:19086882

Memory Dysfunction

PubMed Central

Matthews, Brandy R.

2015-01-01

Purpose of Review: This article highlights the dissociable human memory systems of episodic, semantic, and procedural memory in the context of neurologic illnesses known to adversely affect specific neuroanatomic structures relevant to each memory system. Recent Findings: Advances in functional neuroimaging and refinement of neuropsychological and bedside assessment tools continue to support a model of multiple memory systems that are distinct yet complementary and to support the potential for one system to be engaged as a compensatory strategy when a counterpart system fails. Summary: Episodic memory, the ability to recall personal episodes, is the subtype of memory most often perceived as dysfunctional by patients and informants. Medial temporal lobe structures, especially the hippocampal formation and associated cortical and subcortical structures, are most often associated with episodic memory loss. Episodic memory dysfunction may present acutely, as in concussion; transiently, as in transient global amnesia (TGA); subacutely, as in thiamine deficiency; or chronically, as in Alzheimer disease. Semantic memory refers to acquired knowledge about the world. Anterior and inferior temporal lobe structures are most often associated with semantic memory loss. The semantic variant of primary progressive aphasia (svPPA) is the paradigmatic disorder resulting in predominant semantic memory dysfunction. Working memory, associated with frontal lobe function, is the active maintenance of information in the mind that can be potentially manipulated to complete goal-directed tasks. Procedural memory, the ability to learn skills that become automatic, involves the basal ganglia, cerebellum, and supplementary motor cortex. Parkinson disease and related disorders result in procedural memory deficits. Most memory concerns warrant bedside cognitive or neuropsychological evaluation and neuroimaging to assess for specific neuropathologies and guide treatment. PMID:26039844

Rapid forgetting results from competition over time between items in visual working memory.

PubMed

Pertzov, Yoni; Manohar, Sanjay; Husain, Masud

2017-04-01

Working memory is now established as a fundamental cognitive process across a range of species. Loss of information held in working memory has the potential to disrupt many aspects of cognitive function. However, despite its significance, the mechanisms underlying rapid forgetting remain unclear, with intense recent debate as to whether it is interference between stored items that leads to loss of information or simply temporal decay. Here we show that both factors are essential and interact in a highly specific manner. Although a single item can be maintained in memory with high fidelity, multiple items compete in working memory, progressively degrading each other's representations as time passes. Specifically, interaction between items is associated with both worsening precision and increased reporting errors of object features over time. Importantly, during the period of maintenance, although items are no longer visible, maintenance resources can be selectively redeployed to protect the probability to recall the correct feature and the precision with which cued items can be recalled, as if it was the only item in memory. These findings reveal that the biased competition concept could be applied not only to perceptual processes but also to active maintenance of working memory representations over time. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Alzheimer's Disease. LC Science Tracer Bullet 87-2.

ERIC Educational Resources Information Center

Sammons, Vivian O., Comp.

Alzheimer's disease is characterized by a degeneration and shrinkage of brain tissue; the symptoms include progressive memory loss, bizarre behavior, difficulty in speaking and walking, incontinence, and confusion. Positive diagnosis is possible only upon examination of brain tissue at autopsy. The disease affects not only the patient but also the…

Longitudinal assessment of short-term memory deterioration in a logopenic variant primary progressive aphasia with post-mortem confirmed Alzheimer's Disease pathology.

PubMed

Tree, Jeremy; Kay, Janice

2015-09-01

In the field of dementia research, there are reports of neurodegenerative cases with a focal loss of language, termed primary progressive aphasia (PPA). Currently, this condition has been further sub-classified, with the most recent sub-type dubbed logopenic variant (PPA-LV). As yet, there remains somewhat limited evaluation of the characteristics of this condition, with no studies providing longitudinal assessment accompanied by post-mortem examination. Moreover, a key characteristic of the PPA-LV case is a deterioration of phonological short-term memory, but again little work has scrutinized the nature of this impairment over time. The current study seeks to redress these oversights and presents detailed longitudinal examination of language and memory function in a case of PPA-LV, with special focus on tests linked to components of phonological short-term memory function. Our findings are then considered with reference to a contemporary model of the neuropsychology of phonological short-term memory. Additionally, post-mortem examinations indicated Alzheimer's disease type pathology, providing further evidence that the PPA-LV presentation may reflect an atypical presentation of this condition. © 2014 The British Psychological Society.

Intranasally delivered small interfering RNA-mediated suppression of scavenger receptor Mac-1 attenuates microglial phenotype switching and working memory impairment following hypoxia.

PubMed

Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

2018-05-05

Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene. Here, we implicate Mac-1 scavenger receptor in microglial phenotype switching, neurodegeneration in prefrontal cortex, hippocampus and working memory impairment. RNA mediated silencing of Mac-1 in both in vitro and in vivo model showed significant impact of it on hypoxia induced altered expression of Mac-1 endogenous ligand, signaling cascade proteins, transcription factors and NADPH oxidase pathway. Efficient degradation of Mac-1 mRNA suppressed expression of M1 phenotypic markers, inflammatory chemokines, and cytokines, but on the other hand, it upregulated M2 phenotypic markers and anti-inflammatory cytokines. Neuronal viability and synaptic plasticity markers were also modulated significantly by this strategy. Behavioral study revealed significant downregulation in the number of working memory errors at a time-dependent manner after silencing the Mac-1 gene during continuous hypoxic exposure. The novel findings of this study for the very first time, unmasked the role of Mac-1 receptor in neurodegenerative disease progression under hypoxic condition and at the same time indicated the potential therapeutic value of this non-invasive siRNA delivery approach for treating working memory loss. Copyright © 2018 Elsevier Ltd. All rights reserved.

Permanent global amnesia: case report.

PubMed

Bertolucci, Paulo H F; Siviero, Marilena O; Bueno, Orlando F A; Okamoto, Ivan H; Camargo, Candida H P; Santos, Ruth F

2004-04-01

To present a case of permanent global amnesia related to hippocampal damage. Permanent global amnesia is a very rare condition of unknown etiology; lesions restricted to the hippocampus are uncommon, which hinders investigations of this pattern of memory loss. This case is unusually well documented, as the patient underwent extensive neuropsychological evaluations. A cheerful right-handed, 83-year-old retired electrician was first evaluated in 1990 for progressive difficulty in learning new information and in recalling events over the preceding 3-4 years. Tests over the next 5 years showed that the impairment was confined to episodic declarative memory. New verbal information could be stored only in episodic memory in a restricted manner, limited by short-term memory capacity. A relatively mild retrograde amnesia was detected. Semantic and implicit memory was spared, as were other functions evaluated. The patient's language and executive function were strikingly efficient. Magnetic resonance imaging of the brain showed bilateral atrophy of the hippocampi and amygdalae, ruling out conditions such as tumour growth. A diagnosis of permanent global amnesia was made. In the ensuing years, the retrograde amnesia worsened, but no new deficits were identified. This case, the first with a detailed cognitive examination, is evidence of a relatively pure hippocampal pattern for memory loss in permanent global amnesia.

Cued recall measure predicts the progression of gray matter atrophy in patients with amnesic mild cognitive impairment.

PubMed

Koric, Lejla; Ranjeva, Jean-Philippe; Felician, Olivier; Guye, Maxime; de Anna, Francesca; Soulier, Elisabeth; Didic, Mira; Ceccaldi, Mathieu

2013-01-01

Amnesic mild cognitive impairment (aMCI) is a heterogeneous syndrome that could be subdivided into distinct neuropsychological variants. To investigate relationships between the neuropsychological profile of memory impairment at baseline and the neuroimaging pattern of grey matter (GM) loss over 18 months, we performed a prospective volumetric brain study on 31 aMCI patients and 29 matched controls. All subjects were tested at baseline using a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for the assessment of verbal declarative memory. Over 18 months, patients with impaired free recall but normal total recall (high index of cueing) on the FCSRT developed subcortical and frontal GM loss, while patients with impaired free and total recall (low index of cueing) developed GM atrophy within the left anterior and lateral temporal lobe. In summary, cued recall deficits are associated with a progression of atrophy that closely parallels the spatiotemporal distribution of neurofibrillary degeneration in early Alzheimer's disease (AD), indicating possible AD pathological changes. © 2013 S. Karger AG, Basel.

HIV and T follicular helper cells: a dangerous relationship

PubMed Central

Vinuesa, Carola G.

2012-01-01

HIV infection leads to progressive destruction of infected CD4 T cells, hypergammaglobulinemia, and loss of memory B cells. Germinal centers, which are key to memory B cell formation and protective antibody responses, are major HIV reservoirs in which the virus replicates within T follicular helper (TFH) cells. In this issue of the JCI, the Koup and Streeck groups report that chronic SIV/HIV infection promotes TFH cell accumulation, which may drive B cell dysregulation. Their discoveries suggest that HIV harnesses TFH cells to evade the antibody response. PMID:22922252

Accelerated Loss of TCR Repertoire Diversity in Common Variable Immunodeficiency

PubMed Central

Wong, Gabriel K.; Millar, David; Penny, Sarah; Heather, James M.; Mistry, Punam; Buettner, Nico; Bryon, Jane; Huissoon, Aarnoud P.

2016-01-01

Although common variable immunodeficiency (CVID) has long been considered as a group of primary Ab deficiencies, growing experimental data now suggest a global disruption of the entire adaptive immune response in a segment of patients. Oligoclonality of the TCR repertoire was previously demonstrated; however, the manner in which it relates to other B cell and T cell findings reported in CVID remains unclear. Using a combination approach of high-throughput TCRβ sequencing and multiparametric flow cytometry, we compared the TCR repertoire diversity between various subgroups of CVID patients according to their B cell immunophenotypes. Our data suggest that the reduction in repertoire diversity is predominantly restricted to those patients with severely reduced class-switched memory B cells and an elevated level of CD21lo B cells (Freiburg 1a), and may be driven by a reduced number of naive T cells unmasking underlying memory clonality. Moreover, our data indicate that this loss in repertoire diversity progresses with advancing age far exceeding the expected physiological rate. Radiological evidence supports the loss in thymic volume, correlating with the decrease in repertoire diversity. Evidence now suggests that primary thymic failure along with other well-described B cell abnormalities play an important role in the pathophysiology in Freiburg group 1a patients. Clinically, our findings emphasize the integration of combined B and T cell testing to identify those patients at the greatest risk for infection. Future work should focus on investigating the link between thymic failure and the severe reduction in class-switched memory B cells, while gathering longitudinal laboratory data to examine the progressive nature of the disease. PMID:27481850

The full-length form of the Drosophila amyloid precursor protein is involved in memory formation.

PubMed

Bourdet, Isabelle; Preat, Thomas; Goguel, Valérie

2015-01-21

The APP plays a central role in AD, a pathology that first manifests as a memory decline. Understanding the role of APP in normal cognition is fundamental in understanding the progression of AD, and mammalian studies have pointed to a role of secreted APPα in memory. In Drosophila, we recently showed that APPL, the fly APP ortholog, is required for associative memory. In the present study, we aimed to characterize which form of APPL is involved in this process. We show that expression of a secreted-APPL form in the mushroom bodies, the center for olfactory memory, is able to rescue the memory deficit caused by APPL partial loss of function. We next assessed the impact on memory of the Drosophila α-secretase kuzbanian (KUZ), the enzyme initiating the nonamyloidogenic pathway that produces secreted APPLα. Strikingly, KUZ overexpression not only failed to rescue the memory deficit caused by APPL loss of function, it exacerbated this deficit. We further show that in addition to an increase in secreted-APPL forms, KUZ overexpression caused a decrease of membrane-bound full-length species that could explain the memory deficit. Indeed, we observed that transient expression of a constitutive membrane-bound mutant APPL form is sufficient to rescue the memory deficit caused by APPL reduction, revealing for the first time a role of full-length APPL in memory formation. Our data demonstrate that, in addition to secreted APPL, the noncleaved form is involved in memory, raising the possibility that secreted and full-length APPL act together in memory processes. Copyright © 2015 the authors 0270-6474/15/351043-09$15.00/0.

Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer's disease

PubMed Central

Nobili, Annalisa; Latagliata, Emanuele Claudio; Viscomi, Maria Teresa; Cavallucci, Virve; Cutuli, Debora; Giacovazzo, Giacomo; Krashia, Paraskevi; Rizzo, Francesca Romana; Marino, Ramona; Federici, Mauro; De Bartolo, Paola; Aversa, Daniela; Dell'Acqua, Maria Concetta; Cordella, Alberto; Sancandi, Marco; Keller, Flavio; Petrosini, Laura; Puglisi-Allegra, Stefano; Mercuri, Nicola Biagio; Coccurello, Roberto; Berretta, Nicola; D'Amelio, Marcello

2017-01-01

Alterations of the dopaminergic (DAergic) system are frequently reported in Alzheimer's disease (AD) patients and are commonly linked to cognitive and non-cognitive symptoms. However, the cause of DAergic system dysfunction in AD remains to be elucidated. We investigated alterations of the midbrain DAergic system in the Tg2576 mouse model of AD, overexpressing a mutated human amyloid precursor protein (APPswe). Here, we found an age-dependent DAergic neuron loss in the ventral tegmental area (VTA) at pre-plaque stages, although substantia nigra pars compacta (SNpc) DAergic neurons were intact. The selective VTA DAergic neuron degeneration results in lower DA outflow in the hippocampus and nucleus accumbens (NAc) shell. The progression of DAergic cell death correlates with impairments in CA1 synaptic plasticity, memory performance and food reward processing. We conclude that in this mouse model of AD, degeneration of VTA DAergic neurons at pre-plaque stages contributes to memory deficits and dysfunction of reward processing. PMID:28367951

Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

PubMed

Zhao, Lu; Liu, Sha; Wang, Yin; Zhang, Qiaoyan; Zhao, Wenjuan; Wang, Zejian; Yin, Ming

2015-01-01

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aβ not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Decreased levels of PSD95 and two associated proteins and increased levels of BCl2 and caspase 3 in hippocampus from subjects with amnestic mild cognitive impairment: Insights into their potential roles for loss of synapses and memory, accumulation of Abeta, and neurodegeneration in a prodromal stage of Alzheimer's disease.

PubMed

Sultana, Rukhsana; Banks, William A; Butterfield, D Allan

2010-02-15

Alzheimer's disease (AD) is the most common form of dementia and is pathologically characterized by senile plaques, neurofibrillary tangles, synaptic disruption and loss, and progressive neuronal deficits. The exact mechanism(s) of AD pathogenesis largely remain unknown. With advances in technology diagnosis of a pre-AD stage referred to as amnestic mild cognitive impairment (MCI) has become possible. Amnestic MCI is characterized clinically by memory deficit, but normal activities of daily living and no dementia. In the present study, compared to controls, we observed in hippocampus from subjects with MCI a significantly decreased level of PSD95, a key synaptic protein, and also decreased levels of two proteins associated with PSD95, the N-methyl-D-aspartate receptor, subunit 2A (NR2A) and the low-density lipoprotein receptor-1 (LRP1). PSD95 and NR2A are involved in long-term potentiation, a key component of memory formation, and LRP1 is involved in efflux of amyloid beta-peptide (1-42). Abeta (1-42) conceivably is critical to the pathogenesis of MCI and AD, including the oxidative stress under which brain in both conditions exist. The data obtained from the current study suggest a possible involvement of these proteins in synaptic alterations, apoptosis and consequent decrements in learning and memory associated with the progression of MCI to AD. Copyright 2009 Wiley-Liss, Inc.

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report.

PubMed

Francio, Vinicius T; Boesch, Ron; Tunning, Michael

2015-03-01

Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient's perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option.

‘The quicksand of forgetfulness’: semantic dementia in One Hundred Years of Solitude

PubMed Central

Growdon, Matthew E.; Pardo, Isela R.; Grossman, Scott; Miller, Bruce L.

2009-01-01

This multidisciplinary article compares the pattern of memory loss described in Gabriel García Márquez's One Hundred Years of Solitude to that exhibited by patients with semantic dementia (SD). In his renowned novel, García Márquez depicts the plight of Macondo, a town struck by the dreaded insomnia plague. The most devastating symptom of the plague is not the impossibility of sleep, but rather the loss of ‘the name and notion of things’. In an effort to combat this insidious loss of knowledge, the protagonist, José Arcadio Buendía, ‘marked everything with its name: table, chair, clock, door, wall, bed, pan’. ‘Studying the infinite possibilities of a loss of memory, he realized that the day might come when things would be recognized by their inscriptions but that no one would remember their use’. The cognitive impairments experienced by Macondo's inhabitants are remarkably similar to those observed in SD, a clinical syndrome characterized by a progressive breakdown of conceptual knowledge (semantic memory) in the context of relatively preserved day-to-day (episodic) memory. First recognized in 1975, it is now considered one of the main variants of frontotemporal lobar degeneration. Writing within the realm of magical realism and investigating the power of language as a form of communication, García Márquez provides beautiful descriptions of the loss of ‘the name and notion of things’ typical of the syndrome. He further speculates on ways to cope with this dissolution of meaning, ranging from ‘the spell of an imaginary reality’ to José Arcadio's ‘memory machine’, strategies that resonate with attempts by semantic dementia patients to cope with their disease. Remarkably, García Márquez created a striking literary depiction of collective semantic dementia before the syndrome was recognized in neurology. The novel also provides an inspiring and human account of one town's fight against ‘the quicksand of forgetfulness’. PMID:19447824

'The quicksand of forgetfulness': semantic dementia in One hundred years of solitude.

PubMed

Rascovsky, Katya; Growdon, Matthew E; Pardo, Isela R; Grossman, Scott; Miller, Bruce L

2009-09-01

This multidisciplinary article compares the pattern of memory loss described in Gabriel García Márquez's One Hundred Years of Solitude to that exhibited by patients with semantic dementia (SD). In his renowned novel, García Márquez depicts the plight of Macondo, a town struck by the dreaded insomnia plague. The most devastating symptom of the plague is not the impossibility of sleep, but rather the loss of 'the name and notion of things'. In an effort to combat this insidious loss of knowledge, the protagonist, José Arcadio Buendía, 'marked everything with its name: table, chair, clock, door, wall, bed, pan'. 'Studying the infinite possibilities of a loss of memory, he realized that the day might come when things would be recognized by their inscriptions but that no one would remember their use'. The cognitive impairments experienced by Macondo's inhabitants are remarkably similar to those observed in SD, a clinical syndrome characterized by a progressive breakdown of conceptual knowledge (semantic memory) in the context of relatively preserved day-to-day (episodic) memory. First recognized in 1975, it is now considered one of the main variants of frontotemporal lobar degeneration. Writing within the realm of magical realism and investigating the power of language as a form of communication, García Márquez provides beautiful descriptions of the loss of 'the name and notion of things' typical of the syndrome. He further speculates on ways to cope with this dissolution of meaning, ranging from 'the spell of an imaginary reality' to José Arcadio's 'memory machine', strategies that resonate with attempts by semantic dementia patients to cope with their disease. Remarkably, García Márquez created a striking literary depiction of collective semantic dementia before the syndrome was recognized in neurology. The novel also provides an inspiring and human account of one town's fight against 'the quicksand of forgetfulness'.

Focal autobiographical amnesia in association with transient epileptic amnesia.

PubMed

Manes, F; Hodges, J R; Graham, K S; Zeman, A

2001-03-01

Although problems with remembering significant events from the past (e.g. holidays, weddings, etc.) have been reported previously in patients with transient epileptic amnesia (TEA), to date there have been no detailed studies of autobiographical memory in patients with this disorder. To investigate this issue, a 68-year-old right-handed man (R.G.) who suffered from TEA and reported significant autobiographical memory problems was tested on a battery of neuropsychological tests of anterograde and remote memory. Tests of autobiographical memory revealed that R.G. was unable to evoke detailed autobiographical recollections from a substantial part of his life. By contrast, he performed well on tests of new learning and general knowledge and possessed good personal semantic information about his past. In summary, a distinct form of autobiographical amnesia, which is characterized by loss of experiential remembering of significant events, may be associated with TEA. It is proposed that the autobiographical memory deficit seen in the disorder may result from the progressive erasure of cortically based memory representations. This case adds to growing evidence for a dissociation between mechanisms subserving anterograde memory and those required to evoke remote episodic memories.

Is There a Relation between EEG-Slow Waves and Memory Dysfunction in Epilepsy? A Critical Appraisal

PubMed Central

Höller, Yvonne; Trinka, Eugen

2015-01-01

Is there a relationship between peri-ictal slow waves, loss of consciousness, memory, and slow-wave sleep, in patients with different forms of epilepsy? We hypothesize that mechanisms, which result in peri-ictal slow-wave activity as detected by the electroencephalogram, could negatively affect memory processes. Slow waves (≤4 Hz) can be found in seizures with impairment of consciousness and also occur in focal seizures without impairment of consciousness but with inhibited access to memory functions. Peri-ictal slow waves are regarded as dysfunctional and are probably caused by mechanisms, which are essential to disturb the consolidation of memory entries in these patients. This is in strong contrast to physiological slow-wave activity during deep sleep, which is thought to group memory-consolidating fast oscillatory activity. In patients with epilepsy, slow waves may not only correlate with the peri-ictal clouding of consciousness, but could be the epiphenomenon of mechanisms, which interfere with normal brain function in a wider range. These mechanisms may have transient impacts on memory, such as temporary inhibition of memory systems, altered patterns of hippocampal–neocortical interactions during slow-wave sleep, or disturbed cross-frequency coupling of slow and fast oscillations. In addition, repeated tonic–clonic seizures over the years in uncontrolled chronic epilepsy may cause a progressive cognitive decline. This hypothesis can only be assessed in long-term prospective studies. These studies could disentangle the reversible short-term impacts of seizures, and the impacts of chronic uncontrolled seizures. Chronic uncontrolled seizures lead to irreversible memory impairment. By contrast, short-term impacts do not necessarily lead to a progressive cognitive decline but result in significantly impaired peri-ictal memory performance. PMID:26124717

Designer Receptors Enhance Memory in a Mouse Model of Down Syndrome

PubMed Central

Fortress, Ashley M.; Hamlett, Eric D.; Vazey, Elena M.; Aston-Jones, Gary; Cass, Wayne A.; Boger, Heather A.

2015-01-01

Designer receptors exclusively activated by designer drugs (DREADDs) are novel and powerful tools to investigate discrete neuronal populations in the brain. We have used DREADDs to stimulate degenerating neurons in a Down syndrome (DS) model, Ts65Dn mice. Individuals with DS develop Alzheimer's disease (AD) neuropathology and have elevated risk for dementia starting in their 30s and 40s. Individuals with DS often exhibit working memory deficits coupled with degeneration of the locus coeruleus (LC) norepinephrine (NE) neurons. It is thought that LC degeneration precedes other AD-related neuronal loss, and LC noradrenergic integrity is important for executive function, working memory, and attention. Previous studies have shown that LC-enhancing drugs can slow the progression of AD pathology, including amyloid aggregation, oxidative stress, and inflammation. We have shown that LC degeneration in Ts65Dn mice leads to exaggerated memory loss and neuronal degeneration. We used a DREADD, hM3Dq, administered via adeno-associated virus into the LC under a synthetic promoter, PRSx8, to selectively stimulate LC neurons by exogenous administration of the inert DREADD ligand clozapine-N-oxide. DREADD stimulation of LC-NE enhanced performance in a novel object recognition task and reduced hyperactivity in Ts65Dn mice, without significant behavioral effects in controls. To confirm that the noradrenergic transmitter system was responsible for the enhanced memory function, the NE prodrug l-threo-dihydroxyphenylserine was administered in Ts65Dn and normosomic littermate control mice, and produced similar behavioral results. Thus, NE stimulation may prevent memory loss in Ts65Dn mice, and may hold promise for treatment in individuals with DS and dementia. PMID:25632113

An Item Gains and Losses Analysis of False Memories Suggests Critical Items Receive More Item-Specific Processing than List Items

ERIC Educational Resources Information Center

Burns, Daniel J.; Martens, Nicholas J.; Bertoni, Alicia A.; Sweeney, Emily J.; Lividini, Michelle D.

2006-01-01

In a repeated testing paradigm, list items receiving item-specific processing are more likely to be recovered across successive tests (item gains), whereas items receiving relational processing are likely to be forgotten progressively less on successive tests. Moreover, analysis of cumulative-recall curves has shown that item-specific processing…

Treatment of a patient with posterior cortical atrophy (PCA) with chiropractic manipulation and Dynamic Neuromuscular Stabilization (DNS): A case report

PubMed Central

Francio, Vinicius T.; Boesch, Ron; Tunning, Michael

2015-01-01

Objective: Posterior cortical atrophy (PCA) is a rare progressive neurodegenerative syndrome which unusual symptoms include deficits of balance, bodily orientation, chronic pain syndrome and dysfunctional motor patterns. Current research provides minimal guidance on support, education and recommended evidence-based patient care. This case reports the utilization of chiropractic spinal manipulation, dynamic neuromuscular stabilization (DNS), and other adjunctive procedures along with medical treatment of PCA. Clinical features: A 54-year-old male presented to a chiropractic clinic with non-specific back pain associated with visual disturbances, slight memory loss, and inappropriate cognitive motor control. After physical examination, brain MRI and PET scan, the diagnosis of PCA was recognized. Intervention and Outcome: Chiropractic spinal manipulation and dynamic neuromuscular stabilization were utilized as adjunctive care to conservative pharmacological treatment of PCA. Outcome measurements showed a 60% improvement in the patient’s perception of health with restored functional neuromuscular pattern, improvements in locomotion, posture, pain control, mood, tolerance to activities of daily living (ADLs) and overall satisfactory progress in quality of life. Yet, no changes on memory loss progression, visual space orientation, and speech were observed. Conclusion: PCA is a progressive and debilitating condition. Because of poor awareness of PCA by physicians, patients usually receive incomplete care. Additional efforts must be centered on the musculoskeletal features of PCA, aiming enhancement in quality of life and functional improvements (FI). Adjunctive rehabilitative treatment is considered essential for individuals with cognitive and motor disturbances, and manual medicine procedures may be consider a viable option. PMID:25729084

Influence of non-spatial working memory demands on reach-grasp responses to loss of balance: Effects of age and fall risk.

PubMed

Westlake, Kelly P; Johnson, Brian P; Creath, Robert A; Neff, Rachel M; Rogers, Mark W

2016-03-01

Reactive balance recovery strategies following an unexpected loss of balance are crucial to the prevention of falls, head trauma and other major injuries in older adults. While a longstanding focus has been on understanding lower limb recovery responses, the upper limbs also play a critical role. However, when a fall occurs, little is known about the role of memory and attention shifting on the reach to grasp recovery strategy and what factors determine the speed and precision of this response beyond simple reaction time. The objective of this study was to compare response time and accuracy of a stabilizing grasp following a balance perturbation in older adult fallers compared to non-fallers and younger adults while loading the processing demands of non-spatial, verbal working memory. Working memory was engaged with a progressively challenging verb-generation task that was interrupted by an unexpected sideways platform perturbation and a pre-instructed reach to grasp response. Results revealed that the older adults, particularly those at high fall risk, demonstrated significantly increased movement time to handrail contact and grasping errors during conditions in which non-spatial memory was actively engaged. These findings provide preliminary evidence of the cognitive deficit in attention shifting away from an ongoing working memory task that underlies delayed and inaccurate protective reach to grasp responses in older adult fallers. Copyright © 2016 Elsevier B.V. All rights reserved.

Cotinine improves visual recognition memory and decreases cortical Tau phosphorylation in the Tg6799 mice.

PubMed

Grizzell, J Alex; Patel, Sagar; Barreto, George E; Echeverria, Valentina

2017-08-01

Alzheimer's disease (AD) is associated with the progressive aggregation of hyperphosphorylated forms of the microtubule associated protein Tau in the central nervous system. Cotinine, the main metabolite of nicotine, reduced working memory deficits, synaptic loss, and amyloid β peptide aggregation into oligomers and plaques as well as inhibited the cerebral Tau kinase, glycogen synthase 3β (GSK3β) in the transgenic (Tg)6799 (5XFAD) mice. In this study, the effect of cotinine on visual recognition memory and cortical Tau phosphorylation at the GSK3β sites Serine (Ser)-396/Ser-404 and phospho-CREB were investigated in the Tg6799 and non-transgenic (NT) littermate mice. Tg mice showed short-term visual recognition memory impairment in the novel object recognition test, and higher levels of Tau phosphorylation when compared to NT mice. Cotinine significantly improved visual recognition memory performance increased CREB phosphorylation and reduced cortical Tau phosphorylation. Potential mechanisms underlying theses beneficial effects are discussed. Copyright © 2017. Published by Elsevier Inc.

A progressive breakdown of the body in space.

PubMed

Kourtidou, Evie; Kasselimis, Dimitrios; Makrydakis, George; Chatziantoniou, Lina; Kyrozis, Andreas; Evdokimidis, Ioannis; Potagas, Constantin

2018-06-08

A 74 year-old woman (MD), free of previous neurological history, presented with difficulty in handling cutlery, clothes, writing with what was initially described as an atypical apraxia in acts related to space. Initial neurological evaluation revealed mixed, asymmetric pyramidal, and extrapyramidal semiology. Νeuropsychological testing revealed dressing and constructional deficits, ideomotor apraxia and signs of executive dysfunction in absence of memory, language, and visual perception pathology. The final diagnosis was that of a corticobasal degeneration, where the rare occurrence of a progressively emerging syndrome of self-management loss within peripersonal space is observed.

[Clinical aspects of Alzheimer disease].

PubMed

Soto, Maria; Reynish, Emma; Nourhashémi, Fati; Vellas, Bruno

2007-10-01

Alzheimer disease is diagnosed in only half of the patients with this disease in France. In its typical form, it is characterized at the onset by short-term memory problems, repetitive and unusual oversights and forgetfulness, and difficulties in learning new information. Dementia is responsible for more than 50% of the need for care in the elderly. Disease progression is accompanied by noncognitive complications. The 3 most frequent are psychological and behavioral symptoms, weight loss, and impaired balance and walking. Its progressive nature and potential complications underline the need for multidisciplinary management for patients and their families, with regular medical follow-up.

Progression of hippocampal degeneration in amyotrophic lateral sclerosis with or without memory impairment: distinction from Alzheimer disease.

PubMed

Takeda, Takahiro; Uchihara, Toshiki; Arai, Nobutaka; Mizutani, Toshio; Iwata, Makoto

2009-01-01

The hippocampal involvement in amyotrophic lateral sclerosis (ALS) patients has been known for more than a decade, however, its relationship to clinical manifestations including memory deficits and topographical differentiation from Alzheimer disease (AD) remain unclear. In order to clarify the anatomopathological features in the hippocampus and their relevance to disease-specific memory deficits in ALS patients, topography and cytopathology of the hippocampal lesions along the perforant pathway were quantitatively and semiquantitatively surveyed in 14 ALS patients with extramotor involvement. These pathological findings were compared with clinical characteristics assessed from their clinical records. Cytoplasmic inclusions initially appear in the granular cells of the dentate gyrus (DG) and superficial small neurons of the transentorhinal cortex (TEC) with mild subicular degeneration (stage I: inclusion stage). Subsequent gliosis and neuronal loss of the TEC, concomitant with presynaptic degeneration of the outer molecular layer of the DG, suggests an extension of the degeneration through the perforant pathway (stage II: early perforant stage). In a more advanced stage, the presynaptic degeneration is more evident with moderate to severe neuronal loss in the TEC (stage III: advanced perforant stage). This advanced stage was associated with episodic memory deficits mimicking AD in some ALS patients. This ALS pathology initiated by cytoplasmic inclusions and neuronal loss in layer II-III of the TEC is different from neurofibrillary tangles of AD, dominant in layer II-III of the entorhinal cortex. Because this involvement of the TEC-molecular DG projection and subiculum is specific to ALS, it will provide a basis for clinical characterization of memory deficits of ALS, which could be distinct from those of AD.

Alzheimer disease: focus on computed tomography.

PubMed

Reynolds, April

2013-01-01

Alzheimer disease is the most common type of dementia, affecting approximately 5.3 million Americans. This debilitating disease is marked by memory loss, confusion, and loss of cognitive ability. The exact cause of Alzheimer disease is unknown although research suggests that it might result from a combination of factors. The hallmarks of Alzheimer disease are the presence of beta-amyloid plaques and neurofibrillary tangles in the brain. Radiologic imaging can help physicians detect these structural characteristics and monitor disease progression and brain function. Computed tomography and magnetic resonance imaging are considered first-line imaging modalities for the routine evaluation of Alzheimer disease.

Impact of social relationships on Alzheimer's memory impairment: mechanistic studies.

PubMed

Hsiao, Ya-Hsin; Chang, Chih-Hua; Gean, Po-Wu

2018-01-11

Alzheimer's disease (AD) is characterized by progressive memory and neuronal loss culminating in cognitive impairment that not only affects a person's living ability but also becomes a society's as well as a family's economic burden. AD is the most common form of dementia in older persons. It is expected that the number of people with AD dementia will increase dramatically in the next 30 years, projecting to 75 million in 2030 and 131.5 million in 2050 worldwide. So far, no sufficient evidence is available to support that any medicine is able to prevent or reverse the progression of the disease. Early studies have shown that social environment, particularly social relationships, can affect one's behavior and mental health. A study analyzing the correlation between loneliness and risk of developing AD revealed that lonely persons had higher risk of AD compared with persons who were not lonely. On the other hand, it has been reported that we can prevent cognitive decline and delay the onset of AD if we keep mentally active and frequently participate in social activities. In this review, we focus on the impact of social behaviors on the progression of cognitive deficit in animal models of AD with a particular emphasis on a mechanistic scheme that explains how social isolation exacerbates cognitive impairment and how social interaction with conspecifics rescues AD patients' memory deficit.

Recovering and preventing loss of detailed memory: differential rates of forgetting for detail types in episodic memory

PubMed Central

Bonasia, Kyra; St-Laurent, Marie; Pishdadian, Sara; Winocur, Gordon; Grady, Cheryl; Moscovitch, Morris

2016-01-01

Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired, while memory for central details is relatively spared. Given the sensitivity of memory to loss of details, the present study sought to investigate factors that mediate the forgetting of different types of information from naturalistic episodic memories in young healthy adults. The study investigated (1) time-dependent loss of “central” and “peripheral” details from episodic memories, (2) the effectiveness of cuing with reminders to reinstate memory details, and (3) the role of retrieval in preventing forgetting. Over the course of 7 d, memory for naturalistic events (film clips) underwent a time-dependent loss of peripheral details, while memory for central details (the core or gist of events) showed significantly less loss. Giving brief reminders of the clips just before retrieval reinstated memory for peripheral details, suggesting that loss of details is not always permanent, and may reflect both a storage and retrieval deficit. Furthermore, retrieving a memory shortly after it was encoded prevented loss of both central and peripheral details, thereby promoting retention over time. We consider the implications of these results for behavioral and neurobiological models of retention and forgetting. PMID:26773100

Recovering and preventing loss of detailed memory: differential rates of forgetting for detail types in episodic memory.

PubMed

Sekeres, Melanie J; Bonasia, Kyra; St-Laurent, Marie; Pishdadian, Sara; Winocur, Gordon; Grady, Cheryl; Moscovitch, Morris

2016-02-01

Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired, while memory for central details is relatively spared. Given the sensitivity of memory to loss of details, the present study sought to investigate factors that mediate the forgetting of different types of information from naturalistic episodic memories in young healthy adults. The study investigated (1) time-dependent loss of "central" and "peripheral" details from episodic memories, (2) the effectiveness of cuing with reminders to reinstate memory details, and (3) the role of retrieval in preventing forgetting. Over the course of 7 d, memory for naturalistic events (film clips) underwent a time-dependent loss of peripheral details, while memory for central details (the core or gist of events) showed significantly less loss. Giving brief reminders of the clips just before retrieval reinstated memory for peripheral details, suggesting that loss of details is not always permanent, and may reflect both a storage and retrieval deficit. Furthermore, retrieving a memory shortly after it was encoded prevented loss of both central and peripheral details, thereby promoting retention over time. We consider the implications of these results for behavioral and neurobiological models of retention and forgetting. © 2016 Sekeres et al.; Published by Cold Spring Harbor Laboratory Press.

Single voxel magnetic resonance spectroscopy at 3 Tesla in a memory disorders clinic: early right hippocampal NAA/Cr loss in mildly impaired subjects.

PubMed

Caserta, Maria T; Ragin, Ann; Hermida, Adriana P; Ahrens, R John; Wise, Leon

2008-11-30

In this study, we use magnetic resonance spectroscopy (MRS) at 3 Tesla to measure N-acetyl aspartate (NAA), myo-inositol (mI) and choline (Cho) to creatine (Cr) ratios in R (right) and L (left) hippocampi (H) in 8 mildly memory impaired (MMI), 6 probable Alzheimer's Disease (PRAD), and 17 control subjects. NAA/Cr was significantly reduced in the RH in the MMI group and bilaterally in the PRAD group vs. controls. No other metabolite differences were noted between the three groups. Five MMI subjects have converted to PRAD in follow-up. These findings suggest that RH NAA/Cr ratios measured at 3 Tesla may be a sensitive marker of future progression to dementia in a clinically defined population with isolated memory complaints.

Early fear memory defects are associated with altered synaptic plasticity and molecular architecture in the TgCRND8 Alzheimer's disease mouse model.

PubMed

Steele, John W; Brautigam, Hannah; Short, Jennifer A; Sowa, Allison; Shi, Mengxi; Yadav, Aniruddha; Weaver, Christina M; Westaway, David; Fraser, Paul E; St George-Hyslop, Peter H; Gandy, Sam; Hof, Patrick R; Dickstein, Dara L

2014-07-01

Alzheimer's disease (AD) is a complex and slowly progressing dementing disorder that results in neuronal and synaptic loss, deposition in brain of aberrantly folded proteins, and impairment of spatial and episodic memory. Most studies of mouse models of AD have employed analyses of cognitive status and assessment of amyloid burden, gliosis, and molecular pathology during disease progression. Here we sought to understand the behavioral, cellular, ultrastructural, and molecular changes that occur at a pathological stage equivalent to the early stages of human AD. We studied the TgCRND8 mouse, a model of aggressive AD amyloidosis, at an early stage of plaque pathology (3 months of age) in comparison to their wildtype littermates and assessed changes in cognition, neuron and spine structure, and expression of synaptic glutamate receptor proteins. We found that, at this age, TgCRND8 mice display substantial plaque deposition in the neocortex and hippocampus and impairment on cued and contextual memory tasks. Of particular interest, we also observed a significant decrease in the number of neurons in the hippocampus. Furthermore, analysis of CA1 neurons revealed significant changes in apical and basal dendritic spine types, as well as altered expression of GluN1 and GluA2 receptors. This change in molecular architecture within the hippocampus may reflect a rising representation of inherently less stable thin spine populations, which can cause cognitive decline. These changes, taken together with toxic insults from amyloid-β protein, may underlie the observed neuronal loss. Copyright © 2014 Wiley Periodicals, Inc.

Selective loss of dopaminergic neurons in the substantia nigra pars compacta after systemic administration of MPTP facilitates extinction learning.

PubMed

Kinoshita, Ken-ichi; Tada, Yayoi; Muroi, Yoshikage; Unno, Toshihiro; Ishii, Toshiaki

2015-09-15

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNpc). In PD, thinking and retrieval deficits often arise from cognitive impairments. However, the mechanism of cognitive disorders in PD remains unknown. Therefore, we investigated cognitive function in PD model mice produced by intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which specifically destroys the DAergic neurons in the SNpc. We evaluated the cognitive function of MPTP-treated mice (PD mice) using the contextual fear conditioning test. In the test, each experiment consists of three phases: training, re-exposure, and testing. Mice were trained with a foot shock (a weak unconditioned stimulus: 1mA/2s duration, once, or an intense unconditioned stimulus: 2mA/2s duration, twice), and 24h later, mice were re-exposed to the training context for 3min to determine reconsolidation or 30min to determine extinction. The percentage of time spent freezing was measured during the test session as indexes of memory consolidation, reconsolidation, and extinction. Reconsolidation of PD mice occurred normally but memory extinction was facilitated in PD mice compared to control mice. Moreover, memory retention in PD mice was attenuated earlier than in controls following repeated conditioned stimuli every day. PD mice with selective loss of DAergic neurons in the SNpc showed attenuated memory retention, probably via facilitated extinction learning. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of COX1-2/5-LOX blockade in Alzheimer transgenic 3xTg-AD mice.

PubMed

Bitto, Alessandra; Giuliani, Daniela; Pallio, Giovanni; Irrera, Natasha; Vandini, Eleonora; Canalini, Fabrizio; Zaffe, Davide; Ottani, Alessandra; Minutoli, Letteria; Rinaldi, Mariagrazia; Guarini, Salvatore; Squadrito, Francesco; Altavilla, Domenica

2017-05-01

Alzheimer's disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice. Mice were 3 months at the beginning of the study. Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip). Morris water maze was used to assess learning and memory. Histology was performed to evidence Aβ plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis. Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1-42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals. Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.

Cholinergic degeneration and memory loss delayed by vitamin E in a Down syndrome mouse model

PubMed Central

Lockrow, Jason; Prakasam, Annamalai; Huang, Peng; Bimonte-Nelson, Heather; Sambamurti, Kumar; Granholm, Ann-Charlotte

2009-01-01

Down syndrome (DS) individuals develop several neuropathological hallmarks seen in Alzheimer's disease, including cognitive decline and the early loss of cholinergic markers in the basal forebrain. These deficits are replicated in the Ts65Dn mouse, which contains a partial trisomy of murine chromosome 16, the orthologous genetic segment to human chromosome 21. Oxidative stress levels are elevated early in DS, and may contribute to the neurodegeneration seen in these individuals. We evaluated oxidative stress in Ts65Dn mice, and assessed the efficacy of long-term antioxidant supplementation on memory and basal forebrain pathology. We report that oxidative stress was elevated in the adult Ts65Dn brain, and that supplementation with the antioxidant vitamin E effectively reduced these markers. Also, Ts65Dn mice receiving vitamin E exhibited improved performance on a spatial working memory task and showed an attenuation of cholinergic neuron pathology in the basal forebrain. This study provides evidence that vitamin E delays onset of cognitive and morphological abnormalities in a mouse model of DS, and may represent a safe and effective treatment early in the progression of DS neuropathology. PMID:19135442

Oxidant/Antioxidant Imbalance and the Risk of Alzheimer's Disease

PubMed Central

Abdel Moneim, Ahmed E.

2015-01-01

Alzheimer's disease (AD) is the most common form of dementia characterized by progressive loss of memory and other cognitive functions among older people. Senile plaques and neurofibrillary tangles are the most hallmarks lesions in the brain of AD in addition to neurons loss. Accumulating evidence has shown that oxidative stress–induced damage may play an important role in the initiation and progression of AD pathogenesis. Redox impairment occurs when there is an imbalance between the production and quenching of free radicals from oxygen species. These reactive oxygen species augment the formation and aggregation of amyloid-β and tau protein hyperphosphorylation and vice versa. Currently, there is no available treatments can modify the disease. However, wide varieties of antioxidants show promise to delay or prevent the symptoms of AD and may help in treating the disease. In this review, the role of oxidative stress in AD pathogenesis and the common used antioxidant therapies for AD will summarize. PMID:25817254

[The state of the art research findings on the relationship between chronic periodontitis and Alzheimer's disease: a review].

PubMed

Qian, X S; Ge, S

2018-04-09

Along with the development of periodontal medicine, there is a growing number of evidence showing that periodontitis could influence systemic health. Periodontitis is a chronic inflammatory disease caused by microbial infection mediated by dental plaque. Periodontal pathogenic microorganisms and its toxic products can disseminate through the blood stream or may cause the host immune response, which may lead to pathological changes of cerebral vessels and brain tissues to establish connection with Alzheimer's disease (AD). AD is a progressive neurodegenerative disease characterized by progressive memory loss, language and cognitive dysfunction. This article reviewed the association between chronic periodontitis and AD.

[Calcium hypothesis of Alzheimer disease].

PubMed

Riazantseva, M A; Mozhaeva, G N; Kaznacheeva, E V

2012-01-01

Alzheimer's disease is the most common neurodegenerative disorder characterized by progressive memory and cognitive abilities loss. The etiology of Alzheimer's disease is poorly understood. In this regard, there is no effective treatment for the disease. Various hypotheses to explain the nature of the pathology of Alzheimer's disease led to the development of appropriate therapeutics. Despite of decades of research and clinical trials available therapeutics, at best, can only slow down the progression of the disease, but cannot cure it. This review dedicated to the one of modern hypotheses of Alzheimer's disease pathogenesis implied the impairment of calcium homeostasis as a key event for the development of neurodegenerative processes.

Generalized dissociative amnesia: episodic, semantic and procedural memories lost and found.

PubMed

van der Hart, O; Nijenhuis, E

2001-10-01

This review tests Ribot's classic twofold categorization of generalized amnesia (GA) into Type I, total loss of episodic memory, and Type II, additional more or less extensive loss of semantic and/or procedural memory. It also explores his law of regression, according to which, cast in modern terms, recovery of lost procedural and semantic memories precedes recovery of episodic memory, as well as reported aetiological factors. Clinically and formally assessed cases of GA, published since 1845, were surveyed and further analysed. Over and above authentic episodic memory loss, cases differed widely in the extent of impairment of semantic and procedural memory. Recovery of semantic and procedural memory often preceded recovery of episodic memory. This particularly applied to authenticated trauma memories. To an extent, lost memories affected current functioning, and in some cases were associated with alternating dissociative personalities. Severe memory distortions upon memory recovery were not reported. Most cases were trauma or stress related, while in some cases the aetiology remained unknown. Contrary to the view expressed in DSM-IV, which states that dissociative amnesia pertains to an inability to recall personal information, GA may also involve loss and recovery of semantic and procedural memories. Since the loss of various memory types in GA is dimensional rather than categorical, Ribot's typological distinction does not hold. Some of the reviewed cases suggest a trauma-related aetiology. Generalized amnesia of varying degrees of severity can involve delayed retrieval of trauma memories, as well as the loss and delayed retrieval of the premorbid personality.

Glutamate system, amyloid β peptides and tau protein: functional interrelationships and relevance to Alzheimer disease pathology

PubMed Central

Revett, Timothy J.; Baker, Glen B.; Jhamandas, Jack; Kar, Satyabrata

2013-01-01

Alzheimer disease is the most prevalent form of dementia globally and is characterized premortem by a gradual memory loss and deterioration of higher cognitive functions and postmortem by neuritic plaques containing amyloid β peptide and neurofibrillary tangles containing phospho-tau protein. Glutamate is the most abundant neurotransmitter in the brain and is essential to memory formation through processes such as long-term potentiation and so might be pivotal to Alzheimer disease progression. This review discusses how the glutamatergic system is impaired in Alzheimer disease and how interactions of amyloid β and glutamate influence synaptic function, tau phosphorylation and neurodegeneration. Interestingly, glutamate not only influences amyloid β production, but also amyloid β can alter the levels of glutamate at the synapse, indicating that small changes in the concentrations of both molecules could influence Alzheimer disease progression. Finally, we describe how the glutamate receptor antagonist, memantine, has been used in the treatment of individuals with Alzheimer disease and discuss its effectiveness. PMID:22894822

Age-related changes in decision making: comparing informed and noninformed situations.

PubMed

Van Duijvenvoorde, Anna C K; Jansen, Brenda R J; Bredman, Joren C; Huizenga, Hilde M

2012-01-01

Advantageous decision making progressively develops into early adulthood, most specifically in complex and motivationally salient decision situations in which direct feedback on gains and losses is provided (Figner & Weber, 2011). However, the factors that underlie this developmental improvement in decision making are still not well understood. The current study therefore investigates 2 potential factors, long-term memory and working memory, by assigning a large developmental sample (7-29 years of age) to a condition with either high or low demands on long-term and working memory. The first condition featured an age-adapted version of the Iowa Gambling Task (IGT; Bechara, Damasio, Damasio, & Anderson, 1994; i.e., a noninformed situation), whereas the second condition provided an external store where explicit information on gains, losses, and probabilities per choice option was presented (i.e., an informed situation). Consistent with previous developmental IGT studies, children up to age 12 did not learn to prefer advantageous options in the noninformed condition. In contrast, all age groups learned to prefer the advantageous options in the informed conditions, although a slight developmental increase in advantageous decision making remained. These results indicate that lowering dependence on long-term and working memory improves children's advantageous decision making. The results additionally suggest that other factors, like inhibitory control processes, may play an additional role in the development of advantageous decision making.

Age-dependent neurodegeneration accompanying memory loss in transgenic mice defective in mitochondrial aldehyde dehydrogenase 2 activity.

PubMed

Ohsawa, Ikuroh; Nishimaki, Kiyomi; Murakami, Yayoi; Suzuki, Yuko; Ishikawa, Masahiro; Ohta, Shigeo

2008-06-11

Oxidative stress may underlie age-dependent memory loss and cognitive decline. Toxic aldehydes, including 4-hydroxy-2-nonenal (HNE), an end product of lipid peroxides, are known to accumulate in the brain in neurodegenerative disease. We have previously shown that mitochondrial aldehyde dehydrogenase 2 (ALDH2) detoxifies HNE by oxidizing its aldehyde group. To investigate the role of such toxic aldehydes, we produced transgenic mice, which expressed a dominant-negative form of ALDH2 in the brain. The mice had decreased ability to detoxify HNE in their cortical neurons and accelerated accumulation of HNE in the brain. Consequently, their lifespan was shortened and age-dependent neurodegeneration and hyperphosphorylation of tau were observed. Object recognition and Morris water maze tests revealed that the onset of cognitive impairment correlated with the degeneration, which was further accelerated by APOE (apolipoprotein E) knock-out; therefore, the accumulation of toxic aldehydes is by itself critical in the progression of neurodegenerative disease, which could be suppressed by ALDH2.

The loss of episodic memories in retrograde amnesia: single-case and group studies.

PubMed

Kopelman, M D; Kapur, N

2001-09-29

Retrograde amnesia in neurological disorders is a perplexing and fascinating research topic. The severity of retrograde amnesia is not well correlated with that of anterograde amnesia, and there can be disproportionate impairments of either. Within retrograde amnesia, there are various dissociations which have been claimed-for example, between the more autobiographical (episodic) and more semantic components of memory. However, the associations of different types of retrograde amnesia are also important, and clarification of these issues is confounded by the fact that retrograde amnesia seems to be particularly vulnerable to psychogenic factors. Large frontal and temporal lobe lesions have been postulated as critical in producing retrograde amnesia. Theories of retrograde amnesia have encompassed storage versus access disruption, physiological processes of 'consolidation', the progressive transformation of episodic memories into a more 'semantic' form, and multiple-trace theory. Single-case investigations, group studies and various forms of neuroimaging can all contribute to the resolution of these controversies.

The cost of misremembering: Inferring the loss function in visual working memory.

PubMed

Sims, Chris R

2015-03-04

Visual working memory (VWM) is a highly limited storage system. A basic consequence of this fact is that visual memories cannot perfectly encode or represent the veridical structure of the world. However, in natural tasks, some memory errors might be more costly than others. This raises the intriguing possibility that the nature of memory error reflects the costs of committing different kinds of errors. Many existing theories assume that visual memories are noise-corrupted versions of afferent perceptual signals. However, this additive noise assumption oversimplifies the problem. Implicit in the behavioral phenomena of visual working memory is the concept of a loss function: a mathematical entity that describes the relative cost to the organism of making different types of memory errors. An optimally efficient memory system is one that minimizes the expected loss according to a particular loss function, while subject to a constraint on memory capacity. This paper describes a novel theoretical framework for characterizing visual working memory in terms of its implicit loss function. Using inverse decision theory, the empirical loss function is estimated from the results of a standard delayed recall visual memory experiment. These results are compared to the predicted behavior of a visual working memory system that is optimally efficient for a previously identified natural task, gaze correction following saccadic error. Finally, the approach is compared to alternative models of visual working memory, and shown to offer a superior account of the empirical data across a range of experimental datasets. © 2015 ARVO.

Berberine prevents nigrostriatal dopaminergic neuronal loss and suppresses hippocampal apoptosis in mice with Parkinson's disease.

PubMed

Kim, Mia; Cho, Ki-Ho; Shin, Mal-Soon; Lee, Jae-Min; Cho, Han-Sam; Kim, Chang-Ju; Shin, Dong-Hoon; Yang, Hyeon Jeong

2014-04-01

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of nigral dopaminergic neurons and a reduction in striatal dopaminergic fibers, which result in tremors, rigidity, bradykinesia and gait disturbance. In addition to motor dysfunction, dementia is a widely recognized symptom of patients with PD. Berberine, an isoquinoline alkaloid isolated from Berberis vulgaris L., is known to exert anxiolytic, analgesic, anti-inflammatory, antipsychotic, antidepressant and anti-amnesic effects. In the present study, we investigated the effects of berberine on short-term memory in relation to dopamine depletion and hippocampal neurogenesis using a mouse model of PD, induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/P) treatment. Mice in the berberine-treated groups were orally administered berberine once a day for a total of 5 weeks. Our results revealed that the injection of MPTP/P induced dopaminergic neuronal death in the substantia nigra and fiber loss in the striatum. This resulted in impaired motor balance and coordination, as assessed by the beam walking test. We further demonstrated that MPTP/P-induced apoptosis in the hippocampus deteriorated short-term memory, as shown by the step-down avoidance task. By contrast, neurogenesis in the hippocampal dentate gyrus, which is a compensatory adaptive response to excessive apoptosis, was increased upon PD induction. However, treatment with berberine enhanced motor balance and coordination by preventing dopaminergic neuronal damage. Treatment with berberine also improved short-term memory by inhibiting apoptosis in the hippocampus. Berberine demonstrated maximal potency at 50 mg/kg. Based on these data, treatment with berberine may serve as a potential therapeutic strategy for the alleviation of memory impairment and motor dysfunction in patients with PD.

Curcumin reverses T cell-mediated adaptive immune dysfunctions in tumor-bearing hosts.

PubMed

Bhattacharyya, Sankar; Md Sakib Hossain, Dewan; Mohanty, Suchismita; Sankar Sen, Gouri; Chattopadhyay, Sreya; Banerjee, Shuvomoy; Chakraborty, Juni; Das, Kaushik; Sarkar, Diptendra; Das, Tanya; Sa, Gaurisankar

2010-07-01

Immune dysfunction is well documented during tumor progression and likely contributes to tumor immune evasion. CD8(+) cytotoxic T lymphocytes (CTLs) are involved in antigen-specific tumor destruction and CD4(+) T cells are essential for helping this CD8(+) T cell-dependent tumor eradication. Tumors often target and inhibit T-cell function to escape from immune surveillance. This dysfunction includes loss of effector and memory T cells, bias towards type 2 cytokines and expansion of T regulatory (Treg) cells. Curcumin has previously been shown to have antitumor activity and some research has addressed the immunoprotective potential of this plant-derived polyphenol in tumor-bearing hosts. Here we examined the role of curcumin in the prevention of tumor-induced dysfunction of T cell-based immune responses. We observed severe loss of both effector and memory T-cell populations, downregulation of type 1 and upregulation of type 2 immune responses and decreased proliferation of effector T cells in the presence of tumors. Curcumin, in turn, prevented this loss of T cells, expanded central memory T cell (T(CM))/effector memory T cell (T(EM)) populations, reversed the type 2 immune bias and attenuated the tumor-induced inhibition of T-cell proliferation in tumor-bearing hosts. Further investigation revealed that tumor burden upregulated Treg cell populations and stimulated the production of the immunosuppressive cytokines transforming growth factor (TGF)-beta and IL-10 in these cells. Curcumin, however, inhibited the suppressive activity of Treg cells by downregulating the production of TGF-beta and IL-10 in these cells. More importantly, curcumin treatment enhanced the ability of effector T cells to kill cancer cells. Overall, our observations suggest that the unique properties of curcumin may be exploited for successful attenuation of tumor-induced suppression of cell-mediated immune responses.

Loss of Autonoetic Awareness of Recent Autobiographical Episodes and Accelerated Long-Term Forgetting in a Patient with Previously Unrecognized Glutamic Acid Decarboxylase Antibody Related Limbic Encephalitis.

PubMed

Witt, Juri-Alexander; Vogt, Viola Lara; Widman, Guido; Langen, Karl-Josef; Elger, Christian Erich; Helmstaedter, Christoph

2015-01-01

We describe a 35-year-old male patient presenting with depressed mood and emotional instability, who complained about severe anterograde and retrograde memory deficits characterized by accelerated long-term forgetting and loss of autonoetic awareness regarding autobiographical memories of the last 3 years. Months before he had experienced two breakdowns of unknown etiology giving rise to the differential diagnosis of epileptic seizures after various practitioners and clinics had suggested different etiologies such as a psychosomatic condition, burnout, depression, or dissociative amnesia. Neuropsychological assessment indicated selectively impaired figural memory performance. Extended diagnostics confirmed accelerated forgetting of previously learned and retrievable verbal material. Structural imaging showed bilateral swelling and signal alterations of temporomesial structures (left >right). Video-EEG monitoring revealed a left temporal epileptic focus and subclincal seizure, but no overt seizures. Antibody tests in serum and liquor were positive for glutamic acid decarboxylase antibodies. These findings led to the diagnosis of glutamic acid decarboxylase antibody related limbic encephalitis. Monthly steroid pulses over 6 months led to recovery of subjective memory and to intermediate improvement but subsequent worsening of objective memory performance. During the course of treatment, the patient reported de novo paroxysmal non-responsive states. Thus, antiepileptic treatment was started and the patient finally became seizure free. At the last visit, vocational reintegration was successfully in progress. In conclusion, amygdala swelling, retrograde biographic memory impairment, accelerated long-term forgetting, and emotional instability may serve as indicators of limbic encephalitis, even in the absence of overt epileptic seizures. The monitoring of such patients calls for a standardized and concerted multilevel diagnostic approach with repeated assessments.

Prosopagnosia

MedlinePlus

... to memory dysfunction, memory loss, impaired vision, or learning disabilities. Prosopagnosia is thought to be the result of ... to memory dysfunction, memory loss, impaired vision, or learning disabilities. Prosopagnosia is thought to be the result of ...

Medial temporal lobe structure and cognition in individuals with schizophrenia and in their non-psychotic siblings.

PubMed

Karnik-Henry, Meghana S; Wang, Lei; Barch, Deanna M; Harms, Michael P; Campanella, Carolina; Csernansky, John G

2012-07-01

Medial temporal lobe (MTL) structures play a central role in episodic memory. Prior studies suggest that individuals with schizophrenia have deficits in episodic memory as well as structural abnormalities of the medial temporal lobe (MTL). While correlations have been reported between MTL volume loss and episodic memory deficits in such individuals, it is not clear whether such correlations reflect the influence of the disease state or of underlying genetic influences that might contribute to risk. We used high resolution magnetic resonance imaging and probabilistic algorithms for image analysis to determine whether MTL structure, episodic memory performance and the relationship between the two differed among groups of 47 healthy control subjects, 50 control siblings, 39 schizophrenia subjects, and 33 siblings of schizophrenia subjects. High-dimensional large deformation brain mapping was used to obtain volume measures of the hippocampus. Cortical distance mapping was used to obtain volume and thickness measures of the parahippocampal gyrus (PHG) and its substructures: the entorhinal cortex (ERC), the perirhinal cortex (PRC), and the parahippocampal cortex (PHC). Neuropsychological data was used to establish an episodic memory domain score for each subject. Both schizophrenia subjects and their siblings displayed abnormalities in episodic memory performance. Siblings of individuals with schizophrenia, and to a lesser extent, individuals with schizophrenia themselves, displayed abnormalities in measures of MTL structure (volume loss or cortical thinning) as compared to control groups. Further, we observed correlations between structural measures and memory performance in both schizophrenia subjects and their siblings, but not in their respective control groups. These findings suggest that disease-specific genetic factors present in both patients and their relatives may be responsible for correlated abnormalities of MTL structure and memory impairment. The observed attenuated effect of such factors on MTL structure in individuals with schizophrenia may be due to non-genetic influences related to the development and progression of the disease on global brain structure and cognitive processing. Copyright © 2012 Elsevier B.V. All rights reserved.

Amelioration of cognitive impairment and neurodegeneration by catechin hydrate in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.

PubMed

Ejaz Ahmed, Md; Khan, Mohd Moshahid; Javed, Hayate; Vaibhav, Kumar; Khan, Andleeb; Tabassum, Rizwana; Ashafaq, Mohammad; Islam, Farah; Safhi, Mohammed M; Islam, Fakhrul

2013-03-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20mg/kgb wt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3mg/kgb wt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1β levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer's type (SDAT). Copyright © 2013 Elsevier Ltd. All rights reserved.

A transcriptome-based model of central memory CD4 T cell death in HIV infection.

PubMed

Olvera-García, Gustavo; Aguilar-García, Tania; Gutiérrez-Jasso, Fany; Imaz-Rosshandler, Iván; Rangel-Escareño, Claudia; Orozco, Lorena; Aguilar-Delfín, Irma; Vázquez-Pérez, Joel A; Zúñiga, Joaquín; Pérez-Patrigeon, Santiago; Espinosa, Enrique

2016-11-22

Human central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state. Using gene expression microarrays, we analyzed mRNA expression patterns in naive, central memory, and effector memory CD4 T cells from healthy controls, and naive and central memory CD4 T cells from patients with HIV-1 infection. Differentially expressed genes, defined by Log 2 Fold Change (FC) ≥ |0.5| and Log (odds) > 0, were used in pathway enrichment analyses. Central memory CD4 T cells from patients and controls showed comparable expression of differentiation-related genes, ruling out an effector-like differentiation of central memory CD4 T cells in HIV infection. However, 210 genes were differentially expressed in central memory CD4 T cells from patients compared with those from controls. Expression of 75 of these genes was validated by semi quantitative RT-PCR, and independently reproduced enrichment results from this gene expression signature. The results of functional enrichment analysis indicated movement to cell cycle phases G1 and S (increased CCNE1, MKI67, IL12RB2, ADAM9, decreased FGF9, etc.), but also arrest in G2/M (increased CHK1, RBBP8, KIF11, etc.). Unexpectedly, the results also suggested decreased apoptosis (increased CSTA, NFKBIA, decreased RNASEL, etc.). Results also suggested increased IL-1β, IFN-γ, TNF, and RANTES (CCR5) activity upstream of the central memory CD4 T cells signature, consistent with the demonstrated milieu in HIV infection. Our findings support a model where progressive loss of central memory CD4 T cells in chronic HIV-1 infection is driven by increased cell cycle entry followed by mitotic arrest, leading to a non-apoptotic death pathway without actual proliferation, possibly contributing to increased turnover.

The Importance of Object Memories for Older Adults

ERIC Educational Resources Information Center

Phenice, Lillian A.; Griffore, Robert J.

2013-01-01

The memories of treasured objects are essential in giving life meaning. In the process of development in later adulthood, most changes involve significant loss including loss of physical and mental ability, loss of family and friends, and loss of possessions. Objects and their associated memories are especially important in maintaining an internal…

Case Studies Illustrating Focal Alzheimer's, Fluent Aphasia, Late-Onset Memory Loss, and Rapid Dementia.

PubMed

Camsari, Gamze Balci; Murray, Melissa E; Graff-Radford, Neill R

2016-08-01

Many dementia subtypes have more shared signs and symptoms than defining ones. We review 8 cases with 4 overlapping syndromes and demonstrate how to distinguish the cases. These include focal cortical presentations of Alzheimer's disease (AD; posterior cortical atrophy and corticobasal syndrome [CBS]), fluent aphasia (semantic dementia and logopenic aphasia), late-onset slowly progressive dementia (hippocampal sclerosis and limbic predominant AD) and rapidly progressive dementia (Creutzfeldt-Jakob disease and limbic encephalitis). Recognizing the different syndromes can help the clinician to improve their diagnostic skills, leading to improved patient outcomes by early and accurate diagnosis, prompt treatment, and appropriate counseling and guidance. Copyright © 2016 Elsevier Inc. All rights reserved.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection.

PubMed

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A; Veazey, Ronald S

2007-02-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.

Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

PubMed Central

Wang, Xiaolei; Rasmussen, Terri; Pahar, Bapi; Poonia, Bhawna; Alvarez, Xavier; Lackner, Andrew A.; Veazey, Ronald S.

2007-01-01

Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)–infected adult macaques and human immunodeficiency virus (HIV)–infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that “activated” central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques. PMID:17047153

[Progressive visual agnosia].

PubMed

Sugimoto, Azusa; Futamura, Akinori; Kawamura, Mitsuru

2011-10-01

Progressive visual agnosia was discovered in the 20th century following the discovery of classical non-progressive visual agnosia. In contrast to the classical type, which is caused by cerebral vascular disease or traumatic injury, progressive visual agnosia is a symptom of neurological degeneration. The condition of progressive visual loss, including visual agnosia, and posterior cerebral atrophy was named posterior cortical atrophy (PCA) by Benson et al. (1988). Progressive visual agnosia is also observed in semantic dementia (SD) and other degenerative diseases, but there is a difference in the subtype of visual agnosia associated with these diseases. Lissauer (1890) classified visual agnosia into apperceptive and associative types, and it in most cases, PCA is associated with the apperceptive type. However, SD patients exhibit symptoms of associative visual agnosia before changing to those of semantic memory disorder. Insights into progressive visual agnosia have helped us understand the visual system and discover how we "perceive" the outer world neuronally, with regard to consciousness. Although PCA is a type of atypical dementia, its diagnosis is important to enable patients to live better lives with appropriate functional support.

The effects of sleep restriction and sleep deprivation in producing false memories.

PubMed

Chatburn, Alex; Kohler, Mark J; Payne, Jessica D; Drummond, Sean P A

2017-01-01

False memory has been claimed to be the result of an associative process of generalisation, as well as to be representative of memory errors. These can occur at any stage of memory encoding, consolidation, or retrieval, albeit through varied mechanisms. The aim of this paper is to experimentally determine: (i) if cognitive dysfunction brought about by sleep loss at the time of stimulus encoding can influence false memory production; and (ii) whether this relationship holds across sensory modalities. Subjects undertook both the Deese-Roedigger-McDermott (DRM) false memory task and a visual task designed to produce false memories. Performance was measured while subjects were well-rested (9h Time in Bed or TIB), and then again when subjects were either sleep restricted (4h TIB for 4 nights) or sleep deprived (30h total SD). Results indicate (1) that partial and total sleep loss produced equivalent effects in terms of false and veridical verbal memory, (2) that subjects performed worse after sleep loss (regardless of whether this was partial or total sleep loss) on cued recognition-based false and veridical verbal memory tasks, and that sleep loss interfered with subjects' ability to recall veridical, but not false memories under free recall conditions, and (3) that there were no effects of sleep loss on a visual false memory task. This is argued to represent the dysfunction and slow repair of an online verbal associative process in the brain following inadequate sleep. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioural characterisation of the alpha-mannosidosis guinea pig.

PubMed

Robinson, A J; Crawley, A C; Auclair, D; Weston, P F; Hirte, C; Hemsley, K M; Hopwood, J J

2008-01-25

alpha-Mannosidosis is a lysosomal storage disorder resulting from a functional deficiency of the lysosomal enzyme alpha-mannosidase. This deficiency results in the accumulation of various oligosaccharides in the lysosomes of affected individuals, causing somatic pathology and progressive neurological degeneration that results in cognitive deficits, ataxia, and other neurological symptoms. We have a naturally occurring guinea pig model of this disease which exhibits a deficiency of lysosomal alpha-mannosidase and has a similar clinical presentation to human alpha-mannosidosis. Various tests were developed in the present study to characterise and quantitate the loss of neurological function in alpha-mannosidosis guinea pigs and to follow closely the progression of the disease. General neurological examinations showed progressive differences in alpha-mannosidosis animals from approximately 1 month of age. Significant differences were observed in hind limb gait width from 2 months of age and significant cognitive (memory and learning) deficits were observed from 3 months of age. Evoked response tests showed an increase in somatosensory P1 peak latency in alpha-mannosidosis guinea pigs from approximately 2 months of age, as well as progressive hearing loss using auditory brainstem evoked responses. The alpha-mannosidosis guinea pig therefore appears to exhibit many of the characteristics of the human disease, and will be useful in evaluating therapies for treatment of central nervous system pathology.

Differential alteration of hippocampal function and plasticity in females and males of the APPxPS1 mouse model of Alzheimer's disease.

PubMed

Richetin, Kevin; Petsophonsakul, Petnoi; Roybon, Laurent; Guiard, Bruno P; Rampon, Claire

2017-09-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and impaired cognitive functions. The higher incidence of AD among women indicates that sex is one of the main risk factor for developing the disease. Using the transgenic amyloid precursor protein × presenilin 1 (APPxPS1) mouse model of AD, we investigated sex inequality with regards to memory capacities and hippocampal plasticity. We report that spatial memory is strongly affected in APPxPS1 females while remarkably spared in males, at all ages tested. Given the contribution of adult neurogenesis to hippocampal-dependent memory processes, we examined whether impaired neurogenesis could account for age-related decline of memory functions in APPxPS1 mice. We show that not only limited numbers of new neurons are generated in these mice, but also, that new granule cells display reduced capacity for synaptic connectivity, a default that is exacerbated in females. Moreover, high densities of hypertrophic astrocytes are observed in the dentate gyrus of APPxPS1 females specifically. By revealing sex-dependent hippocampal alterations, our data may provide causal explanation to APPxPS1 females' memory deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Modeling Alzheimer's disease cognitive scores using multi-task sparse group lasso.

PubMed

Liu, Xiaoli; Goncalves, André R; Cao, Peng; Zhao, Dazhe; Banerjee, Arindam

2018-06-01

Alzheimer's disease (AD) is a severe neurodegenerative disorder characterized by loss of memory and reduction in cognitive functions due to progressive degeneration of neurons and their connections, eventually leading to death. In this paper, we consider the problem of simultaneously predicting several different cognitive scores associated with categorizing subjects as normal, mild cognitive impairment (MCI), or Alzheimer's disease (AD) in a multi-task learning framework using features extracted from brain images obtained from ADNI (Alzheimer's Disease Neuroimaging Initiative). To solve the problem, we present a multi-task sparse group lasso (MT-SGL) framework, which estimates sparse features coupled across tasks, and can work with loss functions associated with any Generalized Linear Models. Through comparisons with a variety of baseline models using multiple evaluation metrics, we illustrate the promising predictive performance of MT-SGL on ADNI along with its ability to identify brain regions more likely to help the characterization Alzheimer's disease progression. Copyright © 2017 Elsevier Ltd. All rights reserved.

The relationship among unawareness of memory impairment, depression, and dementia in older adults with memory impairment in Singapore.

PubMed

Liu, Jianlin; Abdin, Edimansyah; Vaingankar, Janhavi A; Shafie, Saleha B; Jeyagurunathan, Anitha; Shahwan, Shazana; Magadi, Harish; Ng, Li Ling; Chong, Siow Ann; Subramaniam, Mythily

2017-11-01

Previous research has studied the relationships among unawareness of memory impairment, depression, and dementia in older adults with severe dementia, but it has not considered the associations and clinical implications at earlier stages of memory impairment. This study therefore sought to examine the relationship among unawareness of memory impairment, depression, and dementia in older adults with memory impairment in Singapore. The participants were 751 older adults with memory impairment in Singapore. They were assessed for objective and subjective memory loss, depression, and dementia severity. Participants' subjective memory loss was determined based on a self-appraisal question on memory, and their objective memory loss was calculated based on their performance on three cognitive tasks. Unawareness was assessed based on the contrast between subjective and objective memory loss. Descriptive statistics revealed a high prevalence of unawareness (80.4%). Logistic regression analysis revealed that gender and marital status were significantly associated with unawareness. Men (odds ratio (OR) = 2.5) and those who were divorced or separated (OR = 23.0) were more likely to be unaware than women and those who were married, respectively. After chronic conditions and demographic characteristics were controlled for, multivariate logistic regression analyses revealed that older adults with depression were less likely (OR = 0.2) to be unaware than those without depression. Unawareness was also related with dementia severity; older adults with questionable (OR = 0.3) and mild dementia (OR = 0.4) were less likely to be unaware than someone without dementia. Unawareness of memory impairment was common among older adults with memory impairment. However, unawareness may be the result of denial as a strategy for coping with memory loss of which the older adult is aware. Psychological care should be integrated into the overall treatment management of dementia to mitigate the possible risk of depression while increasing individual awareness of memory loss. © 2017 Japanese Psychogeriatric Society.

Memory Loss, Alzheimer's Disease and General Anesthesia: A Preoperative Concern.

PubMed

Thaler, Adam; Siry, Read; Cai, Lufan; García, Paul S; Chen, Linda; Liu, Renyu

2012-02-20

The long-term cognitive effects of general anesthesia are under intense scrutiny. Here we present 5 cases from 2 academic institutions to analyze some common features where the patient's or the patient family member has made a request to address their concern on memory loss, Alzheimer's disease and general anesthesia before surgery. Records of anesthesia consultation separate from standard preoperative evaluation were retrieved to identify consultations related to memory loss and Alzheimer's disease from the patient and/or patient family members. The identified cases were extensively reviewed for features in common. We used Google® (http://www. google.com/) to identify available online information using "anesthesia memory loss" as a search phrase. Five cases were collected as a specific preoperative consultation related to memory loss, Alzheimer's disease and general anesthesia from two institutions. All of the individuals either had perceived memory impairment after a prior surgical procedure with general anesthesia or had a family member with Alzheimer's disease. They all accessed public media sources to find articles related to anesthesia and memory loss. On May 2 nd , 2011, searching "anesthesia memory loss" in Google yielded 764,000 hits. Only 3 of the 50 Google top hits were from peer-reviewed journals. Some of the lay media postings made a causal association between general anesthesia and memory loss and/or Alzheimer's disease without conclusive scientific literature support. The potential link between memory loss and Alzheimer's disease with general anesthesia is an important preoperative concern from patients and their family members. This concern arises from individuals who have had history of cognitive impairment or have had a family member with Alzheimer disease and have tried to obtain information from public media. Proper preoperative consultation with the awareness of the lay literature can be useful in reducing patient and patient family member's preoperative anxiety related to this concern.

General intelligence predicts memory change across sleep.

PubMed

Fenn, Kimberly M; Hambrick, David Z

2015-06-01

Psychometric intelligence (g) is often conceptualized as the capability for online information processing but it is also possible that intelligence may be related to offline processing of information. Here, we investigated the relationship between psychometric g and sleep-dependent memory consolidation. Participants studied paired-associates and were tested after a 12-hour retention interval that consisted entirely of wake or included a regular sleep phase. We calculated the number of word-pairs that were gained and lost across the retention interval. In a separate session, participants completed a battery of cognitive ability tests to assess g. In the wake group, g was not correlated with either memory gain or memory loss. In the sleep group, we found that g correlated positively with memory gain and negatively with memory loss. Participants with a higher level of general intelligence showed more memory gain and less memory loss across sleep. Importantly, the correlation between g and memory loss was significantly stronger in the sleep condition than in the wake condition, suggesting that the relationship between g and memory loss across time is specific to time intervals that include sleep. The present research suggests that g not only reflects the capability for online cognitive processing, but also reflects capability for offline processes that operate during sleep.

Aβ25-35 injection into the temporal cortex induces chronic inflammation that contributes to neurodegeneration and spatial memory impairment in rats.

PubMed

Diaz, Alfonso; Limon, Daniel; Chávez, Raúl; Zenteno, Edgar; Guevara, Jorge

2012-01-01

Amyloid-β (Aβ)25-35 is able to cause memory impairment and neurodegenerative events. Recent evidence has shown that the injection of Aβ25-35 into the temporal cortex (TCx) of rats increases the inflammatory response; however, it is unclear how the inflammatory process could be involved in the progression of Aβ25-35 toxicity. In this study we investigated the role of inflammation in the neuronal damage and spatial memory impairment generated by Aβ25-35 in rat TCx using immunohistochemistry, ELISA, and a behavioral test in the radial maze. Our findings show that Aβ25-35 -injection into the TCx induced a reactive gliosis (GFAP and CD11b-reactivity) and an increase of pro-inflammatory cytokines (IL-1β, IL-6, IL-17, and TNF-α) in the TCx and the hippocampus at 5, 15, and 30 days after injection. Thirty days after Aβ25-35 injection, we observed that the inflammatory reaction probably contributed to increase the immunoreactivity of inducible nitric oxide synthase and nitrite levels, as well as to the loss of neurons in TCx and hippocampus. Behavioral performance showed that the neurodegeneration evoked by Aβ25-35 delayed acquisition of learning and impaired spatial memory, because the Aβ25-35-treated animals showed a greater number of errors during the task than the control group. Previous administration of an interleukin receptor antagonist (IL-1ra) (10 and 20 μg/μL, into TCx), an anti-inflammatory agent, suppressed the Aβ25-35-induced inflammatory response and neurodegeneration, as well as memory dysfunction. This study suggests that the chronic inflammatory reaction could contribute to the progression of Aβ25-35 toxicity and cause cognitive impairment.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology.

PubMed

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-08-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer's disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD.

BACE1 inhibition by microdose lithium formulation NP03 rescues memory loss and early stage amyloid neuropathology

PubMed Central

Wilson, E N; Do Carmo, S; Iulita, M F; Hall, H; Ducatenzeiler, A; Marks, A R; Allard, S; Jia, D T; Windheim, J; Cuello, A C

2017-01-01

Lithium is first-line therapy for bipolar affective disorder and has recently been shown to have protective effects in populations at risk for Alzheimer’s disease (AD). However, the mechanism underlying this protection is poorly understood and consequently limits its possible therapeutic application in AD. Moreover, conventional lithium formulations have a narrow therapeutic window and are associated with a severe side effect profile. Here we evaluated a novel microdose formulation of lithium, coded NP03, in a well-characterized rat model of progressive AD-like amyloid pathology. This formulation allows microdose lithium delivery to the brain in the absence of negative side effects. We found that NP03 rescued key initiating components of AD pathology, including inactivating GSK-3β, reducing BACE1 expression and activity, and reducing amyloid levels. Notably, NP03 rescued memory loss, impaired CRTC1 promoter binding of synaptic plasticity genes and hippocampal neurogenesis. These results raise the possibility that NP03 be of therapeutic value in the early or preclinical stages of AD. PMID:28763060

Effects of Aged Garlic Extract on Cholinergic, Glutamatergic and GABAergic Systems with Regard to Cognitive Impairment in Aβ-Induced Rats

PubMed Central

Thorajak, Piyaporn; Pannangrong, Wanassanun; Umka Welbat, Jariya; Chaijaroonkhanarak, Wunnee; Sripanidkulchai, Kittisak; Sripanidkulchai, Bungorn

2017-01-01

Alzheimer’s disease (AD) has been linked to the degeneration of central cholinergic and glutamatergic transmission, which correlates with progressive memory loss and the accumulation of amyloid-β (Aβ). It has been claimed that aged garlic extract (AGE) has a beneficial effect in preventing neurodegeneration in AD. Therefore, the objective of this study was to investigate the effects of AGE on Aβ-induced cognitive dysfunction with a biochemical basis in the cholinergic, glutamatergic, and GABAergic systems in rats. Adult male Wistar rats were orally administered three doses of AGE (125, 250, and 500 mg/kg) daily for 65 days. At day 56, they were injected with 1 μL of aggregated Aβ (1–42) into each lateral ventricle, bilaterally. After six days of Aβ injection, the rats’ working and reference memory was tested using a radial arm maze. The rats were then euthanized to investigate any changes to the cholinergic neurons, vesicular glutamate transporter 1 and 2 proteins (VGLUT1 and VGLUT2), and glutamate decarboxylase (GAD) in the hippocampus. The results showed that AGE significantly improved the working memory and tended to improve the reference memory in cognitively-impaired rats. In addition, AGE significantly ameliorated the loss of cholinergic neurons and increased the VGLUT1 and GAD levels in the hippocampus of rat brains with Aβ-induced toxicity. In contrast, the VGLUT2 protein levels did not change in any of the treated groups. We concluded that AGE was able to attenuate the impairment of working memory via the modification of cholinergic neurons, VGLUT1, and GAD in the hippocampus of Aβ-induced rats. PMID:28671572

Insulin protects against Aβ-induced spatial memory impairment, hippocampal apoptosis and MAPKs signaling disruption.

PubMed

Ghasemi, Rasoul; Zarifkar, Asadollah; Rastegar, Karim; maghsoudi, Nader; Moosavi, Maryam

2014-10-01

Alzheimer disease (AD) is a progressive neurodegenerative disease characterized by extracellular deposits of beta amyloid (Aβ) and neuronal loss particularly in the hippocampus. Accumulating evidences have implied that insulin signaling impairment plays a key role in the pathology of AD; as much as it is considered as type 3 Diabetes. MAPKs are a group of signaling molecules which are involved in pathobiology of AD. Therefore this study was designed to investigate if intrahippocampal insulin hinders Aβ-related memory deterioration, hippocampal apoptosis and MAPKs signaling alteration induced by Aβ. Adult male Sprague-Dawely rats weighing 250-300 g were used in this study. The canules were implanted bilaterally into CA1 region. Aβ25-35 was administered during first 4 days after surgery (5 μg/2.5 μL/daily). Insulin treatment (0.5 or 6 mU) was done during days 4-9. The animal's learning and memory capability was assessed on days 10-13 using Morris water maze. After finishing of behavioral studies the hippocampi was isolated and the amount of hippocampal cleaved caspase 3 (the landmark of apoptosis) and the phosphorylated (activated) forms of P38, JNK and ERK was analyzed by western blot. The results showed that insulin in 6 but not 0.5 mU reversed the memory loss induced by Aβ25-35. Western blot analysis revealed that Aβ25-35 induced elevation of caspase-3 and all 3 MAPks subfamily activity, while insulin in 6 mu restored ERK and P38 activation but has no effect on JNK. This study disclosed that intrahippocampal insulin treatment averts not only Aβ-induced memory deterioration but also hippocampal caspase-3, ERK and P38 activation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Elevated Risk of Type 2 Diabetes for Development of Alzheimer Disease: a Key Role for Oxidative Stress in Brain

PubMed Central

Butterfield, D. Allan; Di Domenico, Fabio; Barone, Eugenio

2014-01-01

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggest that oxidative stress play a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data and interpreted from the point of view of oxidative stress with the aim to highlight progresses in this field. PMID:24949886

Diabetes: Unique to Older Adults

MedlinePlus

... quickly. The earlier depression is treated, the better. Memory Loss Problems with memory and brain function can be more common in ... provider may do some tests to check for memory loss. Be sure to let your provider know ...

A single night of sleep loss impairs objective but not subjective working memory performance in a sex-dependent manner.

PubMed

Rångtell, Frida H; Karamchedu, Swathy; Andersson, Peter; Liethof, Lisanne; Olaya Búcaro, Marcela; Lampola, Lauri; Schiöth, Helgi B; Cedernaes, Jonathan; Benedict, Christian

2018-01-31

Acute sleep deprivation can lead to judgement errors and thereby increases the risk of accidents, possibly due to an impaired working memory. However, whether the adverse effects of acute sleep loss on working memory are modulated by auditory distraction in women and men are not known. Additionally, it is unknown whether sleep loss alters the way in which men and women perceive their working memory performance. Thus, 24 young adults (12 women using oral contraceptives at the time of investigation) participated in two experimental conditions: nocturnal sleep (scheduled between 22:30 and 06:30 hours) versus one night of total sleep loss. Participants were administered a digital working memory test in which eight-digit sequences were learned and retrieved in the morning after each condition. Learning of digital sequences was accompanied by either silence or auditory distraction (equal distribution among trials). After sequence retrieval, each trial ended with a question regarding how certain participants were of the correctness of their response, as a self-estimate of working memory performance. We found that sleep loss impaired objective but not self-estimated working memory performance in women. In contrast, both measures remained unaffected by sleep loss in men. Auditory distraction impaired working memory performance, without modulation by sleep loss or sex. Being unaware of cognitive limitations when sleep-deprived, as seen in our study, could lead to undesirable consequences in, for example, an occupational context. Our findings suggest that sleep-deprived young women are at particular risk for overestimating their working memory performance. © 2018 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.

A direct comparison of popular models of normal memory loss and Alzheimer's disease in samples of African Americans, Mexican Americans, and refugees and immigrants from the former Soviet Union.

PubMed

Schrauf, Robert W; Iris, Madelyn

2011-04-01

To understand how people differentiate normal memory loss from Alzheimer's disease (AD) by investigating cultural models of these conditions. Ethnographic interviews followed by a survey. Cultural consensus analysis was used to test for the presence of group models, derive the "culturally correct" set of beliefs, and compare models of normal memory loss and AD. Chicago, Illinois. One hundred eight individuals from local neighborhoods: African Americans, Mexican Americans, and refugees and immigrants from the former Soviet Union. Participants responded to yes-or-no questions about the nature and causes of normal memory loss and AD and provided information on ethnicity, age, sex, acculturation, and experience with AD. Groups held a common model of AD as a brain-based disease reflecting irreversible cognitive decline. Higher levels of acculturation predicted greater knowledge of AD. Russian speakers favored biological over psychological models of the disease. Groups also held a common model of normal memory loss, including the important belief that "normal" forgetting involves eventual recall of the forgotten material. Popular models of memory loss and AD confirm that patients and clinicians are speaking the same "language" in their discussions of memory loss and AD. Nevertheless, the presence of coherent models of memory loss and AD, and the unequal distribution of that knowledge across groups, suggests that clinicians should include wider circles of patients' families and friends in their consultations. These results frame knowledge as distributed across social groups rather than simply the possession of individual minds. © 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.

Effects of a multimedia project on users' knowledge about normal forgetting and serious memory loss.

PubMed

Mahoney, Diane Feeney; Tarlow, Barbara J; Jones, Richard N; Sandaire, Johnny

2002-01-01

The aim of the project was to develop and evaluate the effectiveness of a CD-ROM-based multimedia program as a tool to increase user's knowledge about the differences between "normal" forgetfulness and more serious memory loss associated with Alzheimer's disease. The research was a controlled randomized study conducted with 113 adults who were recruited from the community and who expressed a concern about memory loss in a family member. The intervention group (n=56) viewed a module entitled "Forgetfulness: What's Normal and What's Not" on a laptop computer in their homes; the control group (n=57) did not. Both groups completed a 25-item knowledge-about-memory-loss test (primary outcome) and a sociodemographic and technology usage questionnaire; the intervention group also completed a CD-ROM user's evaluation. The mean (SD) number of correct responses to the knowledge test was 14.2 (4.5) for controls and 19.7 (3.1) for intervention participants. This highly significant difference (p<0.001) corresponds to a very large effect size. The program was most effective for participants with a lower level of self-reported prior knowledge about memory loss and Alzheimer's disease (p=0.02). Viewers were very satisfied with the program and felt that it was easy to use and understand. They particularly valued having personal access to a confidential source that permitted them to become informed about memory loss without public disclosure. This multimedia CD-ROM technology program provides an efficient and effective means of teaching older adults about memory loss and ways to distinguish benign from serious memory loss. It uniquely balances public community outreach education and personal privacy.

Drosophila PINK1 and parkin loss-of-function mutants display a range of non-motor Parkinson's disease phenotypes.

PubMed

Julienne, Hannah; Buhl, Edgar; Leslie, David S; Hodge, James J L

2017-08-01

Parkinson's disease (PD) is more commonly associated with its motor symptoms and the related degeneration of dopamine (DA) neurons. However, it is becoming increasingly clear that PD patients also display a wide range of non-motor symptoms, including memory deficits and disruptions of their sleep-wake cycles. These have a large impact on their quality of life, and often precede the onset of motor symptoms, but their etiology is poorly understood. The fruit fly Drosophila has already been successfully used to model PD, and has been used extensively to study relevant non-motor behaviours in other contexts, but little attention has yet been paid to modelling non-motor symptoms of PD in this genetically tractable organism. We examined memory performance and circadian rhythms in flies with loss-of-function mutations in two PD genes: PINK1 and parkin. We found learning and memory abnormalities in both mutant genotypes, as well as a weakening of circadian rhythms that is underpinned by electrophysiological changes in clock neurons. Our study paves the way for further work that may help us understand the mechanisms underlying these neglected aspects of PD, thus identifying new targets for treatments to address these non-motor problems specifically and perhaps even to halt disease progression in its prodromal phase. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Content Analysis of Memory and Memory-Related Research Studies on Children with Hearing Loss

ERIC Educational Resources Information Center

Dogan, Murat; Hasanoglu, Gülcihan

2016-01-01

Memory plays a profound role in explaining language development, academic learning, and learning disabilities. Even though there is a large body of research on language development, literacy skills, other academic skills, and intellectual characteristics of children with hearing loss, there is no holistic study on their memory processes.…

Hearing loss is negatively related to episodic and semantic long-term memory but not to short-term memory.

PubMed

Rönnberg, Jerker; Danielsson, Henrik; Rudner, Mary; Arlinger, Stig; Sternäng, Ola; Wahlin, Ake; Nilsson, Lars-Göran

2011-04-01

To test the relationship between degree of hearing loss and different memory systems in hearing aid users. Structural equation modeling (SEM) was used to study the relationship between auditory and visual acuity and different cognitive and memory functions in an age-hetereogenous subsample of 160 hearing aid users without dementia, drawn from the Swedish prospective cohort aging study known as Betula (L.-G. Nilsson et al., 1997). Hearing loss was selectively and negatively related to episodic and semantic long-term memory (LTM) but not short-term memory (STM) performance. This held true for both ears, even when age was accounted for. Visual acuity alone, or in combination with auditory acuity, did not contribute to any acceptable SEM solution. The overall relationships between hearing loss and memory systems were predicted by the ease of language understanding model (J. Rönnberg, 2003), but the exact mechanisms of episodic memory decline in hearing aid users (i.e., mismatch/disuse, attentional resources, or information degradation) remain open for further experiments. The hearing aid industry should strive to design signal processing algorithms that are cognition friendly.

Tartary buckwheat improves cognition and memory function in an in vivo amyloid-β-induced Alzheimer model.

PubMed

Choi, Ji Yeon; Cho, Eun Ju; Lee, Hae Song; Lee, Jeong Min; Yoon, Young-Ho; Lee, Sanghyun

2013-03-01

Protective effects of Tartary buckwheat (TB) and common buckwheat (CB) on amyloid beta (Aβ)-induced impairment of cognition and memory function were investigated in vivo in order to identify potential therapeutic agents against Alzheimer's disease (AD) and its associated progressive memory deficits, cognitive impairment, and personality changes. An in vivo mouse model of AD was created by injecting the brains of ICR mice with Aβ(25-35), a fragment of the full-length Aβ protein. Damage of mice recognition ability through following Aβ(25-35) brain injections was confirmed using the T-maze test, the object recognition test, and the Morris water maze test. Results of behavior tests in AD model showed that oral administration of the methanol (MeOH) extracts of TB and CB improved cognition and memory function following Aβ(25-35) injections. Furthermore, in groups receiving the MeOH extracts of TB and CB, lipid peroxidation was significantly inhibited, and nitric oxide levels in tissue, which are elevated by injection of Aβ(25-35), were also decrease. In particular, the MeOH extract of TB exerted a stronger protective activity than CB against Aβ(25-35)-induced memory and cognition impairment. The results indicate that TB may play a promising role in preventing or reversing memory and cognition loss associated with Aβ(25-35)-induced AD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Short-term memory loss over time without retroactive stimulus interference.

PubMed

Cowan, Nelson; AuBuchon, Angela M

2008-02-01

A key question in cognitive psychology is whether information in short-term memory is lost as a function of time. Lewandowsky, Duncan, and Brown (2004) argued against that memory loss because forgetting in serial recall occurred to the same extent across serial positions regardless of the rate of recall. However, we believe Lewandowsky et al. (2004) only prevented one of two types of rehearsal; they did not prevent nonarticulatory rehearsal via attention. To prevent articulatory and nonarticulatory rehearsal without introducing interference, we presented unevenly timed stimuli for serial recall and, on some trials, required that the timing of stimuli be reproduced in the response. In those trials only, evidence of memory loss over time emerged. Further research is needed to identify whether this memory loss is decay or lost distinctiveness.

Memory Loss, Alzheimer’s Disease and General Anesthesia: A Preoperative Concern

PubMed Central

Thaler, Adam; Siry, Read; Cai, Lufan; García, Paul S.; Chen, Linda; Liu, RenYu

2012-01-01

Background The long-term cognitive effects of general anesthesia are under intense scrutiny. Here we present 5 cases from 2 academic institutions to analyze some common features where the patient’s or the patient family member has made a request to address their concern on memory loss, Alzheimer’s disease and general anesthesia before surgery. Methods Records of anesthesia consultation separate from standard preoperative evaluation were retrieved to identify consultations related to memory loss and Alzheimer’s disease from the patient and/or patient family members. The identified cases were extensively reviewed for features in common. We used Google® (http://www. google.com/) to identify available online information using “anesthesia memory loss” as a search phrase. Results Five cases were collected as a specific preoperative consultation related to memory loss, Alzheimer’s disease and general anesthesia from two institutions. All of the individuals either had perceived memory impairment after a prior surgical procedure with general anesthesia or had a family member with Alzheimer’s disease. They all accessed public media sources to find articles related to anesthesia and memory loss. On May 2nd, 2011, searching “anesthesia memory loss” in Google yielded 764,000 hits. Only 3 of the 50 Google top hits were from peer-reviewed journals. Some of the lay media postings made a causal association between general anesthesia and memory loss and/or Alzheimer’s disease without conclusive scientific literature support. Conclusion The potential link between memory loss and Alzheimer’s disease with general anesthesia is an important preoperative concern from patients and their family members. This concern arises from individuals who have had history of cognitive impairment or have had a family member with Alzheimer disease and have tried to obtain information from public media. Proper preoperative consultation with the awareness of the lay literature can be useful in reducing patient and patient family member’s preoperative anxiety related to this concern. PMID:23853740

Characteristics and Correlates of Caregivers' Perceptions of Their Family Members' Memory Loss.

PubMed

Yu, Hairong; Lingler, Jennifer H; Sereika, Susan M; Erlen, Judith A

Understanding caregiver's perceptions of their family member's memory loss is a necessary step in planning nursing interventions to detect and address caregiver burden. The purpose of this study was to characterize caregivers' perceptions of their family members' memory loss and identify potential correlates within Leventhal's common sense model (CSM). This secondary analysis used baseline data from a larger randomized controlled trial. Patients with memory loss and their caregivers (N = 83 dyads) from the community were included. The adapted Brief Illness Perception Questionnaire (BIPQ) assessed caregivers' illness perceptions. Eight additional instruments measured correlates within the CSM. Responses were described; multiple linear regression was used to predict BIPQ dimension scores, and logistic regression was used to predict dichotomized BIPQ scores. Most caregivers were female, White, and spouses of the patients; they reported a range of perceptions on the nine BIPQ dimensions. Patients' cognitive function consistently emerged as a significant correlate of caregivers' illness perceptions, explaining the most variance in caregivers' perceived consequences, identity, and treatment control (p < .01). Caregivers' reactions to patients' behavioral symptoms and caregivers' trait anxiety were associated with perceived illness coherence (p < .01). Caregivers with higher severity of daily hassles and White caregivers perceived that their family members' memory loss would last longer (p < .001). Caregivers' perceptions of family members' memory loss varied; distinct dimensions of caregivers' illness perception were associated with a range of clinical and psychosocial factors. This exploratory study demonstrates the complexity of applying the CSM to caregivers of persons with memory loss.

A case of persistent retrograde amnesia following a dissociative fugue: neuropsychological and neurofunctional underpinnings of loss of autobiographical memory and self-awareness.

PubMed

Hennig-Fast, Kristina; Meister, Franziska; Frodl, Thomas; Beraldi, Anna; Padberg, Frank; Engel, Rolf R; Reiser, Maximilian; Möller, Hans-Jürgen; Meindl, Thomas

2008-10-01

Autobiographical memory relies on complex interactions between episodic memory contents, associated emotions and a sense of self-continuity over the course of one's life. This paper reports a study based upon the case of the patient NN who suffered from a complete loss of autobiographical memory and awareness of identity subsequent to a dissociative fugue. Neuropsychological, behavioral, and functional neuroimaging tests converged on the conclusion that NN suffered from a selective retrograde amnesia following an episode of dissociative fugue, during which he had lost explicit knowledge and vivid memory of his personal past. NN's loss of self-related memories was mirrored in neurobiological changes after the fugue whereas his semantic memory remained intact. Although NN still claimed to suffer from a stable loss of autobiographical, self-relevant memories 1 year after the fugue state, a proportionate improvement in underlying fronto-temporal neuronal networks was evident at this point in time. In spite of this improvement in neuronal activation, his anterograde visual memory had been decreased. It is posited that our data provide evidence for the important role of visual processing in autobiographical memory as well as for the efficiency of protective control mechanisms that constitute functional retrograde amnesia.

Memory loss in Alzheimer's disease

PubMed Central

Jahn, Holger

2013-01-01

Loss of memory is among the first symptoms reported by patients suffering from Alzheimer's disease (AD) and by their caretakers. Working memory and long-term declarative memory are affected early during the course of the disease. The individual pattern of impaired memory functions correlates with parameters of structural or functional brain integrity. AD pathology interferes with the formation of memories from the molecular level to the framework of neural networks. The investigation of AD memory loss helps to identify the involved neural structures, such as the default mode network, the influence of epigenetic and genetic factors, such as ApoE4 status, and evolutionary aspects of human cognition. Clinically, the analysis of memory assists the definition of AD subtypes, disease grading, and prognostic predictions. Despite new AD criteria that allow the earlier diagnosis of the disease by inclusion of biomarkers derived from cerebrospinal fluid or hippocampal volume analysis, neuropsychological testing remains at the core of AD diagnosis. PMID:24459411

Cognitive impairment and memory loss associated with histoplasmosis: a case study.

PubMed

Loughan, Ashlee R; Perna, Robert; Hertza, Jeremy

2014-01-01

Histoplasmosis is a rare disease caused by inhalation of the fungus Histoplasma capsulatum. It can spread via cerebral circulation to the central nervous system as a manifestation of a disseminated infection; particularly in patients with immune suppression, which can result in isolated ring-enhancing lesions and inflammation in the brain. Of the reported disseminated histoplasmosis cases (approximately 1 in 2000 per year), only 5-20% have evidence of central nervous system involvement. This paper reviews a single case study of a 57-year-old female diagnosed with disseminated CNS histoplasmosis. Patient's complaints included reduced short-term memory, word-finding problems, and difficulty organizing, making decisions, getting lost while driving, recalling names, retaining information while reading, and slowed processing speed. There was also a history of mild depression and anxiety. Direct testing revealed deficits in multiple cognitive domains including complex attention, processing speed, semantic fluency, visual scanning, motor speed, set-shifting, naming, nonverbal memory, and verbal memory. Neuropsychological deficits suggest cortical and subcortical brain dysfunction, including anterior, temporal, and mesial-temporal regions. This case illustrates the need for neuropsychologists to understand histoplasmosis, the related pathophysiology, and the neuropsychological impact; particularly with the potential for delayed progression.

Severe amnesia following a unilateral temporal lobe stroke.

PubMed

Grewal, Raji P

2003-01-01

A 60 year old right-handed man developed severe amnesia following a left medial temporal stroke as documented by cerebral MRI, MRA and SPECT scans. Neuropsychological evaluation 13 weeks after the stroke showed a profound retrograde amnesia characterised by memory loss for public facts and events over the previous four decades. In addition, autobiographical memory showed selective loss of personal episodic memory with relative preservation of personal semantic memory. The development of this degree of amnesia with these features following a unilateral temporal lobe lesion is unusual. The possible neuroanatomical mechanisms underlying the amnesia and how they relate to current theories of memory loss are discussed.

Everyday Cognition in Prodromal Huntington Disease

PubMed Central

Williams, Janet K.; Kim, Ji-In; Downing, Nancy; Farias, Sarah; Harrington, Deborah L.; Long, Jeffrey D.; Mills, James A.; Paulsen, Jane S.

2014-01-01

Objective Assessment of daily functions affected by cognitive loss in prodromal Huntington disease (HD) is necessary in practice and clinical trials. We evaluated baseline and longitudinal sensitivity of the Everyday Cognition (ECog) scales in prodromal HD and compared self- and companion-ratings. Method Everyday cognition was self-assessed by 850 participants with prodromal HD and 768 companions. We examined internal structure using confirmatory factor analysis (CFA) on baseline data. For longitudinal analysis, we stratified participants into Low, Medium, and High disease progression groups. We examined ECog scores for group differences and participant-and-companion differences using linear mixed effects regression (LMER). Comparison with the Total Functional Capacity (TFC) scale was made. Results CFA revealed good fit of a 5-factor model having a global factor (total score), and sub factors (subscales) of memory, language, visuospatial perception, and executive function. At study entry, participants and companions in the Medium and High groups reported significantly worsened everyday cognition as well as significant functional decline over time. Losses became more pronounced and participant and companion ratings diverged as individuals progressed. TFC showed significant functional loss over time in the High group but not in the Medium group. Conclusions Disease progression is associated with reduced self- and companion-reported everyday cognition in prodromal HD participants who are less than 13 years to estimated motor onset. Our findings suggest companion ratings are more sensitive than participants’ for detecting longitudinal change in daily cognitive function. ECog appears more sensitive to specific functional changes in the prodrome of HD than the TFC. PMID:25000321

The role of source memory in gambling task decision making.

PubMed

Whitney, Paul; Hinson, John M

2012-01-01

The role of memory in the Iowa Gambling Task (IGT) was tested in two experiments that dissociated item memory (memory for losses obtained) from source memory (the deck that produced a given loss). In Experiment 1, participants observed 75 choices that had been made by controls or patients in previous research, followed by memory tests, and then 25 active choices from the participant. In Experiment 2, participants made choices for 75 trials, performed the memory tests, and then made 25 final choices. The data show that item and source memory can diverge within the IGT, and that source memory makes a significant contribution to IGT performance.

The Progressive BSSG Rat Model of Parkinson's: Recapitulating Multiple Key Features of the Human Disease

PubMed Central

Van Kampen, Jackalina M.; Baranowski, David C.; Robertson, Harold A.; Shaw, Christopher A.; Kay, Denis G.

2015-01-01

The development of effective neuroprotective therapies for Parkinson's disease (PD) has been severely hindered by the notable lack of an appropriate animal model for preclinical screening. Indeed, most models currently available are either acute in nature or fail to recapitulate all characteristic features of the disease. Here, we present a novel progressive model of PD, with behavioural and cellular features that closely approximate those observed in patients. Chronic exposure to dietary phytosterol glucosides has been found to be neurotoxic. When fed to rats, β-sitosterol β-d-glucoside (BSSG) triggers the progressive development of parkinsonism, with clinical signs and histopathology beginning to appear following cessation of exposure to the neurotoxic insult and continuing to develop over several months. Here, we characterize the progressive nature of this model, its non-motor features, the anatomical spread of synucleinopathy, and response to levodopa administration. In Sprague Dawley rats, chronic BSSG feeding for 4 months triggered the progressive development of a parkinsonian phenotype and pathological events that evolved slowly over time, with neuronal loss beginning only after toxin exposure was terminated. At approximately 3 months following initiation of BSSG exposure, animals displayed the early emergence of an olfactory deficit, in the absence of significant dopaminergic nigral cell loss or locomotor deficits. Locomotor deficits developed gradually over time, initially appearing as locomotor asymmetry and developing into akinesia/bradykinesia, which was reversed by levodopa treatment. Late-stage cognitive impairment was observed in the form of spatial working memory deficits, as assessed by the radial arm maze. In addition to the progressive loss of TH+ cells in the substantia nigra, the appearance of proteinase K-resistant intracellular α-synuclein aggregates was also observed to develop progressively, appearing first in the olfactory bulb, then the striatum, the substantia nigra and, finally, hippocampal and cortical regions. The slowly progressive nature of this model, together with its construct, face and predictive validity, make it ideal for the screening of potential neuroprotective therapies for the treatment of PD. PMID:26439489

Promoting Sleep Oscillations and Their Functional Coupling by Transcranial Stimulation Enhances Memory Consolidation in Mild Cognitive Impairment.

PubMed

Ladenbauer, Julia; Ladenbauer, Josef; Külzow, Nadine; de Boor, Rebecca; Avramova, Elena; Grittner, Ulrike; Flöel, Agnes

2017-07-26

Alzheimer's disease (AD) not only involves loss of memory functions, but also prominent deterioration of sleep physiology, which is already evident at the stage of mild cognitive impairment (MCI). Cortical slow oscillations (SO; 0.5-1 Hz) and thalamocortical spindle activity (12-15 Hz) during sleep, and their temporal coordination, are considered critical for memory formation. We investigated the potential of slow oscillatory transcranial direct current stimulation (so-tDCS), applied during a daytime nap in a sleep-state-dependent manner, to modulate these activity patterns and sleep-related memory consolidation in nine male and seven female human patients with MCI. Stimulation significantly increased overall SO and spindle power, amplified spindle power during SO up-phases, and led to stronger synchronization between SO and spindle power fluctuations in EEG recordings. Moreover, visual declarative memory was improved by so-tDCS compared with sham stimulation and was associated with stronger synchronization. These findings indicate a well-tolerated therapeutic approach for disordered sleep physiology and memory deficits in MCI patients and advance our understanding of offline memory consolidation. SIGNIFICANCE STATEMENT In the light of increasing evidence that sleep disruption is crucially involved in the progression of Alzheimer's disease (AD), sleep appears as a promising treatment target in this pathology, particularly to counteract memory decline. This study demonstrates the potential of a noninvasive brain stimulation method during sleep in patients with mild cognitive impairment (MCI), a precursor of AD, and advances our understanding of its mechanism. We provide first time evidence that slow oscillatory transcranial stimulation amplifies the functional cross-frequency coupling between memory-relevant brain oscillations and improves visual memory consolidation in patients with MCI. Copyright © 2017 the authors 0270-6474/17/377111-14$15.00/0.

Plants and phytochemicals for Huntington's disease.

PubMed

Choudhary, Sunayna; Kumar, Puneet; Malik, Jai

2013-07-01

Huntington's disease (HD) is a neurodegenerative disorder characterized by progressive motor dysfunction, including chorea and dystonia, emotional disturbances, memory, and weight loss. The medium spiny neurons of striatum and cortex are mainly effected in HD. Various hypotheses, including molecular genetics, oxidative stress, excitotoxicity, metabolic dysfunction, and mitochondrial impairment have been proposed to explain the pathogenesis of neuronal dysfunction and cell death. Despite no treatment is available to fully stop the progression of the disease, there are treatments available to help control the chorea. The present review deals with brief pathophysiology of the disease, plants and phytochemicals that have shown beneficial effects against HD like symptoms. The literature for the current review was collected using various databases such as Science direct, Pubmed, Scopus, Sci-finder, Google Scholar, and Cochrane database with a defined search strategy.

Aortic stiffness and hypotension episodes are associated with impaired cognitive function in older subjects with subjective complaints of memory loss.

PubMed

Scuteri, Angelo; Tesauro, Manfredi; Guglini, Letizia; Lauro, Davide; Fini, Massimo; Di Daniele, Nicola

2013-11-20

Though CV risk factors and markers of arterial aging are recognized risky for cognition, no study has simultaneously investigated the impact of multiple cardiac, arterial (large and small vessels), and hemodynamic parameters on cognitive function in older subjects. Two hundred eighty older subjects with subjective complaints of memory loss and no previous stroke (mean age 78.3 ± 6.3 years) were studied. Global cognitive function was evaluated with the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as a MMSE < 21. We measured: traditional CV risk factors; aorta stiffness (Pulse Wave Velocity, PWV); LV mass; presence of WML at neuroimaging; episodes of hypotension (SBP <100 mmHg during 24 h Ambulatory Blood Pressure Monitoring). In both cross-sectional and longitudinal analyses PWV, WML, and episodes of hypotension were significantly associated with poorer cognitive function-controlling for age, sex, education, depression, traditional CV risk factors, and medications. LV mass was no longer associated with cognition in multiple regression. Older subjects with stiffer arteries or episodes of hypotension presented a 4-fold and an 11-fold, respectively, greater odds for progression from normal cognitive function to cognitive impairment. A synergistic effect between PWV, WML, and hypotension was observed: the occurrence of any two of PWV, WML, or hypotension was accompanied by lower MMSE; in the presence of all three factors, a further significant decline in cognitive function was observed. Systemic hemodynamic parameters (higher PWV and hypotension) together with cerebral microvascular damage (WML) are significantly associated with poorer cognitive function and may identify older subjects with subjective complaints of memory loss at higher risk of cognitive decline. © 2013.

Short-term memory loss associated with rosuvastatin.

PubMed

Galatti, Laura; Polimeni, Giovanni; Salvo, Francesco; Romani, Marcello; Sessa, Aurelio; Spina, Edoardo

2006-08-01

Memory loss and cognitive impairment have been reported in the literature in association with several 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), but we found no published case reports associated with rosuvastatin. To our knowledge, this is the first reported case of rosuvastatin-related short-term memory loss. A 53-year-old Caucasian man with hypercholesterolemia experienced memory loss after being treated with rosuvastatin 10 mg/day. He had no other concomitant conditions or drug therapies. After discontinuation of rosuvastatin, the neuropsychiatric adverse reaction resolved gradually, suggesting a probable drug association. During the following year, the patient remained free from neuropsychiatric disturbances. Clinicians should be aware of possible adverse cognitive reactions during statin therapy, including rosuvastatin.

Amyloid-β Peptide Exacerbates the Memory Deficit Caused by Amyloid Precursor Protein Loss-of-Function in Drosophila

PubMed Central

Bourdet, Isabelle; Lampin-Saint-Amaux, Aurélie; Preat, Thomas; Goguel, Valérie

2015-01-01

The amyloid precursor protein (APP) plays a central role in Alzheimer’s disease (AD). APP can undergo two exclusive proteolytic pathways: cleavage by the α-secretase initiates the non-amyloidogenic pathway while cleavage by the β-secretase initiates the amyloidogenic pathway that leads, after a second cleavage by the γ-secretase, to amyloid-β (Aβ) peptides that can form toxic extracellular deposits, a hallmark of AD. The initial events leading to AD are still unknown. Importantly, aside from Aβ toxicity whose molecular mechanisms remain elusive, several studies have shown that APP plays a positive role in memory, raising the possibility that APP loss-of-function may participate to AD. We previously showed that APPL, the Drosophila APP ortholog, is required for associative memory in young flies. In the present report, we provide the first analysis of the amyloidogenic pathway’s influence on memory in the adult. We show that transient overexpression of the β-secretase in the mushroom bodies, the center for olfactory memory, did not alter memory. In sharp contrast, β-secretase overexpression affected memory when associated with APPL partial loss-of-function. Interestingly, similar results were observed with Drosophila Aβ peptide. Because Aβ overexpression impaired memory only when combined to APPL partial loss-of-function, the data suggest that Aβ affects memory through the APPL pathway. Thus, memory is altered by two connected mechanisms—APPL loss-of-function and amyloid peptide toxicity—revealing in Drosophila a functional interaction between APPL and amyloid peptide. PMID:26274614

Sleep stages, memory and learning.

PubMed Central

Dotto, L

1996-01-01

Learning and memory can be impaired by sleep loss during specific vulnerable "windows" for several days after new tasks have been learned. Different types of tasks are differentially vulnerable to the loss of different stages of sleep. Memory required to perform cognitive procedural tasks is affected by the loss of rapid-eye-movement (REM) sleep on the first night after learning occurs and again on the third night after learning. REM-sleep deprivation on the second night after learning does not produce memory deficits. Declarative memory, which is used for the recall of specific facts, is not similarly affected by REM-sleep loss. The learning of procedural motor tasks, including those required in many sports, is impaired by the loss of stage 2 sleep, which occurs primarily in the early hours of the morning. These findings have implications for the academic and athletic performance of students and for anyone whose work involves ongoing learning and demands high standards of performance. Images p1194-a PMID:8612256

Making Art and Making Memories: A Study on the Effects of Art Making as a Possible Intervention to Memory Loss

ERIC Educational Resources Information Center

Carney, Kathleen

2016-01-01

This eight-week action research project examined how art can be a possible intervention to memory loss. Five octogenarians with dementia participated in a qualitative phenomenological case study exploring the connections between memory and making art. Various methods of data collection were employed, including survey, interview, artifacts,…

Hearing Loss Is Negatively Related to Episodic and Semantic Long-Term Memory but Not to Short-Term Memory

ERIC Educational Resources Information Center

Ronnberg, Jerker; Danielsson, Henrik; Rudner, Mary; Arlinger, Stig; Sternang, Ola; Wahlin, Ake; Nilsson, Lars-Goran

2011-01-01

Purpose: To test the relationship between degree of hearing loss and different memory systems in hearing aid users. Method: Structural equation modeling (SEM) was used to study the relationship between auditory and visual acuity and different cognitive and memory functions in an age-hetereogenous subsample of 160 hearing aid users without…

Cholinergic Basal Forebrain Lesion Decreases Neurotrophin Signaling without Affecting Tau Hyperphosphorylation in Genetically Susceptible Mice.

PubMed

Turnbull, Marion T; Coulson, Elizabeth J

2017-01-01

Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Our results reveal that the loss of BFCNs in pre-symptomatic pR5 (P301L) tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals' performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

Elevated risk of type 2 diabetes for development of Alzheimer disease: a key role for oxidative stress in brain.

PubMed

Butterfield, D Allan; Di Domenico, Fabio; Barone, Eugenio

2014-09-01

Alzheimer disease (AD) is the most common form of dementia among the elderly and is characterized by progressive loss of memory and cognition. Epidemiological data show that the incidence of AD increases with age and doubles every 5 years after 65 years of age. From a neuropathological point of view, amyloid-β-peptide (Aβ) leads to senile plaques, which, together with hyperphosphorylated tau-based neurofibrillary tangles and synapse loss, are the principal pathological hallmarks of AD. Aβ is associated with the formation of reactive oxygen (ROS) and nitrogen (RNS) species, and induces calcium-dependent excitotoxicity, impairment of cellular respiration, and alteration of synaptic functions associated with learning and memory. Oxidative stress was found to be associated with type 2 diabetes mellitus (T2DM), which (i) represents another prevalent disease associated with obesity and often aging, and (ii) is considered to be a risk factor for AD development. T2DM is characterized by high blood glucose levels resulting from increased hepatic glucose production, impaired insulin production and peripheral insulin resistance, which close resemble to the brain insulin resistance observed in AD patients. Furthermore, growing evidence suggests that oxidative stress plays a pivotal role in the development of insulin resistance and vice versa. This review article provides molecular aspects and the pharmacological approaches from both preclinical and clinical data interpreted from the point of view of oxidative stress with the aim of highlighting progresses in this field. Copyright © 2014 Elsevier B.V. All rights reserved.

Wnt5a is essential for hippocampal dendritic maintenance and spatial learning and memory in adult mice

PubMed Central

Chen, Chih-Ming; Orefice, Lauren L.; Chiu, Shu-Ling; LeGates, Tara A.; Huganir, Richard L.; Zhao, Haiqing; Xu, Baoji; Kuruvilla, Rejji

2017-01-01

Stability of neuronal connectivity is critical for brain functions, and morphological perturbations are associated with neurodegenerative disorders. However, how neuronal morphology is maintained in the adult brain remains poorly understood. Here, we identify Wnt5a, a member of the Wnt family of secreted morphogens, as an essential factor in maintaining dendritic architecture in the adult hippocampus and for related cognitive functions in mice. Wnt5a expression in hippocampal neurons begins postnatally, and its deletion attenuated CaMKII and Rac1 activity, reduced GluN1 glutamate receptor expression, and impaired synaptic plasticity and spatial learning and memory in 3-mo-old mice. With increased age, Wnt5a loss caused progressive attrition of dendrite arbors and spines in Cornu Ammonis (CA)1 pyramidal neurons and exacerbated behavioral defects. Wnt5a functions cell-autonomously to maintain CA1 dendrites, and exogenous Wnt5a expression corrected structural anomalies even at late-adult stages. These findings reveal a maintenance factor in the adult brain, and highlight a trophic pathway that can be targeted to ameliorate dendrite loss in pathological conditions. PMID:28069946

38 CFR 4.130 - Schedule of ratings-mental disorders.

Code of Federal Regulations, 2010 CFR

2010-07-01

...; impairment of short- and long-term memory (e.g., retention of only highly learned material, forgetting to... (including maintenance of minimal personal hygiene); disorientation to time or place; memory loss for names... or less often), chronic sleep impairment, mild memory loss (such as forgetting names, directions...

Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice.

PubMed

Takeda, Yosuke; Oue, Hiroshi; Okada, Shinsuke; Kawano, Akira; Koretake, Katsunori; Michikawa, Makoto; Akagawa, Yasumasa; Tsuga, Kazuhiro

2016-12-05

It is known that tooth loss is known to be a risk factor for Alzheimer's disease and soft diet feeding induces memory impairment. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is associated with tooth loss or soft diet in young animal model, and that BDNF expression is decreased in patients with Alzheimer's disease. However, single or combined effect of tooth loss and/or soft diet on brain function has not fully understood. Here we examined the effect of molar loss and powder diet on memory ability and the expression of BDNF mRNA in the hippocampus of adult C57BL/6J mice. Twenty eight-weeks-old C57BL/6J mice were divided into intact molar group and extracted molar group. They were randomly divided into the I/S group (Intact upper molar teeth/Solid diet feeding), the E/S group (Extracted upper molar teeth/Solid diet feeding), the I/P group (Intact upper molar teeth/Powder diet feeding), and the E/P group (Extracted upper molar teeth/Powder diet feeding). The observation periods were 4 and 16-week. To analyze the memory ability, the step-through passive avoidance test was conducted. BDNF-related mRNA in the hippocampus was analyzed by real-time polymerase chain reaction (RT-PCR). At 4 weeks later, we performed memory test and isolated brains to analyze. There were no differences in memory function and BDNF mRNA level between these four groups. However, at 16 weeks later, E/S and E/P group showed memory impairment, and decreased level of BDNF mRNA. Whereas, the powder diet had no effect on memory function and BDNF mRNA level even at 16 weeks later. These results suggest that the effect of molar loss and powder diet on memory function and BDNF mRNA levels were different, molar loss may have a greater long-term effect on memory ability than powder diet does.

The BACHD Rat Model of Huntington Disease Shows Signs of Fronto-Striatal Dysfunction in Two Operant Conditioning Tests of Short-Term Memory.

PubMed

Clemensson, Erik Karl Håkan; Clemensson, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc

2017-01-01

The BACHD rat is a recently developed transgenic animal model of Huntington disease, a progressive neurodegenerative disorder characterized by extensive loss of striatal neurons. Cognitive impairments are common among patients, and characterization of similar deficits in animal models of the disease is therefore of interest. The present study assessed the BACHD rats' performance in the delayed alternation and the delayed non-matching to position test, two Skinner box-based tests of short-term memory function. The transgenic rats showed impaired performance in both tests, indicating general problems with handling basic aspects of the tests, while short-term memory appeared to be intact. Similar phenotypes have been found in rats with fronto-striatal lesions, suggesting that Huntington disease-related neuropathology might be present in the BACHD rats. Further analyses indicated that the performance deficit in the delayed alternation test might be due to impaired inhibitory control, which has also been implicated in Huntington disease patients. The study ultimately suggests that the BACHD rats might suffer from neuropathology and cognitive impairments reminiscent of those of Huntington disease patients.

Focal expression of mutated tau in entorhinal cortex neurons of rats impairs spatial working memory.

PubMed

Ramirez, Julio J; Poulton, Winona E; Knelson, Erik; Barton, Cole; King, Michael A; Klein, Ronald L

2011-01-01

Entorhinal cortex neuropathology begins very early in Alzheimer's disease (AD), a disorder characterized by severe memory disruption. Indeed, loss of entorhinal volume is predictive of AD and two of the hallmark neuroanatomical markers of AD, amyloid plaques and neurofibrillary tangles (NFTs), are particularly prevalent in the entorhinal area of AD-afflicted brains. Gene transfer techniques were used to create a model neurofibrillary tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the entorhinal cortex of adult rats. The objective of the present investigation was to determine whether adult onset, spatially restricted tauopathy could be sufficient to reproduce progressive deficits in mnemonic function. Spatial memory on a Y-maze was tested for approximately 3 months post-surgery. Upon completion of behavioral testing the brains were assessed for expression of human tau and evidence of tauopathy. Rats injected with the tau vector became persistently impaired on the task after about 6 weeks of postoperative testing, whereas the control rats injected with a green fluorescent protein vector performed at criterion levels during that period. Histological analysis confirmed the presence of hyperphosphorylated tau and NFTs in the entorhinal cortex and neighboring retrohippocampal areas as well as limited synaptic degeneration of the perforant path. Thus, highly restricted vector-induced tauopathy in retrohippocampal areas is sufficient for producing progressive impairment in mnemonic ability in rats, successfully mimicking a key aspect of tauopathies such as AD. Copyright © 2010 Elsevier B.V. All rights reserved.

Decreased rhythmic GABAergic septal activity and memory-associated theta oscillations after hippocampal amyloid-beta pathology in the rat.

PubMed

Villette, Vincent; Poindessous-Jazat, Frédérique; Simon, Axelle; Léna, Clément; Roullot, Elodie; Bellessort, Brice; Epelbaum, Jacques; Dutar, Patrick; Stéphan, Aline

2010-08-18

The memory deficits associated with Alzheimer's disease result to a great extent from hippocampal network dysfunction. The coordination of this network relies on theta (symbol) oscillations generated in the medial septum. Here, we investigated in rats the impact of hippocampal amyloid beta (Abeta) injections on the physiological and cognitive functions that depend on the septohippocampal system. Hippocampal Abeta injections progressively impaired behavioral performances, the associated hippocampal theta power, and theta frequency response in a visuospatial recognition test. These alterations were associated with a specific reduction in the firing of the identified rhythmic bursting GABAergic neurons responsible for the propagation of the theta rhythm to the hippocampus, but without loss of medial septal neurons. Such results indicate that hippocampal Abeta treatment leads to a specific functional depression of inhibitory projection neurons of the medial septum, resulting in the functional impairment of the temporal network.

Recognition and treatment of Alzheimer's disease: a case-based review.

PubMed

Marseille, Dana M; Silverman, Daniel H S

2006-01-01

Early recognition and treatment initiation are pivotal in managing Alzheimer's disease (AD). Once a diagnosis of AD is made, a treatment plan is developed and should include treatment initiation with cholinesterase inhibitors (ChEIs) to improve cognition, management of comorbid conditions, and treat behavioral symptoms. Caregiver compliance is integral to AD treatment success. The purpose of this report is to present two real case studies of "suspected" AD or related dementia and stress the significance of early and accurate diagnosis in disease management. In case 1, a caregiver reports gradual but progressive loss of memory, and the patient himself complains of memory impairment. Neuroimaging analysis confirms "typical " AD. In case 2, initiation of ChEI therapy is followed by substantial clinical improvement in the face of a complex medical picture, and neuroimaging revealing more neurodegenerative changes than could be accounted for by "pure" AD.

The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer's diseas

PubMed Central

Ferreira, Sergio T; Klein, William L

2015-01-01

Alzheimer's disease is the 3rd most costly disease and is estimated to be the 6th leading cause of death. Alzheimer's disease (AD) is fatal and affected individuals can sometimes linger many years. Current treatments are palliative and transient, not disease modifying. This article reviews progress in the search to identify the primary AD-causing toxins. We summarize the shift from an initial focus on amyloid plaques to the contemporary concept that AD memory failure is caused by small soluble oligomers of the Aβ peptide, toxins that target and disrupt particular synapses. Evidence is presented that links Aβ oligomers to pathogenesis in animal models and humans, with reference to seminal discoveries from cell biology and new ideas concerning pathogenic mechanisms. These findings have established the oligomer hypothesis as a new molecular basis for the cause, diagnosis, and treatment of AD. PMID:21914486

Arctigenin effectively ameliorates memory impairment in Alzheimer's disease model mice targeting both β-amyloid production and clearance.

PubMed

Zhu, Zhiyuan; Yan, Jianming; Jiang, Wei; Yao, Xin-gang; Chen, Jing; Chen, Lili; Li, Chenjing; Hu, Lihong; Jiang, Hualiang; Shen, Xu

2013-08-07

Alzheimer's disease (AD) chiefly characterizes a progressively neurodegenerative disorder of the brain, and eventually leads to irreversible loss of intellectual abilities. The β-amyloid (Aβ)-induced neurodegeneration is believed to be the main pathological mechanism of AD, and Aβ production inhibition or its clearance promotion is one of the promising therapeutic strategies for anti-AD research. Here, we report that the natural product arctigenin from Arctium lappa (L.) can both inhibit Aβ production by suppressing β-site amyloid precursor protein cleavage enzyme 1 expression and promote Aβ clearance by enhancing autophagy through AKT/mTOR signaling inhibition and AMPK/Raptor pathway activation as investigated in cells and APP/PS1 transgenic AD model mice. Moreover, the results showing that treatment of arctigenin in mice highly decreased Aβ formation and senile plaques and efficiently ameliorated AD mouse memory impairment strongly highlight the potential of arctigenin in anti-AD drug discovery.

Spin-transfer torque magnetoresistive random-access memory technologies for normally off computing (invited)

NASA Astrophysics Data System (ADS)

Ando, K.; Fujita, S.; Ito, J.; Yuasa, S.; Suzuki, Y.; Nakatani, Y.; Miyazaki, T.; Yoda, H.

2014-05-01

Most parts of present computer systems are made of volatile devices, and the power to supply them to avoid information loss causes huge energy losses. We can eliminate this meaningless energy loss by utilizing the non-volatile function of advanced spin-transfer torque magnetoresistive random-access memory (STT-MRAM) technology and create a new type of computer, i.e., normally off computers. Critical tasks to achieve normally off computers are implementations of STT-MRAM technologies in the main memory and low-level cache memories. STT-MRAM technology for applications to the main memory has been successfully developed by using perpendicular STT-MRAMs, and faster STT-MRAM technologies for applications to the cache memory are now being developed. The present status of STT-MRAMs and challenges that remain for normally off computers are discussed.

Haemophilus influenzae type B in an immunocompetent, fully vaccinated ALL survivor.

PubMed

Nevin, John; Kanter Washko, Julie; Arnold, John

2013-05-01

A 7-year-old boy with a history of recurrent acute lymphoblastic leukemia (ALL), in remission, presented to primary care clinic after 2 days of progressive right hip pain with weight-bearing activities. He was otherwise asymptomatic at the time of presentation. Blood cultures revealed Gram-negative diplococci, which prompted an MRI that was significant for a hip joint effusion and femoral head bone marrow edema. The patient had no sick contacts and no significant past medical history other than ALL. The patient had been given all recommended childhood vaccinations. Arthrocentesis and needle biopsy of the femoral neck were not diagnostic for malignancy and revealed only mild hip joint inflammation, leading to a diagnosis of osteomyelitis. The organism in the original blood culture was identified as Haemophilus influenzae type b, β-lactamase negative. Review of the patient's medical records showed a history of complete immunization to Haemophilus influenzae type b. An immunologic evaluation was made to determine if the patient retained immunity from his other vaccinations. Pathogen-specific antibody testing revealed detectable antibodies to polio but not measles, mumps, rubella, varicella-zoster virus, tetanus, diphtheria, pertussis, or hepatitis B. This loss of immunologic memory appears to be a rarely described side effect of ALL chemotherapy. There is currently no protocol to evaluate the immunologic memory of patients who underwent chemotherapy for ALL or to revaccinate them after their treatment. It is unclear whether the loss of immunologic memory is genuinely rare or is underdiagnosed because affected patients are protected by herd immunity.

Dementia - daily care

MedlinePlus

... pdf . Accessed on June 27, 2016. Budson AE, Solomon PR. Life adjustments for memory loss, Alzheimer's disease, and dementia. In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia: ...

The relationship between loss of parents in the holocaust, intrusive memories, and distress among child survivors.

PubMed

Letzter-Pouw, Sonia; Werner, Perla

2012-04-01

The prevalence of intrusive memories of the Holocaust and their relationship to distress was examined among 272 child survivors in Israel. Using attachment theory as a conceptual framework, the authors also examined the effects of type of experience and loss of parents in the Holocaust, psychological resources, other life events, and sociodemographic characteristics on distress and symptomatic behavior. Eighty five percent of the participants reported suffering from intrusive memories. Structural equation modeling showed that survivors who lost one or both parents in the Holocaust suffered more distress because of more intrusive memories. These findings suggest that intrusive memories may be part of unfinished mourning processes related to the loss of parents in the Holocaust. © 2012 American Orthopsychiatric Association.

Design of multiple sequence alignment algorithms on parallel, distributed memory supercomputers.

PubMed

Church, Philip C; Goscinski, Andrzej; Holt, Kathryn; Inouye, Michael; Ghoting, Amol; Makarychev, Konstantin; Reumann, Matthias

2011-01-01

The challenge of comparing two or more genomes that have undergone recombination and substantial amounts of segmental loss and gain has recently been addressed for small numbers of genomes. However, datasets of hundreds of genomes are now common and their sizes will only increase in the future. Multiple sequence alignment of hundreds of genomes remains an intractable problem due to quadratic increases in compute time and memory footprint. To date, most alignment algorithms are designed for commodity clusters without parallelism. Hence, we propose the design of a multiple sequence alignment algorithm on massively parallel, distributed memory supercomputers to enable research into comparative genomics on large data sets. Following the methodology of the sequential progressiveMauve algorithm, we design data structures including sequences and sorted k-mer lists on the IBM Blue Gene/P supercomputer (BG/P). Preliminary results show that we can reduce the memory footprint so that we can potentially align over 250 bacterial genomes on a single BG/P compute node. We verify our results on a dataset of E.coli, Shigella and S.pneumoniae genomes. Our implementation returns results matching those of the original algorithm but in 1/2 the time and with 1/4 the memory footprint for scaffold building. In this study, we have laid the basis for multiple sequence alignment of large-scale datasets on a massively parallel, distributed memory supercomputer, thus enabling comparison of hundreds instead of a few genome sequences within reasonable time.

Dementia - home care

MedlinePlus

... with dementia; Home care - dementia References Budson AE, Solomon PR. Why diagnose and treat memory loss, Alzheimer's disease, and dementia? In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia . ...

Differential influence of hippocampal subfields to memory formation: insights from patients with temporal lobe epilepsy.

PubMed

Coras, Roland; Pauli, Elisabeth; Li, Jinmei; Schwarz, Michael; Rössler, Karl; Buchfelder, Michael; Hamer, Hajo; Stefan, Hermann; Blumcke, Ingmar

2014-07-01

To clarify the anatomical organization of human memory remains a major challenge in clinical neuroscience. Experimental data suggest dentate gyrus granule cells play a major role in memory acquisition, i.e. pattern separation and rapid pattern completion, whereas hippocampal CA1 neurons are implicated in place memory and autobiographical memory retrieval. Patients with temporal lobe epilepsy present with a broad spectrum of memory impairment, which can be assessed during clinical examination. Although long seizure histories may contribute to a pathophysiological reorganization of functional connectivity, surgical resection of the epileptic hippocampus offers a unique possibility to anatomically study the differential contribution of hippocampal subfields to compromised learning and memory in humans. Herein, we tested the hypothesis of hippocampal subfield specialization in a series of 100 consecutive patients with temporal lobe epilepsy submitted to epilepsy surgery. Memory profiles were obtained from intracarotid amobarbital testing and non-invasive verbal memory assessment before surgery, and correlated with histopathologically quantified cell loss pattern in hippocampal subfields obtained from the same patients using the new international consensus classification for hippocampal sclerosis proposed by the International League against Epilepsy (HS ILAE). Interestingly, patients with CA1 predominant cell loss (HS ILAE Type 2; n = 13) did not show declarative memory impairment and were indistinguishable from patients without any hippocampal cell loss (n = 19). In contrast, 63 patients with neuronal loss affecting all hippocampal subfields including CA1, CA4 and dentate gyrus (HS ILAE Type 1), or predominant cell loss in CA4 and partially affecting also CA3 and dentate gyrus (HS ILAE Type 3, n = 5) showed significantly reduced declarative memory capacities (intracarotid amobarbital testing: P < 0.001; verbal memory: P < 0.05). Our results suggested an alternative model of how memory processing can be organized amongst hippocampal subfields, and that CA1 pyramidal cells are less critically involved in declarative human memory acquisition compared to dentate gyrus granule cells or CA4/CA3 pyramidal cells. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hold-up power supply for flash memory

NASA Technical Reports Server (NTRS)

Ott, William E. (Inventor)

2004-01-01

A hold-up power supply for flash memory systems is provided. The hold-up power supply provides the flash memory with the power needed to temporarily operate when a power loss exists. This allows the flash memory system to complete any erasures and writes, and thus allows it to shut down gracefully. The hold-up power supply detects when a power loss on a power supply bus is occurring and supplies the power needed for the flash memory system to temporally operate. The hold-up power supply stores power in at least one capacitor. During normal operation, power from a high voltage supply bus is used to charge the storage capacitors. When a power supply loss is detected, the power supply bus is disconnected from the flash memory system. A hold-up controller controls the power flow from the storage capacitors to the flash memory system. The hold-up controller uses feedback to assure that the proper voltage is provided from the storage capacitors to the flash memory system. This power supplied by the storage capacitors allows the flash memory system to complete any erasures and writes, and thus allows the flash memory system to shut down gracefully.

Memory loss

MedlinePlus

... this page: //medlineplus.gov/ency/article/003257.htm Memory loss To use the sharing features on this ... Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health Page last updated: ...

Dementia - what to ask your doctor

MedlinePlus

... recs.pdf . Accessed December 8, 2016. Budson AE, Solomon PR. Life adjustments for memory loss, Alzheimer's disease, and dementia. In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia: ...

Dementia - keeping safe in the home

MedlinePlus

... recs.pdf . Accessed June 27, 2016. Budson AE, Solomon PR. Life adjustments for memory loss, Alzheimer's disease, and dementia. In: Budson AE, Solomon PR, eds. Memory Loss, Alzheimer's Disease, and Dementia: ...

Transient Global Amnesia

MedlinePlus

... global amnesia is a sudden, temporary episode of memory loss that can't be attributed to a ... know well. But that doesn't make your memory loss less disturbing. Fortunately, transient global amnesia is ...

Associations between speech understanding and auditory and visual tests of verbal working memory: effects of linguistic complexity, task, age, and hearing loss

PubMed Central

Smith, Sherri L.; Pichora-Fuller, M. Kathleen

2015-01-01

Listeners with hearing loss commonly report having difficulty understanding speech, particularly in noisy environments. Their difficulties could be due to auditory and cognitive processing problems. Performance on speech-in-noise tests has been correlated with reading working memory span (RWMS), a measure often chosen to avoid the effects of hearing loss. If the goal is to assess the cognitive consequences of listeners’ auditory processing abilities, however, then listening working memory span (LWMS) could be a more informative measure. Some studies have examined the effects of different degrees and types of masking on working memory, but less is known about the demands placed on working memory depending on the linguistic complexity of the target speech or the task used to measure speech understanding in listeners with hearing loss. Compared to RWMS, LWMS measures using different speech targets and maskers may provide a more ecologically valid approach. To examine the contributions of RWMS and LWMS to speech understanding, we administered two working memory measures (a traditional RWMS measure and a new LWMS measure), and a battery of tests varying in the linguistic complexity of the speech materials, the presence of babble masking, and the task. Participants were a group of younger listeners with normal hearing and two groups of older listeners with hearing loss (n = 24 per group). There was a significant group difference and a wider range in performance on LWMS than on RWMS. There was a significant correlation between both working memory measures only for the oldest listeners with hearing loss. Notably, there were only few significant correlations among the working memory and speech understanding measures. These findings suggest that working memory measures reflect individual differences that are distinct from those tapped by these measures of speech understanding. PMID:26441769

miRNA-431 Prevents Amyloid-β-Induced Synapse Loss in Neuronal Cell Culture Model of Alzheimer's Disease by Silencing Kremen1.

PubMed

Ross, Sean P; Baker, Kelly E; Fisher, Amanda; Hoff, Lee; Pak, Elena S; Murashov, Alexander K

2018-01-01

Synapse loss is well regarded as the underlying cause for the progressive decline of memory function over the course of Alzheimer's disease (AD) development. Recent observations suggest that the accumulation of the Wnt antagonist Dickkopf-1 (Dkk1) in the AD brain plays a critical role in triggering synaptic degeneration. Mechanistically, Dkk1 cooperates with Kremen1 (Krm1), its transmembrane receptor, to block the Wnt/β-catenin signaling pathway. Here, we show that silencing Krm1 with miR-431 prevents amyloid-β-mediated synapse loss in cortico-hippocampal cultures isolated from triple transgenic 3xTg-AD mice. Exposure to AβDDL (an amyloid-β derived diffusive ligand) or Dkk1 reduced the number of pre- and post-synaptic puncta in primary neuronal cultures, while treatment with miR-431 prevented synapse loss. In addition, treatment with miR-431 also prevented neurite degeneration. Our findings demonstrate that miR-431 protects synapses and neurites from Aβ-toxicity in an AD cell culture model and may be a promising therapeutic target.

Remembering the best and worst of times: memories for extreme outcomes bias risky decisions.

PubMed

Madan, Christopher R; Ludvig, Elliot A; Spetch, Marcia L

2014-06-01

When making decisions on the basis of past experiences, people must rely on their memories. Human memory has many well-known biases, including the tendency to better remember highly salient events. We propose an extreme-outcome rule, whereby this memory bias leads people to overweight the largest gains and largest losses, leading to more risk seeking for relative gains than for relative losses. To test this rule, in two experiments, people repeatedly chose between fixed and risky options, where the risky option led equiprobably to more or less than did the fixed option. As was predicted, people were more risk seeking for relative gains than for relative losses. In subsequent memory tests, people tended to recall the extreme outcome first and also judged the extreme outcome as having occurred more frequently. Across individuals, risk preferences in the risky-choice task correlated with these memory biases. This extreme-outcome rule presents a novel mechanism through which memory influences decision making.

The Association of Perceived Memory Loss with Osteoarthritis and Related Joint Pain in a Large Appalachian Population.

PubMed

Innes, Kim E; Sambamoorthi, Usha

2017-05-19

Previous studies have documented memory impairment in several chronic pain syndromes. However, the potential link between memory loss and osteoarthritis (OA), the second most common cause of chronic pain, remains little explored. In this cross-sectional study, we examine the association of perceived memory loss to OA and assess the potential mediating influence of sleep and mood disturbance in a large Appalachian population.  Cross-sectional.  US Ohio Valley.  A total of 21,982 Appalachian adults age 40 years or older drawn from the C8 Health Project (N = 19,004 adults without and 2,478 adults with OA). All participants completed a comprehensive health survey between 2005 and 2006. Medical history, including physician diagnosis of OA, lifestyle factors, short- and long-term memory loss, sleep quality, and mood were assessed via self-report.  After adjustment for demographic, lifestyle, health-related, and other factors, participants with OA were almost three times as likely to report frequent memory loss (adjusted odds ratios [ORs] for short- and long-term memory loss, respectively = 2.7, 95% confidence interval [CI] = 2.2-3.3, and 2.6, 95% CI = 2.0-3.3). The magnitude of these associations increased significantly with rising frequency of reported joint pain (adjusted OR for OA with frequent joint pain vs no OA = 3.3, 95% CI = 2.6-4.1, P trend  < 0.00001). Including measures of mood and sleep impairment attenuated but did not eliminate these associations (ORs for any memory loss = 2.0, 95% CI = 1.6-2.4, and 2.1, 95% CI = 1.7-2.8, adjusted for sleep and mood impairment, respectively; OR = 1.8, 95% CI = 1.4-2.2, adjusted for both factors).  In this large cross-sectional study, OA and related joint pain were strongly associated with perceived memory loss; these associations may be partially mediated by sleep and mood disturbance. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Coping with Memory Loss

MedlinePlus

... either using computerized axial tomography (CAT) scans or magnetic resonance imaging (MRI) – can help to identify strokes and tumors, which can sometimes cause memory loss. “The goal is to rule out factors ...

Antigen challenge leads to in vivo activation and elimination of highly polarized TH1 memory T cells

PubMed Central

Hayashi, Nobuki; Liu, Dacai; Min, Booki; Ben-Sasson, Shlomo Z.; Paul, William E.

2002-01-01

TH1 memory T cells derived from T cell receptor transgenic mice, in which the T cell antigen receptor is specific for a cytochrome C peptide in association with I-Ek, were transferred into normal B10.A mice and allowed to adopt a resting phenotype. When challenged, 30–60 days after transfer, with i.v. cytochrome C, the transgenic cells rapidly became activated, expressed mRNA for IFNγ, and began to divide. However, after 48 h, the frequency of the cells fell progressively, reaching levels only slightly above the limit of detection by day 8 and thereafter remain depressed for up to 90 days. The remaining cells were anergic as shown by limitation in proliferation and IFNγ production in response to in vitro antigen stimulation. Even if challenged with antigen emulsified in complete Freund's adjuvant, the overall pattern was similar, except that in the draining lymph nodes, the surviving antigen-specific cells were not anergic, although spleen cells were still strikingly anergic. Thus, antigenic challenge of mice possessing resting memory TH1 CD4 T cells leads to the unanticipated loss of most of the specific cells and an apparent depletion rather than enhancement of immunologic memory. PMID:11959916

Neurodegenerative Models in Drosophila: Polyglutamine Disorders, Parkinson Disease, and Amyotrophic Lateral Sclerosis

PubMed Central

Ambegaokar, Surendra S.; Roy, Bidisha; Jackson, George R.

2010-01-01

Neurodegenerative diseases encompass a large group of neurological disorders. Clinical symptoms can include memory loss, cognitive impairment, loss of movement or loss of control of movement, and loss of sensation. Symptoms are typically adult onset (although severe cases can occur in adolescents) and are reflective of neuronal and glial cell loss in the central nervous system. Neurodegenerative diseases also are considered progressive, with increased severity of symptoms over time, also reflective of increased neuronal cell death. However, various neurodegenerative diseases differentially affect certain brain regions or neuronal or glial cell types. As an example, Alzheimer disease (AD) primarily affects the temporal lobe, whereas neuronal loss in Parkinson disease (PD) is largely (although not exclusively) confined to the nigrostriatal system. Neuronal loss is almost invariably accompanied by abnormal insoluble aggregates, either intra- or extracellular. Thus, neurodegenerative diseases are categorized by (a) the composite of clinical symptoms, (b) the brain regions or types of brain cells primarily affected, and (c) the types of protein aggregates found in the brain. Here we review the methods by which Drosophila melanogaster has been used to model aspects of polyglutamine diseases, Parkinson disease, and amyotrophic lateral sclerosis and key insights into that have been gained from these models; Alzheimer disease and the tauopathies are covered elsewhere in this special issue. PMID:20561920

The effect of functional hearing loss and age on long- and short-term visuospatial memory: evidence from the UK biobank resource.

PubMed

Rönnberg, Jerker; Hygge, Staffan; Keidser, Gitte; Rudner, Mary

2014-01-01

The UK Biobank offers cross-sectional epidemiological data collected on >500,000 individuals in the UK between 40 and 70 years of age. Using the UK Biobank data, the aim of this study was to investigate the effects of functional hearing loss and hearing aid usage on visuospatial memory function. This selection of variables resulted in a sub-sample of 138,098 participants after discarding extreme values. A digit triplets functional hearing test was used to divide the participants into three groups: poor, insufficient and normal hearers. We found negative relationships between functional hearing loss and both visuospatial working memory (i.e., a card pair matching task) and visuospatial, episodic long-term memory (i.e., a prospective memory task), with the strongest association for episodic long-term memory. The use of hearing aids showed a small positive effect for working memory performance for the poor hearers, but did not have any influence on episodic long-term memory. Age also showed strong main effects for both memory tasks and interacted with gender and education for the long-term memory task. Broader theoretical implications based on a memory systems approach will be discussed and compared to theoretical alternatives.

Loss of Visual Working Memory within Seconds: The Combined Use of Refreshable and Non-Refreshable Features

ERIC Educational Resources Information Center

Ricker, Timothy J.; Cowan, Nelson

2010-01-01

We reexamine the role of time in the loss of information from working memory, the limited information accessible for cognitive tasks. The controversial issue of whether working memory deteriorates over time was investigated using arrays of unconventional visual characters. Each array was followed by a postperceptual mask, a variable retention…

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.

A case of dissociative fugue and general amnesia with an 11-year follow-up.

PubMed

Helmes, Edward; Brown, Julie-May; Elliott, Linda

2015-01-01

Dissociative fugue refers to loss of personal identity, often with the associated loss of memories of events (general amnesia). Here we report on the psychological assessment of a 54-year-old woman with loss of identity and memories of 33 years of her life attributed to dissociative fugue, along with a follow-up 11 years later. Significant levels of personal injury and stress preceded the onset of the amnesia. A detailed neuropsychological assessment was completed at a university psychology clinic, with a follow-up assessment there about 11 years later with an intent to determine whether changes in her cognitive status were associated with better recall of her life and with her emotional state. Psychomotor slowing and low scores on measures of attention and both verbal and visual memory were present initially, along with significant psychological distress associated with the diagnosis of posttraumatic stress disorder. Although memories of her life had not returned by follow-up, distress had abated and memory test scores had improved. The passage of time and a better emotional state did not lead to recovery of lost memories. Contrary to expectations, performance on tests of executive functions was good on both occasions. Multiple stressful events are attributed as having a role in maintaining the loss of memories.

Genetic and epigenetic profiling of CLL disease progression reveals limited somatic evolution and suggests a relationship to memory-cell development.

PubMed

Smith, E N; Ghia, E M; DeBoever, C M; Rassenti, L Z; Jepsen, K; Yoon, K-A; Matsui, H; Rozenzhak, S; Alakus, H; Shepard, P J; Dai, Y; Khosroheidari, M; Bina, M; Gunderson, K L; Messer, K; Muthuswamy, L; Hudson, T J; Harismendy, O; Barrett, C L; Jamieson, C H M; Carson, D A; Kipps, T J; Frazer, K A

2015-04-10

We examined genetic and epigenetic changes that occur during disease progression from indolent to aggressive forms of chronic lymphocytic leukemia (CLL) using serial samples from 27 patients. Analysis of DNA mutations grouped the leukemia cases into three categories: evolving (26%), expanding (26%) and static (47%). Thus, approximately three-quarters of the CLL cases had little to no genetic subclonal evolution. However, we identified significant recurrent DNA methylation changes during progression at 4752 CpGs enriched for regions near Polycomb 2 repressive complex (PRC2) targets. Progression-associated CpGs near the PRC2 targets undergo methylation changes in the same direction during disease progression as during normal development from naive to memory B cells. Our study shows that CLL progression does not typically occur via subclonal evolution, but that certain CpG sites undergo recurrent methylation changes. Our results suggest CLL progression may involve developmental processes shared in common with the generation of normal memory B cells.

Early Loss of Splenic Tfh Cells in SIV-Infected Rhesus Macaques

PubMed Central

Moukambi, Félicien; Rabezanahary, Henintsoa; Rodrigues, Vasco; Racine, Gina; Robitaille, Lynda; Krust, Bernard; Andreani, Guadalupe; Soundaramourty, Calayselvy; Silvestre, Ricardo; Laforge, Mireille; Estaquier, Jérôme

2015-01-01

Follicular T helper cells (Tfh), a subset of CD4 T lymphocytes, provide crucial help to B cells in the production of antigen-specific antibodies. Although several studies have analyzed the dynamics of Tfh cells in peripheral blood and lymph nodes (LNs) during Aids, none has yet addressed the impact of SIV infection on the dynamics of Tfh cells in the spleen, the primary organ of B cell activation. We show here a significant decrease in splenic Tfh cells in SIVmac251-infected rhesus macaques (RMs) during the acute phase of infection, which persists thereafter. This profound loss is associated with lack of sustained expression of the Tfh-defining transcription factors, Bcl-6 and c-Maf but with higher expression of the repressors KLF2 and Foxo1. In this context of Tfh abortive differentiation and loss, we found decreased percentages of memory B cell subsets and lower titers of SIV-specific IgG. We further demonstrate a drastic remodeling of the lymphoid architecture of the spleen and LNs, which disrupts the crucial cell-cell interactions necessary to maintain memory B cells and Tfh cells. Finally, our data demonstrated the early infection of Tfh cells. Paradoxically, the frequencies of SIV DNA were higher in splenic Tfh cells of RMs progressing more slowly suggesting sanctuaries for SIV in the spleen. Our findings provide important information regarding the impact of HIV/SIV infection on Tfh cells, and provide new clues for future vaccine strategies. PMID:26640894

Decoupling activation and exhaustion of B cells in spontaneous controllers of HIV infection

PubMed Central

Sciaranghella, Gaia; Tong, Neath; Mahan, Alison E.; Suscovich, Todd J.; Alter, Galit

2013-01-01

Objective To define the impact of chronic viremia and associated immune activation on B-cell exhaustion in HIV infection. Design Progressive HIV infection is marked by B-cell anergy and exhaustion coupled with dramatic hypergammaglobulinemia. Although both upregulation of CD95 and loss of CD21 have been used as markers of infection-associated B-cell dysfunction, little is known regarding the specific profiles of dysfunctional B cells and whether persistent viral replication and its associated immune activation play a central role in driving B-cell dysfunction. Methods Multiparameter flow cytometry was used to define the profile of dysfunctional B cells. The changes in the expression of CD21 and CD95 were tracked on B-cell subpopulations in patients with differential control of viral replication. Results Although the emergence of exhausted, CD21low tissue-like memory B cells followed similar patterns in both progressors and controllers, the frequency of CD21low activated memory B cells was lower in spontaneous controllers. Conclusion Our results suggest that the loss of CD21 and the upregulation of CD95 occur as separate events during the development of B-cell dysfunction. The loss of CD21 is a marker of B-cell exhaustion induced in the absence of appreciable viral replication, whereas the upregulation of CD95 is tightly linked to persistent viral replication and its associated immune activation. Thus, these dysfunctional profiles potentially represent two functionally distinct states within the B-cell compartment. PMID:23135171

Neuropathological changes in brain cortex and hippocampus in a rat model of Alzheimer's disease.

PubMed

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Rahbar Rooshandel, Nahid; Omidzahir, Shila

2011-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and Beta amyloid (ABeta) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 muL of ABeta (1-40) into the hippocampal fissure. In the present study, ABeta (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. ABeta injection CA1 caused ABeta deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group.

Focal retrograde amnesia and the episodic-semantic distinction.

PubMed

Wheeler, M A; McMillan, C T

2001-03-01

This article reports a review of focal retrograde amnesia (FRA), or the phenomenon of organically based severe memory loss restricted to retrograde, or pretraumatic, memory. Cases of FRA are classified according to the type of memory loss: episodic, semantic, or both. A few different clusters of the disorder were identified. Lesions to either the anterior temporal lobes or the posterior/visual cortex can result in an FRA that devastates retrograde episodic memory, while having smaller effects on semantic memory. A number of left-hemisphere patients have FRA confined to semantic memory. There are several additional examples of FRA following minor cerebral trauma that disrupts either episodic memory alone or both episodic and semantic memory that are not accompanied by evidence of structural brain lesions. We discuss these different profiles of FRA and their implications for the understanding of memory retrieval.

The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer's disease.

PubMed

McManus, Meagan J; Murphy, Michael P; Franklin, James L

2011-11-02

Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer's disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienl-yl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated β-amyloid (Aβ)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Δψ(m)) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathology in vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD-like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Aβ accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD.

The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

PubMed Central

McManus, Meagan J.; Murphy, Michael P.; Franklin, James L.

2012-01-01

Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer’s disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienlyl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated β-amyloid (Aβ)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Δψm) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathology in vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD-like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Aβ accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD. PMID:22049413

Severe Depletion of Mucosal CD4+ T Cells in AIDS-Free Simian Immunodeficiency Virus-Infected Sooty Mangabeys1

PubMed Central

Gordon, Shari N.; Klatt, Nichole R.; Bosinger, Steven E.; Brenchley, Jason M.; Milush, Jeffrey M.; Engram, Jessica C.; Dunham, Richard M.; Paiardini, Mirko; Klucking, Sara; Danesh, Ali; Strobert, Elizabeth A.; Apetrei, Cristian; Pandrea, Ivona V.; Kelvin, David; Douek, Daniel C.; Staprans, Silvija I.; Sodora, Donald L.; Silvestri, Guido

2008-01-01

HIV-infected humans and SIV-infected rhesus macaques experience a rapid and dramatic loss of mucosal CD4+ T cells that is considered to be a key determinant of AIDS pathogenesis. In this study, we show that nonpathogenic SIV infection of sooty mangabeys (SMs), a natural host species for SIV, is also associated with an early, severe, and persistent depletion of memory CD4+ T cells from the intestinal and respiratory mucosa. Importantly, the kinetics of the loss of mucosal CD4+ T cells in SMs is similar to that of SIVmac239-infected rhesus macaques. Although the nonpathogenic SIV infection of SMs induces the same pattern of mucosal target cell depletion observed during pathogenic HIV/SIV infections, the depletion in SMs occurs in the context of limited local and systemic immune activation and can be reverted if virus replication is suppressed by antiretroviral treatment. These results indicate that a profound depletion of mucosal CD4+ T cells is not sufficient per se to induce loss of mucosal immunity and disease progression during a primate lentiviral infection. We propose that, in the disease-resistant SIV-infected SMs, evolutionary adaptation to both preserve immune function with fewer mucosal CD4+ T cells and attenuate the immune activation that follows acute viral infection protect these animals from progressing to AIDS. PMID:17709517

Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys.

PubMed

Gordon, Shari N; Klatt, Nichole R; Bosinger, Steven E; Brenchley, Jason M; Milush, Jeffrey M; Engram, Jessica C; Dunham, Richard M; Paiardini, Mirko; Klucking, Sara; Danesh, Ali; Strobert, Elizabeth A; Apetrei, Cristian; Pandrea, Ivona V; Kelvin, David; Douek, Daniel C; Staprans, Silvija I; Sodora, Donald L; Silvestri, Guido

2007-09-01

HIV-infected humans and SIV-infected rhesus macaques experience a rapid and dramatic loss of mucosal CD4+ T cells that is considered to be a key determinant of AIDS pathogenesis. In this study, we show that nonpathogenic SIV infection of sooty mangabeys (SMs), a natural host species for SIV, is also associated with an early, severe, and persistent depletion of memory CD4+ T cells from the intestinal and respiratory mucosa. Importantly, the kinetics of the loss of mucosal CD4+ T cells in SMs is similar to that of SIVmac239-infected rhesus macaques. Although the nonpathogenic SIV infection of SMs induces the same pattern of mucosal target cell depletion observed during pathogenic HIV/SIV infections, the depletion in SMs occurs in the context of limited local and systemic immune activation and can be reverted if virus replication is suppressed by antiretroviral treatment. These results indicate that a profound depletion of mucosal CD4+ T cells is not sufficient per se to induce loss of mucosal immunity and disease progression during a primate lentiviral infection. We propose that, in the disease-resistant SIV-infected SMs, evolutionary adaptation to both preserve immune function with fewer mucosal CD4+ T cells and attenuate the immune activation that follows acute viral infection protect these animals from progressing to AIDS.

A multiresolution halftoning algorithm for progressive display

NASA Astrophysics Data System (ADS)

Mukherjee, Mithun; Sharma, Gaurav

2005-01-01

We describe and implement an algorithmic framework for memory efficient, 'on-the-fly' halftoning in a progressive transmission environment. Instead of a conventional approach which repeatedly recalls the continuous tone image from memory and subsequently halftones it for display, the proposed method achieves significant memory efficiency by storing only the halftoned image and updating it in response to additional information received through progressive transmission. Thus the method requires only a single frame-buffer of bits for storage of the displayed binary image and no additional storage is required for the contone data. The additional image data received through progressive transmission is accommodated through in-place updates of the buffer. The method is thus particularly advantageous for high resolution bi-level displays where it can result in significant savings in memory. The proposed framework is implemented using a suitable multi-resolution, multi-level modification of error diffusion that is motivated by the presence of a single binary frame-buffer. Aggregates of individual display bits constitute the multiple output levels at a given resolution. This creates a natural progression of increasing resolution with decreasing bit-depth.

Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice

PubMed Central

Baglietto-Vargas, David; Chen, Yuncai; Suh, Dongjin; Ager, Rahasson R.; Rodriguez-Ortiz, Carlos J.; Mederios, Rodrigo; Myczek, Kristoffer; Green, Kim N.; Baram, Tallie Z.; LaFerla, Frank M.

2016-01-01

Alzheimer’s disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal ‘modern life-like’ stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. PMID:26077803

The loss of short-term visual representations over time: decay or temporal distinctiveness?

PubMed

Mercer, Tom

2014-12-01

There has been much recent interest in the loss of visual short-term memories over the passage of time. According to decay theory, visual representations are gradually forgotten as time passes, reflecting a slow and steady distortion of the memory trace. However, this is controversial and decay effects can be explained in other ways. The present experiment aimed to reexamine the maintenance and loss of visual information over the short term. Decay and temporal distinctiveness models were tested using a delayed discrimination task, in which participants compared complex and novel objects over unfilled retention intervals of variable length. Experiment 1 found no significant change in the accuracy of visual memory from 2 to 6 s, but the gap separating trials reliably influenced task performance. Experiment 2 found evidence for information loss at a 10-s retention interval, but temporally separating trials restored the fidelity of visual memory, possibly because temporally isolated representations are distinct from older memory traces. In conclusion, visual representations lose accuracy at some point after 6 s, but only within temporally crowded contexts. These findings highlight the importance of temporal distinctiveness within visual short-term memory. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Prefrontocortical dopamine loss in rats delays long-term extinction of contextual conditioned fear, and reduces social interaction without affecting short-term social interaction memory.

PubMed

Fernandez Espejo, Emilio

2003-03-01

Prefrontal dopamine loss delays extinction of cued fear conditioning responses, but its role in contextual fear conditioning has not been explored. Medial prefrontal lesions also enhance social interaction in rats, but the role of prefrontal dopamine loss on social interaction memory is not known. Besides, a role for subcortical accumbal dopamine on mnesic changes after prefrontal dopamine manipulation has been proposed but not explored. The objective was to study the involvement of dopaminergic neurotransmission in the medial prefrontal cortex (mPFC) and nucleus accumbens in two mnesic tasks: contextual fear conditioning and social interaction memory. For contextual fear conditioning, short- and long-term freezing responses after an electric shock were studied, as well as extinction retention. Regarding social interaction memory, the recognition of a juvenile, a very sensitive short-term memory test, was used. Dopamine loss was carried out by injection of 6-hydroxydopamine, and postmortem catecholamine levels were analyzed by high-performance liquid chromatography. Prefrontocortical dopamine loss (>76%) led to a reactive enhancement of accumbal dopamine content (p<0.01), supporting the hypothesis that a hyperdopaminergic tone emerges in the nucleus accumbens after prefrontocortical dopamine loss. In lesioned rats, long-term extinction of contextual fear conditioning was significantly delayed and extinction retention was impaired without changes in acquisition and short-term contextual fear conditioning and, on the other hand, acquisition and short-term social interaction memory were not affected, although time spent on social interaction was significantly reduced. Added dopamine loss in the nucleus accumbens (>76%) did not alter these behavioral changes. In summary, the results of the present study indicate that the dopaminergic network in the mPFC (but not in the nucleus accumbens) coordinates the normal long-term extinction of contextual fear conditioning responses without affecting their acquisition, and it is involved in time spent on social interaction, but not acquisition and short-term social interaction memory.

Combination of chronic stress and ovariectomy causes conditioned fear memory deficits and hippocampal cholinergic neuronal loss in mice.

PubMed

Takuma, K; Mizoguchi, H; Funatsu, Y; Hoshina, Y; Himeno, Y; Fukuzaki, E; Kitahara, Y; Arai, S; Ibi, D; Kamei, H; Matsuda, T; Koike, K; Inoue, M; Nagai, T; Yamada, K

2012-04-05

We have recently found that the combination of ovariectomy (OVX) and chronic restraint stress (CS) causes hippocampal pyramidal cell loss and cognitive dysfunction in female rats and that estrogen replacement prevents the OVX/CS-induced morphological and behavioral changes. In this study, to clarify the mechanisms underlying the OVX/CS-mediated memory impairment further, we examined the roles of cholinergic systems in the OVX/CS-induced memory impairment in mice. Female Slc:ICR strain mice were randomly divided into two groups: OVX and sham-operated groups. Two weeks after the operation, the mice of each group were further assigned to CS (6 h/day) or non-stress group. Following the 3-week-stress period, all mice were subjected to contextual fear conditioning, and context- and tone-dependent memory tests were conducted 1 or 24 h after the conditioning. Overburden with 3 weeks of CS from 2 weeks after OVX impaired context- and tone-dependent freezing and the OVX/CS caused significant Nissl-stained neuron-like cell loss in the hippocampal CA3 region, although OVX and CS alone did not cause such behavioral and histological changes. Replacement of 17β-estradiol for 5 weeks after OVX suppressed OVX/CS-induced memory impairment and hippocampal Nissl-positive cell loss. Furthermore, the OVX/CS mice exhibited a significant decrease in choline acetyltransferase in the hippocampus compared with other groups. The cholinesterase inhibitors donepezil and galantamine ameliorated OVX/CS-induced memory impairment. These data suggest that cholinergic dysfunction may be involved in the OVX/CS-induced conditioned fear memory impairment. Overall, our findings suggest that the OVX/CS mouse model is useful to study the mechanisms underlying estrogen loss-induced memory deficits. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

The overall pathological status of the left hippocampus determines preoperative verbal memory performance in left mesial temporal lobe epilepsy.

PubMed

Witt, Juri-Alexander; Coras, Roland; Schramm, Johannes; Becker, Albert J; Elger, Christian E; Blümcke, Ingmar; Helmstaedter, Christoph

2014-04-01

Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the hippocampus. The overall pathological status of the left hippocampus correlated with verbal memory parameters (r = 0.33-0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50-0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right hippocampus and memory function were found, nor did left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the left hippocampus - rather than a specific subfield pathology - is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right hippocampus, puts the left/right hippocampus verbal/nonverbal memory dichotomy into perspective. Copyright © 2013 Wiley Periodicals, Inc.

Characterization of naïve, memory and effector T cells in progressive multiple sclerosis.

PubMed

Nielsen, Birgitte Romme; Ratzer, Rikke; Börnsen, Lars; von Essen, Marina Rode; Christensen, Jeppe Romme; Sellebjerg, Finn

2017-09-15

We characterized naïve, central memory (CM), effector memory (EM) and terminally differentiated effector memory (TEMRA) CD4 + and CD8 + T cells and their expression of CD49d and CD26 in peripheral blood in patients with multiple sclerosis (MS) and healthy controls. CD26 + CD28 + CD4 + TEMRA T cells were increased in all subtypes of MS, and CD26 + CD28 + CD8 + TEMRA T cells were increased in relapsing-remitting and secondary progressive MS. Conversely, in progressive MS, CD49d + CM T cells were decreased and natalizumab increased the circulating number of all six subsets but reduced the frequency of most subsets expressing CD49d and CD26. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

I Owe You: Age-Related Similarities and Differences in Associative Memory for Gains and Losses

PubMed Central

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

2016-01-01

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

Long-term potentiation decay and memory loss are mediated by AMPAR endocytosis.

PubMed

Dong, Zhifang; Han, Huili; Li, Hongjie; Bai, Yanrui; Wang, Wei; Tu, Man; Peng, Yan; Zhou, Limin; He, Wenting; Wu, Xiaobin; Tan, Tao; Liu, Mingjing; Wu, Xiaoyan; Zhou, Weihui; Jin, Wuyang; Zhang, Shu; Sacktor, Todd Charlton; Li, Tingyu; Song, Weihong; Wang, Yu Tian

2015-01-01

Long-term potentiation (LTP) of synaptic strength between hippocampal neurons is associated with learning and memory, and LTP dysfunction is thought to underlie memory loss. LTP can be temporally and mechanistically classified into decaying (early-phase) LTP and nondecaying (late-phase) LTP. While the nondecaying nature of LTP is thought to depend on protein synthesis and contribute to memory maintenance, little is known about the mechanisms and roles of decaying LTP. Here, we demonstrated that inhibiting endocytosis of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) prevents LTP decay, thereby converting it into nondecaying LTP. Conversely, restoration of AMPAR endocytosis by inhibiting protein kinase Mζ (PKMζ) converted nondecaying LTP into decaying LTP. Similarly, inhibition of AMPAR endocytosis prolonged memory retention in normal animals and reduced memory loss in a murine model of Alzheimer's disease. These results strongly suggest that an active process that involves AMPAR endocytosis mediates the decay of LTP and that inhibition of this process can prolong the longevity of LTP as well as memory under both physiological and pathological conditions.

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.

Genistein improves 3-NPA-induced memory impairment in ovariectomized rats: impact of its antioxidant, anti-inflammatory and acetylcholinesterase modulatory properties.

PubMed

Menze, Esther T; Esmat, Ahmed; Tadros, Mariane G; Abdel-Naim, Ashraf B; Khalifa, Amani E

2015-01-01

Huntington's disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities.

Chronic Lithium Treatment in a Rat Model of Basal Forebrain Cholinergic Depletion: Effects on Memory Impairment and Neurodegeneration.

PubMed

Gelfo, Francesca; Cutuli, Debora; Nobili, Annalisa; De Bartolo, Paola; D'Amelio, Marcello; Petrosini, Laura; Caltagirone, Carlo

2017-01-01

Alzheimer's disease (AD) is an age-related neurodegenerative disorder with multifactorial etiopathogenesis, characterized by progressive loss of memory and other cognitive functions. A fundamental neuropathological feature of AD is the early and severe brain cholinergic neurodegeneration. Lithium is a monovalent cation classically utilized in the treatment of mood disorders, but recent evidence also advances a beneficial potentiality of this compound in neurodegeneration. Interestingly, lithium acts on several processes whose alterations characterize the brain cholinergic impairment at short and long term. On this basis, the aim of the present research was to evaluate the potential beneficial effects of a chronic lithium treatment in preventing the damage that a basal forebrain cholinergic neurodegeneration provokes, by investigating memory functions and neurodegeneration correlates. Adult male rats were lesioned by bilateral injections of the immunotoxin 192 IgG-Saporin into the basal forebrain. Starting 7 days before the surgery, the animals were exposed to a 30-day lithium treatment, consisting of a 0.24% Li2CO3 diet. Memory functions were investigated by the open field test with objects, the sociability and preference for social novelty test, and the Morris water maze. Hippocampal and neocortical choline acetyltransferase (ChAT) levels and caspase-3 activity were determined. Cholinergic depletion significantly impaired spatial and social recognition memory, decreased hippocampal and neocortical ChAT levels and increased caspase-3 activity. The chronic lithium treatment significantly rescued memory performances but did not modulate ChAT availability and caspase-3 activity. The present findings support the lithium protective effects against the cognitive impairment that characterizes the brain cholinergic depletion.

Experience and information loss in auditory and visual memory.

PubMed

Gloede, Michele E; Paulauskas, Emily E; Gregg, Melissa K

2017-07-01

Recent studies show that recognition memory for sounds is inferior to memory for pictures. Four experiments were conducted to examine the nature of auditory and visual memory. Experiments 1-3 were conducted to evaluate the role of experience in auditory and visual memory. Participants received a study phase with pictures/sounds, followed by a recognition memory test. Participants then completed auditory training with each of the sounds, followed by a second memory test. Despite auditory training in Experiments 1 and 2, visual memory was superior to auditory memory. In Experiment 3, we found that it is possible to improve auditory memory, but only after 3 days of specific auditory training and 3 days of visual memory decay. We examined the time course of information loss in auditory and visual memory in Experiment 4 and found a trade-off between visual and auditory recognition memory: Visual memory appears to have a larger capacity, while auditory memory is more enduring. Our results indicate that visual and auditory memory are inherently different memory systems and that differences in visual and auditory recognition memory performance may be due to the different amounts of experience with visual and auditory information, as well as structurally different neural circuitry specialized for information retention.

Quetiapine for hypnogogic musical release hallucinations.

PubMed

David, R R; Fernandez, H H

2000-01-01

Musical release hallucinations are complex auditory phenomena, affecting mostly the deaf geriatric population, in which individuals hear vocal or instrumental music. Progressive hearing loss from otosclerosis disrupts the usual external sensory stimuli necessary to inhibit the emergence of memory traces within the brain, thereby "releasing" previously recorded perceptions. Responses to conventional antipsychotic agents have been variable and extrapyramidal and other side effects have limited their use. We report the first case of hypnogogic release hallucinations successfully treated with the atypical antipsychotic quetiapine. The patient is an 88-year-old woman with progressive deafness who complained of hearing the piano, drums, or a full orchestra every time she was about to fall asleep. She accused her neighbor of hosting loud parties. Physical, neurologic, and psychiatric examination and work-up were unremarkable. She was treated with low-dose quetiapine affording near total resolution of hallucinations without adverse effects.

Surgical techniques in radiation induced temporal lobe necrosis in nasopharyngeal carcinoma patients.

PubMed

Alfotih, Gobran Taha Ahmed; Zheng, Mei Guang; Cai, Wang Qing; Xu, Xin Ke; Hu, Zhen; Li, Fang Cheng

2016-01-01

Radiation induced brain injury ranges from acute reversible edema to late, irreversible radiation necrosis. Radiation induced temporal lobe necrosis is associated with permanent neurological deficits and occasionally progresses to death. We present our experience with surgery on radiation induced temporal lobe necrosis (RTLN) in nasopharyngeal carcinoma (NPC) patients with special consideration of clinical presentation, surgical technique, and outcomes. This retrospective study includes 12 patients with RTLN treated by the senior author between January 2010 and December 2014. Patients initially sought medical treatment due to headache; other symptoms were hearing loss, visual deterioration, seizure, hemiparesis, vertigo, memory loss and agnosia. A temporal approach through a linear incision was performed for all cases. RTLN was found in one side in 7 patients, and bilaterally in 5. 4 patients underwent resection of necrotic tissue bilaterally and 8 patients on one side. No death occurred in this series of cases. There were no post-operative complications, except 1 patient who developed aseptic meningitis. All 12 patients were free from headache. No seizure occurred in patients with preoperative epilepsy. Other symptoms such as hemiparesis and vertigo improved in all patients. Memory loss, agnosia and hearing loss did not change post-operatively in all cases. The follow-up MR images demonstrated no recurrence of necrotic lesions in all 12 patients. Neurosurgical intervention through a temporal approach with linear incision is warranted in patients with radiation induced temporal lobe necrosis with significant symptoms and signs of increased intracranial pressure, minimum space occupying effect on imaging, or neurological deterioration despite conservative management. Copyright © 2016 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Medial prefrontal-hippocampal connectivity during emotional memory encoding predicts individual differences in the loss of associative memory specificity.

PubMed

Berkers, Ruud M W J; Klumpers, Floris; Fernández, Guillén

2016-10-01

Emotionally charged items are often remembered better, whereas a paradoxical loss of specificity is found for associative emotional information (specific memory). The balance between specific and generalized emotional memories appears to show large individual differences, potentially related to differences in (the risk for) affective disorders that are characterized by 'overgeneralized' emotional memories. Here, we investigate the neural underpinnings of individual differences in emotional associative memory. A large group of healthy male participants were scanned while encoding associations of face-photographs and written occupational identities that were of either neutral ('driver') or negative ('murderer') valence. Subsequently, memory was tested by prompting participants to retrieve the occupational identities corresponding to each face. Whereas in both valence categories a similar amount of faces was labeled correctly with 'neutral' and 'negative' identities, (gist memory), specific associations were found to be less accurately remembered when the occupational identity was negative compared to neutral (specific memory). This pattern of results suggests reduced memory specificity for associations containing a negatively valenced component. The encoding of these negative associations was paired with a selective increase in medial prefrontal cortex activity and medial prefrontal-hippocampal connectivity. Individual differences in valence-specific neural connectivity were predictive of valence-specific reduction of memory specificity. The relationship between loss of emotional memory specificity and medial prefrontal-hippocampal connectivity is in line with the hypothesized role of a medial prefrontal-hippocampal circuit in regulating memory specificity, and warrants further investigations in individuals displaying 'overgeneralized' emotional memories. Copyright © 2016 Elsevier Inc. All rights reserved.

Challenges in the Detection of Working Memory and Attention Decrements among Overweight Adolescent Girls.

PubMed

Bauer, Lance O; Manning, Kevin J

2016-01-01

The present study is unique in employing unusually difficult attention and working memory tasks to reveal subtle cognitive decrements among overweight/obese adolescents. It evaluated novel measures of background electroencephalographic (EEG) activity during one of the tasks and tested correlations of these and other measures with psychological and psychiatric predictors of obesity maintenance or progression. Working memory and sustained attention tasks were presented to 158 female adolescents who were rated on dichotomous (body mass index percentile <85 vs. ≥85) and continuous (triceps skinfold thickness) measures of adiposity. The results revealed a significant association between excess adiposity and performance errors during the working memory task. During the sustained attention task, overweight/obese adolescents exhibited more EEG frontal beta power as well as greater intraindividual variability in reaction time and beta power across task periods than their normal-weight peers. Secondary analyses showed that frontal beta power during the sustained attention task was positively correlated with anxiety, panic, borderline personality features, drug abuse, and loss of control over food intake. The findings suggest that working memory and sustained attention decrements do exist among overweight/obese adolescent girls. The reliable detection of the decrements may depend on the difficulty of the tasks as well as the manner in which performance and brain activity are measured. Future studies should examine the relevance of these decrements to dietary education efforts and treatment response. © 2016 S. Karger AG, Basel.

Miliary pattern of brain metastases - a case report of a hyperacute onset in a patient with malignant melanoma documented by magnetic resonance imaging.

PubMed

Reiter, Florian P; Giessen-Jung, Clemens; Dorostkar, Mario M; Ertl-Wagner, Birgit; Denk, Gerald U; Heck, Suzette; Rieger, Christina T; Pfister, Hans W; op den Winkel, Mark

2015-07-19

Miliary brain metastases are a rare condition but associated with an exceedingly poor prognosis. We present the case of a patient suffering from malignant melanoma with an acute progressively worsening of neurological symptoms up to the loss of consciousness. The magnetic resonance imaging (MRI) demonstrated a new onset of disseminated, miliary spread of central nervous system metastases from a malignant melanoma within 4 days. We report on a 57-year-old woman suffering from metastatic malignant melanoma positive for BRAF-V600E mutation who developed an acute onset of neurological symptoms. The patient received vemurafenib and dacarbacin as chemotherapeutic regime for treatment of malignant melanoma. After admission to our hospital due to progressive disturbance of memory and speech difficulty a magnetic resonance tomography (MRI) was performed. This showed no evidence of cerebral tumour manifestation. The symptoms progressed until a loss of consciousness occurred on day five after admission and the patient was admitted to our intensive care unit for orotracheal intubation. No evidence for infectious, metabolic or autoimmune cerebral disorders was found. Due to the inexplicable acute worsening of the neurological symptoms a second MRI was performed on day five. This revealed a new onset of innumerable contrast-enhancing miliary lesions, especially in the grey matter which was proven as metastases from malignant melanoma on histopathology. This case describes an unique hyperacute onset of tumour progression correlating with an acute deterioration of neurological symptoms in a patient suffering from miliary brain metastasis from BRAF positive malignant melanoma.

MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early-life adversity.

PubMed

Molet, Jenny; Maras, Pamela M; Kinney-Lang, Eli; Harris, Neil G; Rashid, Faisal; Ivy, Autumn S; Solodkin, Ana; Obenaus, Andre; Baram, Tallie Z

2016-12-01

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Caloric restriction and memory during aging].

PubMed

Marti-Nicolovius, M; Arevalo-Garcia, R

2018-06-16

To understand the underlying brain mechanisms involved in the aging process and mental deterioration could be key to the development of behavioral patterns that guarantee reaching advanced ages with the highest possible quality of life and reduce the cognitive loss associated with senescence. To describe and analyze different animal and human studies that demonstrate that a caloric restriction diet may rescue cerebral aging and the cognitive decline associated to aging. For more than 100 years it has been known that caloric restriction extends life span in many laboratory animal. This effect seems to derive from the reduction of age-related symptoms, such as obesity, the onset of cancerous tumors and some metabolic diseases. However, while the consequences of caloric restriction on health are well-established, their ability to reverse age-dependent memory deficits remains a controversial issue. The analyses of the effects of caloric restriction on different animals provides progress for the understanding of its beneficial effects on the neurobiology of cognitive processes during aging. Caloric restriction attenuates the normal or pathological aging of the brain and reduces age-related memory problems. Dietary intervention could become a very effective method to promote a better quality of life and prevent the age-related cognitive deficits.

Working memory and semantic involvement in sentence processing: a case of pure progressive amnesia.

PubMed

Fossard, Marion; Rigalleau, François; Puel, Michèle; Nespoulous, Jean-Luc; Viallard, Gérard; Démonet, Jean-François; Cardebat, Dominique

2006-01-01

ED, a 83-year-old woman, meets the criteria of pure progressive amnesia, with gradual impairment of episodic and autobiographical memory, sparing of semantic processing and strong working memory (WM) deficit. The dissociation between disturbed WM and spared semantic processing permitted testing the role of WM in processing anaphors like pronouns or repeated names. Results showed a globally normal anaphoric behavior in two experiments requiring anaphoric processing in sentence production and comprehension. We suggest that preserved semantic processing in ED would have compensated for working memory deficit in anaphoric processing.

Learning and memory in zebrafish larvae

PubMed Central

Roberts, Adam C.; Bill, Brent R.; Glanzman, David L.

2013-01-01

Larval zebrafish possess several experimental advantages for investigating the molecular and neural bases of learning and memory. Despite this, neuroscientists have only recently begun to use these animals to study memory. However, in a relatively short period of time a number of forms of learning have been described in zebrafish larvae, and significant progress has been made toward their understanding. Here we provide a comprehensive review of this progress; we also describe several promising new experimental technologies currently being used in larval zebrafish that are likely to contribute major insights into the processes that underlie learning and memory. PMID:23935566

Biomarker progressions explain higher variability in stage-specific cognitive decline than baseline values in Alzheimer disease.

PubMed

Dodge, Hiroko H; Zhu, Jian; Harvey, Danielle; Saito, Naomi; Silbert, Lisa C; Kaye, Jeffrey A; Koeppe, Robert A; Albin, Roger L

2014-11-01

It is unknown which commonly used Alzheimer disease (AD) biomarker values-baseline or progression-best predict longitudinal cognitive decline. 526 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI). ADNI composite memory and executive scores were the primary outcomes. Individual-specific slope of the longitudinal trajectory of each biomarker was first estimated. These estimates and observed baseline biomarker values were used as predictors of cognitive declines. Variability in cognitive declines explained by baseline biomarker values was compared with variability explained by biomarker progression values. About 40% of variability in memory and executive function declines was explained by ventricular volume progression among mild cognitive impairment patients. A total of 84% of memory and 65% of executive function declines were explained by fluorodeoxyglucose positron emission tomography (FDG-PET) score progression and ventricular volume progression, respectively, among AD patients. For most biomarkers, biomarker progressions explained higher variability in cognitive decline than biomarker baseline values. This has important implications for clinical trials targeted to modify AD biomarkers. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

Autoreactive Memory CD4+ T Lymphocytes that mediate Chronic Uveitis Reside in the Bone Marrow through STAT3-dependent Mechanisms

PubMed Central

Oh, Hyun-Mee; Yu, Cheng-Rong; Lee, YongJun; Chan, Chi-Chao; Maminishkis, Arvydas; Egwuagu, Charles E.

2011-01-01

Organ-specific autoimmune diseases are usually characterized by repeated cycles of remission and recurrent inflammation. However, where the autoreactive memory T-cells reside in-between episodes of recurrent inflammation is largely unknown. In this study, we have established a mouse model of chronic uveitis characterized by progressive photoreceptor-cell loss, retinal-degeneration, focal retinitis, retinal vasculitis, multifocal-choroiditis and choroidal neovascularization, providing for the first time a useful model for studying long-term pathological consequences of chronic inflammation of the neuroretina. We show that several months after inception of acute uveitis that autoreactive memory T-cells specific to retinal autoantigen, IRBP, relocated to bone marrow (BM). The IRBP-specific memory T-cells (IL-7RαHiLy6CHiCD4+) resided in BM in resting state but upon re-stimulation converted to IL-17-/IFN-γ-expressing effectors (IL-7RαLowLy6CLowCD4+) that mediated uveitis. We further show that T-cells from STAT3-deficient (CD4-STAT3KO) mice are defective in α4β1 and osteopontin expression; defects that correlated with inability of IRBP-specific memory CD4-STAT3KO T-cells to traffic into BM. We adoptively transferred uveitis to naïve mice using BM cells from WT mice with chronic uveitis but not BM cells from CD4-STAT3KO, providing direct evidence that memory T-cells that mediate uveitis reside in BM and that STAT3-dependent mechanism may be required for migration into and retention of memory T-cells in BM. Identifying BM as survival-niche for T-cells that cause uveitis, suggests that BM stromal cells that provide survival signals to autoreactive memory T-cells and STAT3-dependent mechanisms that mediate their relocation into BM, are attractive therapeutic targets that can be exploited to selectively deplete memory T-cells that drive chronic inflammation. PMID:21832158

How preserved is episodic memory in behavioral variant frontotemporal dementia?

PubMed

Hornberger, M; Piguet, O; Graham, A J; Nestor, P J; Hodges, J R

2010-02-09

Studies have shown variable memory performance in patients with behavioral variant frontotemporal dementia (bvFTD). Our study investigated whether this variability is due to the admixture of patients with true bvFTD and phenocopy patients. We also sought to compare performance of patients with bvFTD and patients with Alzheimer disease (AD). We analyzed neuropsychological memory performance in patients with a clinical diagnosis of bvFTD divided into those who progressed (n = 50) and those who remained stable (n = 39), patients with AD (n = 64), and healthy controls (n = 64). Patients with progressive bvFTD were impaired on most memory tests to a similar level to that of patients with early AD. Findings from a subset of patients with progressive bvFTD with confirmed FTLD pathology (n = 10) corroborated these findings. By contrast, patients with phenocopy bvFTD performed significantly better than progressors and patients with AD. Logistic regression revealed that patients with bvFTD can be distinguished to a high degree (85%) on the immediate recall score of a word list learning test (Rey Auditory Verbal Learning Test). Our results provide evidence for an underlying memory deficit in "real" or progressive behavioral variant frontotemporal dementia (bvFTD) similar to Alzheimer disease, though the groups differ in orientation scores, with patients with bvFTD being intact. Exclusion solely based on impaired neuropsychological memory performance can potentially lead to an underdiagnosis of FTD.

Motivation Matters: Differing Effects of Pre-Goal and Post-Goal Emotions on Attention and Memory

PubMed Central

Kaplan, Robin L.; Van Damme, Ilse; Levine, Linda J.

2012-01-01

People often show enhanced memory for information that is central to emotional events and impaired memory for peripheral details. The intensity of arousal elicited by an emotional event is commonly held to be the mechanism underlying memory narrowing, with the implication that all sources of emotional arousal should have comparable effects. Discrete emotions differ in their effects on memory, however, with some emotions broadening rather than narrowing the range of information attended to and remembered. Thus, features of emotion other than arousal appear to play a critical role in memory narrowing. We review theory and research on emotional memory narrowing and argue that motivation matters. Recent evidence suggests that emotions experienced prior to goal attainment or loss lead to memory narrowing whereas emotions experienced after goal attainment or loss broaden the range of information encoded in memory. The motivational component of emotion is an important but understudied feature that can help to clarify the conditions under which emotions enhance and impair attention and memory. PMID:23162490

Motivation matters: differing effects of pre-goal and post-goal emotions on attention and memory.

PubMed

Kaplan, Robin L; Van Damme, Ilse; Levine, Linda J

2012-01-01

People often show enhanced memory for information that is central to emotional events and impaired memory for peripheral details. The intensity of arousal elicited by an emotional event is commonly held to be the mechanism underlying memory narrowing, with the implication that all sources of emotional arousal should have comparable effects. Discrete emotions differ in their effects on memory, however, with some emotions broadening rather than narrowing the range of information attended to and remembered. Thus, features of emotion other than arousal appear to play a critical role in memory narrowing. We review theory and research on emotional memory narrowing and argue that motivation matters. Recent evidence suggests that emotions experienced prior to goal attainment or loss lead to memory narrowing whereas emotions experienced after goal attainment or loss broaden the range of information encoded in memory. The motivational component of emotion is an important but understudied feature that can help to clarify the conditions under which emotions enhance and impair attention and memory.

From network heterogeneities to familiarity detection and hippocampal memory management

PubMed Central

Wang, Jane X.; Poe, Gina; Zochowski, Michal

2009-01-01

Hippocampal-neocortical interactions are key to the rapid formation of novel associative memories in the hippocampus and consolidation to long term storage sites in the neocortex. We investigated the role of network correlates during information processing in hippocampal-cortical networks. We found that changes in the intrinsic network dynamics due to the formation of structural network heterogeneities alone act as a dynamical and regulatory mechanism for stimulus novelty and familiarity detection, thereby controlling memory management in the context of memory consolidation. This network dynamic, coupled with an anatomically established feedback between the hippocampus and the neocortex, recovered heretofore unexplained properties of neural activity patterns during memory management tasks which we observed during sleep in multiunit recordings from behaving animals. Our simple dynamical mechanism shows an experimentally matched progressive shift of memory activation from the hippocampus to the neocortex and thus provides the means to achieve an autonomous off-line progression of memory consolidation. PMID:18999453

Hyperactivity with Agitative-Like Behavior in a Mouse Tauopathy Model.

PubMed

Jul, Pia; Volbracht, Christiane; de Jong, Inge E M; Helboe, Lone; Elvang, Anders Brandt; Pedersen, Jan Torleif

2016-01-01

Tauopathies, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD), are characterized by formation of neurofibrillary tangles consisting of hyperphosphorylated tau. In addition to memory loss, patients experience behavioral symptoms such as agitation, aggression, depression, and insomnia. We explored the behavioral phenotype of a mouse model (rTg4510) carrying the human tau P301L mutation found in a familial form of FTD. We tested these mice in locomotor activity assays as well as in the Morris water maze to access spatial memory. In addition to cognitive impairments, rTg4510 mice exhibited a hyperactivity phenotype which correlated with progression of tau pathology and was dependent on P301L tau transgene expression. The hyperactive phenotype was characterized by significantly increased locomotor activity in a novel and in a simulated home cage environment together with a disturbed day/night cycle. The P301L-tau-dependent hyperactivity and agitative-like phenotype suggests that these mice may form a correlate to some of the behavioral disturbances observed in advanced AD and FTD.

Remembering tips

MedlinePlus

Memory aids; Alzheimer disease - remembering tips; Early memory loss - remembering tips; Dementia - remembering tips ... harder for your brain to create a new memory, even while you can remember actions and events ...

Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory.

PubMed

Foscarin, Simona; Raha-Chowdhury, Ruma; Fawcett, James W; Kwok, Jessica C F

2017-06-28

Chondroitin sulfate (CS) proteoglycans in perineuronal nets (PNNs) from the central nervous system (CNS) are involved in the control of plasticity and memory. Removing PNNs reactivates plasticity and restores memory in models of Alzheimer's disease and ageing. Their actions depend on the glycosaminoglycan (GAG) chains of CS proteoglycans, which are mainly sulfated in the 4 (C4S) or 6 (C6S) positions. While C4S is inhibitory, C6S is more permissive to axon growth, regeneration and plasticity. C6S decreases during critical period closure. We asked whether there is a late change in CS-GAG sulfation associated with memory loss in aged rats. Immunohistochemistry revealed a progressive increase in C4S and decrease in C6S from 3 to 18 months. GAGs extracted from brain PNNs showed a large reduction in C6S at 12 and 18 months, increasing the C4S/C6S ratio. There was no significant change in mRNA levels of the chondroitin sulfotransferases. PNN GAGs were more inhibitory to axon growth than those from the diffuse extracellular matrix. The 18-month PNN GAGs were more inhibitory than 3-month PNN GAGs. We suggest that the change in PNN GAG sulfation in aged brains renders the PNNs more inhibitory, which lead to a decrease in plasticity and adversely affect memory.

Copper chelator induced efficient episodic memory recovery in a non-transgenic Alzheimer's mouse model.

PubMed

Ceccom, Johnatan; Coslédan, Frédéric; Halley, Hélène; Francès, Bernard; Lassalle, Jean Michel; Meunier, Bernard

2012-01-01

Alzheimer's disease (AD) is a neurodegenerative syndrom involving many different biological parameters, including the accumulation of copper metal ions in Aβ amyloid peptides due to a perturbation of copper circulation and homeostasis within the brain. Copper-containing amyloids activated by endogenous reductants are able to generate an oxidative stress that is involved in the toxicity of abnormal amyloids and contribute to the progressive loss of neurons in AD. Since only few drugs are currently available for the treatment of AD, we decided to design small molecules able to interact with copper and we evaluated these drug-candidates with non-transgenic mice, since AD is mainly an aging disease, not related to genetic disorders. We created a memory deficit mouse model by a single icv injection of Aβ(1-42) peptide, in order to mimic the early stage of the disease and the key role of amyloid oligomers in AD. No memory deficit was observed in the control mice with the antisense Aβ(42-1) peptide. Here we report the capacity of a new copper-specific chelating agent, a bis-8-aminoquinoline PA1637, to fully reverse the deficit of episodic memory after three weeks of treatment by oral route on non-transgenic amyloid-impaired mice. Clioquinol and memantine have been used as comparators to validate this fast and efficient mouse model.

Dopamine loss alters the hippocampus-nucleus accumbens synaptic transmission in the Tg2576 mouse model of Alzheimer's disease.

PubMed

Cordella, Alberto; Krashia, Paraskevi; Nobili, Annalisa; Pignataro, Annabella; La Barbera, Livia; Viscomi, Maria Teresa; Valzania, Alessandro; Keller, Flavio; Ammassari-Teule, Martine; Mercuri, Nicola Biagio; Berretta, Nicola; D'Amelio, Marcello

2018-08-01

The functional loop involving the ventral tegmental area (VTA), dorsal hippocampus and nucleus accumbens (NAc) plays a pivotal role in the formation of spatial memory and persistent memory traces. In particular, the dopaminergic innervation from the VTA to the hippocampus is critical for hippocampal-related memory function and alterations in the midbrain dopaminergic system are frequently reported in Alzheimer's disease (AD), contributing to age-related decline in memory and non-cognitive functions. However, much less is known about the hippocampus-NAc connectivity in AD. Here, we evaluated the functioning of the hippocampus-to-NAc core connectivity in the Tg2576 mouse model of AD that shows a selective and progressive degeneration of VTA dopaminergic neurons. We show that reduced dopaminergic innervation in the Tg2576 hippocampus results in reduced synaptic plasticity and excitability of dorsal subiculum pyramidal neurons. Importantly, the glutamatergic transmission from the hippocampus to the NAc core is also impaired. Chemogenetic depolarisation of Tg2576 subicular pyramidal neurons with an excitatory Designer Receptor Exclusively Activated by Designer Drugs, or systemic administration of the DA precursor levodopa, can both rescue the deficits in Tg2576 mice. Our data suggest that the dopaminergic signalling in the hippocampus is essential for the proper functioning of the hippocampus-NAc excitatory synaptic transmission. Copyright © 2018 Elsevier Inc. All rights reserved.

Working memory, age, and hearing loss: susceptibility to hearing aid distortion.

PubMed

Arehart, Kathryn H; Souza, Pamela; Baca, Rosalinda; Kates, James M

2013-01-01

Hearing aids use complex processing intended to improve speech recognition. Although many listeners benefit from such processing, it can also introduce distortion that offsets or cancels intended benefits for some individuals. The purpose of the present study was to determine the effects of cognitive ability (working memory) on individual listeners' responses to distortion caused by frequency compression applied to noisy speech. The present study analyzed a large data set of intelligibility scores for frequency-compressed speech presented in quiet and at a range of signal-to-babble ratios. The intelligibility data set was based on scores from 26 adults with hearing loss with ages ranging from 62 to 92 years. The listeners were grouped based on working memory ability. The amount of signal modification (distortion) caused by frequency compression and noise was measured using a sound quality metric. Analysis of variance and hierarchical linear modeling were used to identify meaningful differences between subject groups as a function of signal distortion caused by frequency compression and noise. Working memory was a significant factor in listeners' intelligibility of sentences presented in babble noise and processed with frequency compression based on sinusoidal modeling. At maximum signal modification (caused by both frequency compression and babble noise), the factor of working memory (when controlling for age and hearing loss) accounted for 29.3% of the variance in intelligibility scores. Combining working memory, age, and hearing loss accounted for a total of 47.5% of the variability in intelligibility scores. Furthermore, as the total amount of signal distortion increased, listeners with higher working memory performed better on the intelligibility task than listeners with lower working memory did. Working memory is a significant factor in listeners' responses to total signal distortion caused by cumulative effects of babble noise and frequency compression implemented with sinusoidal modeling. These results, together with other studies focused on wide-dynamic range compression, suggest that older listeners with hearing loss and poor working memory are more susceptible to distortions caused by at least some types of hearing aid signal-processing algorithms and by noise, and that this increased susceptibility should be considered in the hearing aid fitting process.

Neuropsychological and brain volume differences in patients with left- and right-beginning corticobasal syndrome.

PubMed

Jütten, Kerstin; Pieperhoff, Peter; Südmeyer, Martin; Schleicher, Axel; Ferrea, Stefano; Caspers, Svenja; Zilles, Karl; Schnitzler, Alfons; Amunts, Katrin; Lux, Silke

2014-01-01

Corticobasal Syndrome (CBS) is a rare neurodegenerative syndrome characterized by unilaterally beginning frontoparietal and basal ganglia atrophy. The study aimed to prove the hypothesis that there are differences in hemispheric susceptibility to disease-related changes. Two groups of CBS patients with symptoms starting either on the left or right body side were investigated. Groups consisted of four patients each and were matched for sex, age and disease duration. Patient groups and a group of eight healthy age-matched controls were analyzed using deformation field morphometry and neuropsychological testing. To further characterize individual disease progression regarding brain atrophy and neuropsychological performance, two female, disease duration-matched patients differing in initially impaired body side were followed over six months. A distinct pattern of neural atrophy and neuropsychological performance was revealed for both CBS: Patients with initial right-sided impairment (r-CBS) revealed atrophy predominantly in frontoparietal areas and showed, except from apraxia, no other cognitive deficits. In contrast, patients with impairment of the left body side (l-CBS) revealed more widespread atrophy, extending from frontoparietal to orbitofrontal and temporal regions; and apraxia, perceptional and memory deficits could be found. A similar pattern of morphological and neuropsychological differences was found for the individual disease progression in l-CBS and r-CBS single cases. For similar durations of disease, volumetric grey matter loss related to CBS pathology appeared earlier and progressed faster in l-CBS than in r-CBS. Cognitive impairment in r-CBS was characterized by apraxia, and additional memory and perceptional deficits for l-CBS.

Memory--a century of consolidation.

PubMed

McGaugh, J L

2000-01-14

The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the time-dependent processes that create our lasting memories.

Does Working Memory Training Lead to Generalized Improvements in Children with Low Working Memory? A Randomized Controlled Trial

ERIC Educational Resources Information Center

Dunning, Darren L.; Holmes, Joni; Gathercole, Susan E.

2013-01-01

Children with low working memory typically make poor educational progress, and it has been speculated that difficulties in meeting the heavy working memory demands of the classroom may be a contributory factor. Intensive working memory training has been shown to boost performance on untrained memory tasks in a variety of populations. This first…

Neural Protein Synthesis during Aging: Effects on Plasticity and Memory

PubMed Central

Schimanski, Lesley A.; Barnes, Carol A.

2010-01-01

During aging, many experience a decline in cognitive function that includes memory loss. The encoding of long-term memories depends on new protein synthesis, and this is also reduced during aging. Thus, it is possible that changes in the regulation of protein synthesis contribute to the memory impairments observed in older animals. Several lines of evidence support this hypothesis. For instance, protein synthesis is required for a longer period following learning to establish long-term memory in aged rodents. Also, under some conditions, synaptic activity or pharmacological activation can induce de novo protein synthesis and lasting changes in synaptic transmission in aged, but not young, rodents; the opposite results can be observed in other conditions. These changes in plasticity likely play a role in manifesting the altered place field properties observed in awake and behaving aged rats. The collective evidence suggests a link between memory loss and the regulation of protein synthesis in senescence. In fact, pharmaceuticals that target the signaling pathways required for induction of protein synthesis have improved memory, synaptic plasticity, and place cell properties in aged animals. We suggest that a better understanding of the mechanisms that lead to different protein expression patterns in the neural circuits that change as a function of age will enable the development of more effective therapeutic treatments for memory loss. PMID:20802800

Memory enhancing drugs and Alzheimer's disease: enhancing the self or preventing the loss of it?

PubMed

Dekkers, Wim; Rikkert, Marcel Olde

2007-06-01

In this paper we analyse some ethical and philosophical questions related to the development of memory enhancing drugs (MEDs) and anti-dementia drugs. The world of memory enhancement is coloured by utopian thinking and by the desire for quicker, sharper, and more reliable memories. Dementia is characterized by decline, fragility, vulnerability, a loss of the most important cognitive functions and even a loss of self. While MEDs are being developed for self-improvement, in Alzheimer's Disease (AD) the self is being lost. Despite this it is precisely those patients with AD and other forms of dementia that provide the subjects for scientific research on memory improvement. Biomedical research in the field of MEDs and anti-dementia drugs appears to provide a strong impetus for rethinking what we mean by 'memory', 'enhancement', 'therapy', and 'self'. We conclude (1) that the enhancement of memory is still in its infancy, (2) that current MEDs and anti-dementia drugs are at best partially and minimally effective under specific conditions, (3) that 'memory' and 'enhancement' are ambiguous terms, (4) that there is no clear-cut distinction between enhancement and therapy, and (5) that the research into MEDs and anti-dementia drugs encourages a reductionistic view of the human mind and of the self.

Similar autobiographical memory impairment in long-term secondary progressive multiple sclerosis and Alzheimer's disease.

PubMed

Müller, S; Saur, R; Greve, B; Melms, A; Hautzinger, M; Fallgatter, A J; Leyhe, T

2013-02-01

Memory disturbance is a common symptom of multiple sclerosis (MS), but little is known about autobiographical memory deficits in the long-term course of different MS subtypes. Inflammatory activity and demyelination is pronounced in relapsing-remitting multiple sclerosis (RRMS) whereas, similar to Alzheimer's disease, neurodegeneration affecting autobiographical memory-associated areas is seen in secondary progressive multiple sclerosis (SPMS). In light of distinct disease mechanisms, we evaluated autobiographical memory in different MS subtypes and hypothesized similarities between elderly patients with SPMS and Alzheimer's disease. We used the Autobiographical Memory Interview to assess episodic and semantic autobiographical memory in 112 education- and gender-matched participants, including healthy controls and patients with RRMS, SPMS, amnesic mild cognitive impairment (aMCI) and early Alzheimer's dementia (AD). Patients with SPMS, AD, and aMCI, but not with RRMS, exhibited a pattern of episodic autobiographical memory impairment that followed Ribot's Law; older memories were better preserved than more recent memories. In contrast to aMCI and AD, neither SPMS nor RRMS was associated with semantic autobiographical memory impairment. Our neuropsychological findings suggest that episodic autobiographical memory is affected in long-term patients with SPMS, possibly due to neurodegenerative processes in functional relevant brain regions.

Neurocognitive Consequences of Sleep Deprivation

PubMed Central

Goel, Namni; Rao, Hengyi; Durmer, Jeffrey S.; Dinges, David F.

2012-01-01

Sleep deprivation is associated with considerable social, financial, and health-related costs, in large measure because it produces impaired cognitive performance due to increasing sleep propensity and instability of waking neurobehavioral functions. Cognitive functions particularly affected by sleep loss include psychomotor and cognitive speed, vigilant and executive attention, working memory, and higher cognitive abilities. Chronic sleep-restriction experiments—which model the kind of sleep loss experienced by many individuals with sleep fragmentation and premature sleep curtailment due to disorders and lifestyle—demonstrate that cognitive deficits accumulate to severe levels over time without full awareness by the affected individual. Functional neuroimaging has revealed that frequent and progressively longer cognitive lapses, which are a hallmark of sleep deprivation, involve distributed changes in brain regions including frontal and parietal control areas, secondary sensory processing areas, and thalamic areas. There are robust differences among individuals in the degree of their cognitive vulnerability to sleep loss that may involve differences in prefrontal and parietal cortices, and that may have a basis in genes regulating sleep homeostasis and circadian rhythms. Thus, cognitive deficits believed to be a function of the severity of clinical sleep disturbance may be a product of genetic alleles associated with differential cognitive vulnerability to sleep loss. PMID:19742409

Meditation as a Therapeutic Intervention for Adults at Risk for Alzheimer’s Disease – Potential Benefits and Underlying Mechanisms

PubMed Central

Innes, Kim E.; Selfe, Terry Kit

2014-01-01

Alzheimer’s disease (AD) is a chronic, progressive, brain disorder that affects at least 5.3 million Americans at an estimated cost of $148 billion, figures that are expected to rise steeply in coming years. Despite decades of research, there is still no cure for AD, and effective therapies for preventing or slowing progression of cognitive decline in at-risk populations remain elusive. Although the etiology of AD remains uncertain, chronic stress, sleep deficits, and mood disturbance, conditions common in those with cognitive impairment, have been prospectively linked to the development and progression of both chronic illness and memory loss and are significant predictors of AD. Therapies such as meditation that specifically target these risk factors may thus hold promise for slowing and possibly preventing cognitive decline in those at risk. In this study, we briefly review the existing evidence regarding the potential utility of meditation as a therapeutic intervention for those with and at risk for AD, discuss possible mechanisms underlying the observed benefits of meditation, and outline directions for future research. PMID:24795656

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.

Declarative memory and skill-related knowledge: Evidence from a case study of amnesia and implications for theories of memory.

PubMed

Gregory, Emma; McCloskey, Michael; Ovans, Zoe; Landau, Barbara

2016-01-01

Theoretical and empirical studies of memory have long been framed by a distinction between declarative and non-declarative memory. We question the sharpness of the distinction by reporting evidence from amnesic L.S.J., who despite retrograde memory losses in declarative knowledge domains, shows sparing of declarative knowledge related to premorbid skill (e.g., playing an instrument). We previously showed that L.S.J. had severe losses of retrograde declarative knowledge across areas of premorbid expertise (e.g., artists of famous works) and everyday knowledge (e.g., company names for logos). Here we present evidence that L.S.J. has sparing of what we call skill-related declarative knowledge, in four domains in which she had premorbid skill (art, music, aviation, driving). L.S.J.'s pattern of loss and sparing raises questions about the strict separation between classically-defined memory types and aligns with a recent proposal by Stanley and Krakauer [2013. Motor skill depends on knowledge of facts. Frontiers in Human Neuroscience, 7,1-11].

Microdose Induced Data Loss on Floating Gate Memories

NASA Technical Reports Server (NTRS)

Guertin, Steven M.; Nguyen, Duc M.; Patterson, Jeffrey D.

2006-01-01

Heavy ion irradiation of flash memories shows loss of stored data. The fluence dependence is indicative of microdose effects. Other qualitative factors identifying the effect as microdose are discussed. The data is presented, and compared to statistical results of a microdose target-based model.

Risk to verbal memory following anterior temporal lobectomy in patients with severe left-sided hippocampal sclerosis.

PubMed

Martin, Roy C; Kretzmer, Tracy; Palmer, Cheryl; Sawrie, Stephen; Knowlton, Robert; Faught, Edward; Morawetz, Richard; Kuzniecky, Ruben

2002-12-01

Previous investigations indicate low risk for memory loss following anterior temporal lobectomy (ATL) in patients with severe hippocampal sclerosis (HS) compared with patients with mild HS. However, these conclusions have been established primarily with group-level analyses. To investigate individual base rate risk for verbal memory loss following ATL in patients who have pathologically verified mild, moderate, or severe HS. One hundred fifteen patients with unilateral temporal lobe epilepsy (68 with left-sided and 47 with right-sided epilepsy) were included. Acquisition, retrieval, and recognition components of verbal memory, as measured by the California Verbal Learning Test, were assessed before and after ATL. Postoperatively, the degree of neuronal loss and reactive gliosis of the hippocampus was assessed via a 3-tiered rating system establishing mild, moderate, and severe pathologic features. Patients with preoperative magnetic resonance imaging-based evidence of lesions outside the mesial temporal area (side of surgical resection) were excluded. Neither seizure laterality nor severity of HS was associated with preoperative verbal memory performance. Postoperatively, the left-sided ATL group demonstrated significant decline across the acquisition (P<.01), retrival (P<.001), and recognition (P<.001) verbal memory components compared with the right-sided ATL group. Patients who underwent left-sided ATL and had mild HS displayed the largest magnitude and percentage proportion of postoperative decline across all verbal memory components. However, 28 (48%) of the 58 patients who underwent left-sided ATL and who had moderate and severe HS displayed statistically reliable declines on retrieval aspects of verbal memory. Most patients undergoing right-sided ATL, regardless of the extent of hippocampal pathologic features, displayed no postoperative memory change. Substantial individual heterogeneity of memory outcome exists across groups of patients undergoing ATL, with various degrees of pathologically verified HS. Patients undergoing left-sided ATL who have mild HS seem at greatest risk for broad-spectrum verbal memory decline. However, when examining outcome on a patient-by-patient basis, many patients undergoing left-sided ATL who have moderate to severe HS were also vulnerable to verbal memory loss. This risk seems selective to a retrieval-based aspect of verbal memory.

Microlaser-based compact optical neuro-processors (Invited Paper)

NASA Astrophysics Data System (ADS)

Paek, Eung Gi; Chan, Winston K.; Zah, Chung-En; Cheung, Kwok-wai; Curtis, L.; Chang-Hasnain, Constance J.

1992-10-01

This paper reviews the recent progress in the development of holographic neural networks using surface-emitting laser diode arrays (SELDAs). Since the previous work on ultrafast holographic memory readout system and a robust incoherent correlator, progress has been made in several areas: the use of an array of monolithic `neurons' to reconstruct holographic memories; two-dimensional (2-D) wavelength-division multiplexing (WDM) for image transmission through a single-mode fiber; and finally, an associative memory using time- division multiplexing (TDM). Experimental demonstrations on these are presented.

Reversal effects of crocin on amyloid β-induced memory deficit: Modification of autophagy or apoptosis markers.

PubMed

Asadi, Farideh; Jamshidi, Amir Hossein; Khodagholi, Fariba; Yans, Asal; Azimi, Leila; Faizi, Mehrdad; Vali, Leila; Abdollahi, Mohammad; Ghahremani, Mohammad Hossein; Sharifzadeh, Mohammad

2015-12-01

Crocin, as a carotenoid, is one of the main and active constituents of saffron stigmas (Crocus sativus L.) that is widely used in folk medicine. Several studies have pointed out the potent antioxidant and neuroprotective properties of crocin which may have therapeutic values for management of neurodegenerative disorders such as Alzheimer's disease. Alzheimer's disease is the most common form of dementia among the elderly and is characterized by massive neuronal loss and progressive cognitive impairment. Beta amyloid hypothesis is the main theoretical research framework for Alzheimer's disease which states that extracellular aggregation of beta amyloid results in synaptic loss and eventually cell apoptosis. Recent findings suggest that autophagy and apoptosis are extensively involved in Alzheimer's disease. In order to investigate therapeutic values of crocin, we examined the effect of crocin on memory, cell apoptosis, and autophagy using in vivo models of Alzheimer's disease. We also compared the effect of crocin administration on spatial memory with nicotine as positive control. Morris water maze results show that intra-peritoneal and intra-hippocampal administration of crocin significantly improve spatial memory indicators such as escape latency, traveled distance and time spent in target quadrant when compared to beta amyloid injection. Furthermore, we measured certain biomarkers of cell autophagy and apoptosis using Western blot analysis. Our results reveal that crocin administration does not cause any significant alteration in Beclin-1 and ratio of LC3-II/LC3-I compared to the group received beta amyloid by hippocampal injection. However, in contrast to autophagy, crocin administration significantly decreases Bax/Bcl-2 ratio and cleaved Caspase-3 level. This demonstrates that crocin inhibits beta amyloid induced apoptosis, which is possibly associated with its antioxidant properties. Our results further confirm the neuroprotective properties of crocin as a potential pharmaceutical agent for management of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits

PubMed Central

Tamayev, Robert; Matsuda, Shuji; Fà, Mauro; Arancio, Ottavio; D’Adamio, Luciano

2010-01-01

According to the prevailing “amyloid cascade hypothesis,” genetic dementias such as Alzheimer’s disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mechanisms cause Danish dementia. We studied an animal knock-in model of FDD (FDDKI/+) genetically congruous with human cases. FDDKI/+ mice present reduced Bri2 levels, impaired synaptic plasticity and severe hippocampal memory deficits. These animals show no cerebral lesions that are reputed characteristics of human dementia, such as tangles or amyloid plaques. Bri2+/− mice exhibit synaptic and memory deficits similar to FDDKI/+ mice, and memory loss of FDDKI/+ mice is prevented by expression of WT BRI2, indicating that Danish dementia is caused by loss of BRI2 function. Together, the data suggest that clinical dementia in Danish patients occurs via a loss of function mechanism and not as a result of amyloidosis and tauopathy. PMID:21098268

Danish dementia mice suggest that loss of function and not the amyloid cascade causes synaptic plasticity and memory deficits.

PubMed

Tamayev, Robert; Matsuda, Shuji; Fà, Mauro; Arancio, Ottavio; D'Adamio, Luciano

2010-11-30

According to the prevailing "amyloid cascade hypothesis," genetic dementias such as Alzheimer's disease and familial Danish dementia (FDD) are caused by amyloid deposits that trigger tauopathy, neurodegeneration, and behavioral/cognitive alterations. To efficiently reproduce amyloid lesions, murine models of human dementias invariably use transgenic expression systems. However, recent FDD transgenic models showed that Danish amyloidosis does not cause memory defects, suggesting that other mechanisms cause Danish dementia. We studied an animal knock-in model of FDD (FDD(KI/+)) genetically congruous with human cases. FDD(KI/+) mice present reduced Bri2 levels, impaired synaptic plasticity and severe hippocampal memory deficits. These animals show no cerebral lesions that are reputed characteristics of human dementia, such as tangles or amyloid plaques. Bri2(+/-) mice exhibit synaptic and memory deficits similar to FDD(KI/+) mice, and memory loss of FDD(KI/+) mice is prevented by expression of WT BRI2, indicating that Danish dementia is caused by loss of BRI2 function. Together, the data suggest that clinical dementia in Danish patients occurs via a loss of function mechanism and not as a result of amyloidosis and tauopathy.

Neuropathological Changes in Brain Cortex and Hippocampus in a Rat Model of Alzheimer’s Disease

PubMed Central

Nobakht, Maliheh; Hoseini, Seyed Mohammad; Mortazavi, Pejman; Sohrabi, Iraj; Esmailzade, Banafshe; Roosh, Nahid Rahbar; Omidzahir, Shila

2011-01-01

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder with progressive loss of cognitive abilities and memory loss. The aim of this study was to compare neuropathological changes in hippocampus and brain cortex in a rat model of AD. Methods: Adult male Albino Wistar rats (weighing 250-300 g) were used for behavioral and histopathological studies. The rats were randomly assigned to three groups: control, sham and β-amyloid (Aβ) injection. For behavioral analysis, Y-maze and shuttle box were used, respectively at 14 and 16 days post-lesion. For histological studies, Nissl, modified Bielschowsky and modified Congo red staining were performed. The lesion was induced by injection of 4 µL of Aβ (1-40) into the hippocampal fissure. Results: In the present study, Aβ (1-40) injection into hippocampus could decrease the behavioral indexes and the number of CA1 neurons in hippocampus. Aβ injection CA1 caused Aβ deposition in the hippocampus and less than in cortex. We observed the loss of neurons in the hippocampus and cerebral cortex and certain subcortical regions. Y-maze test and single-trial passive avoidance test showed reduced memory retention in AD group. Conclusion: We found a significant decreased acquisition of passive avoidance and alternation behavior responses in AD group compared to control and sham group (P<0.0001). Compacted amyloid cores were present in the cerebral cortex, hippocampus and white matter, whereas, scattered amyloid cores were seen in cortex and hippocampus of AD group. Also, reduced neuronal density was indicated in AD group. PMID:21725500

Astrocyte Transforming Growth Factor Beta 1 Protects Synapses against Aβ Oligomers in Alzheimer's Disease Model.

PubMed

Diniz, Luan Pereira; Tortelli, Vanessa; Matias, Isadora; Morgado, Juliana; Bérgamo Araujo, Ana Paula; Melo, Helen M; Seixas da Silva, Gisele S; Alves-Leon, Soniza V; de Souza, Jorge M; Ferreira, Sergio T; De Felice, Fernanda G; Gomes, Flávia Carvalho Alcantara

2017-07-12

Alzheimer's disease (AD) is characterized by progressive cognitive decline, increasingly attributed to neuronal dysfunction induced by amyloid-β oligomers (AβOs). Although the impact of AβOs on neurons has been extensively studied, only recently have the possible effects of AβOs on astrocytes begun to be investigated. Given the key roles of astrocytes in synapse formation, plasticity, and function, we sought to investigate the impact of AβOs on astrocytes, and to determine whether this impact is related to the deleterious actions of AβOs on synapses. We found that AβOs interact with astrocytes, cause astrocyte activation and trigger abnormal generation of reactive oxygen species, which is accompanied by impairment of astrocyte neuroprotective potential in vitro We further show that both murine and human astrocyte conditioned media (CM) increase synapse density, reduce AβOs binding, and prevent AβO-induced synapse loss in cultured hippocampal neurons. Both a neutralizing anti-transforming growth factor-β1 (TGF-β1) antibody and siRNA-mediated knockdown of TGF-β1, previously identified as an important synaptogenic factor secreted by astrocytes, abrogated the protective action of astrocyte CM against AβO-induced synapse loss. Notably, TGF-β1 prevented hippocampal dendritic spine loss and memory impairment in mice that received an intracerebroventricular infusion of AβOs. Results suggest that astrocyte-derived TGF-β1 is part of an endogenous mechanism that protects synapses against AβOs. By demonstrating that AβOs decrease astrocyte ability to protect synapses, our results unravel a new mechanism underlying the synaptotoxic action of AβOs in AD. SIGNIFICANCE STATEMENT Alzheimer's disease is characterized by progressive cognitive decline, mainly attributed to synaptotoxicity of the amyloid-β oligomers (AβOs). Here, we investigated the impact of AβOs in astrocytes, a less known subject. We show that astrocytes prevent synapse loss induced by AβOs, via production of transforming growth factor-β1 (TGF-β1). We found that AβOs trigger morphological and functional alterations in astrocytes, and impair their neuroprotective potential. Notably, TGF-β1 reduced hippocampal dendritic spine loss and memory impairment in mice that received intracerebroventricular infusions of AβOs. Our results describe a new mechanism underlying the toxicity of AβOs and indicate novel therapeutic targets for Alzheimer's disease, mainly focused on TGF-β1 and astrocytes. Copyright © 2017 the authors 0270-6474/17/376798-13$15.00/0.

Working memory and executive function decline across normal aging, mild cognitive impairment, and Alzheimer's disease.

PubMed

Kirova, Anna-Mariya; Bays, Rebecca B; Lagalwar, Sarita

2015-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease marked by deficits in episodic memory, working memory (WM), and executive function. Examples of executive dysfunction in AD include poor selective and divided attention, failed inhibition of interfering stimuli, and poor manipulation skills. Although episodic deficits during disease progression have been widely studied and are the benchmark of a probable AD diagnosis, more recent research has investigated WM and executive function decline during mild cognitive impairment (MCI), also referred to as the preclinical stage of AD. MCI is a critical period during which cognitive restructuring and neuroplasticity such as compensation still occur; therefore, cognitive therapies could have a beneficial effect on decreasing the likelihood of AD progression during MCI. Monitoring performance on working memory and executive function tasks to track cognitive function may signal progression from normal cognition to MCI to AD. The present review tracks WM decline through normal aging, MCI, and AD to highlight the behavioral and neurological differences that distinguish these three stages in an effort to guide future research on MCI diagnosis, cognitive therapy, and AD prevention.

Neurobiology of the aging dog.

PubMed

Head, Elizabeth

2011-09-01

Aged canines naturally accumulate several types of neuropathology that may have links to cognitive decline. On a gross level, significant cortical atrophy occurs with age along with an increase in ventricular volume based on magnetic resonance imaging studies. Microscopically, there is evidence of select neuron loss and reduced neurogenesis in the hippocampus of aged dogs, an area critical for intact learning and memory. The cause of neuronal loss and dysfunction may be related to the progressive accumulation of toxic proteins, oxidative damage, cerebrovascular pathology, and changes in gene expression. For example, aged dogs naturally accumulate human-type beta-amyloid peptide, a protein critically involved with the development of Alzheimer's disease in humans. Further, oxidative damage to proteins, DNA/RNA and lipids occurs with age in dogs. Although less well explored in the aged canine brain, neuron loss, and cerebrovascular pathology observed with age are similar to human brain aging and may also be linked to cognitive decline. Interestingly, the prefrontal cortex appears to be particularly vulnerable early in the aging process in dogs and this may be reflected in dysfunction in specific cognitive domains with age.

Si-based optical I/O for optical memory interface

NASA Astrophysics Data System (ADS)

Ha, Kyoungho; Shin, Dongjae; Byun, Hyunil; Cho, Kwansik; Na, Kyoungwon; Ji, Hochul; Pyo, Junghyung; Hong, Seokyong; Lee, Kwanghyun; Lee, Beomseok; Shin, Yong-hwack; Kim, Junghye; Kim, Seong-gu; Joe, Insung; Suh, Sungdong; Choi, Sanghoon; Han, Sangdeok; Park, Yoondong; Choi, Hanmei; Kuh, Bongjin; Kim, Kichul; Choi, Jinwoo; Park, Sujin; Kim, Hyeunsu; Kim, Kiho; Choi, Jinyong; Lee, Hyunjoo; Yang, Sujin; Park, Sungho; Lee, Minwoo; Cho, Minchang; Kim, Saebyeol; Jeong, Taejin; Hyun, Seokhun; Cho, Cheongryong; Kim, Jeong-kyoum; Yoon, Hong-gu; Nam, Jeongsik; Kwon, Hyukjoon; Lee, Hocheol; Choi, Junghwan; Jang, Sungjin; Choi, Joosun; Chung, Chilhee

2012-01-01

Optical interconnects may provide solutions to the capacity-bandwidth trade-off of recent memory interface systems. For cost-effective optical memory interfaces, Samsung Electronics has been developing silicon photonics platforms on memory-compatible bulk-Si 300-mm wafers. The waveguide of 0.6 dB/mm propagation loss, vertical grating coupler of 2.7 dB coupling loss, modulator of 10 Gbps speed, and Ge/Si photodiode of 12.5 Gbps bandwidth have been achieved on the bulk-Si platform. 2x6.4 Gbps electrical driver circuits have been also fabricated using a CMOS process.

Considering the role of semantic memory in episodic future thinking: evidence from semantic dementia.

PubMed

Irish, Muireann; Addis, Donna Rose; Hodges, John R; Piguet, Olivier

2012-07-01

Semantic dementia is a progressive neurodegenerative condition characterized by the profound and amodal loss of semantic memory in the context of relatively preserved episodic memory. In contrast, patients with Alzheimer's disease typically display impairments in episodic memory, but with semantic deficits of a much lesser magnitude than in semantic dementia. Our understanding of episodic memory retrieval in these cohorts has greatly increased over the last decade, however, we know relatively little regarding the ability of these patients to imagine and describe possible future events, and whether episodic future thinking is mediated by divergent neural substrates contingent on dementia subtype. Here, we explored episodic future thinking in patients with semantic dementia (n=11) and Alzheimer's disease (n=11), in comparison with healthy control participants (n=10). Participants completed a battery of tests designed to probe episodic and semantic thinking across past and future conditions, as well as standardized tests of episodic and semantic memory. Further, all participants underwent magnetic resonance imaging. Despite their relatively intact episodic retrieval for recent past events, the semantic dementia cohort showed significant impairments for episodic future thinking. In contrast, the group with Alzheimer's disease showed parallel deficits across past and future episodic conditions. Voxel-based morphometry analyses confirmed that atrophy in the left inferior temporal gyrus and bilateral temporal poles, regions strongly implicated in semantic memory, correlated significantly with deficits in episodic future thinking in semantic dementia. Conversely, episodic future thinking performance in Alzheimer's disease correlated with atrophy in regions associated with episodic memory, namely the posterior cingulate, parahippocampal gyrus and frontal pole. These distinct neuroanatomical substrates contingent on dementia group were further qualified by correlational analyses that confirmed the relation between semantic memory deficits and episodic future thinking in semantic dementia, in contrast with the role of episodic memory deficits and episodic future thinking in Alzheimer's disease. Our findings demonstrate that semantic knowledge is critical for the construction of novel future events, providing the necessary scaffolding into which episodic details can be integrated. Further research is necessary to elucidate the precise contribution of semantic memory to future thinking, and to explore how deficits in self-projection manifest on behavioural and social levels in different dementia subtypes.

Psychogenic amnesia: syndromes, outcome, and patterns of retrograde amnesia.

PubMed

Harrison, Neil A; Johnston, Kate; Corno, Federica; Casey, Sarah J; Friedner, Kimberley; Humphreys, Kate; Jaldow, Eli J; Pitkanen, Mervi; Kopelman, Michael D

2017-09-01

There are very few case series of patients with acute psychogenic memory loss (also known as dissociative/functional amnesia), and still fewer studies of outcome, or comparisons with neurological memory-disordered patients. Consequently, the literature on psychogenic amnesia is somewhat fragmented and offers little prognostic value for individual patients. In the present study, we reviewed the case records and neuropsychological findings in 53 psychogenic amnesia cases (ratio of 3:1, males:females), in comparison with 21 consecutively recruited neurological memory-disordered patients and 14 healthy control subjects. In particular, we examined the pattern of retrograde amnesia on an assessment of autobiographical memory (the Autobiographical Memory Interview). We found that our patients with psychogenic memory loss fell into four distinct groups, which we categorized as: (i) fugue state; (ii) fugue-to-focal retrograde amnesia; (iii) psychogenic focal retrograde amnesia following a minor neurological episode; and (iv) patients with gaps in their memories. While neurological cases were characterized by relevant neurological symptoms, a history of a past head injury was actually more common in our psychogenic cases (P = 0.012), perhaps reflecting a 'learning episode' predisposing to later psychological amnesia. As anticipated, loss of the sense of personal identity was confined to the psychogenic group. However, clinical depression, family/relationship problems, financial/employment problems, and failure to recognize the family were also statistically more common in that group. The pattern of autobiographical memory loss differed between the psychogenic groups: fugue cases showed a severe and uniform loss of memories for both facts and events across all time periods, whereas the two focal retrograde amnesia groups showed a 'reversed' temporal gradient with relative sparing of recent memories. After 3-6 months, the fugue patients had improved to normal scores for facts and near-normal scores for events. By contrast, the two focal retrograde amnesia groups showed less improvement and continued to show a reversed temporal gradient. In conclusion, the outcome in psychogenic amnesia, particularly those characterized by fugue, is better than generally supposed. Findings are interpreted in terms of Markowitsch's and Kopelman's models of psychogenic amnesia, and with respect to Anderson's neuroimaging findings in memory inhibition. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

What drives sleep-dependent memory consolidation: greater gain or less loss?

PubMed

Fenn, Kimberly M; Hambrick, David Z

2013-06-01

When memory is tested after a delay, performance is typically better if the retention interval includes sleep. However, it is unclear what accounts for this well-established effect. It is possible that sleep enhances the retrieval of information, but it is also possible that sleep protects against memory loss that normally occurs during waking activity. We developed a new research approach to investigate these possibilities. Participants learned a list of paired-associate items and were tested on the items after a 12-h interval that included waking or sleep. We analyzed the number of items gained versus the number of items lost across time. The sleep condition showed more items gained and fewer items lost than did the wake condition. Furthermore, the difference between the conditions (favoring sleep) in lost items was greater than the difference in gain, suggesting that loss prevention may primarily account for the effect of sleep on declarative memory consolidation. This finding may serve as an empirical constraint on theories of memory consolidation.

Working memory, short-term memory and reading proficiency in school-age children with cochlear implants.

PubMed

Bharadwaj, Sneha V; Maricle, Denise; Green, Laura; Allman, Tamby

2015-10-01

The objective of the study was to examine short-term memory and working memory through both visual and auditory tasks in school-age children with cochlear implants. The relationship between the performance on these cognitive skills and reading as well as language outcomes were examined in these children. Ten children between the ages of 7 and 11 years with early-onset bilateral severe-profound hearing loss participated in the study. Auditory and visual short-term memory, auditory and visual working memory subtests and verbal knowledge measures were assessed using the Woodcock Johnson III Tests of Cognitive Abilities, the Wechsler Intelligence Scale for Children-IV Integrated and the Kaufman Assessment Battery for Children II. Reading outcomes were assessed using the Woodcock Reading Mastery Test III. Performance on visual short-term memory and visual working memory measures in children with cochlear implants was within the average range when compared to the normative mean. However, auditory short-term memory and auditory working memory measures were below average when compared to the normative mean. Performance was also below average on all verbal knowledge measures. Regarding reading outcomes, children with cochlear implants scored below average for listening and passage comprehension tasks and these measures were positively correlated to visual short-term memory, visual working memory and auditory short-term memory. Performance on auditory working memory subtests was not related to reading or language outcomes. The children with cochlear implants in this study demonstrated better performance in visual (spatial) working memory and short-term memory skills than in auditory working memory and auditory short-term memory skills. Significant positive relationships were found between visual working memory and reading outcomes. The results of the study provide support for the idea that WM capacity is modality specific in children with hearing loss. Based on these findings, reading instruction that capitalizes on the strengths in visual short-term memory and working memory is suggested for young children with early-onset hearing loss. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Visual Memory for Objects Following Foveal Vision Loss

ERIC Educational Resources Information Center

Geringswald, Franziska; Herbik, Anne; Hofmüller, Wolfram; Hoffmann, Michael B.; Pollmann, Stefan

2015-01-01

Allocation of visual attention is crucial for encoding items into visual long-term memory. In free vision, attention is closely linked to the center of gaze, raising the question whether foveal vision loss entails suboptimal deployment of attention and subsequent impairment of object encoding. To investigate this question, we examined visual…

Loss and persistence of implicit memory for sound: evidence from auditory stream segregation context effects.

PubMed

Snyder, Joel S; Weintraub, David M

2013-07-01

An important question is the extent to which declines in memory over time are due to passive loss or active interference from other stimuli. The purpose of the present study was to determine the extent to which implicit memory effects in the perceptual organization of sound sequences are subject to loss and interference. Toward this aim, we took advantage of two recently discovered context effects in the perceptual judgments of sound patterns, one that depends on stimulus features of previous sounds and one that depends on the previous perceptual organization of these sounds. The experiments measured how listeners' perceptual organization of a tone sequence (test) was influenced by the frequency separation, or the perceptual organization, of the two preceding sequences (context1 and context2). The results demonstrated clear evidence for loss of context effects over time but little evidence for interference. However, they also revealed that context effects can be surprisingly persistent. The robust effects of loss, followed by persistence, were similar for the two types of context effects. We discuss whether the same auditory memories might contain information about basic stimulus features of sounds (i.e., frequency separation), as well as the perceptual organization of these sounds.

Recovering and Preventing Loss of Detailed Memory: Differential Rates of Forgetting for Detail Types in Episodic Memory

ERIC Educational Resources Information Center

Sekeres, Melanie J.; Bonasia, Kyra; St-Laurent, Marie; Pishdadian, Sara; Winocur, Gordon; Grady, Cheryl; Moscovitch, Morris

2016-01-01

Episodic memories undergo qualitative changes with time, but little is known about how different aspects of memory are affected. Different types of information in a memory, such as perceptual detail, and central themes, may be lost at different rates. In patients with medial temporal lobe damage, memory for perceptual details is severely impaired,…

Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging.

PubMed

Albayram, Onder; Alferink, Judith; Pitsch, Julika; Piyanova, Anastasia; Neitzert, Kim; Poppensieker, Karola; Mauer, Daniela; Michel, Kerstin; Legler, Anne; Becker, Albert; Monory, Krisztina; Lutz, Beat; Zimmer, Andreas; Bilkei-Gorzo, Andras

2011-07-05

Brain aging is associated with cognitive decline that is accompanied by progressive neuroinflammatory changes. The endocannabinoid system (ECS) is involved in the regulation of glial activity and influences the progression of age-related learning and memory deficits. Mice lacking the Cnr1 gene (Cnr1(-/-)), which encodes the cannabinoid receptor 1 (CB1), showed an accelerated age-dependent deficit in spatial learning accompanied by a loss of principal neurons in the hippocampus. The age-dependent decrease in neuronal numbers in Cnr1(-/-) mice was not related to decreased neurogenesis or to epileptic seizures. However, enhanced neuroinflammation characterized by an increased density of astrocytes and activated microglia as well as an enhanced expression of the inflammatory cytokine IL-6 during aging was present in the hippocampus of Cnr1(-/-) mice. The ongoing process of pyramidal cell degeneration and neuroinflammation can exacerbate each other and both contribute to the cognitive deficits. Deletion of CB1 receptors from the forebrain GABAergic, but not from the glutamatergic neurons, led to a similar neuronal loss and increased neuroinflammation in the hippocampus as observed in animals lacking CB1 receptors in all cells. Our results suggest that CB1 receptor activity on hippocampal GABAergic neurons protects against age-dependent cognitive decline by reducing pyramidal cell degeneration and neuroinflammation.

Hippocampus at 25

PubMed Central

Eichenbaum, Howard; Amaral, David G.; Buffalo, Elizabeth A.; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G. M.; Moser, Edvard I.; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

2017-01-01

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. PMID:27399159

Patients with Mild Alzheimer's Disease Fail When Using Their Working Memory: Evidence from the Eye Tracking Technique.

PubMed

Fernández, Gerardo; Manes, Facundo; Politi, Luis E; Orozco, David; Schumacher, Marcela; Castro, Liliana; Agamennoni, Osvaldo; Rotstein, Nora P

2016-01-01

Patients with Alzheimer's disease (AD) develop progressive language, visuoperceptual, attentional, and oculomotor changes that can have an impact on their reading comprehension. However, few studies have examined reading behavior in AD, and none have examined the contribution of predictive cueing in reading performance. For this purpose we analyzed the eye movement behavior of 35 healthy readers (Controls) and 35 patients with probable AD during reading of regular and high-predictable sentences. The cloze predictability of words N - 1, and N + 1 exerted an influence on the reader's gaze duration. The predictabilities of preceding words in high-predictable sentences served as task-appropriate cues that were used by Control readers. In contrast, these effects were not present in AD patients. In Controls, changes in predictability significantly affected fixation duration along the sentence; noteworthy, these changes did not affect fixation durations in AD patients. Hence, only in healthy readers did predictability of upcoming words influence fixation durations via memory retrieval. Our results suggest that Controls used stored information of familiar texts for enhancing their reading performance and imply that contextual-word predictability, whose processing is proposed to require memory retrieval, only affected reading behavior in healthy subjects. In AD patients, this loss reveals impairments in brain areas such as those corresponding to working memory and memory retrieval. These findings might be relevant for expanding the options for the early detection and monitoring in the early stages of AD. Furthermore, evaluation of eye movements during reading could provide a new tool for measuring drug impact on patients' behavior.

Loss of Maged1 results in obesity, deficits of social interactions, impaired sexual behavior and severe alteration of mature oxytocin production in the hypothalamus.

PubMed

Dombret, Carlos; Nguyen, Tuan; Schakman, Olivier; Michaud, Jacques L; Hardin-Pouzet, Hélène; Bertrand, Mathieu J M; De Backer, Olivier

2012-11-01

MAGED1, NECDIN and MAGEL2 are members of the MAGE gene family. The latter two of these genes have been involved in Prader-Willi syndrome (PWS), which includes hyperphagia, repetitive and compulsive behaviors, and cognitive impairment. Here, we show that Maged1-deficient mice develop progressive obesity associated with hyperphagia and reduced motor activity. Loss of Maged1 also results in a complex behavioral syndrome that includes reduced social interactions and memory, deficient sexual behavior, as well as increased anxiety and self-grooming. Oxytocin (OT), which is produced in the hypothalamus, can act as a neurotransmitter that reduces anxiety, promotes social behaviors and regulates food intake. Growing evidences indicate that OT is involved in autism. We found that Maged1 mutants showed a severe reduction in the levels of mature OT, but not of its precursors, in the hypothalamus. Moreover, the administration of OT rescued the deficit in social memory of these mice. We conclude that Maged1 is required for OT processing or stability. A decrease in mature OT levels in Maged1 mutants affects social interactions and possibly other behavioral processes. Our observations suggest that, in human, MAGED1 could play a role in autism or cause a neurodevelopmental condition that is reminiscent of the PWS.

Hydrocephalus as a rare compilation of vertebrobasilar dolichoectasia: A case report and review of the literature.

PubMed

Ebrahimzadeh, Keveh; Bakhtevari, Mehrdad H; Shafizad, Misagh; Rezaei, Omidvar

2017-01-01

Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Hydrocephalus is a rare compilation of VBD. In this study, we report a 68-year-old male presenting with headache, progressive decreased visual acuity, memory loss, imbalance while walking, and episodes of urinary incontinency. The patient was diagnosed with dolichoectasia of basilar artery causing compression of the third ventricular outflow and thus, presenting with hydrocephalus documented with brain computed tomography scan and brain magnetic resonance imaging. The patient underwent surgical operation and ventriculoperitoneal shunt placement. In the case of hydrocephalus or normal pressure hydrocephalous, VBD should be considered as a differential diagnosis.

New Rule Use Drives the Relation between Working Memory Capacity and Raven's Advanced Progressive Matrices

ERIC Educational Resources Information Center

Wiley, Jennifer; Jarosz, Andrew F.; Cushen, Patrick J.; Colflesh, Gregory J. H.

2011-01-01

The correlation between individual differences in working memory capacity and performance on the Raven's Advanced Progressive Matrices (RAPM) is well documented yet poorly understood. The present work proposes a new explanation: that the need to use a new combination of rules on RAPM problems drives the relation between performance and working…

Linalool Ameliorates Memory Loss and Behavioral Impairment Induced by REM-Sleep Deprivation through the Serotonergic Pathway.

PubMed

Lee, Bo Kyung; Jung, An Na; Jung, Yi-Sook

2018-07-01

Rapid eye movement (REM) sleep has an essential role in the process of learning and memory in the hippocampus. It has been reported that linalool, a major component of Lavandula angustifolia , has antioxidant, anti-inflammatory, and neuroprotective effects, along with other effects. However, the effect of linalool on the cognitive impairment and behavioral alterations that are induced by REM-sleep deprivation has not yet been elucidated. Several studies have reported that REM-sleep deprivation-induced memory deficits provide a well-known model of behavioral alterations. In the present study, we examined whether linalool elicited an anti-stress effect, reversing the behavioral alterations observed following REM-sleep deprivation in mice. Furthermore, we investigated the underlying mechanism of the effect of linalool. Spatial memory and learning memory were assessed through Y maze and passive avoidance tests, respectively, and the forced swimming test was used to evaluate anti-stress activity. The mechanisms through which linalool improves memory loss and behavioral alterations in sleep-deprived mice appeared to be through an increase in the serotonin levels. Linalool significantly ameliorated the spatial and learning memory deficits, and stress activity observed in sleep-deprived animals. Moreover, linalool led to serotonin release, and cortisol level reduction. Our findings suggest that linalool has beneficial effects on the memory loss and behavioral alterations induced by REM-sleep deprivation through the regulation of serotonin levels.

Motivation for weight loss affects recall from autobiographical memory in dieters.

PubMed

Johannessen, Kim Berg; Berntsen, Dorthe

2009-01-01

Two studies examined the connection between motivation for weight loss and autobiographical memory by comparing characteristics of autobiographical memories between dieters and non-dieters. Study 1 involved 29 normal/overweight dieters and 48 non-dieters, and Study 2 involved 18 obese dieters and 18 normal weight non-dieters. Memories recalled in response to dieting-related cue words were rated as more central to the person's identity and life story and contained more body- or weight-related elements for the dieters than the non-dieters. No differences between dieters and non-dieters were found on memories recalled in response to neutral cue words. The findings are discussed in relation to the notions of the working self (Conway & Pleydell-Pearce, 2000) and current concerns (Klinger, 1978).

Memory impairment is associated with the loss of regular oestrous cycle and plasma oestradiol levels in an activity-based anorexia animal model.

PubMed

Paulukat, Lisa; Frintrop, Linda; Liesbrock, Johanna; Heussen, Nicole; Johann, Sonja; Exner, Cornelia; Kas, Martien J; Tolba, Rene; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

2016-06-01

Patients with anorexia nervosa (AN) suffer from neuropsychological deficits including memory impairments. Memory partially depends on 17β-oestradiol (E2), which is reduced in patients with AN. We assessed whether memory functions correlate with E2 plasma levels in the activity-based anorexia (ABA) rat model. Nine 4-week-old female Wistar rats were sacrificed directly after weight loss of 20-25% (acute starvation), whereas 17 animals had additional 2-week weight-holding (chronic starvation). E2 serum levels and novel object recognition tasks were tested before and after starvation and compared with 21 normally fed controls. Starvation disrupted menstrual cycle and impaired memory function, which became statistically significant in the chronic state (oestrous cycle (P < 0.001), E2 levels (P = 0.011) and object recognition memory (P = 0.042) compared to controls). E2 reduction also correlated with the loss of memory in the chronic condition (r = 0.633, P = 0.020). Our results demonstrate that starvation reduces the E2 levels which are associated with memory deficits in ABA rats. These effects might explain reduced memory capacity in patients with AN as a consequence of E2 deficiency and the potentially limited effectiveness of psychotherapeutic interventions in the starved state. Future studies should examine whether E2 substitution could prevent cognitive deficits and aid in earlier readiness for therapy.

Progression is caused by angiotensin II-dependent persistent podocyte loss from destabilized glomeruli

PubMed Central

Fukuda, Akihiro; Wickman, Larysa T.; Venkatareddy, Madhusudan; Sato, Yuji; Chowdhury, Mahboob; Wang, Su Q; Shedden, Kerby; Dysko, Robert; Wiggins, Jocelyn E.; Wiggins, Roger C.

2013-01-01

Podocyte depletion is a major mechanism driving glomerulosclerosis. Progression is the process by which progressive glomerulosclerosis leads to End Stage Kidney Disease (ESKD). We therefore tested the hypothesis that progression to ESKD can be caused by persistent podocyte loss using the human diphtheria toxin transgenic rat model. After initial podocyte injury causing >30% loss of podocytes glomeruli became destabilized, resulting in continuous podocyte loss over time until global podocyte depletion (ESKD) occured. Similar patterns of podocyte depletion were observed in the puromycin aminonucleoside and 5/6 nephrectomy rat models of progression. Angiotensin II blockade prevented continuous podocyte loss and progression (restabilized glomeruli). Discontinuing angiotensin II blockade resulted in recurrent glomerular destabilization, podocyte loss and progression. Reduction in blood pressure alone did not reduce proteinuria or prevent podocyte loss from destabilized glomeruli. The protective effect of angiotensin II blockade could be entirely accounted for by reduction in podocyte loss. These data demonstrate that an initiating event that results in a critical degree of podocyte depletion can destabilize glomeruli by setting in train a superimposed angiotensin II-dependent podocyte loss cycle that accelerates the progression process and results in global podocyte depletion and progression to ESKD. These events can be monitored non-invasively through urine mRNA assays. PMID:21937979

Evaluation of a Memory Book intervention with orphaned children in South Africa.

PubMed

Braband, Barbara J; Faris, Tamara; Wilson-Anderson, Kaye

2014-01-01

The purpose of this collaborative research study was to evaluate the use of the Memory Book intervention for orphaned children's grief and loss recovery. A qualitative phenomenological approach was implemented to evaluate the Memory Book intervention with orphaned children at two children's homes in South Africa. Study findings support the ability of children to work through loss and grief when they are assisted in preserving and telling their story. The Memory Book intervention assists children to chronicle their lives and demonstrates the potential to guide future interventions by care providers and nurses in this context. Copyright © 2014 Elsevier Inc. All rights reserved.

Realization of transient memory-loss with NiO-based resistive switching device

NASA Astrophysics Data System (ADS)

Hu, S. G.; Liu, Y.; Chen, T. P.; Liu, Z.; Yu, Q.; Deng, L. J.; Yin, Y.; Hosaka, Sumio

2012-11-01

A resistive switching device based on a nickel-rich nickel oxide thin film, which exhibits inherent learning and memory-loss abilities, is reported in this work. The conductance of the device gradually increases and finally saturates with the number of voltage pulses (or voltage sweepings), which is analogous to the behavior of the short-term and long-term memory in the human brain. Furthermore, the number of the voltage pulses (or sweeping cycles) required to achieve a given conductance state increases with the interval between two consecutive voltage pulses (or sweeping cycles), which is attributed to the heat diffusion in the material of the conductive filaments formed in the nickel oxide thin film. The phenomenon resembles the behavior of the human brain, i.e., forgetting starts immediately after an impression, a larger interval of the impressions leads to more memory loss, thus the memorization needs more impressions to enhance.

Making Physical Activity Accessible to Older Adults with Memory Loss: A Feasibility Study

ERIC Educational Resources Information Center

Logsdon, Rebecca G.; McCurry, Susan M.; Pike, Kenneth C.; Teri, Linda

2009-01-01

Purpose: For individuals with mild cognitive impairment (MCI), memory loss may prevent successful engagement in exercise, a key factor in preventing additional disability. The Resources and Activities for Life Long Independence (RALLI) program uses behavioral principles to make exercise more accessible for these individuals. Exercises are broken…

Short-term memory to long-term memory transition in a nanoscale memristor.

PubMed

Chang, Ting; Jo, Sung-Hyun; Lu, Wei

2011-09-27

"Memory" is an essential building block in learning and decision-making in biological systems. Unlike modern semiconductor memory devices, needless to say, human memory is by no means eternal. Yet, forgetfulness is not always a disadvantage since it releases memory storage for more important or more frequently accessed pieces of information and is thought to be necessary for individuals to adapt to new environments. Eventually, only memories that are of significance are transformed from short-term memory into long-term memory through repeated stimulation. In this study, we show experimentally that the retention loss in a nanoscale memristor device bears striking resemblance to memory loss in biological systems. By stimulating the memristor with repeated voltage pulses, we observe an effect analogous to memory transition in biological systems with much improved retention time accompanied by additional structural changes in the memristor. We verify that not only the shape or the total number of stimuli is influential, but also the time interval between stimulation pulses (i.e., the stimulation rate) plays a crucial role in determining the effectiveness of the transition. The memory enhancement and transition of the memristor device was explained from the microscopic picture of impurity redistribution and can be qualitatively described by the same equations governing biological memories. © 2011 American Chemical Society

Loss of hfe function reverses impaired recognition memory caused by olfactory manganese exposure in mice.

PubMed

Ye, Qi; Kim, Jonghan

2015-03-01

Excessive manganese (Mn) in the brain promotes a variety of abnormal behaviors, including memory deficits, decreased motor skills and psychotic behavior resembling Parkinson's disease. Hereditary hemochromatosis (HH) is a prevalent genetic iron overload disorder worldwide. Dysfunction in HFE gene is the major cause of HH. Our previous study has demonstrated that olfactory Mn uptake is altered by HFE deficiency, suggesting that loss of HFE function could alter manganese-associated neurotoxicity. To test this hypothesis, Hfe-knockout (Hfe (-/-)) and wild-type (Hfe (+/+)) mice mice were intranasally-instilled with manganese chloride (MnCl2 5 mg/kg) or water daily for 3 weeks and examined for memory function. Olfactory Mn diminished both short-term recognition and spatial memory in Hfe (+/+) mice, as examined by novel object recognition task and Barnes maze test, respectively. Interestingly, Hfe (-/-) mice did not show impaired recognition memory caused by Mn exposure, suggesting a potential protective effect of Hfe deficiency against Mn-induced memory deficits. Since many of the neurotoxic effects of manganese are thought to result from increased oxidative stress, we quantified activities of anti-oxidant enzymes in the prefrontal cortex (PFC). Mn instillation decreased superoxide dismutase 1 (SOD1) activity in Hfe (+/+) mice, but not in Hfe (-/-) mice. In addition, Hfe deficiency up-regulated SOD1 and glutathione peroxidase activities. These results suggest a beneficial role of Hfe deficiency in attenuating Mn-induced oxidative stress in the PFC. Furthermore, Mn exposure reduced nicotinic acetylcholine receptor levels in the PFC, indicating that blunted acetylcholine signaling could contribute to impaired memory associated with intranasal manganese. Together, our model suggests that disrupted cholinergic system in the brain is involved in airborne Mn-induced memory deficits and loss of HFE function could in part prevent memory loss via a potential up-regulation of anti-oxidant enzymes in the PFC.

Temporal lobe volume predicts Wada memory test performance in patients with mesial temporal sclerosis.

PubMed

Ding, Kan; Gong, Yunhua; Modur, Pradeep N; Diaz-Arrastia, Ramon; Agostini, Mark; Gupta, Puneet; McColl, Roderick; Hays, Ryan; Van Ness, Paul

2016-02-01

The Wada test is widely used in the presurgical evaluation of potential temporal lobectomy patients to predict postoperative memory function. Expected asymmetry (EA), defined as Wada memory lateralized to the nonsurgical hemisphere, or a higher score after injection of the surgical hemisphere would be considered favorable in terms of postoperative memory outcome. However, in some cases, nonlateralized memory (NM) results, with no appreciable asymmetry, may occur because of impaired scores after both injections, often leading to denial of surgery. The reason for such nonlateralized Wada memory in patients with intractable temporal lobe epilepsy (TLE) remains unclear. Given that quantitative morphometric magnetic resonance imaging studies in TLE patients have shown bilateral regional atrophy in temporal and extratemporal structures, we hypothesized that the volume loss in contralateral temporal structures could contribute to nonlateralized Wada memory performance. To investigate this, we examined the relationship between the volume changes of temporal structures and Wada memory scores in patients with intractable TLE with mesial temporal sclerosis (MTS) using an age- and gender-matched control group. Memory was considered nonlateralized if the absolute difference in the total correct recall scores between ipsilateral and contralateral injections was <11%. Among 21 patients, Wada memory was lateralized in 15 and nonlateralized in 6 patients, with all the nonlateralized scores being observed in left TLE. The recall scores after ipsilateral injection were significantly lower in patients with an NM profile than an EA profile (23 ± 14% vs. 59 ± 18% correct recall, p ≤ 0.001). However, the recall scores after contralateral injection were low but similar between the two groups (25 ± 17% vs. 25 ± 15% correct recall, p=0.97). Compared to controls, all the patients showed greater volume loss in the temporal regions. However, patients with a NM profile showed significantly more volume loss than those with a lateralized memory profile in both contralateral and ipsilateral temporal regions (p<0.05). Left hemispheric Wada memory performance correlated positively with the size of the left mesial and neocortical temporal structures (r=0.49-0.63, p=0.005-0.04). Our study suggests that volume loss in the nonsurgical temporal structures is associated with nonlateralized Wada memory results in patients with intractable TLE. Copyright © 2015 Elsevier B.V. All rights reserved.

Effects of hearing loss on speech recognition under distracting conditions and working memory in the elderly.

PubMed

Na, Wondo; Kim, Gibbeum; Kim, Gungu; Han, Woojae; Kim, Jinsook

2017-01-01

The current study aimed to evaluate hearing-related changes in terms of speech-in-noise processing, fast-rate speech processing, and working memory; and to identify which of these three factors is significantly affected by age-related hearing loss. One hundred subjects aged 65-84 years participated in the study. They were classified into four groups ranging from normal hearing to moderate-to-severe hearing loss. All the participants were tested for speech perception in quiet and noisy conditions and for speech perception with time alteration in quiet conditions. Forward- and backward-digit span tests were also conducted to measure the participants' working memory. 1) As the level of background noise increased, speech perception scores systematically decreased in all the groups. This pattern was more noticeable in the three hearing-impaired groups than in the normal hearing group. 2) As the speech rate increased faster, speech perception scores decreased. A significant interaction was found between speed of speech and hearing loss. In particular, 30% of compressed sentences revealed a clear differentiation between moderate hearing loss and moderate-to-severe hearing loss. 3) Although all the groups showed a longer span on the forward-digit span test than the backward-digit span test, there was no significant difference as a function of hearing loss. The degree of hearing loss strongly affects the speech recognition of babble-masked and time-compressed speech in the elderly but does not affect the working memory. We expect these results to be applied to appropriate rehabilitation strategies for hearing-impaired elderly who experience difficulty in communication.

The impact of corporate memory loss: What happens when a senior executive leaves?

PubMed

Lahaie, Denis

2005-01-01

The author is a nursing management practitioner, whose purpose in writing this paper is twofold: to examine the impact of corporate memory loss on a health care institution, caused by increasing retirement rates of senior executives; and to use this research as an opportunity for action learning where both the author and the institution can benefit from the learning outcomes. Using qualitative research methods based on ethnographic interviewing techniques and grounded theory, the author interviews 12 senior executives from four diverse health care facilities. The purpose is to determine the point at which corporate memory loss, in the form of tacit knowledge in the heads of departing executives, becomes a problem for the institution. The research determined that the requisite managerial competencies normally assumed for senior management positions are insufficient to minimize the negative impacts of corporate memory loss caused by departing senior executives. Effective knowledge management and knowledge transfer within the organization are fundamental for ongoing organizational effectiveness. The research is limited to 12 senior executives. The grounded theory nature of the research provides a framework for more research in other institutions to test and further explore some of the findings. One of the most significant threats facing the majority of health care organizations related to the aging workforce is the greater number of staff who are retiring from all levels within the organization. The development of techniques to reducing the impact of corporate memory loss on the culture of an organization will increase its effectiveness, help build continuity, and provide a more secure footing for the workforce of the future. The exit of knowledge workers is causing a major problem for Canada's health care organizations. This study throws more light on to this problem from the point of view of senior executives who have been specifically impacted by the problem of corporate memory loss.

Hippocampus at 25.

PubMed

Eichenbaum, Howard; Amaral, David G; Buffalo, Elizabeth A; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G M; Moser, Edvard I; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

2016-10-01

The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Postnatal Loss of Mef2c Results in Dissociation of Effects on Synapse Number and Learning and Memory.

PubMed

Adachi, Megumi; Lin, Pei-Yi; Pranav, Heena; Monteggia, Lisa M

2016-07-15

Myocyte enhancer factor 2 (MEF2) transcription factors play critical roles in diverse cellular processes during central nervous system development. Studies attempting to address the role of MEF2 in brain have largely relied on overexpression of a constitutive MEF2 construct that impairs memory formation or knockdown of MEF2 function that increases spine numbers and enhances memory formation. Genetic deletion of individual MEF2 isoforms in brain during embryogenesis demonstrated that Mef2c loss negatively regulates spine numbers resulting in learning and memory deficits, possibly as a result of its essential role in development. To investigate MEF2C function in brain further, we genetically deleted Mef2c during postnatal development in mice. We characterized these conditional Mef2c knockout mice in an array of behavioral paradigms and examined the impact of postnatal loss of Mef2c on long-term potentiation. We observed increased spine numbers in hippocampus of the conditional Mef2c knockout mice. However, the postnatal loss of Mef2c did not impact learning and memory, long-term potentiation, or social and repetitive behaviors. Our findings demonstrate a critical role for MEF2C in the regulation of spine numbers with a dissociation of learning and memory, synaptic plasticity, and measures of autism-related behaviors in postnatal brain. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Bidirectional relationships between sleep and amyloid-beta in the hippocampus.

PubMed

Dufort-Gervais, Julien; Mongrain, Valérie; Brouillette, Jonathan

2018-06-14

Alzheimer's disease (AD) is a debilitating neurodegenerative disease characterized by progressive hippocampal-dependent explicit memory deficits that begin at the onset of the illness. An early hallmark of AD is the accumulation of amyloid-beta (Aß) proteins in brain structures involved in encoding and consolidation of memory, like the hippocampus and prefrontal cortex. Aß neurotoxicity is known to induce synaptic dysfunctions and neuronal death leading to cognitive decline. Another recurrent event observed in AD is sleep disturbances. Decreased sleep duration, sleep fragmentation, and circadian alterations are often observed in early AD. The origin of these disturbances, and especially the specific contribution of the hippocampal Aß pathology, remains to be determined. It is required to identify mechanisms impacting wakefulness and sleep architecture and microarchitecture given the role of sleep in memory encoding and consolidation. Sleep perturbations in AD are thus likely contributing to memory decline in the course of the disease. The central aim of this review is to address the bidirectional relationship between sleep and hippocampal Aß by discussing the literature featuring data on wakefulness and sleep variables (i.e., duration, electroencephalographic activity, daily distribution) in AD mouse models and on the effect of enforced sleep loss on Aß pathology in the hippocampus. The current state of knowledge on this topic emphasizes a clear need for more efforts to assess the precise impact of hippocampal Aß on wakefulness and sleep quality as well as the mechanisms mediating their reciprocal relationship. Copyright © 2018. Published by Elsevier Inc.

Beneficial effects of exercise in a transgenic mouse model of Alzheimer's disease-like Tau pathology.

PubMed

Belarbi, Karim; Burnouf, Sylvie; Fernandez-Gomez, Francisco-Jose; Laurent, Cyril; Lestavel, Sophie; Figeac, Martin; Sultan, Audrey; Troquier, Laetitia; Leboucher, Antoine; Caillierez, Raphaëlle; Grosjean, Marie-Eve; Demeyer, Dominique; Obriot, Hélène; Brion, Ingrid; Barbot, Bérangère; Galas, Marie-Christine; Staels, Bart; Humez, Sandrine; Sergeant, Nicolas; Schraen-Maschke, Susanna; Muhr-Tailleux, Anne; Hamdane, Malika; Buée, Luc; Blum, David

2011-08-01

Tau pathology is encountered in many neurodegenerative disorders known as tauopathies, including Alzheimer's disease. Physical activity is a lifestyle factor affecting processes crucial for memory and synaptic plasticity. Whether long-term voluntary exercise has an impact on Tau pathology and its pathophysiological consequences is currently unknown. To address this question, we investigated the effects of long-term voluntary exercise in the THY-Tau22 transgenic model of Alzheimer's disease-like Tau pathology, characterized by the progressive development of Tau pathology, cholinergic alterations and subsequent memory impairments. Three-month-old THY-Tau22 mice and wild-type littermates were assigned to standard housing or housing supplemented with a running wheel. After 9 months of exercise, mice were evaluated for memory performance and examined for hippocampal Tau pathology, cholinergic defects, inflammation and genes related to cholesterol metabolism. Exercise prevented memory alterations in THY-Tau22 mice. This was accompanied by a decrease in hippocampal Tau pathology and a prevention of the loss of expression of choline acetyltransferase within the medial septum. Whereas the expression of most cholesterol-related genes remained unchanged in the hippocampus of running THY-Tau22 mice, we observed a significant upregulation in mRNA levels of NPC1 and NPC2, genes involved in cholesterol trafficking from the lysosomes. Our data support the view that long-term voluntary physical exercise is an effective strategy capable of mitigating Tau pathology and its pathophysiological consequences. Copyright © 2011 Elsevier Inc. All rights reserved.

Episodic and working memory function in Primary Progressive Aphasia: A meta-analysis.

PubMed

Eikelboom, Willem S; Janssen, Nikki; Jiskoot, Lize C; van den Berg, Esther; Roelofs, Ardi; Kessels, Roy P C

2018-06-18

The distinction between Primary Progressive Aphasia (PPA) variants remains challenging for clinicians, especially for the non-fluent (nfv-PPA) and the logopenic variants (lv-PPA). Previous research suggests that memory tests might aid this differentiation. This meta-analysis compares memory function among PPA variants. Effects sizes were extracted from 41 studies (N = 849). Random-effects models were used to compare performance on episodic and working memory tests among PPA patients and healthy controls, and between the PPA variants. Memory deficits were frequently observed in PPA compared to controls, with large effect sizes for lv-PPA (Hedges' g = -2.04 [-2.58 to -1.49]), nfv-PPA (Hedges' g = -1.34 [-1.69 to -1.00]), and the semantic variant (sv-PPA; Hedges' g = -1.23 [-1.50 to -0.97]). Sv-PPA showed primarily verbal memory deficits, whereas lv-PPA showed worse performance than nfv-PPA on both verbal and non-verbal memory tests. Memory deficits were more pronounced in lv-PPA compared to nfv-PPA. This suggests that memory tests may be helpful to distinguish between these PPA variants. Copyright © 2018. Published by Elsevier Ltd.

Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities.

PubMed

Parent, Maxime J; Zimmer, Eduardo R; Shin, Monica; Kang, Min Su; Fonov, Vladimir S; Mathieu, Axel; Aliaga, Antonio; Kostikov, Alexey; Do Carmo, Sonia; Dea, Doris; Poirier, Judes; Soucy, Jean-Paul; Gauthier, Serge; Cuello, A Claudio; Rosa-Neto, Pedro

2017-12-13

Imaging biomarkers are frequently proposed as endpoints for clinical trials targeting brain amyloidosis in Alzheimer's disease (AD); however, the specific impact of amyloid-β (Aβ) aggregation on biomarker abnormalities remains elusive in AD. Using the McGill-R-Thy1-APP transgenic rat as a model of selective Aβ pathology, we characterized the longitudinal progression of abnormalities in biomarkers commonly used in AD research. Middle-aged (9-11 months) transgenic animals (both male and female) displayed mild spatial memory impairments and disrupted cingulate network connectivity measured by resting-state fMRI, even in the absence of hypometabolism (measured with PET [ 18 F]FDG) or detectable fibrillary amyloidosis (measured with PET [ 18 F]NAV4694). At more advanced ages (16-19 months), cognitive deficits progressed in conjunction with resting connectivity abnormalities; furthermore, hypometabolism, Aβ plaque accumulation, reduction of CSF Aβ 1-42 concentrations, and hippocampal atrophy (structural MRI) were detectable at this stage. The present results emphasize the early impact of Aβ on brain connectivity and support a framework in which persistent Aβ aggregation itself is sufficient to impose memory circuits dysfunction, which propagates to adjacent brain networks at later stages. SIGNIFICANCE STATEMENT The present study proposes a "back translation" of the Alzheimer pathological cascade concept from human to animals. We used the same set of Alzheimer imaging biomarkers typically used in large human cohorts and assessed their progression over time in a transgenic rat model, which allows for a finer spatial resolution not attainable with mice. Using this translational platform, we demonstrated that amyloid-β pathology recapitulates an Alzheimer-like profile of biomarker abnormalities even in the absence of other hallmarks of the disease such as neurofibrillary tangles and widespread neuronal losses. Copyright © 2017 Parent et al.

Multimodal Imaging in Rat Model Recapitulates Alzheimer's Disease Biomarkers Abnormalities

PubMed Central

Parent, Maxime J.; Kang, Min Su; Mathieu, Axel; Aliaga, Antonio; Do Carmo, Sonia; Dea, Doris; Gauthier, Serge; Cuello, A. Claudio

2017-01-01

Imaging biomarkers are frequently proposed as endpoints for clinical trials targeting brain amyloidosis in Alzheimer's disease (AD); however, the specific impact of amyloid-β (Aβ) aggregation on biomarker abnormalities remains elusive in AD. Using the McGill-R-Thy1-APP transgenic rat as a model of selective Aβ pathology, we characterized the longitudinal progression of abnormalities in biomarkers commonly used in AD research. Middle-aged (9–11 months) transgenic animals (both male and female) displayed mild spatial memory impairments and disrupted cingulate network connectivity measured by resting-state fMRI, even in the absence of hypometabolism (measured with PET [18F]FDG) or detectable fibrillary amyloidosis (measured with PET [18F]NAV4694). At more advanced ages (16–19 months), cognitive deficits progressed in conjunction with resting connectivity abnormalities; furthermore, hypometabolism, Aβ plaque accumulation, reduction of CSF Aβ1-42 concentrations, and hippocampal atrophy (structural MRI) were detectable at this stage. The present results emphasize the early impact of Aβ on brain connectivity and support a framework in which persistent Aβ aggregation itself is sufficient to impose memory circuits dysfunction, which propagates to adjacent brain networks at later stages. SIGNIFICANCE STATEMENT The present study proposes a “back translation” of the Alzheimer pathological cascade concept from human to animals. We used the same set of Alzheimer imaging biomarkers typically used in large human cohorts and assessed their progression over time in a transgenic rat model, which allows for a finer spatial resolution not attainable with mice. Using this translational platform, we demonstrated that amyloid-β pathology recapitulates an Alzheimer-like profile of biomarker abnormalities even in the absence of other hallmarks of the disease such as neurofibrillary tangles and widespread neuronal losses. PMID:29097597

KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy speaks to attendees at a memorial service honoring the crew of Columbia. He stands in front of the Space Memorial Mirror at the KSC Visitor Complex. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Attended by many friends, co-workers and families, the memorial service was also open to the public.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - Center Director Jim Kennedy speaks to attendees at a memorial service honoring the crew of Columbia. He stands in front of the Space Memorial Mirror at the KSC Visitor Complex. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Attended by many friends, co-workers and families, the memorial service was also open to the public.

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall.

PubMed

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-07-08

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall.

The Endocrine Dyscrasia that Accompanies Menopause and Andropause Induces Aberrant Cell Cycle Signaling that Triggers Cell Cycle Reentry of Post-mitotic Neurons, Neurodysfunction, Neurodegeneration and Cognitive Disease

PubMed Central

Atwood, Craig S.; Bowen, Richard L.

2016-01-01

Sex hormones are the physiological factors that regulate neurogenesis during embryogenesis and continuing through adulthood. These hormones support the formation of brain structures such as dendritic spines, axons and synapses required for the capture of information (memories). Intriguingly, a recent animal study has demonstrated that induction of neurogenesis results in the loss of previously encoded memories in animals (e.g. infantile amnesia). In this connection, much evidence now indicates that Alzheimer’s disease (AD) also involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Since sex hormones control when and how neurons proliferate and differentiate, the endocrine dyscrasia that accompanies menopause and andropause is a key signaling event that impacts neurogenesis and the acquisition, processing, storage and recall of memories. Here we review the biochemical, epidemiological and clinical evidence that alterations in endocrine signaling with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle with neurite retraction that leads to neuron dysfunction and death. When the reproductive axis is in balance, luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the ratio of LH:sex steroids as driving aberrant mitotic events mediated by the upregulation of tumor necrosis factor, amyloid-β precursor protein processing towards the production of mitogenic Aβ, and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive studies also demonstrate the negative consequences of a high LH:sex steroid ratio on human cognitive performance. Prospective epidemiological and clinical evidence in humans supports lowering the ratio of circulating gonadotropins-GnRH to sex steroids in reducing the incidence of AD and halting cognitive decline. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson’s disease. PMID:26188949

Why does lag affect the durability of memory-based automaticity: loss of memory strength or interference?

PubMed

Wilkins, Nicolas J; Rawson, Katherine A

2013-10-01

In Rickard, Lau, and Pashler's (2008) investigation of the lag effect on memory-based automaticity, response times were faster and proportion of trials retrieved was higher at the end of practice for short lag items than for long lag items. However, during testing after a delay, response times were slower and proportion of trials retrieved was lower for short lag items than for long lag items. The current study investigated the extent to which the lag effect on the durability of memory-based automaticity is due to interference or to the loss of memory strength with time. Participants repeatedly practiced alphabet subtraction items in short lag and long lag conditions. After practice, half of the participants were immediately tested and the other half were tested after a 7-day delay. Results indicate that the lag effect on the durability of memory-based automaticity is primarily due to interference. We discuss potential modification of current memory-based processing theories to account for these effects. © 2013.

Working Memory Training Does Not Improve Intelligence in Healthy Young Adults

ERIC Educational Resources Information Center

Chooi, Weng-Tink; Thompson, Lee A.

2012-01-01

Jaeggi and her colleagues claimed that they were able to improve fluid intelligence by training working memory. Subjects who trained their working memory on a dual n-back task for a period of time showed significant improvements in working memory span tasks and fluid intelligence tests such as the Raven's Progressive Matrices and the Bochumer…

Hippocampal volume and memory performance in children with perinatal stroke.

PubMed

Gold, Jeffrey J; Trauner, Doris A

2014-01-01

Pediatric neurologists and neonatologists often are asked to predict cognitive outcome after perinatal brain injury (including likely memory and learning outcomes). However, relatively few data exist on how accurate predictions can be made. Furthermore, although the consequences of brain injury on hippocampal volume and memory performance have been studied extensively in adults, little work has been done in children. We measured the volume of the hippocampus in 27 children with perinatal stroke and 19 controls, and measured their performance on standardized verbal and non-verbal memory tests. We discovered the following: (1) As a group, children with perinatal stroke had smaller left and right hippocampi compared with control children. (2) Individually, children with perinatal stroke demonstrated 1 of 3 findings: no hippocampal loss, unilateral hippocampal loss, or bilateral hippocampal volume loss compared with control children. (3) Hippocampal volume inversely correlated with memory test performance in the perinatal stroke group, with smaller left and right hippocampal volumes related to poorer verbal and non-verbal memory test performance, respectively. (4) Seizures played a significant role in determining memory deficit and extent of hippocampal volume reduction in patients with perinatal stroke. These findings support the view that, in the developing brain, the left and right hippocampi preferentially support verbal and nonverbal memory respectively, a consistent finding in the adult literature but a subject of debate in the pediatric literature. This is the first work to report that children with focal brain injury incurred from perinatal stroke have volume reduction in the hippocampus and impairments in certain aspects of declarative memory. Copyright © 2014 Elsevier Inc. All rights reserved.

Acceptability and Feasibility Results of a Strength-Based Skills Training Program for Dementia Caregiving Dyads

ERIC Educational Resources Information Center

Judge, Katherine S.; Yarry, Sarah J.; Orsulic-Jeras, Silvia

2010-01-01

Purpose: The current article provides an in-depth description of a dyadic intervention for individuals with dementia and their family caregivers. Using a strength-based approach, caregiving dyads received skills training across 5 key areas: (a) education regarding dementia and memory loss, (b) effective communication, (c) managing memory loss, (d)…

Trauma-Induced Weight Loss and Cognitive Deficits among Former Prisoners of War.

ERIC Educational Resources Information Center

Sutker, Patricia B.; And Others

1990-01-01

Compared former prisoners of war (POWs) reporting confinement weight losses greater than 35 percent (N=60), less than 35 percent (N=113), and non-POW combat veterans (N=50) on Wechsler Adult Intelligence Scale-Revised and Wechsler Memory Scale Logical Memory indices. Findings suggest that severe POW confinement stress reflected by trauma-induced…

Progress In Optical Memory Technology

NASA Astrophysics Data System (ADS)

Tsunoda, Yoshito

1987-01-01

More than 20 years have passed since the concept of optical memory was first proposed in 1966. Since then considerable progress has been made in this area together with the creation of completely new markets of optical memory in consumer and computer application areas. The first generation of optical memory was mainly developed with holographic recording technology in late 1960s and early 1970s. Considerable number of developments have been done in both analog and digital memory applications. Unfortunately, these technologies did not meet a chance to be a commercial product. The second generation of optical memory started at the beginning of 1970s with bit by bit recording technology. Read-only type optical memories such as video disks and compact audio disks have extensively investigated. Since laser diodes were first applied to optical video disk read out in 1976, there have been extensive developments of laser diode pick-ups for optical disk memory systems. The third generation of optical memory started in 1978 with bit by bit read/write technology using laser diodes. Developments of recording materials including both write-once and erasable have been actively pursued at several research institutes. These technologies are mainly focused on the optical memory systems for computer application. Such practical applications of optical memory technology has resulted in the creation of such new products as compact audio disks and computer file memories.

Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: A decision analysis

PubMed Central

Akama-Garren, Elliot H.; Bianchi, Matt T.; Leveroni, Catherine; Cole, Andrew J.; Cash, Sydney S.; Westover, M. Brandon

2016-01-01

SUMMARY Objectives Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. Methods We constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. Results For patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. Significance Our decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis. PMID:25244498

Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: a decision analysis.

PubMed

Akama-Garren, Elliot H; Bianchi, Matt T; Leveroni, Catherine; Cole, Andrew J; Cash, Sydney S; Westover, M Brandon

2014-11-01

Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. We constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. For patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. Our decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Estradiol and luteinizing hormone regulate recognition memory following subchronic phencyclidine: Evidence for hippocampal GABA action.

PubMed

Riordan, Alexander J; Schaler, Ari W; Fried, Jenny; Paine, Tracie A; Thornton, Janice E

2018-05-01

The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP. To modulate E and LH, animals received estradiol capsules or Antide injections. Short-term episodic memory was assessed using the novel object recognition task (NORT). Brain expression of GAD67 was analyzed via western blot, and parvalbumin-containing cells were counted using immunohistochemistry. Some rats received hippocampal infusions of a GABA A agonist, GABA A antagonist, or GAD inhibitor before behavioral testing. We found that PCP reduced hippocampal GAD67 and abolished recognition memory. Antide restored hippocampal GAD67 and rescued recognition memory in PCP-treated animals. Estradiol prevented PCP's amnesic effect in NORT but failed to restore hippocampal GAD67. PCP did not cause significant differences in number of parvalbumin-expressing cells or cortical expression of GAD67. Hippocampal infusions of a GABA A agonist restored recognition memory in PCP-treated rats. Blocking hippocampal GAD or GABA A receptors in ovx animals reproduced recognition memory loss similar to PCP and inhibited estradiol's protection of recognition memory in PCP-treated animals. In summary, decreasing LH or increasing E can lessen short-term episodic memory loss, as measured by novel object recognition, in a PCP model of schizophrenia. Alterations in hippocampal GABA may contribute to both PCP's effects on recognition memory and the hormones' ability to prevent or reverse them. Copyright © 2018 Elsevier Ltd. All rights reserved.

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)

MedlinePlus

... decline, including short-term memory loss, loss of math or spelling skills, difficulty making decisions, and other ... personality changes. Cognitive decline—loss of skills including math, reading, etc. Impotence, loss of bladder or bowel ...

The association of traumatic brain injury with rate of progression of cognitive and functional impairment in a population-based cohort of Alzheimer's disease: the Cache County Dementia Progression Study.

PubMed

Gilbert, Mac; Snyder, Christine; Corcoran, Chris; Norton, Maria C; Lyketsos, Constantine G; Tschanz, JoAnn T

2014-10-01

There is limited research on factors that influence the rate of progression in Alzheimer's disease (AD). A history of traumatic brain injury (TBI) is associated with an increased risk for AD, but its role on the rate of dementia progression after the onset of AD has not been examined. A population-based cohort of 325 persons with incident AD was followed for up to 11 years. The sample was 65% female with a mean (SD) age of dementia onset = 84.4 (6.4) years. History of TBI was categorized as number, severity (with or without loss of consciousness), and timing in relation to dementia onset (within ten years or more than ten years). Cognition was assessed by the Consortium to Establish a Registry of AD battery, and functional ability was assessed by the Clinical Dementia Rating Sum of Boxes. In linear mixed models, a history of TBI within ten years of onset showed faster progression of functional impairment (LR x2 = 10.27, p = 0.006), while those with TBI more than ten years before dementia onset had higher scores on a measure of list learning (β = 1.61, p = 0.003) and semantic memory (β = 0.75, p = 0.0035). History of TBI and its recency may be a useful factor to predict functional progression in the course of AD.

Short-term modern life-like stress exacerbates Aβ-pathology and synapse loss in 3xTg-AD mice.

PubMed

Baglietto-Vargas, David; Chen, Yuncai; Suh, Dongjin; Ager, Rahasson R; Rodriguez-Ortiz, Carlos J; Medeiros, Rodrigo; Myczek, Kristoffer; Green, Kim N; Baram, Tallie Z; LaFerla, Frank M

2015-09-01

Alzheimer's disease (AD) is a progressive neurological disorder that impairs memory and other cognitive functions in the elderly. The social and financial impacts of AD are overwhelming and are escalating exponentially as a result of population aging. Therefore, identifying AD-related risk factors and the development of more efficacious therapeutic approaches are critical to cure this neurological disorder. Current epidemiological evidence indicates that life experiences, including chronic stress, are a risk for AD. However, it is unknown if short-term stress, lasting for hours, influences the onset or progression of AD. Here, we determined the effect of short-term, multi-modal 'modern life-like' stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short-term stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. Epidemiological evidence indicates that life experiences, including chronic stress, are a risk for Alzheimer disease (AD). However, it is unknown if short stress in the range of hours influences the onset or progression of AD. Here, we determined the effect of short, multi-modal 'modern-lifelike'stress on AD pathogenesis and synaptic plasticity in mice bearing three AD mutations (the 3xTg-AD mouse model). We found that combined emotional and physical stress lasting 5 h severely impaired memory in wild-type mice and tended to impact it in already low-performing 3xTg-AD mice. This stress reduced the number of synapse-bearing dendritic spines in 3xTg-AD mice and increased Aβ levels by augmenting AβPP processing. Thus, short stress simulating modern-life conditions may exacerbate cognitive deficits in preclinical AD by accelerating amyloid pathology and reducing synapse numbers. © 2015 International Society for Neurochemistry.

The diary of a nonagenarian-centenarian woman with dementia: Memory loss, life changes, and community care in Japan.

PubMed

Suwa, Sayuri; Otani, Saori; Tsujimura, Mayuko; Nogawa, Kotoko; Shiya, Yoko

2018-04-01

This study aimed to explore the experiences and thoughts of a nonagenarian-centenarian woman with dementia living alone, through detailed analysis of her unsolicited diary. After receiving consent from Aki (a pseudonym), her family and caregivers, copies of her diaries, hand-written in Japanese, were provided for analysis. The content of the diaries was broadly organized into themes and qualitative content analysis carried out for each theme along a sequential timeline. Changes in perspective, expression, quality of script, and frequency of notations were noted over time are compared with clinical assessments of dementia and activities of daily living recorded by health care providers. Demographic history was obtained from family members. On recommendation by her nursing care manager, Aki began keeping a diary. By age 99, Aki was widowed and noted: "I'm lonely by myself." but still expressed hope: "I won't give up on myself." Concerning memory loss, she wrote: "I've already forgotten what happened this afternoon," and "I'll do things for myself." Regarding dependence, she said: "I get help from my children and others outside the family." And commented on the home care staff: "I don't know if they've come to help." "Is it someone I know well?" Although she thought that they took her belongings, she wrote: "I'll try not to forget to be grateful to them." The diaries show that even as the dementia progressed, Aki was aware of her cognitive decline compounded by family losses. She used the diary as a coping method and to address relationships with family and caregivers. © 2018 John Wiley & Sons Australia, Ltd.

RanBP9 overexpression down-regulates phospho-cofilin, causes early synaptic deficits and impaired learning, and accelerates accumulation of amyloid plaques in the mouse brain.

PubMed

Palavicini, Juan Pablo; Wang, Hongjie; Minond, Dmitriy; Bianchi, Elisabetta; Xu, Shaohua; Lakshmana, Madepalli K

2014-01-01

Loss of synaptic proteins and functional synapses in the brains of patients with Alzheimer's disease (AD) as well as transgenic mouse models expressing amyloid-β protein precursor is now well established. However, the earliest age at which such loss of synapses occurs, and whether known markers of AD progression accelerate functional deficits is completely unknown. We previously showed that RanBP9 overexpression leads to enhanced amyloid plaque burden in a mouse model of AD. In this study, we found significant reductions in the levels of synaptophysin and spinophilin, compared with wild-type controls, in both the cortex and the hippocampus of 5- and 6-month old but not 3- or 4-month old APΔE9/RanBP9 triple transgenic mice, and not in APΔE9 double transgenic mice, nor in RanBP9 single transgenic mice. Interestingly, amyloid plaque burden was also increased in the APΔE9/RanBP9 mice at 5-6 months. Consistent with these results, we found significant deficits in learning and memory in the APΔE9/RanBP9 mice at 5 and 6 month. These data suggest that increased amyloid plaques and accelerated learning and memory deficits and loss of synaptic proteins induced by RanBP9 are correlated. Most importantly, APΔE9/RanBP9 mice also showed significantly reduced levels of the phosphorylated form of cofilin in the hippocampus. Taken together these data suggest that RanBP9 overexpression down-regulates cofilin, causes early synaptic deficits and impaired learning, and accelerates accumulation of amyloid plaques in the mouse brain.

Enhancement of Immune Memory Responses to Respiratory Infection

DTIC Science & Technology

2017-08-01

induction of highly specific B and T cell responses against viral infections. Despite recent progress in vaccine development, the molecular mechanisms...highly expressed in memory B cells in mice, and Atg7 is required for maintenance of long-term memory B cells needed to protect against influenza...infection. Human influenza-specific memory B cells also have high levels of autophagy, but whether autophagy protects memory B cell survival in humans

Late-onset Alzheimer's risk variants in memory decline, incident mild cognitive impairment, and Alzheimer's disease.

PubMed

Carrasquillo, Minerva M; Crook, Julia E; Pedraza, Otto; Thomas, Colleen S; Pankratz, V Shane; Allen, Mariet; Nguyen, Thuy; Malphrus, Kimberly G; Ma, Li; Bisceglio, Gina D; Roberts, Rosebud O; Lucas, John A; Smith, Glenn E; Ivnik, Robert J; Machulda, Mary M; Graff-Radford, Neill R; Petersen, Ronald C; Younkin, Steven G; Ertekin-Taner, Nilüfer

2015-01-01

We tested association of nine late-onset Alzheimer's disease (LOAD) risk variants from genome-wide association studies (GWAS) with memory and progression to mild cognitive impairment (MCI) or LOAD (MCI/LOAD) in older Caucasians, cognitively normal at baseline and longitudinally evaluated at Mayo Clinic Rochester and Jacksonville (n>2000). Each variant was tested both individually and collectively using a weighted risk score. APOE-e4 associated with worse baseline memory and increased decline with highly significant overall effect on memory. CLU-rs11136000-G associated with worse baseline memory and incident MCI/LOAD. MS4A6A-rs610932-C associated with increased incident MCI/LOAD and suggestively with lower baseline memory. ABCA7-rs3764650-C and EPHA1-rs11767557-A associated with increased rates of memory decline in subjects with a final diagnosis of MCI/LOAD. PICALM-rs3851179-G had an unexpected protective effect on incident MCI/LOAD. Only APOE-inclusive risk scores associated with worse memory and incident MCI/LOAD. The collective influence of the nine top LOAD GWAS variants on memory decline and progression to MCI/LOAD appears limited. Discovery of biologically functional variants at these loci may uncover stronger effects on memory and incident disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of a Memory Training Program in Older People with Severe Memory Loss

ERIC Educational Resources Information Center

Mateos, Pedro M.; Valentin, Alberto; González-Tablas, Maria del Mar; Espadas, Verónica; Vera, Juan L.; Jorge, Inmaculada García

2016-01-01

Strategies based memory training programs are widely used to enhance the cognitive abilities of the elderly. Participants in these training programs are usually people whose mental abilities remain intact. Occasionally, people with cognitive impairment also participate. The aim of this study was to test if memory training designed specifically for…

Mechanisms of Melatonin in Alleviating Alzheimer’s Disease

PubMed Central

Shukla, Mayuri; Govitrapong, Piyarat; Boontem, Parichart; Reiter, Russel J.; Satayavivad, Jutamaad

2017-01-01

Alzheimer’s disease (AD) is a chronic, progressive and prevalent neurodegenerative disease characterized by the loss of higher cognitive functions and an associated loss of memory. The thus far “incurable” stigma for AD prevails because of variations in the success rates of different treatment protocols in animal and human studies. Among the classical hypotheses explaining AD pathogenesis, the amyloid hypothesis is currently being targeted for drug development. The underlying concept is to prevent the formation of these neurotoxic peptides which play a central role in AD pathology and trigger a multispectral cascade of neurodegenerative processes post-aggregation. This could possibly be achieved by pharmacological inhibition of β- or γ-secretase or stimulating the non-amyloidogenic α-secretase. Melatonin the pineal hormone is a multifunctioning indoleamine. Production of this amphiphilic molecule diminishes with advancing age and this decrease runs parallel with the progression of AD which itself explains the potential benefits of melatonin in line of development and devastating consequences of the disease progression. Our recent studies have revealed a novel mechanism by which melatonin stimulates the nonamyloidogenic processing and inhibits the amyloidogenic processing of β-amyloid precursor protein (βAPP) by stimulating α-secretases and consequently down regulating both β- and γ-secretases at the transcriptional level. In this review, we discuss and evaluate the neuroprotective functions of melatonin in AD pathogenesis, including its role in the classical hypotheses in cellular and animal models and clinical interventions in AD patients, and suggest that with early detection, melatonin treatment is qualified to be an anti-AD therapy. PMID:28294066

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation.

PubMed

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-08-04

Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

Dorsal CA1 interneurons contribute to acute stress-induced spatial memory deficits.

PubMed

Yu, Jing-Ying; Fang, Ping; Wang, Chi; Wang, Xing-Xing; Li, Kun; Gong, Qian; Luo, Ben-Yan; Wang, Xiao-Dong

2018-06-01

Exposure to severely stressful experiences disrupts the activity of neuronal circuits and impairs declarative memory. GABAergic interneurons coordinate neuronal network activity, but their involvement in stress-evoked memory loss remains to be elucidated. Here, we provide evidence that interneurons in area CA1 of the dorsal hippocampus partially modulate acute stress-induced memory deficits. In adult male mice, both acute forced swim stress and restraint stress impaired hippocampus-dependent spatial memory and increased the density of c-fos-positive interneurons in the dorsal CA1. Selective activation of dorsal CA1 interneurons by chemogenetics disrupted memory performance in the spatial object recognition task. In comparison, anxiety-related behavior, spatial working memory and novel object recognition memory remained intact when dorsal CA1 interneurons were overactivated. Moreover, chemogenetic activation of dorsal CA1 interneurons suppressed the activity of adjacent pyramidal neurons, whereas a single exposure to forced swim stress but not restraint stress increased the activity of CA1 pyramidal neurons. However, chemogenetic inhibition of dorsal CA1 interneurons led to spatial memory impairments and failed to attenuate acute stress-induced memory loss. These findings suggest that acute stress may overactivate interneurons in the dorsal CA1, which reduces the activity of pyramidal neurons and in turn disrupts long-term memory. Copyright © 2018 Elsevier Ltd. All rights reserved.

Sign language aphasia from a neurodegenerative disease.

PubMed

Falchook, Adam D; Mayberry, Rachel I; Poizner, Howard; Burtis, David Brandon; Doty, Leilani; Heilman, Kenneth M

2013-01-01

While Alois Alzheimer recognized the effects of the disease he described on speech and language in his original description of the disease in 1907, the effects of Alzheimer's disease (AD) on language in deaf signers has not previously been reported. We evaluated a 55-year-old right-handed congenitally deaf woman with a 2-year history of progressive memory loss and a deterioration of her ability to communicate in American Sign Language, which she learned at the age of eight. Examination revealed that she had impaired episodic memory as well as marked impairments in the production and comprehension of fingerspelling and grammatically complex sentences. She also had signs of anomia as well as an ideomotor apraxia and visual-spatial dysfunction. This report illustrates the challenges in evaluation of a patient for the presence of degenerative dementia when the person is deaf from birth, uses sign language, and has a late age of primary language acquisition. Although our patient could neither speak nor hear, in many respects her cognitive disorders mirror those of patients with AD who had normally learned to speak.

A Reanalysis of Cognitive-Functional Performance in Older Adults: Investigating the Interaction Between Normal Aging, Mild Cognitive Impairment, Mild Alzheimer's Disease Dementia, and Depression

PubMed Central

de Paula, Jonas J.; Bicalho, Maria A.; Ávila, Rafaela T.; Cintra, Marco T. G.; Diniz, Breno S.; Romano-Silva, Marco A.; Malloy-Diniz, Leandro F.

2016-01-01

Depressive symptoms are associated with cognitive-functional impairment in normal aging older adults (NA). However, less is known about this effect on people with mild Cognitive Impairment (MCI) and mild Alzheimer's disease dementia (AD). We investigated this relationship along with the NA-MCI-AD continuum by reanalyzing a previously published dataset. Participants (N = 274) underwent comprehensive neuropsychological assessment including measures of Executive Function, Language/Semantic Memory, Episodic Memory, Visuospatial Abilities, Activities of Daily Living (ADL), and the Geriatric Depression Scale. MANOVA, logistic regression and chi-square tests were performed to assess the association between depression and cognitive-functional performance in each group. In the NA group, depressed participants had a lower performance compared to non-depressed participants in all cognitive and functional domains. However, the same pattern was not observed in the MCI group or in AD. The results suggest a progressive loss of association between depression and worse cognitive-functional performance along the NA-MCI-AD continuum. PMID:26858666

Highlights in BACE1 Inhibitors for Alzheimer's Disease Treatment

NASA Astrophysics Data System (ADS)

Coimbra, Judite R. M.; Marques, Daniela F. F.; Baptista, Salete J.; Pereira, Cláudia M. F.; Moreira, Paula I.; Dinis, Teresa C. P.; Santos, Armanda E.; Salvador, Jorge A. R.

2018-05-01

Alzheimer's Disease (AD) is a severe neurodegenerative disorder and the most common type of dementia in the elderly. The clinical symptoms of AD include a progressive loss of memory and impairment of cognitive functions interfering with daily life activities. The main neuropathological features consist in extracellular Amyloid-β (Aβ) plaque deposition and intracellular Neurofibrillary Tangles (NFTs) of hyperphosphorylated Tau. Understanding the pathophysiological mechanisms that underlie neurodegeneration in AD is essential for rational design of neuroprotective agents able to prevent disease progression. According to the “Amyloid Cascade Hypothesis” the critical molecular event in the pathogenesis of AD is the accumulation of Aβ neurotoxic oligomers. Since the proteolytic processing of Amyloid Precursor Protein (APP) by β-secretase (BACE1) is the rate-limiting step in the production of Aβ, this enzyme is considered a major therapeutic target and BACE1 inhibitors have the potential to be disease-modifying drugs for AD treatment. Therefore, intensive efforts to discover and develop inhibitors that can reach the brain and effectively inhibit BACE1 have been pursued by several groups worldwide. The aim of this review is to highlight the progress in the discovery of potent and selective small BACE1 inhibitors over the past decade.

Ferroelectric Memory Devices and a Proposed Standardized Test System Design

DTIC Science & Technology

1992-06-01

positive clock transition. This provides automatic data protection in case of power loss. The device is being evaluated for applications such as automobile ...systems requiring nonvolatile memory and as these systems become more complex, the demand for reprogrammable nonvolatile memory increases. The...complexity and cost in making conventional nonvolatile memory reprogrammable also increases, so the potential for using ferroelectric memory as a replacement

Neuroprotective effect of ipriflavone against scopolamine-induced memory impairment in rats.

PubMed

Hafez, Hani S; Ghareeb, Doaa A; Saleh, Samar R; Abady, Mariam M; El Demellawy, Maha A; Hussien, Hend; Abdel-Monem, Nihad

2017-10-01

Alzheimer's disease is an age-related neurodegenerative disorder characterized clinically by a progressive loss of memory and cognitive functions resulting in severe dementia. Ipriflavone (IPRI) is a non-hormonal, semi-synthetic isoflavone, clinically used in some countries for the treatment and prevention of postmenopausal osteoporosis. Moreover, ipriflavone is a non-peptidomimetic small molecule AChE inhibitor with an improved bioavailability after systemic administration, due to its efficient blood-brain barrier permeability in comparison with peptidomimetic inhibitors. The present study aimed to evaluate the possible enhancing effects of IPRI on memory impairments caused by scopolamine administration. Male rats were administered IPRI (50 mg/kg, oral) 2 h before scopolamine injection (2 mg/kg, intraperitoneally injected) daily for 4 weeks. Effects of IPRI on acetylcholinesterase activity, amyloid-β precursor processing, and neuroplasticity in the rats' hippocampus were investigated. Daily administration of IPRI reverted memory impairment caused by scopolamine as measured by the reduction of the escape latency. IPRI significantly alleviated the oxidative stress and restored the mRNA expression of both cAMP-response element-binding protein and brain-derived neurotrophic factor in the hippocampus. Furthermore, it significantly increased the expression of ADAM10 and ADAM17 (two putative α-secretase enzymes) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) that associated with decreased expression of β-secretase (BACE) in the hippocampus. Finally, both the amyloid-β (Aβ) and Tau pathologies were reduced. IPRI showed promising neuroprotective effects against scopolamine-induced memory dysfunction in rats. These findings contributed to the stimulation of α-secretase enzymes, the activation of MAPK/ERK1/2, and the alleviation of oxidative stress.

Thalamic pathology and memory loss in early Alzheimer’s disease: moving the focus from the medial temporal lobe to Papez circuit

PubMed Central

Pralus, Agathe; Nelson, Andrew J. D.; Hornberger, Michael

2016-01-01

Abstract It is widely assumed that incipient protein pathology in the medial temporal lobe instigates the loss of episodic memory in Alzheimer’s disease, one of the earliest cognitive deficits in this type of dementia. Within this region, the hippocampus is seen as the most vital for episodic memory. Consequently, research into the causes of memory loss in Alzheimer’s disease continues to centre on hippocampal dysfunction and how disease-modifying therapies in this region can potentially alleviate memory symptomology. The present review questions this entrenched notion by bringing together findings from post-mortem studies, non-invasive imaging (including studies of presymptomatic, at-risk cases) and genetically modified animal models. The combined evidence indicates that the loss of episodic memory in early Alzheimer’s disease reflects much wider neurodegeneration in an extended mnemonic system (Papez circuit), which critically involves the limbic thalamus. Within this system, the anterior thalamic nuclei are prominent, both for their vital contributions to episodic memory and for how these same nuclei appear vulnerable in prodromal Alzheimer’s disease. As thalamic abnormalities occur in some of the earliest stages of the disease, the idea that such changes are merely secondary to medial temporal lobe dysfunctions is challenged. This alternate view is further strengthened by the interdependent relationship between the anterior thalamic nuclei and retrosplenial cortex, given how dysfunctions in the latter cortical area provide some of the earliest in vivo imaging evidence of prodromal Alzheimer’s disease. Appreciating the importance of the anterior thalamic nuclei for memory and attention provides a more balanced understanding of Alzheimer’s disease. Furthermore, this refocus on the limbic thalamus, as well as the rest of Papez circuit, would have significant implications for the diagnostics, modelling, and experimental treatment of cognitive symptoms in Alzheimer’s disease. PMID:27190025

The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis.

PubMed

Koenig, Katherine A; Rao, Stephen M; Lowe, Mark J; Lin, Jian; Sakaie, Ken E; Stone, Lael; Bermel, Robert A; Trapp, Bruce D; Phillips, Micheal D

2018-03-01

Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual-spatial episodic memory. Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. After adjusting for disease duration, immediate recall performance on a visual-spatial episodic memory task was significantly predicted by hippocampal volume ( p < 0.003). Delayed recall on the same task was significantly predicted by volume of the left thalamus ( p < 0.003). For both memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p < 0.002). Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

Hippocampus-dependent spatial memory impairment due to molar tooth loss is ameliorated by an enriched environment.

PubMed

Kondo, Hiroko; Kurahashi, Minori; Mori, Daisuke; Iinuma, Mitsuo; Tamura, Yasuo; Mizutani, Kenmei; Shimpo, Kan; Sonoda, Shigeru; Azuma, Kagaku; Kubo, Kin-ya

2016-01-01

Teeth are crucial, not only for mastication, but for overall nutrition and general health, including cognitive function. Aged mice with chronic stress due to tooth loss exhibit impaired hippocampus-dependent learning and memory. Exposure to an enriched environment restores the reduced hippocampal function. Here, we explored the effects of an enriched environment on learning deficits and hippocampal morphologic changes in aged senescence-accelerated mouse strain P8 (SAMP8) mice with tooth loss. Eight-month-old male aged SAMP8 mice with molar intact or with molars removed were housed in either a standard environment or enriched environment for 3 weeks. The Morris water maze was performed for spatial memory test. The newborn cell proliferation, survival, and differentiation in the hippocampus were analyzed using 5-Bromodeoxyuridine (BrdU) immunohistochemical method. The hippocampal brain-derived neurotrophic factor (BDNF) levels were also measured. Mice with upper molars removed (molarless) exhibited a significant decline in the proliferation and survival of newborn cells in the dentate gyrus (DG) as well as in hippocampal BDNF levels. In addition, neuronal differentiation of newly generated cells was suppressed and hippocampus-dependent spatial memory was impaired. Exposure of molarless mice to an enriched environment attenuated the reductions in the hippocampal BDNF levels and neuronal differentiation, and partially improved the proliferation and survival of newborn cells, as well as the spatial memory ability. These findings indicated that an enriched environment could ameliorate the hippocampus-dependent spatial memory impairment induced by molar tooth loss. Copyright © 2015 Elsevier Ltd. All rights reserved.

Role of Mitochondrial Homeostasis and Dynamics in Alzheimer’s Disease

PubMed Central

Selfridge, J. Eva; Lezi, E; Lu, Jianghua; Swerdlow, Russell H.

2012-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that affects a staggering percentage of the aging population and causes memory loss and cognitive decline. Mitochondrial abnormalities can be observed systemically and in brains of patients suffering from AD, and may account for part of the disease phenotype. In this review, we summarize some of the key findings that indicate mitochondrial dysfunction is present in AD-affected subjects, including cytochrome oxidase deficiency, endophenotype data, and altered mitochondrial morphology. Special attention is given to recently described perturbations in mitochondrial autophagy, fission-fusion dynamics, and biogenesis. We also briefly discuss how mitochondrial dysfunction may influence amyloidosis in Alzheimer’s disease, why mitochondria are a valid therapeutic target, and strategies for addressing AD-specific mitochondrial dysfunction. PMID:22266017

L-Arginine and Alzheimer's Disease

PubMed Central

Yi, Jing; Horky, Laura L.; Friedlich, Avi L.; Shi, Ying; Rogers, Jack T.; Huang, Xudong

2009-01-01

Alzheimer's disease (AD), the most common form of dementia, is characterized by progressive neurodegeneration and loss of cognitive and memory functions. Although the exact causes of AD are still unclear, evidence suggests that atherosclerosis, redox stress, inflammation, neurotransmitter dysregulation, and impaired brain energy metabolism may all be associated with AD pathogenesis. Herein, we explore a possible role for L-arginine (L-arg) in AD, taking into consideration known functions for L-arg in atherosclerosis, redox stress and the inflammatory process, regulation of synaptic plasticity and neurogenesis, and modulation of glucose metabolism and insulin activity. L-arg, a precursor of nitric oxide and polyamine, exhibits multiple functions in human health and may play a prominent role in age-related degenerative diseases such as AD. PMID:19079617

Hydrocephalus as a rare compilation of vertebrobasilar dolichoectasia: A case report and review of the literature

PubMed Central

Ebrahimzadeh, Keveh; Bakhtevari, Mehrdad H.; Shafizad, Misagh; Rezaei, Omidvar

2017-01-01

Background: Vertebrobasilar dolichoectasia (VBD) is a rare disease characterized by significant expansion, elongation, and tortuosity of the vertebrobasilar arteries. Hydrocephalus is a rare compilation of VBD. Case Description: In this study, we report a 68-year-old male presenting with headache, progressive decreased visual acuity, memory loss, imbalance while walking, and episodes of urinary incontinency. The patient was diagnosed with dolichoectasia of basilar artery causing compression of the third ventricular outflow and thus, presenting with hydrocephalus documented with brain computed tomography scan and brain magnetic resonance imaging. The patient underwent surgical operation and ventriculoperitoneal shunt placement. Conclusion: In the case of hydrocephalus or normal pressure hydrocephalous, VBD should be considered as a differential diagnosis. PMID:29184707

Damping of High-temperature Shape Memory Alloys

NASA Technical Reports Server (NTRS)

Duffy, Kirsten P.; Padula, Santo A., II; Scheiman, Daniel A.

2008-01-01

Researchers at NASA Glenn Research Center have been investigating high temperature shape memory alloys as potential damping materials for turbomachinery rotor blades. Analysis shows that a thin layer of SMA with a loss factor of 0.04 or more would be effective at reducing the resonant response of a titanium alloy beam. Two NiTiHf shape memory alloy compositions were tested to determine their loss factors at frequencies from 0.1 to 100 Hz, at temperatures from room temperature to 300 C, and at alternating strain levels of 34-35x10(exp -6). Elevated damping was demonstrated between the M(sub s) and M(sub f) phase transformation temperatures and between the A(sub s) and A(sub f) temperatures. The highest damping occurred at the lowest frequencies, with a loss factor of 0.2-0.26 at 0.1 Hz. However, the peak damping decreased with increasing frequency, and showed significant temperature hysteresis in heating and cooling. Keywords: High-temperature, shape memory alloy, damping, aircraft engine blades, NiTiHf

Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

PubMed

Spalletta, Gianfranco; Cravello, Luca; Gianni, Walter; Piras, Federica; Iorio, Mariangela; Cacciari, Claudia; Casini, Anna Rosa; Chiapponi, Chiara; Sancesario, Giuseppe; Fratangeli, Claudia; Orfei, Maria Donata; Caltagirone, Carlo; Piras, Fabrizio

2016-01-01

Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

[Post-traumatic coma and pre-traumatic memory].

PubMed

Malacrida, R; Piazza, J; Abraham, G

1990-01-01

Instead of thinking that it is impossible to enter in the internal world of a comatose patient, we are now put before a new and encouraging prospective, that of the possibility, even though minimal, of influencing the vital residual organisation of the patient and to induce him perhaps to accept again external stimulations, which previously were too intense. As loss of conscience often causes loss of memory, our intention was to examine the problem of memory loss in comatose patients after accidents. The analysis of 50 questionnaires distributed to trauma-patients awakening from a comatose state and interviews give clear indications that: 1) the patients remember absolutely nothing during the time of the coma; 2) in the majority of cases (34) the patients remember in the moment preceding the accident a clear autodestructive tendency especially if they were the cause of the accident; and 3) almost all patients (41) agree to have benefited greatly from the trauma itself and from its memory.

Long-term consequences of a prolonged febrile seizure in a dual pathology model.

PubMed

Gibbs, Steve; Chattopadhyaya, Bidisha; Desgent, Sébastien; Awad, Patricia N; Clerk-Lamalice, Olivier; Levesque, Maxime; Vianna, Rose-Mari; Rébillard, Rose-Marie; Delsemme, Andrée-Anne; Hébert, David; Tremblay, Luc; Lepage, Martin; Descarries, Laurent; Di Cristo, Graziella; Carmant, Lionel

2011-08-01

Clinical evidence suggests that febrile status epilepticus (SE) in children can lead to acute hippocampal injury and subsequent temporal lobe epilepsy. The contribution of febrile SE to the mechanisms underlying temporal lobe epilepsy are however poorly understood. A rat model of temporal lobe epilepsy following hyperthermic SE was previously established in our laboratory, wherein a focal cortical lesion induced at postnatal day 1 (P1), followed by a hyperthermic SE (more than 30 min) at P10, leads to hippocampal atrophy at P22 (dual pathology model) and spontaneous recurrent seizures (SRS) with mild visuospatial memory deficits in adult rats. The goal of this study was to identify the long term electrophysiological, anatomical and molecular changes in this model. Following hyperthermic SE, all cortically lesioned pups developed progressive SRS as adults, characterized by the onset of highly rhythmic activity in the hippocampus. A reduction of hippocampal volume on the side of the lesion preceded the SRS and was associated with a loss of hippocampal neurons, a marked decrease in pyramidal cell spine density, an increase in the hippocampal levels of NMDA receptor NR2A subunit, but no significant change in GABA receptors. These findings suggest that febrile SE in the abnormal brain leads to hippocampal injury that is followed by progressive network reorganization and molecular changes that contribute to the epileptogenesis as well as the observed memory deficits. Copyright © 2011 Elsevier Inc. All rights reserved.

Andrographolide reduces cognitive impairment in young and mature AβPPswe/PS-1 mice.

PubMed

Serrano, Felipe G; Tapia-Rojas, Cheril; Carvajal, Francisco J; Hancke, Juan; Cerpa, Waldo; Inestrosa, Nibaldo C

2014-12-18

Alzheimer's disease (AD) is a neurodegenerative disorder in which the amyloid-β (Aβ) oligomers are a key factor in synaptic impairment and in spatial memory decline associated with neuronal dysfunction. This impairment includes synaptic failure associated with the loss of synaptic proteins that contribute to AD progression. Interestingly, the use of natural compounds is an emergent conceptual strategy in the search for drugs with therapeutic potentials for treating neurodegenerative disorders. In the present study, we report that andrographolide (ANDRO), which is a labdane diterpene extracted from Andrographis paniculata, increases slope of field excitatory postsynaptic potentials (fEPSP) in the CA1 region of hippocampal slices and inhibits long-term depression (LTD), protecting the long-term potentiation (LTP) against the damage induced by Aβ oligomers in vitro, most likely by inhibiting glycogen synthase kinase-3β (GSK-3β). Additionally, ANDRO prevents changes in neuropathology in two different age groups (7- and 12-month-old mice) of an AβPPswe/PS-1 Alzheimer's model. ANDRO reduces the Aβ levels, changing the ontogeny of amyloid plaques in hippocampi and cortices in 7-month-old mice, and reduces tau phosphorylation around the Aβ oligomeric species in both age groups. Additionally, we observed that ANDRO recovers spatial memory functions that correlate with protecting synaptic plasticity and synaptic proteins in two different age groups. Our results suggest that ANDRO could be used in a potential preventive therapy during AD progression.

Self-Awareness and Self-Monitoring of Cognitive and Behavioral Deficits in Behavioral Variant Frontotemporal Dementia, Primary Progressive Aphasia and Probable Alzheimer’s Disease

PubMed Central

Banks, Sarah; Weintraub, Sandra

2008-01-01

Lack of insight is a core diagnostic criterion for behavioral variant frontotemporal dementia (bvFTD), and is believed to be intact in the early stages of primary progressive aphasia (PPA). In other neurological conditions, symptom-specific insight has been noted, with behavioral symptoms appearing especially vulnerable to reduced insight. Different components of insight, self-awareness and self-monitoring, are also often considered separate phenomena. The current study compared insight in patients with PPA, bvFTD, and probable Alzheimer’s disease (PrAD) and a group of cognitively intact control subjects. Additionally, differences in insight for the domains primarily affected by the three types of dementia, namely, Behavior, Naming, and Memory, were assessed, and self-awareness and self-monitoring were compared. A total of 55 participants were enrolled. Participants were asked to complete self-estimate scales demonstrating their perceived ability immediately prior to, and immediately following a test in each domain of interest. Results indicated that PPA and normal control groups performed very similarly on control (Weight and Eyesight) and cognitive domains, whereas bvFTD and PrAD patients were unable to accurately assess Memory. All three diagnostic groups failed to accurately assess their behavioral symptoms, suggesting that this domain is vulnerable to loss of insight across diagnoses. Naming ability, in contrast, was either accurately assessed or underestimated in all groups. Finally, there were no notable differences between self-awareness and self-monitoring, potential explanations for this are examined. PMID:18194832

Impact of sleep loss before learning on cortical dynamics during memory retrieval.

PubMed

Alberca-Reina, E; Cantero, J L; Atienza, M

2015-12-01

Evidence shows that sleep loss before learning decreases activation of the hippocampus during encoding and promotes forgetting. But it remains to be determined which neural systems are functionally affected during memory retrieval after one night of recovery sleep. To investigate this issue, we evaluated memory for pairs of famous people's faces with the same or different profession (i.e., semantically congruent or incongruent faces) after one night of undisturbed sleep in subjects who either underwent 4hours of acute sleep restriction (ASR, N=20) or who slept 8hours the pre-training night (controls, N=20). EEG recordings were collected during the recognition memory task in both groups, and the cortical sources generating this activity localized by applying a spatial beamforming filter in the frequency domain. Even though sleep restriction did not affect accuracy of memory performance, controls showed a much larger decrease of alpha power relative to a baseline period when compared to sleep-deprived subjects. These group differences affected a widespread frontotemporoparietal network involved in retrieval of episodic/semantic memories. Regression analyses further revealed that associative memory in the ASR group was negatively correlated with alpha power in the occipital regions, whereas the benefit of congruency in the same group was positively correlated with delta power in the left lateral prefrontal cortex. Retrieval-related decreases of alpha power have been associated with the reactivation of material-specific memory representations, whereas increases of delta power have been related to inhibition of interferences that may affect the performance of the task. We can therefore draw the conclusion that a few hours of sleep loss in the pre-training night, though insufficient to change the memory performance, is sufficient to alter the processes involved in retrieving and manipulating episodic and semantic information. Copyright © 2015 Elsevier Inc. All rights reserved.

Positive Outcomes Enhance Incidental Learning for Both Younger and Older Adults

PubMed Central

Mather, Mara; Schoeke, Andrej

2011-01-01

Previous studies suggest that memory encoding is enhanced when people are anticipating a potential reward, consistent with the idea that dopaminergic systems that respond to motivationally relevant information also enhance memory for that information. In the current study, we examined how anticipating and receiving rewards versus losses affect incidental learning of information. In addition, we compared the modulatory effects of reward anticipation and outcome on memory for younger and older adults. Forty-two younger (aged 18–33 years) and 44 older (aged 66–92 years) adults played a game involving pressing a button as soon as they saw a target. Gain trials began with a cue that they would win $0.25 if they pressed the button fast enough, loss trials began with a cue that they would avoid losing $0.25 if they pressed the button fast enough, and no-outcome trials began with a cue indicating no monetary outcome. The target was a different photo-object on each trial (e.g., balloon, dolphin) and performance outcomes were displayed after the photo disappeared. Both younger and older adults recalled and recognized pictures from trials with positive outcomes (either rewarding or loss avoiding) better than from trials with negative outcomes. Positive outcomes were associated with not only enhanced memory for the picture just seen in that trial, but also with enhanced memory for the pictures shown in the next two trials. Although anticipating a reward also enhanced incidental memory, this effect was seen only in recognition memory of positive pictures and was a smaller effect than the outcome effect. The fact that older adults showed similar incidental memory effects of reward anticipation and outcome as younger adults suggests that reward–memory system interactions remain intact in older age. PMID:22125509

FMRI of visual working memory in high school football players.

PubMed

Shenk, Trey E; Robinson, Meghan E; Svaldi, Diana O; Abbas, Kausar; Breedlove, Katherine M; Leverenz, Larry J; Nauman, Eric A; Talavage, Thomas M

2015-01-01

Visual working memory deficits have been observed in at-risk athletes. This study uses a visual N-back working memory functional magnetic resonance imaging task to longitudinally assess asymptomatic football athletes for abnormal activity. Athletes were increasingly "flagged" as the season progressed. Flagging may provide early detection of injury.

Antioxidant Property of Jobelyn as the Possible Mechanism Underlying its Anti-amnesic Activity in Rodents.

PubMed

Umukoro, Solomon; Ugbomah, Adaeze; Aderibigbe, Adegbuyi; Omogbiya, Adrian

2013-01-01

Amnesia or loss of memory is the cardinal hallmark of Alzheimer's disease (AD), a progressive neurodegenerative disorder associated with ageing process. Although, AD had been discovered over a century ago, drugs which could cure or halt the progression of the disease are yet to see the light of the day. However, there has been a growing interest in the use of phytomedicines with multipronged mechanisms of action that could target various aspects of the pathologies of AD. Jobelyn (JB) is a potent antioxidant African polyherbal formulation with active components that have been acclaimed to show neuroprotection. This investigation was carried out to evaluate whether JB has anti-amnesic and antioxidant activities. The alteration of alternation behavior in the Y-maze paradigm was utilized as the test for memory function in mice. The effect of JB on acetylcholinesterase (AChE) activity, malondialdehyde (MDA) level and the concentrations of glutathione (GSH) in the frontal cortex and hippocampus were assessed in rats as means of providing insight into the mechanism underlying its anti-amnesic activity. The animals were given JB (1, 2.5 or 5mg/kg, i.p.) daily for 7 days before the biochemical assays or test for memory functions were carried out. JB was found to produce a significant increase in the level of alternation behavior compared with the control, suggesting anti-amnesic activity. Also, JB reversed the memory impairment induced by scopolamine, which further indicates anti-amnesic property. Furthermore, JB demonstrated a significant inhibition of MDA formation in the frontal cortex and hippocampus of rats, indicating antioxidant property. In addition, it increased the defense armory of the brain tissues, as it significantly increased the concentrations of GSH in the frontal cortex and hippocampus of rats. However, JB did not demonstrate any inhibitory effect against AChE activity in the frontal cortex and hippocampus of rats in comparison with the control group. This investigation provides evidence that suggests that JB has anti-amnesic and antioxidant properties. Although the present data suggest that the anti-amnesic property of JB might be related to its antioxidant activity, more studies are necessary to clarify this observation.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

PubMed Central

2011-01-01

Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time. PMID:21816065

Cognitive improvement following repair of a basal encephalocele.

PubMed

Tulloch, Isabel; Palmer, Siobhan; Scott, Richard; Lozsadi, Dora; Martin, Andrew J

2018-06-01

We report the case of a 55-year-old woman presenting with progressive memory impairment secondary to a transsphenoidal encephalocele involving her dominant medial temporal lobe. Her clinical deterioration was accompanied by radiological progression in the encephalocele's size and associated encephalomalacia. Through a temporal craniotomy, her encephalocele was resected and the defect closed. Baseline neuropsychological assessment indicated global cognitive impairment, but post-operatively, she reported improved memory and concentration. Standardized assessment reflected an improvement in perceptual skills and an associated improved recall of a complex figure. This is the first case report to date of a patient's memory improving following treatment of a basal encephalocele.

Loss of Cdc42 leads to defects in synaptic plasticity and remote memory recall

PubMed Central

Kim, Il Hwan; Wang, Hong; Soderling, Scott H; Yasuda, Ryohei

2014-01-01

Cdc42 is a signaling protein important for reorganization of actin cytoskeleton and morphogenesis of cells. However, the functional role of Cdc42 in synaptic plasticity and in behaviors such as learning and memory are not well understood. Here we report that postnatal forebrain deletion of Cdc42 leads to deficits in synaptic plasticity and in remote memory recall using conditional knockout of Cdc42. We found that deletion of Cdc42 impaired LTP in the Schaffer collateral synapses and postsynaptic structural plasticity of dendritic spines in CA1 pyramidal neurons in the hippocampus. Additionally, loss of Cdc42 did not affect memory acquisition, but instead significantly impaired remote memory recall. Together these results indicate that the postnatal functions of Cdc42 may be crucial for the synaptic plasticity in hippocampal neurons, which contribute to the capacity for remote memory recall. DOI: http://dx.doi.org/10.7554/eLife.02839.001 PMID:25006034

Cdk5 Is Required for Memory Function and Hippocampal Plasticity via the cAMP Signaling Pathway

PubMed Central

Gao, Jun; Joseph, Nadine; Xie, Zhigang; Zhou, Ying; Durak, Omer; Zhang, Lei; Zhu, J. Julius; Clauser, Karl R.; Carr, Steven A.; Tsai, Li-Huei

2011-01-01

Memory formation is modulated by pre- and post-synaptic signaling events in neurons. The neuronal protein kinase Cyclin-Dependent Kinase 5 (Cdk5) phosphorylates a variety of synaptic substrates and is implicated in memory formation. It has also been shown to play a role in homeostatic regulation of synaptic plasticity in cultured neurons. Surprisingly, we found that Cdk5 loss of function in hippocampal circuits results in severe impairments in memory formation and retrieval. Moreover, Cdk5 loss of function in the hippocampus disrupts cAMP signaling due to an aberrant increase in phosphodiesterase (PDE) proteins. Dysregulation of cAMP is associated with defective CREB phosphorylation and disrupted composition of synaptic proteins in Cdk5-deficient mice. Rolipram, a PDE4 inhibitor that prevents cAMP depletion, restores synaptic plasticity and memory formation in Cdk5-deficient mice. Collectively, our results demonstrate a critical role for Cdk5 in the regulation of cAMP-mediated hippocampal functions essential for synaptic plasticity and memory formation. PMID:21984943

Design and Rationale of the Cognitive Intervention to Improve Memory in Heart Failure Patients Study.

PubMed

Pressler, Susan J; Giordani, Bruno; Titler, Marita; Gradus-Pizlo, Irmina; Smith, Dean; Dorsey, Susan G; Gao, Sujuan; Jung, Miyeon

Memory loss is an independent predictor of mortality among heart failure patients. Twenty-three percent to 50% of heart failure patients have comorbid memory loss, but few interventions are available to treat the memory loss. The aims of this 3-arm randomized controlled trial were to (1) evaluate efficacy of computerized cognitive training intervention using BrainHQ to improve primary outcomes of memory and serum brain-derived neurotrophic factor levels and secondary outcomes of working memory, instrumental activities of daily living, and health-related quality of life among heart failure patients; (2) evaluate incremental cost-effectiveness of BrainHQ; and (3) examine depressive symptoms and genomic moderators of BrainHQ effect. A sample of 264 heart failure patients within 4 equal-sized blocks (normal/low baseline cognitive function and gender) will be randomly assigned to (1) BrainHQ, (2) active control computer-based crossword puzzles, and (3) usual care control groups. BrainHQ is an 8-week, 40-hour program individualized to each patient's performance. Data collection will be completed at baseline and at 10 weeks and 4 and 8 months. Descriptive statistics, mixed model analyses, and cost-utility analysis using intent-to-treat approach will be computed. This research will provide new knowledge about the efficacy of BrainHQ to improve memory and increase serum brain-derived neurotrophic factor levels in heart failure. If efficacious, the intervention will provide a new therapeutic approach that is easy to disseminate to treat a serious comorbid condition of heart failure.

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

PubMed Central

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-01-01

Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

PubMed

Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

2016-12-01

Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins

PubMed Central

Kurtulus, S; Sholl, A; Toe, J; Tripathi, P; Raynor, J; Li, K-P; Pellegrini, M; Hildeman, D A

2015-01-01

During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential. PMID:25124553

Bim controls IL-15 availability and limits engagement of multiple BH3-only proteins.

PubMed

Kurtulus, S; Sholl, A; Toe, J; Tripathi, P; Raynor, J; Li, K-P; Pellegrini, M; Hildeman, D A

2015-01-01

During the effector CD8+ T-cell response, transcriptional differentiation programs are engaged that promote effector T cells with varying memory potential. Although these differentiation programs have been used to explain which cells die as effectors and which cells survive and become memory cells, it is unclear if the lack of cell death enhances memory. Here, we investigated effector CD8+ T-cell fate in mice whose death program has been largely disabled because of the loss of Bim. Interestingly, the absence of Bim resulted in a significant enhancement of effector CD8+ T cells with more memory potential. Bim-driven control of memory T-cell development required T-cell-specific, but not dendritic cell-specific, expression of Bim. Both total and T-cell-specific loss of Bim promoted skewing toward memory precursors, by enhancing the survival of memory precursors, and limiting the availability of IL-15. Decreased IL-15 availability in Bim-deficient mice facilitated the elimination of cells with less memory potential via the additional pro-apoptotic molecules Noxa and Puma. Combined, these data show that Bim controls memory development by limiting the survival of pre-memory effector cells. Further, by preventing the consumption of IL-15, Bim limits the role of Noxa and Puma in causing the death of effector cells with less memory potential.

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

PubMed Central

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

2015-01-01

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

Neural Evidence for a Distinction Between Short-Term Memory and the Focus of Attention

PubMed Central

Lewis-Peacock, Jarrod A.; Drysdale, Andrew T.; Oberauer, Klaus; Postle, Bradley R.

2011-01-01

It is widely assumed that the short-term retention of information is accomplished via maintenance of an active neural trace. However, we demonstrate that memory can be preserved across a brief delay despite the apparent loss of sustained representations. Delay-period activity may in fact reflect the focus of attention, rather than short-term memory. We unconfounded attention and memory by causing external and internal shifts of attention away from items that were being actively retained. Multivariate pattern analysis of fMRI indicated that only items within the focus of attention elicited an active neural trace. Activity corresponding to representations of items outside the focus quickly dropped to baseline. Nevertheless, this information was remembered after a brief delay. Our data also show that refocusing attention towards a previously unattended memory item can reactivate its neural signature. The loss of sustained activity has long been thought to indicate a disruption of short-term memory, but our results suggest that, even for small memory loads not exceeding the capacity limits of short-term memory, the active maintenance of a stimulus representation may not be necessary for its short-term retention. PMID:21955164

Bombesin administration impairs memory and does not reverse memory deficit caused by sleep deprivation.

PubMed

Ferreira, L B T; Oliveira, S L B; Raya, J; Esumi, L A; Hipolide, D C

2017-07-28

Sleep deprivation impairs performance in emotional memory tasks, however this effect on memory is not completely understood. Possible mechanisms may involve an alteration in neurotransmission systems, as shown by the fact that many drugs that modulate neural pathways can prevent memory impairment by sleep loss. Gastrin releasing peptide (GRP) is a neuropeptide that emerged as a regulatory molecule of emotional memory through the modulation of other neurotransmission systems. Thus, the present study addressed the effect of intraperitoneal (IP) administration of bombesin (BB) (2.5, 5.0 and 10.0μg/kg), a GRP agonist, on the performance of Wistar rats in a multiple trail inhibitory avoidance (MTIA) task, after sleep deprivation, using the modified multiple platforms method (MMPM). Sleep deprived animals exhibited acquisition and retention impairment that was not prevented by BB injection. In addition, non-sleep deprived animals treated with BB before and after the training session, but not before the test, have shown a retention deficit. In summary, BB did not improve the memory impairment by sleep loss and, under normal conditions, produced a memory consolidation deficit. Copyright © 2017 Elsevier B.V. All rights reserved.

Robust relationship between reading span and speech recognition in noise

PubMed Central

Souza, Pamela; Arehart, Kathryn

2015-01-01

Objective Working memory refers to a cognitive system that manages information processing and temporary storage. Recent work has demonstrated that individual differences in working memory capacity measured using a reading span task are related to ability to recognize speech in noise. In this project, we investigated whether the specific implementation of the reading span task influenced the strength of the relationship between working memory capacity and speech recognition. Design The relationship between speech recognition and working memory capacity was examined for two different working memory tests that varied in approach, using a within-subject design. Data consisted of audiometric results along with the two different working memory tests; one speech-in-noise test; and a reading comprehension test. Study sample The test group included 94 older adults with varying hearing loss and 30 younger adults with normal hearing. Results Listeners with poorer working memory capacity had more difficulty understanding speech in noise after accounting for age and degree of hearing loss. That relationship did not differ significantly between the two different implementations of reading span. Conclusions Our findings suggest that different implementations of a verbal reading span task do not affect the strength of the relationship between working memory capacity and speech recognition. PMID:25975360

Robust relationship between reading span and speech recognition in noise.

PubMed

Souza, Pamela; Arehart, Kathryn

2015-01-01

Working memory refers to a cognitive system that manages information processing and temporary storage. Recent work has demonstrated that individual differences in working memory capacity measured using a reading span task are related to ability to recognize speech in noise. In this project, we investigated whether the specific implementation of the reading span task influenced the strength of the relationship between working memory capacity and speech recognition. The relationship between speech recognition and working memory capacity was examined for two different working memory tests that varied in approach, using a within-subject design. Data consisted of audiometric results along with the two different working memory tests; one speech-in-noise test; and a reading comprehension test. The test group included 94 older adults with varying hearing loss and 30 younger adults with normal hearing. Listeners with poorer working memory capacity had more difficulty understanding speech in noise after accounting for age and degree of hearing loss. That relationship did not differ significantly between the two different implementations of reading span. Our findings suggest that different implementations of a verbal reading span task do not affect the strength of the relationship between working memory capacity and speech recognition.

Relationship Among Signal Fidelity, Hearing Loss, and Working Memory for Digital Noise Suppression.

PubMed

Arehart, Kathryn; Souza, Pamela; Kates, James; Lunner, Thomas; Pedersen, Michael Syskind

2015-01-01

This study considered speech modified by additive babble combined with noise-suppression processing. The purpose was to determine the relative importance of the signal modifications, individual peripheral hearing loss, and individual cognitive capacity on speech intelligibility and speech quality. The participant group consisted of 31 individuals with moderate high-frequency hearing loss ranging in age from 51 to 89 years (mean = 69.6 years). Speech intelligibility and speech quality were measured using low-context sentences presented in babble at several signal-to-noise ratios. Speech stimuli were processed with a binary mask noise-suppression strategy with systematic manipulations of two parameters (error rate and attenuation values). The cumulative effects of signal modification produced by babble and signal processing were quantified using an envelope-distortion metric. Working memory capacity was assessed with a reading span test. Analysis of variance was used to determine the effects of signal processing parameters on perceptual scores. Hierarchical linear modeling was used to determine the role of degree of hearing loss and working memory capacity in individual listener response to the processed noisy speech. The model also considered improvements in envelope fidelity caused by the binary mask and the degradations to envelope caused by error and noise. The participants showed significant benefits in terms of intelligibility scores and quality ratings for noisy speech processed by the ideal binary mask noise-suppression strategy. This benefit was observed across a range of signal-to-noise ratios and persisted when up to a 30% error rate was introduced into the processing. Average intelligibility scores and average quality ratings were well predicted by an objective metric of envelope fidelity. Degree of hearing loss and working memory capacity were significant factors in explaining individual listener's intelligibility scores for binary mask processing applied to speech in babble. Degree of hearing loss and working memory capacity did not predict listeners' quality ratings. The results indicate that envelope fidelity is a primary factor in determining the combined effects of noise and binary mask processing for intelligibility and quality of speech presented in babble noise. Degree of hearing loss and working memory capacity are significant factors in explaining variability in listeners' speech intelligibility scores but not in quality ratings.

T-cell differentiation and CD56+ levels in polypoidal choroidal vasculopathy and neovascular age-related macular degeneration.

PubMed

Subhi, Yousif; Nielsen, Marie Krogh; Molbech, Christopher Rue; Oishi, Akio; Singh, Amardeep; Nissen, Mogens Holst; Sørensen, Torben Lykke

2017-11-20

Polypoidal choroidal vasculopathy (PCV) and neovascular age-related macular degeneration (AMD) are prevalent age-related diseases characterized by exudative changes in the macula. Although they share anatomical and clinical similarities, they are also distinctly characterized by their own features, e.g. vascular abnormalities in PCV and drusen-mediated progression in neovascular AMD. PCV remains etiologically uncharacterized, and ongoing discussion is whether PCV and neovascular AMD share the same etiology or constitute two substantially different diseases. In this study, we investigated T-cell differentiation and aging profile in human patients with PCV, patients with neovascular AMD, and age-matched healthy control individuals. Fresh venous blood was prepared for flow cytometry to investigate CD4 + and CD8 + T-cell differentiation (naïve, central memory, effector memory, effector memory CD45ra + ), loss of differentiation markers CD27 and CD28, and expression of aging marker CD56. Patients with PCV were similar to the healthy controls in all aspects. In patients with neovascular AMD we found significantly accelerated T-cell differentiation (more CD28 - CD27 - cells) and aging (more CD56 + cells) in the CD8 + T-cell compartment. These findings suggest that PCV and neovascular AMD are etiologically different in terms of T cell immunity, and that neovascular AMD is associated with T-cell immunosenescence.

Histone deacetylase inhibitor treatment restores memory-related gene expression and learning ability in neonicotinoid-treated Apis mellifera.

PubMed

Hu, Y-T; Tang, C-K; Wu, C-P; Wu, P-C; Yang, E-C; Tai, C-C; Wu, Y-L

2018-04-25

Apis mellifera plays crucial roles in maintaining the balance of global ecosystems and stability of agricultural systems by helping pollination of flowering plants, including many crops. In recent years, this balance has been disrupted greatly by some pesticides, which results in great losses of honeybees worldwide. Previous studies have found that pesticide-caused memory loss might be one of the major reasons for colony loss. Histone deacetylase inhibitors (HDACis) are chemical compounds that inhibit the activity of histone deacetylases and are known to cause hyperacetylation of histone cores and influence gene expression. In our study, the HDACi sodium butyrate was applied to honeybees as a dietary supplement. The effect of sodium butyrate on the expression profiles of memory-related genes was analysed by quantitative reverse transcription PCR. The results revealed that this HDACi had up-regulation effects on most of the memory-related genes in bees, even in bees treated with imidacloprid. In addition, using the proboscis extension reflex to evaluate olfactory learning in bees, we found that this HDACi boosted the memory formation of bees after impairment owing to imidacloprid exposure. This study investigated the association between gene expression and memory formation from an epigenetic perspective. Additionally, we further demonstrate the possibility of enhancing bee learning using HDACis and provide initial data for future research. © 2018 The Royal Entomological Society.

Protective effects of cultured and fermented ginseng extracts against scopolamine-induced memory loss in a mouse model.

PubMed

Han, Song-Hee; Kim, Sung-June; Yun, Young Won; Nam, Sang Yoon; Lee, Hu-Jang; Lee, Beom-Jun

2018-03-01

This study was performed to investigate the effect of a concentrate of fermented wild ginseng root culture (HLJG0701) on memory improvement in the scopolamine (SPL)-induced memory-deficient mouse model. Eight-week-old male ICR mice were used to evaluate the protective effect of HLJG0701 against the SPL-induced memory loss animal model. The Morris water maze test, which measures hippocampus-dependent learning ability, and the Y-maze test, a short-term memory assessment test, were performed and related markers were analyzed. HLJG0701-treated groups displayed significantly reduced acetylcholinesterase activity and increased acetylcholine level compared with the SPL-administered group (SPL-G) ( P <0.05). In the Y-maze test, the spontaneous alternation in al HLJG0711-treated groups was significantly increased compared with that in SPL-G ( P <0.05). In the Morris water maze test, the escape latency and time spent in the target quadrant in all HLJG0701-treated groups were significantly decreased and increased, respectively, compared with those in SPL-G ( P <0.05). In addition, the brain-derived neurotrophic factor level in groups treated with HLJG0701 300 and 600 mg/kg body weight was significantly increased compared with that in SPL-G ( P <0.05). These results suggest that the HLJG0701 may protect against memory loss by inhibiting acetylcholinesterase activity and preventing acetylcholine deficiency.

Meeting an "impossible challenge" in semantic dementia: outstanding performance in numerical Sudoku and quantitative number knowledge.

PubMed

Papagno, Costanza; Semenza, Carlo; Girelli, Luisa

2013-11-01

This study describes a follow-up investigation of numerical abilities and visuospatial memory in a patient suffering from semantic dementia whose progressive decline of semantic memory variably affected different types of knowledge. Crucially, we investigated in detail her outstanding performance with Sudoku that has been only anecdotally reported in the previous literature. We tested spatial cognition and memory, body representation, number processing, calculation, and Sudoku tasks, and we compared the patient's performance with that of matched controls. In agreement with the neuroanatomical data, showing substantial sparing of the parietal lobes in the face of severe atrophy of the temporal (and frontal) regions, we report full preservation of skills known to be supported by intact parietal-basal ganglia networks, and impaired knowledge related to long-term stored declarative information mediated by temporal regions. Performance in tasks sensitive to parietal dysfunction (such as right-left orientation, finger gnosis, writing, and visuospatial memory) was normal; within the numerical domain, preserved quantity-based number knowledge dissociated from increasing difficulties with nonquantitative number knowledge (such as knowledge of encyclopedic and personal number facts) and arithmetic facts knowledge. This case confirms the relation between numbers and space, and, although indirectly, their anatomical correlates, underlining which abilities are preserved in the case of severe semantic loss. In addition, although Sudoku is not inherently numerical, the patient was able to solve even the most difficult pattern, provided that it required digits and not letters, showing that digits have, in any case, a specific status. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Voluntary Running Attenuates Memory Loss, Decreases Neuropathological Changes and Induces Neurogenesis in a Mouse Model of Alzheimer's Disease.

PubMed

Tapia-Rojas, Cheril; Aranguiz, Florencia; Varela-Nallar, Lorena; Inestrosa, Nibaldo C

2016-01-01

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by loss of memory and cognitive abilities, and the appearance of amyloid plaques composed of the amyloid-β peptide (Aβ) and neurofibrillary tangles formed of tau protein. It has been suggested that exercise might ameliorate the disease; here, we evaluated the effect of voluntary running on several aspects of AD including amyloid deposition, tau phosphorylation, inflammatory reaction, neurogenesis and spatial memory in the double transgenic APPswe/PS1ΔE9 mouse model of AD. We report that voluntary wheel running for 10 weeks decreased Aβ burden, Thioflavin-S-positive plaques and Aβ oligomers in the hippocampus. In addition, runner APPswe/PS1ΔE9 mice showed fewer phosphorylated tau protein and decreased astrogliosis evidenced by lower staining of GFAP. Further, runner APPswe/PS1ΔE9 mice showed increased number of neurons in the hippocampus and exhibited increased cell proliferation and generation of cells positive for the immature neuronal protein doublecortin, indicating that running increased neurogenesis. Finally, runner APPswe/PS1ΔE9 mice showed improved spatial memory performance in the Morris water maze. Altogether, our findings indicate that in APPswe/PS1ΔE9 mice, voluntary running reduced all the neuropathological hallmarks of AD studied, reduced neuronal loss, increased hippocampal neurogenesis and reduced spatial memory loss. These findings support that voluntary exercise might have therapeutic value on AD. © 2015 International Society of Neuropathology.

Transient Relay Function of Midline Thalamic Nuclei during Long-Term Memory Consolidation in Humans

ERIC Educational Resources Information Center

Thielen, Jan-Willem; Takashima, Atsuko; Rutters, Femke; Tendolkar, Indira; Fernández, Guillén

2015-01-01

To test the hypothesis that thalamic midline nuclei play a transient role in memory consolidation, we reanalyzed a prospective functional MRI study, contrasting recent and progressively more remote memory retrieval. We revealed a transient thalamic connectivity increase with the hippocampus, the medial prefrontal cortex (mPFC), and a…

British memory research: a journey through the 20th century.

PubMed

Parkin, A J; Hunkin, N M

2001-02-01

A century of research in memory has generated a wealth of knowledge encompassing theoretical developments within a number of distinct domains of memory. The aim of this article is to explore the progress made in memory research during the 20th century, to indicate critical influences on the direction of research, and to illustrate the important contribution made by British researchers. This article is confined to human memory research, and reviews research findings from the various psychological disciplines studied over the past 100 years.

Noninvasive stimulation of prefrontal cortex strengthens existing episodic memories and reduces forgetting in the elderly

PubMed Central

Sandrini, Marco; Brambilla, Michela; Manenti, Rosa; Rosini, Sandra; Cohen, Leonardo G.; Cotelli, Maria

2014-01-01

Memory consolidation is a dynamic process. Reactivation of consolidated memories by a reminder triggers reconsolidation, a time-limited period during which existing memories can be modified (i.e., weakened or strengthened). Episodic memory refers to our ability to recall specific past events about what happened, including where and when. Difficulties in this form of long-term memory commonly occur in healthy aging. Because episodic memory is critical for daily life functioning, the development of effective interventions to reduce memory loss in elderly individuals is of great importance. Previous studies in young adults showed that the dorsolateral prefrontal cortex (DLPFC) plays a causal role in strengthening of verbal episodic memories through reconsolidation. The aim of the present study was to explore the extent to which facilitatory transcranial direct current stimulation (anodal tDCS) over the left DLPFC would strengthen existing episodic memories through reconsolidation in elderly individuals. On Day 1, older adults learned a list of 20 words. On Day 2 (24 h later), they received a reminder or not, and after 10 min tDCS was applied over the left DLPFC. Memory recall was tested on Day 3 (48 h later) and Day 30 (1 month later). Surprisingly, anodal tDCS over the left DLPFC (i.e., with or without the reminder) strengthened existing verbal episodic memories and reduced forgetting compared to sham stimulation. These results provide a framework for testing the hypothesis that facilitatory tDCS of left DLPFC might strengthen existing episodic memories and reduce memory loss in older adults with amnestic mild cognitive impairment. PMID:25368577

The Impact of Sleep Loss on Hippocampal Function

ERIC Educational Resources Information Center

Prince, Toni-Moi; Abel, Ted

2013-01-01

Hippocampal cellular and molecular processes critical for memory consolidation are affected by the amount and quality of sleep attained. Questions remain with regard to how sleep enhances memory, what parameters of sleep after learning are optimal for memory consolidation, and what underlying hippocampal molecular players are targeted by sleep…

Volumetric correlates of memory and executive function in normal elderly, mild cognitive impairment and Alzheimer’s disease

PubMed Central

Duarte, Audrey; Hayasaka, Satoru; Du, Antao; Schuff, Norbert; Jahng, Geon-Ho; Kramer, Joel; Miller, Bruce; Weiner, Michael

2007-01-01

In Alzheimer’s disease (AD), atrophy negatively impacts cognition while in healthy adults, inverse relationships between brain volume and cognition may occur. We investigated correlations between gray matter volume and cognition in elderly controls, AD and mild cognitive impairment (MCI) patients with memory and executive deficits. AD demonstrated substantial loss in temporal, parietal and frontal regions while MCI exhibited moderate volume loss in temporal and frontal regions. In controls, memory and executive function were negatively correlated with frontal regions, while in AD, memory was positively correlated with temporal and frontal gyri, and executive function with frontal regions. The combination of the two patterns may explain the lack of correlations in MCI. Developmental versus pathological contributions to these relationships are discussed. PMID:16904823

Spin transport and spin torque in antiferromagnetic devices

DOE PAGES

Zelezny, J.; Wadley, P.; Olejnik, K.; ...

2018-03-02

Ferromagnets are key materials for sensing and memory applications. In contrast, antiferromagnets which represent the more common form of magnetically ordered materials, have found less practical application beyond their use for establishing reference magnetic orientations via exchange bias. This might change in the future due to the recent progress in materials research and discoveries of antiferromagnetic spintronic phenomena suitable for device applications. Experimental demonstration of the electrical switching and detection of the Néel order open a route towards memory devices based on antiferromagnets. Apart from the radiation and magnetic-field hardness, memory cells fabricated from antiferromagnets can be inherently multilevel, whichmore » could be used for neuromorphic computing. Switching speeds attainable in antiferromagnets far exceed those of ferromagnetic and semiconductor memory technologies. Here we review the recent progress in electronic spin-transport and spin-torque phenomena in antiferromagnets that are dominantly of the relativistic quantum mechanical origin. We discuss their utility in pure antiferromagnetic or hybrid ferromagnetic/antiferromagnetic memory devices.« less

Spin transport and spin torque in antiferromagnetic devices

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

Zelezny, J.; Wadley, P.; Olejnik, K.

Ferromagnets are key materials for sensing and memory applications. In contrast, antiferromagnets which represent the more common form of magnetically ordered materials, have found less practical application beyond their use for establishing reference magnetic orientations via exchange bias. This might change in the future due to the recent progress in materials research and discoveries of antiferromagnetic spintronic phenomena suitable for device applications. Experimental demonstration of the electrical switching and detection of the Néel order open a route towards memory devices based on antiferromagnets. Apart from the radiation and magnetic-field hardness, memory cells fabricated from antiferromagnets can be inherently multilevel, whichmore » could be used for neuromorphic computing. Switching speeds attainable in antiferromagnets far exceed those of ferromagnetic and semiconductor memory technologies. Here we review the recent progress in electronic spin-transport and spin-torque phenomena in antiferromagnets that are dominantly of the relativistic quantum mechanical origin. We discuss their utility in pure antiferromagnetic or hybrid ferromagnetic/antiferromagnetic memory devices.« less

Progress towards broadband Raman quantum memory in Bose-Einstein condensates

NASA Astrophysics Data System (ADS)

Saglamyurek, Erhan; Hrushevskyi, Taras; Smith, Benjamin; Leblanc, Lindsay

2017-04-01

Optical quantum memories are building blocks for quantum information technologies. Efficient and long-lived storage in combination with high-speed (broadband) operation are key features required for practical applications. While the realization has been a great challenge, Raman memory in Bose-Einstein condensates (BECs) is a promising approach, due to negligible decoherence from diffusion and collisions that leads to seconds-scale memory times, high efficiency due to large atomic density, the possibility for atom-chip integration with micro photonics, and the suitability of the far off-resonant Raman approach with storage of broadband photons (over GHz) [5]. Here we report our progress towards Raman memory in a BEC. We describe our apparatus recently built for producing BEC with 87Rb atoms, and present the observation of nearly pure BEC with 5x105 atoms at 40 nK. After showing our initial characterizations, we discuss the suitability of our system for Raman-based light storage in our BEC.

Spin transport and spin torque in antiferromagnetic devices

NASA Astrophysics Data System (ADS)

Železný, J.; Wadley, P.; Olejník, K.; Hoffmann, A.; Ohno, H.

2018-03-01

Ferromagnets are key materials for sensing and memory applications. In contrast, antiferromagnets, which represent the more common form of magnetically ordered materials, have found less practical application beyond their use for establishing reference magnetic orientations via exchange bias. This might change in the future due to the recent progress in materials research and discoveries of antiferromagnetic spintronic phenomena suitable for device applications. Experimental demonstration of the electrical switching and detection of the Néel order open a route towards memory devices based on antiferromagnets. Apart from the radiation and magnetic-field hardness, memory cells fabricated from antiferromagnets can be inherently multilevel, which could be used for neuromorphic computing. Switching speeds attainable in antiferromagnets far exceed those of ferromagnetic and semiconductor memory technologies. Here, we review the recent progress in electronic spin-transport and spin-torque phenomena in antiferromagnets that are dominantly of the relativistic quantum-mechanical origin. We discuss their utility in pure antiferromagnetic or hybrid ferromagnetic/antiferromagnetic memory devices.

An Exploration of the Associations among Hearing Loss, Physical Health, and Visual Memory in Adults from West Central Alabama

ERIC Educational Resources Information Center

Hay-McCutcheon, Marcia J.; Hyams, Adriana; Yang, Xin; Parton, Jason; Panasiuk, Brianna; Ondocsin, Sarah; James, Mary Margaret; Scogin, Forrest

2017-01-01

Purpose: The purpose of this preliminary study was to explore the associations among hearing loss, physical health, and visual memory in adults living in rural areas, urban clusters, and an urban city in west Central Alabama. Method: Two hundred ninety-seven adults (182 women, 115 men) from rural areas, urban clusters, and an urban city of west…

Working Memory and Speech Recognition in Noise under Ecologically Relevant Listening Conditions: Effects of Visual Cues and Noise Type among Adults with Hearing Loss

ERIC Educational Resources Information Center

Miller, Christi W.; Stewart, Erin K.; Wu, Yu-Hsiang; Bishop, Christopher; Bentler, Ruth A.; Tremblay, Kelly

2017-01-01

Purpose: This study evaluated the relationship between working memory (WM) and speech recognition in noise with different noise types as well as in the presence of visual cues. Method: Seventy-six adults with bilateral, mild to moderately severe sensorineural hearing loss (mean age: 69 years) participated. Using a cross-sectional design, 2…

Rate and Pattern of Rim Area Loss in Healthy and Progressing Glaucoma Eyes

PubMed Central

Hammel, Na’ama; Belghith, Akram; Bowd, Christopher; Medeiros, Felipe A.; Sharpsten, Lucie; Mendoza, Nadia; Tatham, Andrew J.; Khachatryan, Naira; Liebmann, Jeffrey M.; Girkin, Christopher A.; Weinreb, Robert N.; Zangwill, Linda M.

2015-01-01

Objective To characterize the rate and pattern of age-related and glaucomatous neuroretinal rim area changes in subjects of African descent (AD) and European descent (ED). Design Prospective longitudinal study. Subjects 296 eyes of 157 healthy subjects (88 AD and 69 ED) and 73 progressing glaucoma eyes of 67 subjects (24 AD and 43 ED) from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) were included. Methods Global and sectoral rim area was measured using confocal laser scanning ophthalmoscopy (CSLO). Progression of glaucomatous optic disc damage was determined by masked stereophoto review. The rates of absolute rim area loss and percent rim area loss in healthy and progressing glaucomatous eyes were compared using multivariable nested mixed-effects models. Main Outcome Measures Rate of rim area loss over time. Results The median (inter-quartile range) follow-up time was 5.0 years (2.0–7.4) for healthy eyes and 8.3 years (7.5–9.9) for progressing glaucoma eyes. The mean rate of global rim area loss was significantly faster in progressing glaucoma eyes compared with healthy eyes for both rim area loss (−10.2 ×10−3 mm2/year vs. −2.8 ×10−3 mm2/year, respectively, P<.001) and percent rim area loss (−1.1 %/year vs. −0.2 %/year, respectively, P<.001), but there was considerable overlap between the two groups. 63% of progressing glaucoma eyes had a rate of change faster than the 5th quantile of healthy eyes. For both healthy and progressing eyes, the pattern of rim area loss and percent rim area loss was similar; it tended to be fastest in the superior temporal and inferior temporal sectors. The rate of change was similar in AD and ED progressing eyes. Conclusions Compared with healthy eyes, the mean rate of global rim area loss was 3.7 times faster and the mean rate of global percent rim area loss was 5.4 times faster in progressing glaucoma eyes. A reference database of healthy eyes can be used to help clinicians distinguish age-related rim area loss from rim area loss due to glaucoma. PMID:26746597

Signs and symptoms preceding the diagnosis of Alzheimer’s disease: a systematic scoping review of literature from 1937 to 2016

PubMed Central

Bature, Fidelia; Guinn, Barbara-ann; Pang, Dong; Pappas, Yannis

2017-01-01

Objective Late diagnosis of Alzheimer’s disease (AD) may be due to diagnostic uncertainties. We aimed to determine the sequence and timing of the appearance of established early signs and symptoms in people who are subsequently diagnosed with AD. Methods We used systematic review methodology to investigate the existing literature. Articles were reviewed in May 2016, using the following databases: MEDLINE, PsycINFO, CINAHL, British Nursing Index, PubMed central and the Cochrane library, with no language restriction. Data from the included articles were extracted independently by two authors and quality assessment was undertaken with the quality assessment and diagnostic accuracy tool-2 (QUADAS tool-2 quality assessment tool). Results We found that depression and cognitive impairment were the first symptoms to appear in 98.5% and 99.1% of individuals in a study with late-onset AD (LOAD) and 9% and 80%, respectively, in early-onset AD (EOAD). Memory loss presented early and was experienced 12 years before the clinically defined AD dementia in the LOAD. However, the rapidly progressive late-onset AD presented predominantly with 35 non-established focal symptoms and signs including myoclonus (75%), disturbed gait (66%) and rigidity. These were misdiagnosed as symptoms of Creutzfeldt-Jacob disease (CJD) in all the cases. The participant with the lowest mini-mental state examination score of 25 remained stable for 2 years, which is consistent with the score of the healthy family members. Conclusions The findings of this review suggest that neurological and depressive behaviours are an early occurrence in EOAD with depressive and cognitive symptoms in the measure of semantic memory and conceptual formation in LOAD. Misdiagnosis of rapidly progressive AD as CJD and the familial memory score can be confounding factors while establishing a diagnosis. However, the study was limited by the fact that each one of the findings was based on a single study. PMID:28851777

Reduced cGMP levels in CSF of AD patients correlate with severity of dementia and current depression.

PubMed

Hesse, Raphael; Lausser, Ludwig; Gummert, Pauline; Schmid, Florian; Wahler, Anke; Schnack, Cathrin; Kroker, Katja S; Otto, Markus; Tumani, Hayrettin; Kestler, Hans A; Rosenbrock, Holger; von Arnim, Christine A F

2017-03-09

Alzheimer's disease (AD) is a neurodegenerative disorder, primarily affecting memory. That disorder is thought to be a consequence of neuronal network disturbances and synapse loss. Decline in cognitive function is associated with a high burden of neuropsychiatric symptoms (NPSs) such as depression. The cyclic nucleotides cyclic adenosine-3',5'-monophosphate (cAMP) and cyclic guanosine-3',5'-monophosphate (cGMP) are essential second messengers that play a crucial role in memory processing as well as synaptic plasticity and are potential therapeutic targets. Biomarkers that are able to monitor potential treatment effects and that reflect the underlying pathology are of crucial interest. In this study, we measured cGMP and cAMP in cerebrospinal fluid (CSF) in a cohort of 133 subjects including 68 AD patients and 65 control subjects. To address the association with disease progression we correlated cognitive status with cyclic nucleotide levels. Because a high burden of NPSs is associated with decrease in cognitive function, we performed an exhaustive evaluation of AD-relevant marker combinations in a depressive subgroup. We show that cGMP, but not cAMP, levels in the CSF of AD patients are significantly reduced compared with the control group. Reduced cGMP levels in AD patients correlate with memory impairment based on Mini-Mental State Examination score (r = 0.17, p = 0.048) and tau as a marker of neurodegeneration (r = -0.28, p = 0.001). Moreover, we were able to show that AD patients suffering from current depression show reduced cGMP levels (p = 0.07) and exhibit a higher degree of cognitive impairment than non-depressed AD patients. These results provide further evidence for an involvement of cGMP in AD pathogenesis and accompanying co-morbidities, and may contribute to elucidating synaptic plasticity alterations during disease progression.

Content addressable memory project

NASA Technical Reports Server (NTRS)

Hall, Josh; Levy, Saul; Smith, D.; Wei, S.; Miyake, K.; Murdocca, M.

1991-01-01

The progress on the Rutgers CAM (Content Addressable Memory) Project is described. The overall design of the system is completed at the architectural level and described. The machine is composed of two kinds of cells: (1) the CAM cells which include both memory and processor, and support local processing within each cell; and (2) the tree cells, which have smaller instruction set, and provide global processing over the CAM cells. A parameterized design of the basic CAM cell is completed. Progress was made on the final specification of the CPS. The machine architecture was driven by the design of algorithms whose requirements are reflected in the resulted instruction set(s). A few of these algorithms are described.

Synthetic Analog and Digital Circuits for Cellular Computation and Memory

PubMed Central

Purcell, Oliver; Lu, Timothy K.

2014-01-01

Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss recent progress in designing gene circuits that exhibit memory, and how memory and computation have been integrated to yield more complex systems that can both process and record information. Finally, we suggest new directions for engineering biological circuits capable of computation. PMID:24794536

Modality specific semantic knowledge loss for unique items.

PubMed

Kartsounis, L D; Shallice, T

1996-03-01

We report the case of a man who, following a major myocardial infarction, suffered anoxia followed by significant event memory impairment. Investigations indicated that his semantic memory for word concepts and object meanings was well preserved. However, he had great difficulty in identifying in the visual (but not verbal) modality historically known people, such as Queen Elizabeth I and Napoleon, and well known world and London landmarks, such as the Parthenon and Buckingham Palace. This selective impairment could not be accounted for in terms of prosopagnosia or high level visual perceptual deficits and we interpret it as a modality specific semantic memory loss for unique objects.

Effects of capacity limits, memory loss, and sound type in change deafness.

PubMed

Gregg, Melissa K; Irsik, Vanessa C; Snyder, Joel S

2017-11-01

Change deafness, the inability to notice changes to auditory scenes, has the potential to provide insights about sound perception in busy situations typical of everyday life. We determined the extent to which change deafness to sounds is due to the capacity of processing multiple sounds and the loss of memory for sounds over time. We also determined whether these processing limitations work differently for varying types of sounds within a scene. Auditory scenes composed of naturalistic sounds, spectrally dynamic unrecognizable sounds, tones, and noise rhythms were presented in a change-detection task. On each trial, two scenes were presented that were same or different. We manipulated the number of sounds within each scene to measure memory capacity and the silent interval between scenes to measure memory loss. For all sounds, change detection was worse as scene size increased, demonstrating the importance of capacity limits. Change detection to the natural sounds did not deteriorate much as the interval between scenes increased up to 2,000 ms, but it did deteriorate substantially with longer intervals. For artificial sounds, in contrast, change-detection performance suffered even for very short intervals. The results suggest that change detection is generally limited by capacity, regardless of sound type, but that auditory memory is more enduring for sounds with naturalistic acoustic structures.

The effect of souvenaid on functional brain network organisation in patients with mild Alzheimer's disease: a randomised controlled study.

PubMed

de Waal, Hanneke; Stam, Cornelis J; Lansbergen, Marieke M; Wieggers, Rico L; Kamphuis, Patrick J G H; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C W

2014-01-01

Synaptic loss is a major hallmark of Alzheimer's disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. 179 drug-naïve mild AD patients who participated in the Souvenir II study. Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. THE NETWORK MEASURES IN THE BETA BAND WERE SIGNIFICANTLY DIFFERENT BETWEEN GROUPS: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Dutch Trial Register NTR1975.

The Effect of Souvenaid on Functional Brain Network Organisation in Patients with Mild Alzheimer’s Disease: A Randomised Controlled Study

PubMed Central

de Waal, Hanneke; Stam, Cornelis J.; Lansbergen, Marieke M.; Wieggers, Rico L.; Kamphuis, Patrick J. G. H.; Scheltens, Philip; Maestú, Fernando; van Straaten, Elisabeth C. W.

2014-01-01

Background Synaptic loss is a major hallmark of Alzheimer’s disease (AD). Disturbed organisation of large-scale functional brain networks in AD might reflect synaptic loss and disrupted neuronal communication. The medical food Souvenaid, containing the specific nutrient combination Fortasyn Connect, is designed to enhance synapse formation and function and has been shown to improve memory performance in patients with mild AD in two randomised controlled trials. Objective To explore the effect of Souvenaid compared to control product on brain activity-based networks, as a derivative of underlying synaptic function, in patients with mild AD. Design A 24-week randomised, controlled, double-blind, parallel-group, multi-country study. Participants 179 drug-naïve mild AD patients who participated in the Souvenir II study. Intervention Patients were randomised 1∶1 to receive Souvenaid or an iso-caloric control product once daily for 24 weeks. Outcome In a secondary analysis of the Souvenir II study, electroencephalography (EEG) brain networks were constructed and graph theory was used to quantify complex brain structure. Local brain network connectivity (normalised clustering coefficient gamma) and global network integration (normalised characteristic path length lambda) were compared between study groups, and related to memory performance. Results The network measures in the beta band were significantly different between groups: they decreased in the control group, but remained relatively unchanged in the active group. No consistent relationship was found between these network measures and memory performance. Conclusions The current results suggest that Souvenaid preserves the organisation of brain networks in patients with mild AD within 24 weeks, hypothetically counteracting the progressive network disruption over time in AD. The results strengthen the hypothesis that Souvenaid affects synaptic integrity and function. Secondly, we conclude that advanced EEG analysis, using the mathematical framework of graph theory, is useful and feasible for assessing the effects of interventions. Trial registration Dutch Trial Register NTR1975. PMID:24475144

Prevalence of impaired memory in hospitalized adults and associations with in-hospital sleep loss.

PubMed

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

2015-07-01

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. 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. Prospective cohort study. General medicine and hematology/oncology inpatient wards. Fifty-nine hospitalized adults at least 50 years of age with no diagnosed sleep disorder. 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. 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. Mean immediate recall was 3.8 words out of 15 (standard deviation = 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 (interquartile range [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). About half of the 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. © 2015 Society of Hospital Medicine.

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

Insights into Spared Memory Capacity in Amnestic MCI and Alzheimer's Disease via Minimal Interference

ERIC Educational Resources Information Center

Dewar, Michaela; Pesallaccia, Martina; Cowan, Nelson; Provinciali, Leandro; Della Sala, Sergio

2012-01-01

Impairment on standard tests of delayed recall is often already maximal in the aMCI stage of Alzheimer's Disease. Neuropathological work shows that the neural substrates of memory function continue to deteriorate throughout the progression of the disease, hinting that further changes in memory performance could be tracked by a more sensitive test…

Voluntary Running Prevents Progressive Memory Decline and Increases Adult Hippocampal Neurogenesis and Growth Factor Expression After Whole-Brain Irradiation

PubMed Central

Wong-Goodrich, Sarah J.E.; Pfau, Madeline L.; Flores, Catherine T.; Fraser, Jennifer A.; Williams, Christina L.; Jones, Lee W.

2010-01-01

Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention, and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to four months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting one month after sham- or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdU) immunolabeling and ELISA indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdU+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor, and occurred despite irradiation-induced elevations in hippocampal pro-inflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention. PMID:20884629

Some neglected contributions of Wilhelm Wundt to the psychology of memory.

PubMed

Carpenter, Shana K

2005-08-01

Wilhelm Wundt, whose name is rarely associated with the scientific study of memory, conducted a number of memory experiments that appear to have escaped the awareness of modern cognitive psychologists. Aspects of Wundt's system are reviewed, particularly with respect to his experimental work on memory. Wundt investigated phenomena that would fall under the modern headings of iconic memory, short-term memory, and the enactment and generation effects, but this research has been neglected. Revisiting the Wundtian perspective may provide insight into some of the reasons behind the historical course of memory research and in general into the progress of science in psychology.

Objective and subjective memory ratings in cannabis-dependent adolescents.

PubMed

McClure, Erin A; Lydiard, Jessica B; Goddard, Scott D; Gray, Kevin M

2015-01-01

Cannabis is the most widely used illicit substance worldwide, with an estimated 160 million users. Among adolescents, rates of cannabis use are increasing, while the perception of detrimental effects of cannabis use is declining. Difficulty with memory is one of the most frequently noted cognitive deficits associated with cannabis use, but little data exist exploring how well users can identify their own memory deficits, if present. The current secondary analysis sought to characterize objective verbal and visual memory performance via a neurocognitive battery in cannabis-dependent adolescents enrolled in a pharmacotherapeutic cannabis cessation clinical trial (N = 112) and compare this to a single self-reported item assessing difficulties with memory loss. Exploratory analyses also assessed dose-dependent effects of cannabis on memory performance. A small portion of the study sample (10%) endorsed a "serious problem" with memory loss. Those participants reporting "no problem" or "serious problem" scored similarly on visual and verbal memory tasks on the neurocognitive battery. Exploratory analyses suggested a potential relationship between days of cannabis use, amount of cannabis used, and gender with memory performance. This preliminary and exploratory analysis suggests that a sub-set of cannabis users may not accurately perceive difficulties with memory. Further work should test this hypothesis with the use of a control group, comprehensive self-reports of memory problems, and adult populations that may have more years of cannabis use and more severe cognitive deficits. © American Academy of Addiction Psychiatry.

Better together: Left and right hemisphere engagement to reduce age-related memory loss.

PubMed

Brambilla, Michela; Manenti, Rosa; Ferrari, Clarissa; Cotelli, Maria

2015-10-15

Episodic memory is a cognitive function that appears more susceptible than others to the effects of aging. The main aim of this study is to investigate if the magnitude of functional hemispheric lateralization during episodic memory test was positively correlated with memory performance, proving the presence of a beneficial pattern of neural processing in high-performing older adults but not in low-performing participants. We have applied anodal transcranial Direct Current Stimulation (tDCS) or sham stimulation over left and right hemisphere in a group of young subjects and in high-performing and low-performing older participants during an experimental verbal episodic memory task. Remarkably, young individuals and high-performing older adults exhibited similar performances on episodic memory tasks and both groups showed symmetrical recruitment of left and right areas during memory retrieval. In contrast, low-performing older adults, who obtained lower scores on the memory tasks, demonstrated a greater engagement of the left hemisphere during verbal memory task. Furthermore, structural equation model was performed for analyzing the interrelations between the index of interhemispheric asymmetry and several neuropsychological domains. We found that the bilateral engagement of dorsolateral prefrontal cortex and parietal cortex regions had a direct correlation with memory and executive functions evaluated as latent constructs. These findings drew attention to brain maintenance hypothesis. The potential of neurostimulation in cognitive enhancement is particularly promising to prevent memory loss during aging. Copyright © 2015 Elsevier B.V. All rights reserved.

Memory as the "whole brain work": a large-scale model based on "oscillations in super-synergy".

PubMed

Başar, Erol

2005-01-01

According to recent trends, memory depends on several brain structures working in concert across many levels of neural organization; "memory is a constant work-in progress." The proposition of a brain theory based on super-synergy in neural populations is most pertinent for the understanding of this constant work in progress. This report introduces a new model on memory basing on the processes of EEG oscillations and Brain Dynamics. This model is shaped by the following conceptual and experimental steps: 1. The machineries of super-synergy in the whole brain are responsible for formation of sensory-cognitive percepts. 2. The expression "dynamic memory" is used for memory processes that evoke relevant changes in alpha, gamma, theta and delta activities. The concerted action of distributed multiple oscillatory processes provides a major key for understanding of distributed memory. It comprehends also the phyletic memory and reflexes. 3. The evolving memory, which incorporates reciprocal actions or reverberations in the APLR alliance and during working memory processes, is especially emphasized. 4. A new model related to "hierarchy of memories as a continuum" is introduced. 5. The notions of "longer activated memory" and "persistent memory" are proposed instead of long-term memory. 6. The new analysis to recognize faces emphasizes the importance of EEG oscillations in neurophysiology and Gestalt analysis. 7. The proposed basic framework called "Memory in the Whole Brain Work" emphasizes that memory and all brain functions are inseparable and are acting as a "whole" in the whole brain. 8. The role of genetic factors is fundamental in living system settings and oscillations and accordingly in memory, according to recent publications. 9. A link from the "whole brain" to "whole body," and incorporation of vegetative and neurological system, is proposed, EEG oscillations and ultraslow oscillations being a control parameter.

Information processing efficiency in patients with multiple sclerosis.

PubMed

Archibald, C J; Fisk, J D

2000-10-01

Reduced information processing efficiency, consequent to impaired neural transmission, has been proposed as underlying various cognitive problems in patients with Multiple Sclerosis (MS). This study employed two measures developed from experimental psychology that control for the potential confound of perceptual-motor abnormalities (Salthouse, Babcock, & Shaw, 1991; Sternberg, 1966, 1969) to assess the speed of information processing and working memory capacity in patients with mild to moderate MS. Although patients had significantly more cognitive complaints than neurologically intact matched controls, their performance on standard tests of immediate memory span did not differ from control participants and their word list learning was within normal limits. On the experimental measures, both relapsing-remitting and secondary-progressive patients exhibited significantly slowed information processing speed relative to controls. However, only the secondary-progressive patients had an additional decrement in working memory capacity. Depression, fatigue, or neurologic disability did not account for performance differences on these measures. While speed of information processing may be slowed early in the disease process, deficits in working memory capacity may appear only as there is progression of MS. It is these latter deficits, however, that may underlie the impairment of new learning that patients with MS demonstrate.

Vocabulary and Working Memory in Children Fit with Hearing Aids

ERIC Educational Resources Information Center

Stiles, Derek J.; McGregor, Karla K.; Bentler, Ruth A.

2012-01-01

Purpose: To determine whether children with mild-to-moderately severe sensorineural hearing loss (CHL) present with disturbances in working memory and whether these disturbances relate to the size of their receptive vocabularies. Method: Children 6 to 9 years of age participated. Aspects of working memory were tapped by articulation rate, forward…

Working Memory Span Development: A Time-Based Resource-Sharing Model Account

ERIC Educational Resources Information Center

Barrouillet, Pierre; Gavens, Nathalie; Vergauwe, Evie; Gaillard, Vinciane; Camos, Valerie

2009-01-01

The time-based resource-sharing model (P. Barrouillet, S. Bernardin, & V. Camos, 2004) assumes that during complex working memory span tasks, attention is frequently and surreptitiously switched from processing to reactivate decaying memory traces before their complete loss. Three experiments involving children from 5 to 14 years of age…

Persistence and memory timescales in root-zone soil moisture dynamics

Treesearch

Khaled Ghannam; Taro Nakai; Athanasios Paschalis; Andrew C. Oishi; Ayumi Kotani; Yasunori Igarashi; Tomo' omi Kumagai; Gabriel G. Katul

2016-01-01

The memory timescale that characterizes root-zone soil moisture remains the dominant measure in seasonal forecasts of land-climate interactions. This memory is a quasi-deterministic timescale associated with the losses (e.g., evapotranspiration) from the soil column and is often interpreted as persistence in soil moisture states. Persistence, however,...

Consolidation of Long-Term Memory: Evidence and Alternatives

ERIC Educational Resources Information Center

Meeter, Martijn; Murre, Jaap M. J.

2004-01-01

Memory loss in retrograde amnesia has long been held to be larger for recent periods than for remote periods, a pattern usually referred to as the Ribot gradient. One explanation for this gradient is consolidation of long-term memories. Several computational models of such a process have shown how consolidation can explain characteristics of…

A Spectral Analysis Approach for Acoustic Radiation from Composite Panels

NASA Technical Reports Server (NTRS)

Turner, Travis L.; Singh, Mahendra P.; Mei, Chuh

2004-01-01

A method is developed to predict the vibration response of a composite panel and the resulting far-field acoustic radiation due to acoustic excitation. The acoustic excitation is assumed to consist of obliquely incident plane waves. The panel is modeled by a finite element analysis and the radiated field is predicted using Rayleigh's integral. The approach can easily include other effects such as shape memory alloy (SMA) ber reinforcement, large detection thermal postbuckling, and non-symmetric SMA distribution or lamination. Transmission loss predictions for the case of an aluminum panel excited by a harmonic acoustic pressure are shown to compare very well with a classical analysis. Results for a composite panel with and without shape memory alloy reinforcement are also presented. The preliminary results demonstrate that the transmission loss can be significantly increased with shape memory alloy reinforcement. The mechanisms for further transmission loss improvement are identified and discussed.

Selective noradrenaline depletion impairs working memory and hippocampal neurogenesis.

PubMed

Coradazzi, Marino; Gulino, Rosario; Fieramosca, Francesco; Falzacappa, Lucia Verga; Riggi, Margherita; Leanza, Giampiero

2016-12-01

Noradrenergic neurons in the locus coeruleus play a role in learning and memory, and their loss is an early event in Alzheimer's disease pathogenesis. Moreover, noradrenaline may sustain hippocampal neurogenesis; however, whether are these events related is still unknown. Four to five weeks following the selective immunotoxic ablation of locus coeruleus neurons, young adult rats underwent reference and working memory tests, followed by postmortem quantitative morphological analyses to assess the extent of the lesion, as well as the effects on proliferation and/or survival of neural progenitors in the hippocampus. When tested in the Water Maze task, lesioned animals exhibited no reference memory deficit, whereas working memory abilities were seen significantly impaired, as compared with intact or sham-lesioned controls. Stereological analyses confirmed a dramatic noradrenergic neuron loss associated to reduced proliferation, but not survival or differentiation, of 5-bromo-2'deoxyuridine-positive progenitors in the dentate gyrus. Thus, ascending noradrenergic afferents may be involved in more complex aspects of cognitive performance (i.e., working memory) possibly via newly generated progenitors in the hippocampus. Copyright © 2016 Elsevier Inc. All rights reserved.

KENNEDY SPACE CENTER, FLA. - Winston Scott, executive director of Florida Space Authority, speaks to attendees at a memorial service honoring the crew of Columbia. He stands in front of the Space Memorial Mirror at the KSC Visitor Complex. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Scott is a former astronaut who flew on Columbia in 1997. Attended by many friends, co-workers and families, the memorial service was also open to the public.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - Winston Scott, executive director of Florida Space Authority, speaks to attendees at a memorial service honoring the crew of Columbia. He stands in front of the Space Memorial Mirror at the KSC Visitor Complex. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Scott is a former astronaut who flew on Columbia in 1997. Attended by many friends, co-workers and families, the memorial service was also open to the public.

Simian immunodeficiency virus infection induces severe loss of intestinal central memory T cells which impairs CD4+ T-cell restoration during antiretroviral therapy.

PubMed

Verhoeven, D; Sankaran, S; Dandekar, S

2007-08-01

Simian immunodeficiency virus (SIV) infection leads to severe loss of intestinal CD4(+) T cells and, as compared to peripheral blood, restoration of these cells is slow during antiretroviral therapy (ART). Mechanisms for this delay have not been examined in context of which specific CD4(+) memory subsets or lost and fail to regenerate during ART. Fifteen rhesus macaques were infected with SIV, five of which received ART (FTC/PMPA) for 30 weeks. Viral loads were measured by real-time PCR. Flow cytometric analysis determined changes in T-cell subsets and their proliferative state. Changes in proliferative CD4(+) memory subsets during infection accelerated their depletion. This reduced the central memory CD4(+) T-cell pool and contributed to slow CD4(+) T-cell restoration during ART. There was a lack of restoration of the CD4(+) central memory and effector memory T-cell subsets in gut-associated lymphoid tissue during ART, which may contribute to the altered intestinal T-cell homeostasis in SIV infection.

Computer memory power control for the Galileo spacecraft

NASA Technical Reports Server (NTRS)

Detwiler, R. C.

1983-01-01

The developmental history, major design drives, and final topology of the computer memory power system on the Galileo spacecraft are described. A unique method of generating memory backup power directly from the fault current drawn during a spacecraft power overload or fault condition allows this system to provide continuous memory power. This concept provides a unique solution to the problem of volatile memory loss without the use of a battery of other large energy storage elements usually associated with uninterrupted power supply designs.

Inefficient Or Insufficient Encoding As Potential Primary Deficit In Neurodevelopmental Performance Among Children with OSA

PubMed Central

Spruyt, Karen; Capdevila, Oscar Sans; Kheirandish-Gozal, Leila; Gozal, David

2010-01-01

Memory (M) impairments have been suggested in pediatric Obstructive Sleep Apnea along with attention and executive (AE), language (L) and visuospatial (V) dysfunctions. NEPSY assessment of children aged 5–9-years who were either healthy (n= 43), or who had OSA without L, V, AE (OSA−, n= 22) or with L (n=6), V (n=1), AE (n=3) (OSA+, n=10) dysfunctions revealed no gross memory problems in OSA; however, over the 3 learning trials of cross-modal association learning of name with face, the OSA− progressively improved performance, whereas the OSA+ failed to progress. No within-group differences between immediate and delayed memory tasks were apparent. The data suggest the presence of slower information processing, and/or secondary memory problems, in the absence of retrieval or recall impairments among a subset of children with OSA. We hypothesize that inefficient/insufficient encoding may account for the primary deficit. PMID:20183722

KENNEDY SPACE CENTER, FLA. - In front of the Space Memorial Mirror at the KSC Visitor Complex, Center Director Jim Kennedy (right) speaks to visitors gathered for the memorial service honoring the crew of Columbia. At left are KSC Deputy Director Woodrow Whitlow Jr. and Executive Director of Florida Space Authority Winston Scott; at right is Dr. Stephen Feldman, president of the Astronaut Memorial Foundation. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. The public was also invited to the memorial service held at the KSC Visitor Complex.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - In front of the Space Memorial Mirror at the KSC Visitor Complex, Center Director Jim Kennedy (right) speaks to visitors gathered for the memorial service honoring the crew of Columbia. At left are KSC Deputy Director Woodrow Whitlow Jr. and Executive Director of Florida Space Authority Winston Scott; at right is Dr. Stephen Feldman, president of the Astronaut Memorial Foundation. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. The public was also invited to the memorial service held at the KSC Visitor Complex.

Memory Loss: When to Seek Help

MedlinePlus

... a set of symptoms, including impairment in memory, reasoning, judgment, language and other thinking skills. Dementia usually ... et al. Mild cognitive impairment: Epidemiology, pathology and clinical assessment. http://www.uptodate.com/home. Accessed March ...

Memory loss and memory reorganization patterns in temporal lobe epilepsy patients undergoing anterior temporal lobe resection, as demonstrated by pre-versus post-operative functional MRI.

PubMed

Limotai, Chusak; McLachlan, Richard S; Hayman-Abello, Susan; Hayman-Abello, Brent; Brown, Suzan; Bihari, Frank; Mirsattari, Seyed M

2018-06-19

This study was aimed to longitudinally assess memory function and whole-brain memory circuit reorganization in patients with temporal lobe epilepsy (TLE) by comparing activation potentials before versus after anterior temporal lobe (ATL) resection. Nineteen patients with medically-intractable TLE (10 left TLE, 9 right TLE) and 15 healthy controls were enrolled. Group analyses were conducted pre- and post-ATL of a novelty complex scene-encoding paradigm comparing areas of blood oxygen-level-dependent (BOLD) signal activations on functional magnetic resonance imaging (fMRI). None of the pre-operative patient characteristics we studied predicted the extent of pre- to post-operative memory loss. On fMRI, extra-temporal activations were detected pre-operatively in both LTLE and RTLE, particularly in the frontal lobe. Greater activations also were noted in the contralateral hippocampus and parahippocampus in both groups. Performing within-subject comparisons, post-op relative to pre-op, pronounced ipsilateral activations were identified in the left parahippocampal gyrus in LTLE, versus the right middle temporal gyrus in RTLE patients. Memory function was impaired pre-operatively but declined after ATL resection in both RTLE and LTLE patients. Post-operative fMRI results indicate possible functional adaptations to ATL loss, primarily occurring within the left parahippocampal gyrus versus right middle temporal gyrus in LTLE versus RTLE patients, respectively. Copyright © 2018 Elsevier Ltd. All rights reserved.

Transiently Increasing cAMP Levels Selectively in Hippocampal Excitatory Neurons during Sleep Deprivation Prevents Memory Deficits Caused by Sleep Loss

PubMed Central

Bruinenberg, Vibeke M.; Tudor, Jennifer C.; Ferri, Sarah L.; Baumann, Arnd; Meerlo, Peter

2014-01-01

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object–location task. Five hours of total sleep deprivation directly following training impaired the formation of object–location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. PMID:25411499

Transiently increasing cAMP levels selectively in hippocampal excitatory neurons during sleep deprivation prevents memory deficits caused by sleep loss.

PubMed

Havekes, Robbert; Bruinenberg, Vibeke M; Tudor, Jennifer C; Ferri, Sarah L; Baumann, Arnd; Meerlo, Peter; Abel, Ted

2014-11-19

The hippocampus is particularly sensitive to sleep loss. Although previous work has indicated that sleep deprivation impairs hippocampal cAMP signaling, it remains to be determined whether the cognitive deficits associated with sleep deprivation are caused by attenuated cAMP signaling in the hippocampus. Further, it is unclear which cell types are responsible for the memory impairments associated with sleep deprivation. Transgenic approaches lack the spatial resolution to manipulate specific signaling pathways selectively in the hippocampus, while pharmacological strategies are limited in terms of cell-type specificity. Therefore, we used a pharmacogenetic approach based on a virus-mediated expression of a Gαs-coupled Drosophila octopamine receptor selectively in mouse hippocampal excitatory neurons in vivo. With this approach, a systemic injection with the receptor ligand octopamine leads to increased cAMP levels in this specific set of hippocampal neurons. We assessed whether transiently increasing cAMP levels during sleep deprivation prevents memory consolidation deficits associated with sleep loss in an object-location task. Five hours of total sleep deprivation directly following training impaired the formation of object-location memories. Transiently increasing cAMP levels in hippocampal neurons during the course of sleep deprivation prevented these memory consolidation deficits. These findings demonstrate that attenuated cAMP signaling in hippocampal excitatory neurons is a critical component underlying the memory deficits in hippocampus-dependent learning tasks associated with sleep deprivation. Copyright © 2014 the authors 0270-6474/14/3415715-07$15.00/0.

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

PubMed

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

2006-01-01

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

Temporally graded semantic memory loss in amnesia and semantic dementia: Further evidence for opposite gradients.

PubMed

Estmacott, Robyn W; Moscovitch, Morris

2002-03-01

The consolidation theory of long-term memory (e.g., Squire, 1992) predicts that damage to the medial temporal lobes will result in temporally graded retrograde memory loss, with a disproportionate impairment of recent relative to remote knowledge; in contrast, severe atrophy of the temporal neocortex is predicted to result in the reverse temporally graded pattern, with a selective sparing of recent memory (K.S. Graham & Hodges, 1997). Previously, we reported evidence that autobiographical episodic memory does not follow this temporal pattern (Westmacott, Leach, Freedman, & Moscovitch, 2001). In the present study, we found evidence suggesting that semantic memory loss does follow the predicted temporal pattern. We used a set of tasks that tap implicit and explicit memory for famous names and English vocabulary terms from across the 20th century. KC, a person with medial temporal amnesia, consistently demonstrated across tasks a selective deficit for famous names and vocabulary terms from the 5-year period just prior to injury; this deficit was particularly profound for elaborated semantic knowledge (e.g., word definitions, occupation of famous person). However, when asked to guess on unfamiliar items, KC's performance for names and words from this 5-year time period increased substantially, suggesting that he retains some of this knowledge at an implicit or rudimentary level. Conversely, EL, a semantic dementia patient with temporal neocortical atrophy and relative sparing of the medial temporal lobe, demonstrated a selective sparing of names and words from the most recent time period. However, this selective sparing of recent semantic memory was demonstrated in the implicit tasks only; performance on explicit tasks suggested an equally severe impairment of semantics across all time periods. Unlike the data from our previous study of autobiographical episodic memory, these findings are consistent with the predictions both of consolidation theory (Hodges & Graham, 1998; Squire, 1992) and multiple trace theory (Nadel & Moscovitch, 1999) that the hippocampus plays a timelimited role in the acquisition and representation of long-term semantic memories. Moreover, our findings suggest that tasks requiring minimal verbal production and explicit recall may provide a more sensitive and comprehensive assessment of intact memory capacity in brain-damaged individuals.

Treatment for Anomia in Semantic Dementia

PubMed Central

Henry, Maya L.; Beeson, Pélagie M.; Rapcsak, Steven Z.

2009-01-01

Anomia is a striking and consistent clinical feature of semantic dementia (SD), a progressive aphasia syndrome associated with focal cortical atrophy of the anterior temporal lobes. Word retrieval deficits in patients with SD have been attributed to the loss of conceptual knowledge, resulting in an impairment referred to as semantic anomia. Whereas an abundance of research has been dedicated to treatment for anomia in individuals with focal brain damage due to stroke, considerably less work has been done regarding treatment for patients with progressive language decline. The purpose of this article is to review the available literature concerning the nature and treatment of anomia in individuals with SD. Several studies have shown that new lexical learning remains possible in these patients. However, newly learned information is likely to be constrained by the learning context, and increased reliance on perceptual and autobiographical contextual information may be necessary to provide critical support for new vocabulary acquisition. There is also evidence suggesting that treatment may slow the progression of anomia over time, even affording some protective benefit to lexical items that are not yet lost. However, treatment efforts are likely to be most beneficial at early stages of the disease, when residual semantic knowledge as. well as relatively spared episodic memory may support new learning. PMID:18348092

The Association of Aging and Aerobic Fitness With Memory

PubMed Central

Bullock, Alexis M.; Mizzi, Allison L.; Kovacevic, Ana; Heisz, Jennifer J.

2018-01-01

The present study examined the differential effects of aging and fitness on memory. Ninety-five young adults (YA) and 81 older adults (OA) performed the Mnemonic Similarity Task (MST) to assess high-interference memory and general recognition memory. Age-related differences in high-interference memory were observed across the lifespan, with performance progressively worsening from young to old. In contrast, age-related differences in general recognition memory were not observed until after 60 years of age. Furthermore, OA with higher aerobic fitness had better high-interference memory, suggesting that exercise may be an important lifestyle factor influencing this aspect of memory. Overall, these findings suggest different trajectories of decline for high-interference and general recognition memory, with a selective role for physical activity in promoting high-interference memory. PMID:29593524

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. Copyright © 2015 Elsevier Inc. All rights reserved.

Current Concepts of Neurodegenerative Mechanisms in Alzheimer's Disease.

PubMed

Magalingam, Kasthuri Bai; Radhakrishnan, Ammu; Ping, Ng Shee; Haleagrahara, Nagaraja

2018-01-01

Neurodegenerative diseases are hereditary or sporadic conditions that result in the progressive loss of the structure and function of neurons as well as neuronal death. Although a range of diseases lie under this umbrella term, Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative diseases that affect a large population around the globe. Alzheimer's disease is characterized by the abnormal accumulation of extracellular amyloid- β plaques and intraneuronal neurofibrillary tangles in brain regions and manifests as a type of dementia in aged individuals that results in memory loss, multiple cognitive abnormalities, and intellectual disabilities that interfere with quality of life. Since the discovery of AD, a wealth of new information has emerged that delineates the causes, mechanisms of disease, and potential therapeutic agents, but an effective remedy to cure the diseases has not been identified yet. This could be because of the complexity of the disease process, as it involves various contributing factors that include environmental factors and genetic predispositions. This review summarizes the current understanding on neurodegenerative mechanisms that lead to the emergence of the pathology of AD.

Novel conformal organic antireflective coatings for advanced I-line lithography

NASA Astrophysics Data System (ADS)

Deshpande, Shreeram V.; Nowak, Kelly A.; Fowler, Shelly; Williams, Paul; Arjona, Mikko

2001-08-01

Flash memory chips are playing a critical role in semiconductor devices due to increased popularity of hand held electronic communication devices such as cell phones and PDAs (personal Digital Assistants). Flash memory offers two primary advantages in semiconductor devices. First, it offers flexibility of in-circuit programming capability to reduce the loss from programming errors and to significantly reduce commercialization time to market for new devices. Second, flash memory has a double density memory capability through stacked gate structures which increases the memory capability and thus saves significantly on chip real estate. However, due to stacked gate structures the requirements for manufacturing of flash memory devices are significantly different from traditional memory devices. Stacked gate structures also offer unique challenges to lithographic patterning materials such as Bottom Anti-Reflective Coating (BARC) compositions used to achieve CD control and to minimize standing wave effect in photolithography. To be applicable in flash memory manufacturing a BARC should form a conformal coating on high topography of stacked gate features as well as provide the normal anti-reflection properties for CD control. In this paper we report on a new highly conformal advanced i-line BARC for use in design and manufacture of flash memory devices. Conformal BARCs being significantly thinner in trenches than the planarizing BARCs offer the advantage of reducing BARC overetch and thus minimizing resist thickness loss.

Hippocampal Focal Knockout of CBP Affects Specific Histone Modifications, Long-Term Potentiation, and Long-Term Memory

PubMed Central

Barrett, Ruth M; Malvaez, Melissa; Kramar, Eniko; Matheos, Dina P; Arrizon, Abraham; Cabrera, Sara M; Lynch, Gary; Greene, Robert W; Wood, Marcelo A

2011-01-01

To identify the role of the histone acetyltransferase (HAT) CREB-binding protein (CBP) in neurons of the CA1 region of the hippocampus during memory formation, we examine the effects of a focal homozygous knockout of CBP on histone modifications, gene expression, synaptic plasticity, and long-term memory. We show that CBP is critical for the in vivo acetylation of lysines on histones H2B, H3, and H4. CBP's homolog p300 was unable to compensate for the loss of CBP. Neurons lacking CBP maintained phosphorylation of the transcription factor CREB, yet failed to activate CREB:CBP-mediated gene expression. Loss of CBP in dorsal CA1 of the hippocampus resulted in selective impairments to long-term potentiation and long-term memory for contextual fear and object recognition. Together, these results suggest a necessary role for specific chromatin modifications, selectively mediated by CBP in the consolidation of memories. PMID:21508930

Accelerated hand bone mineral density loss is associated with progressive joint damage in hands and feet in recent-onset rheumatoid arthritis.

PubMed

Güler-Yüksel, Melek; Klarenbeek, Naomi B; Goekoop-Ruiterman, Yvonne P M; de Vries-Bouwstra, Jeska K; van der Kooij, Sjoerd M; Gerards, Andreas H; Ronday, H Karel; Huizinga, Tom W J; Dijkmans, Ben A C; Allaart, Cornelia F; Lems, Willem F

2010-01-01

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years. In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years. 68% of the patients had accelerated hand BMD loss (>-0.003 g/cm2) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage. In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.

The endocrine dyscrasia that accompanies menopause and andropause induces aberrant cell cycle signaling that triggers re-entry of post-mitotic neurons into the cell cycle, neurodysfunction, neurodegeneration and cognitive disease.

PubMed

Atwood, Craig S; Bowen, Richard L

2015-11-01

This article is part of a Special Issue "SBN 2014". Sex hormones are physiological factors that promote neurogenesis during embryonic and fetal development. During childhood and adulthood these hormones support the maintenance of brain structure and function via neurogenesis and the formation of dendritic spines, axons and synapses required for the capture, processing and retrieval of information (memories). Not surprisingly, changes in these reproductive hormones that occur with menopause and during andropause are strongly correlated with neurodegeneration and cognitive decline. In this connection, much evidence now indicates that Alzheimer's disease (AD) involves aberrant re-entry of post-mitotic neurons into the cell cycle. Cell cycle abnormalities appear very early in the disease, prior to the appearance of plaques and tangles, and explain the biochemical, neuropathological and cognitive changes observed with disease progression. Intriguingly, a recent animal study has demonstrated that induction of adult neurogenesis results in the loss of previously encoded memories while decreasing neurogenesis after memory formation during infancy mitigated forgetting. Here we review the biochemical, epidemiological and clinical evidence that alterations in sex hormone signaling associated with menopause and andropause drive the aberrant re-entry of post-mitotic neurons into an abortive cell cycle that leads to neurite retraction, neuron dysfunction and neuron death. When the reproductive axis is in balance, gonadotropins such as luteinizing hormone (LH), and its fetal homolog, human chorionic gonadotropin (hCG), promote pluripotent human and totipotent murine embryonic stem cell and neuron proliferation. However, strong evidence supports menopausal/andropausal elevations in the LH:sex steroid ratio as driving aberrant mitotic events. These include the upregulation of tumor necrosis factor; amyloid-β precursor protein processing towards the production of mitogenic Aβ; and the activation of Cdk5, a key regulator of cell cycle progression and tau phosphorylation (a cardinal feature of both neurogenesis and neurodegeneration). Cognitive and biochemical studies confirm the negative consequences of a high LH:sex steroid ratio on dendritic spine density and human cognitive performance. Prospective epidemiological and clinical evidence in humans supports the premise that rebalancing the ratio of circulating gonadotropins:sex steroids reduces the incidence of AD. Together, these data support endocrine dyscrasia and the subsequent loss of cell cycle control as an important etiological event in the development of neurodegenerative diseases including AD, stroke and Parkinson's disease. Published by Elsevier Inc.

Ashwagandha (Withania somnifera) Reverses β-Amyloid1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND)

PubMed Central

Kurapati, Kesava Rao Venkata; Atluri, Venkata Subba Rao; Samikkannu, Thangavel; Nair, Madhavan P. N.

2013-01-01

Alzheimer’s disease (AD) is characterized by progressive dysfunction of memory and higher cognitive functions with abnormal accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles throughout cortical and limbic brain regions. At present no curative treatment is available, and research focuses on drugs for slowing disease progression or providing prophylaxis. Withania somnifera (WS) also known as ‘ashwagandha’ is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer. However, there is a paucity of data on the potential neuroprotective effects of W.somnifera against β-Amyloid (1–42)-induced neuropathogenesis. In the present study, we have tested the neuroprotective effects of methanol:Chloroform (3:1) extract of ashwagandha against β-amyloid induced toxicity and HIV-1Ba-L (clade B) infection using a human neuronal SK-N-MC cell line. Our results showed that β-amyloid induced cytotoxic effects in SK-N-MC cells as shown by decreased cell growth when tested individually. Also, confocal microscopic analysis showed decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC cells compared to uninfected cells. However, when ashwagandha was added to β-amyloid treated and HIV-1 infected samples, the toxic effects were neutralized. Further, the MTT cell viability assays and the peroxisome proliferator-activated receptor-γ (PPARγ) levels supported these observations indicating the neuroprotective effect of WS root extract against β-amyloid and HIV-1Ba-L (clade B) induced neuro-pathogenesis. PMID:24147038

The dynamics of sensory buffers: geometric, spatial, and experience-dependent shaping of iconic memory.

PubMed

Graziano, Martin; Sigman, Mariano

2008-05-23

When a stimulus is presented, its sensory trace decays rapidly, lasting for approximately 1000 ms. This brief and labile memory, referred as iconic memory, serves as a buffer before information is transferred to working memory and executive control. Here we explored the effect of different factors--geometric, spatial, and experience--with respect to the access and the maintenance of information in iconic memory and the progressive distortion of this memory. We studied performance in a partial report paradigm, a design wherein recall of only part of a stimulus array is required. Subjects had to report the identity of a letter in a location that was cued in a variable delay after the stimulus onset. Performance decayed exponentially with time, and we studied the different parameters (time constant, zero-delay value, and decay amplitude) as a function of the different factors. We observed that experience (determined by letter frequency) affected the access to iconic memory but not the temporal decay constant. On the contrary, spatial position affected the temporal course of delay. The entropy of the error distribution increased with time reflecting a progressive morphological distortion of the iconic buffer. We discuss our results on the context of a model of information access to executive control and how it is affected by learning and attention.

Differential Memory Test Sensitivity for Diagnosing Amnestic Mild Cognitive Impairment and Predicting Conversion to Alzheimer's Disease

PubMed Central

Rabin, Laura A.; Paré, Nadia; Saykin, Andrew J.; Brown, Michael J.; Wishart, Heather A.; Flashman, Laura A.; Santulli, Robert B.

2011-01-01

Episodic memory is the first and most severely affected cognitive domain in Alzheimer's disease (AD), and it is also the key early marker in prodromal stages including amnestic mild cognitive impairment (MCI). The relative ability of memory tests to discriminate between MCI and normal aging has not been well characterized. We compared the classification value of widely used verbal memory tests in distinguishing healthy older adults (n = 51) from those with MCI (n = 38). Univariate logistic regression indicated that the total learning score from the California Verbal Learning Test-II (CVLT-II) ranked highest in terms of distinguishing MCI from normal aging (sensitivity = 90.2; specificity = 84.2). Inclusion of the delayed recall condition of a story memory task (i.e., WMS-III Logical Memory, Story A) enhanced the overall accuracy of classification (sensitivity = 92.2; specificity = 94.7). Combining Logical Memory recognition and CVLT-II long delay best predicted progression from MCI to AD over a 4-year period (accurate classification = 87.5%). Learning across multiple trials may provide the most sensitive index for initial diagnosis of MCI, but inclusion of additional variables may enhance overall accuracy and may represent the optimal strategy for identifying individuals most likely to progress to dementia. PMID:19353345

Phenomenological characterization of memory complaints in preclinical and prodromal Alzheimer's disease.

PubMed

Buckley, Rachel F; Ellis, Kathryn A; Ames, David; Rowe, Christopher C; Lautenschlager, Nicola T; Maruff, Paul; Villemagne, Victor L; Macaulay, S Lance; Szoeke, Cassandra; Martins, Ralph N; Masters, Colin L; Savage, Greg; Rainey-Smith, Stephanie R; Rembach, Alan; Saling, Michael M

2015-07-01

To explore the subjective experience of memory change in groups at risk of dementia (those with mild cognitive impairment MCI or high β-amyloid (Aβ+) burden) to determine the existence of potential phenomenological typologies. We recruited 123 healthy controls (HC) and individuals with MCI from the Australian Imaging, Biomarker and Lifestyle (AIBL) study. Sixty-7 (HC = 47,MCI = 20) had Aβ scans available for analysis. Semistructured interviews were administered, transcribed, and meaningful phrases extracted from transcripts. Twelve themes were defined and compared across diagnostic status and Aβ status. MCI endorsed more complaints of burdensome coping strategies, increasing frequency, sense of predomination, poor contextualization, progression, dependency, impact on affect, and dismissive attitudes. HCAβ+ acknowledged a progressive memory decline compared to HCAβ-, while MCIAβ+ expressed more burdensome coping strategies, dismissive attitudes, and dependency comparative to either healthy group. Depression was more likely to be related to complaint themes in HCs, while complaint themes were associated with poorer list-learning performance in individuals with MCI. Complaint themes in those with MCI align with the MCI symptom complex, particularly when accompanied with high Aβ load. Healthy Aβ+ individuals acknowledged progressive memory change, suggesting they are aware of memory changes not yet detectable via neuropsychological measures. Depressive symptomatology associated with HC complaints, suggesting certain themes are affect-driven, while complaints in MCI are associated with organically driven functional impairment. Qualitative analysis of SMCs can inform the earliest clinical manifestations of Alzheimer's disease. Our findings can inform diagnostic approaches to the clinical evaluation of memory complaints in the nondemented elderly. (c) 2015 APA, all rights reserved).

Developmental changes in real life decision making: performance on a gambling task previously shown to depend on the ventromedial prefrontal cortex.

PubMed

Crone, Eveline A; van der Molen, Maurits W

2004-01-01

Patients with bilateral lesions of the ventromedial prefrontal cortex, when performing gambling tasks modeling real-life decision-making, opt for choices that yield high immediate gains in spite of higher future losses. Under the hypothesis that the prefrontal cortex is the last brain region to mature, it was examined whether young children would show a similar preference for immediate prospects. In Experiment 1, 4 age groups (6-9, 10-12, 13-15 and 18-25 years olds) performed 2 versions of a computerized variant of the original Iowa gambling task under 3 different feedback conditions (no feedback, global feedback, and option-specific feedback) and completed the Raven Standard Progressive Matrices as an index of inductive reasoning ability. In Experiment 2, 3 age groups (7-8, 11-12, and 15-16 year olds) performed both task versions in addition to a working memory task ("Digit Span Backwards"). Results showed a developmental increase in the sensitivity to future consequences, positive or negative, that could not be explained by developmental changes in working memory capacity or inductive reasoning. It was concluded that young children share with ventromedial prefrontal patients the failure to anticipate on future outcomes.

Hearing loss in Usher syndrome type II is nonprogressive.

PubMed

Reisser, Christoph F V; Kimberling, William J; Otterstedde, Christian R

2002-12-01

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.

Semantic Memory in the Clinical Progression of Alzheimer Disease.

PubMed

Tchakoute, Christophe T; Sainani, Kristin L; Henderson, Victor W

2017-09-01

Semantic memory measures may be useful in tracking and predicting progression of Alzheimer disease. We investigated relationships among semantic memory tasks and their 1-year predictive value in women with Alzheimer disease. We conducted secondary analyses of a randomized clinical trial of raloxifene in 42 women with late-onset mild-to-moderate Alzheimer disease. We assessed semantic memory with tests of oral confrontation naming, category fluency, semantic recognition and semantic naming, and semantic density in written narrative discourse. We measured global cognition (Alzheimer Disease Assessment Scale, cognitive subscale), dementia severity (Clinical Dementia Rating sum of boxes), and daily function (Activities of Daily Living Inventory) at baseline and 1 year. At baseline and 1 year, most semantic memory scores correlated highly or moderately with each other and with global cognition, dementia severity, and daily function. Semantic memory task performance at 1 year had worsened one-third to one-half standard deviation. Factor analysis of baseline test scores distinguished processes in semantic and lexical retrieval (semantic recognition, semantic naming, confrontation naming) from processes in lexical search (semantic density, category fluency). The semantic-lexical retrieval factor predicted global cognition at 1 year. Considered separately, baseline confrontation naming and category fluency predicted dementia severity, while semantic recognition and a composite of semantic recognition and semantic naming predicted global cognition. No individual semantic memory test predicted daily function. Semantic-lexical retrieval and lexical search may represent distinct aspects of semantic memory. Semantic memory processes are sensitive to cognitive decline and dementia severity in Alzheimer disease.

Does widowhood affect memory performance of older persons?

PubMed

Aartsen, Marja J; Van Tilburg, Theo; Smits, Carolien H M; Comijs, Hannie C; Knipscheer, Kees C P M

2005-02-01

The loss of a spouse has been found to have a negative effect on physical and mental health and leads to increased mortality. Whether conjugal bereavement also affects memory functioning has largely been unexamined. The present study investigates the effect of widowhood on memory functioning in older persons. The sample consisted of 474 married women and 690 married men aged 60-85 years in 1992, followed up in 1995 and 1998. During the study 135 (28%) of the women and 69 (10%) of the men lost their spouse. Linear regression analysis was used to examine whether widowed men and women differed from those who had not been widowed in rate of memory change over 6 years. Cross-domain latent-change models were subsequently used to evaluate the extent to which changes in memory are related to changes in other domains of functioning that may be affected by widowhood. Older adults who lost a spouse during follow-up showed a greater decline in memory over 6 years than those who remained married. A higher level of depressive symptoms at baseline was related to lower levels of memory functioning and a greater decline. Memory decline was unrelated to changes in depressive symptoms and physical health. Loss of the spouse is related to a greater decline in memory in older adults. The absence of an association with physical functioning and the weak association with mental functioning suggest that losing a spouse has an independent effect on memory functioning.

Adenosine A2A receptor blockade prevents synaptotoxicity and memory dysfunction caused by beta-amyloid peptides via p38 mitogen-activated protein kinase pathway.

PubMed

Canas, Paula M; Porciúncula, Lisiane O; Cunha, Geanne M A; Silva, Carla G; Machado, Nuno J; Oliveira, Jorge M A; Oliveira, Catarina R; Cunha, Rodrigo A

2009-11-25

Alzheimer's disease (AD) is characterized by memory impairment, neurochemically by accumulation of beta-amyloid peptide (namely Abeta(1-42)) and morphologically by an initial loss of nerve terminals. Caffeine consumption prevents memory dysfunction in different models, which is mimicked by antagonists of adenosine A(2A) receptors (A(2A)Rs), which are located in synapses. Thus, we now tested whether A(2A)R blockade prevents the early Abeta(1-42)-induced synaptotoxicity and memory dysfunction and what are the underlying signaling pathways. The intracerebral administration of soluble Abeta(1-42) (2 nmol) in rats or mice caused, 2 weeks later, memory impairment (decreased performance in the Y-maze and object recognition tests) and a loss of nerve terminal markers (synaptophysin, SNAP-25) without overt neuronal loss, astrogliosis, or microgliosis. These were prevented by pharmacological blockade [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine (SCH58261); 0.05 mg . kg(-1) . d(-1), i.p.; for 15 d] in rats, and genetic inactivation of A(2A)Rs in mice. Moreover, these were synaptic events since purified nerve terminals acutely exposed to Abeta(1-42) (500 nm) displayed mitochondrial dysfunction, which was prevented by A(2A)R blockade. SCH58261 (50 nm) also prevented the initial synaptotoxicity (loss of MAP-2, synaptophysin, and SNAP-25 immunoreactivity) and subsequent loss of viability of cultured hippocampal neurons exposed to Abeta(1-42) (500 nm). This A(2A)R-mediated control of neurotoxicity involved the control of Abeta(1-42)-induced p38 phosphorylation and was independent from cAMP/PKA (protein kinase A) pathway. Together, these results show that A(2A)Rs play a crucial role in the development of Abeta-induced synaptotoxicity leading to memory dysfunction through a p38 MAPK (mitogen-activated protein kinase)-dependent pathway and provide a molecular basis for the benefits of caffeine consumption in AD.

A program for undergraduate research into the mechanisms of sensory coding and memory decay

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

Calin-Jageman, R J

This is the final technical report for this DOE project, entitltled "A program for undergraduate research into the mechanisms of sensory coding and memory decay". The report summarizes progress on the three research aims: 1) to identify phyisological and genetic correlates of long-term habituation, 2) to understand mechanisms of olfactory coding, and 3) to foster a world-class undergraduate neuroscience program. Progress on the first aim has enabled comparison of learning-regulated transcripts across closely related learning paradigms and species, and results suggest that only a small core of transcripts serve truly general roles in long-term memory. Progress on the second aimmore » has enabled testing of several mutant phenotypes for olfactory behaviors, and results show that responses are not fully consistent with the combinitoral coding hypothesis. Finally, 14 undergraduate students participated in this research, the neuroscience program attracted extramural funding, and we completed a successful summer program to enhance transitions for community-college students into 4-year colleges to persue STEM fields.« less

Memory Loss and the Onset of Alzheimer's Disease Could Be Under the Control of Extracellular Heat Shock Proteins.

PubMed

Arispe, Nelson; De Maio, Antonio

2018-01-01

Alzheimer's disease (AD) is a major contemporary and escalating malady in which amyloid-β (Aβ) peptides are the most likely causative agent. Aβ peptides spontaneously tend to aggregate in extracellular fluids following a progression from a monomeric state, through intermediate forms, ending in amyloid fibers and plaques. It is generally accepted now that the neurotoxic agents leading to cellular death, memory loss, and other AD characteristics are the Aβ intermediate aggregated states. However, Aβ peptides are continuously produced, released into the extracellular space, and rapidly cleared from healthy brains. Coincidentally, members of the heat shock proteins (hsp) family are present in the extracellular medium of healthy cells and body fluids, opening the possibility that hsps and Aβ could meet and interact in the extracellular milieu of the brain. In this perspective and reflection article, we place our investigation showing that the presence of Hsp70s mitigate the formation of low molecular weight Aβ peptide oligomers resulting in a reduction of cellular toxicity, in context of the current understanding of the disease. We propose that it may be an inverse relationship between the presence of Hsp70, the stage of Aβ oligomers, neurotoxicity, and the incidence of AD, particularly since the expression and circulating levels of hsp decrease with aging. Combining these observations, we propose that changes in the dynamics of Hsp70s and Aβ concentrations in the circulating brain fluids during aging defines the control of the formation of Aβ toxic aggregates, thus determining the conditions for neuron degeneration and the incidence of AD.

Acoustic Neuroma: Questions to Discuss with Your Doctor

MedlinePlus

... products will be searched. Shopping Cart Description Qty Price The Harvard Medical School 6-Week Plan for ... Memory: Understanding Age-Related Memory Loss (PDF - Lowest Price!) $18.00 Harvard Health Letter (Print & Online Access ( ...

Colonic Polyps: Questions to Discuss with Your Doctor

MedlinePlus

... products will be searched. Shopping Cart Description Qty Price The Harvard Medical School 6-Week Plan for ... Memory: Understanding Age-Related Memory Loss (PDF - Lowest Price!) $18.00 Harvard Health Letter (Print & Online Access ( ...

When You Visit Your Doctor After a Heart Attack

MedlinePlus

... products will be searched. Shopping Cart Description Qty Price The Harvard Medical School 6-Week Plan for ... Memory: Understanding Age-Related Memory Loss (PDF - Lowest Price!) $18.00 Harvard Health Letter (Print & Online Access ( ...

When You Visit Your Doctor: Irregular Menstrual Periods

MedlinePlus

... products will be searched. Shopping Cart Description Qty Price The Harvard Medical School 6-Week Plan for ... Memory: Understanding Age-Related Memory Loss (PDF - Lowest Price!) $18.00 Harvard Health Letter (Print & Online Access ( ...

Memory Loss: 7 Tips to Improve Your Memory

MedlinePlus

... Volunteer at a local school or community organization. Social interaction helps ward off depression and stress, both of ... most healthy adults, the Department of Health and Human Services recommends at least 150 minutes a week ...

Three-dimensional analysis of synapses in the transentorhinal cortex of Alzheimer's disease patients.

PubMed

Domínguez-Álvaro, M; Montero-Crespo, M; Blazquez-Llorca, L; Insausti, R; DeFelipe, J; Alonso-Nanclares, L

2018-03-02

Synaptic dysfunction or loss in early stages of Alzheimer's disease (AD) is thought to be a major structural correlate of cognitive dysfunction. Early loss of episodic memory, which occurs at the early stage of AD, is closely associated with the progressive degeneration of medial temporal lobe (MTL) structures of which the transentorhinal cortex (TEC) is the first affected area. However, no ultrastructural studies have been performed in this region in human brain samples from AD patients. In the present study, we have performed a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) to investigate possible synaptic alterations in the TEC of patients with AD. Surprisingly, the analysis of the density, morphological features and spatial distribution of synapses in the neuropil showed no significant differences between AD and control samples. However, light microscopy studies showed that cortical thickness of the TEC was severely reduced in AD samples, but there were no changes in the volume occupied by neuronal and glial cell bodies, blood vessels, and neuropil. Thus, the present results indicate that there is a dramatic loss of absolute number of synapses, while the morphology of synaptic junctions and synaptic spatial distribution are maintained. How these changes affect cognitive impairment in AD remains to be elucidated.

Synthetic analog and digital circuits for cellular computation and memory.

PubMed

Purcell, Oliver; Lu, Timothy K

2014-10-01

Biological computation is a major area of focus in synthetic biology because it has the potential to enable a wide range of applications. Synthetic biologists have applied engineering concepts to biological systems in order to construct progressively more complex gene circuits capable of processing information in living cells. Here, we review the current state of computational genetic circuits and describe artificial gene circuits that perform digital and analog computation. We then discuss recent progress in designing gene networks that exhibit memory, and how memory and computation have been integrated to yield more complex systems that can both process and record information. Finally, we suggest new directions for engineering biological circuits capable of computation. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

[Pure progressive amnesia, isolated for 16 years with focal hippocampus atrophy].

PubMed

Richard-Mornas, A; Foyatier-Michel, N; Thomas-Antérion, C

2011-01-01

Pure progressive amnesia is a rare and unusual syndrome involving long preservation of autonomy and absence of progression in other cognitive domains. We report a case which remained quiescent for 16 years characterized by severe isolated episodic amnesia and preservation of spatial, semantic and implicit memory and autonomy. MRI revealed bilateral focal atrophy of the hippocampus. This specific pattern of impairment differs from other types of amnesic syndromes. It is important to identify this kind of amnesia because of its specific course. Studying the topography of the brain lesions may contribute to a better understanding of the neural systems involved in declarative memory. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Rapid Forgetting Results from Competition over Time between Items in Visual Working Memory

ERIC Educational Resources Information Center

Pertzov, Yoni; Manohar, Sanjay; Husain, Masud

2017-01-01

Working memory is now established as a fundamental cognitive process across a range of species. Loss of information held in working memory has the potential to disrupt many aspects of cognitive function. However, despite its significance, the mechanisms underlying rapid forgetting remain unclear, with intense recent debate as to whether it is…

The Dutch Memory Compensation Questionnaire: Psychometric Properties and Regression-Based Norms

ERIC Educational Resources Information Center

Van der Elst, Wim; Hoogenhout, Esther M.; Dixon, Roger A.; De Groot, Renate H. M.; Jolles, Jelle

2011-01-01

The Memory Compensation Questionnaire (MCQ) is a psychometrically sound instrument that assesses the variety and extent to which an individual compensates for actual or perceived memory losses. Until now, only an English version of the MCQ has been psychometrically evaluated. The aim of the present study was to establish a Dutch version of the MCQ…

Retrieval Failure versus Memory Loss in Experimental Amnesia: Definitions and Processes

ERIC Educational Resources Information Center

Miller, Ralph R.; Matzel, Louis D.

2006-01-01

For at least 40 years, there has been a recurring argument concerning the nature of experimental amnesia, with one side arguing that amnesic treatments interfere with the formation of enduring memories and the other side arguing that these treatments interfere with the expression of memories that were effectively encoded. The argument appears to…

Memory-Metal Electromechanical Actuators

NASA Technical Reports Server (NTRS)

Ruoff, C. F.

1984-01-01

Electrically controlled actuator produces predetermined force, torque, or displacement without motors, solenoids, or gears. Using memory-metal elements, actuator responds to digital input without electronic digitalto-analog conversion. To prevent overheating and consequent loss of hotformed shape, each element protected by thermostat turns off current when predetermined temperature is exceeded. Memory metals used to generate fast mechanical response to electric signals.

Role of adult neurogenesis in hippocampal-cortical memory consolidation

PubMed Central

2014-01-01

Acquired memory is initially dependent on the hippocampus (HPC) for permanent memory formation. This hippocampal dependency of memory recall progressively decays with time, a process that is associated with a gradual increase in dependency upon cortical structures. This process is commonly referred to as systems consolidation theory. In this paper, we first review how memory becomes hippocampal dependent to cortical dependent with an emphasis on the interactions that occur between the HPC and cortex during systems consolidation. We also review the mechanisms underlying the gradual decay of HPC dependency during systems consolidation from the perspective of memory erasures by adult hippocampal neurogenesis. Finally, we discuss the relationship between systems consolidation and memory precision. PMID:24552281

A multiplexed quantum memory.

PubMed

Lan, S-Y; Radnaev, A G; Collins, O A; Matsukevich, D N; Kennedy, T A; Kuzmich, A

2009-08-03

A quantum repeater is a system for long-distance quantum communication that employs quantum memory elements to mitigate optical fiber transmission losses. The multiplexed quantum memory (O. A. Collins, S. D. Jenkins, A. Kuzmich, and T. A. B. Kennedy, Phys. Rev. Lett. 98, 060502 (2007)) has been shown theoretically to reduce quantum memory time requirements. We present an initial implementation of a multiplexed quantum memory element in a cold rubidium gas. We show that it is possible to create atomic excitations in arbitrary memory element pairs and demonstrate the violation of Bell's inequality for light fields generated during the write and read processes.

Human Hippocampal Structure: A Novel Biomarker Predicting Mnemonic Vulnerability to, and Recovery from, Sleep Deprivation

PubMed Central

Goldstein-Piekarski, Andrea N.; Greer, Stephanie M.; Stark, Shauna; Stark, Craig E.

2016-01-01

Sleep deprivation impairs the formation of new memories. However, marked interindividual variability exists in the degree to which sleep loss compromises learning, the mechanistic reasons for which are unclear. Furthermore, which physiological sleep processes restore learning ability following sleep deprivation are similarly unknown. Here, we demonstrate that the structural morphology of human hippocampal subfields represents one factor determining vulnerability (and conversely, resilience) to the impact of sleep deprivation on memory formation. Moreover, this same measure of brain morphology was further associated with the quality of nonrapid eye movement slow wave oscillations during recovery sleep, and by way of such activity, determined the success of memory restoration. Such findings provide a novel human biomarker of cognitive susceptibility to, and recovery from, sleep deprivation. Moreover, this metric may be of special predictive utility for professions in which memory function is paramount yet insufficient sleep is pervasive (e.g., aviation, military, and medicine). SIGNIFICANCE STATEMENT Sleep deprivation does not impact all people equally. Some individuals show cognitive resilience to the effects of sleep loss, whereas others express striking vulnerability, the reasons for which remain largely unknown. Here, we demonstrate that structural features of the human brain, specifically those within the hippocampus, accurately predict which individuals are susceptible (or conversely, resilient) to memory impairments caused by sleep deprivation. Moreover, this same structural feature determines the success of memory restoration following subsequent recovery sleep. Therefore, structural properties of the human brain represent a novel biomarker predicting individual vulnerability to (and recovery from) the effects of sleep loss, one with occupational relevance in professions where insufficient sleep is pervasive yet memory function is paramount. PMID:26911684

Treadmill exercise ameliorates Alzheimer disease-associated memory loss through the Wnt signaling pathway in the streptozotocin-induced diabetic rats.

PubMed

Kim, Dae-Young; Jung, Sun-Young; Kim, Kijeong; Kim, Chang-Ju

2016-08-01

Diabetes mellitus is considered as a risk factor for Alzheimer disease. The aim of the present study was to evaluate the possibility whether treadmill exercise ameliorates Alzheimer disease-associated memory loss in the diabetes mellitus. For this study, the effects of treadmill exercise on short-term memory and spatial learning ability in relation with Wnt signaling pathway were evaluated using the streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by intraperitoneal injection of STZ. Step-down avoidance task and 8-arm radial maze test were performed for the memory function. Immunohistochemistry for 5-bro-mo-2'-deoxyridine (BrdU) and doublecortin (DCX) and Western blot for Wnt3 and glycogen synthase kinase-3β (GSK-3β) were conducted. The rats in the exercise groups were made to run on the treadmill for 30 min per one day, 5 times a week, during 12 weeks. In the present results, short-term memory and spatial learning ability were deteriorated by induction of diabetes. Treadmill exercise improved short-term memory and spatial learning ability in the diabetic rats. The numbers of BrdU-positive and DCX-positive cells in the hippocampal dentate gyrus were decreased by induction of diabetes. Treadmill exercise increased these numbers in the diabetic rats. Wnt3 expression in the hippocampus was decreased and GSK-3β expression in the hippocampus was increased by induction of diabetes. Treadmill exercise increased Wnt3 expression and suppressed GSK-3β expression in the diabetic rats. The present study suggests that treadmill exercise alleviates Alzheimer disease-associated memory loss by increasing neurogenesis through activating Wnt signaling pathway in the diabetic rats.

Episodic memories.

PubMed

Conway, Martin A

2009-09-01

An account of episodic memories is developed that focuses on the types of knowledge they represent, their properties, and the functions they might serve. It is proposed that episodic memories consist of episodic elements, summary records of experience often in the form of visual images, associated to a conceptual frame that provides a conceptual context. Episodic memories are embedded in a more complex conceptual system in which they can become the basis of autobiographical memories. However, the function of episodic memories is to keep a record of progress with short-term goals and access to most episodic memories is lost soon after their formation. Finally, it is suggested that developmentally episodic memories form the basis of the conceptual system and it is from sets of episodic memories that early non-verbal conceptual knowledge is abstracted.

Behavioural pharmacology: 40+ years of progress, with a focus on glutamate receptors and cognition

PubMed Central

Robbins, Trevor W.; Murphy, Emily R.

2006-01-01

Behavioural pharmacology is an interdisciplinary field at the intersection of several research areas that ultimately lead to the development of drugs for clinical use and build understanding of how brain functions enable cognition and behaviour. In this article, the development of behavioural pharmacology in the UK is briefly surveyed, and the current status and success of the field is highlighted by the progress in our understanding of learning and memory that has resulted from discoveries in glutamate receptor pharmacology allied to theoretical and methodological advances in behavioural neuroscience. We describe the original breakthrough in terms of the role of NMDA receptors in hippocampal-mediated spatial learning and long-term potentiation, and review recent advances that demonstrate the involvement of glutamate receptor in working memory, recognition memory, stimulus–response learning and memory, and higher cognitive functions. We also discuss the unique functions of NMDA receptors and the fundamental role of AMPA receptors in processes that are common to some of these forms of memory, including encoding, consolidation and retrieval. PMID:16490260

Memory in a fractional-order cardiomyocyte model alters properties of alternans and spontaneous activity

NASA Astrophysics Data System (ADS)

Comlekoglu, T.; Weinberg, S. H.

2017-09-01

Cardiac memory is the dependence of electrical activity on the prior history of one or more system state variables, including transmembrane potential (Vm), ionic current gating, and ion concentrations. While prior work has represented memory either phenomenologically or with biophysical detail, in this study, we consider an intermediate approach of a minimal three-variable cardiomyocyte model, modified with fractional-order dynamics, i.e., a differential equation of order between 0 and 1, to account for history-dependence. Memory is represented via both capacitive memory, due to fractional-order Vm dynamics, that arises due to non-ideal behavior of membrane capacitance; and ionic current gating memory, due to fractional-order gating variable dynamics, that arises due to gating history-dependence. We perform simulations for varying Vm and gating variable fractional-orders and pacing cycle length and measure action potential duration (APD) and incidence of alternans, loss of capture, and spontaneous activity. In the absence of ionic current gating memory, we find that capacitive memory, i.e., decreased Vm fractional-order, typically shortens APD, suppresses alternans, and decreases the minimum cycle length (MCL) for loss of capture. However, in the presence of ionic current gating memory, capacitive memory can prolong APD, promote alternans, and increase MCL. Further, we find that reduced Vm fractional order (typically less than 0.75) can drive phase 4 depolarizations that promote spontaneous activity. Collectively, our results demonstrate that memory reproduced by a fractional-order model can play a role in alternans formation and pacemaking, and in general, can greatly increase the range of electrophysiological characteristics exhibited by a minimal model.

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy

PubMed Central

Booth, Clair A.; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W.; Randall, Andrew D.

2016-01-01

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. SIGNIFICANCE STATEMENT Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. PMID:26758828

Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy.

PubMed

Booth, Clair A; Witton, Jonathan; Nowacki, Jakub; Tsaneva-Atanasova, Krasimira; Jones, Matthew W; Randall, Andrew D; Brown, Jonathan T

2016-01-13

The formation and deposition of tau protein aggregates is proposed to contribute to cognitive impairments in dementia by disrupting neuronal function in brain regions, including the hippocampus. We used a battery of in vivo and in vitro electrophysiological recordings in the rTg4510 transgenic mouse model, which overexpresses a mutant form of human tau protein, to investigate the effects of tau pathology on hippocampal neuronal function in area CA1 of 7- to 8-month-old mice, an age point at which rTg4510 animals exhibit advanced tau pathology and progressive neurodegeneration. In vitro recordings revealed shifted theta-frequency resonance properties of CA1 pyramidal neurons, deficits in synaptic transmission at Schaffer collateral synapses, and blunted plasticity and imbalanced inhibition at temporoammonic synapses. These changes were associated with aberrant CA1 network oscillations, pyramidal neuron bursting, and spatial information coding in vivo. Our findings relate tauopathy-associated changes in cellular neurophysiology to altered behavior-dependent network function. Dementia is characterized by the loss of learning and memory ability. The deposition of tau protein aggregates in the brain is a pathological hallmark of dementia; and the hippocampus, a brain structure known to be critical in processing learning and memory, is one of the first and most heavily affected regions. Our results show that, in area CA1 of hippocampus, a region involved in spatial learning and memory, tau pathology is associated with specific disturbances in synaptic, cellular, and network-level function, culminating in the aberrant encoding of spatial information and spatial memory impairment. These studies identify several novel ways in which hippocampal information processing may be disrupted in dementia, which may provide targets for future therapeutic intervention. Copyright © 2016 Booth, Witton et al.

Modulation of working memory function by motivation through loss-aversion.

PubMed

Krawczyk, Daniel C; D'Esposito, Mark

2013-04-01

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g., stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to nonincentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to nonincentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. Copyright © 2011 Wiley Periodicals, Inc.

Modulation of working memory function by motivation through loss-aversion

PubMed Central

Krawczyk, Daniel C.; D’Esposito, Mark

2012-01-01

Cognitive performance is affected by motivation. Few studies, however, have investigated the neural mechanisms of the influence of motivation through potential monetary punishment on working memory. We employed functional MRI during a delayed recognition task that manipulated top-down control demands with added monetary incentives to some trials in the form of potential losses of bonus money. Behavioral performance on the task was influenced by loss-threatening incentives in the form of faster and more accurate performance. As shown previously, we found enhancement of activity for relevant stimuli occurs throughout all task periods (e.g. stimulus encoding, maintenance, and response) in both prefrontal and visual association cortex. Further, these activation patterns were enhanced for trials with possible monetary loss relative to non-incentive trials. During the incentive cue, the amygdala and striatum showed significantly greater activation when money was at a possible loss on the trial. We also evaluated patterns of functional connectivity between regions responsive to monetary consequences and prefrontal areas responsive to the task. This analysis revealed greater delay period connectivity between and the left insula and prefrontal cortex with possible monetary loss relative to non-incentive trials. Overall, these results reveal that incentive motivation can modulate performance on working memory tasks through top-down signals via amplification of activity within prefrontal and visual association regions selective to processing the perceptual inputs of the stimuli to be remembered. PMID:22113962

Identification of Genes that Maintain Behavioral and Structural Plasticity during Sleep Loss

PubMed Central

Seugnet, Laurent; Dissel, Stephane; Thimgan, Matthew; Cao, Lijuan; Shaw, Paul J.

2017-01-01

Although patients with primary insomnia experience sleep disruption, they are able to maintain normal performance on a variety of cognitive tasks. This observation suggests that insomnia may be a condition where predisposing factors simultaneously increase the risk for insomnia and also mitigate against the deleterious consequences of waking. To gain insight into processes that might regulate sleep and buffer neuronal circuits during sleep loss, we manipulated three genes, fat facet (faf), highwire (hiw) and the GABA receptor Resistance to dieldrin (Rdl), that were differentially modulated in a Drosophila model of insomnia. Our results indicate that increasing faf and decreasing hiw or Rdl within wake-promoting large ventral lateral clock neurons (lLNvs) induces sleep loss. As expected, sleep loss induced by decreasing hiw in the lLNvs results in deficits in short-term memory and increases of synaptic growth. However, sleep loss induced by knocking down Rdl in the lLNvs protects flies from sleep-loss induced deficits in short-term memory and increases in synaptic markers. Surprisingly, decreasing hiw and Rdl within the Mushroom Bodies (MBs) protects against the negative effects of sleep deprivation (SD) as indicated by the absence of a subsequent homeostatic response, or deficits in short-term memory. Together these results indicate that specific genes are able to disrupt sleep and protect against the negative consequences of waking in a circuit dependent manner. PMID:29109678

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma

PubMed Central

Nickerson, John M.; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-jie; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

2015-01-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. PMID:25478814

The spectrum of disease in chronic traumatic encephalopathy.

PubMed

McKee, Ann C; Stern, Robert A; Nowinski, Christopher J; Stein, Thor D; Alvarez, Victor E; Daneshvar, Daniel H; Lee, Hyo-Soon; Wojtowicz, Sydney M; Hall, Garth; Baugh, Christine M; Riley, David O; Kubilus, Caroline A; Cormier, Kerry A; Jacobs, Matthew A; Martin, Brett R; Abraham, Carmela R; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L; Budson, Andrew E; Goldstein, Lee E; Kowall, Neil W; Cantu, Robert C

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I-IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I-III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer's disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.

The spectrum of disease in chronic traumatic encephalopathy

PubMed Central

McKee, Ann C.; Stein, Thor D.; Nowinski, Christopher J.; Stern, Robert A.; Daneshvar, Daniel H.; Alvarez, Victor E.; Lee, Hyo-Soon; Hall, Garth; Wojtowicz, Sydney M.; Baugh, Christine M.; Riley, David O.; Kubilus, Caroline A.; Cormier, Kerry A.; Jacobs, Matthew A.; Martin, Brett R.; Abraham, Carmela R.; Ikezu, Tsuneya; Reichard, Robert Ross; Wolozin, Benjamin L.; Budson, Andrew E.; Goldstein, Lee E.; Kowall, Neil W.; Cantu, Robert C.

2013-01-01

Chronic traumatic encephalopathy is a progressive tauopathy that occurs as a consequence of repetitive mild traumatic brain injury. We analysed post-mortem brains obtained from a cohort of 85 subjects with histories of repetitive mild traumatic brain injury and found evidence of chronic traumatic encephalopathy in 68 subjects: all males, ranging in age from 17 to 98 years (mean 59.5 years), including 64 athletes, 21 military veterans (86% of whom were also athletes) and one individual who engaged in self-injurious head banging behaviour. Eighteen age- and gender-matched individuals without a history of repetitive mild traumatic brain injury served as control subjects. In chronic traumatic encephalopathy, the spectrum of hyperphosphorylated tau pathology ranged in severity from focal perivascular epicentres of neurofibrillary tangles in the frontal neocortex to severe tauopathy affecting widespread brain regions, including the medial temporal lobe, thereby allowing a progressive staging of pathology from stages I–IV. Multifocal axonal varicosities and axonal loss were found in deep cortex and subcortical white matter at all stages of chronic traumatic encephalopathy. TAR DNA-binding protein 43 immunoreactive inclusions and neurites were also found in 85% of cases, ranging from focal pathology in stages I–III to widespread inclusions and neurites in stage IV. Symptoms in stage I chronic traumatic encephalopathy included headache and loss of attention and concentration. Additional symptoms in stage II included depression, explosivity and short-term memory loss. In stage III, executive dysfunction and cognitive impairment were found, and in stage IV, dementia, word-finding difficulty and aggression were characteristic. Data on athletic exposure were available for 34 American football players; the stage of chronic traumatic encephalopathy correlated with increased duration of football play, survival after football and age at death. Chronic traumatic encephalopathy was the sole diagnosis in 43 cases (63%); eight were also diagnosed with motor neuron disease (12%), seven with Alzheimer’s disease (11%), 11 with Lewy body disease (16%) and four with frontotemporal lobar degeneration (6%). There is an ordered and predictable progression of hyperphosphorylated tau abnormalities through the nervous system in chronic traumatic encephalopathy that occurs in conjunction with widespread axonal disruption and loss. The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein. PMID:23208308

Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats.

PubMed

Lauterborn, Julie C; Palmer, Linda C; Jia, Yousheng; Pham, Danielle T; Hou, Bowen; Wang, Weisheng; Trieu, Brian H; Cox, Conor D; Kantorovich, Svetlana; Gall, Christine M; Lynch, Gary

2016-02-03

Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration. Copyright © 2016 the authors 0270-6474/16/361636-11$15.00/0.

Chronic Ampakine Treatments Stimulate Dendritic Growth and Promote Learning in Middle-Aged Rats

PubMed Central

Lauterborn, Julie C.; Palmer, Linda C.; Jia, Yousheng; Pham, Danielle T.; Hou, Bowen; Wang, Weisheng; Trieu, Brian H.; Cox, Conor D.; Kantorovich, Svetlana

2016-01-01

Positive allosteric modulators of AMPA-type glutamate receptors (ampakines) have been shown to rescue synaptic plasticity and reduce neuropathology in rodent models of cognitive disorders. Here we tested whether chronic ampakine treatment offsets age-related dendritic retraction in middle-aged (MA) rats. Starting at 10 months of age, rats were housed in an enriched environment and given daily treatment with a short half-life ampakine or vehicle for 3 months. Dendritic branching and spine measures were collected from 3D reconstructions of Lucifer yellow-filled CA1 pyramidal cells. There was a substantial loss of secondary branches, relative to enriched 2.5-month-old rats, in apical and basal dendritic fields of vehicle-treated, but not ampakine-treated, 13-month-old rats. Baseline synaptic responses in CA1 were only subtly different between the two MA groups, but long-term potentiation was greater in ampakine-treated rats. Unsupervised learning of a complex environment was used to assess treatment effects on behavior. Vehicle- and drug-treated rats behaved similarly during a first 30 min session in the novel environment but differed markedly on subsequent measures of long-term memory. Markov sequence analysis uncovered a clear increase in the predictability of serial movements between behavioral sessions 2 and 3 in the ampakine, but not vehicle, group. These results show that a surprising degree of dendritic retraction occurs by middle age and that this can be mostly offset by pharmacological treatments without evidence for unwanted side effects. The functional consequences of rescue were prominent with regard to memory but also extended to self-organization of behavior. SIGNIFICANCE STATEMENT Brain aging is characterized by a progressive loss of dendritic arbors and the emergence of impairments to learning-related synaptic plasticity. The present studies show that dendritic losses are evident by middle age despite housing in an enriched environment and can be mostly reversed by long-term, oral administration of a positive allosteric modulator of AMPA-type glutamate receptors. Dendritic recovery was accompanied by improvements to both synaptic plasticity and the encoding of long-term memory of a novel, complex environment. Because the short half-life compound had no evident negative effects, the results suggest a plausible strategy for treating age-related neuronal deterioration. PMID:26843645

Effect of traditional medicine brahmi vati and bacoside A-rich fraction of Bacopa monnieri on acute pentylenetetrzole-induced seizures, amphetamine-induced model of schizophrenia, and scopolamine-induced memory loss in laboratory animals.

PubMed

Mishra, Amrita; Mishra, Arun K; Jha, Shivesh

2018-03-01

Brahmi vati (BV) is an Ayurvedic polyherbal formulation used since ancient times and has been prescribed in seizures associated with schizophrenia and related memory loss by Ayurvedic practitioners in India. The aim of the study was to investigate these claims by evaluation of anticonvulsant, antischizophreniac, and memory-enhancing activities. Antioxidant condition of brain was determined by malondialdehyde (MDA) and reduced glutathione (GSH) levels estimations. Acetylcholinesterase (AChE) was quantitatively estimated in the brain tissue. Brahmi vati was prepared in-house by strictly following the traditional Ayurvedic formula. Bacoside A rich fraction (BA) of Bacopa monnieri was prepared by extraction and fractionation. It was than standardized by High Performance Liquid Chromatography (HPLC) and given in the dose of 32.5mg/kg body weight to the different groups of animals for 7days. On the seventh day, activities were performed adopting standard procedures. Brahmi vati showed significant anticonvulsant, memory-enhancing and antischizophrenia activities, when compared with the control groups and BA. It cause significantly higher brain glutathione levels. Acetylcholinesterase activity was found to be significantly low in BV-treated group. The finding of the present study suggests that BV may be used to treat seizures associated with schizophrenia and related memory loss. Copyright © 2018 Elsevier Inc. All rights reserved.

Understanding Memory Loss | NIH MedlinePlus the Magazine

MedlinePlus

... urine. She or he also checks your memory, problem solving, counting, and language skills. The doctor also may suggest a brain scan to show the normal and problem areas in the brain. Once the cause of ...

Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats.

PubMed

Ash, Jessica A; Lu, Hanbing; Taxier, Lisa R; Long, Jeffrey M; Yang, Yihong; Stein, Elliot A; Rapp, Peter R

2016-10-25

Changes in the functional connectivity (FC) of large-scale brain networks are a prominent feature of brain aging, but defining their relationship to variability along the continuum of normal and pathological cognitive outcomes has proved challenging. Here we took advantage of a well-characterized rat model that displays substantial individual differences in hippocampal memory during aging, uncontaminated by slowly progressive, spontaneous neurodegenerative disease. By this approach, we aimed to interrogate the underlying neural network substrates that mediate aging as a uniquely permissive condition and the primary risk for neurodegeneration. Using resting state (rs) blood oxygenation level-dependent fMRI and a restrosplenial/posterior cingulate cortex seed, aged rats demonstrated a large-scale network that had a spatial distribution similar to the default mode network (DMN) in humans, consistent with earlier findings in younger animals. Between-group whole brain contrasts revealed that aged subjects with documented deficits in memory (aged impaired) displayed widespread reductions in cortical FC, prominently including many areas outside the DMN, relative to both young adults (Y) and aged rats with preserved memory (aged unimpaired, AU). Whereas functional connectivity was relatively preserved in AU rats, they exhibited a qualitatively distinct network signature, comprising the loss of an anticorrelated network observed in Y adults. Together the findings demonstrate that changes in rs-FC are specifically coupled to variability in the cognitive outcome of aging, and that successful neurocognitive aging is associated with adaptive remodeling, not simply the persistence of youthful network dynamics.

Phospholipase A2 - nexus of aging, oxidative stress, neuronal excitability, and functional decline of the aging nervous system? Insights from a snail model system of neuronal aging and age-associated memory impairment.

PubMed

Hermann, Petra M; Watson, Shawn N; Wildering, Willem C

2014-01-01

The aging brain undergoes a range of changes varying from subtle structural and physiological changes causing only minor functional decline under healthy normal aging conditions, to severe cognitive or neurological impairment associated with extensive loss of neurons and circuits due to age-associated neurodegenerative disease conditions. Understanding how biological aging processes affect the brain and how they contribute to the onset and progress of age-associated neurodegenerative diseases is a core research goal in contemporary neuroscience. This review focuses on the idea that changes in intrinsic neuronal electrical excitability associated with (per)oxidation of membrane lipids and activation of phospholipase A2 (PLA2) enzymes are an important mechanism of learning and memory failure under normal aging conditions. Specifically, in the context of this special issue on the biology of cognitive aging we portray the opportunities offered by the identifiable neurons and behaviorally characterized neural circuits of the freshwater snail Lymnaea stagnalis in neuronal aging research and recapitulate recent insights indicating a key role of lipid peroxidation-induced PLA2 as instruments of aging, oxidative stress and inflammation in age-associated neuronal and memory impairment in this model system. The findings are discussed in view of accumulating evidence suggesting involvement of analogous mechanisms in the etiology of age-associated dysfunction and disease of the human and mammalian brain.

Telomere Dynamics in Immune Senescence and Exhaustion Triggered by Chronic Viral Infection.

PubMed

Bellon, Marcia; Nicot, Christophe

2017-10-05

The progressive loss of immunological memory during aging correlates with a reduced proliferative capacity and shortened telomeres of T cells. Growing evidence suggests that this phenotype is recapitulated during chronic viral infection. The antigenic volume imposed by persistent and latent viruses exposes the immune system to unique challenges that lead to host T-cell exhaustion, characterized by impaired T-cell functions. These dysfunctional memory T cells lack telomerase, the protein capable of extending and stabilizing chromosome ends, imposing constraints on telomere dynamics. A deleterious consequence of this excessive telomere shortening is the premature induction of replicative senescence of viral-specific CD8+ memory T cells. While senescent cells are unable to expand, they can survive for extended periods of time and are more resistant to apoptotic signals. This review takes a closer look at T-cell exhaustion in chronic viruses known to cause human disease: Epstein-Barr virus (EBV), Hepatitis B/C/D virus (HBV/HCV/HDV), human herpesvirus 8 (HHV-8), human immunodeficiency virus (HIV), human T-cell leukemia virus type I (HTLV-I), human papillomavirus (HPV), herpes simplex virus-1/2(HSV-1/2), and Varicella-Zoster virus (VZV). Current literature linking T-cell exhaustion with critical telomere lengths and immune senescence are discussed. The concept that enduring antigen stimulation leads to T-cell exhaustion that favors telomere attrition and a cell fate marked by enhanced T-cell senescence appears to be a common endpoint to chronic viral infections.

HIV-specific cytotoxic T lymphocyte precursors exist in a CD28-CD8+ T cell subset and increase with loss of CD4 T cells.

PubMed

Lewis, D E; Yang, L; Luo, W; Wang, X; Rodgers, J R

1999-06-18

To determine whether the CD28-CD8+ T cells that develop during HIV infection contain HIV-specific cytotoxic precursor cells. CD8 subpopulations from six asymptomatic HIV-positive adults, with varying degrees of CD4 T cell loss, were sorted by flow cytometry and HIV-specific precursor cytotoxic T lymphocyte frequencies were measured. Three populations of CD8 T cells were tested: CD28+CD5-- T cells, CD28-CD57+ T cells (thought to be memory cells) and CD28-CD57- T cells (function unknown). Sorted CD8 subsets were stimulated with antigen presenting cells expressing HIV-1 Gag/Pol molecules. Cytotoxic T cell assays on Gag/Pol expressing 51Cr-labeled Epstein-Barr virus transformed autologous B cells lines or control targets were performed after 2 weeks. Specific lysis and precursor frequencies were calculated. Both CD28 positive and CD28-CD57+ populations contained appreciable numbers of precursors (9-1720 per 10(6) CD8+ T cells). However, the CD28-CD57- population had fewer precursors in five out of six people studied. More CD28 positive HIV-specific cytotoxic T lymphocyte precursors were found in patients with CD4:CD8 ratios > 1, whereas more CD28-CD57+ precursors were found in patients whose CD4:CD8 ratios were < 1 (r2, 0.68). Memory HIV-specific precursor cytotoxic T lymphocytes are found in both CD28 positive and CD28-CD8+ cells, however, a CD28-CD57- subpopulation had fewer. Because CD28-CD57+ cells are antigen-driven with limited diversity, the loss of CD28 on CD8 T cells during disease progression may reduce the response to new HIV mutations; this requires further testing.

Autobiographical memory loss following a right prefrontal lobe tumour resection: a case report and review of the literature.

PubMed

Jamjoom, A A B; Gallo, P; Kandasamy, J; Phillips, J; Sokol, D

2017-07-01

The right prefrontal lobe has not traditionally been considered eloquent brain. Resection of tumours within this region does not typically lead to permanent functional impairment. In this report, we highlight the case of a patient who developed autobiographical memory loss following an uncomplicated resection of a right prefrontal tumour. A previously fit and well 15-year old presented with a persistent right-sided headache. An MRI demonstrated an expanded right mid-frontal gyrus with changes consistent with a low-grade tumour. The patient underwent a right-sided craniotomy and resection of the lesion which was confirmed as a WHO grade II diffuse astrocytoma. Postoperatively, the patient reported profound retrograde amnesia for a range of memory components, in particular autobiographical memory and semantic memory. Postoperative imaging showed a good resection margin with no evidence of underlying brain injury. Over an 18-month period, the patient showed no improvement in autobiographical memory; however, significant relearning of semantic knowledge took place and her academic performance was found to be in line with expectations for her age. In this report, we discuss a case and review the literature on the role of the right prefrontal cortex in memory and caution on the perception of right prefrontal non-eloquence.

Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism.

PubMed

Brand, Matthias; Eggers, Carsten; Reinhold, Nadine; Fujiwara, Esther; Kessler, Josef; Heiss, Wolf-Dieter; Markowitsch, Hans J

2009-10-30

Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.

Attenuation of cadmium-induced decline in spatial, habituation and recognition memory by long-term administration of almond and walnut supplementation: Role of cholinergic function.

PubMed

Batool, Zehra; Agha, Faiza; Ahmad, Saara; Liaquat, Laraib; Tabassum, Saiqa; Khaliq, Saima; Anis, Lubna; Sajid, Irfan; Emad, Shaista; Perveen, Tahira; Haider, Saida

2017-01-01

Excessive exposure of cadmium which is regarded as a neurotoxin can stimulate aging process by inducing abnormality in neuronal function. It has been reported that supplementation of almond and walnut attenuate age-related memory loss. Present study was designed to investigate the weekly administration of cadmium for one month on learning and memory function with relation to cholinergic activity. Cadmium was administered at the dose of 50 mg/kg/week. Whereas, almond and walnut was supplemented at the dose of 400 mg/kg/day along with cadmium administration to separate set of rats. At the end of experiment, memory function was assessed by Morris water maze, open field test and novel object recognition test. Results of the present study showed that cadmium administration significantly reduced memory retention. Reduced acetylcholine levels and elevated acetyl cholinesterase activity were also observed in frontal cortex and hippocampus of cadmium treated rats. Malondialdehyde levels were also significantly increased following the administration of cadmium. Daily supplementation of almond and walnut for 28 days significantly attenuated cadmium-induced memory impairment in rats. Results of the present study are discussed in term of cholinergic activity in cadmium-induced memory loss and its attenuation by nuts supplementation in rats.

A Special Extract of Bacopa monnieri (CDRI-08)-Restored Memory in CoCl2-Hypoxia Mimetic Mice Is Associated with Upregulation of Fmr-1 Gene Expression in Hippocampus

PubMed Central

Rani, Anupama; Prasad, S.

2015-01-01

Fragile X mental retardation protein (FMRP) is a neuronal translational repressor and has been implicated in learning, memory, and cognition. However, the role of Bacopa monnieri extract (CDRI-08) in enhancing cognitive abilities in hypoxia-induced memory impairment via Fmr-1 gene expression is not known. Here, we have studied effects of CDRI-08 on the expression of Fmr-1 gene in the hippocampus of well validated cobalt chloride (CoCl2)-induced hypoxia mimetic mice and analyzed the data with alterations in spatial memory. Results obtained from Morris water maze test suggest that CoCl2 treatment causes severe loss of spatial memory and CDRI-08 is capable of reversing it towards that in the normal control mice. Our semiquantitative RT-PCR, Western blot, and immunofluorescence microscopic data reveal that CoCl2-induced hypoxia significantly upregulates the expression of Hif-1α and downregulates the Fmr-1 expression in the hippocampus, respectively. Further, CDRI-08 administration reverses the memory loss and this is correlated with significant downregulation of Hif-1α and upregulation of Fmr-1 expression. Our data are novel and may provide mechanisms of hypoxia-induced impairments in the spatial memory and action of CDRI-08 in the recovery of hypoxia led memory impairment involving Fmr-1 gene encoded protein called FMRP. PMID:26413121

Test-retest reliability and validity of the Sniffin' TOM odor memory test.

PubMed

Croy, Ilona; Zehner, Cora; Larsson, Maria; Zucco, Gesualdo M; Hummel, Thomas

2015-03-01

Few attempts have been made to develop an olfactory test that captures episodic retention of olfactory information. Assessment of episodic odor memory is of particular interest in aging and in the cognitively impaired as both episodic memory deficits and olfactory loss have been targeted as reliable hallmarks of cognitive decline and impending dementia. Here, 96 healthy participants (18-92 years) and an additional 19 older people with mild cognitive impairment were tested (73-82 years). Participants were presented with 8 common odors with intentional encoding instructions that were followed by a yes-no recognition test. After recognition completion, participants were asked to identify all odors by means of free or cued identification. A retest of the odor memory test (Sniffin' TOM = test of odor memory) took place 17 days later. The results revealed satisfactory test-retest reliability (0.70) of odor recognition memory. Both recognition and identification performance were negatively affected by age and more pronounced among the cognitively impaired. In conclusion, the present work presents a reliable, valid, and simple test of episodic odor recognition memory that may be used in clinical groups where both episodic memory deficits and olfactory loss are prevalent preclinically such as Alzheimer's disease. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Touching the void - First and third person perspectives in two cases of autobiographical amnesia linked to temporal lobe epilepsy.

PubMed

Zeman, Adam; Byruck, Marcus; Tallis, Peter; Vossel, Keith; Tranel, Daniel

2018-02-01

Temporal lobe epilepsy (TLE) can be associated with a marked impairment of autobiographical memory. This is occasionally its presenting feature. We describe two individuals with severe epilepsy-associated autobiographical memory loss. Both MB and PT were reassured initially that their memory was intact on the basis of standard neuropsychological tests. Both have written detailed accounts of their symptoms. The key neuropsychological features of their cases are the relative normality of performance on standard memory tests, with preservation of semantic memory for impersonal information, in contrast to a profound amnesia for salient autobiographical episodes and an impoverishment of imaginative scene construction. First person accounts from these individuals illustrate the importance of autobiographical memory in sustaining a coherent sense of self, informing interpersonal relationships and supporting future thinking and problem-solving. These cases contribute to the growing evidence for a distinctive pattern of autobiographical memory loss associated with TLE, and indicate that it can take a severe form affecting both personal semantics and episodic recollection. Defining the phase of memory processing most relevant to this form of amnesia, and the roles of physiological and structural pathology, requires further research. The paper's title refers to the introspective 'void' highlighted by both MB and PT in their reports - in PT's words: 'My primary symptom is the void that is my past'. Copyright © 2017. Published by Elsevier Ltd.

How does negative emotion cause false memories?

PubMed

Brainerd, C J; Stein, L M; Silveira, R A; Rohenkohl, G; Reyna, V F

2008-09-01

Remembering negative events can stimulate high levels of false memory, relative to remembering neutral events. In experiments in which the emotional valence of encoded materials was manipulated with their arousal levels controlled, valence produced a continuum of memory falsification. Falsification was highest for negative materials, intermediate for neutral materials, and lowest for positive materials. Conjoint-recognition analysis produced a simple process-level explanation: As one progresses from positive to neutral to negative valence, false memory increases because (a) the perceived meaning resemblance between false and true items increases and (b) subjects are less able to use verbatim memories of true items to suppress errors.

Effects of selective phosphodiesterases-4 inhibitors on learning and memory: a review of recent research.

PubMed

Peng, Sheng; Sun, Haiyan; Zhang, Xiaoqing; Liu, Gongjian; Wang, Guanglei

2014-09-01

Phosphodiesterase-4 (PDE-4) regulates the intracellular level of cyclic adenosine monophosphate. Recent studies demonstrated that PDE-4 inhibitors can counteract deficits in long-term memory caused by aging or increased expression of mutant forms of human amyloid precursor proteins, and can influence the process of memory function and cognitive enhancement. Therapeutics, such as ketamine, a drug used in clinical anesthesia, can also cause memory deficits as adverse effects. Targeting PDE-4 with selective inhibitors may offer a novel therapeutic strategy to prevent, slow the progress, and, eventually, treat memory deficits.

Psychophysiological correlates of cognitive deficits in family caregivers of patients with Alzheimer Disease.

PubMed

Corrêa, M S; Vedovelli, K; Giacobbo, B L; de Souza, C E B; Ferrari, P; de Lima Argimon, I I; Walz, J C; Kapczinski, F; Bromberg, E

2015-02-12

The progressive loss of memory and autonomy of Alzheimer's Disease (AD) patients, together with their characteristic behavioral and psychological symptoms, subjects their family caregivers to chronic stress. Several studies indicate that these caregivers are predisposed to cognitive impairments, but the physiological correlates of these alterations remain to be elucidated. Analyze the effects of chronic stress of family caregivers of AD patients on cognition, cortisol/DHEA ratios and BDNF levels and investigate the relation between these variables. Seventeen family caregivers (64.83 ± 3.64 years) of patients with AD and eighteen non-caregivers (58.29 ± 3.16 years) completed stress, depression and anxiety inventories. Exclusion criteria were current neurological disorders, major unstable medical illnesses, use of medications that could interfere with cognitive or HPA axis function and dementia. Attention, working memory and executive function were assessed with Digit Span and Trail Making tests, and declarative memory was analyzed with the Logical Memory test. Saliva was collected at 8 AM and 10 PM and its cortisol and DHEA levels determined by radioimmunoassay. Serum BDNF levels were measured by sandwich-ELISA. Results were analyzed with independent samples t test, covariance analysis and linear regressions. The statistical significance was set at p<0.05 and all p values were adjusted with Holm's Method. Caregivers showed more stress, depression and anxiety symptoms than non-caregivers, as well as significantly worse performances on attention, working memory and executive function tests. Caregivers also had higher cortisol/DHEA ratios and lower BDNF levels than non-caregivers. Cortisol/DHEA ratios, especially at 10 PM, were negatively related with all cognitive tasks in which caregivers showed impaired performance. On the other hand, the only cognitive task that related with the BDNF level was digit span. This study showed that caregivers' cognitive impairment is related with alterations on cortisol/DHEA ratios, and that chronic stress experienced by these subjects has the potential to alter their BDNF levels. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Neural correlates of working memory training in HIV patients: study protocol for a randomized controlled trial.

PubMed

Chang, L; Løhaugen, G C; Douet, V; Miller, E N; Skranes, J; Ernst, T

2016-02-02

Potent combined antiretroviral therapy decreased the incidence and severity of HIV-associated neurocognitive disorders (HAND); however, no specific effective pharmacotherapy exists for HAND. Patients with HIV commonly have deficits in working memory and attention, which may negatively impact many other cognitive domains, leading to HAND. Since HAND may lead to loss of independence in activities of daily living and negative emotional well-being, and incur a high economic burden, effective treatments for HAND are urgently needed. This study aims to determine whether adaptive working memory training might improve cognitive functions and neural network efficiency and possibly decrease neuroinflammation. This study also aims to assess whether subjects with the LMX1A-rs4657412 TT(AA) genotype show greater training effects from working memory training than TC(AG) or CC(GG)-carriers. 60 HIV-infected and 60 seronegative control participants will be randomized to a double-blind active-controlled study, using adaptive versus non-adaptive Cogmed Working Memory Training® (CWMT), 20-25 sessions over 5-8 weeks. Each subject will be assessed with near- and far-transfer cognitive tasks, self-reported mood and executive function questionnaires, and blood-oxygenation level-dependent functional MRI during working memory (n-back) and visual attention (ball tracking) tasks, at baseline, 1-month, and 6-months after CWMT. Furthermore, genotyping for LMX1A-rs4657412 will be performed to identify whether subjects with the TT(AA)-genotype show greater gain or neural efficiency after CWMT than those with other genotypes. Lastly, cerebrospinal fluid will be obtained before and after CWMT to explore changes in levels of inflammatory proteins (cytokines and chemokines) and monoamines. Improving working memory in HIV patients, using CWMT, might slow the progression or delay the onset of HAND. Observation of decreased brain activation or normalized neural networks, using fMRI, after CWMT would lead to a better understanding of how neural networks are modulated by CWMT. Moreover, validating the greater training gain in subjects with the LMX1A-TT(AA) genotype could lead to a personalized approach for future working memory training studies. Demonstrating and understanding the neural correlates of the efficacy of CWMT in HIV patients could lead to a safe adjunctive therapy for HAND, and possibly other brain disorders. ClinicalTrial.gov, NCT02602418.

Memory Club: A Group Intervention for People with Early-Stage Dementia and Their Care Partners

ERIC Educational Resources Information Center

Zarit, Steven H.; Femia, Elia E.; Watson, Jennifer; Rice-Oeschger, Laura; Kakos, Bernadette

2004-01-01

Purpose: Diagnosis of dementia in its early stages presents a window of opportunity for examining the immediate and long-term consequences of the illness at a point when the individual with memory loss can still participate in decision making. Design and Methods: Memory Club is a l0-session group program designed to provide information about…

KENNEDY SPACE CENTER, FLA. - Among the visitors placing flowers in the wire mesh fence surrounding the Space Memorial Mirror is one of the Indian dancers who performed a healing ceremony during a memorial service for the crew of Columbia. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. The public was invited to the memorial service, which included comments by Center Director Jim Kennedy and Executive Director of Florida Space Authority Winston Scott. Scott is a former astronaut who flew on Columbia in 1997.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - Among the visitors placing flowers in the wire mesh fence surrounding the Space Memorial Mirror is one of the Indian dancers who performed a healing ceremony during a memorial service for the crew of Columbia. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. The public was invited to the memorial service, which included comments by Center Director Jim Kennedy and Executive Director of Florida Space Authority Winston Scott. Scott is a former astronaut who flew on Columbia in 1997.

KENNEDY SPACE CENTER, FLA. - Standing in front of the Space Memorial Mirror at the KSC Visitor Complex, KSC Deputy Director Woodrow Whitlow Jr., Center Director Jim Kennedy and Executive Director of Florida Space Authority Winston Scott bow their heads in prayer during a memorial service remembering and honoring the crew of Columbia. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Scott is a former astronaut who flew on Columbia in 1997. The public was also invited to the memorial service.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - Standing in front of the Space Memorial Mirror at the KSC Visitor Complex, KSC Deputy Director Woodrow Whitlow Jr., Center Director Jim Kennedy and Executive Director of Florida Space Authority Winston Scott bow their heads in prayer during a memorial service remembering and honoring the crew of Columbia. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Scott is a former astronaut who flew on Columbia in 1997. The public was also invited to the memorial service.

AERIAL - MSC SITE - CONSTRUCTION PROGRESS - MSC

NASA Image and Video Library

1963-12-24

S63-23656 (1963) --- Aerial view of construction progress at the Manned Spacecraft Center, Houston, Texas. NOTE: The Manned Spacecraft Center was named Lyndon B. Johnson Space Center in memory of the late President following his death.

How to Constrain and Maintain a Lexicon for the Treatment of Progressive Semantic Naming Deficits: Principles of Item Selection for Formal Semantic Therapy

PubMed Central

Reilly, Jamie

2015-01-01

The progressive degradation of semantic memory is a common feature of many forms of dementia, including Alzheimer’s Disease and the semantic variant of Primary Progressive Aphasia (svPPA). One of the most functionally debilitating effects of this semantic impairment is the inability to name common people and objects (i.e., anomia). Clinical management of a progressive, semantically-based anomia presents extraordinary challenge for neurorehabilitation. Techniques such as errorless learning and spaced-retrieval training show promise for retraining forgotten words. However, we lack complementary detail about what to train (i.e., item selection) and how to flexibly adapt the training to a declining cognitive system. In this position paper, I weigh the relative merits of several treatment rationales (e.g., restore vs. compensate) and advocate for maintenance of known words over reacquisition of forgotten knowledge in the context of semantic treatment paradigms. I propose a system for generating an item pool and outline a set of core principles for training and sustaining a micro-lexicon consisting of approximately 100 words. These principles are informed by lessons learned over the course of a Phase I treatment study targeting language maintenance over a 5-year span in Alzheimer’s Disease and Frontotemporal Degeneration. Finally, I propose a semantic training approach that capitalizes on lexical frequency and repeated training on conceptual structure to offset the loss of key vocabulary as disease severity worsens. PMID:25609229

Headaches -- danger signs

MedlinePlus

... tumor . Brain swelling (brain edema) from altitude sickness, carbon monoxide poisoning, or acute brain injury. Buildup of ... problems moving your arms or legs, loss of balance, confusion, or memory loss with your headache. Your ...

Age

MedlinePlus

... and unaware of surroundings, and have problems with memory and paying attention. It may not start until a few days after surgery, may come and go, and usually disappears after about a ... can lead to long-term memory loss and make it difficult to learn, concentrate ...

Memory of myself: autobiographical memory and identity in Alzheimer's disease.

PubMed

Addis, Donna Rose; Tippett, Lynette J

2004-01-01

A number of theories posit a relationship between autobiographical memory and identity. To test this we assessed the status of autobiographical memory and identity in 20 individuals with Alzheimer's disease (AD) and 20 age-matched controls, and investigated whether degree of autobiographical memory impairment was associated with changes in identity. Two tests of autobiographical memory (Autobiographical Memory Interview, autobiographical fluency) and two measures of identity (Twenty Statements Test, identity items of the Tennessee Self Concept Scale) were administered. AD participants exhibited significant impairments on both memory tests, and changes in the strength, quality, and direction of identity relative to controls. Impairments of some components of autobiographical memory, particularly autobiographical memory for childhood and early adulthood, were related to changes in the strength and quality of identity. These findings support the critical role of early adulthood autobiographical memories (16-25 years) in identity, and suggest autobiographical memory loss affects identity.

The evolving roles of memory immune cells in transplantation

PubMed Central

Chen, Wenhao; Ghobrial, Rafik M.; Li, Xian C.

2015-01-01

Memory cells are the products of immune responses but also exert significant impact on subsequent immunity and immune tolerance, thus placing them in a unique position in transplant research. Memory cells are heterogeneous, including not only memory T cells but also memory B cells and innate memory cells. Memory cells are a critical component of protective immunity against invading pathogens, especially in immunosuppressed patients, but they also mediate graft loss and tolerance resistance. Recent studies suggest that some memory cells unexpectedly act as regulatory cells, promoting rather than hindering transplant survival. This functional diversity makes therapeutic targeting of memory cells a challenging task in transplantation. In this article we highlight recent advances in our understanding of memory cells, focusing on diversity of memory cells and mechanisms involved in their induction and functions. We also provide a broad overview on the challenges and opportunities in targeting memory cells in the induction of transplant tolerance. PMID:26102615

Brain reserve and cognitive reserve protect against cognitive decline over 4.5 years in MS

PubMed Central

Rocca, Maria A.; Leavitt, Victoria M.; Dackovic, Jelena; Mesaros, Sarlota; Drulovic, Jelena; DeLuca, John; Filippi, Massimo

2014-01-01

Objective: Based on the theories of brain reserve and cognitive reserve, we investigated whether larger maximal lifetime brain growth (MLBG) and/or greater lifetime intellectual enrichment protect against cognitive decline over time. Methods: Forty patients with multiple sclerosis (MS) underwent baseline and 4.5-year follow-up evaluations of cognitive efficiency (Symbol Digit Modalities Test, Paced Auditory Serial Addition Task) and memory (Selective Reminding Test, Spatial Recall Test). Baseline and follow-up MRIs quantified disease progression: percentage brain volume change (cerebral atrophy), percentage change in T2 lesion volume. MLBG (brain reserve) was estimated with intracranial volume; intellectual enrichment (cognitive reserve) was estimated with vocabulary. We performed repeated-measures analyses of covariance to investigate whether larger MLBG and/or greater intellectual enrichment moderate/attenuate cognitive decline over time, controlling for disease progression. Results: Patients with MS declined in cognitive efficiency and memory (p < 0.001). MLBG moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.122), with larger MLBG protecting against decline. MLBG did not moderate memory decline (p = 0.234, ηp2 = 0.039). Intellectual enrichment moderated decline in cognitive efficiency (p = 0.031, ηp2 = 0.126) and memory (p = 0.037, ηp2 = 0.115), with greater intellectual enrichment protecting against decline. MS disease progression was more negatively associated with change in cognitive efficiency and memory among patients with lower vs higher MLBG and intellectual enrichment. Conclusion: We provide longitudinal support for theories of brain reserve and cognitive reserve in MS. Larger MLBG protects against decline in cognitive efficiency, and greater intellectual enrichment protects against decline in cognitive efficiency and memory. Consideration of these protective factors should improve prediction of future cognitive decline in patients with MS. PMID:24748670

Impaired event memory and recollection in a case of developmental amnesia.

PubMed

Rosenbaum, R S; Carson, N; Abraham, N; Bowles, B; Kwan, D; Köhler, S; Svoboda, E; Levine, B; Richards, B

2011-10-01

A current debate in the literature is whether all declarative memories and associated memory processes rely on the same neural substrate. Here, we show that H.C., a developmental amnesic person with selective bilateral hippocampal volume loss, has a mild deficit in personal episodic memory, and a more pronounced deficit in public event memory; semantic memory for personal and general knowledge was unimpaired. This was accompanied by a subtle difference in impairment between recollection and familiarity on lab-based tests of recognition memory. Strikingly, H.C.'s recognition did not benefit from a levels-of-processing manipulation. Thus, not all types of declarative memory and related processes can exist independently of the hippocampus even if it is damaged early in life.

Phospho-eIF2α level is important for determining abilities of BACE1 reduction to rescue cholinergic neurodegeneration and memory defects in 5XFAD mice.

PubMed

Devi, Latha; Ohno, Masuo

2010-09-23

β-Site APP-cleaving enzyme 1 (BACE1) initiates amyloid-β (Aβ) generation and thus represents a prime therapeutic target in treating Alzheimer's disease (AD). Notably, increasing evidence indicates that BACE1 levels become elevated in AD brains as disease progresses; however, it remains unclear how the BACE1 upregulation may affect efficacies of therapeutic interventions including BACE1-inhibiting approaches. Here, we crossed heterozygous BACE1 knockout mice with AD transgenic mice (5XFAD model) and compared the abilities of partial BACE1 reduction to rescue AD-like phenotypes at earlier (6-month-old) and advanced (15-18-month-old) stages of disease, which expressed normal (∼100%) and elevated (∼200%) levels of BACE1, respectively. BACE1(+/-) deletion rescued memory deficits as tested by the spontaneous alternation Y-maze task in 5XFAD mice at the earlier stage and prevented their septohippocampal cholinergic deficits associated with significant neuronal loss. Importantly, BACE1(+/-) deletion was no longer able to rescue memory deficits or cholinergic neurodegeneration in 5XFAD mice at the advanced stage. Moreover, BACE1(+/-) deletion significantly reduced levels of Aβ42 and the β-secretase-cleaved C-terminal fragment (C99) in 6-month-old 5XFAD mouse brains, while these neurotoxic β-cleavage products dramatically elevated with age and were not affected by BACE1(+/-) deletion in 15-18-month-old 5XFAD brains. Interestingly, although BACE1(+/-) deletion lowered BACE1 expression by ∼50% in 5XFAD mice irrespective of age in concordance with the reduction in gene copy number, BACE1 equivalent to wild-type controls remained in BACE1(+/-)·5XFAD mice at the advanced age. In accord, phosphorylation of the translation initiation factor eIF2α, an important mediator of BACE1 elevation, was dramatically increased (∼9-fold) in 15-18-month-old 5XFAD mice and remained highly upregulated (∼6-fold) in age-matched BACE1(+/-)·5XFAD mice. Together, our results indicate that partial reduction of BACE1 is not sufficient to block the phospho-eIF2α-dependent BACE1 elevation during the progression of AD, thus limiting its abilities to reduce cerebral Aβ/C99 levels and rescue memory deficits and cholinergic neurodegeneration.

The neurobiological bases of memory formation: from physiological conditions to psychopathology.

PubMed

Bisaz, Reto; Travaglia, Alessio; Alberini, Cristina M

2014-01-01

The formation of long-term memories is a function necessary for an adaptive survival. In the last two decades, great progress has been made in the understanding of the biological bases of memory formation. The identification of mechanisms necessary for memory consolidation and reconsolidation, the processes by which the posttraining and postretrieval fragile memory traces become stronger and insensitive to disruption, has indicated new approaches for investigating and treating psychopathologies. In this review, we will discuss some key biological mechanisms found to be critical for memory consolidation and strengthening, the role/s and mechanisms of memory reconsolidation, and how the interference with consolidation and/or reconsolidation can modulate the retention and/or storage of memories that are linked to psychopathologies. © 2014 S. Karger AG, Basel.

Individual differences in false memory from misinformation: cognitive factors.

PubMed

Zhu, Bi; Chen, Chuansheng; Loftus, Elizabeth F; Lin, Chongde; He, Qinghua; Chen, Chunhui; Li, He; Xue, Gui; Lu, Zhonglin; Dong, Qi

2010-07-01

This research investigated the cognitive correlates of false memories that are induced by the misinformation paradigm. A large sample of Chinese college students (N=436) participated in a misinformation procedure and also took a battery of cognitive tests. Results revealed sizable and systematic individual differences in false memory arising from exposure to misinformation. False memories were significantly and negatively correlated with measures of intelligence (measured with Raven's Advanced Progressive Matrices and Wechsler Adult Intelligence Scale), perception (Motor-Free Visual Perception Test, Change Blindness, and Tone Discrimination), memory (Wechsler Memory Scales and 2-back Working Memory tasks), and face judgement (Face Recognition and Facial Expression Recognition). These findings suggest that people with relatively low intelligence and poor perceptual abilities might be more susceptible to the misinformation effect.

Aversive and non-aversive memory impairment in the mucopolysaccharidosis II mouse model.

PubMed

Azambuja, Amanda Stapenhorst; Correa, Lilian; Gabiatti, Bernardo Pappi; Martins, Giselle Renata; de Oliveira Franco, Álvaro; Ribeiro, Maria Flávia Marques; Baldo, Guilherme

2018-02-01

Hunter syndrome (MPS II, OMIM 309900) is a lysosomal storage disorder due to deficient iduronate sulphatase activity. Patients present multiple cognitive alterations, and the aim of this work was to verify if MPS II mice also present some progressive cognitive alterations. For that, MPS II mice from 2 to 6 months of age were submitted to repeated open field and inhibitory avoidance tests to evaluate memory parameters. MPS II mice presented impaired memory at 6 months evaluated by open field test. They also performed poorly in the inhibitory avoidance test from 4 months. We conclude that MPS II mice develop cognitive alterations as the disease progresses. These tests can be used in the future to study the efficacy of therapeutic approaches in the central nervous system.

Type 2 diabetes mellitus in the pathophysiology of Alzheimer's disease.

PubMed

de Nazareth, Aparecida Marcelino

2017-01-01

Both Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are two common forms of disease worldwide and many studies indicate that people with diabetes, especially DM, are at higher risk of developing AD. AD is characterized by progressive cognitive decline and accumulation of β-amyloid (Aβ) forming senile plaques. DM is a metabolic disorder characterized by hyperglycemia in the context of insulin resistance and relative lack of insulin. Both diseases also share common characteristics such as loss of cognitive function and inflammation. Inflammation resulting from Aβ further induces production of Aβ 1-42 peptides. Inflammation due to overnutrition induces insulin resistance and consequently DM. Memory deficit and a decrease in GLUT4 and hippocampal insulin signaling have been observed in animal models of insulin resistance. The objective of this review was to show the shared characteristics of AD and DM.

Metals and cholesterol: two sides of the same coin in Alzheimer’s disease pathology

PubMed Central

Wong, Bruce X.; Hung, Ya Hui; Bush, Ashley I.; Duce, James A.

2014-01-01

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease. It begins years prior to the onset of clinical symptoms, such as memory loss and cognitive decline. Pathological hallmarks of AD include the accumulation of β-amyloid in plaques and hyperphosphorylated tau in neurofibrillary tangles. Copper, iron, and zinc are abnormally accumulated and distributed in the aging brain. These metal ions can adversely contribute to the progression of AD. Dysregulation of cholesterol metabolism has also been implicated in the development of AD pathology. To date, large bodies of research have been carried out independently to elucidate the role of metals or cholesterol on AD pathology. Interestingly, metals and cholesterol affect parallel molecular and biochemical pathways involved in AD pathology. The possible links between metal dyshomeostasis and altered brain cholesterol metabolism in AD are reviewed. PMID:24860500

Robustness of Many-Body Localization in the Presence of Dissipation

NASA Astrophysics Data System (ADS)

Levi, Emanuele; Heyl, Markus; Lesanovsky, Igor; Garrahan, Juan P.

2016-06-01

Many-body localization (MBL) has emerged as a novel paradigm for robust ergodicity breaking in closed quantum many-body systems. However, it is not yet clear to which extent MBL survives in the presence of dissipative processes induced by the coupling to an environment. Here we study heating and ergodicity for a paradigmatic MBL system—an interacting fermionic chain subject to quenched disorder—in the presence of dephasing. We find that, even though the system is eventually driven into an infinite-temperature state, heating as monitored by the von Neumann entropy can progress logarithmically slowly, implying exponentially large time scales for relaxation. This slow loss of memory of initial conditions makes signatures of nonergodicity visible over a long, but transient, time regime. We point out a potential controlled realization of the considered setup with cold atomic gases held in optical lattices.

Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

PubMed

Wu, Ji-Hong; Zhang, Sheng-Hai; Nickerson, John M; Gao, Feng-Juan; Sun, Zhongmou; Chen, Xin-Ya; Zhang, Shu-Jie; Gao, Feng; Chen, Jun-Yi; Luo, Yi; Wang, Yan; Sun, Xing-Huai

2015-02-01

Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Neural evidence for a distinction between short-term memory and the focus of attention.

PubMed

Lewis-Peacock, Jarrod A; Drysdale, Andrew T; Oberauer, Klaus; Postle, Bradley R

2012-01-01

It is widely assumed that the short-term retention of information is accomplished via maintenance of an active neural trace. However, we demonstrate that memory can be preserved across a brief delay despite the apparent loss of sustained representations. Delay period activity may, in fact, reflect the focus of attention, rather than STM. We unconfounded attention and memory by causing external and internal shifts of attention away from items that were being actively retained. Multivariate pattern analysis of fMRI indicated that only items within the focus of attention elicited an active neural trace. Activity corresponding to representations of items outside the focus quickly dropped to baseline. Nevertheless, this information was remembered after a brief delay. Our data also show that refocusing attention toward a previously unattended memory item can reactivate its neural signature. The loss of sustained activity has long been thought to indicate a disruption of STM, but our results suggest that, even for small memory loads not exceeding the capacity limits of STM, the active maintenance of a stimulus representation may not be necessary for its short-term retention.

Still searching for the engram.

PubMed

Eichenbaum, Howard

2016-09-01

For nearly a century, neurobiologists have searched for the engram-the neural representation of a memory. Early studies showed that the engram is widely distributed both within and across brain areas and is supported by interactions among large networks of neurons. Subsequent research has identified engrams that support memory within dedicated functional systems for habit learning and emotional memory, but the engram for declarative memories has been elusive. Nevertheless, recent years have brought progress from molecular biological approaches that identify neurons and networks that are necessary and sufficient to support memory, and from recording approaches and population analyses that characterize the information coded by large neural networks. These new directions offer the promise of revealing the engrams for episodic and semantic memories.

The case for earlier cochlear implantation in postlingually deaf adults.

PubMed

Dowell, Richard C

2016-01-01

This paper aimed to estimate the difference in speech perception outcomes that may occur due to timing of cochlear implantation in relation to the progression of hearing loss. Data from a large population-based sample of adults with acquired hearing loss using cochlear implants (CIs) was used to estimate the effects of duration of hearing loss, age, and pre-implant auditory skills on outcomes for a hypothetical standard patient. A total of 310 adults with acquired severe/profound bilateral hearing loss who received a CI in Melbourne, Australia between 1994 and 2006 provided the speech perception data and demographic information to derive regression equations for estimating CI outcomes. For a hypothetical CI candidate with progressive sensorineural hearing loss, the estimates of speech perception scores following cochlear implantation are significantly better if implantation occurs relatively soon after onset of severe hearing loss and before the loss of all functional auditory skills. Improved CI outcomes and quality of life benefit may be achieved for adults with progressive severe hearing loss if they are implanted earlier in the progression of the pathology.

[Progress on metaplasticity and its role in learning and memory].

PubMed

Wang, Shao-Li; Lu, Wei

2016-08-25

Long-term potentiation (LTP) and long-term depression (LTD) are two major forms of synaptic plasticity that are widely considered as important cellular models of learning and memory. Metaplasticity is defined as the plasticity of synaptic plasticity and thus is an advanced form of plasticity. The history of synaptic activity can affect the subsequent synaptic plasticity induction. Therefore, it is important to study metaplasticity to explore new mechanisms underlying various brain functions including learning and memory. Since the concept of metaplasticity was proposed, it has aroused widespread concerns and attracted numerous researchers to dig more details on this topic. These new-found experimental phenomena and cellular mechanisms have established the basis of theoretical studies on metaplasticity. In recent years, researchers have found that metaplasticity can not only affect the synaptic plasticity, but also regulate the neural network to encode specific content and enhance the learning and memory. These findings have greatly enriched our knowledge on plasticity and opened a new route to study the mechanism of learning and memory. In this review, we discuss the recent progress on metaplasticity on following three aspects: (1) the molecular mechanisms of metaplasticity; (2) the role of metaplasticity in learning and memory; and (3) the outlook of future study on metaplasticity.

Periodontal profile classes predict periodontal disease progression and tooth loss.

PubMed

Morelli, Thiago; Moss, Kevin L; Preisser, John S; Beck, James D; Divaris, Kimon; Wu, Di; Offenbacher, Steven

2018-02-01

Current periodontal disease taxonomies have limited utility for predicting disease progression and tooth loss; in fact, tooth loss itself can undermine precise person-level periodontal disease classifications. To overcome this limitation, the current group recently introduced a novel patient stratification system using latent class analyses of clinical parameters, including patterns of missing teeth. This investigation sought to determine the clinical utility of the Periodontal Profile Classes and Tooth Profile Classes (PPC/TPC) taxonomy for risk assessment, specifically for predicting periodontal disease progression and incident tooth loss. The analytic sample comprised 4,682 adult participants of two prospective cohort studies (Dental Atherosclerosis Risk in Communities Study and Piedmont Dental Study) with information on periodontal disease progression and incident tooth loss. The PPC/TPC taxonomy includes seven distinct PPCs (person-level disease pattern and severity) and seven TPCs (tooth-level disease). Logistic regression modeling was used to estimate relative risks (RR) and 95% confidence intervals (CI) for the association of these latent classes with disease progression and incident tooth loss, adjusting for examination center, race, sex, age, diabetes, and smoking. To obtain personalized outcome propensities, risk estimates associated with each participant's PPC and TPC were combined into person-level composite risk scores (Index of Periodontal Risk [IPR]). Individuals in two PPCs (PPC-G: Severe Disease and PPC-D: Tooth Loss) had the highest tooth loss risk (RR = 3.6; 95% CI = 2.6 to 5.0 and RR = 3.8; 95% CI = 2.9 to 5.1, respectively). PPC-G also had the highest risk for periodontitis progression (RR = 5.7; 95% CI = 2.2 to 14.7). Personalized IPR scores were positively associated with both periodontitis progression and tooth loss. These findings, upon additional validation, suggest that the periodontal/tooth profile classes and the derived personalized propensity scores provide clinical periodontal definitions that reflect disease patterns in the population and offer a useful system for patient stratification that is predictive for disease progression and tooth loss. © 2018 American Academy of Periodontology.

Analysis of counting errors in the phase/Doppler particle analyzer

NASA Technical Reports Server (NTRS)

Oldenburg, John R.

1987-01-01

NASA is investigating the application of the Phase Doppler measurement technique to provide improved drop sizing and liquid water content measurements in icing research. The magnitude of counting errors were analyzed because these errors contribute to inaccurate liquid water content measurements. The Phase Doppler Particle Analyzer counting errors due to data transfer losses and coincidence losses were analyzed for data input rates from 10 samples/sec to 70,000 samples/sec. Coincidence losses were calculated by determining the Poisson probability of having more than one event occurring during the droplet signal time. The magnitude of the coincidence loss can be determined, and for less than a 15 percent loss, corrections can be made. The data transfer losses were estimated for representative data transfer rates. With direct memory access enabled, data transfer losses are less than 5 percent for input rates below 2000 samples/sec. With direct memory access disabled losses exceeded 20 percent at a rate of 50 samples/sec preventing accurate number density or mass flux measurements. The data transfer losses of a new signal processor were analyzed and found to be less than 1 percent for rates under 65,000 samples/sec.

Influences of Working Memory and Audibility on Word Learning in Children with Hearing Loss

ERIC Educational Resources Information Center

Stiles, Derek Jason

2010-01-01

As a group, children with hearing loss demonstrate delays in language development relative to their peers with normal hearing. Early intervention has a profound impact on language outcomes in children with hearing loss. Data examining the relationship between degree of hearing loss and language outcomes are variable. Two approaches are used in the…

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes

PubMed Central

Petit, Emilie I; Michalak, Zuzanna; Cox, Rachel; O'Tuathaigh, Colm M P; Clarke, Niamh; Tighe, Orna; Talbot, Konrad; Blake, Derek; Joel, Josephine; Shaw, Alexander; Sheardown, Steven A; Morrison, Alastair D; Wilson, Stephen; Shapland, Ellen M; Henshall, David C; Kew, James N; Kirby, Brian P; Waddington, John L

2017-01-01

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A−/−, with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A−/− showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A−/− provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects. PMID:27986973

Review on the APP/PS1KI mouse model: intraneuronal Abeta accumulation triggers axonopathy, neuron loss and working memory impairment.

PubMed

Bayer, T A; Wirths, O

2008-02-01

Accumulating evidence points to an important role of intraneuronal Abeta as a trigger of the pathological cascade of events leading to neurodegeneration and eventually to Alzheimer's disease (AD) with its typical clinical symptoms, like memory impairment and change in personality. As a new concept, intraneuronal accumulation of Abeta instead of extracellular Abeta deposition has been introduced to be the disease-triggering event in AD. The present review compiles current knowledge on the amyloid precursor protein (APP)/PS1KI mouse model with early and massive intraneuronal Abeta42 accumulation: (1) The APP/PS1KI mouse model exhibits early robust brain and spinal cord axonal degeneration and hippocampal CA1 neuron loss. (2) At the same time-point, a dramatic, age-dependent reduced ability to perform working memory and motor tasks is observed. (3) The APP/PS1KI mice are smaller and show development of a thoracolumbar kyphosis, together with an incremental loss of body weight. (4) Onset of the observed behavioral alterations correlates well with robust axonal degeneration in brain and spinal cord and with abundant hippocampal CA1 neuron loss.

Dysregulation of Specialized Delay/Interference-Dependent Working Memory Following Loss of Dysbindin-1A in Schizophrenia-Related Phenotypes.

PubMed

Petit, Emilie I; Michalak, Zuzanna; Cox, Rachel; O'Tuathaigh, Colm M P; Clarke, Niamh; Tighe, Orna; Talbot, Konrad; Blake, Derek; Joel, Josephine; Shaw, Alexander; Sheardown, Steven A; Morrison, Alastair D; Wilson, Stephen; Shapland, Ellen M; Henshall, David C; Kew, James N; Kirby, Brian P; Waddington, John L

2017-05-01

Dysbindin-1, a protein that regulates aspects of early and late brain development, has been implicated in the pathobiology of schizophrenia. As the functional roles of the three major isoforms of dysbindin-1, (A, B, and C) remain unknown, we generated a novel mutant mouse, dys-1A -/- , with selective loss of dysbindin-1A and investigated schizophrenia-related phenotypes in both males and females. Loss of dysbindin-1A resulted in heightened initial exploration and disruption in subsequent habituation to a novel environment, together with heightened anxiety-related behavior in a stressful environment. Loss of dysbindin-1A was not associated with disruption of either long-term (olfactory) memory or spontaneous alternation behavior. However, dys-1A -/- showed enhancement in delay-dependent working memory under high levels of interference relative to controls, ie, impairment in sensitivity to the disruptive effect of such interference. These findings in dys-1A -/- provide the first evidence for differential functional roles for dysbindin-1A vs dysbindin-1C isoforms among phenotypes relevant to the pathobiology of schizophrenia. Future studies should investigate putative sex differences in these phenotypic effects.

Novelty exposure overcomes foot shock-induced spatial-memory impairment by processes of synaptic-tagging in rats.

PubMed

Almaguer-Melian, William; Bergado-Rosado, Jorge; Pavón-Fuentes, Nancy; Alberti-Amador, Esteban; Mercerón-Martínez, Daymara; Frey, Julietta U

2012-01-17

Novelty processing can transform short-term into long-term memory. We propose that this memory-reinforcing effect of novelty could be explained by mechanisms outlined in the "synaptic tagging hypothesis." Initial short-term memory is sustained by a transient plasticity change at activated synapses and sets synaptic tags. These tags are later able to capture and process the plasticity-related proteins (PRPs), which are required to transform a short-term synaptic change into a long-term one. Novelty is involved in inducing the synthesis of PRPs [Moncada D, et al. (2011) Proc Natl Acad Sci USA 108:12937-12936], which are then captured by the tagged synapses, consolidating memory. In contrast to novelty, stress can impair learning, memory, and synaptic plasticity. Here, we address questions as to whether novelty-induced PRPs are able to prevent the loss of memory caused by stress and if the latter would not interact with the tag-setting process. We used water-maze (WM) training as a spatial learning paradigm to test our hypothesis. Stress was induced by a strong foot shock (FS; 5 × 1 mA, 2 s) applied 5 min after WM training. Our data show that FS reduced long-term but not short-term memory in the WM paradigm. This negative effect on memory consolidation was time- and training-dependent. Interestingly, novelty exposure prevented the stress-induced memory loss of the spatial task and increased BDNF and Arc expression. This rescuing effect was blocked by anisomycin, suggesting that WM-tagged synapses were not reset by FS and were thus able to capture the novelty-induced PRPs, re-establishing FS-impaired long-term memory.

Iconic Memories Die a Sudden Death.

PubMed

Pratte, Michael S

2018-06-01

Iconic memory is characterized by its large storage capacity and brief storage duration, whereas visual working memory is characterized by its small storage capacity. The limited information stored in working memory is often modeled as an all-or-none process in which studied information is either successfully stored or lost completely. This view raises a simple question: If almost all viewed information is stored in iconic memory, yet one second later most of it is completely absent from working memory, what happened to it? Here, I characterized how the precision and capacity of iconic memory changed over time and observed a clear dissociation: Iconic memory suffered from a complete loss of visual items, while the precision of items retained in memory was only marginally affected by the passage of time. These results provide new evidence for the discrete-capacity view of working memory and a new characterization of iconic memory decay.

Multiple determinants of lifespan memory differences.

PubMed

Henson, Richard N; Campbell, Karen L; Davis, Simon W; Taylor, Jason R; Emery, Tina; Erzinclioglu, Sharon; Kievit, Rogier A

2016-09-07

Memory problems are among the most common complaints as people grow older. Using structural equation modeling of commensurate scores of anterograde memory from a large (N = 315), population-derived sample (www.cam-can.org), we provide evidence for three memory factors that are supported by distinct brain regions and show differential sensitivity to age. Associative memory and item memory are dramatically affected by age, even after adjusting for education level and fluid intelligence, whereas visual priming is not. Associative memory and item memory are differentially affected by emotional valence, and the age-related decline in associative memory is faster for negative than for positive or neutral stimuli. Gray-matter volume in the hippocampus, parahippocampus and fusiform cortex, and a white-matter index for the fornix, uncinate fasciculus and inferior longitudinal fasciculus, show differential contributions to the three memory factors. Together, these data demonstrate the extent to which differential ageing of the brain leads to differential patterns of memory loss.

The impact of cultural exposure and message framing on oral health behavior: Exploring the role of message memory

PubMed Central

Brick, Cameron; McCully, Scout N.; Updegraff, John A.; Ehret, Phillip J.; Areguin, Maira A.; Sherman, David K.

2015-01-01

Background Health messages are more effective when framed to be congruent with recipient characteristics, and health practitioners can strategically decide on message features to promote adherence to recommended behaviors. We present exposure to United States (U.S.) culture as a moderator of the impact of gain- vs. loss-frame messages. Since U.S. culture emphasizes individualism and approach orientation, greater cultural exposure was expected to predict improved patient choices and memory for gain-framed messages, whereas individuals with less exposure to U.S. culture would show these advantages for loss-framed messages. Methods 223 participants viewed a written oral health message in one of three randomized conditions: gain-frame, loss-frame, or no-message control, and were given ten flosses. Cultural exposure was measured with the proportions of life spent and parents born in the U.S. At baseline and one week later, participants completed recall tests and reported recent flossing behavior. Results Message frame and cultural exposure interacted to predict improved patient decisions (increased flossing) and memory maintenance for the health message over one week. E.g., those with low cultural exposure who saw a loss-frame message flossed more. Incongruent messages led to the same flossing rates as no message. Memory retention did not explain the effect of message congruency on flossing. Limitations Flossing behavior was self-reported. Cultural exposure may only have practical application in either highly individualistic or collectivistic countries. Conclusions In healthcare settings where patients are urged to follow a behavior, asking basic demographic questions could allow medical practitioners to intentionally communicate in terms of gains or losses to improve patient decision making and treatment adherence. PMID:25654986

Impact of Cultural Exposure and Message Framing on Oral Health Behavior: Exploring the Role of Message Memory.

PubMed

Brick, Cameron; McCully, Scout N; Updegraff, John A; Ehret, Phillip J; Areguin, Maira A; Sherman, David K

2016-10-01

Health messages are more effective when framed to be congruent with recipient characteristics, and health practitioners can strategically choose message features to promote adherence to recommended behaviors. We present exposure to US culture as a moderator of the impact of gain-frame versus loss-frame messages. Since US culture emphasizes individualism and approach orientation, greater cultural exposure was expected to predict improved patient choices and memory for gain-framed messages, whereas individuals with less exposure to US culture would show these advantages for loss-framed messages. 223 participants viewed a written oral health message in 1 of 3 randomized conditions-gain-frame, loss-frame, or no-message control-and were given 10 flosses. Cultural exposure was measured with the proportions of life spent and parents born in the US. At baseline and 1 week later, participants completed recall tests and reported recent flossing behavior. Message frame and cultural exposure interacted to predict improved patient decisions (increased flossing) and memory maintenance for the health message over 1 week; for example, those with low cultural exposure who saw a loss-frame message flossed more. Incongruent messages led to the same flossing rates as no message. Memory retention did not explain the effect of message congruency on flossing. Flossing behavior was self-reported. Cultural exposure may only have practical application in either highly individualistic or collectivistic countries. In health care settings where patients are urged to follow a behavior, asking basic demographic questions could allow medical practitioners to intentionally communicate in terms of gains or losses to improve patient decision making and treatment adherence. © The Author(s) 2015.

Histopathologic subtype of hippocampal sclerosis and episodic memory performance before and after temporal lobectomy for epilepsy.

PubMed

Saghafi, Shahram; Ferguson, Lisa; Hogue, Olivia; Gales, Jordan M; Prayson, Richard; Busch, Robyn M

2018-04-01

The International League Against Epilepsy (ILAE) proposed a classification system for hippocampal sclerosis (HS) based on location and extent of hippocampal neuron loss. The literature debates the usefulness of this classification system when studying memory in people with temporal lobe epilepsy (TLE) and determining memory outcome after temporal lobe resection (TLR). This study further explores the relationship between HS ILAE subtypes and episodic memory performance in patients with TLE and examines memory outcomes after TLR. This retrospective study identified 213 patients with TLE who underwent TLR and had histopathological evidence of HS (HS ILAE type 1a = 92; type 1b = 103; type 2 = 18). Patients completed the Wechsler Memory Scale-3rd Edition prior to surgery, and 78% of patients had postoperative scores available. Linear regressions examined differences in preoperative memory scores as a function of pathology classification, controlling for potential confounders. Fisher's exact tests were used to compare pathology subtypes on the magnitude of preoperative memory impairment and the proportion of patients who experienced clinically meaningful postoperative memory decline. Individuals with HS ILAE type 2 demonstrated better preoperative verbal memory performance than patients with HS ILAE type 1; however, individual data revealed verbal and visual episodic memory impairments in many patients with HS ILAE type 2. The base rate of postoperative memory decline was similar among all 3 pathology groups. This is the largest reported overall sample and the largest subset of patients with HS ILAE type 2. Group data suggest that patients with HS ILAE type 2 perform better on preoperative memory measures, but individually there were no differences in the magnitude of memory impairment. Following surgery, there were no statistically significant differences between groups in the proportion of patients who declined. Future research should focus on quantitative measurements of hippocampal neuronal loss, and multicenter collaboration is encouraged. Wiley Periodicals, Inc. © 2018 International League Against Epilepsy.

Progressive Hearing Impairment in Children with Congenital Cytomegalovirus Infection.

ERIC Educational Resources Information Center

Dahle, Arthur J.; And Others

1979-01-01

Audiological assessment of 86 children (mean age 38 months at last evaluation time) with congenital cytomegalovirus infection revealed progressive hearing loss in four of 12 Ss with sensorineural hearing impairments. Case descriptions documented the progression of the hearing loss. (Author)

Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease.

PubMed

Donovan, Nancy J; Amariglio, Rebecca E; Zoller, Amy S; Rudel, Rebecca K; Gomez-Isla, Teresa; Blacker, Deborah; Hyman, Bradley T; Locascio, Joseph J; Johnson, Keith A; Sperling, Reisa A; Marshall, Gad A; Rentz, Dorene M

2014-12-01

To examine neuropsychiatric and neuropsychological predictors of progression from normal to early clinical stages of Alzheimer disease (AD). From a total sample of 559 older adults from the Massachusetts Alzheimer's Disease Research Center longitudinal cohort, 454 were included in the primary analysis: 283 with clinically normal cognition (CN), 115 with mild cognitive impairment (MCI), and 56 with subjective cognitive concerns (SCC) but no objective impairment, a proposed transitional group between CN and MCI. Two latent cognitive factors (memory-semantic, attention-executive) and two neuropsychiatric factors (affective, psychotic) were derived from the Alzheimer's Disease Centers' Uniform Data Set neuropsychological battery and Neuropsychiatric Inventory brief questionnaire. Factors were analyzed as predictors of time to progression to a worse diagnosis using a Cox proportional hazards regression model with backward elimination. Covariates included baseline diagnosis, gender, age, education, prior depression, antidepressant medication, symptom duration, and interaction terms. Higher/better memory-semantic factor score predicted lower hazard of progression (hazard ratio [HR] = 0.4 for 1 standard deviation [SD] increase, p <0.0001), and higher/worse affective factor score predicted higher hazard (HR = 1.3 for one SD increase, p = 0.01). No other predictors were significant in adjusted analyses. Using diagnosis as a sole predictor of transition to MCI, the SCC diagnosis carried a fourfold risk of progression compared with CN (HR = 4.1, p <0.0001). These results identify affective and memory-semantic factors as significant predictors of more rapid progression from normal to early stages of cognitive decline and highlight the subgroup of cognitively normal elderly with SCC as those with elevated risk of progression to MCI. Copyright © 2014 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

CORRELATION OF CLINICAL AND STRUCTURAL PROGRESSION WITH VISUAL ACUITY LOSS IN MACULAR TELANGIECTASIA TYPE 2: MacTel Project Report No. 6-The MacTel Research Group.

PubMed

Peto, Tunde; Heeren, Tjebo F C; Clemons, Traci E; Sallo, Ferenc B; Leung, Irene; Chew, Emily Y; Bird, Alan C

2018-01-01

To evaluate progression of macular telangiectasia Type 2 lesions and their correlation with visual acuity. An international multicenter prospective study with annual examinations including best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, and optical coherence tomography images graded centrally. Mixed models were used to estimate progression rates, and a generalized linear model to compute the relative risk of BCVA loss, loss of ellipsoid zone (EZ) reflectivity, development of pigment plaques, or neovascularization. One thousand and fourteen eyes of 507 participants were followed for 4.2 ± 1.6 years. Best-corrected visual acuity decreased 1.07 ± 0.05 letters (mean ± SE) per year. Of all eyes, 15% lost ≥15 letters after 5 years. Of the eyes without EZ loss, 76% developed a noncentral loss. Of the eyes with noncentral loss, 45% progressed to central EZ loss. The rate of BCVA loss in eyes with noncentral EZ loss at baseline was similar to eyes without EZ loss. The rate of BCVA loss was significantly higher in eyes with central EZ loss at baseline (-1.40 ± 0.14 letters, P < 0.001). Ellipsoid zone loss is frequently found in macular telangiectasia Type 2 and is an important structural component reflecting visual function. Its presence in the fovea significantly correlates with worse visual prognosis.

KSC-03pd0569

NASA Image and Video Library

2003-03-06

KENNEDY SPACE CENTER, FLA. - A view of the Astronaut Memorial Space Mirror at the KSC Visitor Complex. The memorial is a national tribute to 17 American astronauts who previously gave their lives to the quest to explore space. The memorial has had added attention since the loss of the Columbia crew Feb. 1, 2003, when they died in an explosion as they were returning to Earth from mission STS-107.

KSC-03pd0570

NASA Image and Video Library

2003-03-06

KENNEDY SPACE CENTER, FLA. - A view of the Astronaut Memorial Space Mirror at the KSC Visitor Complex. The memorial is a national tribute to 17 American astronauts who previously gave their lives to the quest to explore space. The memorial has had added attention since the loss of the Columbia crew Feb. 1, 2003, when they died in an explosion as they were returning to Earth from mission STS-107.

KSC-03pd0615

NASA Image and Video Library

2003-03-06

KENNEDY SPACE CENTER, FLA. -- A view of the Astronaut Memorial Space Mirror at the KSC Visitor Complex. The memorial is a national tribute to 17 American astronauts who previously gave their lives to the quest to explore space. The memorial has had added attention since the loss of the Columbia crew Feb. 1, 2003, when they died in an explosion as they were returning to Earth from mission STS-107.

Appetite Loss and Neurocognitive Deficits in Late-Life Depression

PubMed Central

Potter, Guy G.; McQuoid, Douglas R.; Steffens, David C.

2015-01-01

Objectives Examine association of appetite loss symptoms to neurocognitive performance in late-life depression (LLD). Methods Cross-sectional data from individuals aged 60+ with Major Depressive Disorder (N =322). Participants received clinical assessment of depression and neuropsychological testing. Factor analysis was used to characterize depression symptom factors, and composite scales were developed for episodic memory, psychomotor executive functions, verbal fluency, and working memory span. Results Factor analysis produced a five-factor solution: (1) Anhedonia/Sadness, (2) Suicidality/Guilt, (3) Appetite/Weight Loss, (4) Sleep Disturbance, and (5) Anxiety/Tension. In separate multivariate models for each neurocognitive domain and including all 5 depression factors, higher appetite-loss-related symptoms were associated with lower performance in episodic memory, psychomotor executive functions, and verbal fluency; results were significant with covariates of age, education, race, sex, age of depression onset, and illness burden. No other depression factors were associated with neurocognitive performance in these models. In an additional set of models, the Appetite factor mediated the association between global depression severity and neurocognitive performance. Discussion A factor of appetite and weight loss symptoms in LLD was uniquely associated with neurocognitive performance, in contrast to lack of association among other depression symptom factors. Conclusion Cognitive deficits are a major adverse outcome of LLD, and prominent appetite loss during acute depression may be a marker for these deficits, independent of overall depression severity. Research is needed to understand the mechanisms that may explain this association, and how it is related to the cognitive and symptomatic course of LLD. PMID:25315155

Entorhinal-Hippocampal Neuronal Circuits Bridge Temporally Discontiguous Events

ERIC Educational Resources Information Center

Kitamura, Takashi; Macdonald, Christopher J.; Tonegawa, Susumu

2015-01-01

The entorhinal cortex (EC)-hippocampal (HPC) network plays an essential role for episodic memory, which preserves spatial and temporal information about the occurrence of past events. Although there has been significant progress toward understanding the neural circuits underlying the spatial dimension of episodic memory, the relevant circuits…

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

2016-04-26

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. Copyright © 2016, American Association for the Advancement of Science.

Dynamic modulation of innate immunity programming and memory.

PubMed

Yuan, Ruoxi; Li, Liwu

2016-01-01

Recent progress harkens back to the old theme of immune memory, except this time in the area of innate immunity, to which traditional paradigm only prescribes a rudimentary first-line defense function with no memory. However, both in vitro and in vivo studies reveal that innate leukocytes may adopt distinct activation states such as priming, tolerance, and exhaustion, depending upon the history of prior challenges. The dynamic programming and potential memory of innate leukocytes may have far-reaching consequences in health and disease. This review aims to provide some salient features of innate programing and memory, patho-physiological consequences, underlying mechanisms, and current pressing issues.

Mnemonic function in small vessel disease and associations with white matter tract microstructure.

PubMed

Metoki, Athanasia; Brookes, Rebecca L; Zeestraten, Eva; Lawrence, Andrew J; Morris, Robin G; Barrick, Thomas R; Markus, Hugh S; Charlton, Rebecca A

2017-09-01

Cerebral small vessel disease (SVD) is associated with deficits in working memory, with a relative sparing of long-term memory; function may be influenced by white matter microstructure. Working and long-term memory were examined in 106 patients with SVD and 35 healthy controls. Microstructure was measured in the uncinate fasciculi and cingula. Working memory was more impaired than long-term memory in SVD, but both abilities were reduced compared to controls. Regression analyses found that having SVD explained the variance in memory functions, with additional variance explained by the cingula (working memory) and uncinate (long-term memory). Performance can be explained in terms of integrity loss in specific white matter tract associated with mnemonic functions. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

AVN-211, Novel and Highly Selective 5-HT6 Receptor Small Molecule Antagonist, for the Treatment of Alzheimer's Disease.

PubMed

Ivachtchenko, Alexandre V; Lavrovsky, Yan; Ivanenkov, Yan A

2016-03-07

Within the past decade several novel targets have been indicated as key players in Alzheimer-type dementia and associated conditions, including a "frightening" memory loss as well as severe cognitive impairments. These proteins are deeply implicated in crucial cell processes, e.g., autophagy, growth and progression, apoptosis, and metabolic equilibrium. Since recently, 5-HT6R has been considered as one of the most prominent biological targets in AD drug therapy. Therefore, we investigated the potential procognitive and neuroprotective effects of our novel selective 5-HT6R antagonist, AVN-211. During an extensive preclinical evaluation the lead compound demonstrated a relatively high therapeutic potential and improved selectivity toward 5-HT6R as compared to reference drug candidates. It was thoroughly examined in different in vivo behavioral models directly related to AD and showed evident improvements in cognition and learning. In many cases, the observed effect was considerably greater than that determined for the reported drugs and drug candidates, including memantine, SB-742457, and Lu AE58054, evaluated under the same conditions. In addition, AVN-211 showed a similar or better anxiolytic efficacy than fenobam, rufinamide, lorazepam, and buspirone in an elevated plus-maze model, elevated platform, and open field tests. The compound demonstrated low toxicity and no side effects in vivo, an appropriate pharmacokinetic profile, and stability. In conclusion, AVN-211 significantly delayed or partially halted the progressive decline in memory function associated with AD, which makes it an interesting drug candidate for the treatment of neurodegenerative and psychiatric disorders. Advanced clinical trials are currently under active discussion and in high priority.

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents metabolic dysfunction and Alzheimer's disease-related memory loss in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet.

PubMed

Kobayashi, Yutaro; Inagawa, Hiroyuki; Kohchi, Chie; Kazumura, Kimiko; Tsuchiya, Hiroshi; Miwa, Toshiyuki; Okazaki, Katsuichiro; Soma, Gen-Ichiro

2018-01-01

The pathogenesis of Alzheimer's disease (AD) remains unclear, but an imbalance between the production and clearance of amyloid-β (Aβ) peptides is known to play a critical role in AD progression. A promising preventative approach is to enhance the normal Aβ clearance activity of brain phagocytes such as microglia. In mice, the intraperitoneal injection of Toll-like receptor 4 agonist was shown to enhance Aβ clearance and exhibit a preventative effect on AD-related pathology. Our previous clinical study demonstrated that orally administered Pantoea agglomerans-derived lipopolysaccharide (LPSp) exhibited an LDL (low-density lipoprotein)-lowering effect in human volunteers with hyperlipidemia, a known risk factor for AD. In vitro studies have shown that LPSp treatment increases Aβ phagocytosis by microglial cells; however it is still unclear whether orally administered LPSp exhibits a preventive effect on AD progression. We show here that in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet, oral administration of LPSp at 0.3 or 1 mg/kg body weight·day for 18 weeks significantly improved glucose metabolism and lipid profiles. The LPSp treatment also reduced pro-inflammatory cytokine expression and oxidative-burst activity in the peripheral blood. Moreover, LPSp significantly reduced brain Aβ burden and memory impairment as seen in the water maze test, although we could not confirm a significant enhancement of Aβ phagocytosis in microglia isolated from the brains after treatment. Taken together, our results show that LPSp holds promise as a preventative therapy for AD or AD-related diseases induced by impairment of metabolic functions.

KENNEDY SPACE CENTER, FLA. - At the podium in front of the Space Memorial Mirror at the KSC Visitor Complex is Dr. Stephen Feldman, president of the Astronaut Memorial Foundation. He spoke to attendees at the memorial service remembering and honoring the crew of Columbia. With him (from left) are KSC Deputy Director Woodrow Whitlow Jr., Center Director Jim Kennedy and Executive Director of Florida Space Authority Winston Scott. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Scott is a former astronaut who flew on Columbia in 1997. Attended by many friends, co-workers and families, the memorial service was also open to the public.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - At the podium in front of the Space Memorial Mirror at the KSC Visitor Complex is Dr. Stephen Feldman, president of the Astronaut Memorial Foundation. He spoke to attendees at the memorial service remembering and honoring the crew of Columbia. With him (from left) are KSC Deputy Director Woodrow Whitlow Jr., Center Director Jim Kennedy and Executive Director of Florida Space Authority Winston Scott. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. Scott is a former astronaut who flew on Columbia in 1997. Attended by many friends, co-workers and families, the memorial service was also open to the public.

Time-Based Loss in Visual Short-Term Memory is from Trace Decay, not Temporal Distinctiveness

PubMed Central

Ricker, Timothy J.; Spiegel, Lauren R.; Cowan, Nelson

2014-01-01

There is no consensus as to why forgetting occurs in short-term memory tasks. In past work, we have shown that forgetting occurs with the passage of time, but there are two classes of theories that can explain this effect. In the present work, we investigate the reason for time-based forgetting by contrasting the predictions of temporal distinctiveness and trace decay in the procedure in which we have observed such loss, involving memory for arrays of characters or letters across several seconds. The first theory, temporal distinctiveness, predicts that increasing the amount of time between trials will lead to less proactive interference, resulting in less forgetting across a retention interval. In the second theory, trace decay, temporal distinctiveness between trials is irrelevant to the loss over a retention interval. Using visual array change detection tasks in four experiments, we find small proactive interference effects on performance under some specific conditions, but no concomitant change in the effect of a retention interval. We conclude that trace decay is the more suitable class of explanations of the time-based forgetting in short-term memory that we have observed, and we suggest the need for further clarity in what the exact basis of that decay may be. PMID:24884646

Collateral brain damage, a potential source of cognitive impairment after selective surgery for control of mesial temporal lobe epilepsy.

PubMed

Helmstaedter, C; Van Roost, D; Clusmann, H; Urbach, H; Elger, C E; Schramm, J

2004-02-01

Highly selective epilepsy surgery in temporal lobe epilepsy is intended to achieve seizure freedom at a lower cognitive risk than standard en bloc resections, but bears the risk of collateral cortical damage resulting from the surgical approach. To investigate cortical damage associated with selective amygdalo-hippocampectomy (SAH). 34 epileptic patients were evaluated. They were randomly assigned to SAH using either a sylvian (9 left/10 right) or a transcortical surgical approach (5 left/10 right). Postoperative MRI signal intensity changes adjacent to the approach were correlated with performance changes in serial word and design list learning. Losses in verbal learning and recognition memory were positively related to signal intensity changes, independent of the side of the resection, the surgical approach, or the extent of the mesial resection. Losses in consolidation/retrieval (memory) were greater after left sided surgery. Losses in design learning were related to right sided surgery and signal intensity changes. Seizure outcome (85% seizure-free) did not differ depending on the side or type of surgery. Collateral damage to cortical tissues adjacent to the surgical approach contributes to postoperative verbal and figural memory outcome after SAH. Controlling for collateral damage may clarify the controversial memory outcomes after SAH reported by different surgical centres.

Improvement of autobiographic memory recovery by means of sad music in Alzheimer's Disease type dementia.

PubMed

Meilán García, Juan José; Iodice, Rosario; Carro, Juan; Sánchez, José Antonio; Palmero, Francisco; Mateos, Ana María

2012-06-01

Autobiographic memory undergoes progressive deterioration during the evolution of Alzheimer's disease (AD). The aim of this study was to analyze mechanisms which facilitate recovery of autobiographic memories. We used a repeatedly employed mechanism, music, with the addition of an emotional factor. Autobiographic memory provoked by a variety of sounds (music which was happy, sad, lacking emotion, ambient noise in a coffee bar and no sound) was analyzed in a sample of 25 patients with AD. Emotional music, especially sad music for remote memories, was found to be the most effective kind for recall of autobiographic experiences. The factor evoking the memory is not the music itself, but rather the emotion associated with it, and is useful for semantic rather than episodic memory.

Effects of almond consumption on the post-lunch dip and long-term cognitive function in energy-restricted overweight and obese adults.

PubMed

Dhillon, Jaapna; Tan, Sze-Yen; Mattes, Richard D

2017-02-01

The post-lunch dip in cognition is a well-established phenomenon of decreased alertness, memory and vigilance after lunch consumption. Lunch composition reportedly influences the post-lunch dip. Moreover, dieting is associated with cognitive function impairments. The negative effects of dieting have been reversed with nut-supplemented diets. The aims of this study were to (1) evaluate the acute effect of an almond-enriched high-fat lunch or high-carbohydrate lunch on the post-lunch decline in cognitive function, and (2) evaluate the effects of chronic almond consumption as part of an energy-restricted diet on the memory and attention domains of cognitive function. In total, eighty-six overweight and obese adults were randomised to consume either an almond-enriched diet (AED) or a nut-free control diet (NFD) over a 12-week weight loss intervention. Participants were also randomised to receive either an almond-enriched high-fat lunch (A-HFL) (>55 % energy from fat, almonds contributing 70-75 % energy) or a high-carbohydrate lunch (HCL) (>85 % energy from carbohydrates) at the beginning and end of the weight loss intervention. Memory and attention performance indices decreased after lunch consumption (P<0·001). The A-HFL group ameliorated the decline in memory scores by 57·7 % compared with the HCL group (P=0·004). Both lunch groups had similar declines in attention. Moreover, memory and attention performance indices increased after the 12-week intervention period (P<0·05) with no difference between the AED and NFD groups. In conclusion, almond consumption at a midday meal can reduce the post-lunch dip in memory. However, long-term almond consumption may not further improve cognitive function outcomes in a weight loss intervention.

Contextual Fear Memories Formed in the Absence of the Dorsal Hippocampus Decay Across Time

PubMed Central

Zelikowsky, Moriel; Bissiere, Stephanie; Fanselow, Michael S.

2012-01-01

Mammals suffering damage to the hippocampus display a dramatic loss of explicit, recently formed memories (retrograde amnesia). In contrast, deficits in the ability to form new memories following hippocampal damage (anterograde amnesia) can be overcome with sufficient training. By combining contextual fear conditioning with lesions of the dorsal hippocampus in rats, we discovered that while animals can form long-term contextual fear memories in the absence of the hippocampus, these memories decay with time, lacking the permanence that is a hallmark characteristic of normal fear memories. These findings indicate that while it is initially possible to acquire explicit memories when the hippocampus is compromised, these memories cannot transfer from a recent to remote state. This suggests that memories formed outside the hippocampus may nevertheless require the hippocampus to undergo systems consolidation, which has important clinical implications for the treatment of memory disorders. PMID:22399761

Fragmentation of Rapid Eye Movement and Nonrapid Eye Movement Sleep without Total Sleep Loss Impairs Hippocampus-Dependent Fear Memory Consolidation

PubMed Central

Lee, Michael L.; Katsuyama, Ângela M.; Duge, Leanne S.; Sriram, Chaitra; Krushelnytskyy, Mykhaylo; Kim, Jeansok J.; de la Iglesia, Horacio O.

2016-01-01

Study Objectives: Sleep is important for consolidation of hippocampus-dependent memories. It is hypothesized that the temporal sequence of nonrapid eye movement (NREM) sleep and rapid eye movement (REM) sleep is critical for the weakening of nonadaptive memories and the subsequent transfer of memories temporarily stored in the hippocampus to more permanent memories in the neocortex. A great body of evidence supporting this hypothesis relies on behavioral, pharmacological, neural, and/or genetic manipulations that induce sleep deprivation or stage-specific sleep deprivation. Methods: We exploit an experimental model of circadian desynchrony in which intact animals are not deprived of any sleep stage but show fragmentation of REM and NREM sleep within nonfragmented sleep bouts. We test the hypothesis that the shortening of NREM and REM sleep durations post-training will impair memory consolidation irrespective of total sleep duration. Results: When circadian-desynchronized animals are trained in a hippocampus-dependent contextual fear-conditioning task they show normal short-term memory but impaired long-term memory consolidation. This impairment in memory consolidation is positively associated with the post-training fragmentation of REM and NREM sleep but is not significantly associated with the fragmentation of total sleep or the total amount of delta activity. We also show that the sleep stage fragmentation resulting from circadian desynchrony has no effect on hippocampus-dependent spatial memory and no effect on hippocampus-independent cued fear-conditioning memory. Conclusions: Our findings in an intact animal model, in which sleep deprivation is not a confounding factor, support the hypothesis that the stereotypic sequence and duration of sleep stages play a specific role in long-term hippocampus-dependent fear memory consolidation. Citation: Lee ML, Katsuyama AM, Duge LS, Sriram C, Krushelnytskyy M, Kim JJ, de la Iglesia HO. Fragmentation of rapid eye movement and nonrapid eye movement sleep without total sleep loss impairs hippocampus-dependent fear memory consolidation. SLEEP 2016;39(11):2021–2031. PMID:27568801

Active Control of Flexible Space Structures Using the Nitinol Shape Memory Actuators

DTIC Science & Technology

1987-10-01

number) FIELD !GROUP SUBGROUP I Active Control, Nitinol Actuators, Space Structures 9. ABSTRACT (Continue on reverse if necessary and identify by block...number) Summarizes research progress in the feasibility demonstration of active vibration control using Nitinol shape memory actuators. Tests on...FLEXIBLE SPACE STRUCTURES USING NITINOL SHAPE MEMORY ACTUATORS FINAL REPORT FOR PHASE I SDIO CONTRACT #F49620-87-C-0035 0 BY DR. AMR M. BAZ KARIM R

Recent progress in tungsten oxides based memristors and their neuromorphological applications

NASA Astrophysics Data System (ADS)

Qu, Bo; Younis, Adnan; Chu, Dewei

2016-09-01

The advance in conventional silicon based semiconductor industry is now becoming indeterminacy as it still along the road of Moore's Law and concomitant problems associated with it are the emergence of a number of practical issues such as short channel effect. In terms of memory applications, it is generally believed that transistors based memory devices will approach to their scaling limits up to 2018. Therefore, one of the most prominent challenges today in semiconductor industry is the need of a new memory technology which is able to combine the best characterises of current devices. The resistive switching memories which are regarded as "memristors" thus gain great attentions thanks to their specific nonlinear electrical properties. More importantly, their behaviour resembles with the transmission characteristic of synapse in biology. Therefore, the research of synapses biomimetic devices based on memristor will certainly bring a great research prospect in studying synapse emulation as well as building artificial neural networks. Tungsten oxides (WO x ) exhibits many essential characteristics as a great candidate for memristive devices including: accredited endurance (over 105 cycles), stoichiometric flexibility, complimentary metal-oxide-semiconductor (CMOS) process compatibility and configurable properties including non-volatile rectification, memorization and learning functions. Herein, recent progress on Tungsten oxide based materials and its associating memory devices had been reviewed. The possible implementation of this material as a bio-inspired artificial synapse is also highlighted. The penultimate section summaries the current research progress for tungsten oxide based biological synapses and end up with several proposals that have been suggested for possible future developments.

Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infection

PubMed Central

Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M.; Hagen, Shoko I.; Walker, Joshua M.; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B.; Planer, Shannon L.; Legasse, Alfred; Sylwester, Andrew W.; Piatak, Michael; Lifson, Jeffrey D.; Maino, Vernon C.; Sodora, Donald L.; Douek, Daniel C.; Axthelm, Michael K.; Grossman, Zvi; Picker, Louis J.

2007-01-01

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4+ CCR5+ effector–memory T (TEM) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4+ memory T cell proliferation appears to prevent collapse of effector site CD4+ TEM cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4+ TEM cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4+ TEM cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4+ TEM cells from central–memory T (TCM) cell precursors. The instability of effector site CD4+ TEM cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5− CD4+ TCM cells. These data suggest that although CD4+ TEM cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4+ TCM cells. PMID:17724130

Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection.

PubMed

Okoye, Afam; Meier-Schellersheim, Martin; Brenchley, Jason M; Hagen, Shoko I; Walker, Joshua M; Rohankhedkar, Mukta; Lum, Richard; Edgar, John B; Planer, Shannon L; Legasse, Alfred; Sylwester, Andrew W; Piatak, Michael; Lifson, Jeffrey D; Maino, Vernon C; Sodora, Donald L; Douek, Daniel C; Axthelm, Michael K; Grossman, Zvi; Picker, Louis J

2007-09-03

Primary simian immunodeficiency virus (SIV) infections of rhesus macaques result in the dramatic depletion of CD4(+) CCR5(+) effector-memory T (T(EM)) cells from extra-lymphoid effector sites, but in most infections, an increased rate of CD4(+) memory T cell proliferation appears to prevent collapse of effector site CD4(+) T(EM) cell populations and acute-phase AIDS. Eventually, persistent SIV replication results in chronic-phase AIDS, but the responsible mechanisms remain controversial. Here, we demonstrate that in the chronic phase of progressive SIV infection, effector site CD4(+) T(EM) cell populations manifest a slow, continuous decline, and that the degree of this depletion remains a highly significant correlate of late-onset AIDS. We further show that due to persistent immune activation, effector site CD4(+) T(EM) cells are predominantly short-lived, and that their homeostasis is strikingly dependent on the production of new CD4(+) T(EM) cells from central-memory T (T(CM)) cell precursors. The instability of effector site CD4(+) T(EM) cell populations over time was not explained by increasing destruction of these cells, but rather was attributable to progressive reduction in their production, secondary to decreasing numbers of CCR5(-) CD4(+) T(CM) cells. These data suggest that although CD4(+) T(EM) cell depletion is a proximate mechanism of immunodeficiency, the tempo of this depletion and the timing of disease onset are largely determined by destruction, failing production, and gradual decline of CD4(+) T(CM) cells.

Progressive Stochastic Reconstruction Technique (PSRT) for cryo electron tomography.

PubMed

Turoňová, Beata; Marsalek, Lukas; Davidovič, Tomáš; Slusallek, Philipp

2015-03-01

Cryo Electron Tomography (cryoET) plays an essential role in Structural Biology, as it is the only technique that allows to study the structure of large macromolecular complexes in their close to native environment in situ. The reconstruction methods currently in use, such as Weighted Back Projection (WBP) or Simultaneous Iterative Reconstruction Technique (SIRT), deliver noisy and low-contrast reconstructions, which complicates the application of high-resolution protocols, such as Subtomogram Averaging (SA). We propose a Progressive Stochastic Reconstruction Technique (PSRT) - a novel iterative approach to tomographic reconstruction in cryoET based on Monte Carlo random walks guided by Metropolis-Hastings sampling strategy. We design a progressive reconstruction scheme to suit the conditions present in cryoET and apply it successfully to reconstructions of macromolecular complexes from both synthetic and experimental datasets. We show how to integrate PSRT into SA, where it provides an elegant solution to the region-of-interest problem and delivers high-contrast reconstructions that significantly improve template-based localization without any loss of high-resolution structural information. Furthermore, the locality of SA is exploited to design an importance sampling scheme which significantly speeds up the otherwise slow Monte Carlo approach. Finally, we design a new memory efficient solution for the specimen-level interior problem of cryoET, removing all associated artifacts. Copyright © 2015 Elsevier Inc. All rights reserved.

Twenty years of audiology in a patient with Norrie disease.

PubMed

Halpin, Chris; Sims, Katherine

2008-11-01

To describe disease progression and treatment outcomes over a 20-year period (ages 5-25) in a young man with Norrie disease (occuloacousticocerebral dysplasia), ND; OMIM #310600. Affected individuals are born blind and develop progressive sensory loss with onset in adolescence. This disease is X-linked and has been associated with mutations of the NDP gene (Xp11.4). The patient was followed using repeated audiograms, as well as reports of educational progress and hearing aid use. The specific mutation was found by molecular analysis. The patient demonstrated progressive sensory loss with good preservation of word recognition. The loss was initially high frequency and asymmetric in adolescence and became more severe, more symmetric and affected practically all frequencies by the end of childhood. Educational progress was affected by the cognitive effects of the syndrome, and hearing aid use was very effective. A bilateral progressive sensory loss with good preservation of word recognition was documented in detail. The residual word recognition supported good use of hearing aids in this case.

Proactive Interference and Item Similarity in Working Memory

ERIC Educational Resources Information Center

Bunting, Michael

2006-01-01

Proactive interference (PI) may influence the predictive utility of working memory span tasks. Participants in one experiment (N=70) completed Ravens Advanced Progressive Matrices (RAPM) and multiple versions of operation span and probed recall, modified for the type of memoranda (digits or words). Changing memoranda within- or across-trials…

Clonal Ordering of 17p and 5q Allelic Losses in Barrett Dysplasia and Adenocarcinoma

NASA Astrophysics Data System (ADS)

Blount, Patricia L.; Meltzer, Stephen J.; Yin, Jing; Huang, Ying; Krasna, Mark J.; Reid, Brian J.

1993-04-01

Both 17p and 5q allelic losses appear to be involved in the pathogenesis or progression of many human solid tumors. In colon carcinogenesis, there is strong evidence that the targets of the 17p and 5q allelic losses are TP53, the gene encoding p53, and APC, respectively. It is widely accepted that 5q allelic losses precede 17p allelic losses in the progression to colonic carcinoma. The data, however, supporting this proposed order are largely based on the prevalence of 17p and 5q allelic losses in adenomas and unrelated adenocarcinomas from different patients. We investigated the order in which 17p and 5q allelic losses developed during neoplastic progression in Barrett esophagus by evaluating multiple aneuploid cell populations from the same patient. Using DNA content flow cytometric cell sorting and polymerase chain reaction, 38 aneuploid cell populations from 14 patients with Barrett esophagus who had high grade dysplasia, cancer or both were evaluated for 17p and 5q allelic losses. 17p allelic losses preceded 5q allelic losses in 7 patients, both 17p and 5q allelic losses were present in all aneuploid populations of 4 patients, and only 17p (without 5q) allelic losses were present in the aneuploid populations of 3 patients. In no patient did we find that a 5q allelic loss preceded a 17p allelic loss. Our data suggest that 17p allelic losses typically occur before 5q allelic losses during neoplastic progression in Barrett esophagus.

Finding the engram.

PubMed

Josselyn, Sheena A; Köhler, Stefan; Frankland, Paul W

2015-09-01

Many attempts have been made to localize the physical trace of a memory, or engram, in the brain. However, until recently, engrams have remained largely elusive. In this Review, we develop four defining criteria that enable us to critically assess the recent progress that has been made towards finding the engram. Recent 'capture' studies use novel approaches to tag populations of neurons that are active during memory encoding, thereby allowing these engram-associated neurons to be manipulated at later times. We propose that findings from these capture studies represent considerable progress in allowing us to observe, erase and express the engram.

NAAG Peptidase Inhibitors Act via mGluR3: Animal Models of Memory, Alzheimer's, and Ethanol Intoxication.

PubMed

Olszewski, Rafal T; Janczura, Karolina J; Bzdega, Tomasz; Der, Elise K; Venzor, Faustino; O'Rourke, Brennen; Hark, Timothy J; Craddock, Kirsten E; Balasubramanian, Shankar; Moussa, Charbel; Neale, Joseph H

2017-09-01

Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1.5 h) and long- (24 h) term novel object recognition tests were used to assess memory. Treatment with ZJ43 or 2-PMPA prior to acquisition trials increased long-term memory in mGluR2, but not mGluR3, ko mice. Nine month-old triple transgenic Alzheimer's disease model mice exhibited impaired short-term novel object recognition memory that was rescued by treatment with a NAAG peptidase inhibitor. NAAG peptidase inhibitors and the group II mGluR agonist, LY354740, reversed the short-term memory deficit induced by acute ethanol administration in wild type mice. 2-PMPA also moderated the effect of ethanol on short-term memory in mGluR2 ko mice but failed to do so in mGluR3 ko mice. LY354740 and ZJ43 blocked ethanol-induced motor activation. Both GCPII inhibitors and LY354740 also significantly moderated the loss of motor coordination induced by 2.1 g/kg ethanol treatment. These data support the conclusion that inhibitors of glutamate carboxypeptidase II are efficacious in object recognition models of normal memory and memory deficits via an mGluR3 mediated process, actions that could have widespread clinical applications.

Progressive Functional Impairments of Hippocampal Neurons in a Tauopathy Mouse Model

PubMed Central

Ciupek, Sarah M.; Cheng, Jingheng; Ali, Yousuf O.; Lu, Hui-Chen

2015-01-01

The age-dependent progression of tau pathology is a major characteristic of tauopathies, including Alzheimer's disease (AD), and plays an important role in the behavioral phenotypes of AD, including memory deficits. Despite extensive molecular and cellular studies on tau pathology, it remains to be determined how it alters the neural circuit functions underlying learning and memory in vivo. In rTg4510 mice, a Tau-P301L tauopathy model, hippocampal place fields that support spatial memories are abnormal at old age (7–9 months) when tau tangles and neurodegeneration are extensive. However, it is unclear how the abnormality in the hippocampal circuit function arises and progresses with the age-dependent progression of tau pathology. Here we show that in young (2–4 months of age) rTg4510 mice, place fields of hippocampal CA1 cells are largely normal, with only subtle differences from those of age-matched wild-type control mice. Second, high-frequency ripple oscillations of local field potentials in the hippocampal CA1 area are significantly reduced in young rTg4510 mice, and even further deteriorated in old rTg4510 mice. The ripple reduction is associated with less bursty firing and altered synchrony of CA1 cells. Together, the data indicate that deficits in ripples and neuronal synchronization occur before overt deficits in place fields in these mice. The results reveal a tau-pathology-induced progression of hippocampal functional changes in vivo. PMID:26019329

Loss of memory CD4+ T-cells in semi-wild mandrills (Mandrillus sphinx) naturally infected with species-specific simian immunodeficiency virus SIVmnd-1.

PubMed

Greenwood, Edward J D; Schmidt, Fabian; Liégeois, Florian; Kondova, Ivanela; Herbert, Anaïs; Ngoubangoye, Barthelemy; Rouet, François; Heeney, Jonathan L

2014-01-01

Simian immunodeficiency virus (SIV) infection is found in a number of African primate species and is thought to be generally non-pathogenic. However, studies of wild primates are limited to two species, with SIV infection appearing to have a considerably different outcome in each. Further examination of SIV-infected primates exposed to their natural environment is therefore warranted. We performed a large cross-sectional study of a cohort of semi-wild mandrills with naturally occurring SIV infection, including 39 SIV-negative and 33 species-specific SIVmnd-1-infected animals. This study was distinguished from previous reports by considerably greater sample size, examination of exclusively naturally infected animals in semi-wild conditions and consideration of simian T-lymphotropic virus (STLV) status in addition to SIVmnd-1 infection. We found that SIVmnd-1 infection was associated with a significant and progressive loss of memory CD4(+) T-cells. Limited but significant increases in markers of immune activation in the T-cell populations, significant increases in plasma neopterin and changes to B-cell subsets were also observed in SIV-infected animals. However, no increase in plasma soluble CD14 was observed. Histological examination of peripheral lymph nodes suggested that SIVmnd-1 infection was not associated with a significant disruption of the lymph node architecture. Whilst this species has evolved numerous strategies to resist the development of AIDS, significant effects of SIV infection could be observed when examined in a natural environment. STLVmnd-1 infection also had significant effects on some markers relevant to understanding SIV infection and thus should be considered in studies of SIV infection of African primates where present.

Apolipoprotein E4 causes age- and Tau-dependent impairment of GABAergic interneurons, leading to learning and memory deficits in mice.

PubMed

Andrews-Zwilling, Yaisa; Bien-Ly, Nga; Xu, Qin; Li, Gang; Bernardo, Aubrey; Yoon, Seo Yeon; Zwilling, Daniel; Yan, Tonya Xue; Chen, Ligong; Huang, Yadong

2010-10-13

Apolipoprotein E4 (apoE4) is the major genetic risk factor for Alzheimer's disease. However, the underlying mechanisms are unclear. We found that female apoE4 knock-in (KI) mice had an age-dependent decrease in hilar GABAergic interneurons that correlated with the extent of learning and memory deficits, as determined in the Morris water maze, in aged mice. Treating apoE4-KI mice with daily peritoneal injections of the GABA(A) receptor potentiator pentobarbital at 20 mg/kg for 4 weeks rescued the learning and memory deficits. In neurotoxic apoE4 fragment transgenic mice, hilar GABAergic interneuron loss was even more pronounced and also correlated with the extent of learning and memory deficits. Neurodegeneration and tauopathy occurred earliest in hilar interneurons in apoE4 fragment transgenic mice; eliminating endogenous Tau prevented hilar GABAergic interneuron loss and the learning and memory deficits. The GABA(A) receptor antagonist picrotoxin abolished this rescue, while pentobarbital rescued learning deficits in the presence of endogenous Tau. Thus, apoE4 causes age- and Tau-dependent impairment of hilar GABAergic interneurons, leading to learning and memory deficits in mice. Consequently, reducing Tau and enhancing GABA signaling are potential strategies to treat or prevent apoE4-related Alzheimer's disease.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task.

PubMed

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. © 2015 S. Karger GmbH, Freiburg.

Diet-Induced Weight Loss Alters Functional Brain Responses during an Episodic Memory Task

PubMed Central

Boraxbekk, Carl-Johan; Stomby, Andreas; Ryberg, Mats; Lindahl, Bernt; Larsson, Christel; Nyberg, Lars; Olsson, Tommy

2015-01-01

Objective It has been suggested that overweight is negatively associated with cognitive functions. The aim of this study was to investigate whether a reduction in body weight by dietary interventions could improve episodic memory performance and alter associated functional brain responses in overweight and obese women. Methods 20 overweight postmenopausal women were randomized to either a modified paleolithic diet or a standard diet adhering to the Nordic Nutrition Recommendations for 6 months. We used functional magnetic resonance imaging to examine brain function during an episodic memory task as well as anthropometric and biochemical data before and after the interventions. Results Episodic memory performance improved significantly (p = 0.010) after the dietary interventions. Concomitantly, brain activity increased in the anterior part of the right hippocampus during memory encoding, without differences between diets. This was associated with decreased levels of plasma free fatty acids (FFA). Brain activity increased in pre-frontal cortex and superior/middle temporal gyri. The magnitude of increase correlated with waist circumference reduction. During episodic retrieval, brain activity decreased in inferior and middle frontal gyri, and increased in middle/superior temporal gyri. Conclusions Diet-induced weight loss, associated with decreased levels of plasma FFA, improves episodic memory linked to increased hippocampal activity. PMID:26139105

KENNEDY SPACE CENTER, FLA. - Friends, co-workers and families gather at the Space Memorial Mirror for KSC’s special service remembering and honoring the crew of Columbia. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. The public was invited to the memorial service held at the KSC Visitor Complex. Participants included Center Director Jim Kennedy, Deputy Director Woodrow Whitlow Jr., Executive Director of Florida Space Authority Winston Scott, Dr. Stephen Feldman, president of the Astronaut Memorial Foundation, and dancers from the Shoshone-Bannock Native American community in Fort Hall, Idaho.

NASA Image and Video Library

2004-02-01

KENNEDY SPACE CENTER, FLA. - Friends, co-workers and families gather at the Space Memorial Mirror for KSC’s special service remembering and honoring the crew of Columbia. Feb. 1 is the one-year anniversary of the loss of the crew and orbiter Columbia in a tragic accident as the ship returned to Earth following mission STS-107. The public was invited to the memorial service held at the KSC Visitor Complex. Participants included Center Director Jim Kennedy, Deputy Director Woodrow Whitlow Jr., Executive Director of Florida Space Authority Winston Scott, Dr. Stephen Feldman, president of the Astronaut Memorial Foundation, and dancers from the Shoshone-Bannock Native American community in Fort Hall, Idaho.