[GLIATILIN CORRECTION OF WORKING AND REFERENCE SPATIAL MEMORY IMPAIRMENT IN AGED RATS].

PubMed

Tyurenkov, I N; Volotova, E V; Kurkin, D V

2015-01-01

This work was aimed at evaluating the influence of gliatilin administration on the spatial memory in aged rats. Cognitive function and spatial memory in animals was evaluated using radial (8-beam) maze test. Errors of working spatial memory and reference memory were used as indicators of impaired cognitive function. It was found that aged (24-month) rats compared with younger (6-months) age group exhibited cognitive impairment, as manifested by deterioration of short- and long-term memory processes. Course administration of gliatilin in rats of the older age group at a dose of 100 mg/kg resulted in significant improvement of the working and reference spatial memory in aged rats.

Other drug use does not impact cognitive impairments in chronic ketamine users.

PubMed

Zhang, Chenxi; Tang, Wai Kwong; Liang, Hua Jun; Ungvari, Gabor Sandor; Lin, Shih-Ku

2018-05-01

Ketamine abuse causes cognitive impairments, which negatively impact on users' abstinence, prognosis, and quality of life. of cognitive impairments in chronic ketamine users have been inconsistent across studies, possibly due to the small sample sizes and the confounding effects of concomitant use of other illicit drugs. This study investigated the cognitive impairment and its related factors in chronic ketamine users with a large sample size and explored the impact of another drug use on cognitive functions. Cognitive functions, including working, verbal and visual memory and executive functions were assessed in ketamine users: 286 non-heavy other drug users and 279 heavy other drug users, and 261 healthy controls. Correlations between cognitive impairment and patterns of ketamine use were analysed. Verbal and visual memory were impaired, but working memory and executive functions were intact for all ketamine users. No significant cognitive differences were found between the two ketamine groups. Greater number of days of ketamine use in the past month was associated with worse visual memory performance in non-heavy other drug users. Higher dose of ketamine use was associated with worse short-term verbal memory in heavy other drug users. Verbal and visual memory are impaired in chronic ketamine users. Other drug use appears to have no impact on ketamine users' cognitive performance. Copyright © 2018. Published by Elsevier B.V.

Assessment and treatment of short-term and working memory impairments in stroke aphasia: a practical tutorial.

PubMed

Salis, Christos; Kelly, Helen; Code, Chris

2015-01-01

Aphasia following stroke refers to impairments that affect the comprehension and expression of spoken and/or written language, and co-occurring cognitive deficits are common. In this paper we focus on short-term and working memory impairments that impact on the ability to retain and manipulate auditory-verbal information. Evidence from diverse paradigms (large group studies, case studies) report close links between short-term/working memory and language functioning in aphasia. This evidence leads to the hypothesis that treating such memory impairments would improve language functioning. This link has only recently been acknowledged in aphasia treatment but has not been embraced widely by clinicians. To examine the association between language, and short-term and working memory impairments in aphasia. To describe practical ways of assessing short-term and working memory functioning that could be used in clinical practice. To discuss and critically appraise treatments of short-term and working memory reported in the literature. Taking a translational research approach, this paper provides clinicians with current evidence from the literature and practical information on how to assess and treat short-term and working memory impairments in people with aphasia. Published treatments of short-term and/or working memory in post-stroke aphasia are discussed through a narrative review. This paper provides the following. A theoretical rationale for adopting short-term and working memory treatments in aphasia. It highlights issues in differentially diagnosing between short-term, working memory disorders and other concomitant impairments, e.g. apraxia of speech. It describes short-term and working memory assessments with practical considerations for use with people with aphasia. It also offers a description of published treatments in terms of participants, treatments and outcomes. Finally, it critically appraises the current evidence base relating to the treatment of short-term and working memory treatments. The links between short-term/working memory functioning and language in aphasia are generally acknowledged. These strongly indicate the need to incorporate assessment of short-term/working memory functioning for people with aphasia. While the supportive evidence for treatment is growing and appears to highlight the benefits of including short-term/working memory in aphasia treatment, the quality of the evidence in its current state is poor. However, because of the clinical needs of people with aphasia and the prevalence of short-term/working memory impairments, incorporating related treatments through practice-based evidence is advocated. © 2015 Royal College of Speech and Language Therapists.

Sleep deprivation during a specific 3-hour time window post-training impairs hippocampal synaptic plasticity and memory

PubMed Central

Prince, Toni-Moi; Wimmer, Mathieu; Choi, Jennifer; Havekes, Robbert; Aton, Sara; Abel, Ted

2014-01-01

Sleep deprivation disrupts hippocampal function and plasticity. In particular, long-term memory consolidation is impaired by sleep deprivation, suggesting that a specific critical period exists following learning during which sleep is necessary. To elucidate the impact of sleep deprivation on long-term memory consolidation and synaptic plasticity, long-term memory was assessed when mice were sleep deprived following training in the hippocampus-dependent object place recognition task. We found that 3 hours of sleep deprivation significantly impaired memory when deprivation began 1 hour after training. In contrast, 3 hours of deprivation beginning immediately post-training did not impair spatial memory. Furthermore, a 3-hour sleep deprivation beginning 1 hour after training impaired hippocampal long-term potentiation (LTP), whereas sleep deprivation immediately after training did not affect LTP. Together, our findings define a specific 3-hour critical period, extending from 1 to 4 hours after training, during which sleep deprivation impairs hippocampal function. PMID:24380868

Medial prefrontal functional connectivity--relation to memory self-appraisal accuracy in older adults with and without memory disorders.

PubMed

Ries, Michele L; McLaren, Donald G; Bendlin, Barbara B; Guofanxu; Rowley, Howard A; Birn, Rasmus; Kastman, Erik K; Sager, Mark A; Asthana, Sanjay; Johnson, Sterling C

2012-04-01

It is tentatively estimated that 25% of people with early Alzheimer's disease (AD) show impaired awareness of disease-related changes in their own cognition. Research examining both normative self-awareness and altered awareness resulting from brain disease or injury points to the central role of the medial prefrontal cortex (MPFC) in generating accurate self-appraisals. The current project builds on this work - examining changes in MPFC functional connectivity that correspond to impaired self-appraisal accuracy early in the AD time course. Our behavioral focus was self-appraisal accuracy for everyday memory function, and this was measured using the Memory Function Scale of the Memory Awareness Rating Scale - an instrument psychometrically validated for this purpose. Using regression analysis of data from people with healthy memory (n=12) and people with impaired memory due to amnestic mild cognitive impairment or early AD (n=12), we tested the hypothesis that altered MPFC functional connectivity - particularly with other cortical midline structures and dorsolateral prefrontal cortex - explains variation in memory self-appraisal accuracy. We spatially constrained (i.e., explicitly masked) our regression analyses to those regions that work in conjunction with the MPFC to evoke self-appraisals in a normative group. This empirically derived explicit mask was generated from the result of a psychophysiological interaction analysis of fMRI self-appraisal task data in a separate, large group of cognitively healthy individuals. Results of our primary analysis (i.e., the regression of memory self-appraisal accuracy on MPFC functional connectivity) were generally consistent with our hypothesis: people who were less accurate in making memory self-appraisals showed attenuated functional connectivity between the MPFC seed region and proximal areas within the MPFC (including subgenual anterior cingulate cortex), bilateral dorsolateral prefrontal cortex, bilateral caudate, and left posterior hippocampus. Contrary to our expectations, MPFC functional connectivity with the posterior cingulate was not significantly related to accuracy of memory self-appraisals. Results reported here corroborate findings of variable memory self-appraisal accuracy during the earliest emergence of AD symptoms and reveal alterations in MPFC functional connectivity that correspond to impaired memory self-appraisal. Copyright © 2012 Elsevier Ltd. All rights reserved.

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

ERIC Educational Resources Information Center

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

2006-01-01

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

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

PubMed

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

2013-08-01

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

Differential impairments underlying decision making in anorexia nervosa and bulimia nervosa: a cognitive modeling analysis.

PubMed

Chan, Trista Wai Sze; Ahn, Woo-Young; Bates, John E; Busemeyer, Jerome R; Guillaume, Sebastien; Redgrave, Graham W; Danner, Unna N; Courtet, Philippe

2014-03-01

This study examined the underlying processes of decision-making impairments in individuals with anorexia nervosa (AN) and bulimia nervosa (BN). We deconstructed their performance on the widely used decision task, the Iowa Gambling Task (IGT) into cognitive, motivational, and response processes using cognitive modeling analysis. We hypothesized that IGT performance would be characterized by impaired memory functions and heightened punishment sensitivity in AN, and by elevated sensitivity to reward as opposed to punishment in BN. We analyzed trial-by-trial data of IGT obtained from 224 individuals: 94 individuals with AN, 63 with BN, and 67 healthy comparison individuals (HC). The prospect valence learning model was used to assess cognitive, motivational, and response processes underlying IGT performance. Individuals with AN showed marginally impaired IGT performance compared to HC. Their performance was characterized by impairments in memory functions. Individuals with BN showed significantly impaired IGT performance compared to HC. They showed greater relative sensitivity to gains as opposed to losses than HC. Memory functions in AN were positively correlated with body mass index. This study identified differential impairments underlying IGT performance in AN and BN. Findings suggest that impaired decision making in AN might involve impaired memory functions. Impaired decision making in BN might involve altered reward and punishment sensitivity. Copyright © 2013 Wiley Periodicals, Inc.

The Influence of Fluid Intelligence, Executive Functions and Premorbid Intelligence on Memory in Frontal Patients.

PubMed

Chan, Edgar; MacPherson, Sarah E; Bozzali, Marco; Shallice, Tim; Cipolotti, Lisa

2018-01-01

Objective: It is commonly thought that memory deficits in frontal patients are a result of impairments in executive functions which impact upon storage and retrieval processes. Yet, few studies have specifically examined the relationship between memory performance and executive functions in frontal patients. Furthermore, the contribution of more general cognitive processes such as fluid intelligence and demographic factors such as age, education, and premorbid intelligence has not been considered. Method: Our study examined the relationship between recall and recognition memory and performance on measures of fluid intelligence, executive functions and premorbid intelligence in 39 frontal patients and 46 healthy controls. Results: Recall memory impairments in frontal patients were strongly correlated with fluid intelligence, executive functions and premorbid intelligence. These factors were all found to be independent predictors of recall performance, with fluid intelligence being the strongest predictor. In contrast, recognition memory impairments were not related to any of these factors. Furthermore, age and education were not significantly correlated with either recall or recognition memory measures. Conclusion: Our findings show that recall memory in frontal patients was related to fluid intelligence, executive functions and premorbid intelligence. In contrast, recognition memory was not. These findings suggest that recall and recognition memory deficits following frontal injury arise from separable cognitive factors. Recognition memory tests may be more useful when assessing memory functions in frontal patients.

The Influence of Fluid Intelligence, Executive Functions and Premorbid Intelligence on Memory in Frontal Patients

PubMed Central

Chan, Edgar; MacPherson, Sarah E.; Bozzali, Marco; Shallice, Tim; Cipolotti, Lisa

2018-01-01

Objective: It is commonly thought that memory deficits in frontal patients are a result of impairments in executive functions which impact upon storage and retrieval processes. Yet, few studies have specifically examined the relationship between memory performance and executive functions in frontal patients. Furthermore, the contribution of more general cognitive processes such as fluid intelligence and demographic factors such as age, education, and premorbid intelligence has not been considered. Method: Our study examined the relationship between recall and recognition memory and performance on measures of fluid intelligence, executive functions and premorbid intelligence in 39 frontal patients and 46 healthy controls. Results: Recall memory impairments in frontal patients were strongly correlated with fluid intelligence, executive functions and premorbid intelligence. These factors were all found to be independent predictors of recall performance, with fluid intelligence being the strongest predictor. In contrast, recognition memory impairments were not related to any of these factors. Furthermore, age and education were not significantly correlated with either recall or recognition memory measures. Conclusion: Our findings show that recall memory in frontal patients was related to fluid intelligence, executive functions and premorbid intelligence. In contrast, recognition memory was not. These findings suggest that recall and recognition memory deficits following frontal injury arise from separable cognitive factors. Recognition memory tests may be more useful when assessing memory functions in frontal patients. PMID:29937746

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

PubMed

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

2016-01-01

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

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

PubMed Central

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

2015-01-01

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

Working Memory, Long-Term Memory, and Medial Temporal Lobe Function

ERIC Educational Resources Information Center

Jeneson, Annette; Squire, Larry R.

2012-01-01

Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance…

Relationships between behavioral syndromes and cognitive domains in Alzheimer disease: the impact of mood and psychosis.

PubMed

Koppel, Jeremy; Goldberg, Terry E; Gordon, Marc L; Huey, Edward; Davies, Peter; Keehlisen, Linda; Huet, Sara; Christen, Erica; Greenwald, Blaine S

2012-11-01

Behavioral disturbances occur in nearly all Alzheimer disease (AD) patients together with an array of cognitive impairments. Prior investigations have failed to demonstrate specific associations between them, suggesting an independent, rather than shared, pathophysiology. The objective of this study was to reexamine this issue using an extensive cognitive battery together with a sensitive neurobehavioral and functional rating scale to correlate behavioral syndromes and cognitive domains across the spectrum of impairment in dementia. Cross-sectional study of comprehensive cognitive and behavioral ratings in subjects with AD and mild cognitive impairment. Memory disorders research center. Fifty subjects with AD and 26 subjects with mild cognitive impairment; and their caregivers. Cognitive rating scales administered included the Mini-Mental State Examination; the Modified Mini-Mental State Examination; the Boston Naming Test; the Benton Visual Retention Test; the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychology Assessment; the Controlled Oral Word Test; the Wechsler Memory Scale logical memory I and logical memory II task; the Wechsler Memory Scale-Revised digit span; the Wechsler Adult Intelligence Scale-Revised digit symbol task; and the Clock Drawing Task together with the Clinical Dementia Rating Scale and the Neuropsychiatric Inventory. Stepwise regression of cognitive domains with symptom domains revealed significant associations of mood with impaired executive function/speed of processing (Δr = 0.22); impaired working memory (Δr = 0.05); impaired visual memory (Δr = 0.07); and worsened Clinical Dementia Rating Scale (Δr = 0.08). Psychosis was significantly associated with impaired working memory (Δr = 0.13). Mood symptoms appear to impact diverse cognitive realms and to compromise functional performance. Among neuropsychological indices, the unique relationship between working memory and psychosis suggests a possible common underlying neurobiology. 2012 American Association for Geriatric Psychiatry

Memory Functioning and Mental Verbs Acquisition in Children with Specific Language Impairment

ERIC Educational Resources Information Center

Spanoudis, George C.; Natsopoulos, Demetrios

2011-01-01

Memory and language operate in synergy. Recent literature stresses the importance of memory functioning in interpreting language deficits. Two groups of 50 children each, ages 8-12 were studied. The first group included children with specific language impairment, while the participants in the second group were typically developing children. The…

Abnormal functional connectivity of hippocampus during episodic memory retrieval processing network in amnestic mild cognitive impairment.

PubMed

Bai, Feng; Zhang, Zhijun; Watson, David R; Yu, Hui; Shi, Yongmei; Yuan, Yonggui; Zang, Yufeng; Zhu, Chaozhe; Qian, Yun

2009-06-01

Functional connectivity magnetic resonance imaging technique has revealed the importance of distributed network structures in higher cognitive processes in the human brain. The hippocampus has a key role in a distributed network supporting memory encoding and retrieval. Hippocampal dysfunction is a recurrent finding in memory disorders of aging such as amnestic mild cognitive impairment (aMCI) in which learning- and memory-related cognitive abilities are the predominant impairment. The functional connectivity method provides a novel approach in our attempts to better understand the changes occurring in this structure in aMCI patients. Functional connectivity analysis was used to examine episodic memory retrieval networks in vivo in twenty 28 aMCI patients and 23 well-matched control subjects, specifically between the hippocampal structures and other brain regions. Compared with control subjects, aMCI patients showed significantly lower hippocampus functional connectivity in a network involving prefrontal lobe, temporal lobe, parietal lobe, and cerebellum, and higher functional connectivity to more diffuse areas of the brain than normal aging control subjects. In addition, those regions associated with increased functional connectivity with the hippocampus demonstrated a significantly negative correlation to episodic memory performance. aMCI patients displayed altered patterns of functional connectivity during memory retrieval. The degree of this disturbance appears to be related to level of impairment of processes involved in memory function. Because aMCI is a putative prodromal syndrome to Alzheimer's disease (AD), these early changes in functional connectivity involving the hippocampus may yield important new data to predict whether a patient will eventually develop AD.

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

PubMed

Celone, Kim A; Calhoun, Vince D; Dickerson, Bradford C; Atri, Alireza; Chua, Elizabeth F; Miller, Saul L; DePeau, Kristina; Rentz, Doreen M; Selkoe, Dennis J; Blacker, Deborah; Albert, Marilyn S; Sperling, Reisa A

2006-10-04

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

Executive Functions Are Employed to Process Episodic and Relational Memories in Children With Autism Spectrum Disorders

PubMed Central

2013-01-01

Objective: Long-term memory functioning in autism spectrum disorders (ASDs) is marked by a characteristic pattern of impairments and strengths. Individuals with ASD show impairment in memory tasks that require the processing of relational and contextual information, but spared performance on tasks requiring more item-based, acontextual processing. Two experiments investigated the cognitive mechanisms underlying this memory profile. Method: A sample of 14 children with a diagnosis of high-functioning ASD (age: M = 12.2 years), and a matched control group of 14 typically developing (TD) children (age: M = 12.1 years), participated in a range of behavioral memory tasks in which we measured both relational and item-based memory abilities. They also completed a battery of executive function measures. Results: The ASD group showed specific deficits in relational memory, but spared or superior performance in item-based memory, across all tasks. Importantly, for ASD children, executive ability was significantly correlated with relational memory but not with item-based memory. No such relationship was present in the control group. This suggests that children with ASD atypically employed effortful, executive strategies to retrieve relational (but not item-specific) information, whereas TD children appeared to use more automatic processes. Conclusions: The relational memory impairment in ASD may result from a specific impairment in automatic associative retrieval processes with an increased reliance on effortful and strategic retrieval processes. Our findings allow specific neural predictions to be made regarding the interactive functioning of the hippocampus, prefrontal cortex, and posterior parietal cortex in ASD as a neural network supporting relational memory processing. PMID:24245930

Memory deficits in amyotrophic lateral sclerosis are not exclusively caused by executive dysfunction: a comparative neuropsychological study of amnestic mild cognitive impairment.

PubMed

Machts, Judith; Bittner, Verena; Kasper, Elisabeth; Schuster, Christina; Prudlo, Johannes; Abdulla, Susanne; Kollewe, Katja; Petri, Susanne; Dengler, Reinhard; Heinze, Hans-Jochen; Vielhaber, Stefan; Schoenfeld, Mircea A; Bittner, Daniel M

2014-06-30

Recent work suggests that ALS and frontotemporal dementia can occur together and share at least in part the same underlying pathophysiology. However, it is unclear at present whether memory deficits in ALS stem from a temporal lobe dysfunction, or are rather driven by frontal executive dysfunction. In this study we sought to investigate the nature of memory deficits by analyzing the neuropsychological performance of 40 ALS patients in comparison to 39 amnestic mild cognitive impairment (aMCI) patients and 40 healthy controls (HC). The neuropsychological battery tested for impairment in executive functions, as well as memory and visuo-spatial skills, the results of which were compared across study groups. In addition, we calculated composite scores for memory (learning, recall, recognition) and executive functions (verbal fluency, cognitive flexibility, working memory). We hypothesized that the nature of memory impairment in ALS will be different from those exhibited by aMCI patients. Patient groups exhibited significant differences in their type of memory deficit, with the ALS group showing impairment only in recognition, whereas aMCI patients showed short and delayed recall performance deficits as well as reduced short-term capacity. Regression analysis revealed a significant impact of executive function on memory performance exclusively for the ALS group, accounting for one fifth of their memory performance. Interestingly, merging all sub scores into a single memory and an executive function score obscured these differences. The presented results indicate that the interpretation of neuropsychological scores needs to take the distinct cognitive profiles in ALS and aMCI into consideration. Importantly, the observed memory deficits in ALS were distinctly different from those observed in aMCI and can be explained only to some extent in the context of comorbid (coexisting) executive dysfunction. These findings highlight the qualitative differences in temporal lobe dysfunction between ALS and aMCI patients, and support temporal lobe dysfunction as a mechanism underlying the distinct cognitive impairments observed in ALS.

Executive functions deficit in mild cognitive impairment.

PubMed

Traykov, Latchezar; Raoux, Nadine; Latour, Florence; Gallo, Livia; Hanon, Olivier; Baudic, Sophie; Bayle, Catherine; Wenisch, Emilie; Remy, Philippe; Rigaud, Anne-Sophie

2007-12-01

To investigate whether patients diagnosed with amnestic mild cognitive impairment (MCI) have also impairment in attention/executive functions, and therefore to clarify whether all subcomponents of executive control are equally affected in MCI. MCI refers to the transitional state between normal aging and dementia. Amnestic MCI is characterized by impaired episodic memory, although subtle impairment of executive functions has been noted on neuropsychologic tests. We investigated 20 MCI patients and 20 normal controls using episodic memory, attention/executive functions, language, and praxis tests. MCI patients had significantly lower scores on all measures of the Free and Cued Selective Reminding Test (P<0.05 to 0.01) than controls. Furthermore, MCI had a greater number of perseverations (P<0.01) on Modified Card Sorting Test and the lowest performance on the Stroop Test (P<0.02). Our findings showed impairment in episodic memory performance in MCI as compared with that of controls. In addition, MCI patients had problems with response inhibition, switching, and cognitive flexibility, which encompass various aspects of executive functions. This suggests that MCI may be identified by using a more detailed procedure for the assessment of cognitive decline than the evaluation of memory alone.

The cognitive profile of occipital lobe epilepsy and the selective association of left temporal lobe hypometabolism with verbal memory impairment.

PubMed

Knopman, Alex A; Wong, Chong H; Stevenson, Richard J; Homewood, Judi; Mohamed, Armin; Somerville, Ernest; Eberl, Stefan; Wen, Lingfeng; Fulham, Michael; Bleasel, Andrew F

2014-08-01

We investigated the cognitive profile of structural occipital lobe epilepsy (OLE) and whether verbal memory impairment is selectively associated with left temporal lobe hypometabolism on [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET). Nine patients with OLE, ages 8-29 years, completed presurgical neuropsychological assessment. Composite measures were calculated for intelligence quotient (IQ), speed, attention, verbal memory, nonverbal memory, and executive functioning. In addition, the Wisconsin Card Sorting Test (WCST) was used as a specific measure of frontal lobe functioning. Presurgical FDG-PET was analyzed with statistical parametric mapping in 8 patients relative to 16 healthy volunteers. Mild impairments were evident for IQ, speed, attention, and executive functioning. Four patients demonstrated moderate or severe verbal memory impairment. Temporal lobe hypometabolism was found in seven of eight patients. Poorer verbal memory was associated with left temporal lobe hypometabolism (p = 0.002), which was stronger (p = 0.03 and p = 0.005, respectively) than the association of left temporal lobe hypometabolism with executive functioning or with performance on the WCST. OLE is associated with widespread cognitive comorbidity, suggesting cortical dysfunction beyond the occipital lobe. Verbal memory impairment is selectively associated with left temporal lobe hypometabolism in OLE, supporting a link between neuropsychological dysfunction and remote hypometabolism in focal epilepsy. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

Are there reliable changes in memory and executive functions after cognitive behavioural therapy in patients with obsessive-compulsive disorder?

PubMed

Vandborg, Sanne Kjær; Hartmann, Tue Borst; Bennedsen, Birgit Egedal; Pedersen, Anders Degn; Thomsen, Per Hove

2015-01-01

Patients with obsessive-compulsive disorder (OCD) have impaired memory and executive functions, but it is unclear whether these functions improve after cognitive behavioural therapy (CBT) of OCD symptoms. The primary aim of this study was to investigate whether memory and executive functions change after CBT in patients with OCD. We assessed 39 patients with OCD before and after CBT with neuropsychological tests of memory and executive functions. To correct for practice effects, 39 healthy controls (HCs) were assessed at two parallel time intervals with the neuropsychological tests. There were no changes in memory and executive functions after CBT in patients with OCD when results were corrected for practice effects. Patients performed worse on a test of visuospatial memory and organisational skills (Rey complex figure test [RCFT]) compared to HCs both before and after CBT (ps = .002-.036). The finding of persistent poor RCFT performances indicates that patients with OCD have impaired visuospatial memory and organisational skills that may be trait-related rather than state-dependent. These impairments may need to be considered in treatment. Our findings underline the importance of correcting for practice effects when investigating changes in cognitive functions.

Working Memory and Executive Function Profiles of Individuals with Borderline Intellectual Functioning

ERIC Educational Resources Information Center

Alloway, T. P.

2010-01-01

Background: The aim of the present study was to investigate the following issues: (1) Do students with borderline intellectual functioning have a pervasive pattern of impaired working memory skills across both verbal and visuo-spatial domains? (2) Is there evidence for impairment in executive function skills, and which tasks indicate greater…

Cognitive consequences of cannabis use: comparison with abuse of stimulants and heroin with regard to attention, memory and executive functions.

PubMed

Lundqvist, Thomas

2005-06-01

This review aims to compare cognitive consequence between cannabis, and stimulants and heroin with regards to attention, memory and executive functions. The available studies using brain imaging techniques and neuropsychological tests show that acutely, all drugs create a disharmony in the neuropsychological network, causing a decrease of activity in areas responsible for short-term memory and attention, with the possible exception of heroin. Cannabis induces loss of internal control and cognitive impairment, especially of attention and memory, for the duration of intoxication. Heavy cannabis use is associated with reduced function of the attentional/executive system, as exhibited by decreased mental flexibility, increased perserveration, and reduced learning, to shift and/or sustain attention. Recent investigations on amphetamine/methamphetamine have documented deficits in learning, delayed recall, processing speed, and working memory. MDMA users exhibit difficulties in coding information into long-term memory, display impaired verbal learning, are more easily distracted, and are less efficient at focusing attention on complex tasks. The degree of executive impairment increases with the severity of use, and the impairments are relatively lasting over time. Chronic cocaine users display impaired attention, learning, memory, reaction time and cognitive flexibility. Heroin addiction may have a negative effect on impulse control, and selective processing.

Temporal context memory in high-functioning autism.

PubMed

Gras-Vincendon, Agnès; Mottron, Laurent; Salamé, Pierre; Bursztejn, Claude; Danion, Jean-Marie

2007-11-01

Episodic memory, i.e. memory for specific episodes situated in space and time, seems impaired in individuals with autism. According to weak central coherence theory, individuals with autism have general difficulty connecting contextual and item information which then impairs their capacity to memorize information in context. This study investigated temporal context memory for visual information in individuals with autism. Eighteen adolescents and adults with high-functioning autism (HFA) or Asperger syndrome (AS) and age- and IQ-matched typically developing participants were tested using a recency judgement task. The performance of the autistic group did not differ from that of the control group, nor did the performance between the AS and HFA groups. We conclude that autism in high-functioning individuals does not impair temporal context memory as assessed on this task. We suggest that individuals with autism are as efficient on this task as typically developing subjects because contextual memory performance here involves more automatic than organizational processing.

Rethinking the Connection between Working Memory and Language Impairment

ERIC Educational Resources Information Center

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

2016-01-01

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

The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function.

PubMed

Nasehi, Mohammad; Alaghmandan-Motlagh, Niyousha; Ebrahimi-Ghiri, Mohaddeseh; Nami, Mohammad; Zarrindast, Mohammad-Reza

2017-10-01

Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.

Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment.

PubMed

Seo, Eun Hyun; Choo, I L Han

2016-06-01

Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer's disease (AD), i.e., aMCI with low beta-amyloid (Aβ) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aβ burden negative (aMCI-Aβ-) and to compare these results with aMCI with Aβ burden positive (aMCI-Aβ+). Individuals with aMCI (n = 498) were selected from the Alzheimer's Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aβ- or aMCI-Aβ+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model. For aMCI-Aβ-, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aβ+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate Our findings indicate that memory impairment in aMCI-Aβ- is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aβ+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aβ burden level.

Cognitive Behavioral Performance of Untreated Depressed Patients with Mild Depressive Symptoms

PubMed Central

Li, Mi; Zhong, Ning; Lu, Shengfu; Wang, Gang; Feng, Lei; Hu, Bin

2016-01-01

This study evaluated the working memory performance of 18 patients experiencing their first onset of mild depression without treatment and 18 healthy matched controls. The results demonstrated that working memory impairment in patients with mild depression occurred when memorizing the position of a picture but not when memorizing the pictures themselves. There was no significant difference between the two groups in the emotional impact on the working memory, indicating that the attenuation of spatial working memory was not affected by negative emotion; however, cognitive control selectively affected spatial working memory. In addition, the accuracy of spatial working memory in the depressed patients was not significantly reduced, but the reaction time was significantly extended compared with the healthy controls. This finding indicated that there was no damage to memory encoding and function maintenance in the patients but rather only impaired memory retrieval, suggesting that the extent of damage to the working memory system and cognitive control abilities was associated with the corresponding depressive symptoms. The development of mild to severe depressive symptoms may be accompanied by spatial working memory damage from the impaired memory retrieval function extending to memory encoding and memory retention impairments. In addition, the impaired cognitive control began with an inadequate capacity to automatically process internal negative emotions and further extended to impairment of the ability to regulate and suppress external emotions. The results of the mood-congruent study showed that the memory of patients with mild symptoms of depression was associated with a mood-congruent memory effect, demonstrating that mood-congruent memory was a typical feature of depression, regardless of the severity of depression. This study provided important information for understanding the development of cognitive dysfunction. PMID:26730597

Episodic and working memory deficits in alcoholic Korsakoff patients: the continuity theory revisited.

PubMed

Pitel, Anne Lise; Beaunieux, Hélène; Witkowski, Thomas; Vabret, François; de la Sayette, Vincent; Viader, Fausto; Desgranges, Béatrice; Eustache, Francis

2008-07-01

The exact nature of episodic and working memory impairments in alcoholic Korsakoff patients (KS) remains unclear, as does the specificity of these neuropsychological deficits compared with those of non-Korsakoff alcoholics (AL). The goals of the present study were therefore to (1) specify the nature of episodic and working memory impairments in KS, (2) determine the specificity of the KS neuropsychological profile compared with the AL profile, and (3) observe the distribution of individual performances within the 2 patient groups. We investigated episodic memory (encoding and retrieval abilities, contextual memory and state of consciousness associated with memories), the slave systems of working memory (phonological loop, visuospatial sketchpad and episodic buffer) and executive functions (inhibition, flexibility, updating and integration abilities) in 14 strictly selected KS, 40 AL and 55 control subjects (CS). Compared with CS, KS displayed impairments of episodic memory encoding and retrieval, contextual memory, recollection, the slave systems of working memory and executive functions. Although episodic memory was more severely impaired in KS than in AL, the single specificity of the KS profile was a disproportionately large encoding deficit. Apart from organizational and updating abilities, the slave systems of working memory and inhibition, flexibility and integration abilities were impaired to the same extent in both alcoholic groups. However, some KS were unable to complete the most difficult executive tasks. There was only a partial overlap of individual performances by KS and AL for episodic memory and a total mixture of the 2 groups for working memory. Korsakoff's syndrome encompasses impairments of the different episodic and working memory components. AL and KS displayed similar profiles of episodic and working memory deficits, in accordance with neuroimaging investigations showing similar patterns of brain damage in both alcoholic groups.

Rubus coreanus Miquel ameliorates scopolamine-induced memory impairments in ICR mice.

PubMed

Choi, Mi-Ran; Lee, Min Young; Hong, Ji Eun; Kim, Jeong Eun; Lee, Jae-Yong; Kim, Tae Hwan; Chun, Jang Woo; Shin, Hyun Kyung; Kim, Eun Ji

2014-10-01

The present study investigated the effect of Rubus coreanus Miquel (RCM) on scopolamine-induced memory impairments in ICR mice. Mice were orally administrated RCM for 4 weeks and scopolamine was intraperitoneally injected into mice to induce memory impairment. RCM improved the scopolamine-induced memory impairment in mice. The increase of acetylcholinesterase activity caused by scopolamine was significantly attenuated by RCM treatment. RCM increased the levels of acetylcholine in the brain and serum of mice. The expression of choline acetyltransferase, phospho-cyclic AMP response element-binding protein, and phospho-extracellular signal-regulated kinase was significantly increased within the brain of mice treated with RCM. The brain antioxidant enzyme activity decreased by scopolamine was increased by RCM. These results demonstrate that RCM exerts a memory-enhancing effect via the improvement of cholinergic function and the potentiated antioxidant activity in memory-impaired mice. The results suggest that RCM may be a useful agent for improving memory impairment.

Differentiating between Alzheimer's Disease and Vascular Cognitive Impairment: Is the "Memory Versus Executive Function" Contrast Still Relevant?

PubMed

Andriuta, Daniela; Roussel, Martine; Barbay, Mélanie; Despretz-Wannepain, Sandrine; Godefroy, Olivier

2018-01-01

The contrast between memory versus executive function impairments is commonly used to differentiate between neurocognitive disorders (NCDs) due to Alzheimer's disease (AD) and vascular cognitive impairment (VCI). We reconsidered this question because of the current use of AD biomarkers and the recent revision of the criteria for AD, VCI, and dysexecutive syndrome. To establish and compare the neuropsychological profiles in AD (i.e., with positive CSF biomarkers) and in VCI. We included 62 patients with mild or major NCDs due to pure AD (with positive CSF biomarker assays), and 174 patients (from the GRECogVASC cohort) with pure VCI. The neuropsychological profiles were compared after stratification for disease severity (mild or major NCD). We defined a memory-executive function index (the mean z score for the third free recall and the delayed free recall in the Free and Cued Selective Reminding Test minus the mean z score for category fluency and the completion time in the Trail Making Test part B) and determined its diagnostic accuracy. Compared with VCI patients, patients with AD had significantly greater memory impairments (p = 0.001). Executive function was impaired to a similar extent in the two groups (p = 0.11). Behavioral executive disorders were more prominent in the AD group (p = 0.001). Although the two groups differed significant with regard to the memory-executive function index (p < 0.001), the latter's diagnostic accuracy was only moderate (sensitivity: 63%, specificity: 87%). Although the contrast between memory and executive function impairments was supported at the group level it does not reliably discriminate between AD and VCI at the individual level.

RBANS memory percentage retention: No evidence of incremental validity beyond RBANS scores for diagnostic classification of mild cognitive impairment and dementia and for prediction of daily function.

PubMed

Jodouin, Kara A; O'Connell, Megan E; Morgan, Debra G

2017-01-01

RBANS percentage retention scores may be useful for diagnosis, but their incremental validity is unclear. Percentage retention versus RBANS immediate and delayed memory subtests and delayed index scores were compared for diagnostic classification and for prediction of function. Data from 173 memory clinic patients with an interdisciplinary diagnosis (no cognitive impairment, amnestic mild cognitive impairment [aMCI], and dementia due to Alzheimer's disease [AD]) and complete RBANS data were analyzed. Across diagnostic contrasts, list percentage retention classification accuracy was similar to List Learning delayed recall, but below the Delayed Memory Index (DMI). Similarly, for classifying no cognitive impairment versus aMCI or dementia due to AD, story percentage retention was similar to Story Memory subtests and below the DMI. For classifying aMCI versus AD; however, Story Memory exceeded the DMI, but was similar to Story Memory subtest scores. Similarly, for prediction of function percentage retention measures did not predict variance beyond that predicted by the RBANS subtest or index scores. In sum, there is no evidence that calculation of percentage retention for RBANS adds clinical utility beyond those provided by the standard RBANS scores.

Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release

PubMed Central

Gupta, Varun K.; Pech, Ulrike; Fulterer, Andreas; Ender, Anatoli; Mauermann, Stephan F.; Andlauer, Till F. M.; Beuschel, Christine; Thriene, Kerstin; Quentin, Christine; Schwärzel, Martin; Mielke, Thorsten; Madeo, Frank; Dengjel, Joern; Fiala, André; Sigrist, Stephan J.

2016-01-01

Memories are assumed to be formed by sets of synapses changing their structural or functional performance. The efficacy of forming new memories declines with advancing age, but the synaptic changes underlying age-induced memory impairment remain poorly understood. Recently, we found spermidine feeding to specifically suppress age-dependent impairments in forming olfactory memories, providing a mean to search for synaptic changes involved in age-dependent memory impairment. Here, we show that a specific synaptic compartment, the presynaptic active zone (AZ), increases the size of its ultrastructural elaboration and releases significantly more synaptic vesicles with advancing age. These age-induced AZ changes, however, were fully suppressed by spermidine feeding. A genetically enforced enlargement of AZ scaffolds (four gene-copies of BRP) impaired memory formation in young animals. Thus, in the Drosophila nervous system, aging AZs seem to steer towards the upper limit of their operational range, limiting synaptic plasticity and contributing to impairment of memory formation. Spermidine feeding suppresses age-dependent memory impairment by counteracting these age-dependent changes directly at the synapse. PMID:27684064

Wearable Cameras Are Useful Tools to Investigate and Remediate Autobiographical Memory Impairment: A Systematic PRISMA Review.

PubMed

Allé, Mélissa C; Manning, Liliann; Potheegadoo, Jevita; Coutelle, Romain; Danion, Jean-Marie; Berna, Fabrice

2017-03-01

Autobiographical memory, central in human cognition and every day functioning, enables past experienced events to be remembered. A variety of disorders affecting autobiographical memory are characterized by the difficulty of retrieving specific detailed memories of past personal events. Owing to the impact of autobiographical memory impairment on patients' daily life, it is necessary to better understand these deficits and develop relevant methods to improve autobiographical memory. The primary objective of the present systematic PRISMA review was to give an overview of the first empirical evidence of the potential of wearable cameras in autobiographical memory investigation in remediating autobiographical memory impairments. The peer-reviewed literature published since 2004 on the usefulness of wearable cameras in research protocols was explored in 3 databases (PUBMED, PsycINFO, and Google Scholar). Twenty-eight published studies that used a protocol involving wearable camera, either to explore wearable camera functioning and impact on daily life, or to investigate autobiographical memory processing or remediate autobiographical memory impairment, were included. This review analyzed the potential of wearable cameras for 1) investigating autobiographical memory processes in healthy volunteers without memory impairment and in clinical populations, and 2) remediating autobiographical memory in patients with various kinds of memory disorder. Mechanisms to account for the efficacy of wearable cameras are also discussed. The review concludes by discussing certain limitations inherent to using cameras, and new research perspectives. Finally, ethical issues raised by this new technology are considered.

A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.

PubMed

Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John; Chiaravalloti, Nancy D

2014-09-01

Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.

Cognitive functioning in dyskinetic cerebral palsy: Its relation to motor function, communication and epilepsy.

PubMed

Ballester-Plané, Júlia; Laporta-Hoyos, Olga; Macaya, Alfons; Póo, Pilar; Meléndez-Plumed, Mar; Toro-Tamargo, Esther; Gimeno, Francisca; Narberhaus, Ana; Segarra, Dolors; Pueyo, Roser

2018-01-01

Cerebral palsy (CP) is a disorder of motor function often accompanied by cognitive impairment. There is a paucity of research focused on cognition in dyskinetic CP and on the potential effect of related factors. To describe the cognitive profile in dyskinetic CP and to assess its relationship with motor function and associated impairments. Fifty-two subjects with dyskinetic CP (28 males, mean age 24 y 10 mo, SD 13 y) and 52 typically-developing controls (age- and gender-matched) completed a comprehensive neuropsychological assessment. Gross Motor Function Classification System (GMFCS), Communication Function Classification System (CFCS) and epilepsy were recorded. Cognitive performance was compared between control and CP groups, also according different levels of GMFCS. The relationship between cognition, CFCS and epilepsy was examined through partial correlation coefficients, controlling for GMFCS. Dyskinetic CP participants performed worse than controls on all cognitive functions except for verbal memory. Milder cases (GMFCS I) only showed impairment in attention, visuoperception and visual memory. Participants with GMFCS II-III also showed impairment in language-related functions. Severe cases (GMFCS IV-V) showed impairment in intelligence and all specific cognitive functions but verbal memory. CFCS was associated with performance in receptive language functions. Epilepsy was related to performance in intelligence, visuospatial abilities, visual memory, grammar comprehension and learning. Cognitive performance in dyskinetic CP varies with the different levels of motor impairment, with more cognitive functions impaired as motor severity increases. This study also demonstrates the relationship between communication and epilepsy and cognitive functioning, even controlling for the effect of motor severity. Copyright © 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Oral administration of grape seed polyphenol extract restores memory deficits in chronic cerebral hypoperfusion rats.

PubMed

Chen, Chen; Zheng, Yake; Wu, Tianwen; Wu, Chuanjie; Cheng, Xuan

2017-04-01

Chronic cerebral hypoperfusion (CCH) has been recognized as an important cause of both vascular dementia and Alzheimer's disease (AD), the two most prominent neurodegenerative diseases causing memory impairment in the elderly. However, an effective therapy for CCH-induced memory impairment has not yet been established. Grape seed polyphenol extract (GSPE) has powerful antioxidant properties and protects neurons and glia during ischemic injury, but its potential use in the prevention of CCH-induced memory impairment has not yet been investigated. Here, CCH-related memory impairment was modeled in rats using permanent bilateral occlusion of the common carotid artery. A Morris water maze task was used to evaluate memory, the levels of acetylcholinesterase, choline acetyltransferase, acetylcholine were used to evaluate cholinergic function, and oxidative stress was assessed by measuring the enzyme activity of superoxide dismutase, glutathione peroxidase, malonic dialdehyde, and catalase. We found that oral administration of GSPE for 1 month can rescue memory deficits. We also found that GSPE restores cholinergic neuronal function and represses oxidative damage in the hippocampus of CCH rats. We propose that GSPE protects memory in CCH rats by reducing ischemia-induced oxidative stress and cholinergic dysfunction. These findings provide a novel application of GSPE in CCH-related memory impairments.

Memory in autistic spectrum disorder.

PubMed

Boucher, Jill; Mayes, Andrew; Bigham, Sally

2012-05-01

Behavioral evidence concerning memory in forms of high-functioning autism (HFA) and in moderately low-functioning autism (M-LFA) is reviewed and compared. Findings on M-LFA are sparse. However, it is provisionally concluded that memory profiles in HFA and M-LFA (relative to ability-matched controls) are similar but that declarative memory impairments are more extensive in M-LFA than in HFA. Specifically, both groups have diminished memory for emotion- or person-related stimuli. Regarding memory for nonsocial stimuli, both groups probably have mental-age-appropriate nondeclarative memory, and within declarative memory, both groups have mental-age-appropriate immediate free recall of within-span or supraspan lists of unrelated items, as well as cued recall and paired associate learning. By contrast, recognition is largely unimpaired in HFA but moderately impaired in M-LFA, and free recall of meaningful or structured stimuli is moderately impaired in HFA but more severely impaired in M-LFA. Theoretical explanations of data on declarative memory in HFA identify problems in the integrative processing, or the consolidation and storage, of complex stimuli or a specific problem of recollection. Proposed neural substrates include the following: disconnectivity of primary sensory and association areas; dysfunctions of medial prefrontal cortex, hippocampus, or posterior parietal lobe; or combinations of these associated with neural disconnectivity. Hypothetically, perirhinal dysfunction might explain the more extensive declarative memory impairments in M-LFA. Foreseeable consequences of uneven memory abilities in HFA and M-LFA are outlined, including possible effects on language and learning in M-LFA. Finally, priorities for future research are identified, highlighting the urgent need for research on memory in lower functioning individuals. 2012 APA, all rights reserved

Profile of Executive and Memory Function Associated with Amphetamine and Opiate Dependence

PubMed Central

Ersche, Karen D; Clark, Luke; London, Mervyn; Robbins, Trevor W; Sahakian, Barbara J

2007-01-01

Cognitive function was assessed in chronic drug users on neurocognitive measures of executive and memory function. Current amphetamine users were contrasted with current opiate users, and these two groups were compared with former users of these substances (abstinent for at least one year). Four groups of participants were recruited: amphetamine-dependent individuals, opiate-dependent individuals, former users of amphetamines, and/or opiates and healthy non-drug taking controls. Participants were administered the Tower of London (TOL) planning task and the 3D-IDED attentional set-shifting task to assess executive function, and Paired Associates Learning and Delayed Pattern Recognition Memory tasks to assess visual memory function. The three groups of substance users showed significant impairments on TOL planning, Pattern Recognition Memory and Paired Associates Learning. Current amphetamine users displayed a greater degree of impairment than current opiate users. Consistent with previous research showing that healthy men are performing better on visuo-spatial tests than women, our male controls remembered significantly more paired associates than their female counterparts. This relationship was reversed in drug users. While performance of female drug users was normal, male drug users showed significant impairment compared to both their female counterparts and male controls. There was no difference in performance between current and former drug users. Neither years of drug abuse nor years of drug abstinence were associated with performance. Chronic drug users display pronounced neuropsychological impairment in the domains of executive and memory function. Impairment persists after several years of drug abstinence and may reflect neuropathology in frontal and temporal cortices. PMID:16160707

Memory and functional brain differences in a national sample of U.S. veterans with Gulf War Illness.

PubMed

Cooper, Crystal M; Briggs, Richard W; Farris, Emily A; Bartlett, James; Haley, Robert W; Odegard, Timothy N

2016-04-30

Roughly 26-32% of U. S. veterans who served in the 1991 Persian Gulf War report suffering from chronic health problems. Memory complaints are regularly reported by ill Gulf War veterans (GWV), but limited data verify their complaints. This study investigated episodic memory and brain function in a nationally representative sample of GWV, using a face-name memory task and functional magnetic resonance imaging during encoding. A syndrome classification system was used to subdivide ill GWV into the three major Gulf War Illness syndrome types, "impaired cognition" (GWV-1), "confusion ataxia" (GWV-2), and "central pain" (GWV-3). Memory and brain function of ill GWV were contrasted to deployed and nondeployed well GWV controls (GWV-C). Ill GWV exhibited impaired memory function relative to GWV-C but the patterns of functional brain differences varied. Brain activation differentiated the GWV-C from the ill GWV. The different syndrome types also differed from one another in several brain regions. Additionally, the current study was the first to observe differences in brain function between deployed and nondeployed GWV-C. These results provide (1) evidence of memory impairment in ill GWV and differentiate the syndrome types at a functional neurobiological level, and (2) the role of deployment in the war on brain function. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Memory functioning and mental verbs acquisition in children with specific language impairment.

PubMed

Spanoudis, George C; Natsopoulos, Demetrios

2011-01-01

Memory and language operate in synergy. Recent literature stresses the importance of memory functioning in interpreting language deficits. Two groups of 50 children each, ages 8-12 were studied. The first group included children with specific language impairment, while the participants in the second group were typically developing children. The two groups, which were matched on age, nonverbal intelligence and varied significantly in verbal ability were examined, using a test battery of four memory functioning (phonological, working and long-term memory) and five mental verb measures. The statistical analyses indicated that the two groups differed significantly in all language and memory measures; a logistic regression analysis revealed that within each main group existed nested subgroups of different developmental patterns with working and long-term memory measures as the most robust discriminate markers of classification. Language impaired children had more difficulties in the acquisition of mental verbs because they are less able to process and store phonological information in working memory and long-term lexicon. Copyright © 2011 Elsevier Ltd. All rights reserved.

More than Memory Impairment in Voltage-Gated Potassium Channel Complex Encephalopathy

PubMed Central

Bettcher, Brianne M.; Gelfand, Jeffrey M.; Irani, Sarosh R.; Neuhaus, John; Forner, Sven; Hess, Christopher P.; Geschwind, Michael D.

2014-01-01

Objective Autoimmune encephalopathies (AE) are a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly endorsed, few reports of AE inclusively assess all cognitive domains in detail. Our aim was to perform an unbiased cognitive evaluation of AE patients with voltage-gated potassium channel complex antibodies (VGKCC-Abs) in order to delineate cognitive strengths and weaknesses. Methods We assessed serial VGKCC-Abs AE subjects (n=12) with a comprehensive evaluation of memory, executive functions, visuospatial skills, and language. Clinical MRI (n=10/12) was evaluated. Five subjects had serial cognitive testing available, permitting descriptive analysis of change. Results Subjects demonstrated mild to moderate impairment in memory (mean Z=−1.9) and executive functions (mean Z=−1.5), with variable impairments in language and sparing of visuospatial skills. MRI findings showed T2 hyperintensities in medial temporal lobe (10/10) and basal ganglia (2/10). Serial cognitive examination revealed heterogeneity in cognitive function; whereas most patients improved in one or more domains, residual impairments were observed in some patients. Conclusions This study augments prior neuropsychological analyses in VGKCC-Ab AE by identifying not only memory and executive function deficits, but also language impairments, with preservation of visuospatial functioning. This study further highlights the importance of domain-specific testing to parse out the complex cognitive phenotypes of VGKCC-Ab AE. PMID:24981998

Evaluation of Memory Impairment in Aging Adult Survivors of Childhood Acute Lymphoblastic Leukemia Treated With Cranial Radiotherapy

PubMed Central

2013-01-01

Background Cranial radiotherapy (CRT) is a known risk factor for neurocognitive impairment in survivors of childhood cancer and may increase risk for mild cognitive impairment and dementia in adulthood. Methods We performed a cross-sectional evaluation of survivors of childhood acute lymphoblastic leukemia (ALL) treated with 18 Gy (n = 127) or 24 Gy (n = 138) CRT. Impairment (age-adjusted score >1 standard deviation below expected mean, two-sided exact binomial test) on the Wechsler Memory Scale IV (WMS-IV) was measured. A subset of survivors (n = 85) completed structural and functional neuroimaging. Results Survivors who received 24 Gy, but not 18 Gy, CRT had impairment in immediate (impairment rate = 33.8%, 95% confidence interval [CI] = 25.9% to 42.4%; P < .001) and delayed memory (impairment rate = 30.2%, 95% CI = 22.6% to 38.6%; P < .001). The mean score for long-term narrative memory among survivors who received 24 Gy CRT was equivalent to that for individuals older than 69 years. Impaired immediate memory was associated with smaller right (P = .02) and left (P = .008) temporal lobe volumes, and impaired delayed memory was associated with thinner parietal and frontal cortices. Lower hippocampal volumes and increased functional magnetic resonance imaging activation were observed with memory impairment. Reduced cognitive status (Brief Cognitive Status Exam from the WMS-IV) was identified after 24 Gy (18.5%, 95% CI = 12.4% to 26.1%; P < .001), but not 18 Gy (8.7%, 95% CI = 4.4% to 15.0%; P = .11), CRT, suggesting a dose–response effect. Employment rates were equivalent (63.8% for 24 Gy CRT and 63.0% for 18 Gy CRT). Conclusions Adult survivors who received 24 Gy CRT had reduced cognitive status and memory, with reduced integrity in neuroanatomical regions essential in memory formation, consistent with early onset mild cognitive impairment. PMID:23584394

A compensatory role for declarative memory in neurodevelopmental disorders.

PubMed

Ullman, Michael T; Pullman, Mariel Y

2015-04-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional in these disorders, and because it can learn and retain numerous types of information, functions, and tasks, this system should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

A compensatory role for declarative memory in neurodevelopmental disorders

PubMed Central

Ullman, Michael T.; Pullman, Mariel Y.

2015-01-01

Most research on neurodevelopmental disorders has focused on their abnormalities. However, what remains intact may also be important. Increasing evidence suggests that declarative memory, a critical learning and memory system in the brain, remains largely functional in a number of neurodevelopmental disorders. Because declarative memory remains functional, and because this system can learn and retain numerous types of information, functions, and tasks, it should be able to play compensatory roles for multiple types of impairments across the disorders. Here, we examine this hypothesis for specific language impairment, dyslexia, autism spectrum disorder, Tourette syndrome, and obsessive-compulsive disorder. We lay out specific predictions for the hypothesis and review existing behavioral, electrophysiological, and neuroimaging evidence. Overall, the evidence suggests that declarative memory indeed plays compensatory roles for a range of impairments across all five disorders. Finally, we discuss diagnostic, therapeutic and other implications. PMID:25597655

Sleep disturbance induces neuroinflammation and impairment of learning and memory.

PubMed

Zhu, Biao; Dong, Yuanlin; Xu, Zhipeng; Gompf, Heinrich S; Ward, Sarah A P; Xue, Zhanggang; Miao, Changhong; Zhang, Yiying; Chamberlin, Nancy L; Xie, Zhongcong

2012-12-01

Hospitalized patients can develop cognitive function decline, the mechanisms of which remain largely to be determined. Sleep disturbance often occurs in hospitalized patients, and neuroinflammation can induce learning and memory impairment. We therefore set out to determine whether sleep disturbance can induce neuroinflammation and impairment of learning and memory in rodents. Five to 6-month-old wild-type C57BL/6J male mice were used in the studies. The mice were placed in rocking cages for 24 h, and two rolling balls were present in each cage. The mice were tested for learning and memory function using the Fear Conditioning Test one and 7 days post-sleep disturbance. Neuroinflammation in the mouse brain tissues was also determined. Of the Fear Conditioning studies at one day and 7 days after sleep disturbance, twenty-four hour sleep disturbance decreased freezing time in the context test, which assesses hippocampus-dependent learning and memory; but not the tone test, which assesses hippocampus-independent learning and memory. Sleep disturbance increased pro-inflammatory cytokine IL-6 levels and induced microglia activation in the mouse hippocampus, but not the cortex. These results suggest that sleep disturbance induces neuroinflammation in the mouse hippocampus, and impairs hippocampus-dependent learning and memory in mice. Pending further studies, these findings suggest that sleep disturbance-induced neuroinflammation and impairment of learning and memory may contribute to the development of cognitive function decline in hospitalized patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Changes in the Hippocampal Proteome Associated with Spatial Memory Impairment after Exposure to Low (20 cGy) Doses of 1 GeV/n 56Fe Radiation.

PubMed

Britten, Richard A; Jewell, Jessica S; Davis, Leslie K; Miller, Vania D; Hadley, Melissa M; Semmes, O John; Lonart, György; Dutta, Sucharita M

2017-03-01

Exposure to low (∼20 cGy) doses of high-energy charged (HZE) particles, such as 1 GeV/n 56 Fe, results in impaired hippocampal-dependent learning and memory (e.g., novel object recognition and spatial memory) in rodents. While these findings raise the possibility that astronauts on deep-space missions may develop cognitive deficits, not all rats develop HZE-induced cognitive impairments, even after exposure to high (200 cGy) HZE doses. The reasons for this differential sensitivity in some animals that develop HZE-induced cognitive failure remain speculative. We employed a robust quantitative mass spectrometry-based workflow, which links early-stage discovery to next-stage quantitative verification, to identify differentially active proteins/pathways in rats that developed spatial memory impairment at three months after exposure to 20 cGy of 1 GeV/n 56 Fe (20/impaired), and in those rats that managed to maintain normal cognitive performance (20/functional). Quantitative data were obtained on 665-828 hippocampal proteins in the various cohorts of rats studied, of which 580 were expressed in all groups. A total of 107 proteins were upregulated in the irradiated rats irrespective of their spatial memory performance status, which included proteins involved in oxidative damage response, calcium transport and signaling. Thirty percent (37/107) of these "radiation biomarkers" formed a functional interactome of the proteasome and the COP9 signalosome. These data suggest that there is persistent oxidative stress, ongoing autophagy and altered synaptic plasticity in the irradiated hippocampus, irrespective of the spatial memory performance status, suggesting that the ultimate phenotype may be determined by how well the hippocampal neurons compensate to the ongoing oxidative stress and associated side effects. There were 67 proteins with expression that correlated with impaired spatial memory performance. Several of the "impaired biomarkers" have been implicated in poor spatial memory performance, neurodegeneration, neuronal loss or neuronal susceptibility to apoptosis, or neuronal synaptic or structural plasticity. Therefore, in addition to the baseline oxidative stress and altered adenosine metabolism observed in all irradiated rats, the 20/impaired rats expressed proteins that led to poor spatial memory performance, enhanced neuronal loss and apoptosis, changes in synaptic plasticity and dendritic remodeling. A total of 46 proteins, which were differentially upregulated in the sham-irradiated and 20/functional rat cohorts, can thus be considered as markers of good spatial memory, while another 95 proteins are associated with the maintenance of good spatial memory in the 20/functional rats. The loss or downregulation of these "good spatial memory" proteins would most likely exacerbate the situation in the 20/impaired rats, having a major impact on their neurocognitive status, given that many of those proteins play an important role in neuronal homeostasis and function. Our large-scale comprehensive proteomic analysis has provided some insight into the processes that are altered after exposure, and the collective data suggests that there are multiple problems with the functionality of the neurons and astrocytes in the irradiated hippocampi, which appear to be further exacerbated in the rats that have impaired spatial memory performance or partially compensated for in the rats with good spatial memory.

Aerobic exercise increases hippocampal volume and improves memory in multiple sclerosis: preliminary findings.

PubMed

Leavitt, V M; Cirnigliaro, C; Cohen, A; Farag, A; Brooks, M; Wecht, J M; Wylie, G R; Chiaravalloti, N D; DeLuca, J; Sumowski, J F

2014-01-01

Multiple sclerosis leads to prominent hippocampal atrophy, which is linked to memory deficits. Indeed, 50% of multiple sclerosis patients suffer memory impairment, with negative consequences for quality of life. There are currently no effective memory treatments for multiple sclerosis either pharmacological or behavioral. Aerobic exercise improves memory and promotes hippocampal neurogenesis in nonhuman animals. Here, we investigate the benefits of aerobic exercise in memory-impaired multiple sclerosis patients. Pilot data were collected from two ambulatory, memory-impaired multiple sclerosis participants randomized to non-aerobic (stretching) and aerobic (stationary cycling) conditions. The following baseline/follow-up measurements were taken: high-resolution MRI (neuroanatomical volumes), fMRI (functional connectivity), and memory assessment. Intervention was 30-minute sessions 3 times per week for 3 months. Aerobic exercise resulted in 16.5% increase in hippocampal volume and 53.7% increase in memory, as well as increased hippocampal resting-state functional connectivity. Improvements were specific, with no comparable changes in overall cerebral gray matter (+2.4%), non-hippocampal deep gray matter structures (thalamus, caudate: -4.0%), or in non-memory cognitive functioning (executive functions, processing speed, working memory: changes ranged from -11% to +4%). Non-aerobic exercise resulted in relatively no change in hippocampal volume (2.8%) or memory (0.0%), and no changes in hippocampal functional connectivity. This is the first evidence for aerobic exercise to increase hippocampal volume and connectivity and improve memory in multiple sclerosis. Aerobic exercise represents a cost-effective, widely available, natural, and self-administered treatment with no adverse side effects that may be the first effective memory treatment for multiple sclerosis patients.

Visuo-Spatial Processing and Executive Functions in Children with Specific Language Impairment

ERIC Educational Resources Information Center

Marton, Klara

2008-01-01

Background: Individual differences in complex working memory tasks reflect simultaneous processing, executive functions, and attention control. Children with specific language impairment (SLI) show a deficit in verbal working memory tasks that involve simultaneous processing of information. Aims: The purpose of the study was to examine executive…

Organizational strategies mediate nonverbal memory impairment in obsessive-compulsive disorder.

PubMed

Savage, C R; Baer, L; Keuthen, N J; Brown, H D; Rauch, S L; Jenike, M A

1999-04-01

Previous neuropsychological studies of obsessive-compulsive disorder (OCD) have indicated impaired executive functioning and nonverbal memory. The extent to which impaired executive functioning impacts nonverbal memory has not been established. The current study investigated the mediating effects of organizational strategies used when copying a figure on subsequent nonverbal memory for that figure. We examined neuropsychological performance in 20 unmedicated subjects with OCD and 20 matched normal control subjects. Subjects were administered the Rey-Osterrieth Complex Figure Test (RCFT) and neuropsychological tests assessing various aspects of executive function. OCD subjects differed significantly from healthy control subjects in the organizational strategies used to copy the RCFT figure, and they recalled significantly less information on both immediate and delayed testing. Multiple regression analyses indicated that group differences in immediate percent recall were significantly mediated by copy organizational strategies. Further exploratory analyses indicated that organizational problems in OCD may be related to difficulties shifting mental and/or spatial set. Immediate nonverbal memory problems in OCD subjects were mediated by impaired organizational strategies used during the initial copy of the RCFT figure. Thus, the primary deficit was one affecting executive function, which then had a secondary effect on immediate memory. These findings are consistent with current theories proposing frontal-striatal system dysfunction in OCD.

Seizure Control and Memory Impairment Are Related to Disrupted Brain Functional Integration in Temporal Lobe Epilepsy.

PubMed

Park, Chang-Hyun; Choi, Yun Seo; Jung, A-Reum; Chung, Hwa-Kyoung; Kim, Hyeon Jin; Yoo, Jeong Hyun; Lee, Hyang Woon

2017-01-01

Brain functional integration can be disrupted in patients with temporal lobe epilepsy (TLE), but the clinical relevance of this disruption is not completely understood. The authors hypothesized that disrupted functional integration over brain regions remote from, as well as adjacent to, the seizure focus could be related to clinical severity in terms of seizure control and memory impairment. Using resting-state functional MRI data acquired from 48 TLE patients and 45 healthy controls, the authors mapped functional brain networks and assessed changes in a network parameter of brain functional integration, efficiency, to examine the distribution of disrupted functional integration within and between brain regions. The authors assessed whether the extent of altered efficiency was influenced by seizure control status and whether the degree of altered efficiency was associated with the severity of memory impairment. Alterations in the efficiency were observed primarily near the subcortical region ipsilateral to the seizure focus in TLE patients. The extent of regional involvement was greater in patients with poor seizure control: it reached the frontal, temporal, occipital, and insular cortices in TLE patients with poor seizure control, whereas it was limited to the limbic and parietal cortices in TLE patients with good seizure control. Furthermore, TLE patients with poor seizure control experienced more severe memory impairment, and this was associated with lower efficiency in the brain regions with altered efficiency. These findings indicate that the distribution of disrupted brain functional integration is clinically relevant, as it is associated with seizure control status and comorbid memory impairment.

Memory assessment in patients with temporal lobe epilepsy to predict memory impairment after surgery: A systematic review.

PubMed

Parra-Díaz, P; García-Casares, N

2017-04-19

Given that surgical treatment of refractory mesial temporal lobe epilepsy may cause memory impairment, determining which patients are eligible for surgery is essential. However, there is little agreement on which presurgical memory assessment methods are best able to predict memory outcome after surgery and identify those patients with a greater risk of surgery-induced memory decline. We conducted a systematic literature review to determine which presurgical memory assessment methods best predict memory outcome. The literature search of PubMed gathered articles published between January 2005 and December 2015 addressing pre- and postsurgical memory assessment in mesial temporal lobe epilepsy patients by means of neuropsychological testing, functional MRI, and other neuroimaging techniques. We obtained 178 articles, 31 of which were included in our review. Most of the studies used neuropsychological tests and fMRI; these methods are considered to have the greatest predictive ability for memory impairment. Other less frequently used techniques included the Wada test and FDG-PET. Current evidence supports performing a presurgical assessment of memory function using both neuropsychological tests and functional MRI to predict memory outcome after surgery. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

Temporal Context Memory in High-Functioning Autism

ERIC Educational Resources Information Center

Gras-Vincendon, Agnes; Mottron, Laurent; Salame, Pierre; Bursztejn, Claude; Danion, Jean-Marie

2007-01-01

Episodic memory, i.e. memory for specific episodes situated in space and time, seems impaired in individuals with autism. According to weak central coherence theory, individuals with autism have general difficulty connecting contextual and item information which then impairs their capacity to memorize information in context. This study…

Executive Functioning Heterogeneity in Pediatric ADHD.

PubMed

Kofler, Michael J; Irwin, Lauren N; Soto, Elia F; Groves, Nicole B; Harmon, Sherelle L; Sarver, Dustin E

2018-04-28

Neurocognitive heterogeneity is increasingly recognized as a valid phenomenon in ADHD, with most estimates suggesting that executive dysfunction is present in only about 33%-50% of these children. However, recent critiques question the veracity of these estimates because our understanding of executive functioning in ADHD is based, in large part, on data from single tasks developed to detect gross neurological impairment rather than the specific executive processes hypothesized to underlie the ADHD phenotype. The current study is the first to comprehensively assess heterogeneity in all three primary executive functions in ADHD using a criterion battery that includes multiple tests per construct (working memory, inhibitory control, set shifting). Children ages 8-13 (M = 10.37, SD = 1.39) with and without ADHD (N = 136; 64 girls; 62% Caucasian/Non-Hispanic) completed a counterbalanced series of executive function tests. Accounting for task unreliability, results indicated significantly improved sensitivity and specificity relative to prior estimates, with 89% of children with ADHD demonstrating objectively-defined impairment on at least one executive function (62% impaired working memory, 27% impaired inhibitory control, 38% impaired set shifting; 54% impaired on one executive function, 35% impaired on two or all three executive functions). Children with working memory deficits showed higher parent- and teacher-reported ADHD inattentive and hyperactive/impulsive symptoms (BF 10  = 5.23 × 10 4 ), and were slightly younger (BF 10  = 11.35) than children without working memory deficits. Children with vs. without set shifting or inhibitory control deficits did not differ on ADHD symptoms, age, gender, IQ, SES, or medication status. Taken together, these findings confirm that ADHD is characterized by neurocognitive heterogeneity, while suggesting that contemporary, cognitively-informed criteria may provide improved precision for identifying a smaller number of neuropsychologically-impaired subtypes than previously described.

Incidence of cognitively defined late-onset Alzheimer's dementia subgroups from a prospective cohort study.

PubMed

Crane, Paul K; Trittschuh, Emily; Mukherjee, Shubhabrata; Saykin, Andrew J; Sanders, R Elizabeth; Larson, Eric B; McCurry, Susan M; McCormick, Wayne; Bowen, James D; Grabowski, Thomas; Moore, Mackenzie; Bauman, Julianna; Gross, Alden L; Keene, C Dirk; Bird, Thomas D; Gibbons, Laura E; Mez, Jesse

2017-12-01

There may be biologically relevant heterogeneity within typical late-onset Alzheimer's dementia. We analyzed cognitive data from people with incident late-onset Alzheimer's dementia from a prospective cohort study. We determined individual averages across memory, visuospatial functioning, language, and executive functioning. We identified domains with substantial impairments relative to that average. We compared demographic, neuropathology, and genetic findings across groups defined by relative impairments. During 32,286 person-years of follow-up, 869 people developed Alzheimer's dementia. There were 393 (48%) with no domain with substantial relative impairments. Some participants had isolated relative impairments in memory (148, 18%), visuospatial functioning (117, 14%), language (71, 9%), and executive functioning (66, 8%). The group with isolated relative memory impairments had higher proportions with ≥ APOE ε4 allele, more extensive Alzheimer's-related neuropathology, and higher proportions with other Alzheimer's dementia genetic risk variants. A cognitive subgrouping strategy may identify biologically distinct subsets of people with Alzheimer's dementia. Copyright © 2017 the Alzheimer's Association. All rights reserved.

High visual working memory capacity in trait social anxiety.

PubMed

Moriya, Jun; Sugiura, Yoshinori

2012-01-01

Working memory capacity is one of the most important cognitive functions influencing individual traits, such as attentional control, fluid intelligence, and also psychopathological traits. Previous research suggests that anxiety is associated with impaired cognitive function, and studies have shown low verbal working memory capacity in individuals with high trait anxiety. However, the relationship between trait anxiety and visual working memory capacity is still unclear. Considering that people allocate visual attention more widely to detect danger under threat, visual working memory capacity might be higher in anxious people. In the present study, we show that visual working memory capacity increases as trait social anxiety increases by using a change detection task. When the demand to inhibit distractors increased, however, high visual working memory capacity diminished in individuals with social anxiety, and instead, impaired filtering of distractors was predicted by trait social anxiety. State anxiety was not correlated with visual working memory capacity. These results indicate that socially anxious people could potentially hold a large amount of information in working memory. However, because of an impaired cognitive function, they could not inhibit goal-irrelevant distractors and their performance decreased under highly demanding conditions.

Effects of desmopressin (DDAVP) on memory impairment following electroconvulsive therapy (ECT).

PubMed

Abdollahian, Ebrahim; Sargolzaee, Mohammad R; Hajzade, Moosareza; Mohebbi, Mohammad D; Javanbakht, Arash

2004-06-01

Memory impairment is a common adverse effect of electroconvulsive therapy (ECT). Studies on animals and humans suggest that vasopressin improves the cognitive function, and positive effects of desmopressin on memory and learning have been reported. This research was performed for evaluation of the effects of desmopressin in the prevention of memory impairment following ECT. This randomized, double-blind controlled clinical trial with placebo administration was performed on 50 patients with psychiatric disorders who were candidates for ECT. Subjects in the case group received 60 µm of intranasal desmopressin daily (in three doses of 20 µm). For the control group 0.9% saline solution was administered in the same way. Memory function was evaluated using Wechsler's Memory Scale three times a week (the first time before the start of ECT and the second and third times after the third and sixth sessions, respectively). Results were analyzed by t-test and Paired t-test. The mean age of patients was 29 years (range 20-40). During the course of ECT, patients in the control group demonstrated a meaningful decrease in memory scores (from a base score of 80.15-75.45 in the second test and 72.60 in the third test). Despite this, a meaningful increase in memory scores was observed during the treatment with desmopressin in the case group (from a base score of 73.27-75.70 and 79.13 in the second and the third tests, respectively). There was a meaningful difference between the two groups (P < 0.0001). This study confirms the protective effect of desmopressin against memory impairment. The results confirm that memory impairment is a common side-effect of ECT and suggest that desmopressin may prevent ECT-induced memory impairment by its effects on memory and the learning process.

Learning and Memory Impairments in Patients with Minimal Hepatic Encephalopathy are Associated with Structural and Functional Connectivity Alterations in Hippocampus.

PubMed

García-García, Raquel; Cruz-Gómez, Álvaro Javier; Urios, Amparo; Mangas-Losada, Alba; Forn, Cristina; Escudero-García, Desamparados; Kosenko, Elena; Torregrosa, Isidro; Tosca, Joan; Giner-Durán, Remedios; Serra, Miguel Angel; Avila, César; Belloch, Vicente; Felipo, Vicente; Montoliu, Carmina

2018-06-25

Patients with minimal hepatic encephalopathy (MHE) show mild cognitive impairment associated with alterations in attentional and executive networks. There are no studies evaluating the relationship between memory in MHE and structural and functional connectivity (FC) changes in the hippocampal system. This study aimed to evaluate verbal learning and long-term memory in cirrhotic patients with (C-MHE) and without MHE (C-NMHE) and healthy controls. We assessed the relationship between alterations in memory and the structural integrity and FC of the hippocampal system. C-MHE patients showed impairments in learning, long-term memory, and recognition, compared to C-NMHE patients and controls. Cirrhotic patients showed reduced fimbria volume compared to controls. Larger volumes in hippocampus subfields were related to better memory performance in C-NMHE patients and controls. C-MHE patients presented lower FC between the L-presubiculum and L-precuneus than C-NMHE patients. Compared to controls, C-MHE patients had reduced FC between L-presubiculum and subiculum seeds and bilateral precuneus, which correlated with cognitive impairment and memory performance. Alterations in the FC of the hippocampal system could contribute to learning and long-term memory impairments in C-MHE patients. This study demonstrates the association between alterations in learning and long-term memory and structural and FC disturbances in hippocampal structures in cirrhotic patients.

Verbal Working Memory in Schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) Study: The Moderating Role of Smoking Status and Antipsychotic Medications

PubMed Central

Lee, Junghee; Green, Michael F.; Calkins, Monica E.; Greenwood, Tiffany A.; Gur, Raquel E.; Gur, Ruben C.; Lazzeroni, Laura C.; Light, Gregory A.; Nuechterlein, Keith H.; Radant, Allen D.; Seidman, Larry J.; Siever, Larry J.; Silverman, Jeremy M.; Sprock, Joyce; Stone, William S.; Sugar, Catherine A.; Swerdlow, Neal R.; Tsuang, Debby W.; Tsuang, Ming T.; Turetsky, Bruce I.; Braff, David L.

2014-01-01

Objectives Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. Methods From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the Letter-Number Span (LNS) Task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the Forward condition, participants repeated the letters and numbers in the order they were presented. In the Reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. Results Schizophrenia patients performed more poorly than controls, with a larger difference on Reorder than Forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the Reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. Conclusions Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke. PMID:25248939

Verbal working memory in schizophrenia from the Consortium on the Genetics of Schizophrenia (COGS) study: the moderating role of smoking status and antipsychotic medications.

PubMed

Lee, Junghee; Green, Michael F; Calkins, Monica E; Greenwood, Tiffany A; Gur, Raquel E; Gur, Ruben C; Lazzeroni, Laura C; Light, Gregory A; Nuechterlein, Keith H; Radant, Allen D; Seidman, Larry J; Siever, Larry J; Silverman, Jeremy M; Sprock, Joyce; Stone, William S; Sugar, Catherine A; Swerdlow, Neal R; Tsuang, Debby W; Tsuang, Ming T; Turetsky, Bruce I; Braff, David L

2015-04-01

Working memory impairment has been extensively studied in schizophrenia, but less is known about moderators of the impairment. Using the Consortium on the Genetics of Schizophrenia case-control study (COGS-2), we examined smoking status, types of antipsychotic medication, and history of substance as moderators for working memory impairment in schizophrenia. From 5 sites, 1377 patients with schizophrenia or schizoaffective, depressed type and 1037 healthy controls completed the letter-number span (LNS) task. The LNS uses intermixed letter and digit stimuli that increase from 2 up to 8 stimuli. In the forward condition, participants repeated the letters and numbers in the order they were presented. In the reorder condition, participants repeated the digits in ascending order followed by letters in alphabetical order. Schizophrenia patients performed more poorly than controls, with a larger difference on reorder than forward conditions. Deficits were associated with symptoms, functional capacity, and functional outcome. Patients who smoked showed larger impairment than nonsmoking patients, primarily due to deficits on the reorder condition. The impairing association of smoking was more pronounced among patients taking first-generation than those taking second-generation antipsychotic medications. Correlations between working memory and community functioning were stronger for nonsmokers. History of substance use did not moderate working memory impairment. Results confirm the working memory impairment in schizophrenia, and indicate smoking status as an important moderator for these deficits. The greater impairment in smokers may reflect added burden of smoking on general health or that patients with greater deficits are more likely to smoke. Copyright © 2014 Elsevier B.V. All rights reserved.

Impairments of spatial working memory and attention following acute psychosocial stress.

PubMed

Olver, James S; Pinney, Myra; Maruff, Paul; Norman, Trevor R

2015-04-01

Few studies have investigated the effect of an acute psychosocial stress paradigm on impaired attention and working memory in humans. Further, the duration of any stress-related cognitive impairment remains unclear. The aim of this study was to examine the effect of an acute psychosocial stress paradigm, the Trier Social Stress, on cognitive function in healthy volunteers. Twenty-three healthy male and female subjects were exposed to an acute psychosocial stress task. Physiological measures (salivary cortisol, heart rate and blood pressure) and subjective stress ratings were measured at baseline, in anticipation of stress, immediately post-stress and after a period of rest. A neuropsychological test battery including spatial working memory and verbal memory was administered at each time point. Acute psychosocial stress produced significant increases in cardiovascular and subjective measures in the anticipatory and post-stress period, which recovered to baseline after rest. Salivary cortisol steadily declined over the testing period. Acute psychosocial stress impaired delayed verbal recall, attention and spatial working memory. Attention remained impaired, and delayed verbal recall continued to decline after rest. Acute psychosocial stress is associated with an impairment of a broad range of cognitive functions in humans and with prolonged abnormalities in attention and memory. Copyright © 2014 John Wiley & Sons, Ltd.

Caspase-2 cleavage of tau reversibly impairs memory.

PubMed

Zhao, Xiaohui; Kotilinek, Linda A; Smith, Benjamin; Hlynialuk, Chris; Zahs, Kathleen; Ramsden, Martin; Cleary, James; Ashe, Karen H

2016-11-01

In Alzheimer's disease (AD) and other tauopathies, the tau protein forms fibrils, which are believed to be neurotoxic. However, fibrillar tau has been dissociated from neuron death and network dysfunction, suggesting the involvement of nonfibrillar species. Here we describe a novel pathological process in which caspase-2 cleavage of tau at Asp314 impairs cognitive and synaptic function in animal and cellular models of tauopathies by promoting the missorting of tau to dendritic spines. The truncation product, Δtau314, resists fibrillation and is present at higher levels in brains from cognitively impaired mice and humans with AD. The expression of tau mutants that resisted caspase-2 cleavage prevented tau from infiltrating spines, dislocating glutamate receptors and impairing synaptic function in cultured neurons, and it prevented memory deficits and neurodegeneration in mice. Decreasing the levels of caspase-2 restored long-term memory in mice that had existing deficits. Our results suggest an overall treatment strategy for re-establishing synaptic function and restoring memory in patients with AD by preventing tau from accumulating in dendritic spines.

Episodic Memory Impairments in Primary Brain Tumor Patients.

PubMed

Durand, Thomas; Berzero, Giulia; Bompaire, Flavie; Hoffmann, Sabine; Léger, Isabelle; Jego, Virginie; Baruteau, Marie; Delgadillo, Daniel; Taillia, Hervé; Psimaras, Dimitri; Ricard, Damien

2018-01-04

Cognitive investigations in brain tumor patients have mostly explored episodic memory without differentiating between encoding, storage, and retrieval deficits. The aim of this study is to offer insight into the memory sub-processes affected in primary brain tumor patients and propose an appropriate assessment method. We retrospectively reviewed the clinical and memory assessments of 158 patients with primary brain tumors who had presented to our departments with cognitive complaints and were investigated using the Free and Cued Selective Reminding Test. Retrieval was the process of episodic memory most frequently affected, with deficits in this domain detected in 92% of patients with episodic memory impairments. Storage and encoding deficits were less prevalent, with impairments, respectively, detected in 41% and 23% of memory-impaired patients. The pattern of episodic memory impairment was similar across different tumor histologies and treatment modalities. Although all processes of episodic memory were found to be impaired, retrieval was by far the most widely affected function. A thorough assessment of all three components of episodic memory should be part of the regular neuropsychological evaluation in patients with primary brain tumors. © The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

PubMed

Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

2017-08-01

Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Intact short-term memory and impaired executive functions in obsessive compulsive disorder.

PubMed

Demeter, Gyula; Racsmány, Mihály; Csigó, Katalin; Harsányi, András; Németh, Attila; Döme, László

2013-01-30

Previous neuropsychological studies produced inconsistent results with tasks tapping short-term verbal and visual-spatial memory and executive functions in obsessive compulsive disorder (OCD). The aim of this study was to investigate the presence of deficits in these cognitive domains. A further goal was to describe the distribution of patients in different impairment ranges for all functions, and clarify the relationship between symptom severity and cognitive impairments. Thirty patients with OCD (DSM-IV) and 30 healthy volunteers were compared using well-known neuropsychological tasks. We assessed short-term verbal memory with the Digit Span Forward and Digit Span Backward Tasks, short-term visual-spatial memory with the Corsi Block Tapping Task, while we measured the level of executive functions with the StroopTask and the Wisconsin Card Sorting Test (WCST). Compared with a matched healthy control group, the performance of OCD patients was in the impaired range only in the two executive tasks. We find a significant positive correlations between the Y-BOCS (Yale-Brown Obsessive Compulsive Scale) total scores and the number of perseverative responses (r(28) = 0.409, p < 0.05) and perseverative errors (r(28) = 0.385, p < 0.05) in the WCST. Our results gave evidence that executive functions are impaired while short-term memory is intact in OCD. This is in line with neuropsychological model of OCD that the deficit of cognitive and behavioral inhibition are responsible for the main cognitive findings of this disorder, most prevalently the deficit in set shifting and prepotent response inhibition.

Dysfunctional overnight memory consolidation in ecstasy users.

PubMed

Smithies, Vanessa; Broadbear, Jillian; Verdejo-Garcia, Antonio; Conduit, Russell

2014-08-01

Sleep plays an important role in the consolidation and integration of memory in a process called overnight memory consolidation. Previous studies indicate that ecstasy users have marked and persistent neurocognitive and sleep-related impairments. We extend past research by examining overnight memory consolidation among regular ecstasy users (n=12) and drug naïve healthy controls (n=26). Memory recall of word pairs was evaluated before and after a period of sleep, with and without interference prior to testing. In addition, we assessed neurocognitive performances across tasks of learning, memory and executive functioning. Ecstasy users demonstrated impaired overnight memory consolidation, a finding that was more pronounced following associative interference. Additionally, ecstasy users demonstrated impairments on tasks recruiting frontostriatal and hippocampal neural circuitry, in the domains of proactive interference memory, long-term memory, encoding, working memory and complex planning. We suggest that ecstasy-associated dysfunction in fronto-temporal circuitry may underlie overnight consolidation memory impairments in regular ecstasy users. © The Author(s) 2014.

Spontaneous ripples in the hippocampus correlate with epileptogenicity and not memory function in patients with refractory epilepsy.

PubMed

Jacobs, Julia; Banks, Sarah; Zelmann, Rina; Zijlmans, Maeike; Jones-Gotman, Marilyn; Gotman, Jean

2016-09-01

High-frequency oscillations (HFOs, 80-500Hz) are newly-described EEG markers of epileptogenicity. The proportion of physiological and pathological HFOs is unclear, as frequency analysis is insufficient for separating the two types of events. For instance, ripples (80-250Hz) also occur physiologically during memory consolidation processes in medial temporal lobe structures. We investigated the correlation between HFO rates and memory performance. Patients investigated with bilateral medial temporal electrodes and an intellectual capacity allowing for memory testing were included. High-frequency oscillations were visually marked, and rates of HFOs were calculated for each channel during slow-wave sleep. Patients underwent three verbal and three nonverbal memory tests. They were grouped into severe impairment, some impairment, mostly intact, or intact for verbal and nonverbal memory. We calculated a Pearson correlation between HFO rates in the hippocampi and the memory category and compared HFO rates in each hippocampus with the corresponding (verbal - left, nonverbal - right) memory result using Wilcoxon rank-sum test. Twenty patients were included; ten had bilateral, five had unilateral, and five had no memory impairment. Unilateral memory impairment was verbal in one patient and nonverbal in four. There was no correlation between HFO rates and memory performance in seizure onset areas. There was, however, a significant negative correlation between the overall memory performance and ripple rates (r=-0.50, p=0.03) outside the seizure onset zone. Our results suggest that the majority of spontaneous hippocampal ripples, as defined in the present study, may reflect pathological activity, taking into account the association with memory impairment. The absence of negative correlation between memory performance and HFO rates in seizure onset areas could be explained by HFO rates in the SOZ being generally so high that differences between areas with remaining and impaired memory function cannot be seen. Copyright © 2016 Elsevier Inc. All rights reserved.

Spatial Working Memory Ability in Individuals at Ultra High Risk for Psychosis

PubMed Central

Goghari, Vina M.; Brett, Caroline; Tabraham, Paul; Johns, Louise; Valmaggia, Lucia; Broome, Matthew; Woolley, James; Bramon, Elvira; Howes, Oliver

2014-01-01

The goal of this investigation was to clarify the nature of spatial working memory difficulties in individuals at ultra high risk (UHR) for psychosis. We evaluated spatial working memory and intelligence in 96 individuals at UHR for psychosis, 28 patients with first episode psychosis (FEP), and 23 healthy controls. Fourteen UHR individuals developed a psychotic disorder during follow-up. Compared to controls, the UHR group was impaired in both the short-term maintenance of material and in the effective use of strategy, but not more immediate memory. These impairments were not as severe as those in the FEP group, as the UHR group performed better than the FEP group. A similar pattern of results was found for the intelligence measures. Discriminant function analyses demonstrated short-term maintenance of material significantly differentiated the UHR and healthy control groups even when accounting for full scale intelligence quotient (IQ); whereas full scale IQ significantly differentiated the UHR and FEP groups and FEP and control groups. Notably, within the UHR group, impaired spatial working memory performance was associated with lower global functioning, but not full scale IQ. The subgroup of UHR individuals who later developed psychosis was not significantly more impaired on any aspect of working memory performance than the group of UHR individuals who did not develop psychosis. Given, the relationship between spatial working memory deficits and functional outcome, these results indicate that cognitive remediation could be useful in individuals at UHR for psychosis to potentially improve functioning. PMID:24398256

Fractionation of visuo-spatial memory processes in bipolar depression: a cognitive scaffolding account.

PubMed

Gallagher, P; Gray, J M; Kessels, R P C

2015-02-01

Previous studies of neurocognitive performance in bipolar disorder (BD) have demonstrated impairments in visuo-spatial memory. The aim of the present study was to use an object-location memory (OLM) paradigm to assess specific, dissociable processes in visuo-spatial memory and examine their relationship with broader neurocognitive performance. Fifty participants (25 patients with BD in a current depressive episode and 25 matched healthy controls) completed the OLM paradigm which assessed three different aspects of visuo-spatial memory: positional memory, object-location binding, and a combined process. Secondary neurocognitive measures of visuo-spatial memory, verbal memory, attention and executive function were also administered. BD patients were significantly impaired on all three OLM processes, with the largest effect in exact positional memory (d = 1.18, p < 0.0001). General deficits were also found across the secondary neurocognitive measures. Using hierarchical regression, verbal learning was found to explain significant variance on the OLM measures where object-identity was present (the object-location binding and combined processes) and accounted for the group difference. The group difference in precise positional memory remained intact. This study demonstrates that patients with bipolar depression manifest deficits in visuo-spatial memory, with substantial impairment in fine-grain, positional memory. The differential profile of processes underpinning the visuo-spatial memory impairment suggests a form of 'cognitive scaffolding', whereby performance on some measures can be supported by verbal memory. These results have important implications for our understanding of the functional cognitive architecture of mood disorder.

Treatment of Unruptured Intracranial Aneurysms and Cognitive Performance: Preliminary Results of a Prospective Clinical Trial.

PubMed

Bründl, Elisabeth; Böhm, Christina; Lürding, Ralf; Schödel, Petra; Bele, Sylvia; Hochreiter, Andreas; Scheitzach, Judith; Zeman, Florian; Brawanski, Alexander; Schebesch, Karl-Michael

2016-10-01

Few studies have addressed the effect of treatment of unruptured intracranial aneurysm (UIA) on cognitive function. Neuropsychological assessment after UIA treatment is underreported, and prospective trials have repeatedly been demanded. In 2014, we conducted a prospective controlled study to evaluate the differences in cognitive processing caused by the treatment of anterior circulation UIAs. Thirty patients were enrolled until September 2015. Ten patients received endovascular aneurysm occlusion (EV), 10 patients were treated microsurgically (MS), and 10 patients with surgically treated degenerative lumbar spine disease (LD) served as control. All patients underwent extended standardized neuropsychological assessment before (t 1 ) and 6 weeks after treatment (t 2 ). Tests included verbal, visual, and visuospatial memory, psychomotor functioning, executive functioning, and its subdomains verbal fluency and cognitive flexibility. We statistically evaluated intragroup and intergroup changes. Intragroup comparisons and group-rate analysis showed no significant impairment in overall neuropsychological performance, either postinterventionally or postoperatively. However, the postoperative performance in cognitive processing speed, cognitive flexibility, and executive functioning was significantly worse in the MS group than in the EV (P = 0.038) and LD group (P = 0.02). Compared with the EV group, patients with MS showed significant postoperative impairment in a subtest for auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. EV P = 0.011). The MS group trended toward posttreatment impairment in subtests for verbal fluency and semantic memory (Regensburg Word Fluency Test; MS vs. EV P = 0.083) and in auditory-verbal memory (Wechsler Memory Scale, Fourth Edition, Logical Memory II; MS vs. LD P = 0.06). Our preliminary data showed no effect of anterior circulation UIA treatment on overall neuropsychological function but impaired short-term executive processing in surgically treated patients. Copyright © 2016 Elsevier Inc. All rights reserved.

The impact of transsphenoidal surgery on neurocognitive function: A systematic review.

PubMed

Alsumali, Adnan; Cote, David J; Regestein, Quentin R; Crocker, Erin; Alzarea, Abdulaziz; Zaidi, Hasan A; Bi, Wenya Linda; Dawood, Hassan Y; Broekman, Marike L; van Zandvoort, Martine J E; Mekary, Rania A; Smith, Timothy R

2017-08-01

Cognitive impairment following transsphenoidal surgery (TSS) among patients with pituitary tumors has been intermittently reported and is not well established. We performed a systematic review to summarize the impact of TSS on cognitive function. We conducted a systematic search of the literature using the PubMed, Cochrane, and Embase databases through October 2014. Studies were selected if they reported cognitive status after surgery and included at least 10 adult patients with pituitary tumors undergoing either endoscopic or microscopic TSS. After removing 69 duplicates, 758 articles were identified, of which 24 were selected for full text review after screening titles and abstracts. After reviewing full texts, nine studies with a combined total of 682 patients were included in the final analysis. Eight studies were cross-sectional and one was longitudinal. These studies used a wide variety of neurocognitive tests to assess memory, attention and executive function post-operatively. Of the eight studies, six reported impairments in verbal and non-verbal memory post-operatively, while others found no association related to memory, and some reported an improvement in episodic, verbal, or logical memory. While four studies found an impaired association between TSS and attention or executive function, another four studies did not. The current literature on cognitive impairments after TSS is limited and inconsistent. This review demonstrates that patients undergoing TSS may experience a variety of effects on executive function and memory post-operatively, but changes in verbal memory are most common. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cognitive deficits associated with impaired awareness of hypoglycaemia in type 1 diabetes.

PubMed

Hansen, Tor I; Olsen, Sandra E; Haferstrom, Elise C D; Sand, Trond; Frier, Brian M; Håberg, Asta K; Bjørgaas, Marit R

2017-06-01

The aim of this study was to compare cognitive function in adults with type 1 diabetes who have impaired awareness of hypoglycaemia with those who have normal awareness of hypoglycaemia. A putative association was sought between cognitive test scores and a history of severe hypoglycaemia. A total of 68 adults with type 1 diabetes were included: 33 had impaired and 35 had normal awareness of hypoglycaemia, as confirmed by formal testing. The groups were matched for age, sex and diabetes duration. Cognitive tests of verbal memory, object-location memory, pattern separation, executive function, working memory and processing speed were administered. Participants with impaired awareness of hypoglycaemia scored significantly lower on the verbal and object-location memory tests and on the pattern separation test (Cohen's d -0.86 to -0.55 [95% CI -1.39, -0.05]). Participants with impaired awareness of hypoglycaemia had reduced planning ability task scores, although the difference was not statistically significant (Cohen's d 0.57 [95% CI 0, 1.14]). Frequency of exposure to severe hypoglycaemia correlated with the number of cognitive tests that had not been performed according to instructions. Impaired awareness of hypoglycaemia was associated with diminished learning, memory and pattern separation. These cognitive tasks all depend on the hippocampus, which is vulnerable to neuroglycopenia. The findings suggest that hypoglycaemia contributes to the observed correlation between impaired awareness of hypoglycaemia and impaired cognition.

Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects.

PubMed

Wezenberg, E; Verkes, R J; Sabbe, B G C; Ruigt, G S F; Hulstijn, W

2005-09-01

The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function. In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects. A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around Tmax for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test). Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine. These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.

Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism

PubMed Central

Barsegyan, Areg; Mackenzie, Scott M.; Kurose, Brian D.; McGaugh, James L.; Roozendaal, Benno

2010-01-01

It is well established that acute administration of adrenocortical hormones enhances the consolidation of memories of emotional experiences and, concurrently, impairs working memory. These different glucocorticoid effects on these two memory functions have generally been considered to be independently regulated processes. Here we report that a glucocorticoid receptor agonist administered into the medial prefrontal cortex (mPFC) of male Sprague-Dawley rats both enhances memory consolidation and impairs working memory. Both memory effects are mediated by activation of a membrane-bound steroid receptor and depend on noradrenergic activity within the mPFC to increase levels of cAMP-dependent protein kinase. These findings provide direct evidence that glucocorticoid effects on both memory consolidation and working memory share a common neural influence within the mPFC. PMID:20810923

Neuroprotective effect of curcumin on okadaic acid induced memory impairment in mice.

PubMed

Rajasekar, N; Dwivedi, Subhash; Tota, Santosh Kumar; Kamat, Pradeep Kumar; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2013-09-05

Okadaic acid (OKA) has been observed to cause memory impairment in human subjects having seafood contaminated with dinoflagellate (Helicondria okadai). OKA induces tau hyperphosphorylation and oxidative stress leading to memory impairment as our previous study has shown. Curcumin a natural antioxidant has demonstrated neuroprotection in various models of neurodegeneration. However, the effect of curcumin has not been explored in OKA induced memory impairment. Therefore, present study evaluated the effect of curcumin on OKA (100ng, intracerebrally) induced memory impairment in male Swiss albino mice as evaluated in Morris water maze (MWM) and passive avoidance tests (PAT). OKA administration resulted in memory impairment with a decreased cerebral blood flow (CBF) (measured by laser doppler flowmetry), ATP level and increased mitochondrial (Ca(2+))i, neuroinflammation (increased TNF-α, IL-1β, COX-2 and GFAP), oxidative-nitrosative stress, increased Caspase-9 and cholinergic dysfunction (decreased AChE activity/expression and α7 nicotinic acetylcholine receptor expression) in cerebral cortex and hippocampus of mice brain. Oral administration of curcumin (50mg/kg) for 13 days significantly improved memory function in both MWM and PAT along with brain energy metabolism, CBF and cholinergic function. It decreased mitochondrial (Ca(2+))i, and ameliorated neuroinflammation and oxidative-nitrostative stress in different brain regions of OKA treated mice. Curcumin also inhibited astrocyte activation as evidenced by decreased GFAP expression. This neuroprotective effect of curcumin is due to its potent anti-oxidant action thus confirming previous studies. Therefore, use of curcumin should be encouraged in people consuming sea food (contaminated with dinoflagellates) to prevent cognitive impairment. © 2013 Elsevier B.V. All rights reserved.

Arginine vasopressin prevents against Abeta(25-35)-induced impairment of spatial learning and memory in rats.

PubMed

Pan, Yan-Fang; Chen, Xiao-Rong; Wu, Mei-Na; Ma, Cun-Gen; Qi, Jin-Shun

2010-04-01

Amyloid beta protein (Abeta) is thought to be responsible for loss of memory in Alzheimer's disease (AD). A significant decrease in [Arg(8)]-vasopressin (AVP) has been found in the AD brain and in plasma; however, it is unclear whether this decrease in AVP is involved in Abeta-induced impairment of spatial cognition and whether AVP can protect against Abeta-induced deficits in cognitive function. The present study examined the effects of intracerebroventricular (i.c.v.) injection of AVP on spatial learning and memory in the Morris water maze test and investigated the potential protective function of AVP against Abeta-induced impairment in spatial cognition. The results were as follows: (1) i.c.v. injection of 25 nmol Abeta(25-35) resulted in a significant decline in spatial learning and memory; (2) 1 nmol and 10 nmol, but not 0.1 nmol, AVP injections markedly improved learning and memory; (3) pretreatment with 1 nmol or 10 nmol, but not 0.1 nmol, AVP effectively reversed the impairment in spatial learning and memory induced by Abeta(25-35); and (4) none of the drugs, including Abeta(25-35) and different concentrations of AVP, affected the vision or swimming speed of the rats. These results indicate that Abeta(25-35) could significantly impair spatial learning and memory in rats, and pretreatment with AVP centrally can enhance spatial learning and effectively prevent the behavioral impairment induced by neurotoxic Abeta(25-35). Thus, the present study provides further insight into the mechanisms by which Abeta impairs spatial learning and memory, suggesting that up-regulation of central AVP might be beneficial in the prevention and treatment of AD. Copyright 2010 Elsevier Inc. All rights reserved.

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.

The chronic effects of cannabis on memory in humans: a review.

PubMed

Solowij, Nadia; Battisti, Robert

2008-01-01

Memory problems are frequently associated with cannabis use, in both the short- and long-term. To date, reviews on the long-term cognitive sequelae of cannabis use have examined a broad range of cognitive functions, with none specifically focused on memory. Consequently, this review sought to examine the literature specific to memory function in cannabis users in the nontoxicated state with the aim of identifying the existence and nature of memory impairment in cannabis users and appraising potentially related mediators or moderators. Literature searches were conducted to extract well-controlled studies that investigated memory function in cannabis users outside of the acute intoxication period, with a focus on reviewing studies published within the past 10 years. Most recent studies have examined working memory and verbal episodic memory and cumulatively, the evidence suggests impaired encoding, storage, manipulation and retrieval mechanisms in long-term or heavy cannabis users. These impairments are not dissimilar to those associated with acute intoxication and have been related to the duration, frequency, dose and age of onset of cannabis use. We consider the impact of not only specific parameters of cannabis use in the manifestation of memory dysfunction, but also such factors as age, neurodevelopmental stage, IQ, gender, various vulnerabilities and other substance-use interactions, in the context of neural efficiency and compensatory mechanisms. The precise nature of memory deficits in cannabis users, their neural substrates and manifestation requires much further exploration through a variety of behavioural, functional brain imaging, prospective and genetic studies.

Acute genistein treatment mimics the effects of estradiol by enhancing place learning and impairing response learning in young adult female rats

PubMed Central

Pisani, Samantha L.; Neese, Steven L.; Doerge, Daniel R.; Helferich, William G.; Schantz, Susan L.; Korol, Donna L.

2012-01-01

Endogenous estrogens have bidirectional effects on learning and memory, enhancing or impairing cognition depending on many variables, including the task and the memory systems that are engaged. Moderate increases in estradiol enhance hippocampus-sensitive place learning, yet impair response learning that taps dorsal striatum function. This memory modulation likely occurs via activation of estrogen receptors, resulting in altered neural function. Supplements containing estrogenic compounds from plants are widely consumed despite limited information about their effects on brain function, including learning and memory. Phytoestrogens can enter the brain and signal through estrogen receptors to affect cognition. Enhancements in spatial memory and impairments in executive function have been found following treatment with soy phytoestrogens, but no tests of actions on striatum-sensitive tasks have been made to date. The present study compared the effects of acute exposure to the isoflavone genistein with the effects of estradiol on performance in place and response learning tasks. Long-Evans rats were ovariectomized, treated with 17β-estradiol benzoate, genistein-containing sucrose pellets, or vehicle (oil or plain sucrose pellets) for two days prior to behavioral training. Compared to vehicle controls, estradiol treatment enhanced place learning at a low (4.5 μg/kg) but not high dose (45 μg/kg), indicating an inverted pattern of spatial memory facilitation. Treatment with 4.4 mg of genistein over two days also significantly enhanced place learning over vehicle controls. For the response task, treatment with estradiol impaired learning at both the low and high doses; likewise, genistein treatment impaired response learning compared to rats receiving vehicle. Overall, genistein was found to mimic estradiol-induced shifts in place and response learning, facilitating hippocampus-sensitive learning and slowing striatum-sensitive learning. These results suggest signaling through estrogen receptor β and membrane-associated estrogen receptors in learning enhancements and impairments given the preferential binding of genistein to the ERβ subtype and affinity for GPER. PMID:22944517

Oligonol improves memory and cognition under an amyloid β(25-35)-induced Alzheimer's mouse model.

PubMed

Choi, Yoon Young; Maeda, Takahiro; Fujii, Hajime; Yokozawa, Takako; Kim, Hyun Young; Cho, Eun Ju; Shibamoto, Takayuki

2014-07-01

Alzheimer's disease is an age-dependent progressive neurodegenerative disorder that results in impairments of memory and cognitive function. It is hypothesized that oligonol has ameliorative effects on memory impairment and reduced cognitive functions in mice with Alzheimer's disease induced by amyloid β(25-35) (Aβ(25-35)) injection. The protective effect of an oligonol against Aβ(25-35)-induced memory impairment was investigated in an in vivo Alzheimer's mouse model. The aggregation of Aβ25-35 was induced by incubation at 37°C for 3 days before injection into mice brains (5 nmol/mouse), and then oligonol was orally administered at 100 and 200 mg/kg of body weight for 2 weeks. Memory and cognition were observed in T-maze, object recognition, and Morris water maze tests. The group injected with Aβ(25-35) showed impairments in both recognition and memory. However, novel object recognition and new route awareness abilities were dose dependently improved by the oral administration of oligonol. In addition, the results of the Morris water maze test indicated that oligonol exerted protective activity against cognitive impairment induced by Aβ(25-35). Furthermore, nitric oxide formation and lipid peroxidation were significantly elevated by Aβ(25-35), whereas oligonol treatment significantly decreased nitric oxide formation and lipid peroxidation in the brain, liver, and kidneys. The present results suggest that oligonol improves Aβ(25-35)-induced memory deficit and cognition impairment. Copyright © 2014 Elsevier Inc. All rights reserved.

Psychogenic amnesia--a malady of the constricted self.

PubMed

Staniloiu, Angelica; Markowitsch, Hans J; Brand, Matthias

2010-09-01

Autobiographical-episodic memory is the conjunction of subjective time, autonoetic consciousness and the experiencing self. Understanding the neural correlates of autobiographical-episodic memory might therefore be essential for shedding light on the neurobiology underlying the experience of being an autonoetic self. In this contribution we illustrate the intimate relationship between autobiographical-episodic memory and self by reviewing the clinical and neuropsychological features and brain functional imaging correlates of psychogenic amnesia - a condition that is usually characterized by severely impaired retrograde memory functioning, in absence of structural brain damage as detected by standard imaging. We demonstrate that in this disorder the autobiographical-episodic memory deficits do not exist in isolation, but occur with impairments of the autonoetic self-consciousness, emotional processing, and theory of mind or executive functions. Furthermore functional and metabolic brain alterations involving regions that are agreed upon to exert crucial roles in memory processes were frequently found to accompany the psychogenic memory "loss". Copyright © 2010 Elsevier Inc. All rights reserved.

Medial prefrontal lesions in mice impair sustained attention but spare maintenance of information in working memory.

PubMed

Kahn, Julia B; Ward, Ryan D; Kahn, Lora W; Rudy, Nicole M; Kandel, Eric R; Balsam, Peter D; Simpson, Eleanor H

2012-10-16

Working memory and attention are complex cognitive functions that are disrupted in several neuropsychiatric disorders. Mouse models of such human diseases are commonly subjected to maze-based tests that can neither distinguish between these cognitive functions nor isolate specific aspects of either function. Here, we have adapted a simple visual discrimination task, and by varying only the timing of events within the same task construct, we are able to measure independently the behavioral response to increasing attentional demand and increasing length of time that information must be maintained in working memory. We determined that mPFC lesions in mice impair attention but not working memory maintenance.

Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist.

PubMed

Newman, L A; Gold, P E

2016-03-01

Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors. The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function. Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release. These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist-to decrease scopolamine-induced increases in acetylcholine output or to decrease postsynaptic acetylcholine receptor activation-may mediate the negative effects on memory of muscarinic antagonists.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

Neuropsychological impairments on the NEPSY-II among children with FASD.

PubMed

Rasmussen, Carmen; Tamana, Sukhpreet; Baugh, Lauren; Andrew, Gail; Tough, Suzanne; Zwaigenbaum, Lonnie

2013-01-01

We examined the pattern of neuropsychological impairments of children with FASD (compared to controls) on NEPSY-II measures of attention and executive functioning, language, memory, visuospatial processing, and social perception. Participants included 32 children with FASD and 30 typically developing control children, ranging in age from 6 to 16 years. Children were tested on the following subtests of the NEPSY-II: Attention and Executive Functioning (animal sorting, auditory attention/response set, and inhibition), Language (comprehension of instructions and speeded naming), Memory (memory for names/delayed memory for names), Visual-Spatial Processing (arrows), and Social Perception (theory of mind). Groups were compared using MANOVA. Children with FASD were impaired relative to controls on the following subtests: animal sorting, response set, inhibition (naming and switching conditions), comprehension of instructions, speeded naming, and memory for names total and delayed, but group differences were not significant on auditory attention, inhibition (inhibition condition), arrows, and theory of mind. Among the FASD group, IQ scores were not correlated with performance on the NEPSY-II subtests, and there were no significant differences between those with and without comorbid ADHD. The NEPSY-II is an effective and useful tool for measuring a variety of neuropsychological impairments among children with FASD. Children with FASD displayed a pattern of results with impairments (relative to controls) on measures of executive functioning (set shifting, concept formation, and inhibition), language, and memory, and relative strengths on measures of basic attention, visual spatial processing, and social perception.

Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory

PubMed Central

Jung, Wookyoung; Lee, Seung-Hwan

2016-01-01

It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD) patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed. PMID:27274250

Implicit Memory in Korsakoff’s Syndrome: A Review of Procedural Learning and Priming Studies

PubMed Central

Hayes, Scott M.; Fortier, Catherine B.; Levine, Andrea; Milberg, William P.; McGlinchey, Regina

2013-01-01

Korsakoff’s syndrome (KS) is characterized by dense anterograde amnesia resulting from damage to the diencephalon region, typically resulting from chronic alcohol abuse and thiamine deficiency. This review assesses the integrity of the implicit memory system in KS, focusing on studies of procedural learning and priming. KS patients are impaired on several measures of procedural memory, most likely due to impairment in cognitive functions associated with alcohol-related neural damage outside of the diencephalon. The pattern of performance on tasks of implicit priming suggests reliance on a residual, non-flexible memory operating more or less in an automatic fashion. Our review concludes that whether measures of implicit memory reveal intact or impaired performance in individuals with KS depends heavily on specific task parameters and demands, including timing between stimuli, the specific nature of the stimuli used in a task, and the integrity of supportive cognitive functions necessary for performance. PMID:22592661

Structural Connectivity Changes Underlying Altered Working Memory Networks in Mild Cognitive Impairment: A Three-Way Image Fusion Analysis.

PubMed

Teipel, Stefan; Ehlers, Inga; Erbe, Anna; Holzmann, Carsten; Lau, Esther; Hauenstein, Karlheinz; Berger, Christoph

2015-01-01

Working memory impairment is among the earliest signs of cognitive decline in Alzheimer's disease (AD) and mild cognitive impairment (MCI). We aimed to study the functional and structural substrate of working memory impairment in early AD dementia and MCI. We studied a group of 12 MCI and AD subjects compared to 12 age- and gender-matched healthy elderly controls using diffusion tensor imaging (DTI), and functional magnetic resonance imaging (fMRI) during a 2-back versus 1-back letter recognition task. We performed a three-way image fusion analysis with joint independent component analysis of cortical activation during working memory, and DTI derived measures of fractional anisotropy (FA) and the mode of anisotropy. We found significant hypoactivation in posterior brain areas and relative hyperactivation in anterior brain areas during working memory in AD/MCI subjects compared to controls. Corresponding independent components from DTI data revealed reduced FA and reduced mode of anisotropy in intracortical projecting fiber tracts with posterior predominance and increased FA and increased mode along the corticospinal tract in AD/MCI compared to controls. Our findings suggest that impairments of structural fiber tract integrity accompany breakdown of posterior and relatively preserved anterior cortical activation during working memory performance in MCI/AD subjects. Copyright © 2014 by the American Society of Neuroimaging.

Persistent impairment in working memory following severe hyperglycemia in newly diagnosed type 2 diabetes.

PubMed

Cerasuolo, Joseph; Izzo, Anthony

2017-01-01

Acute hyperglycemia has been shown to cause cognitive impairments in animal models. There is growing appreciation of the numerous effects of hyperglycemia on neuronal function as well as blood-brain barrier function. In humans, hypoglycemia is well known to cause cognitive deficits acutely, but hyperglycemia has been less well studied. We present a case of selective neurocognitive deficits in the setting of acute hyperglycemia. A 60-year-old man was admitted to the hospital for an episode of acute hyperglycemia in the setting of newly diagnosed diabetes mellitus precipitated by steroid use. He was managed with insulin therapy and discharged home, and later, presented with complaints of memory impairment. Deficits included impairment in his declarative and working memory, to the point of significant impairment in his overall functioning. The patient had no structural lesions on MRI imaging of the brain or other systemic illnesses to explain his specific deficits. We suggest that his acute hyperglycemia may have caused neurological injury, and may be responsible for our patient's memory complaints. Acute hyperglycemia has been associated with poor outcomes in several different central nervous system injuries including cerebrovascular accident and hypoxic injury.Hyperglycemia is responsible for accumulation of reactive oxygen species in the brain, resulting in advanced glycosylated end products and a proinflammatory response that may lead to cellular injury.Further research is needed to define the impact of both acute and chronic hyperglycemia on cognitive impairment and memory.

Effects of Ganglioside on Working Memory and the Default Mode Network in Individuals with Subjective Cognitive Impairment: A Randomized Controlled Trial.

PubMed

Jeon, Yujin; Kim, Binna; Kim, Jieun E; Kim, Bori R; Ban, Soonhyun; Jeong, Jee Hyang; Kwon, Oran; Rhie, Sandy Jeong; Ahn, Chang-Won; Kim, Jong-Hoon; Jung, Sung Ug; Park, Soo-Hyun; Lyoo, In Kyoon; Yoon, Sujung

2016-01-01

This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).

Bisphenol A impairs the memory function and glutamatergic homeostasis in a sex-dependent manner in mice: Beneficial effects of diphenyl diselenide.

PubMed

Jardim, Natália S; Sartori, Glaúbia; Sari, Marcel H M; Müller, Sabrina G; Nogueira, Cristina W

2017-08-15

Bisphenol A (BPA) is a compound integrated in commodities, which consequently increases the human exposure to this toxicant. The deleterious effects of BPA exposure during periods of brain development have been documented mainly concerning the impairment in memory functions. Diphenyl diselenide (PhSe) 2 , an organoselenium compound, shows protective/restorative effects against memory deficits in experimental models. Thus, this study investigated the effects of (PhSe) 2 on the memory impairments induced by BPA exposure to male and female mice and the possible involvement of glutamatergic system in these effects. Three-week-old male and female Swiss mice received BPA (5mg/kg), intragastrically, from 21st to 60th postnatal day. After, the animals were intragastrically treated with (PhSe) 2 (1mg/kg) during seven days. The mice performed the behavioral memory tests and the [ 3 H] glutamate uptake and NMDA receptor subunits (2A and 2B) analyses were carried out in the hippocampus and cerebral cortex of mice. The results demonstrated that the BPA exposure induced impairment of object recognition memory in both sexes. However, it caused impairments in spatial memory in female and in the passive avoidance memory in male mice. Besides, BPA caused a decrease in the [ 3 H] glutamate uptake and NMDA receptor subunit levels in the cortical and hippocampal regions depending on the sex. Treatment with (PhSe) 2 reversed in a sex-independent manner the behavioral impairments and molecular alterations. In conclusion, BPA had a negative effect in different memory types as well as in the glutamatergic parameters in a sex-dependent manner and (PhSe) 2 treatment was effective against these alterations. Copyright © 2017 Elsevier Inc. All rights reserved.

Is selective mutism associated with deficits in memory span and visual memory?: An exploratory case-control study.

PubMed

Kristensen, Hanne; Oerbeck, Beate

2006-01-01

Our main aim in this study was to explore the association between selective mutism (SM) and aspects of nonverbal cognition such as visual memory span and visual memory. Auditory-verbal memory span was also examined. The etiology of SM is unclear, and it probably represents a heterogeneous condition. SM is associated with language impairment, but nonspecific neurodevelopmental factors, including motor problems, are also reported in SM without language impairment. Furthermore, SM is described in Asperger's syndrome. Studies on nonverbal cognition in SM thus merit further investigation. Neuropsychological tests were administered to a clinical sample of 32 children and adolescents with SM (ages 6-17 years, 14 boys and 18 girls) and 62 nonreferred controls matched for age, gender, and socioeconomic status. We used independent t-tests to compare groups with regard to auditory-verbal memory span, visual memory span, and visual memory (Benton Visual Retention Test), and employed linear regression analysis to study the impact of SM on visual memory, controlling for IQ and measures of language and motor function. The SM group differed from controls on auditory-verbal memory span but not on visual memory span. Controlled for IQ, language, and motor function, the SM group did not differ from controls on visual memory. Motor function was the strongest predictor of visual memory performance. SM does not appear to be associated with deficits in visual memory span or visual memory. The reduced auditory-verbal memory span supports the association between SM and language impairment. More comprehensive neuropsychological studies are needed.

A Differential Deficit in Time- versus Event-based Prospective Memory in Parkinson's Disease

PubMed Central

Raskin, Sarah A.; Woods, Steven Paul; Poquette, Amelia J.; McTaggart, April B.; Sethna, Jim; Williams, Rebecca C.; Tröster, Alexander I.

2010-01-01

Objective The aim of the current study was to clarify the nature and extent of impairment in time- versus event-based prospective memory in Parkinson's disease (PD). Prospective memory is thought to involve cognitive processes that are mediated by prefrontal systems and are executive in nature. Given that individuals with PD frequently show executive dysfunction, it is important to determine whether these individuals may have deficits in prospective memory that could impact daily functions, such as taking medications. Although it has been reported that individuals with PD evidence impairment in prospective memory, it is still unclear whether they show a greater deficit for time- versus event-based cues. Method Fifty-four individuals with PD and 34 demographically similar healthy adults were administered a standardized measure of prospective memory that allows for a direct comparison of time-based and event-based cues. In addition, participants were administered a series of standardized measures of retrospective memory and executive functions. Results Individuals with PD demonstrated impaired prospective memory performance compared to the healthy adults, with a greater impairment demonstrated for the time-based tasks. Time-based prospective memory performance was moderately correlated with measures of executive functioning, but only the Stroop Neuropsychological Screening Test emerged as a unique predictor in a linear regression. Conclusions Findings are interpreted within the context of McDaniel and Einstein's (2000) multi-process theory to suggest that individuals with PD experience particular difficulty executing a future intention when the cue to execute the prescribed intention requires higher levels of executive control. PMID:21090895

Apathy, but not depression, is associated with executive dysfunction in cerebral small vessel disease

PubMed Central

Hollocks, Matthew J.; Morris, Robin G.; Markus, Hugh S.

2017-01-01

Objective To determine the prevalence of apathy and depression in cerebral small vessel disease (SVD), and the relationships between both apathy and depression with cognition. To examine whether apathy is specifically related to impairment in executive functioning and processing speed. Methods 196 patients with a clinical lacunar stroke and an anatomically corresponding lacunar infarct on MRI were compared to 300 stroke-free controls. Apathy and depression were measured using the Geriatric Depression Scale, and cognitive functioning was assessed using an SVD cognitive screening tool, the Brief Memory and Executive Test, which measures executive functioning/processing speed and memory/orientation. Path analysis and binary logistic regression were used to assess the relation between apathy, depression and cognitive impairment. Results 31 participants with SVD (15.8%) met criteria for apathy only, 23 (11.8%) for both apathy and depression, and 2 (1.0%) for depression only. In the SVD group the presence of apathy was related to global cognition, and specifically to impaired executive functioning/processing speed, but not memory/orientation. The presence of depression was not related to global cognition, impaired executive functioning/processing speed or memory/orientation. Conclusions Apathy is a common feature of SVD and is associated with impaired executive functioning/processing speed suggesting the two may share biological mechanisms. Screening for apathy should be considered in SVD, and further work is required to develop and evaluate effective apathy treatment or management in SVD. PMID:28493898

A model of memory impairment in schizophrenia: cognitive and clinical factors associated with memory efficiency and memory errors.

PubMed

Brébion, Gildas; Bressan, Rodrigo A; Ohlsen, Ruth I; David, Anthony S

2013-12-01

Memory impairments in patients with schizophrenia have been associated with various cognitive and clinical factors. Hallucinations have been more specifically associated with errors stemming from source monitoring failure. We conducted a broad investigation of verbal memory and visual memory as well as source memory functioning in a sample of patients with schizophrenia. Various memory measures were tallied, and we studied their associations with processing speed, working memory span, and positive, negative, and depressive symptoms. Superficial and deep memory processes were differentially associated with processing speed, working memory span, avolition, depression, and attention disorders. Auditory/verbal and visual hallucinations were differentially associated with specific types of source memory error. We integrated all the results into a revised version of a previously published model of memory functioning in schizophrenia. The model describes the factors that affect memory efficiency, as well as the cognitive underpinnings of hallucinations within the source monitoring framework. © 2013.

Dissociation of long-term verbal memory and fronto-executive impairment in first-episode psychosis

PubMed Central

Leeson, V. C.; Robbins, T. W.; Franklin, C.; Harrison, M.; Harrison, I.; Ron, M. A.; Barnes, T. R. E.; Joyce, E. M.

2009-01-01

Background Verbal memory is frequently and severely affected in schizophrenia and has been implicated as a mediator of poor clinical outcome. Whereas encoding deficits are well demonstrated, it is unclear whether retention is impaired. This distinction is important because accelerated forgetting implies impaired consolidation attributable to medial temporal lobe (MTL) dysfunction whereas impaired encoding and retrieval implicates involvement of prefrontal cortex. Method We assessed a group of healthy volunteers (n=97) and pre-morbid IQ- and sex-matched first-episode psychosis patients (n=97), the majority of whom developed schizophrenia. We compared performance of verbal learning and recall with measures of visuospatial working memory, planning and attentional set-shifting, and also current IQ. Results All measures of performance, including verbal memory retention, a memory savings score that accounted for learning impairments, were significantly impaired in the schizophrenia group. The difference between groups for delayed recall remained even after the influence of learning and recall was accounted for. Factor analyses showed that, in patients, all variables except verbal memory retention loaded on a single factor, whereas in controls verbal memory and fronto-executive measures were separable. Conclusions The results suggest that IQ, executive function and verbal learning deficits in schizophrenia may reflect a common abnormality of information processing in prefrontal cortex rather than specific impairments in different cognitive domains. Verbal memory retention impairments, however, may have a different aetiology. PMID:19419594

The self-imagination effect: benefits of a self-referential encoding strategy on cued recall in memory-impaired individuals with neurological damage.

PubMed

Grilli, Matthew D; Glisky, Elizabeth L

2011-09-01

Knowledge of oneself is preserved in many memory-impaired individuals with neurological damage. Therefore, cognitive strategies that capitalize on mechanisms related to the self may be particularly effective at enhancing memory in this population. The present study investigated the effect of "self-imagining," imagining an event from a personal perspective, on short and long delayed cued recall in memory-impaired individuals with neurological damage. Sixteen patients intentionally encoded word pairs under four separate conditions: visual imagery, semantic elaboration, other person imagining, and self-imagining. The results revealed that self-imagining led to better performance than other-imagining, semantic elaboration, and visual imagery. Furthermore, the "self-imagination effect" (SIE) was preserved after a 30-min delay and was independent of memory functioning. These findings indicate that self-imagining provides a mnemonic advantage in brain-injured individuals, even those with relatively poor memory functioning, and suggest that self-imagining may tap into mnemonic mechanisms related to the self.

Effects of Physical Activity and Ginkgo Biloba on Cognitive Function and Oxidative Stress Modulation in Ischemic Rats.

PubMed

Vaghef, Ladan; Bafandeh Gharamaleki, Hassan

2017-09-01

Either exercise or Ginkgo biloba is reported to improve cognitive functioning. The aim of this study is to compare the protective effects of forced exercise and Ginkgo biloba on oxidative stress as well as memory impairments induced by transient cerebral ischemia. Adult male Wistar rats were treated with treadmill running or Ginkgo biloba extract for 2 weeks before cerebral ischemia. Memory was assessed using a Morris water maze (MWM) task. At the end of the behavioral testing, oxidative stress biomarkers were evaluated in the hippocampus tissue. As expected, the cerebral ischemia induced memory impairment in the MWM task, and oxidative stress in the hippocampus. These effects were significantly prevented by treadmill running. Indeed, it ameliorated oxidative stress and memory deficits induced by ischemia. In contrast, Ginkgo biloba was not as effective as exercise in preventing ischemia-induced memory impairments. The results confirmed the neuroprotective effects of treadmill running on hippocampus-dependent memory.

Depression and Cognitive Impairment in Peritoneal Dialysis: A Multicenter Cross-sectional Study.

PubMed

Dong, Jie; Pi, Hai-Chen; Xiong, Zu-Ying; Liao, Jin-Lan; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia

2016-01-01

Depression and cognitive impairment have been identified as independent risk factors for mortality in peritoneal dialysis (PD) patients. The relationship between depression and global and specific cognitive functions in PD patients was investigated in this study. Multicenter cross-sectional study. 458 clinically stable patients, drawn from 5 PD units, who performed PD for at least 3 months were enrolled. Depression, defined as depression severity index score > 0.5 using the Zung Self-rating Depression Scale. Global and specific cognitive impairment. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. Prevalences of depression and cognitive impairment evaluated by the 3MS were 52% and 28.4%, respectively. Patients with mild or moderate/severe depression had higher prevalences of general cognitive impairment, executive dysfunction, and impaired immediate and delayed memory. After adjusting for demographics, comorbid conditions, and clinical parameters, depression scores were independently associated with lower 3MS scores, lower immediate and delayed memory and language ability scores, and longer completion times of Trails A and B. Even mild depression was independently associated with higher risk for cognitive impairment, executive dysfunction, and impaired immediate and delayed memory after multivariable adjustments. The causal relationship between depression and cognitive impairment could not be determined, and the potential copathogenesis behind depression and cognitive impairment was not fully investigated. Even mild depression is closely associated with global and specific cognitive impairment in PD patients. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Prefrontal atrophy, disrupted NREM slow waves, and impaired hippocampal-dependent memory in aging

PubMed Central

Mander, Bryce A.; Rao, Vikram; Lu, Brandon; Saletin, Jared M.; Lindquist, John R.; Ancoli-Israel, Sonia; Jagust, William; Walker, Matthew P.

2014-01-01

Aging has independently been associated with regional brain atrophy, reduced non-rapid eye movement (NREM) slow-wave activity (SWA), and impaired long-term retention of episodic memories. However, that the interaction of these factors represents a neuropatholgical pathway associated with cognitive decline in later life remains unknown. Here, we show that age-related medial prefrontal cortex (mPFC) grey-matter atrophy is associated with reduced NREM SWA activity in older adults, the extent to which statistically mediates the impairment of overnight sleep-dependent memory retention. Moreover, this memory impairment was further associated with persistent hippocampal activation and reduced task-related hippocampal-prefrontal cortex connectivity, potentially representing impoverished hippocampal-neocortical memory transformation. Together, these data support a model in which age-related mPFC atrophy diminishes SWA, the functional consequence of which is impaired long-term memory. Such findings suggest that sleep disruption in the elderly, mediated by structural brain changes, represent a novel contributing factor to age-related cognitive decline in later life. PMID:23354332

Quieting the overactive hippocampus restores memory in aging.

PubMed

Baxter, Mark G

2012-07-01

A recent study by Bakker et al. shows that a low dose of the antiepileptic drug levetiracetam reduces hippocampal hyperactivity in elderly humans with amnestic mild cognitive impairment and improves hippocampal memory function. This points towards a new treatment strategy for age-related memory impairment by reducing deleterious overactivity of the hippocampus. Copyright © 2012 Elsevier Ltd. All rights reserved.

Thalamic and hippocampal volume associated with memory functions in multiple sclerosis.

PubMed

Tremblay, Alexandra; Jobin, Céline; Demers, Mélanie; Dagenais, Emmanuelle; Narayanan, Sridar; Araújo, David; Douglas, Arnold L; Roger, Elaine; Chamelian, Laury; Duquette, Pierre; Rouleau, Isabelle

2018-06-08

Although multiple sclerosis (MS) has long been considered to primarily affect white matter, it is now recognized that cognitive deficits in MS are also related to neocortical, thalamic and hippocampal damage. However, the association between damage to these structures and memory deficits in MS is unclear. This study examines whether MS patients with cognitive impairment have a reduction of hippocampal and/or thalamic volumes compared to cognitively intact patients, and whether these volume reductions correlate with various aspects of memory function. Volumetric MRI measures of thalamus and hippocampus of forty-one patients with MS were performed. The patients were divided in two groups depending on the presence or absence of cognitive impairment, based on their neuropsychological tests scores. Right hippocampal volume was found to be associated with learning, and the left thalamic volume was found to predict performance in verbal memory. Cognitively impaired patients had a tendency to have a reduced left thalamic volume compared to cognitively intact patients. This study does not support a direct relationship between hippocampal atrophy and verbal memory. These results add to the growing evidence of the involvement of thalamus in cognitive impairment in MS and its association with verbal memory deficits. Copyright © 2018. Published by Elsevier Inc.

Dissociative amnesia.

PubMed

Staniloiu, Angelica; Markowitsch, Hans J

2014-08-01

Dissociative amnesia is one of the most enigmatic and controversial psychiatric disorders. In the past two decades, interest in the understanding of its pathophysiology has surged. In this report, we review new data about the epidemiology, neurobiology, and neuroimaging of dissociative amnesia and show how advances in memory research and neurobiology of dissociation inform proposed pathogenetic models of the disorder. Dissociative amnesia is characterised by functional impairment. Additionally, preliminary data suggest that affected people have an increased and possibly underestimated suicide risk. The prevalence of dissociative amnesia differs substantially across countries and populations. Symptoms and disease course also vary, indicating a possibly heterogeneous disorder. The accompanying clinical features differ across cultural groups. Most dissociative amnesias are retrograde, with memory impairments mainly involving the episodic-autobiographical memory domain. Anterograde dissociative amnesia occurring without significant retrograde memory impairments is rare. Functional neuroimaging studies of dissociative amnesia with prevailing retrograde memory impairments show changes in the network that subserves autobiographical memory. At present, no evidence-based treatments are available for dissociative amnesia and no broad framework exists for its rehabilitation. Further research is needed into its neurobiology, course, treatment options, and strategies to improve differential diagnoses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Spatial versus verbal memory impairments in patients with fibromyalgia.

PubMed

Kim, Seong-Ho; Kim, Sang-Hyon; Kim, Seong-Kyu; Nam, Eun Jung; Han, Seung Woo; Lee, Seung Jae

2012-05-01

Mounting evidence suggests that individuals with fibromyalgia (FM) have impairments in general cognitive functions. However, few studies have explored the possibility of dissociation between verbal and visuospatial memory impairments in FM. Therefore, the purpose of this study was to investigate the asymmetrical impairment of cognitive functions between verbal and visuospatial memory and between short-term and long-term memory. Neuropsychological assessments were carried out on 23 female patients with FM and 24 healthy female controls. Verbal memory abilities were assessed using the Korean version of the Rey auditory verbal learning test (KAVLT) and digit span task, and visuospatial memory abilities were assessed using the Korean version of the Rey complex figure test (KCFT) and spatial span task. The analysis of covariance was used to assess group differences in performance on cognitive tests after controlling for depression. The two groups did not significantly differ in terms of age, years of education, or in their estimated verbal and performance IQ, but FM patients reported more severe depressive symptoms than did controls on the Beck depression inventory. Significant group differences were found in immediate and delayed recall on the KCFT (F (1,44) = 6.49, p = 0.014 and F (1,44) = 6.96, p = 0.011, respectively), whereas no difference was found in immediate and delayed recall on the KAVLT. In terms of short-term memory, neither the digit span task nor spatial span task showed any difference between groups, regardless of whether repetition was forward or backward. These findings suggest that spatial memory abilities may be more impaired than verbal memory abilities in patients with FM.

Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

PubMed

Battini, R; Chieffo, D; Bulgheroni, S; Piccini, G; Pecini, C; Lucibello, S; Lenzi, S; Moriconi, F; Pane, M; Astrea, G; Baranello, G; Alfieri, P; Vicari, S; Riva, D; Cioni, G; Mercuri, E

2018-02-01

The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy. Copyright © 2017 Elsevier B.V. All rights reserved.

Changes in Neuropsychological Status during the Initial Phase of Abstinence in Alcohol Use Disorder: Neurocognitive Impairment and Implications for Clinical Care.

PubMed

Mulhauser, Kyler; Weinstock, Jeremiah; Ruppert, Phillip; Benware, Jeffrey

2018-05-12

Neuropsychological deficits are common in individuals with alcohol use disorder (AUD) and impact daily functioning and AUD treatment outcomes. Longitudinal studies demonstrate that extended abstinence improves neuropsychological functioning. The effects of short-term abstinence are less clear. This study examined changes in neuropsychological functioning after acute detoxification over a 10-day period at the beginning of residential AUD treatment. Notably, this study evaluated cognitive functioning according to diagnostic classifications for neurocognitive disorder according to DSM-5. Using a within-subjects design, neuropsychological functioning of participants (N = 28) undergoing a 14-day residential AUD treatment program was assessed at two time points over 10 days (i.e., treatment entry, prior to treatment discharge). Tests of immediate memory, visuospatial abilities, attention, language abilities, delayed memory, and executive functioning were administered. After completing acute detoxification, almost all participants (93%) were clinically impaired in at least one of the five cognitive domains at residential treatment entry, with one third of the sample impaired on ≥3 domains. Ten days later, 71% remained clinically impaired in at least one of five cognitive domains, with 29% of the sample impaired on ≥3 domains. Significant improvement over the 10-day period was observed for immediate memory, visuospatial abilities, and overall cognitive functioning. Clinical significance of these changes is also reported. Conclusions/Importance: The results from this study help to characterize cognitive functioning in terms of neurocognitive impairment. A brief period of abstinence begins to ameliorate neuropsychological deficits, but many individuals remain cognitively impaired throughout treatment. Implications for treatment are discussed.

Does Working Memory Impact Functional Outcomes in Individuals With ADHD: A Qualitative and Comprehensive Literature Review.

PubMed

Fried, Ronna; Abrams, Jessica; Hall, Anna; Feinberg, Leah; Pope, Amanda; Biederman, Joseph

2017-09-01

Working Memory (WM) is a domain of executive functioning often impaired in individuals with ADHD. Although assumed to cause difficulties across functioning, the scope of impairments from WM deficits in ADHD has not been investigated. The aim of this study was to examine outcomes associated with WM deficits in ADHD. We conducted a search of the scientific literature on WM deficits, and Freedom From Distractibility (FFD), in ADHD using PubMed and PsycInfo databases. The final sample included 11 controlled studies of WM/FFD deficits in ADHD with operationalized assessment of outcomes in academic, social, and emotional areas. WM assessment was divided into auditory-verbal memory (AVM) and spatial-visual memory (SWM). Seven studies examined WM deficits in academic functioning, eight studies assessed WM deficits in social functioning, and three assessed WM deficits in psychopathology. The majority of the literature suggests that WM deficits affect primarily academic functioning.

Sequenced neurocognitive and behavioral parent training for the treatment of ADHD in school-age children.

PubMed

Chacko, A; Bedard, A-C V; Marks, D; Gopalan, G; Feirsen, N; Uderman, J; Chimiklis, A; Heber, E; Cornwell, M; Anderson, L; Zwilling, A; Ramon, M

2018-05-01

The present study examines the potential of sequencing a neurocognitive intervention with behavioral parent training (BPT) to improve executive functions (EFs), psychiatric symptoms, and multiple indices of functional impairment in school-age children aged 7 to 11 years who have been diagnosed with attention-deficit/hyperactivity disorder (ADHD). Specifically, in a randomized controlled trial design, 85 children were assigned to either Cogmed Working Memory Training (CWMT) followed by an empirically supported, manualized BPT intervention, or to a placebo version of CWMT followed by the same BPT intervention. Working memory maintenance (i.e., attention control/short-term memory), working memory processing and manipulation, ADHD and oppositional defiant disorder (ODD) symptoms, impairment in parent-child dynamics, familial impairment, and overall functional compromise were evaluated as outcomes. The results suggest specific effects of the combined CWMT and BPT program on verbal and nonverbal working memory storage and nonverbal working memory processing and manipulation but no incremental benefits in regard to ADHD symptoms, ODD symptoms, and functional outcomes. The present findings do not support the hypothesis regarding the complementary and augmentative benefits of sequenced neurocognitive and BPT interventions for the treatment of ADHD. These results, the study's limitations, and future directions for research are further discussed.

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

PubMed Central

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

2015-01-01

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

The effect of cannabis use on memory function: an update.

PubMed

Schoeler, Tabea; Bhattacharyya, Sagnik

2013-01-01

Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis-induced memory impairments occur and to elucidate underlying neurobiological mechanisms.

The effect of cannabis use on memory function: an update

PubMed Central

Schoeler, Tabea; Bhattacharyya, Sagnik

2013-01-01

Investigating the effects of cannabis use on memory function appears challenging. While early observational investigations aimed to elucidate the longer-term effects of cannabis use on memory function in humans, findings remained equivocal and pointed to a pattern of interacting factors impacting on the relationship between cannabis use and memory function, rather than a simple direct effect of cannabis. Only recently, a clearer picture of the chronic and acute effects of cannabis use on memory function has emerged once studies have controlled for potential confounding factors and started to investigate the acute effects of delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), the main ingredients in the extract of the cannabis plant in pharmacological challenge experiments. Relatively consistent findings have been reported regarding the acute impairments induced by a single dose of Δ9-THC on verbal and working memory. It is unclear whether they may persist beyond the intoxication state. In the long-term, these impairments seem particularly likely to manifest and may also persist following abstinence if regular and heavy use of cannabis strains high in Δ9-THC is started at an early age. Although still at an early stage, studies that employed advanced neuroimaging techniques have started to model the neural underpinnings of the effects of cannabis use and implicate a network of functional and morphological alterations that may moderate the effects of cannabis on memory function. Future experimental and epidemiological studies that take into consideration individual differences, particularly previous cannabis history and demographic characteristics, but also the precise mixture of the ingredients of the consumed cannabis are necessary to clarify the magnitude and the mechanisms by which cannabis-induced memory impairments occur and to elucidate underlying neurobiological mechanisms. PMID:24648785

Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence.

PubMed

Driesen, Naomi R; Leung, Hoi-Chung; Calhoun, Vincent D; Constable, R Todd; Gueorguieva, Ralitza; Hoffman, Ralph; Skudlarski, Pawel; Goldman-Rakic, Patricia S; Krystal, John H

2008-12-15

Comparing prefrontal cortical activity during particular phases of working memory in healthy subjects and individuals diagnosed with schizophrenia might help to define the phase-specific deficits in cortical function that contribute to cognitive impairments associated with schizophrenia. This study featured a spatial working memory task, similar to that used in nonhuman primates, that was designed to facilitate separating brain activation into encoding, maintenance, and response phases. Fourteen patients with schizophrenia (4 medication-free) and 12 healthy comparison participants completed functional magnetic resonance imaging while performing a spatial working memory task with two levels of memory load. Task accuracy was similar in patients and healthy participants. However, patients showed reductions in brain activation during maintenance and response phases but not during the encoding phase. The reduced prefrontal activity during the maintenance phase of working memory was attributed to a greater rate of decay of prefrontal activity over time in patients. Cortical deficits in patients did not appear to be related to antipsychotic treatment. In patients and in healthy subjects, the time-dependent reduction in prefrontal activity during working memory maintenance correlated with poorer performance on the memory task. Overall, these data highlight that basic research insights into the distinct neurobiologies of the maintenance and response phases of working memory are of potential importance for understanding the neurobiology of cognitive impairment in schizophrenia and advancing its treatment.

Application of new WAIS-III/WMS-III discrepancy scores for evaluating memory functioning: relationship between intellectual and memory ability.

PubMed

Lange, Rael T; Chelune, Gordon J

2006-05-01

Analysis of the discrepancy between memory and intellectual ability has received some support as a means for evaluating memory impairment. Recently, comprehensive base rate tables for General Ability Index (GAI) minus memory discrepancy scores (i.e., GAI-memory) were developed using the WAIS-III/WMS-III standardization sample (Lange, Chelune, & Tulsky, in press). The purpose of this study was to evaluate the clinical utility of GAI-memory discrepancy scores to identify memory impairment in 34 patients with Alzheimer's type dementia (DAT) versus a sample of 34 demographically matched healthy participants. On average, patients with DAT obtained significantly lower scores on all WAIS-III and WMS-III indexes and had larger GAI-memory discrepancy scores. Clinical outcome analyses revealed that GAI-memory scores were useful at identifying memory impairment in patients with DAT versus matched healthy participants. However, GAI-memory discrepancy scores failed to provide unique interpretive information beyond that which is gained from the memory indexes alone. Implications and future research directions are discussed.

Persistent anterograde amnesia following limbic encephalitis associated with antibodies to the voltage-gated potassium channel complex.

PubMed

Butler, Christopher R; Miller, Thomas D; Kaur, Manveer S; Baker, Ian W; Boothroyd, Georgie D; Illman, Nathan A; Rosenthal, Clive R; Vincent, Angela; Buckley, Camilla J

2014-04-01

Limbic encephalitis (LE) associated with antibodies to the voltage-gated potassium channel complex (VGKC) is a potentially reversible cause of cognitive impairment. Despite the prominence of cognitive dysfunction in this syndrome, little is known about patients' neuropsychological profile at presentation or their long-term cognitive outcome. We used a comprehensive neuropsychological test battery to evaluate cognitive function longitudinally in 19 patients with VGKC-LE. Before immunotherapy, the group had significant impairment of memory, processing speed and executive function, whereas language and perceptual organisation were intact. At follow-up, cognitive impairment was restricted to the memory domain, with processing speed and executive function having returned to the normal range. Residual memory function was predicted by the antibody titre at presentation. The results show that, despite broad cognitive dysfunction in the acute phase, patients with VGKC-LE often make a substantial recovery with immunotherapy but may be left with permanent anterograde amnesia.

D-Serine rescues the deficits of hippocampal long-term potentiation and learning and memory induced by sodium fluoroacetate.

PubMed

Han, Huili; Peng, Yan; Dong, Zhifang

2015-06-01

It is well known that bidirectional glia-neuron interactions play important roles in the neurophysiological and neuropathological processes. It is reported that impairing glial functions with sodium fluoroacetate (FAC) impaired hippocampal long-term depression (LTD) and spatial memory retrieval. However, it remains unknown whether FAC impairs hippocampal long-term potentiation (LTP) and learning and/or memory, and if so, whether pharmacological treatment with exogenous d-serine can recuse the impairment. Here, we reported that systemic administration of FAC (3mg/kg, i.p.) before training resulted in dramatic impairments of spatial learning and memory in water maze and fear memory in contextual fear conditioning. Furthermore, the behavioral deficits were accompanied by impaired LTP induction in the hippocampal CA1 area of brain slices. More importantly, exogenous d-serine treatment succeeded in recusing the deficits of hippocampal LTP and learning and memory induced by FAC. Together, these results suggest that astrocytic d-serine may be essential for hippocampal synaptic plasticity and memory, and that alteration of its levels may be relevant to the induction and potentially treatment of psychiatric and neurological disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

Memory and executive functions in patients with obsessive-compulsive disorder.

PubMed

Vandborg, Sanne Kjær; Hartmann, Tue Borst; Bennedsen, Birgit Egedal; Pedersen, Anders Degn; Thomsen, Per Hove

2014-03-01

We investigated whether patients with obsessive-compulsive disorder have poorer memory and executive functions than healthy controls. The relatively inconsistent previous findings on this question reflect a lack of well-matched control groups, the inclusion of patients with comorbidity, and the use of noncomparable neuropsychological tests to assess memory and executive functions. We used well-accepted neuropsychological tests of memory and executive functions to assess 42 patients who had obsessive-compulsive disorder without comorbidity, and 42 healthy controls. We matched the patients and controls pairwise by sex, age, and years of education. The patients performed significantly worse than the controls on the Rey Complex Figure Test, which assesses visuospatial memory and organizational skills. This group difference remained after we controlled for age, education, intelligence, and severity of depressive symptoms. The findings indicate that patients with obsessive-compulsive disorder may have impaired visuospatial memory and organizational skills, and these impairments should be considered in treatment. ClinicalTrials.gov NCT00792038.

The Acceptability and Potential Utility of Cognitive Training to Improve Working Memory in Persons Living With HIV: A Preliminary Randomized Trial.

PubMed

Towe, Sheri L; Patel, Puja; Meade, Christina S

HIV-associated neurocognitive impairments that impact daily function persist in the era of effective antiretroviral therapy. Cognitive training, a promising low-cost intervention, has been shown to improve neurocognitive functioning in some clinical populations. We tested the feasibility, acceptability, and preliminary effects of computerized cognitive training to improve working memory in persons living with HIV infection (PLWH) and working memory impairment. In this randomized clinical trial, we assigned 21 adult PLWH to either an experimental cognitive training intervention or an attention-matched control training intervention. Participants completed 12 training sessions across 10 weeks with assessments at baseline and post-training. Session attendance was excellent and participants rated the program positively. Participants in the experimental arm demonstrated improved working memory function over time; participants in the control arm showed no change. Our results suggest that cognitive training may be a promising intervention for working memory impairment in PLWH and should be evaluated further. Copyright © 2017 Association of Nurses in AIDS Care. Published by Elsevier Inc. All rights reserved.

Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist

PubMed Central

Newman, L. A.

2015-01-01

Rationale Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors. Objectives The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function. Results Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release. Conclusions These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist—to decrease scopolamine-induced increases in acetylcholine output or to decrease post-synaptic acetylcholine receptor activation—may mediate the negative effects on memory of muscarinic antagonists. PMID:26660295

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.

Remote semantic memory for public figures in HIV infection, alcoholism, and their comorbidity.

PubMed

Fama, Rosemary; Rosenbloom, Margaret J; Sassoon, Stephanie A; Thompson, Megan A; Pfefferbaum, Adolf; Sullivan, Edith V

2011-02-01

Impairments in component processes of working and episodic memory mark both HIV infection and chronic alcoholism, with compounded deficits often observed in individuals comorbid for these conditions. Remote semantic memory processes, however, have only seldom been studied in these diagnostic groups. Examination of remote semantic memory could provide insight into the underlying processes associated with storage and retrieval of learned information over extended time periods while elucidating spared and impaired cognitive functions in these clinical groups. We examined component processes of remote semantic memory in HIV infection and chronic alcoholism in 4 subject groups (HIV, ALC, HIV + ALC, and age-matched healthy adults) using a modified version of the Presidents Test. Free recall, recognition, and sequencing of presidential candidates and election dates were assessed. In addition, component processes of working, episodic, and semantic memory were assessed with ancillary cognitive tests. The comorbid group (HIV + ALC) was significantly impaired on sequencing of remote semantic information compared with age-matched healthy adults. Free recall of remote semantic information was also modestly impaired in the HIV + ALC group, but normal performance for recognition of this information was observed. Few differences were observed between the single diagnosis groups (HIV, ALC) and healthy adults, although examination of the component processes underlying remote semantic memory scores elicited differences between the HIV and ALC groups. Selective remote memory processes were related to lifetime alcohol consumption in the ALC group and to viral load and depression level in the HIV group. Hepatitis C diagnosis was associated with lower remote semantic memory scores in all 3 clinical groups. Education level did not account for group differences reported. This study provides behavioral support for the existence of adverse effects associated with the comorbidity of HIV infection and chronic alcoholism on selective component processes of memory function, with untoward effects exacerbated by Hepatitis C infection. The pattern of remote semantic memory function in HIV + ALC is consistent with those observed in neurological conditions primarily affecting frontostriatal pathways and suggests that remote memory dysfunction in HIV + ALC may be a result of impaired retrieval processes rather than loss of remote semantic information per se. Copyright © 2010 by the Research Society on Alcoholism.

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.

Working memory and reward association learning impairments in obesity.

PubMed

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

2014-12-01

Obesity has been associated with impaired executive functions including working memory. Less explored is the influence of obesity on learning and memory. In the current study we assessed stimulus reward association learning, explicit learning and memory and working memory in healthy weight, overweight and obese individuals. Explicit learning and memory did not differ as a function of group. In contrast, working memory was significantly and similarly impaired in both overweight and obese individuals compared to the healthy weight group. In the first reward association learning task the obese, but not healthy weight or overweight participants consistently formed paradoxical preferences for a pattern associated with a negative outcome (fewer food rewards). To determine if the deficit was specific to food reward a second experiment was conducted using money. Consistent with Experiment 1, obese individuals selected the pattern associated with a negative outcome (fewer monetary rewards) more frequently than healthy weight individuals and thus failed to develop a significant preference for the most rewarded patterns as was observed in the healthy weight group. Finally, on a probabilistic learning task, obese compared to healthy weight individuals showed deficits in negative, but not positive outcome learning. Taken together, our results demonstrate deficits in working memory and stimulus reward learning in obesity and suggest that obese individuals are impaired in learning to avoid negative outcomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Smad4 SUMOylation is essential for memory formation through upregulation of the skeletal myopathy gene TPM2.

PubMed

Hsu, Wei L; Ma, Yun L; Liu, Yen C; Lee, Eminy H Y

2017-11-28

Smad4 is a critical effector of TGF-β signaling that regulates a variety of cellular functions. However, its role in the brain has rarely been studied. Here, we examined the molecular mechanisms underlying the post-translational regulation of Smad4 function by SUMOylation, and its role in spatial memory formation. In the hippocampus, Smad4 is SUMOylated by the E3 ligase PIAS1 at Lys-113 and Lys-159. Both spatial training and NMDA injection enhanced Smad4 SUMOylation. Inhibition of Smad4 SUMOylation impaired spatial learning and memory in rats by downregulating TPM2, a gene associated with skeletal myopathies. Similarly, knockdown of TPM2 expression impaired spatial learning and memory, while TPM2 mRNA and protein expression increased after spatial training. Among the TPM2 mutations associated with skeletal myopathies, the TPM2E122K mutation was found to reduce TPM2 expression and impair spatial learning and memory in rats. We have identified a novel role of Smad4 SUMOylation and TPM2 in learning and memory formation. These results suggest that patients with skeletal myopathies who carry the TPM2E122K mutation may also have deficits in learning and memory functions.

Distinct and shared cognitive functions mediate event- and time-based prospective memory impairment in normal ageing

PubMed Central

Gonneaud, Julie; Kalpouzos, Grégoria; Bon, Laetitia; Viader, Fausto; Eustache, Francis; Desgranges, Béatrice

2011-01-01

Prospective memory (PM) is the ability to remember to perform an action at a specific point in the future. Regarded as multidimensional, PM involves several cognitive functions that are known to be impaired in normal aging. In the present study, we set out to investigate the cognitive correlates of PM impairment in normal aging. Manipulating cognitive load, we assessed event- and time-based PM, as well as several cognitive functions, including executive functions, working memory and retrospective episodic memory, in healthy subjects covering the entire adulthood. We found that normal aging was characterized by PM decline in all conditions and that event-based PM was more sensitive to the effects of aging than time-based PM. Whatever the conditions, PM was linked to inhibition and processing speed. However, while event-based PM was mainly mediated by binding and retrospective memory processes, time-based PM was mainly related to inhibition. The only distinction between high- and low-load PM cognitive correlates lays in an additional, but marginal, correlation between updating and the high-load PM condition. The association of distinct cognitive functions, as well as shared mechanisms with event- and time-based PM confirms that each type of PM relies on a different set of processes. PMID:21678154

Dopaminergic basis for deficits in working memory but not attentional set-shifting in Parkinson's disease.

PubMed

Lewis, Simon J G; Slabosz, Aleksandra; Robbins, Trevor W; Barker, Roger A; Owen, Adrian M

2005-01-01

Although Parkinson's disease is a common neurodegenerative disorder characterised by its motoric symptoms, there is an increasing recognition of accompanying impairments in cognition that have a profound impact on the quality of life of these patients. These deficits predominantly affect executive function and impairments of working memory have been frequently reported. However, the underlying neurochemical and pathological basis for these deficits are not well understood. In this study, 20 patients were tested 'on' and 'off' levodopa (L-dopa) medication on a task that allowed different aspects of working memory function such as maintenance, retrieval and manipulation to be tested within the same general paradigm as well as on an unrelated test of attentional set-shifting, which is known to be sensitive to deficits in early Parkinson's disease. Compared to healthy volunteers, PD patients were impaired at manipulation more than maintenance or retrieval of information within working memory. The patients were also impaired at the attentional set-shifting task. However, whereas L-dopa ameliorated the working memory deficit in manipulation (improving both accuracy and cognitive response time), it had no effect on the attentional set-shifting impairment. These results confirm that working memory deficits in PD are both psychologically specific and related to dopamine depletion. It is anticipated that greater understanding of these mechanisms will lead to future therapeutic improvements.

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

PubMed

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

2015-10-29

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

Working memory and social functioning in children.

PubMed

McQuade, Julia D; Murray-Close, Dianna; Shoulberg, Erin K; Hoza, Betsy

2013-07-01

This study extends previous research and examines whether working memory (WM) is associated with multiple measures of concurrent social functioning (peer rejection, overall social competence, relational aggression, physical aggression, and conflict resolutions skills) in typically developing fourth- and fifth-grade children (N=116). Poor central executive WM was associated with both broad social impairments (peer rejection and poor overall social competence) and specific social impairments (physical aggression, relational aggression, and impaired conflict resolution skills); poor verbal storage was associated only with greater peer rejection, and spatial storage was not associated with any measures of social impairment. Analyses also examined whether specific impairments in aggressive behavior and conflict resolution skills mediated the association between central executive and broad measures of social functioning. Greater physical aggression and impaired conflict resolution skills were both significant mediators; relational aggression was not. Implications for theory and future research are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

Impaired social recognition memory in Recombination Activating Gene 1-deficient mice

PubMed Central

McGowan, Patrick O.; Hope, Thomas A.; Meck, Warren H.; Kelsoe, Garnett; Williams, Christina L.

2012-01-01

The Recombination Activating Genes (RAGs) encode two enzymes that play key roles in the adaptive immune system. RAG1 and RAG2 mediate VDJ recombination, a process necessary for the maturation of B- and T-cells. Interestingly, RAG1 is also expressed in the brain, particularly in areas of high neural density such as the hippocampus, although its function is unknown. We tested evidence that RAG1 plays a role in brain function using a social recognition memory task, an assessment of the acquisition and retention of conspecific identity. In a first experiment, we found that RAG1-deficient mice show impaired social recognition memory compared to mice wildtype for the RAG1 allele. In a second experiment, by breeding to homogenize background genotype we found that RAG1-deficient mice show impaired social recognition memory relative to heterozygous or RAG2-deficient littermates. Because RAG1 and RAG2 null mice are both immunodeficient, the results suggest that the memory impairment is not an indirect effect of immunological dysfunction. RAG1-deficient mice show normal habituation to non-socially derived odors and habituation to an open-field, indicating that the observed effect is not likely a result of a general deficit in habituation to novelty. These data trace the origin of the impairment in social recognition memory in RAG1-deficient mice to the RAG1 gene locus and implicate RAG1 in memory formation. PMID:21354115

Emotional intelligence and social functioning in persons with schizotypy.

PubMed

Aguirre, Fabian; Sergi, Mark J; Levy, Cynthia A

2008-09-01

The present study is the first to examine emotional intelligence in persons with schizotypy. Over 2100 undergraduates were screened for schizotypy with the Schizotypal Personality Questionnaire-Brief Version. Forty participants identified as persons with high schizotypy and 56 participants identified as persons with low schizotypy completed assessments of emotional intelligence (Mayer-Salovey-Caruso Emotional Intelligence Test), social functioning (Social Adjustment Scale-Self Report), verbal episodic (secondary) memory (California Verbal Learning Test), and executive functioning (Wisconsin Card Sorting Test). Persons high in schizotypy were impaired in overall emotional intelligence and two aspects of emotional intelligence, the ability to perceive emotions and the ability to manage emotions. Persons high in schizotypy were also impaired in three aspects of social functioning: peer relationships, family relationships, and academic functioning. Group differences in verbal episodic (secondary) memory and executive functioning were not observed. For persons with high schizotypy, overall emotional intelligence and two aspects of emotional intelligence, the ability to perceive emotions and the ability to manage emotions, were associated with peer relationship functioning. Overall emotional intelligence was associated with verbal episodic (secondary) memory, but not executive functioning, in persons with high schizotypy. The current findings suggest that emotional intelligence is impaired in persons with schizotypy and that these impairments affect their social functioning.

White Matter Integrity Linked To Functional Impairments in Aging and Early Alzheimer’s Disease

PubMed Central

Kavcic, Voyko; Ni, Hongyan; Zhu, Tong; Zhong, Jianhui; Duffy, Charles J.

2008-01-01

Background Alzheimer’s disease (AD) is associated with changes in cerebral white matter (WM) but the functional significance of such findings is not yet established. We hypothesized that diffusion tensor imaging (DTI) might reveal links between regional WM changes and specific neuropsychologically and psychophysically defined impairments in early AD. Methods Older adult control subjects (OA, n=18) and mildly impaired AD patients (n=14) underwent neuropsychological and visual perceptual testing along with DTI of cerebral WM. DTI yielded factional anisotropy (FA) and mean diffusivity () maps for nine ROIs in three brain regions that were then compared to the performance measures. Results AD patients showed non-significant trends toward lower FAs in the posterior region’s callosal and sub-cortical ROIs. However, posterior callosal FA was significantly correlated with verbal fluency and figural memory impairments, whereas posterior subcortical FA was correlated with delayed verbal memory, figural memory, and optic flow perceptual impairments. Conclusions WM changes in early AD are concentrated in posterior cerebral areas with distributions that correspond to specific functional impairments. DTI can be used to assess regional pathology related to individual’s deficits in early AD. PMID:19012862

Cognitive Impairment and Structural Abnormalities in Late Life Depression with Olfactory Identification Impairment: an Alzheimer's Disease-Like Pattern.

PubMed

Chen, Ben; Zhong, Xiaomei; Mai, Naikeng; Peng, Qi; Wu, Zhangying; Ouyang, Cong; Zhang, Weiru; Liang, Wanyuan; Wu, Yujie; Liu, Sha; Chen, Lijian; Ning, Yuping

2018-03-15

Late-life depression patients are at a high risk of developing Alzheimer's disease, and diminished olfactory identification is an indicator in early screening for Alzheimer's disease in the elderly. However, whether diminished olfactory identification is associated with risk of developing Alzheimer's disease in late-life depression patients remains unclear. One hundred and twenty-five late-life depression patients, 50 Alzheimer's disease patients, and 60 normal controls were continuously recruited. The participants underwent a clinical evaluation, olfactory test, neuropsychological assessment, and neuroimaging assessment. The olfactory identification impairment in late-life depression patients was milder than that in Alzheimer's disease patients. Diminished olfactory identification was significantly correlated with worse cognitive performance (global function, memory language, executive function, and attention) and reduced grey matter volume (olfactory bulb and hippocampus) in the late-life depression patients. According to a multiple linear regression analysis, olfactory identification was significantly associated with the memory scores in late-life depression group (B=1.623, P<.001). The late-life depression with olfactory identification impairment group had worse cognitive performance (global, memory, language, and executive function) and more structural abnormalities in Alzheimer's disease-related regions than the late-life depression without olfactory identification impairment group, and global cognitive function and logical memory in the late-life depression without olfactory identification impairment group was intact. Reduced volume observed in many areas (hippocampus, precuneus, etc.) in the Alzheimer's disease group was also observed in late-life depression with olfactory identification impairment group but not in the late-life depression without olfactory identification impairment group. The patterns of cognitive impairment and structural abnormalities in late-life depression with olfactory identification impairment patients were similar to those in Alzheimer's disease; olfactory identification may help identify late-life depression patients who are at a high risk of developing Alzheimer's disease.

Life satisfaction two-years after stroke onset: the effects of gender, sex occupational status, memory function and quality of life among stroke patients (Newsqol) and their family caregivers (Whoqol-bref) in Luxembourg

PubMed Central

2012-01-01

Background Life satisfaction (LS) of cerebrovascular disease survivors and their family caregivers may relate to socioeconomic factors, impaired functions, health-related quality of life (QoL), but their respective influences remain unclear. This study assessed, two years post-stroke onset, the effects of these factors on patients’ LS and family caregivers’ LS in Luxembourg. Methods All stroke patients admitted to all hospitals in Luxembourg were identified by the ‘Inspection Général de la Sécurité Sociale’ using the only national system database for care expenditure reimbursement. Their diagnosis was confirmed by medical investigator. The sample included ninety four patients living at home having given consent (mean age 65.5 years) and sixty two main caregivers (mean age 59.3 years). Questionnaires were completed during face-to-face interviews. LS was assessed via European single question (range 1–10), survivors’ QoL via Newsqol (11 dimensions), and caregivers’ QoL via Whoqol-bref (4 domains) (range 0–100). Data were analysed using multiple regression models. Results Two years after stroke onset, 44.7% of patients suffered from impaired sensory function, 35.1% from impaired motor function, and 31.9% from impaired memory function. Mean patient’ LS was 7.1/10 (SD 1.9). It was higher in women (+12.4) and lower among unemployed socioeconomically active patients (−13.1, vs. retired people). Adjusted for sex, occupation, impaired motor and memory functions, LS positively correlated with scores of Newsqol feelings, sleep, emotion, cognition and pain dimensions (slopes 0.20 to 0.31), but did not correlate with those of caregivers’ Whoqol-bref domains. Family caregiver’ LS was 7.2 (SD 1.7). It was lower in those with patients suffering from impaired memory function (−12.8) as well as from feelings and emotion issues (slopes 0.22). It was associated with all caregivers’ Whoqol-bref domains (physical health, psychological health, environment, and social relationships) (slopes 0.53 to 0.68). Conclusions Two-year post-cerebrovascular disease patient’ LS was associated with gender, occupation, and impaired memory function. It correlated with feelings, sleep, emotion, cognition, and pain issues. Family caregivers of patients with impaired memory function had lower LS. Family caregiver’ LS correlated with dimensions of patients’ feelings (less independent, yourself, life changed, depressed, useless, less control because of stroke) and emotion (get more emotional, fear of another stroke or to become dependent on others), and with their own QoL. LS, Newsqol, and Whoqol appeared to be appropriate tools. Our findings may be useful for policy makers in relation to family and medical-social issues of stroke home-based rehabilitation. PMID:23009364

Life satisfaction two-years after stroke onset: the effects of gender, sex occupational status, memory function and quality of life among stroke patients (Newsqol) and their family caregivers (Whoqol-bref) in Luxembourg.

PubMed

Baumann, Michèle; Couffignal, Sophie; Le Bihan, Etienne; Chau, Nearkasen

2012-09-25

Life satisfaction (LS) of cerebrovascular disease survivors and their family caregivers may relate to socioeconomic factors, impaired functions, health-related quality of life (QoL), but their respective influences remain unclear. This study assessed, two years post-stroke onset, the effects of these factors on patients' LS and family caregivers' LS in Luxembourg. All stroke patients admitted to all hospitals in Luxembourg were identified by the 'Inspection Général de la Sécurité Sociale' using the only national system database for care expenditure reimbursement. Their diagnosis was confirmed by medical investigator. The sample included ninety four patients living at home having given consent (mean age 65.5 years) and sixty two main caregivers (mean age 59.3 years). Questionnaires were completed during face-to-face interviews. LS was assessed via European single question (range 1-10), survivors' QoL via Newsqol (11 dimensions), and caregivers' QoL via Whoqol-bref (4 domains) (range 0-100). Data were analysed using multiple regression models. Two years after stroke onset, 44.7% of patients suffered from impaired sensory function, 35.1% from impaired motor function, and 31.9% from impaired memory function. Mean patient' LS was 7.1/10 (SD 1.9). It was higher in women (+12.4) and lower among unemployed socioeconomically active patients (-13.1, vs. retired people). Adjusted for sex, occupation, impaired motor and memory functions, LS positively correlated with scores of Newsqol feelings, sleep, emotion, cognition and pain dimensions (slopes 0.20 to 0.31), but did not correlate with those of caregivers' Whoqol-bref domains. Family caregiver' LS was 7.2 (SD 1.7). It was lower in those with patients suffering from impaired memory function (-12.8) as well as from feelings and emotion issues (slopes 0.22). It was associated with all caregivers' Whoqol-bref domains (physical health, psychological health, environment, and social relationships) (slopes 0.53 to 0.68). Two-year post-cerebrovascular disease patient' LS was associated with gender, occupation, and impaired memory function. It correlated with feelings, sleep, emotion, cognition, and pain issues. Family caregivers of patients with impaired memory function had lower LS. Family caregiver' LS correlated with dimensions of patients' feelings (less independent, yourself, life changed, depressed, useless, less control because of stroke) and emotion (get more emotional, fear of another stroke or to become dependent on others), and with their own QoL. LS, Newsqol, and Whoqol appeared to be appropriate tools. Our findings may be useful for policy makers in relation to family and medical-social issues of stroke home-based rehabilitation.

Isoflurane anesthesia exacerbates learning and memory impairment in zinc-deficient APP/PS1 transgenic mice.

PubMed

Feng, Chunsheng; Liu, Ya; Yuan, Ye; Cui, Weiwei; Zheng, Feng; Ma, Yuan; Piao, Meihua

2016-12-01

Zinc (Zn) is known to play crucial roles in numerous brain functions including learning and memory. Zn deficiency is believed to be widespread throughout the world, particularly in patients with Alzheimer's disease (AD). A number of studies have shown that volatile anesthetics, such as isoflurane, might be potential risk factors for the development of AD. However, whether isoflurane exposure accelerates the process of AD and cognitive impairment in AD patients with Zn deficiency is yet to be documented. The aim of the present study was to explore the effects of 1.4% isoflurane exposure for 2 h on learning and memory function, and neuropathogenesis in 10-month-old Zn-adequate, Zn-deficient, and Zn-treated APP/PS1 mice with the following parameters: behavioral tests, neuronal apoptosis, Aβ, and tau pathology. The results demonstrated that isoflurane exposure showed no impact on learning and memory function, but induced transient elevation of neuroapoptosis in Zn-adequate APP/PS1 mice. Exposure of isoflurane exhibited significant neuroapoptosis, Aβ generation, tau phosphorylation, and learning and memory impairment in APP/PS1 mice in the presence of Zn deficiency. Appropriate Zn treatment improved learning and memory function, and prevented isoflurane-induced neuroapoptosis in APP/PS1 mice. Isoflurane exposure may cause potential neurotoxicity, which is tolerated to some extent in Zn-adequate APP/PS1 mice. When this tolerance is limited, like in AD with Zn deficiency, isoflurane exposure markedly exacerbated learning and memory impairment, and neuropathology, indicating that AD patients with certain conditions such as Zn deficiency may be vulnerable to volatile anesthetic isoflurane. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impaired cognitive plasticity and goal-directed control in adolescent obsessive-compulsive disorder.

PubMed

Gottwald, Julia; de Wit, Sanne; Apergis-Schoute, Annemieke M; Morein-Zamir, Sharon; Kaser, Muzaffer; Cormack, Francesca; Sule, Akeem; Limmer, Winifred; Morris, Anna Conway; Robbins, Trevor W; Sahakian, Barbara J

2018-01-22

Youths with obsessive-compulsive disorder (OCD) experience severe distress and impaired functioning at school and at home. Critical cognitive domains for daily functioning and academic success are learning, memory, cognitive flexibility and goal-directed behavioural control. Performance in these important domains among teenagers with OCD was therefore investigated in this study. A total of 36 youths with OCD and 36 healthy comparison subjects completed two memory tasks: Pattern Recognition Memory (PRM) and Paired Associates Learning (PAL); as well as the Intra-Extra Dimensional Set Shift (IED) task to quantitatively gauge learning as well as cognitive flexibility. A subset of 30 participants of each group also completed a Differential-Outcome Effect (DOE) task followed by a Slips-of-Action Task, designed to assess the balance of goal-directed and habitual behavioural control. Adolescent OCD patients showed a significant learning and memory impairment. Compared with healthy comparison subjects, they made more errors on PRM and PAL and in the first stages of IED involving discrimination and reversal learning. Patients were also slower to learn about contingencies in the DOE task and were less sensitive to outcome devaluation, suggesting an impairment in goal-directed control. This study advances the characterization of juvenile OCD. Patients demonstrated impairments in all learning and memory tasks. We also provide the first experimental evidence of impaired goal-directed control and lack of cognitive plasticity early in the development of OCD. The extent to which the impairments in these cognitive domains impact academic performance and symptom development warrants further investigation.

The puzzle of processing speed, memory, and executive function impairments in schizophrenia: fitting the pieces together.

PubMed

Knowles, Emma E M; Weiser, Mark; David, Anthony S; Glahn, David C; Davidson, Michael; Reichenberg, Abraham

2015-12-01

Substantial impairment in performance on the digit-symbol substitution task in patients with schizophrenia is well established, which has been widely interpreted as denoting a specific impairment in processing speed. However, other higher order cognitive functions might be more critical to performance on this task. To date, this idea has not been rigorously investigated in patients with schizophrenia. Neuropsychological measures of processing speed, memory, and executive functioning were completed by 125 patients with schizophrenia and 272 control subjects. We implemented a series of confirmatory factor and structural regression modeling to build an integrated model of processing speed, memory, and executive function with which to deconstruct the digit-symbol substitution task and characterize discrepancies between patients with schizophrenia and control subjects. The overall structure of the processing speed, memory, and executive function model was the same across groups (χ(2) = 208.86, p > .05), but the contribution of the specific cognitive domains to coding task performance differed significantly. When completing the task, control subjects relied on executive function and, indirectly, on working memory ability, whereas patients with schizophrenia used an alternative set of cognitive operations whereby they relied on the same processes required to complete verbal fluency tasks. Successful coding task performance relies predominantly on executive function, rather than processing speed or memory. Patients with schizophrenia perform poorly on this task because of an apparent lack of appropriate executive function input; they rely instead on an alternative cognitive pathway. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Discrete memory impairments in largely pure chronic users of MDMA.

PubMed

Wunderli, Michael D; Vonmoos, Matthias; Fürst, Marina; Schädelin, Katrin; Kraemer, Thomas; Baumgartner, Markus R; Seifritz, Erich; Quednow, Boris B

2017-10-01

Chronic use of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has repeatedly been associated with deficits in working memory, declarative memory, and executive functions. However, previous findings regarding working memory and executive function are inconclusive yet, as in most studies concomitant stimulant use, which is known to affect these functions, was not adequately controlled for. Therefore, we compared the cognitive performance of 26 stimulant-free and largely pure (primary) MDMA users, 25 stimulant-using polydrug MDMA users, and 56 MDMA/stimulant-naïve controls by applying a comprehensive neuropsychological test battery. Neuropsychological tests were grouped into four cognitive domains. Recent drug use was objectively quantified by 6-month hair analyses on 17 substances and metabolites. Considerably lower mean hair concentrations of stimulants (amphetamine, methamphetamine, methylphenidate, cocaine), opioids (morphine, methadone, codeine), and hallucinogens (ketamine, 2C-B) were detected in primary compared to polydrug users, while both user groups did not differ in their MDMA hair concentration. Cohen's d effect sizes for both comparisons, i.e., primary MDMA users vs. controls and polydrug MDMA users vs. controls, were highest for declarative memory (d primary =.90, d polydrug =1.21), followed by working memory (d primary =.52, d polydrug =.96), executive functions (d primary =.46, d polydrug =.86), and attention (d primary =.23, d polydrug =.70). Thus, primary MDMA users showed strong and relatively discrete declarative memory impairments, whereas MDMA polydrug users displayed broad and unspecific cognitive impairments. Consequently, even largely pure chronic MDMA use is associated with decreased performance in declarative memory, while additional deficits in working memory and executive functions displayed by polydrug MDMA users are likely driven by stimulant co-use. Copyright © 2017 Elsevier B.V. and ECNP. All rights reserved.

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence

PubMed Central

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C.

2015-01-01

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1 mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05 mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. PMID:26234588

Dissociable performance on scene learning and strategy implementation after lesions to magnocellular mediodorsal thalamic nucleus

PubMed Central

Mitchell, Anna S.; Baxter, Mark G.; Gaffan, David

2008-01-01

Monkeys with aspiration lesions of the magnocellular division of the mediodorsal thalamus (MDmc) are impaired in object-in-place scene learning, object recognition and stimulus-reward association. These data have been interpreted to mean that projections from MDmc to prefrontal cortex are required to sustain normal prefrontal function in a variety of task settings. In the present study, we investigated the extent to which bilateral neurotoxic lesions of the MDmc impair a pre-operatively learnt strategy implementation task that is impaired by a crossed lesion technique that disconnects the frontal cortex in one hemisphere from the contralateral inferotemporal cortex. Postoperative memory impairments were also examined using the object-in-place scene memory task. Monkeys learnt both strategy implementation and scene memory tasks separately to a stable level pre-operatively. Bilateral neurotoxic lesions of the MDmc, produced by 10 × 1 μl injections of a mixture of ibotenate and N-methyl-D-aspartate did not affect performance in the strategy implementation task. However, new learning of object-in-place scene memory was substantially impaired. These results provide new evidence about the role of the magnocellular mediodorsal thalamic nucleus in memory processing, indicating that interconnections with the prefrontal cortex are essential during new learning but are not required when implementing a preoperatively acquired strategy task. Thus not all functions of the prefrontal cortex require MDmc input. Instead the involvement of MDmc in prefrontal function may be limited to situations in which new learning must occur. PMID:17978029

Contribution of N-methyl-D-aspartate receptors to attention and episodic spatial memory during senescence.

PubMed

Guidi, Michael; Rani, Asha; Karic, Semir; Severance, Barrett; Kumar, Ashok; Foster, Thomas C

2015-11-01

A decrease in N-methyl-D-aspartate receptor (NMDAR) function is associated with age-related cognitive impairments. However, NMDAR antagonists are prescribed for cognitive decline associated with age-related neurodegenerative disease, raising questions as to the role of NMDAR activity in cognitive function during aging. The current studies examined effects of NMDAR blockade on cognitive task that are sensitive to aging. Young and middle-age rats were trained on the five-choice serial reaction time task (5-CSRTT) and challenged with MK-801 (0.025, 0.05, and 0.1mg/kg or vehicle). Attention deficits were apparent in middle-age and performance of young and middle-age rats was enhanced for low doses of MK-801 (0.025 and 0.05). The beneficial effects on attention were reversed by the highest dose of MK-801. Older animals exhibited a delay-dependent impairment of episodic spatial memory examined on a delayed-matching to place water maze task. Similarly, a low dose of MK-801 (0.05mg/kg) impaired performance with increasing delay and aged animals were more susceptible to disruption by NMDAR blockade. Despite MK-801 impairment of episodic spatial memory, MK-801 had minimal effects on spatial reference memory. Our results confirm that NMDARs contribute to rapidly acquired and flexible spatial memory and support the idea that a decline in NMDAR function contributes to the age-related impairments in cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Episodic memory in aspects of large-scale brain networks

PubMed Central

Jeong, Woorim; Chung, Chun Kee; Kim, June Sic

2015-01-01

Understanding human episodic memory in aspects of large-scale brain networks has become one of the central themes in neuroscience over the last decade. Traditionally, episodic memory was regarded as mostly relying on medial temporal lobe (MTL) structures. However, recent studies have suggested involvement of more widely distributed cortical network and the importance of its interactive roles in the memory process. Both direct and indirect neuro-modulations of the memory network have been tried in experimental treatments of memory disorders. In this review, we focus on the functional organization of the MTL and other neocortical areas in episodic memory. Task-related neuroimaging studies together with lesion studies suggested that specific sub-regions of the MTL are responsible for specific components of memory. However, recent studies have emphasized that connectivity within MTL structures and even their network dynamics with other cortical areas are essential in the memory process. Resting-state functional network studies also have revealed that memory function is subserved by not only the MTL system but also a distributed network, particularly the default-mode network (DMN). Furthermore, researchers have begun to investigate memory networks throughout the entire brain not restricted to the specific resting-state network (RSN). Altered patterns of functional connectivity (FC) among distributed brain regions were observed in patients with memory impairments. Recently, studies have shown that brain stimulation may impact memory through modulating functional networks, carrying future implications of a novel interventional therapy for memory impairment. PMID:26321939

The effect of hippocampal function, volume and connectivity on posterior cingulate cortex functioning during episodic memory fMRI in mild cognitive impairment.

PubMed

Papma, Janne M; Smits, Marion; de Groot, Marius; Mattace Raso, Francesco U; van der Lugt, Aad; Vrooman, Henri A; Niessen, Wiro J; Koudstaal, Peter J; van Swieten, John C; van der Veen, Frederik M; Prins, Niels D

2017-09-01

Diminished function of the posterior cingulate cortex (PCC) is a typical finding in early Alzheimer's disease (AD). It is hypothesized that in early stage AD, PCC functioning relates to or reflects hippocampal dysfunction or atrophy. The aim of this study was to examine the relationship between hippocampus function, volume and structural connectivity, and PCC activation during an episodic memory task-related fMRI study in mild cognitive impairment (MCI). MCI patients (n = 27) underwent episodic memory task-related fMRI, 3D-T1w MRI, 2D T2-FLAIR MRI and diffusion tensor imaging. Stepwise linear regression analysis was performed to examine the relationship between PCC activation and hippocampal activation, hippocampal volume and diffusion measures within the cingulum along the hippocampus. We found a significant relationship between PCC and hippocampus activation during successful episodic memory encoding and correct recognition in MCI patients. We found no relationship between the PCC and structural hippocampal predictors. Our results indicate a relationship between PCC and hippocampus activation during episodic memory engagement in MCI. This may suggest that during episodic memory, functional network deterioration is the most important predictor of PCC functioning in MCI. • PCC functioning during episodic memory relates to hippocampal functioning in MCI. • PCC functioning during episodic memory does not relate to hippocampal structure in MCI. • Functional network changes are an important predictor of PCC functioning in MCI.

Memory and mood during MDMA intoxication, with and without memantine pretreatment.

PubMed

de Sousa Fernandes Perna, E B; Theunissen, E L; Kuypers, K P C; Heckman, P; de la Torre, R; Farre, M; Ramaekers, J G

2014-12-01

Previous studies have shown that single doses of MDMA can affect mood and impair memory in humans. The neuropharmacological mechanisms involved in MDMA-induced memory impairment are not clear. Memantine, an NMDA and alpha 7 nicotinic acetylcholine (ACh) receptor antagonist, was able to reverse MDMA-induced memory impairment in rats. This study investigated whether treatment with memantine can prevent MDMA-induced memory impairment in humans. 15 subjects participated in a double-blind, placebo controlled, within-subject design. Subjects received both pre-treatment (placebo/memantine 20 mg) (T1) and treatment (placebo/MDMA 75 mg) (T2) on separate test days. T1 preceded T2 by 120 min. Memory function was assessed 90 min after T2 by means of a Visual Verbal Learning Task, a Prospective Memory Task, the Sternberg Memory Task and the Abstract Visual Pattern Learning Task. Profile of Mood State and psychomotor performance were also assessed to control whether MDMA and memantine interactions would selectively pertain to memory or transfer to other domains as well. MDMA significantly impaired performance in the visual verbal learning task and abstract visual pattern learning task. Pre-treatment with memantine did not prevent MDMA-induced memory impairment in these two tasks. Both positive (vigour, arousal, elation) and negative mood effects (anxiety) were increased by MDMA. The responses were not altered by pretreatment with memantine which had no effect on memory or mood when given alone. These preliminary results suggest that memantine does not reverse MDMA-induced memory impairment and mood in humans. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

Memory in ASD: Have We Been Barking up the Wrong Tree?

ERIC Educational Resources Information Center

Boucher, Jill; Mayes, Andrew

2012-01-01

In this theoretical note, possible neural causes of episodic memory impairment in individuals with ASD and currently normal intellectual and linguistic function are considered. The neural causes most commonly argued for are hippocampal or prefrontal cortex dysfunction, associated with impaired neural connectivity. It is argued here that a…

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

The nature of verbal memory impairment in multiple sclerosis: a list-learning and meta-analytic study.

PubMed

Lafosse, Jose M; Mitchell, Sandra M; Corboy, John R; Filley, Christopher M

2013-10-01

The primary purpose of this study was to test the hypothesis that multiple sclerosis (MS) patients have impaired acquisition rather than a retrieval deficit. Verbal memory impairment in MS was examined in 53 relapsing-remitting MS patients and 31 healthy controls (HC), and in a meta-analysis of studies that examined memory functioning in MS with list-learning tasks. The MS group demonstrated significantly lower acquisition and delayed recall performance than the HC group, and the meta-analysis revealed that the largest effect sizes were obtained for acquisition measures relative to delayed recall and recognition. Our data argue against a retrieval deficit as the sole explanation for verbal memory impairment in MS, and make a consistent case for the position that deficient acquisition contributes to the memory dysfunction of MS patients. Deficient acquisition may result from demyelination in relevant white matter tracts that reduces encoding efficiency as a result of impaired speed of information processing.

Working Memory and Cognitive Flexibility Mediates Visuoconstructional Abilities in Older Adults with Heterogeneous Cognitive Ability.

PubMed

Ávila, Rafaela T; de Paula, Jonas J; Bicalho, Maria A; Moraes, Edgar N; Nicolato, Rodrigo; Malloy-Diniz, Leandro F; Diniz, Breno S

2015-05-01

Previous studies suggest that executive functions influence the performance on visuoconstructional tasks. This study aims to investigate whether the relationship between planning ability and the copy of complex figures is mediated by distinct components of executive functions (i.e., working memory, inhibitory control and cognitive flexibility). We included a 129 older adults with Alzheimer's disease (n=36, AD), mild cognitive impairment (MCI, n=67), and with no evidence of cognitive impairment (controls, n=26). We evaluated the mediation effect of planning abilities, working memory, cognitive flexibility and inhibitory control on visuoconstructional tasks using a multiple mediation models. We found a significant direct effect of planning on visuoconstructional abilities and a partial mediation effect of working memory and cognitive flexibility on visuoconstructional abilities. The present results indicate that the performance on visuoconstructional task is mediated by multiple interrelated executive functions components, in particular working memory and cognitive flexibility.

Spatial Navigation Impairments Among Intellectually High-Functioning Adults With Autism Spectrum Disorder: Exploring Relations With Theory of Mind, Episodic Memory, and Episodic Future Thinking

PubMed Central

2013-01-01

Research suggests that spatial navigation relies on the same neural network as episodic memory, episodic future thinking, and theory of mind (ToM). Such findings have stimulated theories (e.g., the scene construction and self-projection hypotheses) concerning possible common underlying cognitive capacities. Consistent with such theories, autism spectrum disorder (ASD) is characterized by concurrent impairments in episodic memory, episodic future thinking, and ToM. However, it is currently unclear whether spatial navigation is also impaired. Hence, ASD provides a test case for the scene construction and self-projection theories. The study of spatial navigation in ASD also provides a test of the extreme male brain theory of ASD, which predicts intact or superior navigation (purportedly a systemizing skill) performance among individuals with ASD. Thus, the aim of the current study was to establish whether spatial navigation in ASD is impaired, intact, or superior. Twenty-seven intellectually high-functioning adults with ASD and 28 sex-, age-, and IQ-matched neurotypical comparison adults completed the memory island virtual navigation task. Tests of episodic memory, episodic future thinking, and ToM were also completed. Participants with ASD showed significantly diminished performance on the memory island task, and performance was positively related to ToM and episodic memory, but not episodic future thinking. These results suggest that (contra the extreme male brain theory) individuals with ASD have impaired survey-based navigation skills—that is, difficulties generating cognitive maps of the environment—and adds weight to the idea that scene construction/self-projection are impaired in ASD. The theoretical and clinical implications of these results are discussed. PMID:24364620

Cognitive functioning following traumatic brain injury: A five-year follow-up.

PubMed

Marsh, Nigel V; Ludbrook, Maria R; Gaffaney, Lauren C

2016-01-01

To describe the long-term prevalence and severity of cognitive deficits following significant (i.e., ventilation required for >24 hours) traumatic brain injury. To assess a comprehensive range of cognitive functions using psychometric measures with established normative, reliability, and validity data. A group of 71 adults was assessed at approximately five years (mean = 66 months) following injury. Assessment of cognitive functioning covered the domains of intelligence, attention, verbal and visual memory, visual-spatial construction, and executive functions. Impairment was evident across all domains but prevalence varied both within and between domains. Across aspects of intelligence clinical impairment ranged from 8-25% , attention 39-62% , verbal memory 16-46% , visual memory 23-51% , visual-spatial construction 38% , and executive functions (verbal fluency) 13% . In addition, 3-23% of performances across the measures were in the borderline range, suggesting a high prevalence of subclinical deficit. Although the prevalence of impairment may vary across cognitive domains, long-term follow-up documented deficits in all six domains. These findings provide further evidence that while improvement of cognitive functioning following significant traumatic brain injury may be possible, recovery of function is unlikely.

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

PubMed

Drago, Ilaria; Davis, Ronald L

2016-09-06

The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Time-based and event-based prospective memory in autism spectrum disorder: the roles of executive function and theory of mind, and time-estimation.

PubMed

Williams, David; Boucher, Jill; Lind, Sophie; Jarrold, Christopher

2013-07-01

Prospective memory (remembering to carry out an action in the future) has been studied relatively little in ASD. We explored time-based (carry out an action at a pre-specified time) and event-based (carry out an action upon the occurrence of a pre-specified event) prospective memory, as well as possible cognitive correlates, among 21 intellectually high-functioning children with ASD, and 21 age- and IQ-matched neurotypical comparison children. We found impaired time-based, but undiminished event-based, prospective memory among children with ASD. In the ASD group, time-based prospective memory performance was associated significantly with diminished theory of mind, but not with diminished cognitive flexibility. There was no evidence that time-estimation ability contributed to time-based prospective memory impairment in ASD.

Free and Cued Recall Memory in Parkinson’s Disease Associated with Amnestic Mild Cognitive Impairment

PubMed Central

Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A.

2014-01-01

The hypothesis has been advanced that memory disorders in individuals with Parkinson’s disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients’ performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning. PMID:24465977

Delay-dependent working memory impairment in young-adult and aged 5-HT1BKO mice as assessed in a radial-arm water maze.

PubMed

Wolff, Mathieu; Benhassine, Narimane; Costet, Pierre; Hen, Rene; Segu, Louis; Buhot, Marie-Christine

2003-01-01

Serotonin (5-HT) plays a modulatory role in mnemonic functions, especially by interacting with the cholinergic system. The 5-HT1B receptor is a key target of this interaction. The 5-HT1B receptor knockout mice were found previously to exhibit a facilitation in hippocampal-dependent spatial reference memory learning. In the present study, we submitted mice to a delayed spatial working memory task, allowing the introduction of various delays between an exposure trial and a test trial. The 5-HT1BKO and wild-type mice learned the task in a radial-arm water maze (returning to the most recent presented arm containing the escape platform), and exhibited a high level of performance at delays of 0 and 5 min. However, at the delay of 60 min, only 5-HT1BKO mice exhibited an impairment. At a delay of 90 min, all mice were impaired. Treatment by scopolamine (0.8 mg/kg) induced the same pattern of performance in wild type as did the mutation for short (5 min, no impairment) and long (60 min, impairment) delays. The 22-month-old wild-type and knockout mice exhibited an impairment at short delays (5 and 15 min). The effect of the mutation affected both young-adult and aged mice at delays of 15, 30, and 60 min. Neurobiological data show that stimulation of the 5-HT1B receptor inhibits the release of acetylcholine in the hippocampus, but stimulates this in the frontal cortex. This dual function might, at least in part, explain the opposite effect of the mutation on reference memory (facilitation) and delay-dependent working memory (impairment). These results support the idea that cholinergic-serotonergic interactions play an important role in memory processes.

Free and cued recall memory in Parkinson's disease associated with amnestic mild cognitive impairment.

PubMed

Costa, Alberto; Monaco, Marco; Zabberoni, Silvia; Peppe, Antonella; Perri, Roberta; Fadda, Lucia; Iannarelli, Francesca; Caltagirone, Carlo; Carlesimo, Giovanni A

2014-01-01

The hypothesis has been advanced that memory disorders in individuals with Parkinson's disease (PD) are related to either retrieval or consolidation failure. However, the characteristics of the memory impairments of PD patients with amnestic mild cognitive impairment have not been clarified. This study was aimed at investigating whether memory deficits in PD patients with amnestic mild cognitive impairment (PDaMCI) are due to failure of retrieval or consolidation processes. Sixteen individuals with PDaMCI, 20 with amnestic mild cognitive impairment without PD (aMCINPD), and 20 healthy controls were recruited. Participants were administered the Free and Cued Selective Reminding Test. An index of cueing was computed for each subject to capture the advantage in retrieval of cued compared to free recall. Individuals with PDaMCI performed worse than healthy controls on the free recall (p<0.01) but not the cued recall (p>0.10) task, and they performed better than aMCINPD subjects on both recall measures (p<0.01). The index of cueing of subjects with PD was comparable to that of healthy controls (p>0.10) but it was significantly higher than that of the aMCINPD sample (p<0.01). Moreover, PD patients' performance on free recall trials was significantly predicted by scores on a test investigating executive functions (i.e., the Modified Card Sorting Test; p = 0.042). Findings of the study document that, in subjects with amnestic mild cognitive impairment associated to PD, episodic memory impairment is related to retrieval rather than to consolidation failure. The same data suggest that, in these individuals, memory deficits might be due to altered frontal-related executive functioning.

Behavioral profiles in frontal lobe epilepsy: Autobiographic memory versus mood impairment.

PubMed

Rayner, Genevieve; Jackson, Graeme D; Wilson, Sarah J

2015-02-01

Autobiographic memory encompasses the encoding and retrieval of episodes, people, and places encountered in everyday life. It can be impaired in both epilepsy and frontal lobe damage. Here, we performed an initial investigation of how autobiographic memory is impacted by chronic frontal lobe epilepsy (FLE) together with its underlying pathology. We prospectively studied a series of nine consecutive patients with medically refractory FLE, relative to 24 matched healthy controls. Seven of the nine patients had frontal lobe structural abnormalities. Episodic and semantic autobiographic memory functioning was profiled, and factors associated with impaired autobiographic memory were identified among epileptologic, neuroimaging, neuropsychiatric, and cognitive variables including auditory-verbal and visual memory, and the executive function of cognitive control. Results showed that the FLE group experienced significantly higher rates of autobiographic memory and mood disturbance (p < 0.001), with detailed assessment of individual patients revealing two profiles of impairment, primarily characterized by cognitive or mood disturbance. Five of the patients (56%) exhibited significant episodic autobiographic memory deficits, whereas in three of these, knowledge of semantic autobiographic facts was preserved. Four of them also had reduced cognitive control. Mood disorder was largely unrelated to poor autobiographic memory. In contrast, the four cases with preserved autobiographic memory were notable for their past or current depressive symptoms. These findings provide preliminary data that frontal lobe seizure activity with its underlying pathology may selectively disrupt large-scale cognitive or affective networks, giving rise to different neurobehavioral profiles that may be used to inform clinical management. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

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

PubMed

Malstädt, Nadine; Hasselhorn, Marcus; Lehmann, Martin

2012-11-01

This study examined supraspan free recall in children with and without spelling impairment. A repeated free recall task involving overt rehearsal and three computer-based adaptive working memory tasks were administered to 54 eight-year-old children. Children without spelling impairments tended to recall more items than did those children with spelling deficits. Video analyses revealed that recall behaviour was similar in impaired and unimpaired children, indicating that both groups applied similar learning activities. Group differences in number of recalled items were attributed to differences in working memory subcapacities between children with and without spelling impairment, especially with regard to central executive and phonological loop functioning. Copyright © 2012 John Wiley & Sons, Ltd.

Reduced prefrontal activation during working and long-term memory tasks and impaired patient-reported cognition among cancer survivors postchemotherapy compared with healthy controls.

PubMed

Wang, Lei; Apple, Alexandra C; Schroeder, Matthew P; Ryals, Anthony J; Voss, Joel L; Gitelman, Darren; Sweet, Jerry J; Butt, Zeeshan A; Cella, David; Wagner, Lynne I

2016-01-15

Patients who receive adjuvant chemotherapy have reported cognitive impairments that may last for years after the completion of treatment. Working memory-related and long-term memory-related changes in this population are not well understood. The objective of this study was to demonstrate that cancer-related cognitive impairments are associated with the under recruitment of brain regions involved in working and recognition memory compared with controls. Oncology patients (n = 15) who were receiving adjuvant chemotherapy and had evidence of cognitive impairment according to neuropsychological testing and self-report and a group of age-matched, education group-matched, cognitively normal control participants (n = 14) underwent functional magnetic resonance imaging. During functional magnetic resonance imaging, participants performed a nonverbal n-back working memory task and a visual recognition task. On the working memory task, when 1-back and 2-back data were averaged and contrasted with 0-back data, significantly reduced activation was observed in the right dorsolateral prefrontal cortex for oncology patients versus controls. On the recognition task, oncology patients displayed decreased activity of the left-middle hippocampus compared with controls. Neuroimaging results were not associated with patient-reported cognition. Decreased recruitment of brain regions associated with the encoding of working memory and recognition memory was observed in the oncology patients compared with the control group. These results suggest that there is a reduction in neural functioning postchemotherapy and corroborate patient-reported cognitive difficulties after cancer treatment, although a direct association was not observed. Cancer 2016;122:258-268. © 2015 American Cancer Society. © 2015 American Cancer Society.

Melatonin reverses H-89 induced spatial memory deficit: Involvement of oxidative stress and mitochondrial function.

PubMed

Sharif, Rojin; Aghsami, Mehdi; Gharghabi, Mehdi; Sanati, Mehdi; Khorshidahmad, Tina; Vakilzadeh, Gelareh; Mehdizadeh, Hajar; Gholizadeh, Shervin; Taghizadeh, Ghorban; Sharifzadeh, Mohammad

2017-01-01

Oxidative stress and mitochondrial dysfunction play indispensable role in memory and learning impairment. Growing evidences have shed light on anti-oxidative role for melatonin in memory deficit. We have previously reported that inhibition of protein kinase A by H-89 can induce memory impairment. Here, we investigated the effect of melatonin on H-89 induced spatial memory deficit and pursued their interactive consequences on oxidative stress and mitochondrial function in Morris Water Maze model. Rats received melatonin (50 and 100μg/kg/side) and H-89(10μM) intra-hippocampally 30min before each day of training. Animals were trained for 4 consecutive days, each containing one block from four trials. Oxidative stress indices, including thiobarbituric acid (TBARS), reactive oxygen species (ROS), thiol groups, and ferric reducing antioxidant power (FRAP) were assessed using spectrophotometer. Mitochondrial function was evaluated through measuring ROS production, mitochondrial membrane potential (MMP), swelling, outer membrane damage, and cytochrome c release. As expected from our previous report, H-89 remarkably impaired memory by increasing the escape latency and traveled distance. Intriguingly, H-89 significantly augmented TBARS and ROS levels, caused mitochondrial ROS production, swelling, outer membrane damage, and cytochrome c release. Moreover, H-89 lowered thiol, FRAP, and MMP values. Intriguingly, melatonin pre-treatment not only effectively hampered H-89-mediated spatial memory deficit at both doses, but also reversed the H-89 effects on mitochondrial and biochemical indices upon higher dose. Collectively, these findings highlight a protective role for melatonin against H-89-induced memory impairment and indicate that melatonin may play a therapeutic role in the treatment of oxidative- related neurodegenerative disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

Neurocognitive Functioning and Treatment Outcome Following Detoxification Among Asian Alcohol-Dependent Inpatients.

PubMed

Manning, Victoria; Teo, Hui Chin; Guo, Song; Wong, Kim Eng; Li, Ting-Kai

2016-01-28

The prevalence of alcohol use disorders in Asia is increasing and relapse among treated populations remains the norm, not the exception. The extent to which cognitive impairment influences clinical outcome remains unclear, with research dominated by studies of Caucasian populations. This study examines behavioral and self-reported cognitive functioning in detoxified alcohol-dependent (AD) patients in Singapore and its association with outcome. The cognitive performance of 30 recently-detoxified AD inpatients and 30 demographically-matched controls was compared using visuospatial memory, working memory, set-shifting, planning and reflection impulsivity tests of the CANTAB®, and self-reported dysexecutive symptoms and everyday cognitive difficulties. Patients' alcohol use and self-reported cognitive functioning were reassessed 3-months post-discharge. Compared to matched controls, AD inpatients exhibited significantly poorer fluid intelligence, visuospatial memory, working memory, set-shifting flexibility and planning/organization, but not reflection impulsivity. In support of Western studies, a significant proportion (three-quarters) were "clinically impaired" on subtests. Significant reductions were observed in alcohol units, frequency and dependency scores at follow-up, though improvements in self-reported cognitive functioning were limited to abstainers. Baseline cognitive performance did not differentiate those who had abstained from alcohol and relapsed at follow-up. Memory and executive functioning impairments were evident among Asian AD patients alongside self-reported cognitive difficulties, thus cognitively demanding psychological interventions may have limited impact during early detoxification. Future studies can build on these findings, with larger samples and measurement of moderating and mediating factors to extend our understanding of how cognitive impairment influences outcome.

Does remembering emotional items impair recall of same-emotion items?

PubMed

Sison, Jo Ann G; Mather, Mara

2007-04-01

In the part-set cuing effect, cuing a subset of previously studied items impairs recall of the remaining noncued items. This experiment reveals that cuing participants with previously-studied emotional pictures (e.g., fear-evoking pictures of people) can impair recall of pictures involving the same emotion but different content (e.g., fear-evoking pictures of animals). This indicates that new events can be organized in memory using emotion as a grouping function to create associations. However, whether new information is organized in memory along emotional or nonemotional lines appears to be a flexible process that depends on people's current focus. Mentioning in the instructions that the pictures were either amusement- or fear-related led to memory impairment for pictures with the same emotion as cued pictures, whereas mentioning that the pictures depicted either animals or people led to memory impairment for pictures with the same type of actor.

Delayed degeneration of the left fornical crus with verbal memory impairment in a patient with mild traumatic brain injury

PubMed Central

Jang, Sung Ho; Seo, Jeong Pyo

2017-01-01

Abstract Rationale: We report on a patient who showed delayed degeneration of the left fornical crus with verbal memory impairment following mild traumatic brain injury (TBI), which was demonstrated by diffusion tensor tractography (DTT). Patient concerns: fter flexion and hyperextension of her head to the opposite side, the patient experienced a dazed feeling for a while at the time of head trauma. The patient's Glasgow Coma Scale score was 15, and mini-mental state examination score was 30. Diagnoses: A 50-year-old right-handed female with 12 years of education suffered from head trauma resulting from a car accident. Interventions: A The patient showed normal memory function at one year after onset: the Memory Assessment Scale (global memory: 124 (95 percentile (%ile)), verbal memory: 111 (77%ile), and visual memory: 132 (98%ile) (A percentile is a measure used in statistics indicating the value below which a given percentage of observations in a group of observations fall). However, the patient began to experience decline of memory function such as forgetfulness at approximately 1.5 years after onset. On the 2-year evaluation, she showed decrement of memory function (global memory: 108 (70%ile), verbal memory: 86 (18%ile), and visual memory: 129 (97%ile). Outcomes: On 1-year DTT, the integrity of the fornix was well preserved between the fornical column and fornical crus. However, on 2-year DTT, a discontinuation was observed in the left fornical crus. Lessons: Delayed degeneration of the left fornical crus was demonstrated in a patient who showed delayed onset of verbal memory impairment following mild TBI. PMID:29390470

Disturbance of time orientation, attention, and verbal memory in amnesic patients with confabulation.

PubMed

Shingaki, Honoka; Park, Paeksoon; Ueda, Keita; Murai, Toshiya; Tsukiura, Takashi

2016-01-01

Confabulation is often observed in amnesic patients after brain damage. However, evidence regarding the relationship between confabulation and other neuropsychological functions is scarce. In addition, previous studies have proposed two possibilities of the relationship between confabulation and false memory, in which patients with confabulation are likely to retrieve false memories, or confabulations are relatively independent of false memories. The present study investigated how confabulation is related to various cognitive functions, including orientation, attention, frontal lobe function, memory, and mental status, and to false memories, as assessed by the Deese-Roediger-Mcdermott (DRM) paradigm. Patients with organic amnesia participated, and confabulations were evaluated using the Confabulation Battery. Amnestic patients were classified into two groups: confabulating (CP) and nonconfabulating patients (NCP). The CP group was significantly impaired in time orientation, attention, and verbal memory, compared to the NCP group and age-matched healthy controls (HC). Results of the DRM paradigm revealed no significant difference in false memory retrieval induced by critical lures across CP, NCP, and HC groups. Confabulating responses in organic amnesia could be in part induced by disturbance of time consciousness and attention control in severe impairment of verbal memories, and confabulation and false memory could be modulated by different cognitive systems.

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

PubMed

Liao, Jin-Lan; Xiong, Zu-Ying; Yang, Zhi-Kai; Hao, Li; Liu, Gui-Ling; Ren, Ye-Ping; Wang, Qin; Duan, Li-Ping; Zheng, Zhao-Xia; Dong, Jie

2017-01-01

Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Cognitive dysfunction in lower motor neuron disease: executive and memory deficits in progressive muscular atrophy.

PubMed

Raaphorst, Joost; de Visser, Marianne; van Tol, Marie-José; Linssen, Wim H J P; van der Kooi, Anneke J; de Haan, Rob J; van den Berg, Leonard H; Schmand, Ben

2011-02-01

In contrast with findings in amyotrophic lateral sclerosis (ALS), cognitive impairments have as yet not been shown in the lower motor neuron variant of motor neuron disease, progressive spinal muscular atrophy (PMA). The objective of this study was to investigate cognitive function in PMA and to compare the cognitive profile with that of ALS. In addition, visuospatial functions were assessed comprehensively; these tests are underrepresented in earlier neuropsychological investigations in ALS. 23 PMA and 30 ALS patients (vital capacity >70% of predicted value) underwent a neuropsychological assessment adapted to motor impairments: global cognitive and executive functioning, psychomotor speed, memory, language, attention and visuospatial skills. The results were compared with age, education and sex matched controls and with normative data. Compared with controls, PMA patients performed worse on attention/working memory (digit span backward), category fluency and the Mini-Mental State Examination. Compared with normative data, PMA patients most frequently showed impairment on three measures: letter-number sequencing, and immediate and delayed story recall. 17% of PMA patients showed cognitive impairment, defined as performance below 2 SDs from the mean of normative data on at least three neuropsychological tests. In ALS, similar but more extensive cognitive deficits were found. Visuospatial dysfunction was not found in PMA and ALS. 17% of PMA patients have executive and memory impairments. PMA with cognitive impairment adds a formerly unknown phenotype to the existing classification of motor neuron diseases.

Aβ Damages Learning and Memory in Alzheimer's Disease Rats with Kidney-Yang Deficiency

PubMed Central

Qi, Dongmei; Qiao, Yongfa; Zhang, Xin; Yu, Huijuan; Cheng, Bin; Qiao, Haifa

2012-01-01

Previous studies demonstrated that Alzheimer's disease was considered as the consequence produced by deficiency of Kidney essence. However, the mechanism underlying the symptoms also remains elusive. Here we report that spatial learning and memory, escape, and swimming capacities were damaged significantly in Kidney-yang deficiency rats. Indeed, both hippocampal Aβ 40 and 42 increases in Kidney-yang deficiency contribute to the learning and memory impairments. Specifically, damage of synaptic plasticity is involved in the learning and memory impairment of Kidney-yang deficiency rats. We determined that the learning and memory damage in Kidney-yang deficiency due to synaptic plasticity impairment and increases of Aβ 40 and 42 was not caused via NMDA receptor internalization induced by Aβ increase. β-Adrenergic receptor agonist can rescue the impaired long-term potential (LTP) in Kidney-yang rats. Taken together, our results suggest that spatial learning and memory inhibited in Kidney-yang deficiency might be induced by Aβ increase and the decrease of β 2 receptor function in glia. PMID:22645624

KCNQ Channels Regulate Age-Related Memory Impairment

PubMed Central

Cavaliere, Sonia; Malik, Bilal R.; Hodge, James J. L.

2013-01-01

In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment. PMID:23638087

The mere exposure effect in patients with schizophrenia.

PubMed

Marie, A; Gabrieli, J D; Vaidya, C; Brown, B; Pratto, F; Zajonc, R B; Shaw, R J

2001-01-01

The mere exposure effect refers to the development of an emotional preference for previously unfamiliar material because of frequent exposure to that material. This study compared schizophrenia subjects (n = 20) to normal controls (n = 21) to determine whether implicit memory, as demonstrated by the mere exposure effect, was intact. Patients with schizophrenia demonstrated a normal preference for both verbal and visual materials seen earlier relative to novel materials, despite impaired performance on a recognition task for explicit memory using similar materials. Previous studies of schizophrenia subjects have shown a dissociation between implicit and explicit memory on verbal tasks. We found a similar dissociation demonstrated by normal functioning on an implicit memory task and impaired functioning on an explicit memory task. Potential implications of these findings are discussed with regard to treatment and rehabilitation.

Memory Age Identity as a predictor of cognitive function in the elderly: A 2-year follow-up study.

PubMed

Chang, Ki Jung; Hong, Chang Hyung; Lee, Yun Hwan; Chung, Young Ki; Lim, Ki Young; Noh, Jai Sung; Kim, Jin-Ju; Kim, Haena; Kim, Hyun-Chung; Son, Sang Joon

2018-01-01

There is a growing interest in finding psychosocial predictors related to cognitive function. In our previous research, we conducted a cross-sectional study on memory age identity (MAI) and found that MAI might be associated with objective cognitive performance in non-cognitively impaired elderly. A longitudinal study was conducted to better understand the importance of MAI as a psychosocial predictor related to objective cognitive function. Data obtained from 1345 Korean subjects aged 60 years and above were analyzed. During the two-year follow-up, subjective memory age was assessed on three occasions using the following question: How old do you feel based on your memory? Discrepancy between subjective memory age and chronological age was then calculated. We defined this value as 'memory age identity (MAI)'. A generalized estimating equation (GEE) was then obtained to demonstrate the relationship between MAI and Korean version-Mini Mental State Examination (K-MMSE) score over the 2 years of study. MAI was found to significantly (β=-0.03, p< 0.0001) predict objective cognitive performance in the non-cognitively impaired elderly. MAI may be a potential psychosocial predictor related to objective cognitive performance in the non-cognitively impaired elderly. Copyright © 2017 Elsevier B.V. All rights reserved.

Cognitive status in patients with multiple sclerosis in Lanzarote.

PubMed

Pérez-Martín, María Yaiza; Eguia-Del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

2016-01-01

Cognitive impairment is a common feature in multiple sclerosis affecting ~43%-72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety.

Cognitive status in patients with multiple sclerosis in Lanzarote

PubMed Central

Pérez-Martín, María Yaiza; Eguia-del Río, Pablo; González-Platas, Montserrat; Jiménez-Sosa, Alejandro

2016-01-01

Objectives Cognitive impairment is a common feature in multiple sclerosis affecting ~43%–72% of patients, which involves cognitive functions such as memory, processing speed, attention, and executive function. The aim of this study was to describe the extent and pattern of the involvement of cognitive impairment and psychological status in all patients with multiple sclerosis on a small Spanish island. Patients and methods In all, 70 patients and 56 healthy controls were included in the study between February 2013 and May 2013. All participants were assessed using the Brief Repeatable Battery of Neuropsychological Test. The patients also completed instruments to evaluate the presence of fatigue, perceived cognitive dysfunction, and symptoms of anxiety and depression. All procedures were performed in a single session. Results Cognitive impairment, defined as a score <1.5 standard deviation on two subtests of the battery, was present in 35% of the participants. The most frequently affected domain was working memory, followed by verbal memory and processing speed. Disease duration showed a moderate correlation with visuospatial memory and processing speed. The Expanded Disability Status Scale score correlated with verbal and processing speed. Verbal memory was correlated with depression symptoms and fatigue. Conclusion Cognitive impairment was present in 35% of the study population. The most affected domains were working memory and verbal memory. Working memory and verbal fluency deficit are independent factors of disease evolution. Cognitive decline is related to clinical variables and psychological measures such as fatigue or depression but not to anxiety. PMID:27418825

The Neuropsychology of Amphetamine and Opiate Dependence: Implications for Treatment

PubMed Central

Sahakian, Barbara J

2013-01-01

Chronic use of amphetamines and/or opiates has been associated with a wide range of cognitive deficits, involving domains of attention, inhibitory control, planning, decision-making, learning and memory. Although both amphetamine and opiate users show marked impairment in various aspects of cognitive function, the impairment profile is distinctly different according to the substance of abuse. In light of evidence showing that cognitive impairment in drug users has a negative impact on treatment engagement and efficacy, we review substance-specific deficits on executive and memory function, and discuss possibilities to address these during treatment intervention. PMID:17690986

Impaired hippocampus-dependent and -independent learning in IL-6 deficient mice.

PubMed

Baier, Paul Christian; May, Ulrike; Scheller, Jürgen; Rose-John, Stefan; Schiffelholz, Thomas

2009-06-08

Interleukin-6 (IL-6) is a cytokine that, in addition to its essential role in the function of the immune system, is present in the central nervous system (CNS). In particular, pathologically increased CNS IL-6 has been linked to impairments in memory performance. Thus, the aim of our present study was to investigate hippocampus-dependent and -independent memory, in combination with exploratory and anxiety related behaviour in IL-6 knock-out (IL-6KO) mice. The experiments were performed with 9 male IL-6KO and 9 age matched male wild-type (CTRL) mice. Hippocampus-dependent learning was assessed with the Morris water maze (MWM), hippocampus-independent learning with the novel object recognition memory test (NORM). The test-battery for additional behavioural assessments included open field (OF), elevated plus maze (EPM) and forced swim test (FST). IL-6KO mice showed impaired memory processes in the NORM as well in the MWM test. This could not be explained by reduced general activity or increased baseline anxiety. But, there was evidence for a higher susceptibility for stress and reduced exploratory behaviour in IL-6KO mice. In conclusion, absent CNS IL-6 does not lead to an improvement in memory function, but instead to an impairment. As "too little and too much spoils everything", our findings do not contradict the hypothesis of an involvement of IL-6 in memory processes. However, it remains unclear if impairments of memory are a specific result of disturbed IL-6 signalling, or rather an epiphenomenon associated with reduced exploratory behaviour and stress resistance.

Neuropsychological impairments in panic disorder: a systematic review.

PubMed

O'Sullivan, Kate; Newman, Emily F

2014-01-01

There is a growing body of literature investigating the neuropsychological profile of panic disorder (PD), some of which suggests potential cognitive dysfunction. This paper systematically reviews the existing literature on neuropsychological performance in PD. PsycINFO, EMBASE, MEDLINE and PsycARTICLES databases were searched to identify articles reporting on neuropsychological function in PD published in English during the time period 1980 to March 2012. 14 studies were identified. There was limited support for impairment in short term memory among individuals with PD, although this was not found across all studies. Overall, the reviewed studies did not support the presence of impairment in other areas of cognitive functioning, including executive function, long term memory, visuospatial or perceptual abilities and working memory. Studies with samples of fewer than 15 participants per group were excluded from this review. A limited amount of research has been published on this topic and small sample sizes (under 25 per group) have been used by many studies. Therefore, the current review is based on a small number of studies with limited power. There is limited evidence of specific neuropsychological impairments in participants with PD. Impairments in short term memory warrant further investigation to establish their relevance to clinical practice. Larger sample sizes and appropriate statistical adjustment for multiple comparisons in future studies is highly recommended. Copyright © 2014 Elsevier B.V. All rights reserved.

Protective Effects of Lithium on Sumatriptan-Induced Memory Impairment in Mice.

PubMed

Nikoui, Vahid; Javadi-Paydar, Mehrak; Salehi, Mahtab; Behestani, Selda; Dehpour, Ahmad-Reza

2016-04-01

Lithium is a drug used for the treatment of bipolar disorder. It has several mechanisms of action, and recently it is shown that lithium can antagonize the 5-HT1B/1D serotonin receptors. Sumatriptan is a 5-HT1B/1D receptor agonist used for the treatment of cluster headaches and migraine which might cause memory impairment as a potential side effect. In this study, effects of lithium on sumatriptan-induced memory impairment have been determined in a two-trial recognition Y-maze and passive avoidance tests. Male mice weighing 25-30 g were divided into several groups randomly. In Y-maze test, effects of lithium (1,5,10,20,40,80 mg/kg) and sumatriptan (1,5,10 mg/kg) were assessed on memory acquisition, then lithium (0.1,1,10 mg/kg) and sumatriptan (1,10 mg/kg) were studied in passive avoidance test. Effects of lithium (1mg/kg) on sumatriptan (10 mg/kg)-induced memory impairment were studied in both of tests. The present study demonstrated that sumatriptan impaired memory in Y-maze and passive avoidance tests (P<0.05, P<0.01, respectively). Lithium did not show any significant effect on memory function compared to saline-treated control group in both tests (P>0.05), but significantly reversed sumatriptan-induced memory impairment in Y-maze and passive avoidance tests (P<0.001, P<0.05, respectively). It is concluded that lithium reverses the sumatriptan-induced memory impairment probably through 5-HT1B/1D receptors antagonism.

Combined mnemonic strategy training and high-definition transcranial direct current stimulation for memory deficits in mild cognitive impairment.

PubMed

Hampstead, Benjamin M; Sathian, Krishnankutty; Bikson, Marom; Stringer, Anthony Y

2017-09-01

Memory deficits characterize Alzheimer's dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level-dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS). This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses. The results will provide important information about the efficacy of cognitive and neuromodulatory techniques as well as the synergistic interaction between these promising approaches. Exploratory results will examine patient characteristics that affect treatment efficacy, thereby identifying those most appropriate for intervention.

Cognitive, neurophysiological, and functional correlates of proverb interpretation abnormalities in schizophrenia.

PubMed

Kiang, Michael; Light, Gregory A; Prugh, Jocelyn; Coulson, Seana; Braff, David L; Kutas, Marta

2007-07-01

A hallmark of schizophrenia is impaired proverb interpretation, which could be due to: (1) aberrant activation of disorganized semantic associations, or (2) working memory (WM) deficits. We assessed 18 schizophrenia patients and 18 normal control participants on proverb interpretation, and evaluated these two hypotheses by examining within patients the correlations of proverb interpretation with disorganized symptoms and auditory WM, respectively. Secondarily, we also explored the relationships between proverb interpretation and a spectrum of cognitive functions including auditory sensory-memory encoding (as indexed by the mismatch negativity (MMN) event-related brain potential (ERP)); executive function; and social/occupational function. As expected, schizophrenia patients produced less accurate and less abstract descriptions of proverbs than did controls. These proverb interpretation difficulties in patients were not significantly correlated with disorganization or other symptom factors, but were significantly correlated (p < .05) with WM impairment, as well as with impairments in sensory-memory encoding, executive function, and social/occupational function. These results offer no support for disorganized associations in abnormal proverb interpretation in schizophrenia, but implicate WM deficits, perhaps as a part of a syndrome related to generalized frontal cortical dysfunction.

Contribution of the Cholinergic System to Verbal Memory Performance in Mild Cognitive Impairment.

PubMed

Peter, Jessica; Lahr, Jacob; Minkova, Lora; Lauer, Eliza; Grothe, Michel J; Teipel, Stefan; Köstering, Lena; Kaller, Christoph P; Heimbach, Bernhard; Hüll, Michael; Normann, Claus; Nissen, Christoph; Reis, Janine; Klöppel, Stefan

2016-06-18

Acetylcholine is critically involved in modulating learning and memory function, which both decline in neurodegeneration. It remains unclear to what extent structural and functional changes in the cholinergic system contribute to episodic memory dysfunction in mild cognitive impairment (MCI), in addition to hippocampal degeneration. A better understanding is critical, given that the cholinergic system is the main target of current symptomatic treatment in mild to moderate Alzheimer's disease. We simultaneously assessed the structural and functional integrity of the cholinergic system in 20 patients with MCI and 20 matched healthy controls and examined their effect on verbal episodic memory via multivariate regression analyses. Mediating effects of either cholinergic function or hippocampal volume on the relationship between cholinergic structure and episodic memory were computed. In MCI, a less intact structure and function of the cholinergic system was found. A smaller cholinergic structure was significantly correlated with a functionally more active cholinergic system in patients, but not in controls. This association was not modulated by age or disease severity, arguing against compensational processes. Further analyses indicated that neither functional nor structural changes in the cholinergic system influence verbal episodic memory at the MCI stage. In fact, those associations were fully mediated by hippocampal volume. Although the cholinergic system is structurally and functionally altered in MCI, episodic memory dysfunction results primarily from hippocampal neurodegeneration, which may explain the inefficiency of cholinergic treatment at this disease stage.

Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

PubMed

Saunders, Nichole L J; Summers, Mathew J

2011-03-01

Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp² = .054) with a significant decline on a task of divided attention (ηp² = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (c) 2011 APA, all rights reserved

Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

PubMed

Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

2002-12-01

Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function.

Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

NASA Astrophysics Data System (ADS)

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

2004-10-01

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

Protein kinase C overactivity impairs prefrontal cortical regulation of working memory.

PubMed

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

2004-10-29

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

Effects of social instability stress in adolescence on long-term, not short-term, spatial memory performance.

PubMed

Green, Matthew R; McCormick, Cheryl M

2013-11-01

There is evidence that exposure to stressors in adolescence leads to lasting deficits on hippocampal-dependent tasks, but whether medial prefrontal cortical function is also impaired is unknown. We previously found that rats exposed to social instability stress in adolescence (SS; daily 1h isolation and subsequent change of cage partner between postnatal days 30 and 45) had impaired memory performance on a Spatial Object Location test and in memory for fear conditioning context, tasks that depend on the integrity of the hippocampus. Here we investigated whether impaired performance would be evident after adolescent SS in male rats on a different test of hippocampal function, spatial learning and memory in the Morris water maze (MWM) and on a working memory task for which performance depends on the integrity of the medial prefrontal cortex, the Delayed Alternation task (DAT). During MWM testing, SS rats showed greater improvements in performance across trials within days compared to control (CTL) rats, but showed less retention of learning between days (48 h) compared to CTL rats. Similarly, SS rats had impaired long-term memory in the Spatial Object Location test after a long delay (240 min), but not after shorter delays (15 or 60 min) compared to CTL rats. No group differences were observed on the DAT, which assessed working memory across brief delays (5-90 s). Thus, deficits in memory performance after chronic social stress in adolescence may be limited to long-term memory. Copyright © 2013 Elsevier B.V. All rights reserved.

Evidence for a differential contribution of early perceptual and late cognitive processes during encoding to episodic memory impairment in schizophrenia.

PubMed

Green, Amity E; Fitzgerald, Paul B; Johnston, Patrick J; Nathan, Pradeep J; Kulkarni, Jayashri; Croft, Rodney J

2017-08-01

Schizophrenia is characterised by significant episodic memory impairment that is thought to be related to problems with encoding, however the neuro-functional mechanisms underlying these deficits are not well understood. The present study used a subsequent recognition memory paradigm and event-related potentials (ERPs) to investigate temporal aspects of episodic memory encoding deficits in schizophrenia. Electroencephalographic data was recorded in 24 patients and 19 healthy controls whilst participants categorised single words as pleasant/unpleasant. ERPs were generated to subsequently recognised versus unrecognised words on the basis of a forced-choice recognition memory task. Subsequent memory effects were examined with the late positive component (LPP). Group differences in N1, P2, N400 and LPP were examined for words correctly recognised. Patients performed more poorly than controls on the recognition task. During encoding patients had significantly reduced N400 and LPP amplitudes than controls. LPP amplitude correlated with task performance however amplitudes did not differ between patients and controls as a function of subsequent memory. No significant differences in N1 or P2 amplitude or latency were observed. The present results indicate that early sensory processes are intact and dysfunctional higher order cognitive processes during encoding are contributing to episodic memory impairments in schizophrenia.

Normal-range verbal-declarative memory in schizophrenia.

PubMed

Heinrichs, R Walter; Parlar, Melissa; Pinnock, Farena

2017-10-01

Cognitive impairment is prevalent and related to functional outcome in schizophrenia, but a significant minority of the patient population overlaps with healthy controls on many performance measures, including declarative-verbal-memory tasks. In this study, we assessed the validity, clinical, and functional implications of normal-range (NR), verbal-declarative memory in schizophrenia. Performance normality was defined using normative data for 8 basic California Verbal Learning Test (CVLT-II; Delis, Kramer, Kaplan, & Ober, 2000) recall and recognition trials. Schizophrenia patients (n = 155) and healthy control participants (n = 74) were assessed for performance normality, defined as scores within 1 SD of the normative mean on all 8 trials, and assigned to normal- and below-NR memory groups. NR schizophrenia patients (n = 26) and control participants (n = 51) did not differ in general verbal ability, on a reading-based estimate of premorbid ability, across all 8 CVLT-II-score comparisons or in terms of intrusion and false-positive errors and auditory working memory. NR memory patients did not differ from memory-impaired patients (n = 129) in symptom severity, and both patient groups were significantly and similarly disabled in terms of functional status in the community. These results confirm a subpopulation of schizophrenia patients with normal, verbal-declarative-memory performance and no evidence of decline from higher premorbid ability levels. However, NR patients did not experience less severe psychopathology, nor did they show advantage in community adjustment relative to impaired patients. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

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

PubMed Central

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

2015-01-01

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with “moderate” hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. SIGNIFICANCE STATEMENT In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function. PMID:26490854

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

PubMed

Guderian, Sebastian; Dzieciol, Anna M; Gadian, David G; Jentschke, Sebastian; Doeller, Christian F; Burgess, Neil; Mishkin, Mortimer; Vargha-Khadem, Faraneh

2015-10-21

The extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated allocentric spatial recall using a virtual environment in a group of patients with severe hippocampal damage (SHD), a group of patients with "moderate" hippocampal damage (MHD), and a normal control group. Through four learning blocks with feedback, participants learned the target locations of four different objects in a circular arena. Distal cues were present throughout the experiment to provide orientation. A circular boundary as well as an intra-arena landmark provided spatial reference frames. During a subsequent test phase, recall of all four objects was tested with only the boundary or the landmark being present. Patients with SHD were impaired in both phases of this task. Across groups, performance on both types of spatial recall was highly correlated with memory quotient (MQ), but not with intelligence quotient (IQ), age, or sex. However, both measures of spatial recall separated experimental groups beyond what would be expected based on MQ, a widely used measure of general memory function. Boundary-based and landmark-based spatial recall were both strongly related to bilateral hippocampal volumes, but not to volumes of the thalamus, putamen, pallidum, nucleus accumbens, or caudate nucleus. The results show that boundary-based and landmark-based allocentric spatial recall are similarly impaired in patients with SHD, that both types of recall are impaired beyond that predicted by MQ, and that recall deficits are best explained by a reduction in bilateral hippocampal volumes. In humans, bilateral hippocampal atrophy can lead to profound impairments in episodic memory. Across species, perhaps the most well-established contribution of the hippocampus to memory is not to episodic memory generally but to allocentric spatial memory. However, the extent to which navigational spatial memory depends on hippocampal integrity in humans is not well documented. We investigated spatial recall using a virtual environment in two groups of patients with hippocampal damage (moderate/severe) and a normal control group. The results showed that patients with severe hippocampal damage are impaired in learning and recalling allocentric spatial information. Furthermore, hippocampal volume reduction impaired allocentric navigation beyond what can be predicted by memory quotient as a widely used measure of general memory function. Copyright © 2015 Guderian et al.

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.

Impairment of cognitive functioning during Sunitinib or Sorafenib treatment in cancer patients: a cross sectional study

PubMed Central

2014-01-01

Background Impairment of cognitive functioning has been reported in several studies in patients treated with chemotherapy. So far, no studies have been published on the effects of the vascular endothelial growth factor receptor (VEGFR) inhibitors on cognitive functioning. We investigated the objective and subjective cognitive function of patients during treatment with VEGFR tyrosine kinase inhibitors (VEGFR TKI). Methods Three groups of participants, matched on age, sex and education, were enrolled; 1. metastatic renal cell cancer (mRCC) or GIST patients treated with sunitinib or sorafenib (VEGFR TKI patients n = 30); 2. patients with mRCC not receiving systemic treatment (patient controls n = 20); 3. healthy controls (n = 30). Sixteen neuropsychological tests examining the main cognitive domains (intelligence, memory, attention and concentration, executive functions and abstract reasoning) were administered by a neuropsychologist. Four questionnaires were used to assess subjective cognitive complaints, mood, fatigue and psychological wellbeing. Results No significant differences in mean age, sex distribution, education level or IQ were found between the three groups. Both patient groups performed significantly worse on the cognitive domains Learning & Memory and Executive Functions (Response Generation and Problem Solving) compared to healthy controls. However only the VEGFR TKI patients showed impairments on the Executive subdomain Response Generation. Effect sizes of cognitive dysfunction in patients using VEGFR TKI were larger on the domains Learning & Memory and Executive Functions, compared to patient controls. Both patients groups performed on the domain Attention & Concentration the same as the healthy controls. Longer duration of treatment on VEGFR TKI was associated with a worse score on Working Memory tasks. Conclusions Our data suggest that treatment with VEGFR TKI has a negative impact on cognitive functioning, specifically on Learning & Memory, and Executive Functioning. We propose that patients who are treated with VEGFR TKI are monitored and informed for possible signs or symptoms associated with cognitive impairment. Trial registration ClinicalTrials.gov Identifier: NCT01246843. PMID:24661373

Identification of the key molecules involved in chronic copper exposure-aggravated memory impairment in transgenic mice of Alzheimer's disease using proteomic analysis.

PubMed

Yu, Jun; Luo, Xiaobin; Xu, Hua; Ma, Quan; Yuan, Jianhui; Li, Xuling; Chang, Raymond Chuen-Chung; Qu, Zhongsen; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by a progressive impairment of cognitive functions including spatial learning and memory. Excess copper exposure accelerates the development of AD; however, the potential mechanisms by which copper exacerbates the symptoms of AD remain unknown. In this study, we explored the effects of chronic copper exposure on cognitive function by treating 6 month-old triple AD transgenic (3xTg-AD) mice with 250 ppm copper sulfate in drinking water for 6 months, and identified several potential key molecules involved in the effects of chronic copper exposure on memory by proteomic analysis. The behavioral test showed that chronic copper exposure aggravated memory impairment of 3xTg-AD mice. Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry revealed a total of 44 differentially expressed proteins (18 upregulated and 26 down-regulated) in hippocampus between the wild-type (WT) mice and non-exposed 3xTg-AD mice. A total of 40 differentially expressed proteins were revealed (20 upregulated and 20 down-regulated) in hippocampus between copper exposed and non-exposed 3xTg-AD mice. Among these differentially expressed proteins, complexin-1 and complexin-2, two memory associated proteins, were significantly decreased in hippocampus of 3xTg-AD mice compared with the WT mice. Furthermore, the expression of these two proteins was further down-regulated in 3xTg-AD mice when exposed to copper. The abnormal expression of complexin-1 and complexin-2 identified by proteomic analysis was verified by western blot analysis. Taken together, our data showed that chronic copper exposure accelerated memory impairment and altered the expression of proteins in hippocampus in 3xTg-AD mice. The functional analysis on the differentially expressed proteins suggested that complexin-1 and complexin-2 may be the key molecules involved in chronic copper exposure-aggravated memory impairment in AD.

Usefulness of a single item in a mail survey to identify persons with possible dementia: a new strategy for finding high-risk elders.

PubMed

Brody, Kathleen K; Maslow, Katie; Perrin, Nancy A; Crooks, Valerie; DellaPenna, Richard; Kuang, Daniel

2005-04-01

The objective of this study was to examine the characteristics of elderly persons who responded positively to a question about "severe memory problems" on a mailed health questionnaire yet were missed by the existing health risk algorithm to identify vulnerable elderly persons. A total of 324,471 respondents aged 65 and older completed a primary care health status questionnaire that gathered clinical information to quickly identify members with functional impairment, multiple chronic diseases, and higher medical care needs. The respondents were part of a large, integrated, not-for-profit managed care organization that implemented a model of care for elders using a uniform risk identification method across eight regions. Respondents with severe memory problems were compared to general respondents by morbidity, geriatric syndromes, functional impairments, service utilization, sensory impairments, sociodemographic characteristics, and activities of daily living. Of the respondents, 13,902 persons (4.3%) reported severe memory problems; the existing health risk algorithm missed 47.1% of these. When severe memory problems were included in the risk algorithm, identification increased from 11% to 13%, and risk prevalence by age groups ranged from 4.4% to 40.5%; one third had severe memory problems, a finding that was fairly consistent within age groups (28.4% to 36.5%). A question about severe memory problems should be incorporated into population risk-identification techniques. While false-negative rates are unknown, the false-positive rate of a self-report mail survey appears to be minimal. Persons reporting severe memory problems clearly have multiple comorbidities, higher prevalence of geriatric syndromes, and greater functional and sensory impairments.

Distinguishing neurocognitive deficits in adult patients with NP-C from early onset Alzheimer's dementia.

PubMed

Johnen, Andreas; Pawlowski, Matthias; Duning, Thomas

2018-06-05

Niemann-Pick disease type C (NP-C) is a rare, progressive neurodegenerative disease caused by mutations in the NPC1 or the NPC2 gene. Neurocognitive deficits are common in NP-C, particularly in patients with the adolescent/adult-onset form. As a disease-specific therapy is available, it is important to distinguish clinically between the cognitive profiles in NP-C and primary dementia (e.g., early Alzheimer's disease; eAD). In a prospective observational study, we directly compared the neurocognitive profiles of patients with confirmed NP-C (n = 7) and eAD (n = 15). All patients underwent neurocognitive assessment using dementia screening tests (mini-mental status examination [MMSE] and frontal assessment battery [FAB]) and an extensive battery of tests assessing verbal memory, visuoconstructive abilities, visual memory, executive functions and verbal fluency. Overall cognitive impairment (MMSE) was significantly greater in eAD vs. NP-C (p = 0.010). The frequency of patients classified as cognitively 'impaired' was also significantly greater in eAD vs. NP-C (p = 0.025). Patients with NP-C showed relatively preserved verbal memory, but frequent impairment in visual memory, visuoconstruction, executive functions and in particular, verbal fluency. In the eAD group, a wider profile of more frequent and more severe neurocognitive deficits was seen, primarily featuring severe verbal and visual memory deficits along with major executive impairment. Delayed verbal memory recall was a particularly strong distinguishing factor between the two groups. A combination of detailed yet easy-to-apply neurocognitive tests assessing verbal memory, executive functions and verbal fluency may help distinguish NP-C cases from those with primary dementia due to eAD.

Memory loss and decreased executive function are associated with limited functional capacity in patients with heart failure compared to patients with other medical conditions.

PubMed

Kim, JinShil; Shin, Mi-Seung; Hwang, Seon Young; Park, Eunok; Lim, Young-Hyo; Shim, Jae Lan; Kim, Sun Hwa; Kim, Yeon Hee; An, Minjeong

There is limited evidence on the degree of cognitive impairment and its association with physical functional capacity among patients with heart failure (HF) in Korea. In this study, we compared cognitive impairment between patients with HF and community-dwelling participants with non-HF medical conditions (medical participants) and its association with physical functional capacity. We conducted a cross-sectional comparative study and assessed the neuropsychological cognitive status (Seoul Neuropsychological Screening Battery) and physical functional capacity (Duke Activity Status Index) of patients with HF and medical participants using face-to-face interviews. One hundred and eighteen patients with HF (age, 65.45 ± 9.38 years; men, 57.6%; left ventricular ejection fraction, 34.93 ± 8.72%) and 83 medical participants (age, 66.02 ± 8.28 years; men, 47.0%) were included. Using seventh-percentile medical participant Z-scores as cutoffs, memory and executive function were worse in patients with HF than in medical participants: immediate (35.0% vs. 6.0%) and delayed recall memory (34.5% vs. 8.4%), and executive function (28.6% vs. 6.0%). Independent of age, sex, education, comorbidity, and HF status, executive function was a significant predictor of physical functional capacity (b = 1.82, p = .021). More patients with HF had impaired memory and executive function, which were associated with their physical functional capacities. Copyright © 2017 Elsevier Inc. All rights reserved.

Arbitrary and semantic associations in subjective memory impairment and amnestic mild cognitive impairment among Taiwanese individuals: A cross-sectional study.

PubMed

Chang, Hsin-Te; Chen, Ta-Fu; Cheng, Ting-Wen; Lai, Ya-Mei; Hua, Mau-Sun

2018-05-01

Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT), referred to as subjective memory impairment (SMI), with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI. Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI), or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n = 30) and individuals with SMI (n = 61), aMCI-single domain (n = 24), aMCI-multiple domain (n = 33), or DAT (n = 35). The Word Sequence Learning Test (WSLT) was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations. Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations. Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT. Copyright © 2017. Published by Elsevier B.V.

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

Individual differences in associative memory among older adults explained by hippocampal subfield structure and function.

PubMed

Carr, Valerie A; Bernstein, Jeffrey D; Favila, Serra E; Rutt, Brian K; Kerchner, Geoffrey A; Wagner, Anthony D

2017-11-07

Older adults experience impairments in episodic memory, ranging from mild to clinically significant. Given the critical role of the medial temporal lobe (MTL) in episodic memory, age-related changes in MTL structure and function may partially account for individual differences in memory. Using ultra-high-field 7T structural MRI and high-resolution 3T functional MRI (hr-fMRI), we evaluated MTL subfield thickness and function in older adults representing a spectrum of cognitive health. Participants performed an associative memory task during hr-fMRI in which they encoded and later retrieved face-name pairs. Motivated by prior research, we hypothesized that differences in performance would be explained by the following: ( i ) entorhinal cortex (ERC) and CA1 apical neuropil layer [CA1-stratum radiatum lacunosum moleculare (SRLM)] thickness, and ( ii ) activity in ERC and the dentate gyrus (DG)/CA3 region. Regression analyses revealed that this combination of factors significantly accounted for variability in memory performance. Among these metrics, CA1-SRLM thickness was positively associated with memory, whereas DG/CA3 retrieval activity was negatively associated with memory. Furthermore, including structural and functional metrics in the same model better accounted for performance than did single-modality models. These results advance the understanding of how independent but converging influences of both MTL subfield structure and function contribute to age-related memory impairment, complementing findings in the rodent and human postmortem literatures.

The impact of marijuana use on memory in HIV-infected patients: a comprehensive review of the HIV and marijuana literatures

PubMed Central

Skalski, Linda M.; Towe, Sheri L.; Sikkema, Kathleen J.; Meade, Christina S.

2016-01-01

Background The most robust neurocognitive effect of marijuana use is memory impairment. Memory deficits are also high among persons living with HIV/AIDS, and marijuana is the most commonly used drug in this population. Yet research examining neurocognitive outcomes resulting from co-occurring marijuana and HIV is limited. Objective The primary objectives of this comprehensive review are to: (1) examine the literature on memory functioning in HIV-infected individuals; (2) examine the literature on memory functioning in marijuana users; (3) synthesize findings and propose a theoretical framework to guide future research. Method PubMed was searched for English publications 2000–2013. Twenty-two studies met inclusion criteria in the HIV literature, and 23 studies in the marijuana literature. Results Among HIV-infected individuals, memory deficits with medium to large effect sizes were observed. Marijuana users also demonstrated memory problems, but results were less consistent due to the diversity of samples. Conclusion A compensatory hypothesis, based on the cognitive aging literature, is proposed to provide a framework to explore the interaction between marijuana and HIV. There is some evidence that individuals infected with HIV recruit additional brain regions during memory tasks to compensate for HIV-related declines in neurocognitive functioning. Marijuana use causes impairment in similar brain systems, and thus it is hypothesized that the added neural strain of marijuana can exhaust neural resources, resulting in pronounced memory impairment. It will be important to test this hypothesis empirically, and future research priorities are discussed. PMID:27138170

Learning and Memory Impairments in a Congenic C57BL/6 Strain of Mice That Lacks the M2 Muscarinic Acetylcholine Receptor Subtype

PubMed Central

Bainbridge, Natalie K.; Koselke, Lisa R.; Jeon, Jongrye; Bailey, Kathleen R.; Wess, Jürgen; Crawley, Jacqueline N.; Wrenn, Craige C.

2009-01-01

The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M1-M5). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M2 muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M2 muscarinic receptor gene (M2−/− mice). Comprehensive assessment of general health and neurological function found no major differences between M2−/− and wild-type (M2+/+) mice. In tests of learning and memory, M2−/− mice were impaired in the acquisition (trials to criterion), but not the retention (72 hr) of a passive avoidance task. In a novel open field, M2−/− mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M2−/− mice committed more errors in working memory than M2+/+ mice. Reference memory did not differ between the genotypes. M2−/− mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M2 receptor plays a critical role in specific components of cognitive abilities. PMID:18346798

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.

A behavioral rehabilitation intervention for amnestic Mild Cognitive Impairment

PubMed Central

Greenaway, Melanie C.; Hanna, Sherrie M.; Lepore, Susan W.; Smith, Glenn E.

2010-01-01

Individuals with amnestic Mild Cognitive Impairment (MCI) currently have few treatment options for combating their memory loss. The Memory Support System (MSS) is a calendar and organization system with accompanying 6-week curriculum designed for individuals with progressive memory impairment. Ability to learn the MSS and its utility were assessed in 20 participants. Participants were significantly more likely to successfully use the calendar system after training. Ninety-five percent were compliant with the MSS at training completion, and 89% continued to be compliant at follow-up. Outcome measures revealed a medium effect size for improvement in functional ability. Subjects further reported improved independence, self-confidence, and mood. This initial examination of the MSS suggests that with appropriate training, individuals with amnestic MCI can and will use a memory notebook system to help compensate for memory loss. These results are encouraging that the MSS may help with the symptoms of memory decline in MCI. PMID:18955724

Episodic Memory and Episodic Future Thinking Impairments in High-Functioning Autism Spectrum Disorder: An Underlying Difficulty With Scene Construction or Self-Projection?

PubMed Central

2013-01-01

Objective: There appears to be a common network of brain regions that underlie the ability to recall past personal experiences (episodic memory) and the ability to imagine possible future personal experiences (episodic future thinking). At the cognitive level, these abilities are thought to rely on “scene construction” (the ability to bind together multimodal elements of a scene in mind—dependent on hippocampal functioning) and temporal “self-projection” (the ability to mentally project oneself through time—dependent on prefrontal cortex functioning). Although autism spectrum disorder (ASD) is characterized by diminished episodic memory, it is unclear whether episodic future thinking is correspondingly impaired. Moreover, the underlying basis of such impairments (difficulties with scene construction, self-projection, or both) is yet to be established. The current study therefore aimed to elucidate these issues. Method: Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ-matched neurotypical comparison adults were asked to describe (a) imagined atemporal, non-self-relevant fictitious scenes (assessing scene construction), (b) imagined plausible self-relevant future episodes (assessing episodic future thinking), and (c) recalled personally experienced past episodes (assessing episodic memory). Tests of narrative ability and theory of mind were also completed. Results: Performances of participants with ASD were significantly and equally diminished in each condition and, crucially, this diminution was independent of general narrative ability. Conclusions: Given that participants with ASD were impaired in the fictitious scene condition, which does not involve self-projection, we suggest the underlying difficulty with episodic memory/future thinking is one of scene construction. PMID:24015827

Episodic memory and episodic future thinking impairments in high-functioning autism spectrum disorder: an underlying difficulty with scene construction or self-projection?

PubMed

Lind, Sophie E; Williams, David M; Bowler, Dermot M; Peel, Anna

2014-01-01

There appears to be a common network of brain regions that underlie the ability to recall past personal experiences (episodic memory) and the ability to imagine possible future personal experiences (episodic future thinking). At the cognitive level, these abilities are thought to rely on "scene construction" (the ability to bind together multimodal elements of a scene in mind--dependent on hippocampal functioning) and temporal "self-projection" (the ability to mentally project oneself through time--dependent on prefrontal cortex functioning). Although autism spectrum disorder (ASD) is characterized by diminished episodic memory, it is unclear whether episodic future thinking is correspondingly impaired. Moreover, the underlying basis of such impairments (difficulties with scene construction, self-projection, or both) is yet to be established. The current study therefore aimed to elucidate these issues. Twenty-seven intellectually high-functioning adults with ASD and 29 age- and IQ-matched neurotypical comparison adults were asked to describe (a) imagined atemporal, non-self-relevant fictitious scenes (assessing scene construction), (b) imagined plausible self-relevant future episodes (assessing episodic future thinking), and (c) recalled personally experienced past episodes (assessing episodic memory). Tests of narrative ability and theory of mind were also completed. Performances of participants with ASD were significantly and equally diminished in each condition and, crucially, this diminution was independent of general narrative ability. Given that participants with ASD were impaired in the fictitious scene condition, which does not involve self-projection, we suggest the underlying difficulty with episodic memory/future thinking is one of scene construction.

Impaired inhibition and working memory in response to internet-related words among adolescents with internet addiction: A comparison with attention-deficit/hyperactivity disorder.

PubMed

Nie, Jia; Zhang, Wei; Chen, Jia; Li, Wendi

2016-02-28

Impairments in response inhibition and working memory functions have been found to be closely associated with internet addiction (IA) symptoms and attention-deficit/hyperactivity disorder (ADHD) symptoms. In this study, we examined response inhibition and working memory processes with two different materials (internet-related and internet-unrelated stimuli) among adolescents with IA, ADHD and co-morbid IA/ADHD. Twenty-four individuals with IA, 28 individuals with ADHD, 17 individuals with IA/ADHD, and 26 matched normal controls (NC) individuals were recruited. All participants were measured with a Stop-Signal Task and 2-Back Task under the same experimental conditions. In comparison to the NC group, subjects with IA, ADHD and IA/ADHD demonstrated impaired inhibition and working memory. In addition, in comparison to internet-unrelated conditions, IA and co-morbid subjects performed worse on the internet-related condition in the Stop trials during the stop-signal task, and they showed better working memory on the internet-related condition in the 2-Back Task. The findings of our study suggest individuals with IA and IA/ADHD may be impaired in inhibition and working memory functions that might be linked to poor inhibition specifically related to internet-related stimuli, which will advance our understanding of IA and contribute to prevention and intervention strategies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Neural Correlates of Feigned Memory Impairment are Distinguishable from Answering Randomly and Answering Incorrectly: An fMRI and Behavioral Study

ERIC Educational Resources Information Center

Liang, Chun-Yu; Xu, Zhi-Yuan; Mei, Wei; Wang, Li-Li; Xue, Li; Lu, De Jian; Zhao, Hu

2012-01-01

Previous functional magnetic resonance imaging (fMRI) studies have identified activation in the prefrontal-parietal-sub-cortical circuit during feigned memory impairment when comparing with truthful telling. Here, we used fMRI to determine whether neural activity can differentiate between answering correctly, answering randomly, answering…

Cognitive functions in preschool children with specific language impairment.

PubMed

Reichenbach, Katrin; Bastian, Laura; Rohrbach, Saskia; Gross, Manfred; Sarrar, Lea

2016-07-01

A growing body of research has focused on executive functions in children with specific language impairment (SLI). However, results show limited convergence, particularly in preschool age. The current neuropsychological study compared performance of cognitive functions focused on executive components and working memory in preschool children with SLI to typically developing controls. Performance on the measures cognitive flexibility, inhibition, processing speed and phonological short-term memory was assessed. The monolingual, Caucasian study sample consisted of 30 children with SLI (Mage = 63.3 months, SD = 4.3 months) and 30 healthy controls (Mage = 62.2 months, SD = 3.7 months). Groups were matched for age and nonverbal IQ. Socioeconomic status of the participating families was included. Children with SLI had significantly poorer abilities of phonological short-term memory than matched controls. A tendency of poorer abilities in the SLI group was found for inhibition and processing speed. We confirmed phonological short-term memory to be a reliable marker of SLI in preschoolers. Our results do not give definite support for impaired executive function in SLI, possibly owing to limited sensitivity of test instruments in this age group. We argue for a standardization of executive function tests for research use. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Cognitive function in patients with primary adrenal insufficiency (Addison's disease).

PubMed

Schultebraucks, Katharina; Wingenfeld, Katja; Heimes, Jana; Quinkler, Marcus; Otte, Christian

2015-05-01

Patients with primary adrenal insufficiency (AI) need to replace glucocorticoids and mineralocorticoids that act on glucocorticoid (GR) and mineralocorticoid receptors (MR). Both receptors are highly expressed in the hippocampus and are closely associated with cognitive function, which might be impaired by insufficient or increased GR and MR stimulation. However, little is known about cognitive function in patients with AI. It was examined whether patients with AI exhibit worse cognitive function compared to sex-, age-, and education-matched controls. Cognitive function (executive function, concentration, verbal memory, visual memory, working memory, and autobiographical memory) was assessed in 30 patients with AI (mean age 52.4 yrs. ±14.4, n=21 women, mean duration of illness 18.2 yrs. ±11.1) and 30 matched controls. We also measured depressive symptoms, body mass index (BMI), and blood pressure. Patients with AI showed more depressive symptoms, had a greater BMI and lower systolic blood pressure compared to controls. Adjusted analyses controlling for these variables revealed that patients with AI performed significantly worse in verbal learning (F=7.8, p=.007). Executive function, concentration, working memory, verbal memory, visuospatial memory, and autobiographical memory did not differ between groups. No clinically relevant cognitive impairment was found in patients with AI compared to matched controls. Even long-term glucocorticoid and mineralocorticoid substitution over almost two decades appears to have only subtle effects on cognition in patients with AI. Copyright © 2015 Elsevier Ltd. All rights reserved.

The influence of age and mild cognitive impairment on associative memory performance and underlying brain networks.

PubMed

Oedekoven, Christiane S H; Jansen, Andreas; Keidel, James L; Kircher, Tilo; Leube, Dirk

2015-12-01

Associative memory is essential to everyday activities, such as the binding of faces and corresponding names to form single bits of information. However, this ability often becomes impaired with increasing age. The most important neural substrate of associative memory is the hippocampus, a structure crucially implicated in the pathogenesis of Alzheimer's disease (AD). The main aim of this study was to compare neural correlates of associative memory in healthy aging and mild cognitive impairment (MCI), an at-risk state for AD. We used fMRI to investigate differences in brain activation and connectivity between young controls (n = 20), elderly controls (n = 32) and MCI patients (n = 21) during associative memory retrieval. We observed lower hippocampal activation in MCI patients than control groups during a face-name recognition task, and the magnitude of this decrement was correlated with lower associative memory performance. Further, increased activation in precentral regions in all older adults indicated a stronger involvement of the task positive network (TPN) with age. Finally, functional connectivity analysis revealed a stronger link of hippocampal and striatal components in older adults in comparison to young controls, regardless of memory impairment. In elderly controls, this went hand-in-hand with a stronger activation of striatal areas. Increased TPN activation may be linked to greater reliance on cognitive control in both older groups, while increased functional connectivity between the hippocampus and the striatum may suggest dedifferentiation, especially in elderly controls.

Pathophysiology and Treatment of Memory Dysfunction after Traumatic Brain Injury

PubMed Central

Paterno, Rosalia; Folweiler, Kaitlin A.; Cohen, Akiva S.

2018-01-01

Memory is fundamental to everyday life, and cognitive impairments resulting from traumatic brain injury (TBI) have devastating effects on TBI survivors. A contributing component to memory impairments caused by TBI are alterations in the neural circuits associated with memory function. In this review, we aim to bring together experimental findings that characterize behavioral memory deficits and the underlying pathophysiology of memory-involved circuits after TBI. While there is little doubt that TBI causes memory and cognitive dysfunction, it is difficult to conclude which memory phase i.e., encoding, maintenance or retrieval is specifically altered by TBI. This is most likely due to variation in behavioral protocols and experimental models. Additionally we review a selection of experimental treatments that hold translational potential to mitigate memory dysfunction following injury. PMID:28500417

The reduction of adult neurogenesis in depression impairs the retrieval of new as well as remote episodic memory

PubMed Central

Fang, Jing; Demic, Selver; Cheng, Sen

2018-01-01

Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance. PMID:29879169

The reduction of adult neurogenesis in depression impairs the retrieval of new as well as remote episodic memory.

PubMed

Fang, Jing; Demic, Selver; Cheng, Sen

2018-01-01

Major depressive disorder (MDD) is associated with an impairment of episodic memory, but the mechanisms underlying this deficit remain unclear. Animal models of MDD find impaired adult neurogenesis (AN) in the dentate gyrus (DG), and AN in DG has been suggested to play a critical role in reducing the interference between overlapping memories through pattern separation. Here, we study the effect of reduced AN in MDD on the accuracy of episodic memory using computational modeling. We focus on how memory is affected when periods with a normal rate of AN (asymptomatic states) alternate with periods with a low rate (depressive episodes), which has never been studied before. Also, unlike previous models of adult neurogenesis, which consider memories as static patterns, we model episodic memory as sequences of neural activity patterns. In our model, AN adds additional random components to the memory patterns, which results in the decorrelation of similar patterns. Consistent with previous studies, higher rates of AN lead to higher memory accuracy in our model, which implies that memories stored in the depressive state are impaired. Intriguingly, our model makes the novel prediction that memories stored in an earlier asymptomatic state are also impaired by a later depressive episode. This retrograde effect exacerbates with increased duration of the depressive episode. Finally, pattern separation at the sensory processing stage does not improve, but rather worsens, the accuracy of episodic memory retrieval, suggesting an explanation for why AN is found in brain areas serving memory rather than sensory function. In conclusion, while cognitive retrieval biases might contribute to episodic memory deficits in MDD, our model suggests a mechanistic explanation that affects all episodic memories, regardless of emotional relevance.

Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia

PubMed Central

Takao, Keizo; Toyama, Keiko; Nakanishi, Kazuo; Hattori, Satoko; Takamura, Hironori; Takeda, Masatoshi; Miyakawa, Tsuyoshi; Hashimoto, Ryota

2008-01-01

Background Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. The dystrobrevin-binding protein 1 (DTNBP1: dysbindin-1) gene is a major susceptibility gene for schizophrenia. Genetic variations in DTNBP1 are associated with cognitive functions, general cognitive ability and memory function, and clinical features of patients with schizophrenia including negative symptoms and cognitive decline. Since reduced expression of dysbindin-1 has been observed in postmortem brains of patients with schizophrenia, the sandy (sdy) mouse, which has a deletion in the Dtnbp1 gene and expresses no dysbindin-1 protein, could be an animal model of schizophrenia. To address this issue, we have carried out a comprehensive behavioral analysis of the sdy mouse in this study. Results In a rotarod test, sdy mice did not exhibit motor learning whilst the wild type mice did. In a Barnes circular maze test both sdy mice and wild type mice learned to selectively locate the escape hole during the course of the training period and in the probe trial conducted 24 hours after last training. However, sdy mice did not locate the correct hole in the retention probe tests 7 days after the last training trial, whereas wild type mice did, indicating impaired long-term memory retention. A T-maze forced alternation task, a task of working memory, revealed no effect of training in sdy mice despite the obvious effect of training in wild type mice, suggesting a working memory deficit. Conclusion Sdy mouse showed impaired long-term memory retention and working memory. Since genetic variation in DTNBP1 is associated with both schizophrenia and memory function, and memory function is compromised in patients with schizophrenia, the sdy mouse may represent a useful animal model to investigate the mechanisms of memory dysfunction in the disorder. PMID:18945333

Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia.

PubMed

Takao, Keizo; Toyama, Keiko; Nakanishi, Kazuo; Hattori, Satoko; Takamura, Hironori; Takeda, Masatoshi; Miyakawa, Tsuyoshi; Hashimoto, Ryota

2008-10-22

Schizophrenia is a complex genetic disorder caused by multiple genetic and environmental factors. The dystrobrevin-binding protein 1 (DTNBP1: dysbindin-1) gene is a major susceptibility gene for schizophrenia. Genetic variations in DTNBP1 are associated with cognitive functions, general cognitive ability and memory function, and clinical features of patients with schizophrenia including negative symptoms and cognitive decline. Since reduced expression of dysbindin-1 has been observed in postmortem brains of patients with schizophrenia, the sandy (sdy) mouse, which has a deletion in the Dtnbp1 gene and expresses no dysbindin-1 protein, could be an animal model of schizophrenia. To address this issue, we have carried out a comprehensive behavioral analysis of the sdy mouse in this study. In a rotarod test, sdy mice did not exhibit motor learning whilst the wild type mice did. In a Barnes circular maze test both sdy mice and wild type mice learned to selectively locate the escape hole during the course of the training period and in the probe trial conducted 24 hours after last training. However, sdy mice did not locate the correct hole in the retention probe tests 7 days after the last training trial, whereas wild type mice did, indicating impaired long-term memory retention. A T-maze forced alternation task, a task of working memory, revealed no effect of training in sdy mice despite the obvious effect of training in wild type mice, suggesting a working memory deficit. Sdy mouse showed impaired long-term memory retention and working memory. Since genetic variation in DTNBP1 is associated with both schizophrenia and memory function, and memory function is compromised in patients with schizophrenia, the sdy mouse may represent a useful animal model to investigate the mechanisms of memory dysfunction in the disorder.

The impact of brain-derived neurotrophic factor Val66Met polymorphism on cognition and functional brain networks in patients with intractable partial epilepsy.

PubMed

Sidhu, Meneka K; Thompson, Pamela J; Wandschneider, Britta; Foulkes, Alexandra; de Tisi, Jane; Stretton, Jason; Perona, Marina; Thom, Maria; Bonelli, Silvia B; Burdett, Jane; Williams, Elaine; Duncan, John S; Matarin, Mar

2018-06-27

Medial temporal lobe epilepsy (mTLE) is the most common refractory focal epilepsy in adults. Around 30%-40% of patients have prominent memory impairment and experience significant postoperative memory and language decline after surgical treatment. BDNF Val66Met polymorphism has also been associated with cognition and variability in structural and functional hippocampal indices in healthy controls and some patient groups. We examined whether BDNF Val66Met variation was associated with cognitive impairment in mTLE. In this study, we investigated the association of Val66Met polymorphism with cognitive performance (n = 276), postoperative cognitive change (n = 126) and fMRI activation patterns during memory encoding and language paradigms in 2 groups of patients with mTLE (n = 37 and 34). mTLE patients carrying the Met allele performed more poorly on memory tasks and showed reduced medial temporal lobe activation and reduced task-related deactivations within the default mode networks in both the fMRI memory and language tasks than Val/Val patients. Although cognitive impairment in epilepsy is the result of a complex interaction of factors, our results suggest a role of genetic factors on cognitive impairment in mTLE. © 2018 John Wiley & Sons Ltd.

Voluntary exercise impact on cognitive impairments in sleep-deprived intact female rats.

PubMed

Rajizadeh, Mohammad Amin; Esmaeilpour, Khadijeh; Masoumi-Ardakani, Yaser; Bejeshk, Mohammad Abbas; Shabani, Mohammad; Nakhaee, Nouzar; Ranjbar, Mohammad Pour; Borzadaran, Fatemeh Mohtashami; Sheibani, Vahid

2018-05-01

Sleep loss is a common problem in modern societies affecting different aspects of individuals' lives. Many studies have reported that sleep deprivation (SD) leads to impairments in various types of learning and memory. Physical exercise has been suggested to attenuate the cognitive impairments induced by sleep deprivation in male rats. Our previous studies have shown that forced exercise by treadmill improved learning and memory impairments following SD. The aim of the current study was to investigate the effects of voluntary exercise by running wheel on cognitive, motor and anxiety-like behavior functions of female rats following 72 h SD. Intact female rats were used in the present study. The multiple platform method was applied for the induction of 72 h SD. The exercise protocol was 4 weeks of running wheel and the cognitive function was evaluated using Morris water maze (MWM), passive avoidance and novel object recognition tests. Open field test and measurement of plasma corticosterone level were performed for evaluation of anxiety-like behaviors. Motor balance evaluation was surveyed by rotarod test. In this study, remarkable learning and long-term memory impairments were observed in sleep deprived rats in comparison to the other groups. Running wheel exercise ameliorated the SD-induced learning and memory impairments. Voluntary and mandatory locomotion and balance situation were not statistically significant among the different groups. Our study confirmed the negative effects of SD on cognitive function and approved protective effects of voluntary exercise on these negative effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Toxoplasma gondii impairs memory in infected seniors.

PubMed

Gajewski, Patrick D; Falkenstein, Michael; Hengstler, Jan G; Golka, Klaus

2014-02-01

Almost 30% of humans present a Toxoplasma gondii positive antibody status and its prevalence increases with age. The central nervous system is the main target. However, little is known about the influence of asymptomatic i.e. latent Toxoplasmosis on cognitive functions in humans. To investigate neurocognitive dysfunctions in asymptomatic older adults with T. gondii positive antibody status a double-blinded neuropsychological study was conducted. The participants were classified from a population-based sample (N=131) of healthy participants with an age of 65 years and older into two groups with 42 individuals each: Toxoplasmosis positive (T-pos; IgG>50 IU/ml) and Toxoplasmosis negative (T-neg; IgG=0 IU/ml). The outcome measures were a computer-based working-memory test (2-back) and several standardized psychometric tests of memory and executive cognitive functions. T-pos seniors showed an impairment of different aspects of memory. The rate of correctly detected target symbols in a 2-back task was decreased by nearly 9% (P=0.020), corresponding to a performance reduction of about 35% in working memory relative to the T-neg group. Moreover, T-pos seniors had a lower performance in a verbal memory test, both regarding immediate recall (10% reduction; P=0.022), delayed recognition (6%; P=0.037) and recall from long-term memory assessed by the word fluency tests (12%; P=0.029). In contrast, executive functions were not affected. The effects remained mostly unchanged after controlling for medication. The impairment of memory functions in T-pos seniors was accompanied by a decreased self-reported quality of life. Because of the high prevalence of asymptomatic Toxoplasmosis and an increasing population of older adults this finding is of high relevance for public health. Copyright © 2013 Elsevier Inc. All rights reserved.

Cognitive Impairment in Adults with Non-CNS Cancers (PDQ®)—Health Professional Version

Cancer.gov

Cognitive impairment in adult cancer survivors may include problems with memory, concentration, information processing, and executive function. Get comprehensive information about assessing and managing cognitive impairment in this summary for clinicians.

Autobiographical Memory in Semantic Dementia: A Longitudinal fMRI Study

ERIC Educational Resources Information Center

Maguire, Eleanor A.; Kumaran, Dharshan; Hassabis, Demis; Kopelman, Michael D.

2010-01-01

Whilst patients with semantic dementia (SD) are known to suffer from semantic memory and language impairments, there is less agreement about whether memory for personal everyday experiences, autobiographical memory, is compromised. In healthy individuals, functional MRI (fMRI) has helped to delineate a consistent and distributed brain network…

Enhanced clonal burst size corrects an otherwise defective memory response by CD8+ recent thymic emigrants

PubMed Central

Deets, Katherine A.; Berkley, Amy M.; Bergsbaken, Tessa; Fink, Pamela J.

2016-01-01

The youngest peripheral T cells (recent thymic emigrants or RTEs) are functionally distinct from naïve T cells that have completed post-thymic maturation. We now assess the RTE memory response, and find that RTEs produced less granzyme B than their mature counterparts during infection, but proliferated more and therefore generated equivalent target killing in vivo. After infection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. PMID:26873989

Cutting Edge: Enhanced Clonal Burst Size Corrects an Otherwise Defective Memory Response by CD8+ Recent Thymic Emigrants.

PubMed

Deets, Katherine A; Berkley, Amy M; Bergsbaken, Tessa; Fink, Pamela J

2016-03-15

The youngest peripheral T cells (recent thymic emigrants [RTEs]) are functionally distinct from naive T cells that have completed postthymic maturation. We assessed the RTE memory response and found that RTEs produced less granzyme B than their mature counterparts during infection but proliferated more and, therefore, generated equivalent target killing in vivo. Postinfection, RTE numbers contracted less dramatically than those of mature T cells, but RTEs were delayed in their transition to central memory, displaying impaired expression of CD62L, IL-2, Eomesodermin, and CXCR4, which resulted in impaired bone marrow localization. RTE-derived and mature memory cells expanded equivalently during rechallenge, indicating that the robust proliferative capacity of RTEs was maintained independently of central memory phenotype. Thus, the diminished effector function and delayed central memory differentiation of RTE-derived memory cells are counterbalanced by their increased proliferative capacity, driving the efficacy of the RTE response to that of mature T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

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.

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.

Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects.

PubMed

Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

2014-01-01

Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats.

Characterizing “fibrofog”: Subjective appraisal, objective performance, and task-related brain activity during a working memory task

PubMed Central

Walitt, Brian; Čeko, Marta; Khatiwada, Manish; Gracely, John L.; Rayhan, Rakib; VanMeter, John W.; Gracely, Richard H.

2016-01-01

The subjective experience of cognitive dysfunction (“fibrofog”) is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self-Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, “fibrofog” appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks. PMID:26955513

Characterizing "fibrofog": Subjective appraisal, objective performance, and task-related brain activity during a working memory task.

PubMed

Walitt, Brian; Čeko, Marta; Khatiwada, Manish; Gracely, John L; Rayhan, Rakib; VanMeter, John W; Gracely, Richard H

2016-01-01

The subjective experience of cognitive dysfunction ("fibrofog") is common in fibromyalgia. This study investigated the relation between subjective appraisal of cognitive function, objective cognitive task performance, and brain activity during a cognitive task using functional magnetic resonance imaging (fMRI). Sixteen fibromyalgia patients and 13 healthy pain-free controls completed a battery of questionnaires, including the Multiple Ability Self-Report Questionnaire (MASQ), a measure of self-perceived cognitive difficulties. Participants were evaluated for working memory performance using a modified N-back working memory task while undergoing Blood Oxygen Level Dependent (BOLD) fMRI measurements. Fibromyalgia patients and controls did not differ in working memory performance. Subjective appraisal of cognitive function was associated with better performance (accuracy) on the working memory task in healthy controls but not in fibromyalgia patients. In fibromyalgia patients, increased perceived cognitive difficulty was positively correlated with the severity of their symptoms. BOLD response during the working memory task did not differ between the groups. BOLD response correlated with task accuracy in control subjects but not in fibromyalgia patients. Increased subjective cognitive impairment correlated with decreased BOLD response in both groups but in different anatomic regions. In conclusion, "fibrofog" appears to be better characterized by subjective rather than objective impairment. Neurologic correlates of this subjective experience of impairment might be separate from those involved in the performance of cognitive tasks.

Memory and mood during the night and in the morning after repeated evening doses of MDMA.

PubMed

Kuypers, K P C; Wingen, M; Ramaekers, J G

2008-11-01

Previously it has been shown that MDMA causes memory impairment during daytime testing. However, MDMA is usually taken in the evening or during the night. In addition, it is known that sleep deprivation also causes memory impairment. The present study aimed to assess whether evening doses of MDMA added to, or interacted with the memory impairment due to sleep deprivation. Fourteen healthy subjects participated in a double-blind, placebo-controlled, two-way cross-over study. Treatments consisted of MDMA 75 and 50 mg divided over the evening or double placebo. Memory tests and subjective measures of mood were conducted at baseline and three times post dosing that is at 6.30 pm, 9.30 pm, 1.30 am and 7 am, respectively -1.5, 1.5, 5.5 and 11 h relative to drug intake (first dose). Memory performance detoriated progessively over time as a function of sleep loss, independent of treatment. MDMA added to this impairment as indicated by a significant main effect of MDMA on verbal and spatial memory performance. Mood ratings and response speed revealed an MDMA by Time interaction. After administration of MDMA response speed improved and feelings of vigor, friendliness, elation, anxiety, confusion, arousal and positive mood increased in magnitude during the night, while all these parameters returned to placebo-like levels on the final morning session. It is concluded that evening doses of MDMA selectively impair memory performance, and that this impairment is additional to the effect of sleep deprivation on memory performance.

Association of Source of Memory Complaints and Increased Risk of Cognitive Impairment and Cognitive Decline: A Community-Based Study.

PubMed

Qi, Xue-Mei; Gu, Lin; Tang, Hui-Dong; Chen, Sheng-Di; Ma, Jian-Fang

2018-04-20

Memory complaint is common in the elderly. Recently, it was shown that self-report memory complaint was predictive of cognitive decline. This study aimed to investigate the predictive value of the source of memory complaints on the risk of cognitive impairment and cognitive decline in a community-based cohort. Data on memory complaints and cognitive function were collected among 1840 Chinese participants (aged ≥55 years old) in an urban community at baseline interview and 5-year follow-up. Incident cognitive impairment was identified based on education-adjusted Mini-Mental State Examination score. Logistic regression model was used to estimate the association between the source of memory complaints and risk of cognitive impairment conversion and cognitive decline, after adjusting for covariates. A total of 1840 participants were included into this study including 1713 normal participants and 127 cognitive impairment participants in 2009. Among 1713 normal participants in 2009, 130 participants were converted to cognitive impairment after 5 years of follow-up. In 2014, 606 participants were identified as cognitive decline. Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment (odds ratio [OR] = 1.60, 95% confidence interval [CI]: 1.04-2.48) and cognitive decline (OR = 1.30, 95% CI: 1.01-1.68). Furthermore, this association was more significant in males (OR = 2.10, 95% CI: 1.04-4.24 for cognitive impairment and OR = 1.87, 95% CI: 1.20-2.99 for cognitive decline) and in higher education level (OR = 1.79, 95% CI: 1.02-3.15 for cognitive impairment and OR = 1.40, 95% CI: 1.02-1.91 for cognitive decline). Both self- and informant-reported memory complaints were associated with an increased risk of cognitive impairment conversion and cognitive decline, especially in persons with male gender and high educational background.

ANOSOGNOSIA FOR MEMORY IMPAIRMENT IN ADDICTION: INSIGHTS FROM NEUROIMAGING AND NEUROPSYCHOLOGICAL ASSESSMENT OF METAMEMORY

PubMed Central

Le Berre, Anne-Pascale; Sullivan, Edith V.

2016-01-01

In addiction, notably, Alcohol Use Disorder (AUD), patients often have a tendency to fail to acknowledge the reality of the disease and to minimize the physical, psychological, and social difficulties attendant to chronic alcohol consumption. This lack of awareness can reduce the chances of initiating and maintaining sobriety. Presented here is a model focusing on compromised awareness in individuals with AUD of mild to moderate cognitive deficits, in particular, for episodic memory impairment—the ability to learn new information, such as recent personal experiences. Early in abstinence, alcoholics can be unaware of their memory deficits and overestimate their mnemonic capacities, which can be investigated with metamemory paradigms. Relevant neuropsychological and neuroimaging results considered suggest that the alcoholics’ impairment of awareness of their attenuated memory function can be a clinical manifestation explained mechanistically by neurobiological factors, including compromise of brain systems that result in a mild form of mnemonic anosognosia. Specifically, unawareness of memory impairment in AUD may result from a lack of personal knowledge updating attributable to damage in brain regions or connections supporting conscious recollection in episodic memory. Likely candidates are posterior parietal and medial frontal regions known to be integral part of the Default Mode Network (DMN) and the insula leading to an impaired switching mechanism between the DMN and the Central-Executive Control (i.e., Lateral Prefronto-Parietal) Network. The cognitive concepts and neural substrates noted for addictive disorders may also be relevant for problems in self-identification of functional impairment resulting from injury following war-related blast, sport-related concussion, and insidiously occurring dementia. PMID:27447979

Episodic memory functions in first episode psychosis and clinical high risk individuals.

PubMed

Greenland-White, Sarah E; Ragland, J Daniel; Niendam, Tara A; Ferrer, Emilio; Carter, Cameron S

2017-10-01

Individuals with schizophrenia have disproportionate memory impairments when encoding relational versus item-specific information, and when using recollection versus familiarity during retrieval. It is unclear whether this pattern is unique to people with chronic schizophrenia, or if it occurs in individuals after a first episode of psychosis (FE), or when at clinical high-risk for psychosis (CHR). We administered the Relational and Item-Specific Memory task (RiSE) to 22 CHR, 101 FE, and 58 typically developing (TD) participants. We examined group differences in item and relational encoding, and familiarity-based and recollection-based retrieval using parametric analysis and structural equation modeling (SEM). Longitudinal data allowed us to examine relations between baseline RiSE performance and change in clinical symptoms at 1-year follow-up in the FE group. Groups did not differ on familiarity. FE and CHR groups were equally impaired on overall recognition accuracy. Although recollection was impaired in both FE and CHR groups following relational encoding, only the FE group had impaired recollection following item encoding. SEM showed atypical relationships between familiarity and recollection, as well as familiarity and item recognition for both the FE and CHR groups. For FE individuals, better baseline recognition accuracy predicted less severe negative symptoms at 1-year follow-up. Impaired relational and recollective memory may reflect neurodevelopmental abnormalities predating conversion to psychosis. These memory deficits appear related to negative symptom changes. In contrast, item specific recollection deficits appear to occur after the development of full psychosis. Familiarity appears to be a relatively preserved memory function across the psychosis spectrum. Copyright © 2017 Elsevier B.V. All rights reserved.

Disruptions of network connectivity predict impairment in multiple behavioral domains after stroke

PubMed Central

Ramsey, Lenny E.; Metcalf, Nicholas V.; Chacko, Ravi V.; Weinberger, Kilian; Baldassarre, Antonello; Hacker, Carl D.; Shulman, Gordon L.; Corbetta, Maurizio

2016-01-01

Deficits following stroke are classically attributed to focal damage, but recent evidence suggests a key role of distributed brain network disruption. We measured resting functional connectivity (FC), lesion topography, and behavior in multiple domains (attention, visual memory, verbal memory, language, motor, and visual) in a cohort of 132 stroke patients, and used machine-learning models to predict neurological impairment in individual subjects. We found that visual memory and verbal memory were better predicted by FC, whereas visual and motor impairments were better predicted by lesion topography. Attention and language deficits were well predicted by both. Next, we identified a general pattern of physiological network dysfunction consisting of decrease of interhemispheric integration and intrahemispheric segregation, which strongly related to behavioral impairment in multiple domains. Network-specific patterns of dysfunction predicted specific behavioral deficits, and loss of interhemispheric communication across a set of regions was associated with impairment across multiple behavioral domains. These results link key organizational features of brain networks to brain–behavior relationships in stroke. PMID:27402738

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Structural correlates of impaired working memory in hippocampal sclerosis.

PubMed

Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S

2013-07-01

Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Structural correlates of impaired working memory in hippocampal sclerosis

PubMed Central

Winston, Gavin P; Stretton, Jason; Sidhu, Meneka K; Symms, Mark R; Thompson, Pamela J; Duncan, John S

2013-01-01

Purpose: Temporal lobe epilepsy (TLE) has been considered to impair long-term memory, whilst not affecting working memory, but recent evidence suggests that working memory is compromised. Functional MRI (fMRI) studies demonstrate that working memory involves a bilateral frontoparietal network the activation of which is disrupted in hippocampal sclerosis (HS). A specific role of the hippocampus to deactivate during working memory has been proposed with this mechanism faulty in patients with HS. Structural correlates of disrupted working memory in HS have not been explored. Methods: We studied 54 individuals with medically refractory TLE and unilateral HS (29 left) and 28 healthy controls. Subjects underwent 3T structural MRI, a visuospatial n-back fMRI paradigm and diffusion tensor imaging (DTI). Working memory capacity assessed by three span tasks (digit span backwards, gesture span, motor sequences) was combined with performance in the visuospatial paradigm to give a global working memory measure. Gray and white matter changes were investigated using voxel-based morphometry and voxel-based analysis of DTI, respectively. Key Findings: Individuals with left or right HS performed less well than healthy controls on all measures of working memory. fMRI demonstrated a bilateral frontoparietal network during the working memory task with reduced activation of the right parietal lobe in both patient groups. In left HS, gray matter loss was seen in the ipsilateral hippocampus and parietal lobe, with maintenance of the gray matter volume of the contralateral parietal lobe associated with better performance. White matter integrity within the frontoparietal network, in particular the superior longitudinal fasciculus and cingulum, and the contralateral temporal lobe, was associated with working memory performance. In right HS, gray matter loss was also seen in the ipsilateral hippocampus and parietal lobe. Working memory performance correlated with the gray matter volume of both frontal lobes and white matter integrity within the frontoparietal network and contralateral temporal lobe. Significance: Our data provide further evidence that working memory is disrupted in HS and impaired integrity of both gray and white matter is seen in functionally relevant areas. We suggest this forms the structural basis of the impairment of working memory, indicating widespread and functionally significant structural changes in patients with apparently isolated HS. PMID:23614459

Relationship between personality disorder dimensions and verbal memory functioning in a community population.

PubMed

Park, Subin; Hong, Jin Pyo; Lee, Hochang B; Samuels, Jack; Bienvenu, O Joseph; Chung, Hye Yoon; Eaton, William W; Costa, Paul T; Nestadt, Gerald

2012-03-30

Based on the Baltimore Epidemiologic Catchment Area (ECA) follow-up survey, we examined relationships between dimensions of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) personality disorders and both subjective and objective memory functioning in a community population. Our study subjects consisted of 736 individuals from the ECA follow-up study of the original Baltimore ECA cohort, conducted between 1993 and 1996 and available for assessment in the Hopkins Epidemiology Study of Personality Disorders from 1997 to 1999. Subjects were assessed for DSM-IV personality disorders using a semi-structured instrument, the International Personality Disorder Examination, and were asked about a subjective appraisal of memory. Verbal memory function, including immediate recall, delayed recall, and recognition, were also evaluated. Multiple linear regression analyses were used to determine associations between personality dimensions of DSM-IV Axis II traits and subjective and objective memory functioning. Scores on schizoid and schizotypal personality dimensions were associated with subjective and objective memory dysfunction, both with and without adjustment for Axis I disorders. Borderline, antisocial, avoidant, and dependent personality disorder scores were associated with subjective memory impairment only, both with and without adjustment for Axis I disorders. This study suggests that subjective feelings of memory impairment and/or objective memory dysfunction are associated with specific personality disorder dimensions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Reduced Mastication Impairs Memory Function.

PubMed

Fukushima-Nakayama, Y; Ono, Takehito; Hayashi, M; Inoue, M; Wake, H; Ono, Takashi; Nakashima, T

2017-08-01

Mastication is an indispensable oral function related to physical, mental, and social health throughout life. The elderly tend to have a masticatory dysfunction due to tooth loss and fragility in the masticatory muscles with aging, potentially resulting in impaired cognitive function. Masticatory stimulation has influence on the development of the central nervous system (CNS) as well as the growth of maxillofacial tissue in children. Although the relationship between mastication and cognitive function is potentially important in the growth period, the cellular and molecular mechanisms have not been sufficiently elucidated. Here, we show that the reduced mastication resulted in impaired spatial memory and learning function owing to the morphological change and decreased activity in the hippocampus. We used an in vivo model for reduced masticatory stimuli, in which juvenile mice were fed with powder diet and found that masticatory stimulation during the growth period positively regulated long-term spatial memory to promote cognitive function. The functional linkage between mastication and brain was validated by the decrease in neurons, neurogenesis, neuronal activity, and brain-derived neurotrophic factor (BDNF) expression in the hippocampus. These findings taken together provide in vivo evidence for a functional linkage between mastication and cognitive function in the growth period, suggesting a need for novel therapeutic strategies in masticatory function-related cognitive dysfunction.

Prospective memory impairment in "ecstasy" (MDMA) users.

PubMed

Rendell, Peter G; Gray, Timothy J; Henry, Julie D; Tolan, Anne

2007-11-01

Considerable research indicates that "ecstasy" users perceive their memory for future intentions (prospective memory) to be impaired. However, only one empirical study to date has directly tested how this capacity is affected by ecstasy use, and this study provided relatively limited information regarding the extent, scope, or implications of problems experienced. The present study assessed prospective performance on a laboratory measure of prospective memory that closely represents the types of prospective memory tasks that actually occur in everyday life and provides an opportunity to investigate the different sorts of prospective memory failures that occur ("Virtual Week"). Ecstasy user group (27 current users and 34 nonusers) was between participants, and prospective memory task (regular, irregular, time-check) was within participants. A measure sensitive to specific aspects of psychopathology was also administered. Ecstasy users were significantly impaired on Virtual Week, and these deficits were of a comparable magnitude irrespective of the specific prospective memory task demands. The pattern of results was unchanged after controlling for marijuana use, level of psychopathology, and sleep quality. Further, prospective memory was shown to be significantly impaired for both relatively infrequent and relatively frequent ecstasy users, although for the latter group the magnitude of this deficit was greater. Prospective memory performance is sensitive to regular and even moderate ecstasy use. Importantly, ecstasy users experience generalized difficulties with prospective memory, suggesting that these deficits are likely to have important implications for day-to-day functioning.

Face Memory and Object Recognition in Children with High-Functioning Autism or Asperger Syndrome and in Their Parents

ERIC Educational Resources Information Center

Kuusikko-Gauffin, Sanna; Jansson-Verkasalo, Eira; Carter, Alice; Pollock-Wurman, Rachel; Jussila, Katja; Mattila, Marja-Leena; Rahko, Jukka; Ebeling, Hanna; Pauls, David; Moilanen, Irma

2011-01-01

Children with Autism Spectrum Disorders (ASDs) have reported to have impairments in face, recognition and face memory, but intact object recognition and object memory. Potential abnormalities, in these fields at the family level of high-functioning children with ASD remains understudied despite, the ever-mounting evidence that ASDs are genetic and…

Impact of neurocognition on social and role functioning in individuals at clinical high risk for psychosis.

PubMed

Carrión, Ricardo E; Goldberg, Terry E; McLaughlin, Danielle; Auther, Andrea M; Correll, Christoph U; Cornblatt, Barbara A

2011-08-01

Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning.

Impact of Neurocognition on Social and Role Functioning in Individuals at Clinical High Risk for Psychosis

PubMed Central

Carrión, Ricardo E.; Goldberg, Terry E.; McLaughlin, Danielle; Auther, Andrea M.; Correll, Christoph U.; Cornblatt, Barbara A.

2011-01-01

Objective Cognitive deficits have been well documented in schizophrenia and have been shown to impair quality of life and to compromise everyday functioning. Recent studies of adolescents and young adults at high risk for developing psychosis show that neurocognitive impairments are detectable before the onset of psychotic symptoms. However, it remains unclear how cognitive impairments affect functioning before the onset of psychosis. The authors assessed cognitive impairment in adolescents at clinical high risk for psychosis and examined its impact on social and role functioning. Method A sample of 127 treatment-seeking patients at clinical high risk for psychosis and a group of 80 healthy comparison subjects were identified and recruited for research in the Recognition and Prevention Program. At baseline, participants were assessed with a comprehensive neurocognitive battery as well as measures of social and role functioning. Results Relative to healthy comparison subjects, clinical high-risk patients showed significant impairments in the domains of processing speed, verbal memory, executive function, working memory, visuospatial processing, motor speed, sustained attention, and language. Clinical high-risk patients also displayed impaired social and role functioning at baseline. Among patients with attenuated positive symptoms, processing speed was related to social and role functioning at baseline. Conclusions These findings demonstrate that cognitive and functional impairments are detectable in patients at clinical high risk for psychosis before the onset of psychotic illness and that processing speed appears to be an important cognitive predictor of poor functioning. PMID:21536691

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

PubMed Central

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

2013-01-01

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

Wnt signaling inhibits CTL memory programming

PubMed Central

Xiao, Zhengguo; Sun, Zhifeng; Smyth, Kendra; Li, Lei

2013-01-01

Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers. PMID:23911398

Cholinergic modulation of the hippocampal region and memory function.

PubMed

Haam, Juhee; Yakel, Jerrel L

2017-08-01

Acetylcholine (ACh) plays an important role in memory function and has been implicated in aging-related dementia, in which the impairment of hippocampus-dependent learning strongly manifests. Cholinergic neurons densely innervate the hippocampus, mediating the formation of episodic as well as semantic memory. Here, we will review recent findings on acetylcholine's modulation of memory function, with a particular focus on hippocampus-dependent learning, and the circuits involved. In addition, we will discuss the complexity of ACh actions in memory function to better understand the physiological role of ACh in memory. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

Cognitive functioning in the first-episode of major depressive disorder: A systematic review and meta-analysis.

PubMed

Ahern, Elayne; Semkovska, Maria

2017-01-01

Cognitive deficits are frequently observed in major depression. Yet, when these deficits emerge and how they relate to the depressed state is unclear. The aim of this 2-part systematic review and meta-analysis is to determine the pattern and extent of cognitive deficits during a first-episode of depression (FED) and their persistence following FED remission. Published, peer-reviewed articles on cognitive function in FED patients through October 2015 were searched. Meta-analyses with random-effects modeling were conducted. Part 1 assessed weighted, mean effect sizes of cognitive function in FED patients relative to healthy controls. Moderator analyses of clinical and demographical variables effects were conducted. Part 2 assessed weighted, mean effect sizes of change in cognitive function at remission compared with acute FED performance in longitudinal studies. Thirty-one studies including 994 FED patients were retained in Part 1. Relative to healthy controls, small to large impairments were observed across most cognitive domains. Remission was associated with a normalization of function in processing speed, learning and memory, autobiographical memory, shifting, and IQ. Lower FED age was associated with higher IQ, but more impairment in word-list delayed memory. Four studies including 92 FED patients were retained in Part 2. Following remission, FED patients showed small improvements in processing speed and shifting but persistent impairment in inhibition and verbal fluency. Significant cognitive deficits are already identifiable during a FED, with some functions showing persistent impairment upon remission. Clinicians must consider cognitive impairment alongside mood symptoms to ensure functional recovery from the FED. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Subtle cognitive impairments in patients with long-term cure of Cushing's disease.

PubMed

Tiemensma, Jitske; Kokshoorn, Nieke E; Biermasz, Nienke R; Keijser, Bart-Jan S A; Wassenaar, Moniek J E; Middelkoop, Huub A M; Pereira, Alberto M; Romijn, Johannes A

2010-06-01

Active Cushing's disease is associated with cognitive impairments. We hypothesized that previous hypercortisolism in patients with Cushing's disease results in irreversible impairments in cognitive functioning. Therefore, our aim was to assess cognitive functioning after long-term cure of Cushing's disease. Cognitive assessment consisted of 11 tests, which evaluated global cognitive functioning, memory, and executive functioning. We included 74 patients cured of Cushing's disease and 74 controls matched for age, gender, and education. Furthermore, we included 54 patients previously treated for nonfunctioning pituitary macroadenomas (NFMA) and 54 controls matched for age, gender, and education. Compared with NFMA patients, patients cured from Cushing's disease had lower scores on the Mini Mental State Examination (P = 0.001), and on the memory quotient of the Wechsler Memory Scale (P = 0.050). Furthermore, patients cured from Cushing's disease tended to recall fewer words on the imprinting (P = 0.013), immediate recall (P = 0.012), and delayed recall (P = 0.003) trials of the Verbal Learning Test of Rey. On the Rey Complex Figure Test, patients cured from Cushing's disease had lower scores on both trials (P = 0.002 and P = 0.007) compared with NFMA patients. Patients cured from Cushing's disease also made fewer correct substitutions on the Letter-Digit Substitution Test (P = 0.039) and came up with fewer correct patterns on the Figure Fluency Test (P = 0.003) compared with treated NFMA patients. Cognitive function, reflecting memory and executive functions, is impaired in patients despite long-term cure of Cushing's disease. These observations indicate irreversible effects of previous hypercortisolism on cognitive function and, thus, on the central nervous system. These observations may also be of relevance for patients treated with high-dose exogenous glucocorticoids.

Preschoolers with Down Syndrome Do Not yet Show the Learning and Memory Impairments Seen in Adults with Down Syndrome

ERIC Educational Resources Information Center

Roberts, Lynette V.; Richmond, Jenny L.

2015-01-01

Individuals with Down syndrome (DS) exhibit a behavioral phenotype of specific strengths and weaknesses, in addition to a generalized cognitive delay. In particular, adults with DS exhibit specific deficits in learning and memory processes that depend on the hippocampus, and there is some suggestion of impairments on executive function tasks that…

The Effect of Insulin and Insulin-Like Growth Factors on Hippocampus- and Amygdala-Dependent Long-Term Memory Formation

ERIC Educational Resources Information Center

Stern, Sarah A.; Chen, Dillon Y.; Alberini, Cristina M.

2014-01-01

Recent work has reported that the insulin-like growth factor 2 (IGF2) promotes memory enhancement. Furthermore, impaired insulin or IGF1 functions have been suggested to play a role in the pathogenesis of neurodegeneration and cognitive impairments, hence implicating the insulin/IGF system as an important target for cognitive enhancement and/or…

The neurobiology of cognitive disorders in temporal lobe epilepsy

PubMed Central

Bell, Brian; Lin, Jack J.; Seidenberg, Michael; Hermann, Bruce

2013-01-01

Cognitive impairment and especially memory disruption is a major complicating feature of the epilepsies. In this review we begin with a focus on the problem of memory impairment in temporal lobe epilepsy. We start with a brief overview of the early development of knowledge regarding the anatomic substrates of memory disorder in temporal lobe epilepsy, followed by discussion of the refinement of that knowledge over time as informed by the outcomes of epilepsy surgery (anterior temporal lobectomy) and the clinical efforts to predict those patients at greatest risk of adverse cognitive outcomes following epilepsy surgery. These efforts also yielded new theoretical insights regarding the function of the human hippocampus and a few examples of these insights are touched on briefly. Finally, the vastly changing view of temporal lobe epilepsy is examined including findings demonstrating that anatomic abnormalities extend far outside the temporal lobe, cognitive impairments extend beyond memory function, with linkage of these distributed cognitive and anatomic abnormalities pointing to a new understanding of the anatomic architecture of cognitive impairment in epilepsy. Challenges remain in understanding the origin of these cognitive and anatomic abnormalities, their progression over time, and most importantly, how to intervene to protect cognitive and brain health in epilepsy. PMID:21304484

Modulation of working memory load distinguishes individuals with and without balance impairments following mild traumatic brain injury.

PubMed

Woytowicz, Elizabeth J; Sours, Chandler; Gullapalli, Rao P; Rosenberg, Joseph; Westlake, Kelly P

2018-01-01

Balance and gait deficits can persist after mild traumatic brain injury (TBI), yet an understanding of the underlying neural mechanism remains limited. The purpose of this study was to investigate differences in attention network modulation in patients with and without balance impairments 2-8 weeks following mild TBI. Using functional magnetic resonance imaging, we compared activity and functional connectivity of cognitive brain regions of the default mode, central-executive and salience networks during a 2-back working memory task in participants with mild TBI and balance impairments (n = 7, age 47 ± 15 years) or no balance impairments (n = 7, age 47 ± 15 years). We first identified greater activation in the lateral occipital cortex in the balance impaired group. Second, we observed stronger connectivity of left pre-supplementary motor cortex in the balance impaired group during the working memory task, which was related to decreased activation of regions within the salience and central executive networks and greater suppression of the default mode network. Results suggest a link between impaired balance and modulation of cognitive resources in patients in mTBI. Findings also highlight the potential importance of moving beyond traditional balance assessments towards an integrative assessment of cognition and balance in this population.

Memory in children with epilepsy: a systematic review.

PubMed

Menlove, Leanne; Reilly, Colin

2015-02-01

Research suggests an increased risk for cognitive impairment in childhood epilepsy with memory being one area of cognition most likely to be affected. Understanding the prevalence and predictors of memory difficulties may help improve awareness of the difficulties and allow efficacious supports to be put in place. A systematic review was carried out using the search terms 'memory', 'children' and 'epilepsy' in the database PUBMED. Eighty-eight studies met inclusion criteria. The review focuses on comparisons of memory scores of children with epilepsy and controls, and comparison of memory scores of children with epilepsy to normative scores. Predictors of memory impairment and the effect of surgery on memory functioning are also reviewed. The majority (78%) of studies reviewed revealed that children with epilepsy scored lower than controls and normative scores on measures of memory. Post-surgery, memory scores were reported to improve in 50% of studies. Predictors of memory impairment included a greater number of AEDs used, younger age of onset, increased seizure frequency and longer duration of epilepsy. Children with epilepsy have a high frequency of memory impairments. However, the exact prevalence of difficulties is not clear due to the lack of population-based data. Most studies have not controlled for IQ and thus it is unclear if difficulties are always related to global cognitive difficulties. There is need for future population-based studies and studies focussing on the neurobiology of memory problems in children with epilepsy. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Prefrontal gray matter morphology mediates the association between serum anticholinergicity and cognitive functioning in early course schizophrenia.

PubMed

Wojtalik, Jessica A; Eack, Shaun M; Pollock, Bruce G; Keshavan, Matcheri S

2012-11-30

Antipsychotic and other medications used in the treatment of schizophrenia place a burden on the cholinergic subsystems of the brain, which have been associated with increased cognitive impairment in the disorder. This study sought to examine the neurobiologic correlates of the association between serum anticholinergic activity (SAA) and cognitive impairments in early schizophrenia. Neurocognitive performance on measures of memory and executive function, structural magnetic resonance imaging (MRI) scans, and SAA assays were collected from 47 early course, stabilized outpatients with schizophrenia or schizoaffective disorder. Voxel-based morphometry analyses employing general linear models, adjusting for demographic and illness-related confounds, were used to investigate the associations between SAA, gray matter morphology, and neurocognitive impairment. SAA was related to working memory and executive function impairments. Higher SAA was significantly associated with lower gray matter density in broad regions of the frontal and medial-temporal lobes, including the dorsolateral prefrontal cortex (DLPFC), hippocampus, and striatum. Lower gray matter volume in the left DLPFC was found to significantly mediate the association between SAA and working memory impairment. Disease- and/or medication-related cholinergic dysfunction may be associated with brain volume abnormalities in early course schizophrenia, which may account for the association between SAA and cognitive dysfunction in the disorder. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Assessing Mild Cognitive Impairment among Older African Americans

PubMed Central

Gamaldo, Alyssa A.; Allaire, Jason C.; Sims, Regina C.; Whitfield, Keith E.

2009-01-01

OBJECTIVES To examine the frequency of MCI in African American older adults. The study also plans to explore the specific cognitive domains of impairment as well as whether there are differences in demographics, health, and cognitive performance between MCI and normal participants. DESIGN Cross-sectional. SETTING Independent-living sample of urban dwelling elders in Baltimore, Maryland. PARTICIPANTS The sample consisted of 554 subjects ranging in age from 50 to 95 (mean = 68.79 ± 9.60). MEASUREMENTS Socio-demographics and health were assessed. Several cognitive measures were administered to assess inductive reasoning, declarative memory, perceptual speed, working memory, executive functioning, language, global cognitive functioning. RESULTS Approximately 22% of participants were considered MCI (i.e. 18% non-amnestic vs. 4% amnestic). A majority of the non-amnestic MCI participants had impairment in one cognitive domain, particularly language and executive function. Individuals classified as non-amnestic MCI were significantly older and had more years of education than normal individuals. The MCI groups were not significantly different than cognitively normal individuals on health factors. Individuals classified as MCI performed significantly worse on global cognitive measures as well as across specific cognitive domains than cognitively normal individuals. CONCLUSION This study demonstrates that impairment in a non-memory domain may be an early indicator of cognitive impairment, particularly among African Americans. PMID:20069588

Functional retrograde amnesia: a quantitative case study.

PubMed

Schacter, D L; Wang, P L; Tulving, E; Freedman, M

1982-01-01

The memory impairment of a patient suffering from functional retrograde amnesia was assessed both during the amnesic episode and after its termination. The patient's performance on a task tapping semantic memory was nearly identical on the two test occasions, but his performance on a task tapping episodic memory substantially changed across test sessions. Cueing procedures revealed that in spite of the patient's restricted access to episodic memory during the amnesic period, a relatively intact "island" of episodic memories could be uncovered. The distinction between episodic and semantic memory, as well as the relation between organic and functional retrograde amnesia, are discussed in light of the case study.

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.

Cognitive Performance in Older Adults with Stable Heart Failure: Longitudinal Evidence for Stability and Improvement

PubMed Central

Alosco, Michael L.; Garcia, Sarah; Spitznagel, Mary Beth; van Dulmen, Manfred; Cohen, Ronald; Sweet, Lawrence H.; Josephson, Richard; Hughes, Joel; Rosneck, Jim; Gunstad, John

2013-01-01

Cognitive impairment is prevalent in heart failure (HF), though substantial variability in the pattern of cognitive impairment is found across studies. To clarify the nature of cognitive impairment in HF, we examined longitudinal trajectories across multiple domains of cognition in HF patients using latent growth class modeling. 115 HF patients completed a neuropsychological battery at baseline, 3-months and 12-months. Participants also completed the Beck Depression Inventory-II (BDI-II). Latent class growth analyses revealed a three-class model for attention/executive function, four-class model for memory, and a three-class model for language. The slope for attention/executive function and language remained stable, while improvements were noted in memory performance. Education and BDI-II significantly predicted the intercept for attention/executive function and language abilities. The BDI-II also predicted baseline memory. The current findings suggest that multiple performance-based classes of neuropsychological test performance exist within cognitive domains, though case-controlled prospective studies with extended follow-ups are needed to fully elucidate changes and predictors of cognitive function in HF. PMID:23906182

Association of homocysteine level and vascular burden and cognitive function in middle-aged and older adults with chronic kidney disease.

PubMed

Yeh, Yi-Chun; Huang, Mei-Feng; Hwang, Shang-Jyh; Tsai, Jer-Chia; Liu, Tai-Ling; Hsiao, Shih-Ming; Yang, Yi-Hsin; Kuo, Mei-Chuan; Chen, Cheng-Sheng

2016-07-01

Patients with chronic kidney disease (CKD) have been found to have cognitive impairment. However, the core features and clinical correlates of cognitive impairment are still unclear. Elevated homocysteine levels are present in CKD, and this is a risk factor for cognitive impairment and vascular diseases in the general population. Thus, this study investigated the core domains of cognitive impairment and investigated the associations of homocysteine level and vascular burden with cognitive function in patients with CKD. Patients with CKD aged ≥ 50 years and age- and sex-matched normal comparisons were enrolled. The total fasting serum homocysteine level was measured. Vascular burden was assessed using the Framingham Cardiovascular Risk Scale. Cognitive function was evaluated using comprehensive neuropsychological tests. A total of 230 patients with CKD and 92 comparisons completed the study. Memory impairment and executive dysfunction were identified as core features of cognitive impairment in the CKD patients. Among the patients with CKD, higher serum homocysteine levels (β = -0.17, p = 0.035) and higher Framingham Cardiovascular Risk Scale scores (β = -0.18, p = 0.013) were correlated with poor executive function independently. However, an association with memory function was not noted. Our results showed that an elevated homocysteine level and an increased vascular burden were independently associated with executive function, but not memory, in CKD patients. This findings suggested the co-existence of vascular and non-vascular hypotheses regarding executive dysfunction in CKD patients. Meanwhile, other risk factors related to CKD itself should be investigated in the future. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

A Calendar Savant with Episodic Memory Impairments

PubMed Central

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

2010-01-01

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

Cognitive function in Japanese women with posttraumatic stress disorder: Association with exercise habits.

PubMed

Narita-Ohtaki, Ryoko; Hori, Hiroaki; Itoh, Mariko; Lin, Mingming; Niwa, Madoka; Ino, Keiko; Imai, Risa; Ogawa, Sei; Sekiguchi, Atsushi; Matsui, Mie; Kunugi, Hiroshi; Kamo, Toshiko; Kim, Yoshiharu

2018-08-15

Posttraumatic stress disorder (PTSD) has been associated with cognitive impairments, yet little is documented on the cognitive function of PTSD patients in Asian countries. It is shown that regular exercise can reduce PTSD symptoms, while no study has investigated the association between exercise and cognition in PTSD patients. This study aimed to examine cognitive functions of Japanese women with PTSD, and to explore the association between regular exercise and cognitive functions. Forty-two women with DSM-IV PTSD and 66 demographically matched healthy control women participated in this study. Most of the patients developed PTSD after experiencing interpersonal violence. Cognitive functions were assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Regular exercise habit was assessed by a self-reported questionnaire. Compared to controls, PTSD patients performed significantly more poorly in all cognitive domains examined, including immediate memory, visuospatial construction, language, attention, delayed memory, as well as the total score of RBANS (all p < 0.001). Compared to PTSD patients without the habit of exercise, those who habitually exercised showed significantly better performance on delayed memory (p = 0.006), which survived after controlling for potentially confounding variables in a multiple regression model. The cross-sectional design and relatively small sample size limited our findings. PTSD in Japanese women is associated with pervasively impaired cognitive functions, including notable impairments in verbal memory. Such memory deficits might be improved by regular exercise, although further studies are needed to investigate the causal relationship between exercise and cognition in PTSD. Copyright © 2018 Elsevier B.V. All rights reserved.

"Everyday Memory" Impairments in Autism Spectrum Disorders

ERIC Educational Resources Information Center

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

2011-01-01

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

Opposite Effects of Cortisol on Consolidation of Temporal Sequence Memory during Waking and Sleep

ERIC Educational Resources Information Center

Wilhelm, Ines; Wagner, Ullrich; Born, Jan

2011-01-01

Memory functions involve three stages: encoding, consolidation, and retrieval. Modulating effects of glucocorticoids (GCs) have been consistently observed for declarative memory with GCs enhancing encoding and impairing retrieval, but surprisingly, little is known on how GCs affect memory consolidation. Studies in rats suggest a beneficial effect…

Increased functional connectivity in the default mode network in mild cognitive impairment: a maladaptive compensatory mechanism associated with poor semantic memory performance.

PubMed

Gardini, Simona; Venneri, Annalena; Sambataro, Fabio; Cuetos, Fernando; Fasano, Fabrizio; Marchi, Massimo; Crisi, Girolamo; Caffarra, Paolo

2015-01-01

Semantic memory decline and changes of default mode network (DMN) connectivity have been reported in mild cognitive impairment (MCI). Only a few studies, however, have investigated the role of changes of activity in the DMN on semantic memory in this clinical condition. The present study aimed to investigate more extensively the relationship between semantic memory impairment and DMN intrinsic connectivity in MCI. Twenty-one MCI patients and 21 healthy elderly controls matched for demographic variables took part in this study. All participants underwent a comprehensive semantic battery including tasks of category fluency, visual naming and naming from definition for objects, actions and famous people, word-association for early and late acquired words and reading. A subgroup of the original sample (16 MCI patients and 20 healthy elderly controls) was also scanned with resting state functional magnetic resonance imaging and DMN connectivity was estimated using a seed-based approach. Compared with healthy elderly, patients showed an extensive semantic memory decline in category fluency, visual naming, naming from definition, words-association, and reading tasks. Patients presented increased DMN connectivity between the medial prefrontal regions and the posterior cingulate and between the posterior cingulate and the parahippocampus and anterior hippocampus. MCI patients also showed a significant negative correlation of medial prefrontal gyrus connectivity with parahippocampus and posterior hippocampus and visual naming performance. Our findings suggest that increasing DMN connectivity may contribute to semantic memory deficits in MCI, specifically in visual naming. Increased DMN connectivity with posterior cingulate and medio-temporal regions seems to represent a maladaptive reorganization of brain functions in MCI, which detrimentally contributes to cognitive impairment in this clinical population.

Task- and Treatment Length–Dependent Effects of Vortioxetine on Scopolamine-Induced Cognitive Dysfunction and Hippocampal Extracellular Acetylcholine in Rats

PubMed Central

Pehrson, Alan L.; Hillhouse, Todd M.; Haddjeri, Nasser; Rovera, Renaud; Porter, Joseph H.; Mørk, Arne; Smagin, Gennady; Song, Dekun; Budac, David; Cajina, Manuel

2016-01-01

Major depressive disorder (MDD) is a common psychiatric disorder that often features impairments in cognitive function, and these cognitive symptoms can be important determinants of functional ability. Vortioxetine is a multimodal antidepressant that may improve some aspects of cognitive function in patients with MDD, including attention, processing speed, executive function, and memory. However, the cause of these effects is unclear, and there are several competing theories on the underlying mechanism, notably including regionally-selective downstream enhancement of glutamate neurotransmission and increased acetylcholine (ACh) neurotransmission. The current work sought to evaluate the ACh hypothesis by examining vortioxetine’s ability to reverse scopolamine-induced impairments in rodent tests of memory and attention. Additionally, vortioxetine’s effects on hippocampal extracellular ACh levels were examined alongside studies of vortioxetine’s pharmacokinetic profile. We found that acute vortioxetine reversed scopolamine-induced impairments in social and object recognition memory, but did not alter scopolamine-induced impairments in attention. Acute vortioxetine also induced a modest and short-lived increase in hippocampal ACh levels. However, this short-term effect is at variance with vortioxetine’s moderately long brain half life (5.1 hours). Interestingly, subchronic vortioxetine treatment failed to reverse scopolamine-induced social recognition memory deficits and had no effects on basal hippocampal ACh levels. These data suggest that vortioxetine has some effects on memory that could be mediated through cholinergic neurotransmission, however these effects are modest and only seen under acute dosing conditions. These limitations may argue against cholinergic mechanisms being the primary mediator of vortioxetine′s cognitive effects, which are observed under chronic dosing conditions in patients with MDD. PMID:27402279

Verbal learning on depressive pseudodementia: accentuate impairment of free recall, moderate on learning processes, and spared short-term and recognition memory.

PubMed

Paula, Jonas Jardim de; Miranda, Débora Marques; Nicolato, Rodrigo; Moraes, Edgar Nunes de; Bicalho, Maria Aparecida Camargos; Malloy-Diniz, Leandro Fernandes

2013-09-01

Depressive pseudodementia (DPD) is a clinical condition characterized by depressive symptoms followed by cognitive and functional impairment characteristics of dementia. Memory complaints are one of the most related cognitive symptoms in DPD. The present study aims to assess the verbal learning profile of elderly patients with DPD. Ninety-six older adults (34 DPD and 62 controls) were assessed by neuropsychological tests including the Rey auditory-verbal learning test (RAVLT). A multivariate general linear model was used to assess group differences and controlled for demographic factors. Moderate or large effects were found on all RAVLT components, except for short-term and recognition memory. DPD impairs verbal memory, with large effect size on free recall and moderate effect size on the learning. Short-term storage and recognition memory are useful in clinical contexts when the differential diagnosis is required.

Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

PubMed

Uddin, Raihan; Singh, Shiva M

2017-01-01

As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they provide a new insight and generate new hypotheses into the molecular mechanisms responsible for age associated learning impairment, including spatial learning.

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

PubMed

Aicardi, Giorgio

2012-10-01

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

The effect of stress induction on working memory in patients with psychogenic nonepileptic seizures.

PubMed

Bakvis, Patricia; Spinhoven, Philip; Putman, Peter; Zitman, Frans G; Roelofs, Karin

2010-11-01

Although psychogenic nonepileptic seizures (PNES) are considered a stress-induced paroxysmal disintegration of cognitive functions, it remains unknown whether stress indeed impairs cognitive integrative functions, such as working memory (WM), in patients with PNES. An N-back task with emotional distracters (angry, happy, and neutral faces) was administered at baseline and after stress induction (Cold Pressor Test) to 19 patients with PNES and 20 matched healthy controls. At baseline, patients displayed increased WM interference for the facial distracters. After stress induction, group differences generalized to the no-distracter condition. Within patients, high cortisol stress responses were associated with larger stress-induced WM impairments in the no-distracter condition. These findings demonstrate that patients' cognitive integrative functions are impaired by social distracters and stress induction. Moreover, the stress- and cortisol-related generalization of the relative WM impairments offers a promising experimental model for the characteristic paroxysmal disintegration of attentional and mnemonic functions in patients with PNES associated with stress. Copyright © 2010 Elsevier Inc. All rights reserved.

The impact of cognitive impairment, neurological soft signs and subdepressive symptoms on functional outcome in bipolar disorder.

PubMed

Baş, Tuba Öcek; Poyraz, Cana Aksoy; Baş, Alper; Poyraz, Burç Çağrı; Tosun, Musa

2015-03-15

Cognitive impairments and subsyndromal depressive symptoms are present during euthymic periods of bipolar disorder (BD). Most studies have determined that cognitive impairments and residual depressive symptoms have major impacts on psychosocial functioning. The aim of the present study was to identify the major factor responsible for low psychosocial functioning in a subgroup of patients with BD despite clinical recovery. Sixty patients with bipolar I disorder and 41 healthy subjects were enrolled in this study. Cognitive performance, neurological soft signs (NSSs), psychosocial functioning, residual mood symptoms and illness characteristics were assessed. Using the median value of the Functioning Assessment Short Test (FAST) as the cut-off point, the patients were divided into two groups, high- (n=29) or low-functioning (n=31), and they were compared based on total NSS, residual depressive symptoms, cognitive performance and clinical variables. Performances on the verbal memory tests and social functioning were significantly worse in the euthymic patients with BD. Increased rates of NSS were identified in the patients compared with the normal controls. The low-functioning patients performed significantly worse on verbal memory, and their NSS and residual depressive symptoms were significantly higher compared to high-functioning patients. In the regression analysis, subsyndromal depressive symptoms and verbal learning measures were identified as the best predictors of psychosocial functioning. The patients were artificially separated into two groups based on a FAST score cut-off. In this study, residual depressive symptoms and verbal memory impairments were the most prominent factors associated with the level of functioning. Copyright © 2014 Elsevier B.V. All rights reserved.

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.

Pheromone-Induced Olfactory Memory in Newborn Rabbits: Involvement of Consolidation and Reconsolidation Processes

ERIC Educational Resources Information Center

Coureaud, Gerard; Languille, Solene; Schaal, Benoist; Hars, Bernard

2009-01-01

Mammary pheromone (MP)-induced odor memory is a new model of appetitive memory functioning early in a mammal, the newborn rabbit. Some properties of this associative memory are analyzed by the use of anisomycin as an amnesic agent. Long-term memory (LTM) was impaired by anisomycin delivered immediately, but not 4 h after either acquisition or…

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

Conditional forebrain inactivation of nicastrin causes progressive memory impairment and age-related neurodegeneration.

PubMed

Tabuchi, Katsuhiko; Chen, Guiquan; Südhof, Thomas C; Shen, Jie

2009-06-03

Loss of presenilin function in adult mouse brains causes memory loss and age-related neurodegeneration. Since presenilin possesses gamma-secretase-dependent and -independent activities, it remains unknown which activity is required for presenilin-dependent memory formation and neuronal survival. To address this question, we generated postnatal forebrain-specific nicastrin conditional knock-out (cKO) mice, in which nicastrin, a subunit of gamma-secretase, is inactivated selectively in mature excitatory neurons of the cerebral cortex. nicastrin cKO mice display progressive impairment in learning and memory and exhibit age-dependent cortical neuronal loss, accompanied by astrocytosis, microgliosis, and hyperphosphorylation of the microtubule-associated protein Tau. The neurodegeneration observed in nicastrin cKO mice likely occurs via apoptosis, as evidenced by increased numbers of apoptotic neurons. These findings demonstrate an essential role of nicastrin in the execution of learning and memory and the maintenance of neuronal survival in the brain and suggest that presenilin functions in memory and neuronal survival via its role as a gamma-secretase subunit.

Cognitive rehabilitation for memory deficits following stroke.

PubMed

Majid, M J; Lincoln, N B; Weyman, N

2000-01-01

Memory problems occur following stroke. Cognitive rehabilitation programmes are provided to retrain memory function or to teach patients strategies to cope despite memory impairment. To determine the effects of cognitive rehabilitation for memory problems following stroke. We searched the Cochrane Stroke Group Trials Register, Medline, EMBASE, CINHAL and CLIN PSYCH databases and reference lists from relevant articles. Date of most recent searches: December 1998. Controlled trials of memory retraining in stroke. Studies with mixed aetiology groups were excluded unless they had more than 75% of stroke patients or separate data were available for the stroke patients. Two reviewers extracted trial data and assessed trial quality. Reviewers contacted investigators for further details of trials. One trial was identified with 12 participants. This showed memory strategy training had no significant effect on memory impairment or subjective memory complaints. There is insufficient evidence to support or refute the effectiveness of cognitive rehabilitation for memory problems after stroke.

The basolateral amygdala dopaminergic system contributes to the improving effect of nicotine on stress-induced memory impairment in rats.

PubMed

Keshavarzian, Elnaz; Ghasemzadeh, Zahra; Rezayof, Ameneh

2018-05-18

Stress seems to be an important risk factor in the beginning and continuing stages of cigarette tobacco smoking in humans. Considering that both of nicotine administration and stress exposure affect cognitive functions including memory formation, the aim of the present study was 1) to evaluate the effect of subcutaneous (s.c.) administration of nicotine on memory formation under stress and 2) to assess the possible role of the basolateral amygdala (BLA) dopamine D1 and D2 receptors in the effect of nicotine on stress-induced memory retrieval impairment. Adult male wistar rats were bilaterally implanted in the BLA. A step-through type passive avoidance task was used to measure memory retrieval. To induce acute stress, the animals were placed on an elevated platform. The results showed that pre-test exposure to 20 and 30 min stress, but not 10 min, impaired memory retrieval. Nicotine administration (0.05 mg/kg, s.c.) improved stress-induced memory retrieval impairment. The activation of the BLA dopamine receptors via bilateral microinjection of apomorphine (0.025-0.4 μg/rat), a non-selective dopamine receptor agonist, potentiated the effect of nicotine on stress-induced memory retrieval impairment. Interestingly, intra-BLA microinjection of SCH23390 (a selective dopamine D1 receptor antagonist; 0.02-0.5 μg/rat) or sulpiride (a selective dopamine D2 receptor antagonist; 0.02-0.5 μg/rat) dose-dependently inhibited nicotine-induced improvement of the stress amnesic effect. Taken together, it can be concluded that stress-induced impairment of memory retrieval can be improved by nicotine administration. Moreover, the dopaminergic neurotransmission in the BLA through D1 and D2 receptors mediates the improving effect of nicotine on stress-induced memory retrieval impairment. Copyright © 2018 Elsevier Inc. All rights reserved.

Transcranial near-infrared photobiomodulation attenuates memory impairment and hippocampal oxidative stress in sleep-deprived mice.

PubMed

Salehpour, Farzad; Farajdokht, Fereshteh; Erfani, Marjan; Sadigh-Eteghad, Saeed; Shotorbani, Siamak Sandoghchian; Hamblin, Michael R; Karimi, Pouran; Rasta, Seyed Hossein; Mahmoudi, Javad

2018-03-01

Sleep deprivation (SD) causes oxidative stress in the hippocampus and subsequent memory impairment. In this study, the effect of near-infrared (NIR) photobiomodulation (PBM) on learning and memory impairment induced by acute SD was investigated. The mice were subjected to an acute SD protocol for 72 h. Simultaneously, NIR PBM using a laser at 810 nm was delivered (once a day for 3 days) transcranially to the head to affect the entire brain of mice. The Barnes maze and the What-Where-Which task were used to assess spatial and episodic-like memories. The hippocampal levels of antioxidant enzymes and oxidative stress biomarkers were evaluated. The results showed that NIR PBM prevented cognitive impairment induced by SD. Moreover, NIR PBM therapy enhanced the antioxidant status and increased mitochondrial activity in the hippocampus of SD mice. Our findings revealed that hippocampus-related mitochondrial damage and extensive oxidative stress contribute to the occurrence of memory impairment. In contrast, NIR PBM reduced hippocampal oxidative damage, supporting the ability of 810 nm laser light to improve the antioxidant defense system and maintain mitochondrial survival. This confirms that non-invasive transcranial NIR PBM therapy ameliorates hippocampal dysfunction, which is reflected in enhanced memory function. Copyright © 2018 Elsevier B.V. All rights reserved.

Working memory and executive functions in transient global amnesia.

PubMed

Quinette, Peggy; Guillery, Bérengère; Desgranges, Béatrice; de la Sayette, Vincent; Viader, Fausto; Eustache, Francis

2003-09-01

Transient global amnesia (TGA) is usually considered to produce a profound impairment of long-term episodic memory, while at the same time sparing working memory. However, this neuropsychological dissociation has rarely been examined in detail. While a few studies have assessed some components of working memory in TGA, the results that have been obtained are far from conclusive. To clarify this issue, we carried out a comprehensive investigation of working memory in 10 patients during a TGA attack. In the first study, we report the results from three patients examined with a battery of neuropsychological tests designed to assess each of the three subcomponents of Baddeley's model of working memory. In a second study, seven different patients underwent neuropsychological investigations that focused specifically on the central executive system, using a protocol derived from a study by Miyake and colleagues. Our findings showed that subcomponents of working memory, such as the phonological loop and visuo-spatial sketch pad, were spared in TGA patients. Specific executive functions that entailed inhibitory control, dual task performance, updating and shifting mechanisms were also found to be normal. However, we found significantly impaired performance for the Brown-Peterson test, and that TGA patients were significantly impaired in the recollection of their episodic memories. They also made reduced numbers of 'remember' compared with 'know' judgments in the episodic memory test several days after TGA. On the basis of our findings, it would appear that the episodic memory deficit during TGA is not related to elementary aspects of executive functioning. Our data also highlight the nature of the cognitive mechanisms involved in the Brown-Peterson task, which may well depend on long-term memory (such as the process of semantic encoding). Lastly, the selective deficit in recollective episodic memories observed in TGA may be principally related to medial temporal lobe abnormalities that have been reported in this syndrome.

PERK Regulates Working Memory and Protein Synthesis-Dependent Memory Flexibility

PubMed Central

Zhu, Siying; Henninger, Keely; McGrath, Barbara C.; Cavener, Douglas R.

2016-01-01

PERK (EIF2AK3) is an ER-resident eIF2α kinase required for memory flexibility and metabotropic glutamate receptor-dependent long-term depression, processes known to be dependent on new protein synthesis. Here we investigated PERK’s role in working memory, a cognitive ability that is independent of new protein synthesis, but instead is dependent on cellular Ca2+ dynamics. We found that working memory is impaired in forebrain-specific Perk knockout and pharmacologically PERK-inhibited mice. Moreover, inhibition of PERK in wild-type mice mimics the fear extinction impairment observed in forebrain-specific Perk knockout mice. Our findings reveal a novel role of PERK in cognitive functions and suggest that PERK regulates both Ca2+ -dependent working memory and protein synthesis-dependent memory flexibility. PMID:27627766

Accelerated long-term forgetting in temporal lobe epilepsy: evidence of improvement after left temporal pole lobectomy.

PubMed

Gallassi, Roberto; Sambati, Luisa; Poda, Roberto; Stanzani Maserati, Michelangelo; Oppi, Federico; Giulioni, Marco; Tinuper, Paolo

2011-12-01

Accelerated long term forgetting (ALF) is a characteristic cognitive aspect in patients affected by temporal lobe epilepsy that is probably due to an impairment of memory consolidation and retrieval caused by epileptic activity in hippocampal and parahippocampal regions. We describe a case of a patient with TLE who showed improvement in ALF and in remote memory impairment after an anterior left temporal pole lobectomy including the uncus and amygdala. Our findings confirm that impairment of hippocampal functioning leads to pathological ALF, whereas restoration of hippocampal functioning brings ALF to a level comparable to that of controls. Copyright © 2011 Elsevier Inc. All rights reserved.

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

PubMed

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

2016-09-15

The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats. The animals were bilaterally implanted with the cannulas in the BLA and submitted to a step-through type passive avoidance task to measure the memory formation. The results showed that intraperitoneal (i.p.) administration of different doses of scopolamine (0.5-1.5mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA; 1-4ng/rat), into the BLA significantly improved scopolamine-induced memory consolidation impairment. On the other hand, co-administration of AM251, a cannabinoid CB1 receptor antagonist (0.25-1ng/rat, intra-BLA), with an ineffective dose of scopolamine (0.5mg/kg, i.p.), significantly impaired memory consolidation and mimicked the response of a higher dose of scopolamine. It is important to note that post-training intra-BLA microinjections of the same doses of ACPA or AM251 alone had no effect on memory consolidation. Moreover, the blockade of the BLA CB1 receptors by 0.3ng/rat of AM251 prevented ACPA-induced improvement of the scopolamine response. In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment. Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation. Copyright © 2016. Published by Elsevier B.V.

Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

PubMed

Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

2009-12-01

The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (P<0.05) more errors than untreated control group in trials 6 through 9 of day 4. In memory tests, chronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

The roles of Eph receptors in contextual fear conditioning memory formation.

PubMed

Dines, Monica; Grinberg, Svetlana; Vassiliev, Maria; Ram, Alon; Tamir, Tal; Lamprecht, Raphael

2015-10-01

Eph receptors regulate glutamate receptors functions, neuronal morphology and synaptic plasticity, cellular events believed to be involved in memory formation. In this study we aim to explore the roles of Eph receptors in learning and memory. Toward that end, we examined the roles of EphB2 and EphA4 receptors, key regulators of synaptic functions, in fear conditioning memory formation. We show that mice lacking EphB2 (EphB2(-/-)) are impaired in short- and long-term contextual fear conditioning memory. Mice that express a carboxy-terminally truncated form of EphB2 that lacks forward signaling, instead of the full EphB2, are impaired in long-term, but not short-term, contextual fear conditioning memory. Long-term contextual fear conditioning memory is attenuated in CaMKII-cre;EphA4(lx/-) mice where EphA4 is removed from all pyramidal neurons of the forebrain. Mutant mice with targeted kinase-dead EphA4 (EphA4(KD)) exhibit intact long-term contextual fear conditioning memory showing that EphA4 kinase-mediated forward signaling is not needed for contextual fear memory formation. The ability to form long-term conditioned taste aversion (CTA) memory is not impaired in the EphB2(-/-) and CaMKII-cre;EphA4(lx/-) mice. We conclude that EphB2 forward signaling is required for long-term contextual fear conditioning memory formation. In contrast, EphB2 mediates short-term contextual fear conditioning memory formation in a forward signaling-independent manner. EphA4 mediates long-term contextual fear conditioning memory formation in a kinase-independent manner. Copyright © 2015 Elsevier Inc. All rights reserved.

'Tagging' along memories in aging: Synaptic tagging and capture mechanisms in the aged hippocampus.

PubMed

Shivarama Shetty, Mahesh; Sajikumar, Sreedharan

2017-05-01

Aging is accompanied by a general decline in the physiological functions of the body with the deteriorating organ systems. Brain is no exception to this and deficits in cognitive functions are quite common in advanced aging. Though a variety of age-related alterations are observed in the structure and function throughout the brain, certain regions show selective vulnerability. Medial temporal lobe, especially the hippocampus, is one such preferentially vulnerable region and is a crucial structure involved in the learning and long-term memory functions. Hippocampal synaptic plasticity, such as long-term potentiation (LTP) and depression (LTD), are candidate cellular correlates of learning and memory and alterations in these properties have been well documented in aging. A related phenomenon called synaptic tagging and capture (STC) has been proposed as a mechanism for cellular memory consolidation and to account for temporal association of memories. Mounting evidences from behavioral settings suggest that STC could be a physiological phenomenon. In this article, we review the recent data concerning STC and provide a framework for how alterations in STC-related mechanisms could contribute to the age-associated memory impairments. The enormity of impairment in learning and memory functions demands an understanding of age-associated memory deficits at the fundamental level given its impact in the everyday tasks, thereby in the quality of life. Such an understanding is also crucial for designing interventions and preventive measures for successful brain aging. Copyright © 2017 National University of Singapore. Published by Elsevier B.V. All rights reserved.

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.

Objectively Measured Physical Activity and Cognitive Function in Older Adults.

PubMed

Zhu, Wenfei; Wadley, Virginia G; Howard, Virginia J; Hutto, Brent; Blair, Steven N; Hooker, Steven P

2017-01-01

Emerging evidence suggests physical activity (PA) is associated with cognitive function. To overcome limitations of self-report PA measures, this study investigated the association of accelerometer-measured PA with incident cognitive impairment and longitudinal cognition among older adults. Participants were recruited from the cohort study Reasons for Geographic and Racial Differences in Stroke in the United States. Accelerometers provided PA measures, including the percentage of total accelerometer wearing time spent in moderate-to-vigorous-intensity PA (MVPA%), light-intensity PA, and sedentary time for four to seven consecutive days at baseline. Cognitive impairment was defined by the Six-Item Screener. Letter fluency, animal fluency, word list learning, and Montreal Cognitive Assessment (orientation and recall) were conducted to assess executive function and memory. Participants (N = 6452, 69.7 ± 8.5 yr, 55.3% women, 30.5% Black) with usable accelerometer and cognition measures spent extremely limited time in MVPA (1.5% ± 1.9% of accelerometer wearing time). During an average of 3 yr of follow-up, 346 cases of incident cognitive impairment were observed. After adjustments, participants in higher MVPA% quartiles had a lower risk of cognitive impairment (i.e., quartile 2: odds ratio = 0.64, 95% confidence interval = 0.48-0.84) and better maintenance in executive function (≥0.03 z-score units) and memory (≥0.12 z-score units) compared with quartile 1 (P < 0.05). Stratified analyses showed the same association among White adults, but higher MVPA% was associated with better maintenance of only memory among Black adults. No significance was found for light-intensity PA or sedentary time. There was a dose-response relationship between MVPA% and cognitive function in older adults, with higher levels associated with a 36% or lower risk of cognitive impairment and better maintenance of memory and executive function over time, particularly in White adults.

Heterogeneity in ADHD: Neurocognitive predictors of peer, family, and academic functioning.

PubMed

Kofler, Michael J; Sarver, Dustin E; Spiegel, Jamie A; Day, Taylor N; Harmon, Sherelle L; Wells, Erica L

2017-08-01

Childhood attention-deficit/hyperactivity disorder (ADHD) is associated with impairments in peer, family, and academic functioning. Although impairment is required for diagnosis, children with ADHD vary significantly in the areas in which they demonstrate clinically significant impairment. However, relatively little is known about the mechanisms and processes underlying these individual differences. The current study examined neurocognitive predictors of heterogeneity in peer, family, and academic functioning in a well-defined sample of 44 children with ADHD aged 8-13 years (M = 10.31, SD = 1.42; 31 boys, 13 girls; 81% Caucasian). Reliable change analysis indicated that 98% of the sample demonstrated objectively-defined impairment on at least one assessed outcome measure; 65% were impaired in two or all three areas of functioning. ADHD children with quantifiable deficits in academic success and family functioning performed worse on tests of working memory (d = 0.68 to 1.09), whereas children with impaired parent-reported social functioning demonstrated slower processing speed (d = 0.53). Dimensional analyses identified additional predictors of peer, family, and academic functioning. Working memory abilities were associated with individual differences in all three functional domains, processing speed predicted social functioning, and inhibitory control predicted family functioning. These results add to a growing literature implicating neurocognitive abilities not only in explaining behavioral differences between ADHD and non-ADHD groups, but also in the substantial heterogeneity in ecologically-valid functional outcomes associated with the disorder.

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.

Medial Prefrontal Lesions in Mice Impair Sustained Attention but Spare Maintenance of Information in Working Memory

ERIC Educational Resources Information Center

Kahn, Julia B.; Ward, Ryan D.; Kahn, Lora W.; Rudy, Nicole M.; Kandel, Eric R.; Balsam, Peter D.; Simpson, Eleanor H.

2012-01-01

Working memory and attention are complex cognitive functions that are disrupted in several neuropsychiatric disorders. Mouse models of such human diseases are commonly subjected to maze-based tests that can neither distinguish between these cognitive functions nor isolate specific aspects of either function. Here, we have adapted a simple visual…

Misremembering Future Intentions in Methamphetamine Dependent Individuals

PubMed Central

Iudicello, Jennifer E.; Weber, Erica; Grant, Igor; Weinborn, Michael; Woods, Steven Paul

2012-01-01

Methamphetamine (MA) dependence is associated with neural abnormalities (e.g., frontal systems neurotoxicity) and corresponding cognitive deficits, including impairment in episodic memory and executive functions. This study evaluated the hypothesis that MA use is associated with impairment in memory for intentions, or prospective memory (ProM), which is an ecologically relevant aspect of episodic memory that involves the execution of a previously encoded intention at an appropriate moment in the future and is known to rely on frontal systems integrity. Thirty-nine MA-dependent individuals and 26 demographically similar non-MA-using comparison subjects were administered the Memory for Intentions Screening Test (MIST). The MA group performed significantly lower than the comparison participants on overall ProM, an effect that could not be better explained by demographics, psychiatric factors, infectious disease comorbidity, or other substance use disorders. The ProM impairment observed in the MA group was comparable on time- and event-based tasks and was marked by an increased rate of task substitution (i.e., intrusions) and loss of time (e.g., early responding) errors. Within the MA cohort, ProM impairment was associated with executive dysfunction and earlier age at first MA use. Findings suggest that individuals with MA dependence experience difficulty in the strategic components involved in the retrieval of future intentions and are discussed with regard to their implications for everyday functioning. PMID:21331980

Everyday memory impairment in patients with temporal lobe epilepsy caused by hippocampal sclerosis.

PubMed

Rzezak, Patrícia; Lima, Ellen Marise; Gargaro, Ana Carolina; Coimbra, Erica; de Vincentiis, Silvia; Velasco, Tonicarlo Rodrigues; Leite, João Pereira; Busatto, Geraldo F; Valente, Kette D

2017-04-01

Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints. Copyright © 2017 Elsevier Inc. All rights reserved.

Targeting Treatments to Improve Cognitive Function in Mood Disorder: Suggestions From Trials Using Erythropoietin.

PubMed

Miskowiak, Kamilla Woznica; Rush, A John; Gerds, Thomas A; Vinberg, Maj; Kessing, Lars V

2016-12-01

There is no established efficacious treatment for cognitive dysfunction in unipolar and bipolar disorder. This may be partially due to lack of consensus regarding the need to screen for cognitive impairment in cognition trials or which screening criteria to use. We have demonstrated in 2 randomized placebo-controlled trials that 8 weeks of erythropoietin (EPO) treatment has beneficial effects on verbal memory across unipolar and bipolar disorder, with 58% of EPO-treated patients displaying a clinically relevant memory improvement as compared to 15% of those treated with placebo. We reassessed the data from our 2 EPO trials conducted between September 2009 and October 2012 to determine whether objective performance-based memory impairment or subjective self-rated cognitive impairment at baseline was related to the effect of EPO on cognitive function as assessed by Rey Auditory Verbal Learning Test (RAVLT) total recall with multiple logistic regression adjusted for diagnosis, age, gender, symptom severity, and education levels. We included 79 patients with an ICD-10 diagnosis of unipolar or bipolar disorder, of whom 39 received EPO and 40 received placebo (saline). For EPO-treated patients with objective memory dysfunction at baseline (n = 16) (defined as RAVLT total recall ≤ 43), the odds of a clinically relevant memory improvement were increased by a factor of 290.6 (95% CI, 2.7-31,316.4; P = .02) compared to patients with no baseline impairment (n = 23). Subjective cognitive complaints (measured with the Cognitive and Physical Functioning Questionnaire) and longer illness duration were associated with small increases in patients' chances of treatment efficacy on memory (53% and 16% increase, respectively; P ≤ .04). Diagnosis, gender, age, baseline depression severity, and number of mood episodes did not significantly change the chances of EPO treatment success (P ≥ .06). In the placebo-treated group, the odds of memory improvement were not significantly different for patients with or without objectively defined memory dysfunction (P ≥ .59) or subjective complaints at baseline (P ≥ .06). Baseline objectively assessed memory impairments and-to a lesser degree-subjective cognitive complaints increased the chances of treatment efficacy on cognition in unipolar and bipolar disorder. ClinicalTrials.gov identifier: NCT00916552. © Copyright 2016 Physicians Postgraduate Press, Inc.

Sarcosine attenuates toluene-induced motor incoordination, memory impairment, and hypothermia but not brain stimulation reward enhancement in mice

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

Chan, Ming-Huan; Institute of Neuroscience, National Changchi University, Taipei, Taiwan; Chung, Shiang-Sheng

Toluene, a widely used and commonly abused organic solvent, produces various behavioral disturbances, including motor incoordination and cognitive impairment. Toluene alters the function of a large number of receptors and ion channels. Blockade of N-methyl-D-aspartate (NMDA) receptors has been suggested to play a critical role in toluene-induced behavioral manifestations. The present study determined the effects of various toluene doses on motor coordination, recognition memory, body temperature, and intracranial self-stimulation (ICSS) thresholds in mice. Additionally, the effects of sarcosine on the behavioral and physiological effects induced by toluene were evaluated. Sarcosine may reverse toluene-induced behavioral manifestations by acting as an NMDAmore » receptor co-agonist and by inhibiting the effects of the type I glycine transporter (GlyT1). Mice were treated with toluene alone or combined with sarcosine pretreatment and assessed for rotarod performance, object recognition memory, rectal temperature, and ICSS thresholds. Toluene dose-dependently induced motor incoordination, recognition memory impairment, and hypothermia and lowered ICSS thresholds. Sarcosine pretreatment reversed toluene-induced changes in rotarod performance, novel object recognition, and rectal temperature but not ICSS thresholds. These findings suggest that the sarcosine-induced potentiation of NMDA receptors may reverse motor incoordination, memory impairment, and hypothermia but not the enhancement of brain stimulation reward function associated with toluene exposure. Sarcosine may be a promising compound to prevent acute toluene intoxications by occupational or intentional exposure. -- Highlights: ► Toluene induces impairments in Rotarod test and novel object recognition test. ► Toluene lowers rectal temperature and ICSS thresholds in mice. ► Sarcosine reverses toluene-induced changes in motor, memory and body temperature. ► Sarcosine pretreatment does not affect toluene-induced reward enhancement.« less

Effect of episodic and working memory impairments on semantic and cognitive procedural learning at alcohol treatment entry.

PubMed

Pitel, Anne Lise; Witkowski, Thomas; Vabret, François; Guillery-Girard, Bérengère; Desgranges, Béatrice; Eustache, Francis; Beaunieux, Hélène

2007-02-01

Chronic alcoholism is known to impair the functioning of episodic and working memory, which may consequently reduce the ability to learn complex novel information. Nevertheless, semantic and cognitive procedural learning have not been properly explored at alcohol treatment entry, despite its potential clinical relevance. The goal of the present study was therefore to determine whether alcoholic patients, immediately after the weaning phase, are cognitively able to acquire complex new knowledge, given their episodic and working memory deficits. Twenty alcoholic inpatients with episodic memory and working memory deficits at alcohol treatment entry and a control group of 20 healthy subjects underwent a protocol of semantic acquisition and cognitive procedural learning. The semantic learning task consisted of the acquisition of 10 novel concepts, while subjects were administered the Tower of Toronto task to measure cognitive procedural learning. Analyses showed that although alcoholic subjects were able to acquire the category and features of the semantic concepts, albeit slowly, they presented impaired label learning. In the control group, executive functions and episodic memory predicted semantic learning in the first and second halves of the protocol, respectively. In addition to the cognitive processes involved in the learning strategies invoked by controls, alcoholic subjects seem to attempt to compensate for their impaired cognitive functions, invoking capacities of short-term passive storage. Regarding cognitive procedural learning, although the patients eventually achieved the same results as the controls, they failed to automate the procedure. Contrary to the control group, the alcoholic groups' learning performance was predicted by controlled cognitive functions throughout the protocol. At alcohol treatment entry, alcoholic patients with neuropsychological deficits have difficulty acquiring novel semantic and cognitive procedural knowledge. Compared with controls, they seem to use more costly learning strategies, which are nonetheless less efficient. These learning disabilities need to be considered when treatment requiring the acquisition of complex novel information is envisaged.

Acute Effects of Ecstasy on Memory Are more Extensive than Chronic Effects

PubMed Central

Shariati, Mohamad Bakhtiar Hesam; Sohrabi, Maryam; Shahidi, Siamak; Nikkhah, Ali; Mirzaei, Fatemeh; Medizadeh, Mehdi; Asl, Sara Soleimani

2014-01-01

Introduction Exposure to 3, 4- methylenedioxymethamphetamine (MDMA) could lead to serotonergic system toxicity in the brain. This system is responsible for learning and memory functions. Studies show that MDMA causes memory impairment dose-dependently and acutely. The present study was designed to evaluate the chronic and acute effects of MDMD on spatial memory and acquisition of passive avoidance. Methods Adult male Wistar rats (200-250 g) were given single or multiple injections of MDMA (10 mg/kg, IP). Using passive avoidance and Morris Water Maze (MWM) tasks, learning and spatial memory functions were assessed. The data were analyzed by SPSS 16 software and one- way analysis of variance (ANOVA) test. Results Our results showed that there were significant differences in latency to enter the dark compartment (STL) between sham and MDMA- treated groups. Acute group significantly showed more STL in comparison with chronic group. Furthermore, MDMA groups spent more time in dark compartment (TDS) than the sham group. Administration of single dose of MDMA significantly caused an increase in TDS compared with the chronic group. In the MWM, MDMA treatment significantly increased the traveled distance and escaped latency compared to the sham group. Like to passive avoidance task, percentage of time spent in the target quadrant in MDMA- treated animals impaired in MWM compared with sham group. Discussion These data suggest that MDMA treatment impairs learning and memory functions that are more extensive in acute- treated rats. PMID:25337384

Frontoparietal cognitive control of verbal memory recall in Alzheimer's disease.

PubMed

Dhanjal, Novraj S; Wise, Richard J S

2014-08-01

Episodic memory retrieval is reliant upon cognitive control systems, of which 2 have been identified with functional neuroimaging: a cingulo-opercular salience network (SN) and a frontoparietal executive network (EN). In Alzheimer's disease (AD), pathology is distributed throughout higher-order cortices. The hypotheses were that this frontoparietal pathology would impair activity associated with verbal memory recall; and that central cholinesterase inhibition (ChI) would modulate this, improving memory recall. Functional magnetic resonance imaging was used to study normal participants and 2 patient groups: mild cognitive impairment (MCI) and AD. Activity within the EN and SN was observed during free recall of previously heard sentences, and related to measures of recall accuracy. In normal subjects, trials with reduced recall were associated with greater activity in both the SN and EN. Better recall was associated with greater activity in medial regions of the default mode network. By comparison, AD patients showed attenuated responses in both the SN and EN compared with either controls or MCI patients, even after recall performance was matched between groups. Following ChI, AD patients showed no modulation of activity within the SN, but increased activity within the EN. There was also enhanced activity within regions associated with episodic and semantic memory during less successful recall, requiring greater cognitive control. The results indicate that in AD, impaired responses of cognitive control networks during verbal memory recall are partly responsible for reduced recall performance. One action of symptom-modifying treatment is partially to reverse the abnormal function of frontoparietal cognitive control and temporal lobe memory networks. © 2014 American Neurological Association.

Lowered performance in working memory and attentional sub-processes are most prominent in multi-domain amnestic mild cognitive impairment subtypes.

PubMed

Klekociuk, Shannon Z; Summers, Mathew J

2014-03-01

Research suggests that working memory and attention deficits may be present in mild cognitive impairment (MCI). However, the functional status of these domains within revised MCI subtypes remains unclear, particularly because previous studies have examined these cognitive domains with the same tests that were used to classify MCI subtypes. The aim of this study was to examine working memory and attention function in MCI subtypes on a battery of neuropsychological tests that were distinct from those used to classify MCI subtypes A total of 122 adults aged 60-90 years were classified at baseline as amnestic MCI, non-amnestic MCI, and multi-domain amnestic (a-MCI+). The attentional and working memory capacity of participants was examined using a battery of tests distinct from those used to classify MCI at screening. The a-MCI+ group demonstrated the poorest performance on all working memory tasks and specific sub-processes of attention. The non-amnestic MCI group had lowered performance on visual span and complex sustained attention only. There was no evidence of either attentional or working memory impairment in the amnestic MCI participants. When MCI cohorts are assessed on measures distinct from those used at classification, a-MCI+ subjects had the most compromised working memory and attention function. These results support previous findings that suggest a-MCI+ more closely resembles early stage Alzheimer's disease and those with a-MCI+ may be at increased rate of future cognitive decline compared to those with other MCI subtypes. © 2014 The Authors. Psychogeriatrics © 2014 Japanese Psychogeriatric Society.

Developmental amnesia: a new pattern of dissociation with intact episodic memory.

PubMed

Temple, Christine M; Richardson, Paul

2004-01-01

A case of developmental amnesia is reported for a child, CL, of normal intelligence, who has intact episodic memory but impaired semantic memory for both semantic knowledge of facts and semantic knowledge of words, including general world knowledge, knowledge of word meanings and superordinate knowledge of words. In contrast to the deficits in semantic memory, there are no impairments in episodic memory for verbal or visual material, assessed by recall or recognition. Lexical decision was also intact, indicating impairment in semantic knowledge of vocabulary rather than absence of lexical representations. The case forms a double dissociation to the cases of Vargha-Khadem et al. [Science 277 (1997) 376; Episodic memory: new directions in research (2002) 153]; Gadian et al. [Brain 123 (2000) 499] for whom semantic memory was intact but episodic memory was impaired. This double dissociation suggests that semantic memory and episodic memory have the capacity to develop separately and supports models of modularity within memory development and a functional architecture for the developmental disorders within which there is residual normality rather than pervasive abnormality. Knowledge of arithmetical facts is also spared for CL, consistent with adult studies arguing for numeracy knowledge distinct from other semantics. Reading was characterised by difficulty with irregular words and homophones but intact reading of nonwords. CL has surface dyslexia with poor lexico-semantic reading skills but good phonological reading skills. The case was identified following screening from a population of normal schoolchildren suggesting that developmental amnesias may be more pervasive than has been recognised previously.

Short- and long-term cognitive effects of chronic cannabinoids administration in late-adolescence rats.

PubMed

Abush, Hila; Akirav, Irit

2012-01-01

The use of cannabis can impair cognitive function, especially short-term memory. A controversial question is whether long-term cannabis use during the late-adolescence period can cause irreversible deficits in higher brain function that persist after drug use stops. In order to examine the short- and long-term effects of chronic exposure to cannabinoids, rats were administered chronic i.p. treatment with the CB1/CB2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg) for two weeks during the late adolescence period (post-natal days 45-60) and tested for behavioral and electrophysiological measures of cognitive performance 24 hrs, 10 and 30 days after the last drug injection. The impairing effects of chronic WIN on short-term memory in the water maze and the object recognition tasks as well as long-term potentiation (LTP) in the ventral subiculum (vSub)-nucleus accumbens (NAc) pathway were temporary as they lasted only 24 h or 10 d after withdrawal. However, chronic WIN significantly impaired hippocampal dependent short-term memory measured in the object location task 24 hrs, 10, 30, and 75 days after the last drug injection. Our findings suggest that some forms of hippocampal-dependent short-term memory are sensitive to chronic cannabinoid administration but other cognitive impairments are temporary and probably result from a residue of cannabinoids in the brain or acute withdrawal effects from cannabinoids. Understanding the effects of cannabinoids on cognitive function may provide us with tools to overcome these impairments and for cannabinoids to be more favorably considered for clinical use.

Insensitivity of visual short-term memory to irrelevant visual information.

PubMed

Andrade, Jackie; Kemps, Eva; Werniers, Yves; May, Jon; Szmalec, Arnaud

2002-07-01

Several authors have hypothesized that visuo-spatial working memory is functionally analogous to verbal working memory. Irrelevant background speech impairs verbal short-term memory. We investigated whether irrelevant visual information has an analogous effect on visual short-term memory, using a dynamic visual noise (DVN) technique known to disrupt visual imagery (Quinn & McConnell, 1996b). Experiment I replicated the effect of DVN on pegword imagery. Experiments 2 and 3 showed no effect of DVN on recall of static matrix patterns, despite a significant effect of a concurrent spatial tapping task. Experiment 4 showed no effect of DVN on encoding or maintenance of arrays of matrix patterns, despite testing memory by a recognition procedure to encourage visual rather than spatial processing. Serial position curves showed a one-item recency effect typical of visual short-term memory. Experiment 5 showed no effect of DVN on short-term recognition of Chinese characters, despite effects of visual similarity and a concurrent colour memory task that confirmed visual processing of the characters. We conclude that irrelevant visual noise does not impair visual short-term memory. Visual working memory may not be functionally analogous to verbal working memory, and different cognitive processes may underlie visual short-term memory and visual imagery.

Effects of functional remediation on neurocognitively impaired bipolar patients: enhancement of verbal memory.

PubMed

Bonnin, C M; Reinares, M; Martínez-Arán, A; Balanzá-Martínez, V; Sole, B; Torrent, C; Tabarés-Seisdedos, R; García-Portilla, M P; Ibáñez, A; Amann, B L; Arango, C; Ayuso-Mateos, J L; Crespo, J M; González-Pinto, A; Colom, F; Vieta, E

2016-01-01

Functional remediation is a novel intervention with demonstrated efficacy at improving functional outcome in euthymic bipolar patients. However, in a previous trial no significant changes in neurocognitive measures were detected. The objective of the present analysis was to test the efficacy of this therapy in the enhancement of neuropsychological functions in a subgroup of neurocognitively impaired bipolar patients. A total of 188 out of 239 DSM-IV euthymic bipolar patients performing below two standard deviations from the mean of normative data in any neurocognitive test were included in this subanalysis. Repeated-measures analyses of variance were conducted to assess the impact of the treatment arms [functional remediation, psychoeducation, or treatment as usual (TAU)] on participants' neurocognitive and functional outcomes in the subgroup of neurocognitively impaired patients. Patients receiving functional remediation (n = 56) showed an improvement on delayed free recall when compared with the TAU (n = 63) and psychoeducation (n = 69) groups as shown by the group × time interaction at 6-month follow-up [F 2,158 = 3.37, degrees of freedom (df) = 2, p = 0.037]. However, Tukey post-hoc analyses revealed that functional remediation was only superior when compared with TAU (p = 0.04), but not with psychoeducation (p = 0.10). Finally, the patients in the functional remediation group also benefited from the treatment in terms of functional outcome (F 2,158 = 4.26, df = 2, p = 0.016). Functional remediation is effective at improving verbal memory and psychosocial functioning in a sample of neurocognitively impaired bipolar patients at 6-month follow-up. Neurocognitive enhancement may be one of the active ingredients of this novel intervention, and, specifically, verbal memory appears to be the most sensitive function that improves with functional remediation.

The sensitivity and specificity of the Middlesex Elderly Assessment of Mental State (MEAMS) for detecting cognitive impairment after stroke.

PubMed

Cartoni, A; Lincoln, N B

2005-03-01

The aim of the study was to assess the sensitivity and specificity of the MEAMS (Golding, 1989) for detecting cognitive impairment after stroke. Stroke patients admitted to hospital received a cognitive screening assessment, the MEAMS, and a detailed cognitive assessment. The information obtained from the detailed assessment was summarised in a structured written report. From the conclusions in these reports, patients were classified as "impaired" or "not impaired" in perception, memory, executive function and language. The sensitivity and specificity of the MEAMS subtests and the overall number of tests passed were determined in relation to the presence of impairment, as given in the overall conclusion of the written reports. There were 30 stroke patients, aged 58 to 92 (mean 75.80, SD 7.94) years. Of these, 17 were men and 13 were women. The sensitivity of the MEAMS subtests ranged from 11% to 100% and the specificity ranged from 69% to 100%. The sensitivity of the overall MEAMS score was 52% and the specificity was 100%, using a cut-off score of 3 or more fails to indicate impairment. Three subtests, Orientation, Naming and Unusual views had 81% sensitivity and 50% specificity for detecting problems in language, perception or memory. The MEAMS was not a sensitive screen for overall cognitive impairment or for memory, perceptual, language, or executive function problems after stroke, but it was specific. Although screening for cognitive impairment is important, the MEAMS is not recommended as the sole method, as it produces an unacceptably high false negative rate. Three subtests (Orientation, Naming and Unusual views) had 81% sensitivity and 50% specificity for detecting cognitive problems in language, perception or memory after stroke.

Organizational and visual memory deficits in schizophrenia and bipolar psychoses using the Rey-Osterrieth complex figure: effects of duration of illness.

PubMed

Seidman, Larry J; Lanca, Margaret; Kremen, William S; Faraone, Stephen V; Tsuang, Ming T

2003-10-01

Verbal declarative memory deficits in schizophrenia are well documented whereas visual declarative memory is less studied. Moreover, there are limited data on whether organizational and visual memory deficits are specific to schizophrenic psychoses. We compared visual memory and organizational function in patients with chronic schizophrenia (n=79) and chronic bipolar psychotic disorder (n=14), and in healthy controls (n=84) using the Rey-Osterrieth Complex Figure (ROCF), testing whether organizational impairments (i.e., executive dysfunctions) account for the visual memory deficit. Groups were comparable on age, handedness and expected intellectual ability (based on single word reading). Using analyses of covariance with sex, parental SES and ethnicity as co-variates, patients with schizophrenia were significantly more impaired than controls on copy accuracy, on recall accuracy, and on percent accuracy of recall. Patients with schizophrenia used a more detail-oriented style on copy and recall and had significantly worse recognition memory. After co-varying IQ, copy organization was also significantly different between the groups. Results for accuracy of copy and recall were not significantly attenuated when controlling for copy organization. Duration of illness was associated with visual memory. Bipolar patients performed at an intermediate level between controls and patients with schizophrenia. The data suggest that in schizophrenia, patients have a visual memory disorder characterized by both organizational processing impairments and retention difficulties, and that there is a decline in visual memory functions with duration of illness. Further research is required to determine whether similar mechanisms underlie the neurocognitive deficits in these psychotic disorders.

Impaired spatial memory and enhanced long-term potentiation in mice with forebrain-specific ablation of the Stim genes

PubMed Central

Garcia-Alvarez, Gisela; Shetty, Mahesh S.; Lu, Bo; Yap, Kenrick An Fu; Oh-Hora, Masatsugu; Sajikumar, Sreedharan; Bichler, Zoë; Fivaz, Marc

2015-01-01

Recent findings point to a central role of the endoplasmic reticulum-resident STIM (Stromal Interaction Molecule) proteins in shaping the structure and function of excitatory synapses in the mammalian brain. The impact of the Stim genes on cognitive functions remains, however, poorly understood. To explore the function of the Stim genes in learning and memory, we generated three mouse strains with conditional deletion (cKO) of Stim1 and/or Stim2 in the forebrain. Stim1, Stim2, and double Stim1/Stim2 cKO mice show no obvious brain structural defects or locomotor impairment. Analysis of spatial reference memory in the Morris water maze revealed a mild learning delay in Stim1 cKO mice, while learning and memory in Stim2 cKO mice was indistinguishable from their control littermates. Deletion of both Stim genes in the forebrain resulted, however, in a pronounced impairment in spatial learning and memory reflecting a synergistic effect of the Stim genes on the underlying neural circuits. Notably, long-term potentiation (LTP) at CA3-CA1 hippocampal synapses was markedly enhanced in Stim1/Stim2 cKO mice and was associated with increased phosphorylation of the AMPA receptor subunit GluA1, the transcriptional regulator CREB and the L-type Voltage-dependent Ca2+ channel Cav1.2 on protein kinase A (PKA) sites. We conclude that STIM1 and STIM2 are key regulators of PKA signaling and synaptic plasticity in neural circuits encoding spatial memory. Our findings also reveal an inverse correlation between LTP and spatial learning/memory and suggest that abnormal enhancement of cAMP/PKA signaling and synaptic efficacy disrupts the formation of new memories. PMID:26236206

Functional Impairments in Attention Deficit Hyperactivity Disorder: The Mediating Role of Neuropsychological Functioning

PubMed Central

Sjöwall, Douglas; Thorell, Lisa B.

2014-01-01

Attention deficit hyperactivity disorder (ADHD) is associated with multiple neuropsychological deficits and the present study aimed to investigate to what extent these deficits are related to the functional impairments associated with the disorder. The results showed that all executive functioning deficits and reaction time variability acted as mediators in the relation between ADHD and academic achievement. However, only the effect of working memory for language skills, and the effects of reaction time variability and working memory for mathematics, remained significant when studying independent effects. Regulation of anger was a significant mediator for peer problems. Gender or symptoms of oppositional defiant disorder (ODD) or conduct disorder (CD) did not moderate these findings. PMID:24742310

Case-finding for cognitive impairment among people with Type 2 diabetes in primary care using the Test Your Memory and Self-Administered Gerocognitive Examination questionnaires: the Cog-ID study.

PubMed

Koekkoek, P S; Janssen, J; Kooistra, M; Biesbroek, J M; Groeneveld, O; van den Berg, E; Kappelle, L J; Biessels, G J; Rutten, G E H M

2016-06-01

To evaluate two cognitive tests for case-finding for cognitive impairment in older patients with Type 2 diabetes. Of 1243 invited patients with Type 2 diabetes, aged ≥70 years, 228 participated in a prospective cohort study. Exclusion criteria were: diagnosis of dementia; previous investigation at a memory clinic; and inability to write or read. Patients first filled out two self-administered cognitive tests (Test Your Memory and Self-Administered Gerocognitive Examination). Secondly, a general practitioner, blinded to Test Your Memory and Self-Administered Gerocognitive Examination scores, performed a structured evaluation using the Mini-Mental State Examination. Subsequently, patients suspected of cognitive impairment (on either the cognitive tests or general practitioner evaluation) and a random sample of 30% of patients not suspected of cognitive impairment were evaluated at a memory clinic. Diagnostic accuracy and area under the curve were determined for the Test Your Memory, Self-Administered Gerocognitive Examination and general practitioner evaluation compared with a memory clinic evaluation to detect cognitive impairment (mild cognitive impairment or dementia). A total of 44 participants were diagnosed with cognitive impairment. The Test Your Memory and Self-Administered Gerocognitive Examination questionnaires had negative predictive values of 81 and 85%, respectively. Positive predictive values were 39 and 40%, respectively. The general practitioner evaluation had a negative predictive value of 83% and positive predictive value of 64%. The area under the curve was ~0.70 for all tests. Both the tests evaluated in the present study can easily be used in case-finding strategies for cognitive impairment in patients with Type 2 diabetes in primary care. The Self-Administered Gerocognitive Examination had the best diagnostic accuracy and therefore we would have a slight preference for this test. Applying the Self-Administered Gerocognitive Examination would considerably reduce the number of patients in whom the general practitioner needs to evaluate cognitive functioning to tailor diabetes treatment. © 2015 Diabetes UK.

Using Functional Near-Infrared Spectroscopy to Measure Effects of Delta 9-Tetrahydrocannabinol on Prefrontal Activity and Working Memory in Cannabis Users.

PubMed

Keles, Hasan O; Radoman, Milena; Pachas, Gladys N; Evins, A Eden; Gilman, Jodi M

2017-01-01

Intoxication from cannabis impairs cognitive performance, in part due to the effects of Δ9-tetrahydrocannabinol (THC, the primary psychoactive compound in cannabis) on prefrontal cortex (PFC) function. However, a relationship between impairment in cognitive functioning with THC administration and THC-induced change in hemodynamic response has not been demonstrated. We explored the feasibility of using functional near-infrared spectroscopy (fNIRS) to examine the functional changes of the human PFC associated with cannabis intoxication and cognitive impairment. Eighteen adult regular cannabis users (final sample, n = 13) performed a working memory task ( n -back) during fNIRS recordings, before and after receiving a single dose of oral synthetic THC (dronabinol; 20-50 mg). Functional data were collected using a continuous-wave NIRS device, in which 8 Sources and 7 detectors were placed on the forehead, resulting in 20 channels covering PFC regions. Physiological changes and subjective intoxication measures were collected. We found a significant increase in the oxygenated hemoglobin (HbO) concentration after THC administration in several channels on the PFC during both the high working memory load (2-back) and the low working memory load (0-back) condition. The increased HbO response was accompanied by a trend toward an increased number of omission errors after THC administration. The current study suggests that cannabis intoxication is associated with increases in hemodynamic blood flow to the PFC, and that this increase can be detected with fNIRS.

Object location and object recognition memory impairments, motivation deficits and depression in a model of Gulf War illness.

PubMed

Hattiangady, Bharathi; Mishra, Vikas; Kodali, Maheedhar; Shuai, Bing; Rao, Xiolan; Shetty, Ashok K

2014-01-01

Memory and mood deficits are the enduring brain-related symptoms in Gulf War illness (GWI). Both animal model and epidemiological investigations have indicated that these impairments in a majority of GW veterans are linked to exposures to chemicals such as pyridostigmine bromide (PB, an antinerve gas drug), permethrin (PM, an insecticide) and DEET (a mosquito repellant) encountered during the Persian Gulf War-1. Our previous study in a rat model has shown that combined exposures to low doses of GWI-related (GWIR) chemicals PB, PM, and DEET with or without 5-min of restraint stress (a mild stress paradigm) causes hippocampus-dependent spatial memory dysfunction in a water maze test (WMT) and increased depressive-like behavior in a forced swim test (FST). In this study, using a larger cohort of rats exposed to GWIR-chemicals and stress, we investigated whether the memory deficiency identified earlier in a WMT is reproducible with an alternative and stress free hippocampus-dependent memory test such as the object location test (OLT). We also ascertained the possible co-existence of hippocampus-independent memory dysfunction using a novel object recognition test (NORT), and alterations in mood function with additional tests for motivation and depression. Our results provide new evidence that exposure to low doses of GWIR-chemicals and mild stress for 4 weeks causes deficits in hippocampus-dependent object location memory and perirhinal cortex-dependent novel object recognition memory. An open field test performed prior to other behavioral analyses revealed that memory impairments were not associated with increased anxiety or deficits in general motor ability. However, behavioral tests for mood function such as a voluntary physical exercise paradigm and a novelty suppressed feeding test (NSFT) demonstrated decreased motivation levels and depression. Thus, exposure to GWIR-chemicals and stress causes both hippocampus-dependent and hippocampus-independent memory impairments as well as mood dysfunction in a rat model.

Impaired quality and efficiency of sleep impairs cognitive functioning in Addison's disease.

PubMed

Henry, Michelle; Ross, Ian Louis; Wolf, Pedro Sofio Abril; Thomas, Kevin Garth Flusk

2017-04-01

Standard replacement therapy for Addison's disease (AD) does not restore a normal circadian rhythm. Periods of sub- and supra- physiological cortisol levels experienced by patients with AD likely induce disrupted sleep. Given that healthy sleep plays an important role in memory consolidation, the novelty of the current study was to characterise, using objective measures, the relationship between sleep and memory in patients with AD, and to examine the hypothesis that poor sleep is a biological mechanism underlying memory impairment in those patients. We used a within-subjects design. Ten patients with AD and 10 matched healthy controls completed standardised neuropsychological tests assessing declarative memory (Rey Auditory Verbal Learning Test) and procedural memory (Finger Tapping Task) before and after a period of actigraphy-measured sleep, and before and after a period of waking. Relative to healthy controls, patients with AD experienced disrupted sleep characterised by poorer sleep efficiency and more time spent awake. Patients also showed impaired verbal learning and memory relative to healthy controls (p=0.007). Furthermore, whereas healthy controls' declarative memory performance benefited from a period of sleep compared to waking (p=0.032), patients with AD derived no such benefit from sleep (p=0.448). Regarding the procedural memory task, analyses detected no significant between-group differences (all p's<0.065), and neither group showed significant sleep-enhanced performance. We demonstrated, using actigraphy and standardized measures of memory performance, an association between sleep disturbances and cognitive deficits in patients with AD. These results suggest that, in patients with AD, the source of memory deficits is, at least to some extent, disrupted sleep patterns that interfere with optimal consolidation of previously-learned declarative information. Hence, treating the sleep disturbances that are frequently experienced by patients with AD may improve their cognitive functioning. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neurocognitive impairment and psychosis in bipolar I disorder during early remission from an acute episode of mood disturbance.

PubMed

Levy, Boaz; Weiss, Roger D

2010-02-01

Recent studies have reported greater neurocognitive impairment in euthymic bipolar disorder patients with a history of psychosis relative to patients without such a history. To further explore the relation between psychosis and cognitive dysfunction in bipolar disorder, the current study examined the cognitive functioning of patients during early remission from a discrete episode of mood disturbance. The study aimed to determine whether the presence of psychosis during inpatient hospitalization was associated with greater cognitive impairment at the time of hospital discharge. Fifty-nine inpatients who met DSM-IV criteria for bipolar disorder (24 admitted with psychosis, 35 admitted without psychosis), ages 18-59 years, completed a neuropsychological battery and mood measures 24-48 hours before discharge. The cognitive battery included standardized tests of IQ, attention and working memory, visual memory, verbal memory, and executive functioning. A multivariate analysis of variance detected group differences on measures of verbal memory (P < .001) and executive functioning (P < .003), using mood measures and previous number of psychiatric admissions as covariates. Post hoc analysis of between-subjects effects revealed significantly poorer performance on the California Verbal Learning Test-Second Edition, logical memory subtest from Wechsler Memory Scale-Revised, Stroop Word/Color Interference test, and the Wisconsin Card Sorting Test for patients who were admitted to the hospital with psychosis. These results remained significant after matching the groups for past psychosis, with the exception of the logical memory subtest. The results of this study indicate that patients with bipolar disorder who were admitted to the hospital due to psychosis exhibited significantly more severe cognitive impairment at the time of discharge than patients admitted for an acute mood disturbance without psychosis. These findings may be important for improving discharge planning and the development of more effective outpatient services. Copyright 2010 Physicians Postgraduate Press, Inc.

Implicit perceptual-motor skill learning in mild cognitive impairment and Parkinson's disease.

PubMed

Gobel, Eric W; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandra; Reber, Paul J

2013-05-01

Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation as to whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n = 11) and patients with PD (n = 15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n = 20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system.

Characteristic of cognitive decline in Parkinson's disease: a 1-year follow-up.

PubMed

McKinlay, Audrey; Grace, Randolph C

2011-10-01

The aim of this study was to track the evolution of cognitive decline in Parkinson's disease (PD) patients 1 year after baseline testing. Thirty-three PD patients, divided according to three previously determined subgroups based on their initial cognitive performance, and a healthy comparison group were reassessed after a 1-year interval. Participants were assessed in the following five domains: Executive Function, Problem Solving, Working Memory/Attention, Memory, and Visuospatial Ability. The PD groups differed on the domains of Executive Function, Problem Solving, and Working Memory, with the most severe deficits being evident for the group that had previously shown the greatest level of impairment. Increased cognitive problems were also associated with decreased functioning in activities of daily living. The most severely impaired group had evidence of global cognitive decline, possibly reflecting a stage of preclinical dementia.

Memory and Learning in Pediatric Bipolar Disorder.

ERIC Educational Resources Information Center

McClure, Erin B.; Treland, Julia E.; Snow, Joseph; Dickstein, Daniel P.; Towbin, Kenneth E.; Charney, Dennis S.; Pine, Daniel S.; Leibenluft, Ellen

2005-01-01

Objective: To test the hypothesis that patients with pediatric bipolar disorder (PBPD) would demonstrate impairment relative to diagnosis-free controls of comparable age, gender, and IQ on measures of memory functioning. Method: The authors administered a battery of verbal and visuospatial memory tests to 35 outpatients with PBPD and 20 healthy…

Working Memory Weaknesses in Students with ADHD: Implications for Instruction

ERIC Educational Resources Information Center

Martinussen, Rhonda; Major, Ashley

2011-01-01

Students with attention deficit hyperactivity disorder (ADHD) are at risk for academic underachievement. Children and youth with ADHD have been found to exhibit impairments on neuropsychological measures of executive functions, including working memory. Working memory is important to attentional control and learning. This article defines working…

Verbal Memory in Parkinson’s Disease: A Combined DTI and fMRI Study

PubMed Central

Lucas-Jiménez, Olaia; Díez-Cirarda, María; Ojeda, Natalia; Peña, Javier; Cabrera-Zubizarreta, Alberto; Ibarretxe-Bilbao, Naroa

2015-01-01

Background: While significant progress has been made to determine the functional role of specific gray matter areas underlying verbal memory in Parkinson’s disease (PD), very little is known about the relationship between these regions and their underlying white matter structures. Objective: The objectives of this study were (1) to investigate verbal memory, fractional anisotropy and brain activation differences between PD patients and healthy controls (HC), (2) to explore the neuroanatomical and neurofunctional correlates of verbal memory in PD, and (3) to investigate the relationship between these neuroanatomical and neurofunctional verbal memory correlates in PD. Methods: Functional magnetic resonance imaging (fMRI) while performing a verbal memory paradigm and diffusion tensor imaging data (DTI), were acquired in 37 PD patients and 15 age-, sex-, and education-matched HC. Results: PD patients showed verbal recognition memory impairment, lower fractional anisotropy in the anterior cingulate tract, and lower brain activation in the inferior orbitofrontal cortex compared to HC. Brain activation in the inferior orbitofrontal cortex correlated significantly with verbal recognition memory impairment in PD patients. In addition, a relationship between brain activation in the inferior orbitofrontal cortex and fractional anisotropy of the uncinate fasciculus was found in PD. Conclusions: These results reveal that deficits in verbal memory in PD are accompanied by functional brain activation changes, but also have specific structural correlates related to white matter microstructural integrity. PMID:27070003

Subjective and objective cognitive function among older adults with a history of traumatic brain injury: A population-based cohort study.

PubMed

Gardner, Raquel C; Langa, Kenneth M; Yaffe, Kristine

2017-03-01

Traumatic brain injury (TBI) is extremely common across the lifespan and is an established risk factor for dementia. The cognitive profile of the large and growing population of older adults with prior TBI who do not have a diagnosis of dementia, however, has not been well described. Our aim was to describe the cognitive profile associated with prior TBI exposure among community-dwelling older adults without dementia-an understudied but potentially vulnerable population. In this population-based cohort study, we studied 984 community-dwelling older adults (age 51 y and older and their spouses) without dementia who had been randomly selected from respondents to the 2014 wave of the Health and Retirement Study to participate in a comprehensive TBI survey and who either reported no prior TBI (n = 737) or prior symptomatic TBI resulting in treatment in a hospital (n = 247). Mean time since first TBI was 38 ± 19 y. Outcomes assessed included measures of global cognitive function, verbal episodic memory, semantic fluency, and calculation as well as a measure of subjective memory ("How would you rate your memory at the present time?"). We compared outcomes between the two TBI groups using regression models adjusting for demographics, medical comorbidities, and depression. Sensitivity analyses were performed stratified by TBI severity (no TBI, TBI without loss of consciousness [LOC], and TBI with LOC). Respondents with TBI were younger (mean age 64 ± 10 y versus 68 ± 11 y), were less likely to be female, and had higher prevalence of medical comorbidities and depression than respondents without TBI. Respondents with TBI did not perform significantly differently from respondents without TBI on any measure of objective cognitive function in either raw or adjusted models (fully adjusted: global cognitive function score 15.4 versus 15.2, p = 0.68; verbal episodic memory score 4.4 versus 4.3, p = 0.79; semantic fluency score 15.7 versus 14.0, p = 0.21; calculation impairment 22% versus 26%, risk ratio [RR] [95% CI] = 0.86 [0.67-1.11], p = 0.24). Sensitivity analyses stratified by TBI severity produced similar results. TBI was associated with significantly increased risk for subjective memory impairment in models adjusted for demographics and medical comorbidities (29% versus 24%; RR [95% CI]: 1.26 [1.02-1.57], p = 0.036). After further adjustment for active depression, however, risk for subjective memory impairment was no longer significant (RR [95% CI]: 1.18 [0.95-1.47], p = 0.13). Sensitivity analyses revealed that risk of subjective memory impairment was increased only among respondents with TBI with LOC and not among those with TBI without LOC. Furthermore, the risk of subjective memory impairment was significantly greater among those with TBI with LOC versus those without TBI even after adjustment for depression (RR [95% CI]: partially adjusted, 1.38 [1.09-1.74], p = 0.008; fully adjusted, 1.28 [1.01-1.61], p = 0.039). In this population-based study of community-dwelling older adults without dementia, those with prior TBI with LOC were more likely to report subjective memory impairment compared to those without TBI even after adjustment for demographics, medical comorbidities, and active depression. Lack of greater objective cognitive impairment among those with versus without TBI may be due to poor sensitivity of the cognitive battery or survival bias, or may suggest that post-TBI cognitive impairment primarily affects executive function and processing speed, which were not rigorously assessed in this study. Our findings show that among community-dwelling non-demented older adults, history of TBI is common but may not preferentially impact cognitive domains of episodic memory, attention, working memory, verbal semantic fluency, or calculation.

Dentate gyrus supports slope recognition memory, shades of grey-context pattern separation and recognition memory, and CA3 supports pattern completion for object memory.

PubMed

Kesner, Raymond P; Kirk, Ryan A; Yu, Zhenghui; Polansky, Caitlin; Musso, Nick D

2016-03-01

In order to examine the role of the dorsal dentate gyrus (dDG) in slope (vertical space) recognition and possible pattern separation, various slope (vertical space) degrees were used in a novel exploratory paradigm to measure novelty detection for changes in slope (vertical space) recognition memory and slope memory pattern separation in Experiment 1. The results of the experiment indicate that control rats displayed a slope recognition memory function with a pattern separation process for slope memory that is dependent upon the magnitude of change in slope between study and test phases. In contrast, the dDG lesioned rats displayed an impairment in slope recognition memory, though because there was no significant interaction between the two groups and slope memory, a reliable pattern separation impairment for slope could not be firmly established in the DG lesioned rats. In Experiment 2, in order to determine whether, the dDG plays a role in shades of grey spatial context recognition and possible pattern separation, shades of grey were used in a novel exploratory paradigm to measure novelty detection for changes in the shades of grey context environment. The results of the experiment indicate that control rats displayed a shades of grey-context pattern separation effect across levels of separation of context (shades of grey). In contrast, the DG lesioned rats displayed a significant interaction between the two groups and levels of shades of grey suggesting impairment in a pattern separation function for levels of shades of grey. In Experiment 3 in order to determine whether the dorsal CA3 (dCA3) plays a role in object pattern completion, a new task requiring less training and using a choice that was based on choosing the correct set of objects on a two-choice discrimination task was used. The results indicated that control rats displayed a pattern completion function based on the availability of one, two, three or four cues. In contrast, the dCA3 lesioned rats displayed a significant interaction between the two groups and the number of available objects suggesting impairment in a pattern completion function for object cues. Copyright © 2015 Elsevier Inc. All rights reserved.

HIV-associated Prospective Memory Impairment Increases Risk of Dependence in Everyday Functioning

PubMed Central

Woods, Steven Paul; Iudicello, Jennifer E.; Moran, Lisa M.; Carey, Catherine L.; Dawson, Matthew S.; Grant, Igor

2007-01-01

HIV infection is associated with impairments in prospective memory (ProM), an aspect of episodic memory that refers to the ability to execute a future intention, such as remembering to take a medication at a specific time. The current study sought to examine the relationship between HIV-associated ProM impairment and the successful management of independent activities of daily living (IADLs). In a cohort of 66 HIV-infected individuals, ProM accounted for a significant proportion of variance in self-reported IADL dependence over and above that which was explained by retrospective memory and current affective distress. Analysis of component cognitive processes revealed that the relationship between HIV-associated ProM deficits and IADL dependence was driven by impaired cue detection and self-initiated intention retrieval. Results were not better explained by demographic factors, HIV disease severity, psychiatric comorbidity, or substance use. Collectively, these data support the potential incremental ecological validity of ProM as a predictor of dependence in IADLs among persons living with HIV infection. PMID:18211160

Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report from the Childhood Cancer Survivor Study

PubMed Central

Ellenberg, Leah; Liu, Qi; Gioia, Gerard; Yasui, Yutaka; Packer, Roger J.; Mertens, Ann; Donaldson, Sarah S.; Stovall, Marilyn; Kadan-Lottick, Nina; Armstrong, Gregory; Robison, Leslie L.; Zeltzer, Lonnie K.

2009-01-01

Background Among survivors of childhood cancer, those with Central Nervous System (CNS) malignancies have been found to be at greatest risk for neuropsychological dysfunction in the first few years following diagnosis and treatment. This study follows survivors to adulthood to assess the long term impact of childhood CNS malignancy and its treatment on neurocognitive functioning. Participants & Methods As part of the Childhood Cancer Survivor Study (CCSS), 802 survivors of childhood CNS malignancy, 5937 survivors of non-CNS malignancy and 382 siblings without cancer completed a 25 item Neurocognitive Questionnaire (CCSS-NCQ) at least 16 years post cancer diagnosis assessing task efficiency, emotional regulation, organizational skills and memory. Neurocognitive functioning in survivors of CNS malignancy was compared to that of non-CNS malignancy survivors and a sibling cohort. Within the group of CNS malignancy survivors, multiple linear regression was used to assess the contribution of demographic, illness and treatment variables to reported neurocognitive functioning and the relationship of reported neurocognitive functioning to educational, employment and income status. Results Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all factors assessed by the CCSS-NCQ than non-CNS cancer survivors or siblings (p<.01), with mean T scores of CNS malignancy survivors substantially more impaired that those of the sibling cohort (p<.001), with a large effect size for Task Efficiency (1.16) and a medium effect size for Memory (.68). Within the CNS malignancy group, medical complications, including hearing deficits, paralysis and cerebrovascular incidents resulted in a greater likelihood of reported deficits on all of the CCSS-NCQ factors, with generally small effect sizes (.22-.50). Total brain irradiation predicted greater impairment on Task Efficiency and Memory (Effect sizes: .65 and .63, respectively), as did partial brain irradiation, with smaller effect sizes (.49 and .43, respectively). Ventriculoperitoneal (VP) shunt placement was associated with small deficits on the same scales (Effect sizes: Task Efficiency .26, Memory .32). Female gender predicted a greater likelihood of impaired scores on 2 scales, with small effect sizes (Task Efficiency .38, Emotional Regulation .45), while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor with a moderate effect size (.64). CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p<.01), less household income (p<.001) and less full time employment (p<.001). Conclusions Survivors of childhood CNS malignancy are at significant risk for impairment in neurocognitive functioning in adulthood, particularly if they have received cranial radiation, had a VP shunt placed, suffered a cerebrovascular incident or are left with hearing or motor impairments. Reported neurocognitive impairment adversely affected important adult outcomes, including education, employment, income and marital status. PMID:19899829

Sulforaphane Ameliorates Okadaic Acid-Induced Memory Impairment in Rats by Activating the Nrf2/HO-1 Antioxidant Pathway.

PubMed

Dwivedi, Subhash; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2016-10-01

Okadaic acid (OKA) causes memory impairment and attenuates nuclear factor erythroid 2-related factor 2 (Nrf2) along with oxidative stress and neuroinflammation in rats. Sulforaphane (dietary isothiocyanate compound), an activator of Nrf2 signaling, exhibits neuroprotective effects. However, the protective effect of sulforaphane in OKA-induced neurotoxicity remains uninvestigated. Therefore, in the present study, the role of sulforaphane in OKA-induced memory impairment in rats was explored. A significant increased Nrf2 expression in the hippocampus and cerebral cortex was observed in trained (Morris water maze) rats, and a significant decreased Nrf2 expression in memory-impaired (OKA, 200 ng icv) rats indicated its involvement in memory function. Sulforaphane administration (5 and 10 mg/kg, ip, days 1 and 2) ameliorates OKA-induced memory impairment in rats. The treatment also restored Nrf2 and its downstream antioxidant protein expression (GCLC, HO-1) and attenuated oxidative stress (ROS, nitrite, GSH), neuroinflammation (NF-κB, TNF-α, IL-10), and neuronal apoptosis in the cerebral cortex and hippocampus of OKA-treated rats. Further, to determine whether modulation of Nrf2 signaling is responsible for the protective effect of sulforaphane, in vitro, Nrf2 siRNA and its downstream HO-1 inhibition studies were carried out in a rat astrocytoma cell line (C6). The protective effects of sulforaphane were abolished with Nrf2 siRNA and HO-1 inhibition in astrocytes. The results suggest that Nrf2-dependent activation of cellular antioxidant machinery results in sulforaphane-mediated protection against OKA-induced memory impairment in rats. Graphical Abstract ᅟ.

Neurocognitive Aging and the Hippocampus Across Species

PubMed Central

Leal, Stephanie L; Yassa, Michael A.

2016-01-01

There is extensive evidence that aging is associated with impairments in episodic memory. Many of these changes have been ascribed to neurobiological alterations to the hippocampal network and its input pathways. A cross-species consensus is beginning to emerge suggesting that subtle synaptic and functional changes within this network may underlie the majority of age-related memory impairments. In this review, we survey convergent data from animal and human studies that have contributed significantly to our understanding of the brain-behavior relationships in this network, particularly in the aging brain. We utilize a cognitive as well as a neurobiological perspective, and synthesize data across approaches and species to reach a more detailed understanding of age-related alterations in hippocampal memory function. PMID:26607684

Hypertension exacerbates predisposition to neurodegeneration and memory impairment in the presence of a neuroinflammatory stimulus: Protection by angiotensin converting enzyme inhibition.

PubMed

Goel, Ruby; Bhat, Shahnawaz Ali; Rajasekar, N; Hanif, Kashif; Nath, Chandishwar; Shukla, Rakesh

2015-06-01

Hypertension is a risk factor for cognitive impairment. Furthermore, neuroinflammation and neurodegeneration are intricately associated with memory impairment. Therefore, the present study aimed to explore the involvement of hypertension and angiotensin system in neurodegeneration and memory dysfunction in the presence of neuroinflammatory stimulus. Memory impairment was induced by chronic neuroinflammation that was developed by repeated intracerebroventricular (ICV) injections of lipopolysaccharide (LPS) on the 1st, 4th, 7th, and 10th day. Memory functions were evaluated by the Morris water maze (MWM) test on days 13-15, followed by biochemical and molecular studies in the cortex and hippocampus regions of rat brain. LPS at the dose of 25μg ICV caused memory impairment in spontaneously hypertensive rats (SHRs) but not in normotensive Wistar rats (NWRs). Memory deficit was obtained with 50μg of LPS (ICV) in NWRs. Control SHRs already exhibited increased angiotensin converting enzyme (ACE) activity and expression, neuroinflammation (increased TNF-α, GFAP, COX-2 and NF-kB), oxidative stress (increased iNOS, ROS and nitrite levels), TLR-4 expression and TUNEL positive cells as compared to control NWRs. Further, LPS (25μg ICV) exaggerated inflammatory response, oxidative stress and apoptosis in SHRs but similar effects were witnessed at 50μg of LPS (ICV) in NWRs. Oral administration of perindopril (ACE inhibitor), at non-antihypertensive dose (0.1mg/kg), for 15days attenuated LPS induced deleterious changes in both NWRs and SHRs. Our data suggest that susceptibility of the brain for neurodegeneration and memory impairment induced by neuroinflammation is enhanced in hypertension, and that can be protected by ACE inhibition. Copyright © 2015 Elsevier Inc. All rights reserved.

Novel fMRI working memory paradigm accurately detects cognitive impairment in Multiple Sclerosis

PubMed Central

Nelson, Flavia; Akhtar, Mohammad A.; Zúñiga, Edward; Perez, Carlos A.; Hasan, Khader M.; Wilken, Jeffrey; Wolinsky, Jerry S.; Narayana, Ponnada A.; Steinberg, Joel L.

2016-01-01

Background Cognitive impairment (CI) cannot be diagnosed by MRI. Functional MRI (fMRI) paradigms such as the immediate/delayed memory task (I/DMT), detect varying degrees of working memory. Preliminary findings using I/DMT, showed differences in Blood Oxygenation Level Dependent (BOLD) activation between impaired (MSCI, n=12) and non-impaired (MSNI, n=9) MS patients. Objectives To confirm CI detection based on I/DMT’ BOLD activation in a larger cohort of MS patients. The role of T2 lesion volume (LV) and EDSS in magnitude of BOLD signal were also sought. Methods Fifty patients [EDSS mean (m) = 3.2, DD m =12 yr., age m =40yr.] underwent the Minimal Assessment of Cognitive Function in MS (MACFIMS) and the I/DMT. Working-memory activation (WMa) represents BOLD signal during DMT minus signal during IMT. CI was based on MACFIMS. Results 10 MSNI, 30 MSCI and 4 borderline patients were included in analyses. ANOVA showed MSNI had significantly greater WMa than MSCI, in the left (L) prefrontal cortex and L supplementary motor area (p = 0.032). Regression analysis showed significant inverse correlations between WMa and T2 LV/EDSS in similar areas (p = 0.005, 0.004 respectively). Conclusion I/DMT-based BOLD activation detects CI in MS, larger studies are needed to confirm these findings. PMID:27613119

Intelligence or years of education: which is better correlated with memory function in normal elderly Japanese subjects?

PubMed

Murayama, Norio; Iseki, Eizo; Tagaya, Hirokuni; Ota, Kazumi; Kasanuki, Koji; Fujishiro, Hiroshige; Arai, Heii; Sato, Kiyoshi

2013-03-01

We compared differences in intelligence and memory function between normal elderly Japanese subjects with more years of education and those with fewer years of education. We also investigated clinical and neuropsychological factors that are strongly correlated with memory function. There were 118 normal elderly subjects who underwent the Mini-Mental State Examination, Wechsler Adult Intelligence Scale, 3rd edition (WAIS-III), and Wechsler Memory Scale Revised. Subjects with at least 13 years of education were categorized as the H group, and those with 12 years of education or less were categorized as the L group. Age and Mini-Mental State Examination scores were not significantly different between the two groups. On the WAIS-III, there were significant differences between the two groups in Verbal IQ and Full Scale IQ. On the Wechsler Memory Scale Revised, there were significant differences between the two groups in Visual Memory, General Memory, and Delayed Recall. Correlation coefficients between memory function and the other factors demonstrated significant but weak correlations between years of education and General Memory (R = 0.22) and between years of education and Delayed Recall (R = 0.20). Strong correlations were found between Verbal IQ and Verbal Memory (R = 0.45), between Verbal IQ and General Memory (R = 0.49), between Full Scale IQ and General Memory (R = 0.50) and between Full Scale IQ and Delayed Recall (R = 0.48). In normal elderly Japanese subjects, years of education weakly correlated with memory function while Verbal IQ, Full Scale IQ and Verbal Comprehension on WAIS-III had stronger correlations with memory function. Verbal IQ and Verbal Comprehension on WAIS-III were found to be insusceptible to the cognitive decline characteristic of Alzheimer's disease or amnestic mild cognitive impairment. Therefore, verbal intelligence, as measured by Verbal IQ and Verbal Comprehension, may be the most useful factor for inferring premorbid memory function in Alzheimer's disease or amnestic mild cognitive impairment patients. © 2013 The Authors. Psychogeriatrics © 2013 Japanese Psychogeriatric Society.

Retrograde Amnesia for Episodic and Semantic Memories in Amnestic Mild Cognitive Impairment.

PubMed

De Simone, Maria Stefania; Fadda, Lucia; Perri, Roberta; De Tollis, Massimo; Aloisi, Marta; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2017-01-01

Retrograde amnesia (RA), which includes loss of memory for past personal events (autobiographical RA) and for acquired knowledge (semantic RA), has been largely documented in patients with amnestic mild cognitive impairment (aMCI). However, previous studies have produced controversial results particularly concerning the temporal extent of memory impairment. Here we investigated whether, with the onset of hippocampal pathology, age of memory acquisition and retrieval frequency play different roles in modulating the progressive loss of semantic and episodic contents of retrograde memory respectively. For this purpose, aMCI patients and healthy controls were tested for the ability to recall semantic and autobiographical information related to famous public events as a function of both age of acquisition and retrieval frequency. In aMCI patients, we found that the impairment in recollecting past personal incidents was modulated by the combined action of memory age and retrieval frequency, because older and more frequently retrieved episodes are less susceptible to loss than more recent and less frequently retrieved ones. On the other side, we found that the loss of semantic information depended only on memory age, because the remoteness of the trace allows for better preservation of the memory. Our results provide evidence that the loss of the two components of retrograde memory is regulated by different mechanisms. This supports the view that diverse neural mechanisms are involved in episodic and semantic memory trace storage and retrieval, as postulated by the Multiple Trace Theory.

Korsakoff Syndrome in Non-alcoholic Psychiatric Patients. Variable Cognitive Presentation and Impaired Frontotemporal Connectivity.

PubMed

Nikolakaros, Georgios; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G; Vataja, Risto; Ilonen, Tuula

2018-01-01

Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI) data are scarce. Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men) with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems. Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient. Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the uncinate fasciculus, may be a feature of non-alcoholic Korsakoff syndrome in psychiatric patients.

Korsakoff Syndrome in Non-alcoholic Psychiatric Patients. Variable Cognitive Presentation and Impaired Frontotemporal Connectivity

PubMed Central

Nikolakaros, Georgios; Kurki, Timo; Paju, Janina; Papageorgiou, Sokratis G.; Vataja, Risto; Ilonen, Tuula

2018-01-01

Background: Non-alcoholic Wernicke's encephalopathy and Korsakoff syndrome are greatly underdiagnosed. There are very few reported cases of neuropsychologically documented non-alcoholic Korsakoff syndrome, and diffusion tensor imaging (DTI) data are scarce. Methods: We report clinical characteristics and neuropsychological as well as radiological findings from three psychiatric patients (one woman and two men) with a history of probable undiagnosed non-alcoholic Wernicke's encephalopathy and subsequent chronic memory problems. Results: All patients had abnormal neuropsychological test results, predominantly in memory. Thus, the neuropsychological findings were compatible with Korsakoff syndrome. However, the neuropsychological findings were not uniform. The impairment of delayed verbal memory of the first patient was evident only when the results of the memory tests were compared to her general cognitive level. In addition, the logical memory test and the verbal working memory test were abnormal, but the word list memory test was normal. The second patient had impaired attention and psychomotor speed in addition to impaired memory. In the third patient, the word list memory test was abnormal, but the logical memory test was normal. All patients had intrusions in the neuropsychological examination. Executive functions were preserved, except for planning and foresight, which were impaired in two patients. Conventional MRI examination was normal. DTI showed reduced fractional anisotropy values in the uncinate fasciculus in two patients, and in the corpus callosum and in the subgenual cingulum in one patient. Conclusions: Non-alcoholic Korsakoff syndrome can have diverse neuropsychological findings. This may partly explain its marked underdiagnosis. Therefore, a strong index of suspicion is needed. The presence of intrusions in the neuropsychological examination supports the diagnosis. Damage in frontotemporal white matter tracts, particularly in the uncinate fasciculus, may be a feature of non-alcoholic Korsakoff syndrome in psychiatric patients.

TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition.

PubMed

Blank, Martina; Petry, Fernanda S; Lichtenfels, Martina; Valiati, Fernanda E; Dornelles, Arethuza S; Roesler, Rafael

2016-03-01

Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.

Working, declarative and procedural memory in specific language impairment

PubMed Central

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

2012-01-01

According to the Procedural Deficit Hypothesis (PDH), abnormalities of brain structures underlying procedural memory largely explain the language deficits in children with specific language impairment (SLI). These abnormalities are posited to result in core deficits of procedural memory, which in turn explain the grammar problems in the disorder. The abnormalities are also likely to lead to problems with other, non-procedural functions, such as working memory, that rely at least partly on the affected brain structures. In contrast, declarative memory is expected to remain largely intact, and should play an important compensatory role for grammar. These claims were tested by examining measures of working, declarative and procedural memory in 51 children with SLI and 51 matched typically-developing (TD) children (mean age 10). Working memory was assessed with the Working Memory Test Battery for Children, declarative memory with the Children’s Memory Scale, and procedural memory with a visuo-spatial Serial Reaction Time task. As compared to the TD children, the children with SLI were impaired at procedural memory, even when holding working memory constant. In contrast, they were spared at declarative memory for visual information, and at declarative memory in the verbal domain after controlling for working memory and language. Visuo-spatial short-term memory was intact, whereas verbal working memory was impaired, even when language deficits were held constant. Correlation analyses showed neither visuo-spatial nor verbal working memory was associated with either lexical or grammatical abilities in either the SLI or TD children. Declarative memory correlated with lexical abilities in both groups of children. Finally, grammatical abilities were associated with procedural memory in the TD children, but with declarative memory in the children with SLI. These findings replicate and extend previous studies of working, declarative and procedural memory in SLI. Overall, we suggest that the evidence largely supports the predictions of the PDH. PMID:21774923

Personal memory function in mild cognitive impairment and subjective memory complaints: results from the Australian Imaging, Biomarkers, and Lifestyle (AIBL) Study of Ageing.

PubMed

Buckley, Rachel F; Saling, Michael M; Irish, Muireann; Ames, David; Rowe, Christopher C; Lautenschlager, Nicola T; Maruff, Paul; Macaulay, S Lance; Martins, Ralph N; Masters, Colin L; Rainey-Smith, Stephanie R; Rembach, Alan; Savage, Greg; Szoeke, Cassandra; Ellis, Kathryn A

2014-01-01

Autobiographical memory (ABM) refers to the recollection of individual experiences, while personal semantic memory (PSM) refers to personally relevant, but shared, facts. Mild cognitive impairment (MCI) is routinely diagnosed with the aid of neuropsychological tests, which do not tap the ABM and PSM domains. We aimed to characterize the nature of ABM and PSM retrieval in cognitively healthy (HC) memory complainers, non-memory complainers, and MCI participants, and to investigate the relationship between neuropsychological tests and personal memory. Gender- and education-matched participants (HC = 80 and MCI = 43) completed the Episodic ABM Interview (EAMI) and a battery of neuropsychological tests. ABM and PSM did not differ between complainers and non-complainers, but were poorer in MCI participants, after accounting for age and depressive symptomatology. There were significant associations between personal memory and objective memory measures were found in MCI participants, but standard cognitive measures were more sensitive to MCI. Personal memory was compromised in MCI, reflected by lower scores on the EAMI. Memory complaining, assessed by current approaches, did not have an impact on personal memory. Standard subjective questionnaires might not reflect the sorts of concerns that bring individuals to clinical attention. Understanding personal memory function in the elderly may aid in the development of a more sensitive measure of subjective memory concerns.

Age–dependent regulation of synaptic connections by dopamine D2 receptors

PubMed Central

Jia, Jie–Min; Zhao, Jun; Hu, Zhonghua; Lindberg, Daniel; Li, Zheng

2013-01-01

Dopamine D2 receptors (D2R) are G protein–coupled receptors that modulate synaptic transmission and play an important role in various brain functions including affect learning and working memory. Abnormal D2R signaling has been implicated in psychiatric disorders such as schizophrenia. Here we report a new function of D2R in dendritic spine morphogenesis. Activation of D2R reduces spine number via GluN2B– and cAMP–dependent mechanisms in mice. Notably, this regulation takes place only during adolescence. During this period, D2R overactivation caused by mutations in the schizophrenia–risk–gene dysbindin leads to spine deficiency, dysconnectivity within the entorhinal–hippocampal circuit and impairment of spatial working memory. Notably, these defects can be ameliorated by D2R blockers administered during adolescence. These findings uncover a novel age–dependent function of D2R in spine development, provide evidence that D2R dysfunction during adolescence impairs neuronal circuits and working memory, and suggest that adolescent interventions of aberrant D2R activity protect against cognitive impairment. PMID:24121738

Memory for music in Alzheimer's disease: unforgettable?

PubMed

Baird, Amee; Samson, Séverine

2009-03-01

The notion that memory for music can be preserved in patients with Alzheimer's Disease (AD) has been raised by a number of case studies. In this paper, we review the current research examining musical memory in patients with AD. In keeping with models of memory described in the non-musical domain, we propose that various forms of musical memory exist, and may be differentially impaired in AD, reflecting the pattern of neuropathological changes associated with the condition. Our synthesis of this literature reveals a dissociation between explicit and implicit musical memory functions. Implicit, specifically procedural musical memory, or the ability to play a musical instrument, can be spared in musicians with AD. In contrast, explicit musical memory, or the recognition of familiar or unfamiliar melodies, is typically impaired. Thus, the notion that music is unforgettable in AD is not wholly supported. Rather, it appears that the ability to play a musical instrument may be unforgettable in some musicians with AD.

Genes and signaling pathways involved in memory enhancement in mutant mice

PubMed Central

2014-01-01

Mutant mice have been used successfully as a tool for investigating the mechanisms of memory at multiple levels, from genes to behavior. In most cases, manipulating a gene expressed in the brain impairs cognitive functions such as memory and their underlying cellular mechanisms, including synaptic plasticity. However, a remarkable number of mutations have been shown to enhance memory in mice. Understanding how to improve a system provides valuable insights into how the system works under normal conditions, because this involves understanding what the crucial components are. Therefore, more can be learned about the basic mechanisms of memory by studying mutant mice with enhanced memory. This review will summarize the genes and signaling pathways that are altered in the mutants with enhanced memory, as well as their roles in synaptic plasticity. Finally, I will discuss how knowledge of memory-enhancing mechanisms could be used to develop treatments for cognitive disorders associated with impaired plasticity. PMID:24894914

Cognitive and subjective dose-response effects of acute oral Delta 9-tetrahydrocannabinol (THC) in infrequent cannabis users.

PubMed

Curran, H Valerie; Brignell, Catherine; Fletcher, Sally; Middleton, Paul; Henry, John

2002-10-01

Although some aspects of memory functions are known to be acutely impaired by delta(9)-tetrahydrocannabinol (delta(9)-THC; the main active constituent of marijuana), effects on other aspects of memory are not known and the time course of functional impairments is unclear. The present study aimed to detail the acute and residual cognitive effects of delta(9)-THC in infrequent cannabis users. A balanced, double-blind cross-over design was used to compare the effects of 7.5 mg and 15 mg delta(9)-THC with matched placebo in 15 male volunteers. Participants were assessed pre and 1, 2, 4, 6, 8, 24 and 48 h post-drug. Delta(9)-THC 15 mg impaired performance on two explicit memory tasks at the time of peak plasma concentration (2 h post-drug). At the same time point, performance on an implicit memory task was preserved intact. The higher dose of delta(9)-THC resulted in no learning whatsoever occurring over a three-trial selective reminding task at 2 h. Working memory was generally unaffected by delta(9)-THC. In several tasks, delta(9)-THC increased both speed and error rates, reflecting "riskier" speed-accuracy trade-offs. Subjective effects were also most marked at 2 h but often persisted longer, with participants rating themselves as "stoned" for 8 h. Participants experienced a strong drug effect, liked this effect and, until 4 h, wanted more oral delta(9)-THC. No effects of delta(9)-THC were found 24 or 48 h following ingestion indicating that the residual effects of oral delta(9)-THC are minimal. These data demonstrate that oral delta(9)-THC impairs episodic memory and learning in a dose-dependent manner whilst sparing perceptual priming and working memory.

The acute effects of cannabinoids on memory in humans: a review.

PubMed

Ranganathan, Mohini; D'Souza, Deepak Cyril

2006-11-01

Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors' function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects. The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings. Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels. This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.

Testosterone Treatment and Cognitive Function in Older Men With Low Testosterone and Age-Associated Memory Impairment.

PubMed

Resnick, Susan M; Matsumoto, Alvin M; Stephens-Shields, Alisa J; Ellenberg, Susan S; Gill, Thomas M; Shumaker, Sally A; Pleasants, Debbie D; Barrett-Connor, Elizabeth; Bhasin, Shalender; Cauley, Jane A; Cella, David; Crandall, Jill P; Cunningham, Glenn R; Ensrud, Kristine E; Farrar, John T; Lewis, Cora E; Molitch, Mark E; Pahor, Marco; Swerdloff, Ronald S; Cifelli, Denise; Anton, Stephen; Basaria, Shehzad; Diem, Susan J; Wang, Christina; Hou, Xiaoling; Snyder, Peter J

2017-02-21

Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. To determine if testosterone treatment compared with placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to -26), executive function (Trail-Making Test B minus A; range, -290 to 290), and spatial ability (Card Rotation Test; score range, -80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. Among the 493 men with AAMI (mean age, 72.3 years [SD, 5.8]; mean baseline testosterone, 234 ng/dL [SD, 65.1]), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, -0.07 [95% CI, -0.92 to 0.79]; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (-0.28 [95% CI, -0.76 to 0.19]; P = .24), executive function (-5.51 [95% CI, -12.91 to 1.88]; P = .14), or spatial ability (-0.12 [95% CI, -1.89 to 1.65]; P = .89). Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions. clinicaltrials.gov Identifier: NCT00799617.

Do organizational strategies mediate nonverbal memory impairment in drug-naïve patients with obsessive-compulsive disorder?

PubMed

Shin, Na Young; Kang, Do-Hyung; Choi, Jung-Seok; Jung, Myung Hun; Jang, Joon Hwan; Kwon, Jun Soo

2010-07-01

The present study aimed to examine nonverbal memory and organizational skill functions in psychotropic-naïve patients with OCD. Forty-one drug-naïve, 41 medicated OCD patients and 41 healthy controls, all of whom were matched for gender, age, education and intelligence, were included in the study. The Rey-Osterrieth Complex Figure Test (RCFT) was administered to evaluate nonverbal memory ability and organizational skill. OCD patients demonstrated impaired nonverbal memory irrespective of medication status (F = 6.54, p < .01, eta(2)p = .098 for immediate recall; F = 7.76, p < .01, eta(2)p = .114 for delayed recall). Medicated patients showed deficits in organizational strategies (eta(2)p = .079), which mediated nonverbal memory impairment (Z = -2.20, p = .027). The difference of organizational skill between drug-naïve and control groups did not reach statistical significance (eta(2)p = .054) and the association between organization and nonverbal memory was weak in the drug-naïve sample (Z = -1.74, = .081). There was no significant difference between the patient groups in RCFT indices. Our findings suggest that the organizational strategies may not be an effective mediator of nonverbal memory impairment in OCD and indicate that the clinical characteristics may be important to be considered in future research. Further studies are needed to improve understanding of the nature of nonverbal memory dysfunction in OCD.

Intraindividual Cognitive Variability in Middle Age Predicts Cognitive Impairment 8-10 Years Later: Results from the Wisconsin Registry for Alzheimer's Prevention.

PubMed

Koscik, Rebecca L; Berman, Sara E; Clark, Lindsay R; Mueller, Kimberly D; Okonkwo, Ozioma C; Gleason, Carey E; Hermann, Bruce P; Sager, Mark A; Johnson, Sterling C

2016-11-01

Intraindividual cognitive variability (IICV) has been shown to differentiate between groups with normal cognition, mild cognitive impairment (MCI), and dementia. This study examined whether baseline IICV predicted subsequent mild to moderate cognitive impairment in a cognitively normal baseline sample. Participants with 4 waves of cognitive assessment were drawn from the Wisconsin Registry for Alzheimer's Prevention (WRAP; n=684; 53.6(6.6) baseline age; 9.1(1.0) years follow-up; 70% female; 74.6% parental history of Alzheimer's disease). The primary outcome was Wave 4 cognitive status ("cognitively normal" vs. "impaired") determined by consensus conference; "impaired" included early MCI (n=109), clinical MCI (n=11), or dementia (n=1). Primary predictors included two IICV variables, each based on the standard deviation of a set of scores: "6 Factor IICV" and "4 Test IICV". Each IICV variable was tested in a series of logistic regression models to determine whether IICV predicted cognitive status. In exploratory analyses, distribution-based cutoffs incorporating memory, executive function, and IICV patterns were used to create and test an MCI risk variable. Results were similar for the IICV variables: higher IICV was associated with greater risk of subsequent impairment after covariate adjustment. After adjusting for memory and executive functioning scores contributing to IICV, IICV was not significant. The MCI risk variable also predicted risk of impairment. While IICV in middle-age predicts subsequent impairment, it is a weaker risk indicator than the memory and executive function scores contributing to its calculation. Exploratory analyses suggest potential to incorporate IICV patterns into risk assessment in clinical settings. (JINS, 2016, 22, 1016-1025).

ADRA2B genotype modulates effects of acute psychosocial stress on emotional memory retrieval in healthy young men.

PubMed

Li, Shijia; Weerda, Riklef; Guenzel, Friederike; Wolf, Oliver T; Thiel, Christiane M

2013-07-01

Previous studies have shown that acute psychosocial stress impairs retrieval of declarative memory with emotional material being especially sensitive to this effect. A functional deletion variant of the ADRA2B gene encoding the α2B-adrenergic receptor has been shown to increase emotional memory and neural activity in the amygdala. We investigated the effects of acute psychosocial stress and the ADRA2B allele on recognition memory for emotional and neutral faces. Fourty-two healthy, non-smoker male volunteers (30 deletion carriers, 12 noncarriers) were tested with a face recognition paradigm. During encoding they were presented with emotional and neutral faces. One hour later, participants underwent either a stress ("Trier Social Stress Test (TSST)") or a control procedure which was followed immediately by the retrieval session where subjects had to indicate whether the presented face was old or new. Stress increased salivary cortisol concentrations, blood pressure and pulse and impaired recognition memory for faces independent of emotional valence and genotype. Participants showed generally slower reaction times to emotional faces. Carriers of the ADRA2B functional deletion variant showed an impaired recognition and slower retrieval of neutral faces under stress. Further, they were significantly slower in retrieving fearful faces in the control condition. The findings indicate that a genetic variation of the noradrenergic system may preserve emotional faces from stress-induced memory impairments seen for neutral faces and heighten reactivity to emotional stimuli under control conditions. Copyright © 2013 Elsevier Inc. All rights reserved.

Subjective memory complaints, depressive symptoms and instrumental activities of daily living in mild cognitive impairment.

PubMed

Ryu, Seon Young; Lee, Sang Bong; Kim, Tae Woo; Lee, Taek Jun

2016-03-01

The diagnostic relevance of subjective memory complaints (SMCs) in mild cognitive impairment (MCI) remains to be unresolved. The aim of this study is to determine clinical correlates of SMCs in MCI. Furthermore, we examined whether there are the differences due to different aspects of complaints (i.e. prospective memory (PM) versus retrospective memory (RM) complaints). We examined the cross-sectional associations between SMCs and depressive symptoms, instrumental activities of daily living (IADL), and cognitive measures in sixty-six individuals with MCI (mean age: 65.7 ± 8.01 years). The criteria for MCI included SMCs, objective cognitive impairment, normal general cognitive function, largely intact functional activities, and absence of dementia. SMCs were assessed using the Prospective and Retrospective Memory Questionnaire (PRMQ), which contains 16 items describing everyday memory failure of both PM and RM. SMC severity (i.e. PRMQ total score) was associated with stronger depressive symptoms and worse IADL performance. SMCs were not related to cognitive measures. For PM and RM subscores, both depressive symptoms and IADL were related to the PRMQ-PM and -RM scores. The main contributors to these PM and RM scores were depressive symptoms and IADL impairment, respectively. This study suggests that SMCs are more associated with depressive symptoms and IADL problems than with cognitive performance in individuals with MCI. Furthermore, while PM and RM complaints are related to both depressive symptoms and IADL, the differences between these main contributors suggest that RM complaints based on IADL could be more associated with the organically driven pathological features of MCI.

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.

Effect of physical activity on memory function in older adults with mild Alzheimer's disease and mild cognitive impairment.

PubMed

Tanigawa, Takanori; Takechi, Hajime; Arai, Hidenori; Yamada, Minoru; Nishiguchi, Shu; Aoyama, Tomoki

2014-10-01

It is very important to maintain cognitive function in patients with mild cognitive disorder. The aim of the present study was to determine whether the amount of physical activity is associated with memory function in older adults with mild cognitive disorder. A total of 47 older adults with mild cognitive disorder were studied; 30 were diagnosed with mild Alzheimer's disease and 17 with mild cognitive impairment. The global cognitive function, memory function, physical performance and amount of physical activity were measured in these patients. We divided these patients according to their walking speed (<1 m/s or >1 m/s). A total of 26 elderly patients were classified as the slow walking group, whereas 21 were classified as the normal walking group. The normal walking group was younger and had significantly better scores than the slow walking group in physical performance. Stepwise multiple linear regression analysis showed that only the daily step counts were associated with the Scenery Picture Memory Test in patients of the slow walking group (β=0.471, P=0.031), but not other variables. No variable was significantly associated with the Scenery Picture Memory Test in the normal walking group. Memory function was strongly associated with the amount of physical activity in patients with mild cognitive disorder who showed slow walking speed. The results show that lower physical activities could be a risk factor for cognitive decline, and that cognitive function in the elderly whose motor function and cognitive function are declining can be improved by increasing the amount of physical activity. © 2014 Japan Geriatrics Society.

Altered Memory Circulating T Follicular Helper-B Cell Interaction in Early Acute HIV Infection

PubMed Central

Muir, Roshell; Metcalf, Talibah; Tardif, Virginie; Takata, Hiroshi; Phanuphak, Nittaya; Kroon, Eugene; Colby, Donn J.; Trichavaroj, Rapee; Valcour, Victor; Robb, Merlin L.; Michael, Nelson L.; Ananworanich, Jintanat; Trautmann, Lydie; Haddad, Elias K.

2016-01-01

The RV254 cohort of HIV-infected very early acute (4thG stage 1 and 2) (stage 1/2) and late acute (4thG stage 3) (stage 3) individuals was used to study T helper- B cell responses in acute HIV infection and the impact of early antiretroviral treatment (ART) on T and B cell function. To investigate this, the function of circulating T follicular helper cells (cTfh) from this cohort was examined, and cTfh and memory B cell populations were phenotyped. Impaired cTfh cell function was observed in individuals treated in stage 3 when compared to stage 1/2. The cTfh/B cell cocultures showed lower B cell survival and IgG secretion at stage 3 compared to stage 1/2. This coincided with lower IL-10 and increased RANTES and TNF-α suggesting a role for inflammation in altering cTfh and B cell responses. Elevated plasma viral load in stage 3 was found to correlate with decreased cTfh-mediated B cell IgG production indicating a role for increased viremia in cTfh impairment and dysfunctional humoral response. Phenotypic perturbations were also evident in the mature B cell compartment, most notably a decrease in resting memory B cells in stage 3 compared to stage 1/2, coinciding with higher viremia. Our coculture assay also suggested that intrinsic memory B cell defects could contribute to the impaired response despite at a lower level. Overall, cTfh-mediated B cell responses are significantly altered in stage 3 compared to stage 1/2, coinciding with increased inflammation and a reduction in memory B cells. These data suggest that early ART for acutely HIV infected individuals could prevent immune dysregulation while preserving cTfh function and B cell memory. PMID:27463374

Amygdala volume and verbal memory performance in schizophrenia and bipolar disorder.

PubMed

Killgore, William D S; Rosso, Isabelle M; Gruber, Staci A; Yurgelun-Todd, Deborah A

2009-03-01

To clarify the relationship between amygdala-hippocampal volume and cognitive performance in schizophrenia and bipolar disorder. Abnormalities of the amygdala-hippocampal complex and memory deficits have been reported in both schizophrenia and bipolar illness. We examined memory performance and its relationship to the volumes of the whole brain, lateral ventricles, hippocampus, and amygdala using morphometric magnetic resonance imaging in 19 patients with schizophrenia, 11 bipolar patients, and 20 healthy controls. Schizophrenia patients performed more poorly than bipolar patients and controls on indices of memory functioning, whereas patients with bipolar disorder showed milder impairments relative to controls. The schizophrenia group showed reduced total cerebral volume and enlarged ventricles relative to controls, but no group differences were found for amygdala or hippocampal volume. Left amygdala volume was predictive of memory performance in both groups, correlating positively with better immediate and delayed verbal memory for bipolar patients and negatively with immediate and delayed verbal recall for schizophrenia patients. Amygdala volume was unrelated to memory performance in healthy subjects. Schizophrenia and bipolar disorder both seem to be associated with anomalous and differential limbic volume-function relationships, such that the amygdala may facilitate hippocampal-dependent memory processes in bipolar disorder but impair these same processes in schizophrenia.

An Evaluation of Deficits in Semantic Cuing, Proactive and Retroactive Interference as Early Features of Alzheimer’s disease

PubMed Central

Crocco, Elizabeth; Curiel, Rosie E.; Acevedo, Amarilis; Czaja, Sara J.; Loewenstein, David A.

2015-01-01

OBJECTIVE To determine the degree to which susceptibility to different types of semantic interference may reflect the earliest manifestations of early Alzheimer disease (AD) beyond the effects of global memory impairment. METHODS Normal elderly (NE) subjects (n= 47), subjects with amnestic mild cognitive impairment (aMCI: n=34) and 40 subjects with probable AD were evaluated using a unique cued recall paradigm that allowed for an evaluation of both proactive and retroactive interference effects while controlling for global memory impairment (LASSI-L procedure). RESULTS Controlling for overall memory impairment, aMCI subjects had much greater proactive and retroactive interference effects than NE subjects. LASSI-L indices of learning using cued recall evidenced high levels of sensitivity and specificity with an overall correct classification rate of 90%. These provided better discrimination than traditional neuropsychological measures of memory function. CONCLUSION The LASSI-L paradigm is unique and unlike other assessments of memory in that items presented for cued recall are explicitly presented, and semantic interference and cuing effects can be assessed while controlling for initial level of memory impairment. This represents a powerful procedure allowing the participant to serve as his or her own control. The high levels of discrimination between subjects with aMCI and normal cognition that exceeded traditional neuropsychological measures makes the LASSI-L worthy of further research in the detection of early AD. PMID:23768680

Source Memory in Korsakoff Syndrome: Disentangling the Mechanisms of Temporal Confusion.

PubMed

Brion, Mélanie; de Timary, Philippe; Pitel, Anne-Lise; Maurage, Pierre

2017-03-01

Korsakoff syndrome (KS), most frequently resulting from alcohol dependence (ALC), is characterized by severe anterograde amnesia. It has been suggested that these deficits may extend to other memory components, and notably source memory deficits involved in the disorientation and temporal confusion frequently observed in KS. However, the extent of this source memory impairment in KS and its usefulness for the differential diagnosis between ALC and KS remain unexplored. Nineteen patients with KS were compared with 19 alcohol-dependent individuals and 19 controls in a source memory test exploring temporal context confusions ("continuous recognition task"). Episodic memory and psychopathological comorbidities were controlled for. While no source memory deficit was observed in ALC, KS was associated with a significant presence of temporal context confusion, even when the influence of comorbidities was taken into account. This source memory impairment did not appear to be related to performances on episodic memory or executive functions. Patients with KS displayed source memory deficits, as indexed by temporal context confusions. The absence of a relationship with episodic memory performances seems to indicate that source memory impairment is not a mere by-product of amnesia. As ALC was associated with preserved source memory, the presence of temporal context confusion may serve as a complementary tool for the differential diagnosis between ALC and KS. Copyright © 2017 by the Research Society on Alcoholism.

Caffeine Reverts Memory But Not Mood Impairment in a Depression-Prone Mouse Strain with Up-Regulated Adenosine A2A Receptor in Hippocampal Glutamate Synapses.

PubMed

Machado, Nuno J; Simões, Ana Patrícia; Silva, Henrique B; Ardais, Ana Paula; Kaster, Manuella P; Garção, Pedro; Rodrigues, Diana I; Pochmann, Daniela; Santos, Ana Isabel; Araújo, Inês M; Porciúncula, Lisiane O; Tomé, Ângelo R; Köfalvi, Attila; Vaugeois, Jean-Marie; Agostinho, Paula; El Yacoubi, Malika; Cunha, Rodrigo A; Gomes, Catarina A

2017-03-01

Caffeine prophylactically prevents mood and memory impairments through adenosine A 2A receptor (A 2A R) antagonism. A 2A R antagonists also therapeutically revert mood and memory impairments, but it is not known if caffeine is also therapeutically or only prophylactically effective. Since depression is accompanied by mood and memory alterations, we now explored if chronic (4 weeks) caffeine consumption (0.3 g/L) reverts mood and memory impairment in helpless mice (HM, 12 weeks old), a bred-based model of depression. HM displayed higher immobility in the tail suspension and forced swimming tests, greater anxiety in the elevated plus maze, and poorer memory performance (modified Y-maze and object recognition). HM also had reduced density of synaptic (synaptophysin, SNAP-25), namely, glutamatergic (vGluT1; -22 ± 7 %) and GABAergic (vGAT; -23 ± 8 %) markers in the hippocampus. HM displayed higher A 2A R density (72 ± 6 %) in hippocampal synapses, an enhanced facilitation of hippocampal glutamate release by the A 2A R agonist, CGS21680 (30 nM), and a larger LTP amplitude (54 ± 8 % vs. 21 ± 5 % in controls) that was restored to control levels (30 ± 10 %) by the A 2A R antagonist, SCH58261 (50 nM). Notably, caffeine intake reverted memory deficits and reverted the loss of hippocampal synaptic markers but did not affect helpless or anxiety behavior. These results reinforce the validity of HM as an animal model of depression by showing that they also display reference memory deficits. Furthermore, caffeine intake selectively reverted memory but not mood deficits displayed by HM, which are associated with an increased density and functional impact of hippocampal A 2A R controlling synaptic glutamatergic function.

Sulforaphane alleviates scopolamine-induced memory impairment in mice.

PubMed

Lee, Siyoung; Kim, Jisung; Seo, Sang Gwon; Choi, Bo-Ryoung; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

2014-07-01

Sulforaphane, an organosulfur compound present in cruciferous vegetables, has been shown to exert neuroprotective effects in experimental in vitro and in vivo models of neurodegeneration. To determine whether sulforaphane can preserve cognitive function, we examined its effects on scopolamine-induced memory impairment in mice using the Morris water maze test. Sulforaphane (10 or 50mg/kg) was administered to C57BL/6 mice by oral gavage for 14 days (days 1-14), and memory impairment was induced by intraperitoneal injection of scopolamine (1mg/kg) for 7 days (days 8-14). Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity in the hippocampus and frontal cortex, as indicated by a decreased acetylcholine (ACh) level and an increased acetylcholinesterase (AChE) activity. Sulforaphane significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex. These effects of sulforaphane on cholinergic system reactivity were confirmed in vitro. Sulforaphane (10 or 20μM) increased the ACh level, decreased the AChE activity, and increased ChAT expression in scopolamine-treated primary cortical neurons. These observations suggest that sulforaphane might exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment. Copyright © 2014. Published by Elsevier Ltd.

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.

Propofol ameliorates electroconvulsive shock-induced learning and memory impairment by regulation of synaptic metaplasticity via autophosphorylation of CaMKIIa at Thr 305 in stressed rats.

PubMed

Ren, Li; Zhang, Fan; Min, Su; Hao, Xuechao; Qin, Peipei; Zhu, Xianlin

2016-06-30

Electroconvulsive therapy (ECT) is an effective treatment for depression, but it can induce learning and memory impairment. Our previous study found propofol (γ-aminobutyric acid (GABA) receptor agonist) could ameliorate electroconvulsive shock (ECS, an analog of ECT to animals)-induced cognitive impairment, however, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of propofol on metaplasticity and autophosphorylation of CaMKIIa in stressed rats receiving ECS. Depressive-like behavior and learning and memory function were assessed by sucrose preference test and Morris water test respectively. LTP were tested by electrophysiological experiment, the expression of CaMKIIa, p-T305-CaMKII in hippocampus and CaMKIIα in hippocampal PSD fraction were evaluated by western blot. Results suggested ECS raised the baseline fEPSP and impaired the subsequent LTP, increased the expression of p-T305-CaMKII and decreased the expression of CaMKIIα in hippocampal PSD fraction, leading to cognitive dysfunction in stressed rats. Propofol could down-regulate the baseline fEPSP and reversed the impairment of LTP partly, decreased the expression of p-T305-CaMKII and increased the expression of CaMKIIα in hippocampal PSD fraction and alleviated ECS-induced learning and memory impairment. In conclusion, propofol ameliorates ECS-induced learning and memory impairment, possibly by regulation of synaptic metaplasticity via p-T305-CaMKII. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Clinical characteristics and brain PET findings in 3 cases of dissociative amnesia: disproportionate retrograde deficit and posterior middle temporal gyrus hypometabolism.

PubMed

Thomas-Antérion, C; Dubas, F; Decousus, M; Jeanguillaume, C; Guedj, E

2014-10-01

Precipitated by psychological stress, dissociative amnesia occurs in the absence of identifiable brain damage. Its clinical characteristics and functional neural basis are still a matter of controversy. In the present paper, we report 3 cases of retrograde autobiographical amnesia, characterized by an acute onset concomitant with emotional/neurological precipitants. We present 2 cases of dissociative amnesia with fugue (cases 1 and 2), and one case of focal dissociative amnesia after a minor head trauma (case 3). The individual case histories and neuropsychological characteristics are reported, as well as the whole-brain voxel-based 18FDG-PET metabolic findings obtained at group-level in comparison to 15 healthy subjects. All patients suffered from autobiographical memory loss, in the absence of structural lesion. They had no significant impairment of anterograde memory or of executive function. Impairment of autobiographical memory was complete for two of the three patients, with loss of personal identity (cases 1 and 2). A clinical recovery was found for the two patients in whom follow-up was available (cases 2 and 3). Voxel-based group analysis highlighted a metabolic impairment of the right posterior middle temporal gyrus. 18FDG-PET was repeated in case 3, and showed a complete functional brain recovery. The situation of dissociative amnesia with disproportionate retrograde amnesia is clinically heterogeneous between individuals. Our findings may suggest that impairment of high-level integration of visual and/or emotional information processing involving dysfunction of the right posterior middle temporal gyrus could reduce triggering of multi-modal visual memory traces, thus impeding reactivation of aversive memories. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Corpus callosal atrophy and associations with cognitive impairment in Parkinson disease

PubMed Central

Bledsoe, Ian O.; Merkitch, Doug; Dinh, Vy; Bernard, Bryan; Stebbins, Glenn T.

2017-01-01

Objective: To investigate atrophy of the corpus callosum on MRI in Parkinson disease (PD) and its relationship to cognitive impairment. Methods: One hundred patients with PD and 24 healthy control participants underwent clinical and neuropsychological evaluations and structural MRI brain scans. Participants with PD were classified as cognitively normal (PD-NC; n = 28), having mild cognitive impairment (PD-MCI; n = 47), or having dementia (PDD; n = 25) by Movement Disorder Society criteria. Cognitive domain (attention/working memory, executive function, memory, language, visuospatial function) z scores were calculated. With the use of FreeSurfer image processing, volumes for total corpus callosum and its subsections (anterior, midanterior, central, midposterior, posterior) were computed and normalized by total intracranial volume. Callosal volumes were compared between participants with PD and controls and among PD cognitive groups, covarying for age, sex, and PD duration and with multiple comparison corrections. Regression analyses were performed to evaluate relationships between callosal volumes and performance in cognitive domains. Results: Participants with PD had reduced corpus callosum volumes in midanterior and central regions compared to healthy controls. Participants with PDD demonstrated decreased callosal volumes involving multiple subsections spanning anterior to posterior compared to participants with PD-MCI and PD-NC. Regional callosal atrophy predicted cognitive domain performance such that central volumes were associated with the attention/working memory domain; midposterior volumes with executive function, language, and memory domains; and posterior volumes with memory and visuospatial domains. Conclusions: Notable volume loss occurs in the corpus callosum in PD, with specific neuroanatomic distributions in PDD and relationships of regional atrophy to different cognitive domains. Callosal volume loss may contribute to clinical manifestations of PD cognitive impairment. PMID:28235816

Subjective cognitive function in hoarding disorder.

PubMed

Tolin, David F; Hallion, Lauren S; Wootton, Bethany M; Levy, Hannah C; Billingsley, Amber L; Das, Akanksha; Katz, Benjamin W; Stevens, Michael C

2018-07-01

The aim of the present study was to examine subjective cognitive impairment among adult patients with hoarding disorder (HD). Eighty-three patients with HD and 46 age- and gender-matched healthy control (HC) participants received a diagnostic interview and completed measures of subjective cognitive functioning and motivations for saving behavior, as well as measures of hoarding severity, depression, anxiety, stress, and obsessive-compulsive disorder (OCD) symptoms. The HD group reported more impairment than did the HC group in domains of memory, distractibility, blunders, memory for names, and inattention. These differences generally remained significant when controlling for comorbid symptoms. In the HD group, the degree of cognitive impairment was significantly correlated with severity of saving and acquiring behaviors, although results were attenuated when controlling for comorbid symptoms (overall HD severity, but not saving behavior specifically, remained significantly correlated with cognitive impairment). Subjective cognitive impairment was further associated with a desire to save possessions in order to avoid forgetting, and these results remained significant when controlling for comorbid symptoms. These results comport with current behavioral models of HD that emphasize decision-making deficits, as well as clinician observations suggestive of impaired cognitive function, and complement a growing body of neuropsychological testing studies. Copyright © 2018. Published by Elsevier B.V.

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory.

PubMed

Tsai, Sheng-Feng; Ku, Nai-Wen; Wang, Tzu-Feng; Yang, Yan-Hsiang; Shih, Yao-Hsiang; Wu, Shih-Ying; Lee, Chu-Wan; Yu, Megan; Yang, Ting-Ting; Kuo, Yu-Min

2018-05-07

Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline. © 2018 S. Karger AG, Basel.

Executive functioning in chronic alcoholism and Korsakoff syndrome.

PubMed

Maharasingam, Malini; Macniven, Jamie A B; Mason, Oliver J

2013-01-01

Korsakoff syndrome (KS) is characterized by dense anterograde and retrograde amnesia. There is often a temporal gradient to the retrograde amnesia, with earlier memories more readily recalled than recent memories. Executive functioning has also been found to be impaired in KS. However, research comparing executive functioning between chronic alcoholics (AL) and patients with KS has been relatively sparse to date. In a group comparison design, executive functioning in 15 KS patients and 16 chronic alcoholic patients was assessed using the Behavioural Assessment of the Dysexecutive Syndrome test (BADS) and other secondary measures. The KS group was found to be significantly more impaired than the AL group on overall performance on the BADS (p < .05). Korsakoff patients are significantly more impaired in executive functioning than non-Korsakoff chronic alcoholics. We thank the participants of the study and also acknowledge the support of the University of Nottingham, particularly Nadina Lincoln, and the North East London NHS Foundation Trust. We are also very grateful to the anonymous reviewers of earlier drafts of this manuscript for their invaluable comments.

Human Behaviour and Development under High-Altitude Conditions

ERIC Educational Resources Information Center

Virues-Ortega, Javier; Garrido, Eduardo; Javierre, Casimiro; Kloezeman, Karen C.

2006-01-01

Although we are far from a universally accepted pattern of impaired function at altitude, there is evidence indicating motor, perceptual, memory and behavioural deficits in adults. Even relatively low altitudes (2500 m) may delay reaction time, and impair motor function. Extreme altitude exposure (greater than 5000 m) may result in more pronounced…

A Comprehensive Investigation of Memory Impairment in Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder

ERIC Educational Resources Information Center

Rhodes, Sinead M.; Park, Joanne; Seth, Sarah; Coghill, David R.

2012-01-01

Background: We conducted a comprehensive and systematic assessment of memory functioning in drug-naive boys with attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD). Methods: Boys performed verbal and spatial working memory (WM) component (storage and central executive) and verbal and spatial storage load tasks,…

Working Memory Training for Adolescents with Cannabis Use Disorders: A Randomized Controlled Trial

ERIC Educational Resources Information Center

Sweeney, Mary M.; Rass, Olga; DiClemente, Cara; Schacht, Rebecca L.; Vo, Hoa T.; Fishman, Marc J.; Leoutsakos, Jeannie-Marie S.; Mintzer, Miriam Z.; Johnson, Matthew W.

2018-01-01

Adolescent cannabis use is associated with working memory impairment. The present randomized controlled trial assigned adolescents ages 14 to 21 enrolled in cannabis use treatment to receive either working memory training (experimental group) or a control training (control group) as an adjunctive treatment. Cognitive function, drug use, and other…

Defective synaptic transmission and structure in the dentate gyrus and selective fear memory impairment in the Rsk2 mutant mouse model of Coffin-Lowry syndrome.

PubMed

Morice, Elise; Farley, Séverine; Poirier, Roseline; Dallerac, Glenn; Chagneau, Carine; Pannetier, Solange; Hanauer, André; Davis, Sabrina; Vaillend, Cyrille; Laroche, Serge

2013-10-01

The Coffin-Lowry syndrome (CLS) is a syndromic form of intellectual disability caused by loss-of-function of the RSK2 serine/threonine kinase encoded by the rsk2 gene. Rsk2 knockout mice, a murine model of CLS, exhibit spatial learning and memory impairments, yet the underlying neural mechanisms are unknown. In the current study, we examined the performance of Rsk2 knockout mice in cued, trace and contextual fear memory paradigms and identified selective deficits in the consolidation and reconsolidation of hippocampal-dependent fear memories as task difficulty and hippocampal demand increase. Electrophysiological, biochemical and electron microscopy analyses were carried out in the dentate gyrus of the hippocampus to explore potential alterations in neuronal functions and structure. In vivo and in vitro electrophysiology revealed impaired synaptic transmission, decreased network excitability and reduced AMPA and NMDA conductance in Rsk2 knockout mice. In the absence of RSK2, standard measures of short-term and long-term potentiation (LTP) were normal, however LTP-induced CREB phosphorylation and expression of the transcription factors EGR1/ZIF268 were reduced and that of the scaffolding protein SHANK3 was blocked, indicating impaired activity-dependent gene regulation. At the structural level, the density of perforated and non-perforated synapses and of multiple spine boutons was not altered, however, a clear enlargement of spine neck width and post-synaptic densities indicates altered synapse ultrastructure. These findings show that RSK2 loss-of-function is associated in the dentate gyrus with multi-level alterations that encompass modifications of glutamate receptor channel properties, synaptic transmission, plasticity-associated gene expression and spine morphology, providing novel insights into the mechanisms contributing to cognitive impairments in CLS. Copyright © 2013 Elsevier Inc. All rights reserved.

Neuronal Nitric Oxide Synthase and NADPH Oxidase Interact to Affect Cognitive, Affective, and Social Behaviors in Mice

PubMed Central

Walton, James C.; Selvakumar, Balakrishnan; Weil, Zachary M.; Snyder, Solomon H.; Nelson, Randy J.

2013-01-01

Both nitric oxide (NO) and reactive oxygen species (ROS) generated by nNOS and NADPH oxidase (NOX), respectively, in the brain have been implicated in an array of behaviors ranging from learning and memory to social interactions. Although recent work has elucidated how these separate redox pathways regulate neural function and behavior, the interaction of these two pathways in the regulation of neural function and behavior remains unspecified. Toward this end, the p47phox subunit of NOX, and nNOS were deleted to generate double knockout mice that were used to characterize the behavioral outcomes of concurrent impairment of the NO and ROS pathways in the brain. Mice were tested in a battery of behavioral tasks to evaluate learning and memory, as well as social, affective, and cognitive behaviors. p47phox deletion did not affect depressive-like behavior, whereas nNOS deletion abolished it. Both p47phox and nNOS deletion singly reduced anxiety-like behavior, increased general locomotor activity, impaired spatial learning and memory, and impaired preference for social novelty. Deletion of both genes concurrently had synergistic effects to elevate locomotor activity, impair spatial learning and memory, and disrupt prepulse inhibition of acoustic startle. Although preference for social novelty was impaired in single knockouts, double knockout mice displayed elevated levels of preference for social novelty above that of wild type littermates. These data demonstrate that, depending upon modality, deletion of p47phox and nNOS genes have dissimilar, similar, or additive effects. The current findings provide evidence that the NOX and nNOS redox signaling cascades interact in the brain to affect both cognitive function and social behavior. PMID:23948215

Neurogranin as a predictor of memory and executive function decline in MCI patients.

PubMed

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p < 0.0001). CSF Ng predicted both memory and executive function decline over time (β = -0.0313, p = 0.0068 and β = -0.0346, p = 0.0169, respectively) independently of age, sex, education, and APOE ε4 status. When the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Obstructive sleep apnea exaggerates cognitive dysfunction in stroke patients.

PubMed

Zhang, Yan; Wang, Wanhua; Cai, Sijie; Sheng, Qi; Pan, Shenggui; Shen, Fang; Tang, Qing; Liu, Yang

2017-05-01

Obstructive sleep apnea (OSA) is very common in stroke survivors. It potentially worsens the cognitive dysfunction and inhibits their functional recovery. However, whether OSA independently damages the cognitive function in stroke patients is unclear. A simple method for evaluating OSA-induced cognitive impairment is also missing. Forty-four stroke patients six weeks after onset and 24 non-stroke patients with snoring were recruited for the polysomnographic study of OSA and sleep architecture. Their cognitive status was evaluated with a validated Chinese version of Cambridge Prospective Memory Test. The relationship between memory deficits and respiratory, sleeping, and dementia-related clinical variables were analyzed with correlation and multiple linear regression tests. OSA significantly and independently damaged time- and event-based prospective memory in stroke patients, although it had less power than the stroke itself. The impairment of prospective memory was correlated with increased apnea-hypopnea index, decreased minimal and mean levels of peripheral oxygen saturation, and disrupted sleeping continuity (reduced sleep efficiency and increased microarousal index). The further regression analysis identified minimal levels of peripheral oxygen saturation and sleep efficiency to be the two most important predictors for the decreased time-based prospective memory in stroke patients. OSA independently contributes to the cognitive dysfunction in stroke patients, potentially through OSA-caused hypoxemia and sleeping discontinuity. The prospective memory test is a simple but sensitive method to detect OSA-induced cognitive impairment in stroke patients. Proper therapies of OSA might improve the cognitive function and increase the life quality of stroke patients. Copyright © 2017 Elsevier B.V. All rights reserved.

[Clinical Neuropsychology of Dementia with Lewy Bodies].

PubMed

Nagahama, Yasuhiro

2016-02-01

Dementia with Lewy bodies (DLB) shows lesser memory impairment and more severe visuospatial disability than Alzheimer disease (AD). Although deficits in both consolidation and retrieval underlie the memory impairment, retrieval deficit is predominant in DLB. Visuospatial dysfunctions in DLB are related to the impairments in both ventral and dorsal streams of higher visual information processing, and lower visual processing in V1/V2 may also be impaired. Attention and executive functions are more widely disturbed in DLB than in AD. Imitation of finger gestures is impaired more frequently in DLB than in other mild dementia, and provides additional information for diagnosis of mild dementia, especially for DLB. Pareidolia, which lies between hallucination and visual misperception, is found frequently in DLB, but its mechanism is still under investigation.

Fractionation of memory in medial temporal lobe amnesia.

PubMed

Bird, Chris M; Shallice, Tim; Cipolotti, Lisa

2007-03-25

We report a comprehensive investigation of the anterograde memory functions of two patients with memory impairments (RH and JC). RH had neuroradiological evidence of apparently selective right-sided hippocampal damage and an intact cognitive profile apart from selective memory impairments. JC, had neuroradiological evidence of bilateral hippocampal damage following anoxia due to cardiac arrest. He had anomic and "executive" difficulties in addition to a global amnesia, suggesting atrophy extending beyond hippocampal regions. Their performance is compared with that of a previously reported hippocampal amnesic patient who showed preserved recollection and familiarity for faces in the context of severe verbal and topographical memory impairment [VC; Cipolotti, L., Bird, C., Good, T., Macmanus, D., Rudge, P., & Shallice, T. (2006). Recollection and familiarity in dense hippocampal amnesia: A case study. Neuropsychologia, 44, 489-506.] The patients were administered experimental tests using verbal (words) and two types of non-verbal materials (faces and buildings). Receiver operating characteristic analyses were used to estimate the contribution of recollection and familiarity to recognition performance on the experimental tests. RH had preserved verbal recognition memory. Interestingly, her face recognition memory was also spared, whilst topographical recognition memory was impaired. JC was impaired for all types of verbal and non-verbal materials. In both patients, deficits in recollection were invariably associated with deficits in familiarity. JC's data demonstrate the need for a comprehensive cognitive investigation in patients with apparently selective hippocampal damage following anoxia. The data from RH suggest that the right hippocampus is necessary for recollection and familiarity for topographical materials, whilst the left hippocampus is sufficient to underpin these processes for at least some types of verbal materials. Face recognition memory may be adequately subserved by areas outside of the hippocampus.

Neurocognition in College-Aged Daily Marijuana Users

PubMed Central

Becker, Mary P.; Collins, Paul F.; Luciana, Monica

2014-01-01

Background Marijuana is the most commonly used illicit substance in the United States. Use, particularly when it occurs early, has been associated with cognitive impairments in executive functioning, learning, and memory. Methods This study comprehensively measured cognitive ability as well as comorbid psychopathology and substance use history to determine the neurocognitive profile associated with young adult marijuana use. College-aged marijuana users who initiated use prior to age 17 (n=35) were compared to demographically-matched controls (n=35). Results Marijuana users were high functioning, demonstrating comparable IQs to controls and relatively better processing speed. Marijuana users demonstrated relative cognitive impairments in verbal memory, spatial working memory, spatial planning, and motivated decision-making. Comorbid use of alcohol, which was heavier in marijuana users, was unexpectedly found to be associated with better performance in some of these areas. Conclusions This study provides additional evidence of neurocognitive impairment in the context of adolescent and young adult marijuana use. Findings are discussed in relation to marijuana’s effects on intrinsic motivation and discrete aspects of cognition. PMID:24620756

Memory evaluation in mild cognitive impairment using recall and recognition tests.

PubMed

Bennett, Ilana J; Golob, Edward J; Parker, Elizabeth S; Starr, Arnold

2006-11-01

Amnestic mild cognitive impairment (MCI) is a selective episodic memory deficit that often indicates early Alzheimer's disease. Episodic memory function in MCI is typically defined by deficits in free recall, but can also be tested using recognition procedures. To assess both recall and recognition in MCI, MCI (n = 21) and older comparison (n = 30) groups completed the USC-Repeatable Episodic Memory Test. Subjects memorized two verbally presented 15-item lists. One list was used for three free recall trials, immediately followed by yes/no recognition. The second list was used for three-alternative forced-choice recognition. Relative to the comparison group, MCI had significantly fewer hits and more false alarms in yes/no recognition, and were less accurate in forced-choice recognition. Signal detection analysis showed that group differences were not due to response bias. Discriminant function analysis showed that yes/no recognition was a better predictor of group membership than free recall or forced-choice measures. MCI subjects recalled fewer items than comparison subjects, with no group differences in repetitions, intrusions, serial position effects, or measures of recall strategy (subjective organization, recall consistency). Performance deficits on free recall and recognition in MCI suggest a combination of both tests may be useful for defining episodic memory impairment associated with MCI and early Alzheimer's disease.

Effects of cinnamic acid on memory deficits and brain oxidative stress in streptozotocin-induced diabetic mice

PubMed Central

Hemmati, Ali Asghar; Ahangarpour, Akram

2018-01-01

The present study aimed to evaluate the cinnamic acid effect on memory impairment, oxidative stress, and cholinergic dysfunction in streptozotocin (STZ)-induced diabetic model in mice. In this experimental study, 48 male Naval Medical Research Institute (NMRI) mice (30–35 g) were chosen and were randomly divided into six groups: control, cinnamic acid (20 mg/kg day, i.p. ), diabetic, and cinnamic acid-treated diabetic (10, 20 and 40 mg/kg day, i.p. ). Memory was impaired by administering an intraperitoneal STZ injection of 50 mg/kg. Cinnamic acid was injected for 40 days starting from the 21st day after confirming STZ-induced dementia to observe its therapeutic effect. Memory function was assessed using cross-arm maze, morris water maze and passive avoidance test. After the administration, biochemical parameters of oxidative stress and cholinergic function were estimated in the brain. Present data indicated that inducing STZ caused significant memory impairment, whereas administration of cinnamic acid caused significant and dose-dependent memory improvement. Assessment of brain homogenates indicated cholinergic dysfunction, increase in lipid peroxidation and reactive oxygen species (ROS) levels, and decrease in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the diabetic group compared to the control animals, whereas cinnamic acid administration ameliorated these indices in the diabetic mice. The present study demonstrated that cinnamic acid improves memory by reducing the oxidative stress and cholinergic dysfunction in the brain of diabetic mice. PMID:29719448

Effects of cinnamic acid on memory deficits and brain oxidative stress in streptozotocin-induced diabetic mice.

PubMed

Hemmati, Ali Asghar; Alboghobeish, Soheila; Ahangarpour, Akram

2018-05-01

The present study aimed to evaluate the cinnamic acid effect on memory impairment, oxidative stress, and cholinergic dysfunction in streptozotocin (STZ)-induced diabetic model in mice. In this experimental study, 48 male Naval Medical Research Institute (NMRI) mice (30-35 g) were chosen and were randomly divided into six groups: control, cinnamic acid (20 mg/kg day, i.p. ), diabetic, and cinnamic acid-treated diabetic (10, 20 and 40 mg/kg day, i.p. ). Memory was impaired by administering an intraperitoneal STZ injection of 50 mg/kg. Cinnamic acid was injected for 40 days starting from the 21st day after confirming STZ-induced dementia to observe its therapeutic effect. Memory function was assessed using cross-arm maze, morris water maze and passive avoidance test. After the administration, biochemical parameters of oxidative stress and cholinergic function were estimated in the brain. Present data indicated that inducing STZ caused significant memory impairment, whereas administration of cinnamic acid caused significant and dose-dependent memory improvement. Assessment of brain homogenates indicated cholinergic dysfunction, increase in lipid peroxidation and reactive oxygen species (ROS) levels, and decrease in glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities in the diabetic group compared to the control animals, whereas cinnamic acid administration ameliorated these indices in the diabetic mice. The present study demonstrated that cinnamic acid improves memory by reducing the oxidative stress and cholinergic dysfunction in the brain of diabetic mice.

Impaired decision making and delayed memory are related with anxiety and depressive symptoms in acromegaly.

PubMed

Crespo, Iris; Santos, Alicia; Valassi, Elena; Pires, Patricia; Webb, Susan M; Resmini, Eugenia

2015-12-01

Evaluation of cognitive function in acromegaly has revealed contradictory findings; some studies report normal cognition in patients with long-term cured acromegaly, while others show attention and memory deficits. Moreover, the presence of affective disorders in these patients is common. Our aim was to evaluate memory and decision making in acromegalic patients and explore their relationship with affective disorders like anxiety and depressive symptoms. Thirty-one patients with acromegaly (mean age 49.5 ± 8.5 years, 14 females and 17 males) and thirty-one healthy controls participated in this study. The Iowa Gambling Task (IGT), Rey Auditory Verbal Learning Test, State-Trait Anxiety Inventory, and Beck Depression Inventory-II (BDI-II) were used to evaluate decision making, verbal memory, anxiety, and depressive symptoms, respectively. Acromegalic patients showed impairments in delayed verbal memory (p < 0.05) and more anxiety and depressive symptoms (p < 0.05) than controls. In the IGT, acromegalic patients presented an altered decision-making strategy compared to controls, choosing a lower number of the safer cards (p < 0.05) and higher number of the riskier cards (p < 0.05). Moreover, multiple correlations between anxiety and depressive symptoms and performance in memory and decision making were found. Impaired delayed memory and decision making observed in acromegalic patients are related to anxiety and depressive symptoms. Providing emotional support to the patients could improve their cognitive function. A key clinical application of this research is the finding that depressive symptoms and anxiety are essentially modifiable factors.

The effects of GABAA and NMDA receptors in the shell-accumbens on spatial memory of METH-treated rats.

PubMed

Heysieattalab, Soomaayeh; Naghdi, Nasser; Zarrindast, Mohammad-Reza; Haghparast, Abbas; Mehr, Shahram Ejtemaei; Khoshbouei, Habibeh

2016-03-01

Methamphetamine (METH) is a highly addictive and neurotoxic psychostimulant. Its use in humans is often associated with neurocognitive impairment and deficits in hippocampal plasticity. Striatal dopamine system is one of the main targets of METH. The dopamine neurons in the striatum directly or indirectly regulate the GABA and glutamatergic signaling in this region and thus their outputs. This is consistent with previous reports showing modification of neuronal activity in the striatum modulates the expression of hippocampal LTP and hippocampal-dependent memory tasks such as Morris water maze (MWM). Therefore, reversing or preventing METH-induced synaptic modifications via pharmacological manipulations of the shell-nucleus accumbens (shell-NAc) may introduce a viable therapeutic target to attenuate the METH-induced memory deficits. This study is designed to investigate the role of intra-shell NAc manipulation of GABAA and NMDA receptors and their interaction with METH on memory performance in MWM task. Pharmacological manipulations were performed in rats received METH or saline. We found systemic saline plus intra-shell NAc infusions of muscimol dose-dependently impaired performance, while bicuculline had no effect. Surprisingly, the intra-NAc infusions of 0.005μg/rat muscimol that has no effect on memory performance (ineffective dose) prevented METH-induced memory impairment. In the contrary, the intra-NAc infusions of bicuculline (0.2μg/rat) increased METH-induced memory impairment. However, pre-training intra-NAc infusions of D-AP5 dose-dependently impaired performance, while NMDA had no effect in rats received systemic saline (control group). The intra-NAc infusions with an ineffective dose of NMDA (0.1μg/rat) increased METH-induced memory impairment. Furthermore, intra-NAc infusions of D-AP5 with an ineffective dose (0.1μg/rat) prevented METH-induced memory impairment. Our result is consistent with the interpretation that METH-mediated learning deficit might be due to modification of hippocampus-VTA loop and that augmentation of GABAA receptor function in the shell-NAc may provide a new therapeutic target for alleviating METH-induced memory deficits. Copyright © 2015. Published by Elsevier Inc.

Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study

PubMed Central

Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

2016-01-01

Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~ 30 dB(A); urban noise: building site noise, 68–78 dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68–78 dB(A)], 7–14 days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits. PMID:27017491

Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study.

PubMed

Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

2016-05-01

Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~30dB(A); urban noise: building site noise, 68-78dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68-78dB(A)], 7-14days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

[Use of nondeclarative and automatic memory processes in motor learning: how to mitigate the effects of aging].

PubMed

Chauvel, Guillaume; Maquestiaux, François; Didierjean, André; Joubert, Sven; Dieudonné, Bénédicte; Verny, Marc

2011-12-01

Does normal aging inexorably lead to diminished motor learning abilities? This article provides an overview of the literature on the question, with particular emphasis on the functional dissociation between two sets of memory processes: declarative, effortful processes, and non-declarative, automatic processes. There is abundant evidence suggesting that aging does impair learning when past memories of former actions are required (episodic memory) and recollected through controlled processing (working memory). However, other studies have shown that aging does not impair learning when motor actions are performed non verbally and automatically (tapping procedural memory). These findings led us to hypothesize that one can minimize the impact of aging on the ability to learn new motor actions by favouring procedural learning. Recent data validating this hypothesis are presented. Our findings underline the importance of developing new motor learning strategies, which "bypass" declarative, effortful memory processes.

Cortisol Excess and the Brain.

PubMed

Resmini, Eugenia; Santos, Alicia; Webb, Susan M

2016-01-01

Until the last decade, little was known about the effects of chronic hypercortisolism on the brain. In the last few years, new data have arisen thanks to advances in imaging techniques; therefore, it is now possible to investigate brain activity in vivo. Memory impairments are present in patients with Cushing's syndrome (CS) and are related to hippocampal damage; functional dysfunctions would precede structural abnormalities as detected by brain imaging. Earlier diagnosis and rapid normalization of hypercortisolism could stop the progression of hippocampal damage and memory impairments. Impairments of executive functions (including decision-making) and other functions such as visuoconstructive skills, language, motor functions and information processing speed are also present in CS patients. There is controversy concerning the reversibility of brain impairment. It seems that longer disease duration and older age are associated with less recovery of brain functioning. Conversely, earlier diagnosis and rapid normalization of hypercortisolism appear to stop progression of brain damage and functional impairments. Moreover, brain tissue functioning and neuroplasticity can be influenced by many factors. Currently available studies appear to be complementary, evaluating the same phenomenon from different points of view, but are often not directly comparable. Finally, CS patients have a high prevalence of psychopathology, such as depression and anxiety which do not completely revert after cure. Thus, psychological or psychiatric evaluation could be recommended in CS patients, so that treatment may be prescribed if required. © 2016 S. Karger AG, Basel.

Zinc supplementation in rats impairs hippocampal-dependent memory consolidation and dampens post-traumatic recollection of stressful event.

PubMed

Contestabile, Antonio; Peña-Altamira, Emiliano; Virgili, Marco; Monti, Barbara

2016-06-01

Zinc is a trace element important for synaptic plasticity, learning and memory. Zinc deficiency, both during pregnancy and after birth, impairs cognitive performance and, in addition to memory deficits, also results in alterations of attention, activity, neuropsychological behavior and motor development. The effects of zinc supplementation on cognition, particularly in the adult, are less clear. We demonstrate here in adult rats, that 4 week-long zinc supplementation given by drinking water, and approximately doubling normal daily intake, strongly impairs consolidation of hippocampal-dependent memory, tested through contextual fear conditioning and inhibitory avoidance. Furthermore, the same treatment started after memory consolidation of training for the same behavioral tests, substantially dampens the recall of the stressful event occurred 4 weeks before. A molecular correlate of the amnesic effect of zinc supplementation is represented by a dysregulated function of GSK-3ß in the hippocampus, a kinase that participates in memory processes. The possible relevance of these data for humans, in particular regarding post-traumatic stress disorders, is discussed in view of future investigation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Dissociations in cognitive memory: the syndrome of developmental amnesia.

PubMed

Vargha-Khadem, F; Gadian, D G; Mishkin, M

2001-09-29

The dearth of studies on amnesia in children has led to the assumption that when damage to the medial temporal lobe system occurs early in life, the compensatory capacity of the immature brain rescues memory functions. An alternative view is that such damage so interferes with the development of learning and memory that it results not in selective cognitive impairments but in general mental retardation. Data will be presented to counter both of these arguments. Results obtained from a series of 11 amnesic patients with a history of hypoxic ischaemic damage sustained perinatally or during childhood indicate that regardless of age at onset of hippocampal pathology, there is a pronounced dissociation between episodic memory, which is severely impaired, and semantic memory, which is relatively preserved. A second dissociation is characterized by markedly impaired recall and relatively spared recognition leading to a distinction between recollection-based versus familiarity-based judgements. These findings are discussed in terms of the locus and extent of neuropathology associated with hypoxic ischaemic damage, the neural basis of 'remembering' versus 'knowing', and a hierarchical model of cognitive memory.

Memory and selective attention in multiple sclerosis: cross-sectional computer-based assessment in a large outpatient sample.

PubMed

Adler, Georg; Lembach, Yvonne

2015-08-01

Cognitive impairments may have a severe impact on everyday functioning and quality of life of patients with multiple sclerosis (MS). However, there are some methodological problems in the assessment and only a few studies allow a representative estimate of the prevalence and severity of cognitive impairments in MS patients. We applied a computer-based method, the memory and attention test (MAT), in 531 outpatients with MS, who were assessed at nine neurological practices or specialized outpatient clinics. The findings were compared with those obtained in an age-, sex- and education-matched control group of 84 healthy subjects. Episodic short-term memory was substantially decreased in the MS patients. About 20% of them reached a score of only less than two standard deviations below the mean of the control group. The episodic short-term memory score was negatively correlated with the EDSS score. Minor but also significant impairments in the MS patients were found for verbal short-term memory, episodic working memory and selective attention. The computer-based MAT was found to be useful for a routine assessment of cognition in MS outpatients.

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.

Chronic stress impairs spatial memory and motivation for reward without disrupting motor ability and motivation to explore.

PubMed

Kleen, Jonathan K; Sitomer, Matthew T; Killeen, Peter R; Conrad, Cheryl D

2006-08-01

This study uses an operant, behavioral model to assess the daily changes in the decay rate of short-term memory, motivation, and motor ability in rats exposed to chronic restraint. Restraint decreased reward-related motivation by 50% without altering memory decay rate or motor ability. Moreover, chronic restraint impaired hippocampal-dependent spatial memory on the Y maze (4-hr delay) and produced CA3 dendritic retraction without altering hippocampal-independent maze navigation (1-min delay) or locomotion. Thus, mechanisms underlying motivation for food reward differ from those underlying Y maze exploration, and neurobiological substrates of spatial memory, such as the hippocampus, differ from those that underlie short-term memory. Chronic restraint produces functional, neuromorphological, and physiological alterations that parallel symptoms of depression in humans. Copyright 2006 APA, all rights reserved.

Comparison of odor identification among amnestic and non-amnestic mild cognitive impairment, subjective cognitive decline, and early Alzheimer's dementia.

PubMed

Park, Sung-Jin; Lee, Jee-Eun; Lee, Kwang-Soo; Kim, Joong-Seok

2018-03-01

Olfactory impairment might be an important clinical marker and predictor of Alzheimer's disease (AD). In the present study, we aimed to compare the degree of olfactory identification impairment in each mild cognitive impairment (MCI) subtype, subjective memory impairment, and early AD dementia and assessed the relationship between olfactory identification and cognitive performance. We consecutively included 50 patients with amnestic MCI, 28 patients with non-amnestic MCI, 20 patients with mild AD, and 17 patients with subjective memory impairment (SMI). All patients underwent clinical and neuropsychological assessments. A multiple choice olfactory identification cross-cultural smell identification test was also utilized. Controlling for age and gender, olfactory impairment was significantly more severe in patients with AD and amnestic MCI compared with the results from the non-amnestic MCI and SMI groups. Higher scores on MMSE, verbal and non-verbal memory, and frontal executive function tests were significantly related to olfactory identification ability. In conclusion, olfactory identification is impaired in amnestic MCI and AD. These findings are consistent with previous studies. In amnestic MCI patients, this dysfunction is considered to be caused by underlying AD pathology.

The effect of surgical and psychological stress on learning and memory function in aged C57BL/6 mice.

PubMed

Zhang, C; Li, C; Xu, Z; Zhao, S; Li, P; Cao, J; Mi, W

2016-04-21

Postoperative cognitive dysfunction (POCD) is an important complication following major surgery and general anesthesia in older patients. However, the etiology of POCD remains largely to be determined. It is unknown how surgical stress and psychological stress affect the postoperative learning and memory function in geriatric patients. We therefore established a pre-clinical model in aged C57BL/6 mice and aimed to investigate the effects of surgical stress and psychological stress on learning and memory function and the possible roles of the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway. The surgical stress was induced by abdominal surgery under local anesthesia, and the psychological stress was induced by a communication box. Cognitive functions and markers of the AKT/mTOR pathway were assessed at 1, 3 and 7 days following the stress. The impairments of learning and memory function existed for up to 7 days following surgical stress and surgical stress plus psychological stress, whereas the psychological stress did not affect the cognitive function alone or combined with surgical stress. Analysis of brain tissue revealed a significant involvement of the AKT/mTOR pathway in the impairment of cognition. These data suggested that surgical stress could induce cognitive impairment in aged mice and perioperative psychological stress is not a constitutive factor of POCD. The AKT/mTOR pathway is likely involved as one of the underlying mechanisms of the development of POCD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Late Enrichment Maintains Accurate Recent and Remote Spatial Memory Only in Aged Rats That Were Unimpaired When Middle Aged

ERIC Educational Resources Information Center

Fuchs, Fanny; Herbeaux, Karine; Aufrere, Noémie; Kelche, Christian; Mathis, Chantal; Barbelivien, Alexandra; Majchrzak, Monique

2016-01-01

Exposure of rodents to a stimulating environment has beneficial effects on some cognitive functions that are impaired during physiological aging, and especially spatial reference memory. The present study investigated whether environmental enrichment rescues these functions in already declining subjects and/or protects them from subsequent…

Implicit Perceptual-Motor Skill Learning in Mild Cognitive Impairment and Parkinson's Disease

PubMed Central

Gobel, Eric W.; Blomeke, Kelsey; Zadikoff, Cindy; Simuni, Tanya; Weintraub, Sandy; Reber, Paul J.

2015-01-01

Objective Implicit skill learning is hypothesized to depend on nondeclarative memory that operates independent of the medial temporal lobe (MTL) memory system and instead depends on cortico-striatal circuits between the basal ganglia and cortical areas supporting motor function and planning. Research with the Serial Reaction Time (SRT) task suggests that patients with memory-disorders due to MTL damage exhibit normal implicit sequence learning. However, reports of intact learning rely on observations of no group differences, leading to speculation whether implicit sequence learning is fully intact in these patients. Patients with Parkinson's Disease (PD) often exhibit impaired sequence learning, but this impairment is not universally observed. Method Implicit perceptual-motor sequence learning was examined using the Serial Interception Sequence Learning (SISL) task in patients with amnestic Mild Cognitive Impairment (MCI; n=11) and patients with PD (n=15). Sequence learning in SISL is resistant to explicit learning and individually adapted task difficulty controls for baseline performance differences. Results Patients with MCI exhibited robust sequence learning, equivalent to healthy older adults (n=20), supporting the hypothesis that the MTL does not contribute to learning in this task. In contrast, the majority of patients with PD exhibited no sequence-specific learning in spite of matched overall task performance. Two patients with PD exhibited performance indicative of an explicit compensatory strategy suggesting that impaired implicit learning may lead to greater reliance on explicit memory in some individuals. Conclusion The differences in learning between patient groups provides strong evidence in favor of implicit sequence learning depending solely on intact basal ganglia function with no contribution from the MTL memory system. PMID:23688213

Effects of tobacco smoke constituents, anabasine and anatabine, on memory and attention in female rats.

PubMed

Levin, Edward D; Hao, Ian; Burke, Dennis A; Cauley, Marty; Hall, Brandon J; Rezvani, Amir H

2014-10-01

Nicotine has been well characterized to improve memory and attention. Nicotine is the primary, but not only neuroactive compound in tobacco. Other tobacco constituents such as anabasine and anatabine also have agonist actions on nicotinic receptors. The current study investigated the effects of anabasine and anatabine on memory and attention. Adult female Sprague-Dawley rats were trained on a win-shift spatial working and reference memory task in the 16-arm radial maze or a visual signal detection operant task to test attention. Acute dose-effect functions of anabasine and anatabine over two orders of magnitude were evaluated for both tasks. In the radial-arm maze memory test, anabasine but not anatabine significantly reduced the memory impairment caused by the NMDA antagonist dizocilpine (MK-801). In the signal detection attentional task, anatabine but not anabasine significantly attenuated the attentional impairment caused by dizocilpine. These studies show that non-nicotine nicotinic agonists in tobacco, similar to nicotine, can significantly improve memory and attentional function. Both anabasine and anatabine produced cognitive improvement, but their effectiveness differed with regard to memory and attention. Follow-up studies with anabasine and anatabine are called for to determine their efficacy as therapeutics for memory and attentional dysfunction. © The Author(s) 2014.

Working memory, long-term memory, and medial temporal lobe function

PubMed Central

Jeneson, Annette; Squire, Larry R.

2012-01-01

Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance in patients with MTL lesions on tasks with short retention intervals, or no retention interval, and neuroimaging findings with similar tasks have been interpreted to mean that the MTL is sometimes needed for working memory and possibly even for visual perception itself. We present a reappraisal of this interpretation. Our main conclusion is that, if the material to be learned exceeds working memory capacity, if the material is difficult to rehearse, or if attention is diverted, performance depends on long-term memory even when the retention interval is brief. This fundamental notion is better captured by the terms subspan memory and supraspan memory than by the terms short-term memory and long-term memory. We propose methods for determining when performance on short-delay tasks must depend on long-term (supraspan) memory and suggest that MTL lesions impair performance only when immediate memory and working memory are insufficient to support performance. In neuroimaging studies, MTL activity during encoding is influenced by the memory load and correlates positively with long-term retention of the material that was presented. The most parsimonious and consistent interpretation of all the data is that subspan memoranda are supported by immediate memory and working memory and are independent of the MTL. PMID:22180053

Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity

PubMed Central

Brennaman, Leann H.; Kochlamazashvili, Gaga; Stoenica, Luminita; Nonneman, Randall J.; Moy, Sheryl S.; Schachner, Melitta; Dityatev, Alexander; Maness, Patricia F.

2011-01-01

The neural cell adhesion molecule, NCAM, is a pivotal regulator of neural development, with key roles in axonal and dendritic growth and synaptic plasticity. Alterations in NCAM expression or proteolytic cleavage have been linked to human neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer’s disease, and may contribute to cognitive dysfunction. We have generated mice overexpressing the NCAM extracellular (EC) proteolytic cleavage fragment which has been reported to be increased in schizophrenic versus normal brains. These mice show impaired GABAergic innervation and reduced number of apical dendritic spines on pyramidal neurons in the prefrontal cortex (PFC). Here, these NCAM-EC transgenic mice were subjected to behavioral tasks and electrophysiological measurements to determine the impact of structural abnormalities in the PFC on synaptic and cognitive functions. NCAM-EC mice exhibited impaired working memory in a delayed non-match-to-sample task, which requires PFC function, but showed no differences in anxiety, olfactory abilities, or sociability. Transgenic mice displayed impaired long- and short-term potentiation in the PFC but normal synaptic plasticity in the hippocampus, suggesting that the abnormal synaptic innervation in NCAM-EC mice impairs PFC plasticity and alters working memory. These findings may have implications for cognitive dysfunctions observed in neuropsychiatric disorders. PMID:21515372

Cognitive dysfunction in schizophrenia: convergence of gamma-aminobutyric acid and glutamate alterations.

PubMed

Lewis, David A; Moghaddam, Bita

2006-10-01

Impairments in certain cognitive functions mediated by the dorsolateral prefrontal cortex, such as working memory, are core features of schizophrenia. Convergent findings suggest that these disturbances are associated with alterations in markers of inhibitory gamma-aminobutyric acid and excitatory glutamate neurotransmission in the dorsolateral prefrontal cortex. Specifically, reduced gamma-aminobutyric acid synthesis is present in the subpopulation of gamma-aminobutyric acid neurons that express the calcium-binding protein parvalbumin. Despite presynaptic and postsynaptic compensatory responses, the resulting impaired inhibitory regulation of pyramidal neurons contributes to a reduction in the synchronized neuronal activity that is required for working memory function. Several lines of evidence suggest that these changes may be either secondary to or exacerbated by impaired signaling via the N-methyl-d-aspartate class of glutamate receptors. These findings suggest specific targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia.

Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice

PubMed Central

Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je

2016-01-01

Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer’s disease. PMID:27133261

Cognitive-Enhancing Effect of Dianthus superbus var. Longicalycinus on Scopolamine-Induced Memory Impairment in Mice.

PubMed

Weon, Jin Bae; Jung, Youn Sik; Ma, Choong Je

2016-05-01

Dianthus superbus (D. superbus) is a traditional crude drug used for the treatment of urethritis, carbuncles and carcinomas. The objective of this study was to confirm the cognitive enhancing effect of D. superbus in memory impairment induced mice and to elucidate the possible potential mechanism. Effect of D. superbus on scopolamine induced memory impairment on mice was evaluated using the Morris water maze and passive avoidance tests. We also investigated acetylcholinesterase (AChE) activity and brain-derived neurotropic factor (BDNF) expression in scopolamine-induced mice. HPLC-DAD analysis was performed to identify active compounds in D. superbus. The results revealed that D. superbus attenuated the learning and memory impairment induced by scopolamine. D. superbus also inhibited AChE levels in the hippocampi of the scopolamine-injected mice. Moreover, D. superbus increased BDNF expression in the hippocampus. Eight compounds were identified using HPLC-DAD analysis. The content of 4-hydroxyphenyl acetic acid was higher than contents of other compounds. These results indicated that D. superbus improved memory functioning accompanied by inhibition of AChE and upregulation of BDNF, suggesting that D. superbus may be a useful therapeutic agent for the prevention or treatment of Alzheimer's disease.

Declarative verbal memory impairments in middle-aged women who are caregivers of offspring with autism spectrum disorders: The role of negative affect and testosterone.

PubMed

Romero-Martínez, A; González-Bono, E; Salvador, A; Moya-Albiol, L

2016-01-01

Caring for offspring diagnosed with a chronic psychological disorder such as autism spectrum disorder (ASD) is used in research as a model of chronic stress. This chronic stress has been reported to have deleterious effects on caregivers' cognition, particularly in verbal declarative memory. Moreover, such cognitive decline may be mediated by testosterone (T) levels and negative affect, understood as depressive mood together with high anxiety and anger. This study aimed to compare declarative memory function in middle-aged women who were caregivers for individuals with ASD (n = 24; mean age = 45) and female controls (n = 22; mean age = 45), using a standardised memory test (Rey's Auditory Verbal Learning Test). It also sought to examine the role of care recipient characteristics, negative mood and T levels in memory impairments. ASD caregivers were highly sensitive to proactive interference and verbal forgetting. In addition, they had higher negative affect and T levels, both of which have been associated with poorer verbal memory performance. Moreover, the number of years of caregiving affected memory performance and negative affect, especially, in terms of anger feelings. On the other hand, T levels in caregivers had a curvilinear relationship with verbal memory performance; that is, increases in T were associated with improvements in verbal memory performance up to a certain point, but subsequently, memory performance decreased with increasing T. Chronic stress may produce disturbances in mood and hormonal levels, which in turn might increase the likelihood of developing declarative memory impairments although caregivers do not show a generalised decline in memory. These findings should be taken into account for understanding the impact of cognitive impairments on the ability to provide optimal caregiving.

Inhibition of local estrogen synthesis in the hippocampus impairs hippocampal memory consolidation in ovariectomized female mice

PubMed Central

Tuscher, Jennifer J.; Szinte, Julia S.; Starrett, Joseph R.; Krentzel, Amanda A.; Fortress, Ashley M.; Remage-Healey, Luke; Frick, Karyn M.

2016-01-01

The potent estrogen 17β-Estradiol (E2) plays a critical role in mediating hippocampal function, yet the precise mechanisms through which E2 enhances hippocampal memory remain unclear. In young adult female rodents, the beneficial effects of E2 on memory are generally attributed to ovarian-synthesized E2. However, E2 is also synthesized in the adult brain in numerous species, where it regulates synaptic plasticity and is synthesized in response to experiences such as exposure to females or conspecific song. Although de novo E2 synthesis has been demonstrated in rodent hippocampal cultures, little is known about the functional role of local E2 synthesis in mediating hippocampal memory function. Therefore, the present study examined the role of hippocampal E2 synthesis in hippocampal memory consolidation. Using bilateral dorsal hippocampal infusions of the aromatase inhibitor letrozole, we first found that blockade of dorsal hippocampal E2 synthesis impaired hippocampal memory consolidation. We next found that elevated levels of E2 in dorsal hippocampus observed 30 min after object training were blocked by dorsal hippocampal infusion of letrozole, suggesting that behavioral experience increases acute and local E2 synthesis. Finally, aromatase inhibition did not prevent exogenous E2 from enhancing hippocampal memory consolidation, indicating that hippocampal E2 synthesis is not necessary for exogenous E2 to enhance hippocampal memory. Combined, these data are consistent with the hypothesis that hippocampally-synthesized E2 is necessary for hippocampus-dependent memory consolidation in rodents. PMID:27178577

Comparison of the montreal cognitive assessment and the mini-mental state examination as screening tests in hemodialysis patients without symptoms.

PubMed

Lee, Sun Hwa; Cho, AJin; Min, Yang-Ki; Lee, Young-Ki; Jung, San

2018-11-01

Cognitive impairment in end-stage renal disease patients is associated with an increased risk of mortality. We examined the cognitive function in hemodialysis (HD) patients and compared the Korean versions of the Montreal Cognitive Assessment (K-MoCA) and of the Mini-Mental State Examination (K-MMSE) to identify the better cognitive screening instrument in these patients. Thirty patients undergoing hemodialysis and 30 matched reference group of apparently healthy control were included. All subjects underwent the K-MoCA, K-MMSE and a neuropsychological test battery to measure attention, visuospatial function, language, memory and executive function. All cognitive data were converted to z-scores with appropriate age and education level prior to group comparisons. Cognitive performance 1.0 SD below the mean was defined as modest cognitve impairment while 1.5 below the mean was defined as severe cognitive impairment. Modest cognitive impairment in memory plus other cognitive domains was detected in 27 patients (90%) while severe cognitive impairment in memory plus other cognitive domains was detected in 23 (77%) patients. Total scores in the K-MoCA were significantly lower in HD patients than in the reference group. However, no significant group difference was found in the K-MMSE. The K-MMSE ROC AUC (95% confidence interval) was 0.72 (0.59-0.85) and K-MoCA ROC AUC was 0.77 (0.65-0.89). Cognitive impairment is common but under-diagnosed in this population. The K-MoCA seems to be more sensitive than the K-MMSE in HD patients.

Protective effects of physical exercise on MDMA-induced cognitive and mitochondrial impairment.

PubMed

Taghizadeh, Ghorban; Pourahmad, Jalal; Mehdizadeh, Hajar; Foroumadi, Alireza; Torkaman-Boutorabi, Anahita; Hassani, Shokoufeh; Naserzadeh, Parvaneh; Shariatmadari, Reyhaneh; Gholami, Mahdi; Rouini, Mohammad Reza; Sharifzadeh, Mohammad

2016-10-01

Debate continues about the effect of 3, 4-methylenedioxymethamphetamine (MDMA) on cognitive and mitochondrial function through the CNS. It has been shown that physical exercise has an important protective effect on cellular damage and death. Therefore, we investigated the effect of physical exercise on MDMA-induced impairments of spatial learning and memory as well as MDMA effects on brain mitochondrial function in rats. Male wistar rats underwent short-term (2 weeks) or long-term (4 weeks) treadmill exercise. After completion of exercise duration, acquisition and retention of spatial memory were evaluated by Morris water maze (MWM) test. Rats were intraperitoneally (I.P) injected with MDMA (5, 10, and 15mg/kg) 30min before the first training trial in 4 training days of MWM. Different parameters of brain mitochondrial function were measured including the level of ROS production, mitochondrial membrane potential (MMP), mitochondrial swelling, mitochondrial outermembrane damage, the amount of cytochrome c release from the mitochondria, and ADP/ATP ratio. MDMA damaged the spatial learning and memory in a dose-dependent manner. Brain mitochondria isolated from the rats treated with MDMA showed significant increase in ROS formation, collapse of MMP, mitochondrial swelling, and outer membrane damage, cytochrome c release from the mitochondria, and finally increased ADP/ATP ratio. This study also found that physical exercise significantly decreased the MDMA-induced impairments of spatial learning and memory and also mitochondrial dysfunction. The results indicated that MDMA-induced neurotoxicity leads to brain mitochondrial dysfunction and subsequent oxidative stress is followed by cognitive impairments. However, physical exercise could reduce these deleterious effects of MDMA through protective effects on brain mitochondrial function. Copyright © 2016 Elsevier Inc. All rights reserved.

Cortical connectivity and memory performance in cognitive decline: A study via graph theory from EEG data.

PubMed

Vecchio, F; Miraglia, F; Quaranta, D; Granata, G; Romanello, R; Marra, C; Bramanti, P; Rossini, P M

2016-03-01

Functional brain abnormalities including memory loss are found to be associated with pathological changes in connectivity and network neural structures. Alzheimer's disease (AD) interferes with memory formation from the molecular level, to synaptic functions and neural networks organization. Here, we determined whether brain connectivity of resting-state networks correlate with memory in patients affected by AD and in subjects with mild cognitive impairment (MCI). One hundred and forty-four subjects were recruited: 70 AD (MMSE Mini Mental State Evaluation 21.4), 50 MCI (MMSE 25.2) and 24 healthy subjects (MMSE 29.8). Undirected and weighted cortical brain network was built to evaluate graph core measures to obtain Small World parameters. eLORETA lagged linear connectivity as extracted by electroencephalogram (EEG) signals was used to weight the network. A high statistical correlation between Small World and memory performance was found. Namely, higher Small World characteristic in EEG gamma frequency band during the resting state, better performance in short-term memory as evaluated by the digit span tests. Such Small World pattern might represent a biomarker of working memory impairment in older people both in physiological and pathological conditions. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Mood state and cerebral metabolism in persons with age-associated memory impairment.

PubMed

Cherrier, M M; Small, G W; Komo, S; La Rue, A

1997-12-30

People undergoing medical procedures sometimes experience feelings that may influence the results. In this study, we explore the relationship between changes in mood state self-ratings and cerebral glucose metabolism during positron emission tomography (PET) in persons with age-associated memory impairment (mean age 59.4 +/- 9.8 years). Brain regions of interest involved in both mood and memory were examined. Mood ratings of increased boredom correlated significantly with mesial temporal and parietal asymmetry and decreased parietal metabolism. Mood ratings of increased fatigue correlated with basal ganglia asymmetry and the right basal ganglia and left mesial temporal metabolism. These findings suggest that subjective mood state changes during PET may influence metabolism in brain regions implicated in emotion and memory function in people with age-related memory complaints.

Mutation in the Fas Pathway Impairs CD8+ T Cell Memory1

PubMed Central

Dudani, Renu; Russell, Marsha; van Faassen, Henk; Krishnan, Lakshmi; Sad, Subash

2014-01-01

Fas death pathway is important for lymphocyte homeostasis, but the role of Fas pathway in T cell memory development is not clear. We show that whereas the expansion and contraction of CD8+ T cell response against Listeria monocytogenes were similar for wild-type (WT) and Fas ligand (FasL) mutant mice, the majority of memory CD8+ T cells in FasL mutant mice displayed an effector memory phenotype in the long-term in comparison with the mainly central memory phenotype displayed by memory CD8+ T cells in WT mice. Memory CD8+ T cells in FasL mutant mice expressed reduced levels of IFN-γ and displayed poor homeostatic and Ag-induced proliferation. Impairment in CD8+ T cell memory in FasL mutant hosts was not due to defective programming or the expression of mutant FasL on CD8+ T cells, but was caused by perturbed cytokine environment in FasL mutant mice. Although adoptively transferred WT memory CD8+ T cells mediated protection against L. monocytogenes in either the WT or FasL mutant hosts, FasL mutant memory CD8+ T cells failed to mediate protection even in WT hosts. Thus, in individuals with mutation in Fas pathway, impairment in the function of the memory CD8+ T cells may increase their susceptibility to recurrent/latent infections. PMID:18292515

Early developmental bisphenol-A exposure sex-independently impairs spatial memory by remodeling hippocampal dendritic architecture and synaptic transmission in rats

NASA Astrophysics Data System (ADS)

Liu, Zhi-Hua; Ding, Jin-Jun; Yang, Qian-Qian; Song, Hua-Zeng; Chen, Xiang-Tao; Xu, Yi; Xiao, Gui-Ran; Wang, Hui-Li

2016-08-01

Bisphenol-A (BPA, 4, 4‧-isopropylidene-2-diphenol), a synthetic xenoestrogen that widely used in the production of polycarbonate plastics, has been reported to impair hippocampal development and function. Our previous study has shown that BPA exposure impairs Sprague-Dawley (SD) male hippocampal dendritic spine outgrowth. In this study, the sex-effect of chronic BPA exposure on spatial memory in SD male and female rats and the related synaptic mechanism were further investigated. We found that chronic BPA exposure impaired spatial memory in both SD male and female rats, suggesting a dysfunction of hippocampus without gender-specific effect. Further investigation indicated that BPA exposure causes significant impairment of dendrite and spine structure, manifested as decreased dendritic complexity, dendritic spine density and percentage of mushroom shaped spines in hippocampal CA1 and dentate gyrus (DG) neurons. Furthermore, a significant reduction in Arc expression was detected upon BPA exposure. Strikingly, BPA exposure significantly increased the mIPSC amplitude without altering the mEPSC amplitude or frequency, accompanied by increased GABAARβ2/3 on postsynaptic membrane in cultured CA1 neurons. In summary, our study indicated that Arc, together with the increased surface GABAARβ2/3, contributed to BPA induced spatial memory deficits, providing a novel molecular basis for BPA achieved brain impairment.

Functional neuroanatomical associations of working memory in early-onset Alzheimer's disease.

PubMed

Kobylecki, Christopher; Haense, Cathleen; Harris, Jennifer M; Stopford, Cheryl L; Segobin, Shailendra H; Jones, Matthew; Richardson, Anna M T; Gerhard, Alexander; Anton-Rodriguez, José; Thompson, Jennifer C; Herholz, Karl; Snowden, Julie S

2018-01-01

To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early-onset Alzheimer's disease. Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Twenty-four patients with predominantly early-onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1-weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region-of-interest approach. Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left-sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Our findings support the hypothesis that working memory changes in early-onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Alfentanil and memory function. A comparison with fentanyl for day case termination of pregnancy.

PubMed

Kennedy, D J; Ogg, T W

1985-06-01

Two groups of 20 patients undergoing day case vaginal termination of pregnancy received either methohexitone and alfentanil 7.5 micrograms/kg or methohexitone and fentanyl 1.5 micrograms/kg. Their recovery times and memory function at 1 and 2 hours after surgery were compared. No difference in the recovery of the 2 groups was noted but at 2 hours after operation the alfentanil group showed impairment of memory for new facts compared with pre-operative memory function testing. This was not evident in the fentanyl group. Apart from this finding alfentanil was adjudged to be a suitable agent for day case anaesthesia.

Amelioration of Metabolic Syndrome-Associated Cognitive Impairments in Mice via a Reduction in Dietary Fat Content or Infusion of Non-Diabetic Plasma

PubMed Central

Johnson, Lance A.; Zuloaga, Kristen L.; Kugelman, Tara L.; Mader, Kevin S.; Morré, Jeff T.; Zuloaga, Damian G.; Weber, Sydney; Marzulla, Tessa; Mulford, Amelia; Button, Dana; Lindner, Jonathan R.; Alkayed, Nabil J.; Stevens, Jan F.; Raber, Jacob

2015-01-01

Obesity, metabolic syndrome (MetS) and type 2 diabetes (T2D) are associated with decreased cognitive function. While weight loss and T2D remission result in improvements in metabolism and vascular function, it is less clear if these benefits extend to cognitive performance. Here, we highlight the malleable nature of MetS-associated cognitive dysfunction using a mouse model of high fat diet (HFD)-induced MetS. While learning and memory was generally unaffected in mice with type 1 diabetes (T1D), multiple cognitive impairments were associated with MetS, including deficits in novel object recognition, cued fear memory, and spatial learning and memory. However, a brief reduction in dietary fat content in chronic HFD-fed mice led to a complete rescue of cognitive function. Cerebral blood volume (CBV), a measure of vascular perfusion, was decreased during MetS, was associated with long term memory, and recovered following the intervention. Finally, repeated infusion of plasma collected from age-matched, low fat diet-fed mice improved memory in HFD mice, and was associated with a distinct metabolic profile. Thus, the cognitive dysfunction accompanying MetS appears to be amenable to treatment, related to cerebrovascular function, and mitigated by systemic factors. PMID:26870815

Memory flexibility training for autobiographical memory as an intervention for maintaining social and mental well-being in older adults.

PubMed

Leahy, Fiona; Ridout, Nathan; Holland, Carol

2018-05-07

Autobiographical memory specificity (AMS) reduces with increasing age and is associated with depression, social problem-solving and functional limitations. However, ability to switch between general and specific, as well as between positive and negative retrieval, may be more important for the strategic use of autobiographical information in everyday life. Ability to switch between retrieval modes is likely to rely on aspects of executive function. We propose that age-related deficits in cognitive flexibility impair AMS, but the "positivity effect" protects positively valenced memories from impaired specificity. A training programme to improve the ability to flexibly retrieve different types of memories in depressed adults (MemFlex) was examined in non-depressed older adults to determine effects on AMS, valence and the executive functions underlying cognitive flexibility. Thirty-nine participants aged 70+ (MemFlex, n = 20; control, n = 19) took part. AMS and the inhibition aspect of executive function improved in both groups, suggesting these abilities are amenable to change, although not differentially affected by this type of training. Lower baseline inhibition scores correlated with increased negative, but not positive AMS, suggesting that positive AMS is an automatic process in older adults. Changes in AMS correlated with changes in social problem-solving, emphasising the usefulness of AMs in a social environment.

Neurotoxicity of developmental hypothyroxinemia and hypothyroidism in rats: Impairments of long-term potentiation are mediated by phosphatidylinositol 3-kinase signaling pathway

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

Wang, Yi; Wei, Wei; Wang, Yuan

Neurotoxicity of iodine deficiency-induced hypothyroidism during developmental period results in serious impairments of brain function, such as learning and memory. These impairments are largely irreversible, and the underlying mechanisms remain unclear. In addition to hypothyroidism, iodine deficiency may cause hypothyroxinemia, a relatively subtle form of thyroid hormone deficiency. Neurotoxicity of developmental hypothyroxinemia also potentially impairs learning and memory. However, more direct evidence of the associations between developmental hypothyroxinemia and impairments of learning and memory should be provided, and the underlying mechanisms remain to be elucidated. Thus, in the present study, we investigated the effects of developmental hypothyroxinemia and hypothyroidism onmore » long-term potentiation (LTP), a widely accepted cellular model of learning and memory, in the hippocampal CA1 region. The activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway – a pathway closely associated with synaptic plasticity and learning and memory – was also investigated. Wistar rats were treated with iodine deficient diet or methimazole (MMZ) to induce developmental hypothyroxinemia or hypothyroidism. The results showed that developmental hypothyroxinemia caused by mild iodine deficiency and developmental hypothyroidism caused by severe iodine deficiency or MMZ significantly reduced the field-excitatory postsynaptic potential (f-EPSP) slope and the population spike (PS) amplitude. Decreased activation of the PI3K signaling pathway was also observed in rats subjected to developmental hypothyroxinemia or hypothyroidism. Our results may support the hypothesis that neurotoxicity of both developmental hypothyroxinemia and hypothyroidism causes damages to learning and memory. Our results also suggest that decreased activation of the PI3K signaling pathway may contribute to impairments of LTP caused by neurotoxicity of both developmental hypothyroxinemia and hypothyroidism. - Highlights: • Neurotoxicity of developmental hypothyroxinemia impaired LTP. • Decreased activation of PI3K signaling contributed to LTP impairments. • The recovery of TH after the developmental period did not prevent LTP impairments. • ID diet successfully induced neurotoxicity of developmental hypothyroxinemia.« less

AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation.

PubMed

Li, Xiao-Hong; Lv, Bing-Ling; Xie, Jia-Zhao; Liu, Jing; Zhou, Xin-Wen; Wang, Jian-Zhi

2012-07-01

Accumulation of β-amyloid and hyperphosphorylated tau with synapse damage and memory deterioration are hallmark lesions of Alzheimer disease (AD), but the upstream causative factors are elusive. The advanced glycation endproducts (AGEs) are elevated in AD brains and the AGEs can stimulate β-amyloid production. Whether and how AGEs may cause AD-like tau hyperphosphorylation and memory-related deficits is not known. Here we report that AGEs induce tau hyperphosphorylation, memory deterioration, decline of synaptic proteins, and impairment of long-term potentiation (LTP) in rats. In SK-NS-H cells, upregulation of AGEs receptor (RAGE), inhibition of Akt, and activation of glycogen synthase kinase-3 (GSK-3), Erk1/2, and p38 were observed after treatment with AGEs. In rats, blockage of RAGE attenuated the AGE-induced GSK-3 activation, tau hyperphosphorylation, and memory deficit with restoration of synaptic functions, and simultaneous inhibition of GSK-3 also antagonized the AGE-induced impairments. Our data reveal that AGEs can induce tau hyperphosphorylation and impair synapse and memory through RAGE-mediated GSK-3 activation and targeting RAGE/GSK-3 pathway can efficiently improve the AD-like histopathological changes and memory deterioration. Copyright © 2012 Elsevier Inc. All rights reserved.

delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

PubMed

Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

2011-10-01

Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

Association between cognitive impairments and obsessive-compulsive spectrum presentations following traumatic brain injury.

PubMed

Rydon-Grange, Michelle; Coetzer, Rudi

2017-01-02

This study examined the association between self-reported obsessive-compulsive spectrum symptomatology and cognitive performance in a sample of patients with traumatic brain injury (TBI). Twenty-four adults with a moderate-severe TBI accessing a community brain injury rehabilitation service were recruited. Age ranged between 19 and 69 years. Participants completed a battery of neuropsychological tasks assessing memory, executive functioning, and speed of information processing. Self-report questionnaires assessing obsessive-compulsive (OC) symptoms and obsessive-compulsive personality disorder (OCPD) traits were also completed. Correlational analyses revealed that deficits in cognitive flexibility were associated with greater self-reported OC symptomatology and severity. Greater OC symptom severity was significantly related to poorer performance on a visual memory task. Verbal memory and speed of information processing impairments were unrelated to OC symptoms. Performance on tasks of memory, executive functioning, and speed of information processing were not associated with OCPD traits. Overall, results indicate that greater OC symptomatology and severity were associated with specific neuropsychological functions (i.e., cognitive flexibility, visual memory). OCPD personality traits were unrelated to cognitive performance. Further research is needed to examine the potential causal relationship and longer-term interactions between cognitive sequelae and obsessive-compulsive spectrum presentations post-TBI.

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.

Deficits in verbal long-term memory and learning in children with poor phonological short-term memory skills.

PubMed

Gathercole, Susan E; Briscoe, Josie; Thorn, Annabel; Tiffany, Claire

2008-03-01

Possible links between phonological short-term memory and both longer term memory and learning in 8-year-old children were investigated in this study. Performance on a range of tests of long-term memory and learning was compared for a group of 16 children with poor phonological short-term memory skills and a comparison group of children of the same age with matched nonverbal reasoning abilities but memory scores in the average range. The low-phonological-memory group were impaired on longer term memory and learning tasks that taxed memory for arbitrary verbal material such as names and nonwords. However, the two groups performed at comparable levels on tasks requiring the retention of visuo-spatial information and of meaningful material and at carrying out prospective memory tasks in which the children were asked to carry out actions at a future point in time. The results are consistent with the view that poor short-term memory function impairs the longer-term retention and ease of learning of novel verbal material.

The Effects of Acute Stress on Core Executive Functions: A Meta-Analysis and Comparison with Cortisol

PubMed Central

Shields, Grant S.; Sazma, Matthew A.; Yonelinas, Andrew P.

2016-01-01

Core executive functions such as working memory, inhibition, and cognitive flexibility are integral to daily life. A growing body of research has suggested that acute stress may impair core executive functions. However, there are a number of inconsistencies in the literature, leading to uncertainty about how or even if acute stress influences core executive functions. We addressed this by conducting a meta-analysis of acute stress effects on working memory, inhibition, and cognitive flexibility. We found that stress impaired working memory and cognitive flexibility, whereas it had nuanced effects on inhibition. Many of these effects were moderated by other variables, such as sex. In addition, we compared effects of acute stress on core executive functions to effects of cortisol administration and found some striking differences. Our findings indicate that stress works through mechanisms aside from or in addition to cortisol to produce a state characterized by more reactive processing of salient stimuli but greater control over actions. We conclude by highlighting some important future directions for stress and executive function research. PMID:27371161

Effects of cholestasis on learning and locomotor activity in bile duct ligated rats.

PubMed

Hosseini, Nasrin; Alaei, Hojjatallah; Nasehi, Mohammad; Radahmadi, Maryam; Mohammad Reza, Zarrindast

2014-01-01

Cognitive functions are impaired in patients with liver disease. Bile duct ligation causes cholestasis that impairs liver function. This study investigated the impact of cholestasis progression on the acquisition and retention times in the passive avoidance test and on the locomotor activity of rats. Cholestasis was induced in male Wistar rats by ligating the main bile duct. Locomotor activity, learning and memory were assessed by the passive avoidance learning test at day 7, day 14, and day 21 post-bile duct ligation. The serum levels of bilirubin, alanine aminotransferase, and alkaline phosphatase were measured. The results showed that acquisition time and locomotor activity were not affected at day 7 and day 14, but they were significantly (P < 0.05) impaired at day 21 post-bile duct ligation compared with the results for the control group. Additionally, memory was significantly impaired on day 7 (P < 0.01), day 14, and day 21 (P < 0.001) compared with the control groups. The levels of total bilirubin, direct bilirubin, indirect bilirubin, alanine aminotransferase, and alkaline phosphatase were significantly higher at day 7, day 14, and day 21 post-bile duct ligation compared with the levels in the sham group. Based on these findings, both liver and memory function were affected in the early stage of cholestasis (7 days after bile duct ligation), while learning and locomotor activity were impaired at 21 days after bile duct ligation following the progression of cholestasis.

What is your patient’s cognitive profile? Three distinct subgroups of cognitive function in persons with heart failure

PubMed Central

Hawkins, Misty A.W.; Schaefer, Julie T.; Gunstad, John; Dolansky, Mary A.; Redle, Joseph D.; Josephson, Richard; Moore, Shirley M.; Hughes, Joel W.

2014-01-01

Purpose To determine whether patients with heart failure (HF) have distinct profiles of cognitive impairment. Background Cognitive impairment is common in HF. Recent work found three cognitive profiles in HF patients— (1) intact, (2) impaired, and (3) memory-impaired. We examined the reproducibility of these profiles and clarified mechanisms. Methods HF patients (68.6±9.7years; N=329) completed neuropsychological testing. Composite scores were created for cognitive domains and used to identify clusters via agglomerative-hierarchical cluster analysis. Results A 3-cluster solution emerged. Cluster 1 (n=109) had intact cognition. Cluster 2 (n=123) was impaired across all domains. Cluster 3 (n=97) had impaired memory only. Clusters differed in age, race, education, SES, IQ, BMI, and diabetes (ps ≤.026) but not in mood, anxiety, cardiovascular, or pulmonary disease (ps≥.118). Conclusions We replicated three distinct patterns of cognitive function in persons with HF. These profiles may help providers offer tailored care to patients with different cognitive and clinical needs. PMID:25510559

Cognitive syndromes after the first stroke.

PubMed

Salihović, Denisa; Smajlović, Dževdet; Mijajlović, Milija; Zoletić, Emina; Ibrahimagić, Omer Ć

2018-05-19

The aim of this study is to determine impairments of certain cognitive functions in certain vascular cognitive syndromes and to identify predictors of dementia. One-year prospective study included 275 patients, who were hospitalized at the Department of Neurology Tuzla and therefore fulfilled certain criteria. Patients were divided into following subgroups of vascular cognitive impairment (VCI): dementia of strategic infarct (DSI), cortical dementia (CD), sub cortical dementia (SCD), hemorrhagic dementia (HD), and patients without dementia. Each of the patients underwent the clinical examination and scoring with appropriate measurement scales. Some of the types of VCI were verified in 190 (69%) patients, and the most common was SCD (58%). There was statistically significant connection between the level of intelligence and occurrence of VCI in patients after stroke (p < 0.001). We found significant connection between occurrence of dementia and impairment in narrative memory, numerical memory, visual perceptive, and visual constructive functions in patients with dementia compared with non-demented (p = 0.0001). The executive functions were statistically impaired in patients with CD (p = 0.004) and SCD (p < 0.001). Patients without dementia have significantly better quality of life than the demented ones (p < 0.0001). The algorithm "tree of decision" can help us in the prediction of dementia based on the impairment of certain cognitive functions. Vascular cognitive syndromes are common after stroke. Some of the cognitive functions are significantly impaired in patients with dementia. Impairment of the certain cognitive functions can help in predicting the onset of dementia. Patients without dementia have better quality of life.

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

PubMed

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

2011-08-01

An unfortunate result of the rapid rise in geriatric populations worldwide is the increasing prevalence of age-related cognitive disorders such as Alzheimer's disease (AD). AD is a devastating neurodegenerative illness that is characterized by a profound impairment of cognitive function, marked physical disability, and an enormous economic burden on the afflicted individual, caregivers, and society in general. The rise in elderly populations is also resulting in an increase in individuals with related (potentially treatable) conditions such as "Mild Cognitive Impairment" (MCI) which is characterized by a less severe (but abnormal) level of cognitive impairment and a high-risk for developing dementia. Even in the absence of a diagnosable disorder of cognition (e.g., AD and MCI), the perception of increased forgetfulness and declining mental function is a clear source of apprehension in the elderly. This is a valid concern given that even a modest impairment of cognitive function is likely to be associated with significant disability in a rapidly evolving, technology-based society. Unfortunately, the currently available therapies designed to improve cognition (i.e., for AD and other forms of dementia) are limited by modest efficacy and adverse side effects, and their effects on cognitive function are not sustained over time. Accordingly, it is incumbent on the scientific community to develop safer and more effective therapies that improve and/or sustain cognitive function in the elderly allowing them to remain mentally active and productive for as long as possible. As diagnostic criteria for memory disorders evolve, the demand for pro-cognitive therapeutic agents is likely to surpass AD and dementia to include MCI and potentially even less severe forms of memory decline. The purpose of this review is to provide an overview of the contemporary therapeutic targets and preclinical pharmacologic approaches (with representative drug examples) designed to enhance memory function. Copyright © 2011 Elsevier Inc. All rights reserved.

Impaired memory is more closely associated with brain beta-amyloid than leukoaraiosis in hypertensive patients with cognitive symptoms.

PubMed

Smith, Eric E; Muzikansky, Alona; McCreary, Cheryl R; Batool, Saima; Viswanathan, Anand; Dickerson, Bradford C; Johnson, Keith; Greenberg, Steven M; Blacker, Deborah

2018-01-01

Hypertension is the strongest modifiable risk factor for subcortical ischemic changes and is also a risk factor for Alzheimer's dementia. We used neuroimaging to investigate the pathological basis of early cognitive symptoms in patients with hypertension. In this cross-sectional cohort study 67 patients age >60 years with hypertension and Clinical Dementia Rating scale score of 0.5 without dementia, and without history of symptomatic stroke, underwent MRI for measurement of subcortical vascular changes and positron emission tomography (PET) scan with Pittsburgh Compound B (PiB-PET) to detect beta-amyloid deposition. These imaging measures were related to neuropsychological tests of memory, executive function and processing speed. Mean age was 75.0 (standard deviation, SD, 7.3). Mean neuropsychological Z scores were: episodic memory -0.63 (SD 1.23), executive function -0.40 (SD 1.10), processing speed -0.24 (SD 0.88); 22 of the 67 subjects met criteria for mild cognitive impairment (MCI) and the remaining 45 subjects had subjective cognitive concerns only. In multivariable models adjusting for age and years of education, each 0.1 unit increase in mean cortical PiB-PET binding was associated with 0.14 lower mean Z score for episodic memory (95% CI -0.28 to -0.01). This means that for every 0.1 unit increase in mean cortical PiB-PET, episodic memory was 0.14 standard deviations lower. White matter hyperintensity volume, silent brain infarcts and microbleeds were not associated with neuropsychological test scores. Episodic memory was prominently affected in hypertensive participants with MCI or subjective cognitive concerns, and was associated with PiB-PET binding. This suggests a prominent role for Alzheimer pathology in cognitive impairment even in hypertensive participants at elevated risk for vascular cognitive impairment.

Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees.

PubMed

Williamson, Sally M; Wright, Geraldine A

2013-05-15

Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes.

Exposure to multiple cholinergic pesticides impairs olfactory learning and memory in honeybees

PubMed Central

Williamson, Sally M.; Wright, Geraldine A.

2013-01-01

SUMMARY Pesticides are important agricultural tools often used in combination to avoid resistance in target pest species, but there is growing concern that their widespread use contributes to the decline of pollinator populations. Pollinators perform sophisticated behaviours while foraging that require them to learn and remember floral traits associated with food, but we know relatively little about the way that combined exposure to multiple pesticides affects neural function and behaviour. The experiments reported here show that prolonged exposure to field-realistic concentrations of the neonicotinoid imidacloprid and the organophosphate acetylcholinesterase inhibitor coumaphos and their combination impairs olfactory learning and memory formation in the honeybee. Using a method for classical conditioning of proboscis extension, honeybees were trained in either a massed or spaced conditioning protocol to examine how these pesticides affected performance during learning and short- and long-term memory tasks. We found that bees exposed to imidacloprid, coumaphos, or a combination of these compounds, were less likely to express conditioned proboscis extension towards an odor associated with reward. Bees exposed to imidacloprid were less likely to form a long-term memory, whereas bees exposed to coumaphos were only less likely to respond during the short-term memory test after massed conditioning. Imidacloprid, coumaphos and a combination of the two compounds impaired the bees' ability to differentiate the conditioned odour from a novel odour during the memory test. Our results demonstrate that exposure to sublethal doses of combined cholinergic pesticides significantly impairs important behaviours involved in foraging, implying that pollinator population decline could be the result of a failure of neural function of bees exposed to pesticides in agricultural landscapes. PMID:23393272

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…

Impaired Performance of Children Exposed in Utero to Cocaine on a Novel Test of Visuospatial Working Memory

ERIC Educational Resources Information Center

Schroder, Marie D.; Snyder, Peter J.; Sielski, Ireneusz; Mayes, Linda

2004-01-01

The present study examines the potentially harmful effects of prenatal cocaine exposure on later visuospatial memory functions. A novel neuropsychological measure of immediate- and short-term memory for visuospatial information was administered to 40 children, who were identified as cocaine-exposed, and 11 age and socioeconomic status matched…

The Diagnostic Utility of Behavioral Checklists in Identifying Children with ADHD and Children with Working Memory Deficits

ERIC Educational Resources Information Center

Alloway, Tracy Packiam; Gathercole, Susan E.; Holmes, Joni; Place, Maurice; Elliott, Julian G.; Hilton, Kerry

2009-01-01

The present study investigated whether children with ADHD and those with working memory impairments have a common behavioral profile in the classroom. Three teacher checklists were used: the Conners' teacher rating scale (CTRS), the behavior rating inventory of executive function (BRIEF), and the working memory rating scale. The Conners'…

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

PubMed

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

2016-03-01

Clinical tests used for psychodiagnostic purposes, such as the well-known Alzheimer's Disease Assessment Scale: Cognitive subscale (ADAS-Cog), include a free-recall task. The free-recall task taps into latent cognitive processes associated with learning and memory components of human cognition, any of which might be impaired with the progression of Alzheimer's disease (AD). A Hidden Markov model of free recall is developed to measure latent cognitive processes used during the free-recall task. In return, these cognitive measurements give us insight into the degree to which normal cognitive functions are differentially impaired by medical conditions, such as AD and related disorders. The model is used to analyze the free-recall data obtained from healthy elderly participants, participants diagnosed as having mild cognitive impairment, and participants diagnosed with early AD. The model is specified hierarchically to handle item differences because of the serial position curve in free recall, as well as within-group individual differences in participants' recall abilities. Bayesian hierarchical inference is used to estimate the model. The model analysis suggests that the impaired patients have the following: (1) long-term memory encoding deficits, (2) short-term memory (STM) retrieval deficits for all but very short time intervals, (3) poorer transfer into long-term memory for items successfully retrieved from STM, and (4) poorer retention of items encoded into long-term memory after longer delays. Yet, impaired patients appear to have no deficit in immediate recall of encoded words in long-term memory or for very short time intervals in STM. (c) 2016 APA, all rights reserved).

Genetic overexpression of glutathione peroxidase-1 attenuates microcystin-leucine-arginine-induced memory impairment in mice.

PubMed

Shin, Eun-Joo; Hwang, Yeong Gwang; Pham, Duc Toan; Lee, Ji Won; Lee, Yu Jeung; Pyo, Dongjin; Lei, Xin Gen; Jeong, Ji Hoon; Kim, Hyoung-Chun

2018-06-13

Microcystin-leucine-arginine (MCLR) is the most common form of microcystins, which are environmental toxins produced by cyanobacteria, and its hepatotoxicity has been well-documented. However, the neurotoxic potential of MCLR remains to be further elucidated. In the present study, we investigated whether intracerebroventricular (i.c.v.) infusion of MCLR induces mortality and neuronal loss in the hippocampus of mice. Because we found that MCLR impairs memory function in the hippocampus at a low dose (4 ng/μl/mouse, i.c.v.) without a significant neuronal loss, we focused on this dose for further analyses. Results showed that MCLR (4 ng/μl/mouse, i.c.v.) significantly increased oxidative stress (i.e., malondialdehyde, protein carbonyl, and synaptosomal ROS) in the hippocampus. In addition, MCLR significantly increased superoxide dismutase (SOD) activity without corresponding induction of glutathione peroxidase (GPx) activity, and thus led to significant decrease in the ratio of GPx/SODs activity. The GSH/GSSG ratio was also significantly reduced after MCLR treatment. GPx-1 overexpressing transgenic mice (GPx-1 Tg) were significantly protected from MCLR-induced memory impairment and oxidative stress. The DNA binding activity of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) in these mice was significantly enhanced, and the ratios of GPx/SODs activity and GSH/GSSG returned to near control levels in the hippocampus. Importantly, memory function exhibited a significant positive correlation with the ratios of GPx/SODs activity and GSH/GSSG in the hippocampus of MCLR-treated non-transgenic (non-Tg)- and GPx-1 Tg-mice. Combined, our results suggest that MCLR induces oxidative stress and memory impairment without significant neuronal loss, and that GPx-1 gene constitutes an important protectant against MCLR-induced memory impairment and oxidative stress via maintaining antioxidant defense system homeostasis, possibly through the induction of Nrf2 transcription factor. Copyright © 2018. Published by Elsevier Ltd.

Propofol and midazolam inhibit conscious memory processes very soon after encoding: an event-related potential study of familiarity and recollection in volunteers.

PubMed

Veselis, Robert A; Pryor, Kane O; Reinsel, Ruth A; Li, Yuelin; Mehta, Meghana; Johnson, Ray

2009-02-01

Intravenous drugs active via gamma-aminobutyric acid receptors to produce memory impairment during conscious sedation. Memory function was assessed using event-related potentials (ERPs) while drug was present. The continuous recognition task measured recognition of photographs from working (6 s) and long-term (27 s) memory while ERPs were recorded from Cz (familiarity recognition) and Pz electrodes (recollection recognition). Volunteer participants received sequential doses of one of placebo (n = 11), 0.45 and 0.9 microg/ml propofol (n = 10), 20 and 40 ng/ml midazolam (n = 12), 1.5 and 3 microg/ml thiopental (n = 11), or 0.25 and 0.4 ng/ml dexmedetomidine (n = 11). End-of-day yes/no recognition 225 min after the end of drug infusion tested memory retention of pictures encoded on the continuous recognition tasks. Active drugs increased reaction times and impaired memory on the continuous recognition task equally, except for a greater effect of midazolam (P < 0.04). Forgetting from continuous recognition tasks to end of day was similar for all drugs (P = 0.40), greater than placebo (P < 0.001). Propofol and midazolam decreased the area between first presentation (new) and recognized (old, 27 s later) ERP waveforms from long-term memory for familiarity (P = 0.03) and possibly for recollection processes (P = 0.12). Propofol shifted ERP amplitudes to smaller voltages (P < 0.002). Dexmedetomidine may have impaired familiarity more than recollection processes (P = 0.10). Thiopental had no effect on ERPs. Propofol and midazolam impaired recognition ERPs from long-term memory but not working memory. ERP measures of memory revealed different pathways to end-of-day memory loss as early as 27 s after encoding.

Association between memory impairment and brain metabolite concentrations in North Korean refugees with posttraumatic stress disorder.

PubMed

Shin, Jung Eun; Choi, Chi-Hoon; Lee, Jong Min; Kwon, Jun Soo; Lee, So Hee; Kim, Hyun-Chung; Han, Na Young; Choi, Soo-Hee; Yoo, So Young

2017-01-01

Individuals with posttraumatic stress disorder (PTSD) had experiences of enormous psychological stress that can result in neurocognitive and neurochemical changes. To date, the causal relationship between them remains unclear. The present study is to investigate the association between neurocognitive characteristics and neural metabolite concentrations in North Korean refugees with PTSD. A total of 53 North Korean refugees with or without PTSD underwent neurocognitive function tests. For neural metabolite scanning, magnetic resonance spectroscopy of the hippocampus and anterior cingulate cortex (ACC) has been conducted. We assessed between-group differences in neurocognitive test scores and metabolite levels. Additionally, a multiple regression analysis was carried out to evaluate the association between neurocognitive function and metabolite levels in patients with PTSD. Memory function, but not other neurocognitive functions, was significantly lower in the PTSD group compared with the non-PTSD group. Hippocampal N-acetylaspartate (NAA) levels were not different between groups; however, NAA levels were significantly lower in the ACC of the PTSD group than the non-PTSD group (t = 2.424, p = 0.019). The multiple regression analysis showed a negative association between hippocampal NAA levels and delayed recall score on the auditory verbal learning test (β = -1.744, p = 0.011) in the non-PTSD group, but not in the PTSD group. We identified specific memory impairment and the role of NAA levels in PTSD. Our findings suggest that hippocampal NAA has a protective role in memory impairment and development of PTSD after exposure to traumatic events.

Crystallized verbal skills in schizophrenia: relationship to neurocognition, symptoms, and functional status.

PubMed

Kurtz, Matthew M; Donato, Jad; Rose, Jennifer

2011-11-01

To study the relationship of superior (i.e., ≥ 90th percentile), average (11th-89th percentile) or extremely low (i.e., ≤ 10th percentile) crystallized verbal skills to neurocognitive profiles, symptoms and everyday life function in schizophrenia. Crystallized verbal skill was derived from Vocabulary subtest scores from the Wechsler Adult Intelligence Scale (WAIS). Out of a sample of 165 stable outpatients with schizophrenia we identified 25 participants with superior crystallized verbal skill, 104 participants with average verbal skill, and 36 participants with extremely low crystallized verbal skill. Each participant was administered measures of attention, working memory, verbal learning and memory, problem-solving and processing speed, as well as symptom and performance-based adaptive life skill assessments. The magnitude of neuropsychological impairment across the three groups was different, after adjusting for group differences in education and duration of illness. Working memory, and verbal learning and memory skills were different across all three groups, while processing speed differentiated the extremely low verbal skill group from the other two groups and problem-solving differentiated the very low verbal skill group from the superior verbal skill group. There were no group differences in sustained attention. Capacity measures of everyday life skills were different across each of the three groups. Crystallized verbal skill in schizophrenia is related to the magnitude of impairment in neurocognitive function and performance-based skills in everyday life function. Patterns of neuropsychological impairment were similar across different levels of crystallized verbal skill.

Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine and of men and women.

PubMed

van der Plas, Ellen A A; Crone, Eveline A; van den Wildenberg, Wery P M; Tranel, Daniel; Bechara, Antoine

2009-08-01

Substance dependence is associated with executive function deficits, but the nature of these executive defects and the effect that different drugs and sex have on these defects have not been fully clarified. Therefore, we compared the performance of alcohol- (n = 33; 18 women), cocaine- (n = 27; 14 women), and methamphetamine-dependent individuals (n = 38; 25 women) with sex-matched healthy comparisons (n = 36; 17 women) on complex decision making as measured with the Iowa Gambling Task, working memory, cognitive flexibility, and response inhibition. Cocaine- and methamphetamine-dependent individuals were impaired on complex decision making, working memory, and cognitive flexibility, but not on response inhibition. The deficits in working memory and cognitive flexibility were milder than the decision-making deficits and did not change as a function of memory load or task switching. Interestingly, decision making was significantly more impaired in women addicted to cocaine or methamphetamine than in men addicted to these drugs. Together, these findings suggest that drug of choice and sex have different effects on executive functioning, which, if replicated, may help tailor intervention.

Semantic Processing Impairment in Patients with Temporal Lobe Epilepsy

PubMed Central

Jaimes-Bautista, Amanda G.; Rodríguez-Camacho, Mario; Martínez-Juárez, Iris E.; Rodríguez-Agudelo, Yaneth

2015-01-01

The impairment in episodic memory system is the best-known cognitive deficit in patients with temporal lobe epilepsy (TLE). Recent studies have shown evidence of semantic disorders, but they have been less studied than episodic memory. The semantic dysfunction in TLE has various cognitive manifestations, such as the presence of language disorders characterized by defects in naming, verbal fluency, or remote semantic information retrieval, which affects the ability of patients to interact with their surroundings. This paper is a review of recent research about the consequences of TLE on semantic processing, considering neuropsychological, electrophysiological, and neuroimaging findings, as well as the functional role of the hippocampus in semantic processing. The evidence from these studies shows disturbance of semantic memory in patients with TLE and supports the theory of declarative memory of the hippocampus. Functional neuroimaging studies show an inefficient compensatory functional reorganization of semantic networks and electrophysiological studies show a lack of N400 effect that could indicate that the deficit in semantic processing in patients with TLE could be due to a failure in the mechanisms of automatic access to lexicon. PMID:26257956

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

Long-term prospective memory impairment following mild traumatic brain injury with loss of consciousness: findings from the Canadian Longitudinal Study on Aging.

PubMed

Bedard, Marc; Taler, Vanessa; Steffener, Jason

2017-12-18

We aimed to examine the extent to which loss of consciousness (LOC) following mild traumatic brain injury (mTBI) may be associated with impairments in time- and event-based prospective memory (PM). PM is thought to involve executive processes and be subserved by prefrontal regions. Neuroimaging research suggests alterations to these areas of the brain several years after mTBI, particularly if LOC was experienced. However, it remains unclear whether impairments in time- or event-based functioning may persist more than a year after mTBI, and what the link with duration of LOC may be. Analyses were run on data from the Canadian Longitudinal Study on Aging, a nationwide study on health and aging involving individuals between the ages of 45-85. The present study consisted of 1937 participants who experienced mTBI more than 12 months prior, of whom 1146 reported spending less than 1 min unconscious, and 791 had LOC between 1 and 20 min, and 13,525 cognitively healthy adults. Participants were administered the Miami Prospective Memory Test, and tests of retrospective memory and executive functioning. Both mTBI groups were impaired in time-based PM relative to people with no history of TBI. Time- and event-based impairments were predicted by older age, and executive dysfunction among those who spent more time unconscious. Those with mTBI with LOC may experience impairments in PM, particularly in conditions of high demand on executive processes (time-based PM). Implications for interventions aimed at ameliorating PM among those who have experienced mTBI are discussed.

Patterns of False Memory in Patients with Huntington's Disease.

PubMed

Chen, I-Wen; Chen, Chiung-Mei; Wu, Yih-Ru; Hua, Mau-Sun

2017-06-01

Increased false memory recognition in patients with Huntington's disease (HD) has been widely reported; however, the underlying memory constructive processes remain unclear. The present study explored gist memory, item-specific memory, and monitoring ability in patients with HD. Twenty-five patients (including 13 patients with mild HD and 12 patients with moderate-to-severe HD) and 30 healthy comparison participants (HC) were recruited. We used the Deese-Roediger-McDermott (DRM) paradigm to investigate participants' false recognition patterns, along with neuropsychological tests to assess general cognitive function. Both mild and moderate-to-severe patients with HD showed significant executive functioning and episodic memory impairment. On the DRM tasks, both HD patient groups showed significantly impaired performance in tasks assessing unrelated false recognition and item-specific memory as compared to the HC group; moderate-to-severe patients performed more poorly than mild patients did. Only moderate-severe patients exhibited significantly poorer related false recognition index scores than HCs in the verbal DRM task; performance of HD patient groups was comparable to the HC group on the pictorial DRM task. It appears that diminished verbatim memory and monitoring ability are early signs of cognitive decline during the HD course. Conversely, gist memory is relatively robust, with only partial decline during advanced-stage HD. Our findings suggest that medial temporal lobe function is relatively preserved compared to that of frontal-related structures in early HD. Thus, gist-based memory rehabilitation programs might be beneficial for patients with HD. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The role of speed versus working memory in predicting learning new information in multiple sclerosis.

PubMed

Chiaravalloti, Nancy D; Stojanovic-Radic, Jelena; DeLuca, John

2013-01-01

The most common cognitive impairments in multiple sclerosis (MS) have been documented in specific domains, including new learning and memory, working memory, and information processing speed. However, little attempt has been made to increase our understanding of their relationship to one another. While recent studies have shown that processing speed impacts new learning and memory abilities in MS, the role of working memory in this relationship has received less attention. The present study examines the relative contribution of impaired working memory versus processing speed in new learning and memory functions in MS. Participants consisted of 51 individuals with clinically definite MS. Participants completed two measures of processing speed, two measures of working memory, and two measures of episodic memory. Data were analyzed via correlational and multiple regression analysis. Results indicate that the variance in new learning abilities in this sample was primarily associated with processing speed, with working memory exerting much less of an influence. Results are discussed in terms of the role of cognitive rehabilitation of new learning and memory abilities in persons with MS.

Ecological validity of virtual reality daily living activities screening for early dementia: longitudinal study.

PubMed

Tarnanas, Ioannis; Schlee, Winfried; Tsolaki, Magda; Müri, René; Mosimann, Urs; Nef, Tobias

2013-08-06

Dementia is a multifaceted disorder that impairs cognitive functions, such as memory, language, and executive functions necessary to plan, organize, and prioritize tasks required for goal-directed behaviors. In most cases, individuals with dementia experience difficulties interacting with physical and social environments. The purpose of this study was to establish ecological validity and initial construct validity of a fire evacuation Virtual Reality Day-Out Task (VR-DOT) environment based on performance profiles as a screening tool for early dementia. The objectives were (1) to examine the relationships among the performances of 3 groups of participants in the VR-DOT and traditional neuropsychological tests employed to assess executive functions, and (2) to compare the performance of participants with mild Alzheimer's-type dementia (AD) to those with amnestic single-domain mild cognitive impairment (MCI) and healthy controls in the VR-DOT and traditional neuropsychological tests used to assess executive functions. We hypothesized that the 2 cognitively impaired groups would have distinct performance profiles and show significantly impaired independent functioning in ADL compared to the healthy controls. The study population included 3 groups: 72 healthy control elderly participants, 65 amnestic MCI participants, and 68 mild AD participants. A natural user interface framework based on a fire evacuation VR-DOT environment was used for assessing physical and cognitive abilities of seniors over 3 years. VR-DOT focuses on the subtle errors and patterns in performing everyday activities and has the advantage of not depending on a subjective rating of an individual person. We further assessed functional capacity by both neuropsychological tests (including measures of attention, memory, working memory, executive functions, language, and depression). We also evaluated performance in finger tapping, grip strength, stride length, gait speed, and chair stands separately and while performing VR-DOTs in order to correlate performance in these measures with VR-DOTs because performance while navigating a virtual environment is a valid and reliable indicator of cognitive decline in elderly persons. The mild AD group was more impaired than the amnestic MCI group, and both were more impaired than healthy controls. The novel VR-DOT functional index correlated strongly with standard cognitive and functional measurements, such as mini-mental state examination (MMSE; rho=0.26, P=.01) and Bristol Activities of Daily Living (ADL) scale scores (rho=0.32, P=.001). Functional impairment is a defining characteristic of predementia and is partly dependent on the degree of cognitive impairment. The novel virtual reality measures of functional ability seem more sensitive to functional impairment than qualitative measures in predementia, thus accurately differentiating from healthy controls. We conclude that VR-DOT is an effective tool for discriminating predementia and mild AD from controls by detecting differences in terms of errors, omissions, and perseverations while measuring ADL functional ability.

Education as a Protective Factor Moderating the Effect of Depression on Memory Impairment in Elderly Women.

PubMed

Lee, Jiyoun; Park, Heyeon; Chey, Jeanyung

2018-01-01

The cognitive reserve theory explicates individual differences observed in the clinical manifestation of dementia despite similar brain pathology. Education, a popular proxy of the cognitive reserve, has been shown to have protective effects delaying the onset of clinical symptoms including memory. This study was conducted to test whether education can moderate the negative effect of depressive mood on memory performance in elderly women residing in the community. 29 elderly "unschooled" female (less than 6 years of formal education) and 49 "schooled" female (6 or more years) people were compared with regard to association between depressive mood and verbal memory functioning, which were measured by the Geriatric Depression Scale and the Elderly Verbal Learning Test, respectively. The results showed that completing or receiving more than primary school education significantly reduced the negative association between depressive mood and memory performance. Participants who did not complete primary schooling showed a decline in memory test scores depending on the level of depressive mood; whereas participants who have completed or received more than primary education displayed relatively stable memory function despite varying level of depressive mood. Our findings imply that education in early life may have protective effects against memory impairment related to elderly depression.

Activation of Gαq Signaling Enhances Memory Consolidation and Slows Cognitive Decline.

PubMed

Arey, Rachel N; Stein, Geneva M; Kaletsky, Rachel; Kauffman, Amanda; Murphy, Coleen T

2018-05-02

Perhaps the most devastating decline with age is the loss of memory. Therefore, identifying mechanisms to restore memory function with age is critical. Using C. elegans associative learning and memory assays, we identified a gain-of-function G αq signaling pathway mutant that forms a long-term (cAMP response element binding protein [CREB]-dependent) memory following one conditioned stimulus-unconditioned stimulus (CS-US) pairing, which usually requires seven CS-US pairings. Increased CREB activity in AIM interneurons reduces the threshold for memory consolidation through transcription of a set of previously identified "long-term memory" genes. Enhanced G αq signaling in the AWC sensory neuron is both necessary and sufficient for improved memory and increased AIM CREB activity, and activation of G αq specifically in aged animals rescues the ability to form memory. Activation of G αq in AWC sensory neurons non-cell autonomously induces consolidation after one CS-US pairing, enabling both cognitive function maintenance with age and restoration of memory function in animals with impaired memory performance without decreased longevity. Copyright © 2018 Elsevier Inc. All rights reserved.

Plastic modulation of episodic memory networks in the aging brain with cognitive decline.

PubMed

Bai, Feng; Yuan, Yonggui; Yu, Hui; Zhang, Zhijun

2016-07-15

Social-cognitive processing has been posited to underlie general functions such as episodic memory. Episodic memory impairment is a recognized hallmark of amnestic mild cognitive impairment (aMCI) who is at a high risk for dementia. Three canonical networks, self-referential processing, executive control processing and salience processing, have distinct roles in episodic memory retrieval processing. It remains unclear whether and how these sub-networks of the episodic memory retrieval system would be affected in aMCI. This task-state fMRI study constructed systems-level episodic memory retrieval sub-networks in 28 aMCI and 23 controls using two computational approaches: a multiple region-of-interest based approach and a voxel-level functional connectivity-based approach, respectively. These approaches produced the remarkably similar findings that the self-referential processing network made critical contributions to episodic memory retrieval in aMCI. More conspicuous alterations in self-referential processing of the episodic memory retrieval network were identified in aMCI. In order to complete a given episodic memory retrieval task, increases in cooperation between the self-referential processing network and other sub-networks were mobilized in aMCI. Self-referential processing mediate the cooperation of the episodic memory retrieval sub-networks as it may help to achieve neural plasticity and may contribute to the prevention and treatment of dementia. Copyright © 2016 Elsevier B.V. All rights reserved.

NFκB–Pim-1–Eomesodermin axis is critical for maintaining CD8 T-cell memory quality

PubMed Central

Knudson, Karin M.; Saxena, Vikas; Altman, Amnon; Daniels, Mark A.; Teixeiro, Emma

2017-01-01

T-cell memory is critical for long-term immunity. However, the factors involved in maintaining the persistence, function, and phenotype of the memory pool are undefined. Eomesodermin (Eomes) is required for the establishment of the memory pool. Here, we show that in T cells transitioning to memory, the expression of high levels of Eomes is not constitutive but rather requires a continuum of cell-intrinsic NFκB signaling. Failure to maintain NFκB signals after the peak of the response led to impaired Eomes expression and a defect in the maintenance of CD8 T-cell memory. Strikingly, we found that antigen receptor [T-cell receptor (TCR)] signaling regulates this process through expression of the NFκB-dependent kinase proviral integration site for Moloney murine leukemia virus-1 (PIM-1), which in turn regulates NFκB and Eomes. T cells defective in TCR-dependent NFκB signaling were impaired in late expression of Pim-1, Eomes, and CD8 memory. These defects were rescued when TCR-dependent NFκB signaling was restored. We also found that NFκB–Pim-1 signals were required at memory to maintain memory CD8 T-cell longevity, effector function, and Eomes expression. Hence, an NFκB–Pim-1–Eomes axis regulates Eomes levels to maintain memory fitness. PMID:28193872

Deficits in episodic memory and mental time travel in patients with post-traumatic stress disorder.

PubMed

Zlomuzica, Armin; Woud, Marcella L; Machulska, Alla; Kleimt, Katharina; Dietrich, Lisa; Wolf, Oliver T; Assion, Hans-Joerg; Huston, Joseph P; De Souza Silva, Maria A; Dere, Ekrem; Margraf, Jürgen

2018-04-20

Post-traumatic stress disorder (PTSD) is characterized by impairments in mnestic functions, especially in the domain of episodic memory. These alterations might affect different aspects of episodic memory functioning. Here we tested PTSD patients and healthy controls (matched for age, sex and education) in a newly developed virtual reality episodic memory test (VR-EMT), a test for mental time travel, episodic future thinking, and prospective memory (M3xT). In a cross-validation experiment, their performance was further evaluated in the Rivermead Behavioral Memory Test (RBMT). PTSD patients demonstrated impairments in episodic memory formation and mental time travel and showed difficulties in utilizing information from episodic memory to solve problems. Diminished attention and concentration in PTSD did not account for performance deficits in these tasks but higher levels of negative arousal were found in PTSD patients. Furthermore, performance in the VR-EMT and RBMT in PTSD patients correlated negatively with self-reported measures of stress and depression. Our results suggest that deficits in episodic memory formation and mental time travel in PTSD lead to difficulties in utilizing the content of episodic memories for solving problems in the present or to plan future behavior. Clinical implications of these findings and suggestions for cognitive-behavioral treatment of PTSD are discussed. Copyright © 2018 Elsevier Inc. All rights reserved.

Psychotic Experiences and Neuropsychological Functioning in a Population-based Sample.

PubMed

Mollon, Josephine; David, Anthony S; Morgan, Craig; Frissa, Souci; Glahn, David; Pilecka, Izabela; Hatch, Stephani L; Hotopf, Matthew; Reichenberg, Abraham

2016-02-01

Psychotic experiences in early life are associated with neuropsychological impairment and the risk for later psychiatric disorders. Psychotic experiences are also prevalent in adults, but neuropsychological investigations spanning adulthood are limited, and confounding factors have not been examined rigorously. To characterize neuropsychological functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and familial factors and investigating the effect of age. The South East London Community Health (SELCoH) study is a population-based household survey of physical and mental health in individuals 16 years or older conducted from June 1, 2008, to December 31, 2010, in 2 London boroughs. The study included 1698 participants from 1075 households. Data were analyzed from May 6, 2014, to April 22, 2015. Psychotic experiences measured using the Psychosis Screening Questionnaire. Neuropsychological functioning measured using tests assessing verbal knowledge (Wechsler Test of Adult Reading), working memory (Spatial Delayed Response Task), memory (Visual Object Learning Task), and processing speed (digit symbol coding task). A composite IQ score of general cognitive ability was calculated. A total of 1677 participants with a mean (SD) age of 40 (17) years were included in the analysis. Compared with the group without psychotic experiences, the 171 (9.7%) adults with psychotic experiences did not show a statistically significant impairment on mean (SD) measures of IQ (95.25 [16.58] vs 100.45 [14.77]; Cohen d, -0.22; P = .06) or processing speed (40.63 [13.06] vs 42.17 [13.79]; Cohen d, -0.03; P = .73) but were impaired on measures of verbal knowledge (31.36 [15.78] vs 38.83 [12.64]; Cohen d, -0.37; P = .003), working memory (20.97 [4.12] vs 22.51 [3.26]; Cohen d, -0.34; P = .005), and memory (43.80 [8.45] vs 46.53 [7.06]; Cohen d, -0.28; P = .01). Only participants 50 years and older with psychotic experiences showed medium to large impairments in neuropsychological functioning (mean [SD]) on measures of IQ (81.22 [15.97] vs 91.28 [14.31]; Cohen d, -0.70), verbal knowledge (28.31 [13.83] vs 38.51 [11.50]; Cohen d, -0.88), working memory (19.11 [4.77] vs 21.99 [3.42]; Cohen d, -0.82), and memory (39.17 [8.23] vs 44.09 [6.51]; Cohen d, -0.45) after adjusting for socioeconomic status, cannabis use, and common mental disorders. Medium impairments (mean [SD]) on measures of working memory (21.27 [3.64] vs 22.62 [2.97]; Cohen d, -0.45) and memory (44.32 [5.84] vs 46.91 [5.74]; Cohen d, -0.45) were seen in those aged 35 to 49 years and on a measure of verbal knowledge (30.81 [14.17] vs 37.60 [10.48]; Cohen d, -0.62) in those aged 16 to 24 years. First-degree relatives of adults with psychotic experiences showed a small impairment on a measure of verbal knowledge (34.71 [12.10] vs 38.63 [10.97]; Cohen d, -0.36; P = .02), and unrelated cohabitants showed no neuropsychological impairment. The profile of cognitive impairment in adults with psychotic experiences differed from that seen in adults with psychotic disorders, suggesting important differences between subclinical and clinical psychosis.

Mechanisms of Memory Dysfunction during High Altitude Hypoxia Training in Military Aircrew.

PubMed

Nation, Daniel A; Bondi, Mark W; Gayles, Ellis; Delis, Dean C

2017-01-01

Cognitive dysfunction from high altitude exposure is a major cause of civilian and military air disasters. Pilot training improves recognition of the early symptoms of altitude exposure so that countermeasures may be taken before loss of consciousness. Little is known regarding the nature of cognitive impairments manifesting within this critical window when life-saving measures may still be taken. Prior studies evaluating cognition during high altitude simulation have predominantly focused on measures of reaction time and other basic attention or motor processes. Memory encoding, retention, and retrieval represent critical cognitive functions that may be vulnerable to acute hypoxic/ischemic events and could play a major role in survival of air emergencies, yet these processes have not been studied in the context of high altitude simulation training. In a series of experiments, military aircrew underwent neuropsychological testing before, during, and after brief (15 min) exposure to high altitude simulation (20,000 ft) in a pressure-controlled chamber. Acute exposure to high altitude simulation caused rapid impairment in learning and memory with relative preservation of basic visual and auditory attention. Memory dysfunction was predominantly characterized by deficiencies in memory encoding, as memory for information learned during high altitude exposure did not improve after washout at sea level. Retrieval and retention of memories learned shortly before altitude exposure were also impaired, suggesting further impairment in memory retention. Deficits in memory encoding and retention are rapidly induced upon exposure to high altitude, an effect that could impact life-saving situational awareness and response. (JINS, 2017, 23, 1-10).

Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks.

PubMed

Ramanan, Vijay K; Kim, Sungeun; Holohan, Kelly; Shen, Li; Nho, Kwangsik; Risacher, Shannon L; Foroud, Tatiana M; Mukherjee, Shubhabrata; Crane, Paul K; Aisen, Paul S; Petersen, Ronald C; Weiner, Michael W; Saykin, Andrew J

2012-12-01

Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value < 0.05) against this composite memory score. Processes classically understood to be involved in memory consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions.

Overexpression of the NR2A subunit in the forebrain impairs long-term social recognition and non-social olfactory memory.

PubMed

Jacobs, S A; Tsien, J Z

2014-04-01

Animals must recognize and remember conspecifics and potential mates, and distinguish these animals from potential heterospecific competitors and predators. Despite its necessity, aged animals are known to exhibit impaired social recognition memory. As the brain ages, the ratio of NR2A:NR2B in the brain increases over time and has been postulated to underlie the cognitive decline observed during the aging process. Here, we test the hypothesis that an increased NR2A:NR2B subunit ratio underlies long-term social recognition memory. Using transgenic overexpression of NR2A in the forebrain regions, we investigated the ability of these mice to learn and remember male and female conspecifics, mice of another strain and animals of another rodent species, the rat. Furthermore, due to the importance of olfaction in social recognition, we tested the olfactory memory in the NR2A transgenic mice. Our series of behavioral experiments revealed significant impairments in the NR2A transgenic mice in long-term social memory of both male and female conspecifics. Additionally, the NR2A transgenic mice are unable to recognize mice of another strain or rats. The NR2A transgenic mice also exhibited long-term memory impairments in the olfactory recognition task. Taken together, our results provide evidence that an increased NR2A:NR2B ratio in the forebrain leads to reduced long-term memory function, including the ethologically important memories such as social recognition and olfactory memory.

Decreased acetylcholine release delays the consolidation of object recognition memory.

PubMed

De Jaeger, Xavier; Cammarota, Martín; Prado, Marco A M; Izquierdo, Iván; Prado, Vania F; Pereira, Grace S

2013-02-01

Acetylcholine (ACh) is important for different cognitive functions such as learning, memory and attention. The release of ACh depends on its vesicular loading by the vesicular acetylcholine transporter (VAChT). It has been demonstrated that VAChT expression can modulate object recognition memory. However, the role of VAChT expression on object recognition memory persistence still remains to be understood. To address this question we used distinct mouse lines with reduced expression of VAChT, as well as pharmacological manipulations of the cholinergic system. We showed that reduction of cholinergic tone impairs object recognition memory measured at 24h. Surprisingly, object recognition memory, measured at 4 days after training, was impaired by substantial, but not moderate, reduction in VAChT expression. Our results suggest that levels of acetylcholine release strongly modulate object recognition memory consolidation and appear to be of particular importance for memory persistence 4 days after training. Copyright © 2012 Elsevier B.V. All rights reserved.

Cortisol, learning, memory, and attention in relation to smaller hippocampal volume in police officers with posttraumatic stress disorder.

PubMed

Lindauer, Ramón J L; Olff, Miranda; van Meijel, Els P M; Carlier, Ingrid V E; Gersons, Berthold P R

2006-01-15

A proposed explanation for memory impairments in posttraumatic stress disorder (PTSD) is stress-induced hippocampal damage due to elevated cortisol levels. We have previously reported smaller hippocampi in police officers with PTSD. In this study, we examined changes in and associations between cortisol, learning, memory, attention, and hippocampal volume in PTSD. In a case-matched control study, 12 police officers with PTSD and 12 traumatized police officers without lifetime PTSD were examined with magnetic resonance imaging (for hippocampal volume), salivary cortisol tests, and neurocognitive assessments. Significantly smaller hippocampi and higher early morning salivary cortisol levels were found in PTSD. Subjects with PTSD performed worse on a delayed visual memory recall task at trend level, and made more perseverations and intrusions on a verbal memory task. Negative correlations were found between PTSD symptom severity and immediate recall function, and between re-experiencing symptoms and left hippocampal volume. A positive correlation was found between salivary cortisol level in early morning and right hippocampal volume; however, hippocampal volume did not correlate with memory. Smaller hippocampi, higher cortisol levels, and memory impairments were associated with PTSD but were not directly correlated to one another. Memory impairments in PTSD do not seem to be a direct consequence of hippocampal size.

Cognitive profile in Wilson's disease: a case series of 31 patients.

PubMed

Wenisch, E; De Tassigny, A; Trocello, J-M; Beretti, J; Girardot-Tinant, N; Woimant, F

2013-12-01

Wilson's disease (WD) is a rare autosomal recessive disorder of copper metabolism. If untreated, WD, which is initially a liver disease, can turn into a multi-systemic disease with neurological involvement. Very few studies have described cognitive impairment in WD. The aim of this study is to report the cognitive profile of 31 treated WD patients. Patients were classed into two groups using the Unified Wilson Disease Rating Scale (UWDRS): WD patients without neurological signs (WD-N(-)) (n=13), and WD patients with neurological signs (WD-N(+)) (n=18). The patients participated in a neuropsychological assessment evaluating memory, executive function and visuo-spatial abilities. Both groups performed well for verbal intelligence and episodic memory skills. However, the majority of these patients exhibited altered performance for at least one cognitive test, particularly in the executive domain. The WD-N(+) group performed less well than the WD-N(-) group on cognitive tests involving rapid motor function, abstract thinking, working memory and top-down inhibitory control. Cognitive impairment in treated WD patients essentially affects executive function involving fronto-striatal circuits. Verbal intelligence and episodic memory abilities seem to be remarkably preserved. Neuropsychological assessment is a valuable tool to evaluate the presence and the consequences of these cognitive impairments in WD patients with or without neurological signs in the course of this chronic disease. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Cognitive deficits and predictors 3 years after diagnosis of a pilocytic astrocytoma in childhood.

PubMed

Aarsen, Femke K; Paquier, Philippe F; Arts, Willem-Frans; Van Veelen, Marie-Lise; Michiels, Erna; Lequin, Maarten; Catsman-Berrevoets, Coriene E

2009-07-20

PURPOSE To prospectively study cognitive deficits and predictors 3 years after diagnosis in a large series of pediatric patients treated for pilocytic astrocytoma (PA). PATIENTS AND METHODS Sixty-one of 67 children were grouped according to infratentorial, supratentorial midline, and supratentorial hemispheric site. Intelligence, memory, attention, language, visual-spatial, and executive functions were assessed. Included predictors were sex, age, relapse, diagnosis-assessment interval, hydrocephalus, kind of treatment, and tumor variables. Results All children with PA had problems with sustained attention and speed. In the infratentorial group, there also were deficits in verbal intelligence, visual-spatial memory, executive functioning, and naming. Verbal intelligence and verbal memory problems occurred in the brainstem tumor group. The supratentorial hemispheric tumor group had additional problems with selective attention and executive functioning, and the supratentorial midline tumor group displayed no extra impairments. More specifically, the dorsal supratentorial midline tumor group displayed problems with language and verbal memory. Predictors for lower cognitive functioning were hydrocephalus, radiotherapy, residual tumor size, and age; predictors for better functioning were chemotherapy or treatment of hydrocephalus. Almost 60% of children had problems with academic achievement, for which risk factors were relapse and younger age at diagnosis. CONCLUSION Despite normal intelligence at long-term follow-up, children treated for PA display invalidating cognitive impairments. Adequate treatment of hydrocephalus is important for a more favorable long-term cognitive outcome. Even children without initial severe deficits may develop cognitive impairments years after diagnosis, partly because of the phenomenon of growing into deficit, which has devastating implications for academic achievement and quality of life (QOL).

Cognitive impairments in poly-drug ketamine users.

PubMed

Liang, H J; Lau, C G; Tang, A; Chan, F; Ungvari, G S; Tang, W K

2013-11-01

Cognitive impairment has been found to be reversible in people with substance abuse, particularly those using ketamine. Ketamine users are often poly-substance users. This study compared the cognitive functions of current and former ketamine users who were also abusing other psychoactive substances with those of non-users of illicit drugs as controls. One hundred ketamine poly-drug users and 100 controls were recruited. Drug users were divided into current (n = 32) and ex-users (n = 64) according to the duration of abstinence from ketamine (>30 days). The Beck Depression Inventory (BDI), the Hospital Anxiety Depression Scale (HADSA) and the Severity of Dependence Scale (SDS) were used to evaluate depression and anxiety symptoms and the severity of drug use, respectively. The cognitive test battery comprised verbal memory (Wechsler Memory Scale III: Logic Memory and Word List), visual memory (Rey-Osterrieth Complex Figure, ROCF), executive function (Stroop, Wisconsin Card Sorting Test, and Modified Verbal Fluency Test), working memory (Digit Span Backward), and general intelligence (Information, Arithmetic and Digit-Symbol Coding) tests. Current users had higher BDI and HADSA scores than ex-users (p < 0.001 for BDI and p = 0.022 for HADSA) and controls (p < 0.001 for BDI and p = 0.002 for HADSA). Ex-users had higher BDI (p = 0.006) but equal HADSA scores (p = 1.000) compared to controls. Both current and ex-users had lower scores on Logical Memory delayed recall (p = 0.038 for current users and p = 0.032 for ex-users) and ROCF delayed recall (p = 0.033 for current users and p = 0.014 for ex-users) than controls. Current users also performed worse on ROCF recognition than controls (p = 0.002). No difference was found between the cognitive functions of current and ex-users. Ketamine poly-drug users displayed predominantly verbal and visual memory impairments, which persisted in ex-users. The interactive effect of ketamine and poly-drug use on memory needs further investigation. © 2013 Elsevier Ltd. All rights reserved.

The posterior parietal cortex in recognition memory: a neuropsychological study.

PubMed

Haramati, Sharon; Soroker, Nachum; Dudai, Yadin; Levy, Daniel A

2008-01-01

Several recent functional neuroimaging studies have reported robust bilateral activation (L>R) in lateral posterior parietal cortex and precuneus during recognition memory retrieval tasks. It has not yet been determined what cognitive processes are represented by those activations. In order to examine whether parietal lobe-based processes are necessary for basic episodic recognition abilities, we tested a group of 17 first-incident CVA patients whose cortical damage included (but was not limited to) extensive unilateral posterior parietal lesions. These patients performed a series of tasks that yielded parietal activations in previous fMRI studies: yes/no recognition judgments on visual words and on colored object pictures and identifiable environmental sounds. We found that patients with left hemisphere lesions were not impaired compared to controls in any of the tasks. Patients with right hemisphere lesions were not significantly impaired in memory for visual words, but were impaired in recognition of object pictures and sounds. Two lesion--behavior analyses--area-based correlations and voxel-based lesion symptom mapping (VLSM)---indicate that these impairments resulted from extra-parietal damage, specifically to frontal and lateral temporal areas. These findings suggest that extensive parietal damage does not impair recognition performance. We suggest that parietal activations recorded during recognition memory tasks might reflect peri-retrieval processes, such as the storage of retrieved memoranda in a working memory buffer for further cognitive processing.

Mouse model for deficiency of methionine synthase reductase exhibits short-term memory impairment and disturbances in brain choline metabolism.

PubMed

Jadavji, Nafisa M; Bahous, Renata H; Deng, Liyuan; Malysheva, Olga; Grand'maison, Marilyn; Bedell, Barry J; Caudill, Marie A; Rozen, Rima

2014-07-15

Hyperhomocysteinaemia can contribute to cognitive impairment and brain atrophy. MTRR (methionine synthase reductase) activates methionine synthase, which catalyses homocysteine remethylation to methionine. Severe MTRR deficiency results in homocystinuria with cognitive and motor impairments. An MTRR polymorphism may influence homocysteine levels and reproductive outcomes. The goal of the present study was to determine whether mild hyperhomocysteinaemia affects neurological function in a mouse model with Mtrr deficiency. Mtrr+/+, Mtrr+/gt and Mtrrgt/gt mice (3 months old) were assessed for short-term memory, brain volumes and hippocampal morphology. We also measured DNA methylation, apoptosis, neurogenesis, choline metabolites and expression of ChAT (choline acetyltransferase) and AChE (acetylcholinesterase) in the hippocampus. Mtrrgt/gt mice exhibited short-term memory impairment on two tasks. They had global DNA hypomethylation and decreased choline, betaine and acetylcholine levels. Expression of ChAT and AChE was increased and decreased respectively. At 3 weeks of age, they showed increased neurogenesis. In the cerebellum, mutant mice had DNA hypomethylation, decreased choline and increased expression of ChAT. Our work demonstrates that mild hyperhomocysteinaemia is associated with memory impairment. We propose a mechanism whereby a deficiency in methionine synthesis leads to hypomethylation and compensatory disturbances in choline metabolism in the hippocampus. This disturbance affects the levels of acetylcholine, a critical neurotransmitter in learning and memory.

Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

PubMed Central

Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

2014-01-01

To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism. PMID:24672632

Mangifera indica fruit extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment.

PubMed

Wattanathorn, Jintanaporn; Muchimapura, Supaporn; Thukham-Mee, Wipawee; Ingkaninan, Kornkanok; Wittaya-Areekul, Sakchai

2014-01-01

To date, the effective preventive paradigm against mild cognitive impairment (MCI) is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180-200 g, were orally given the extract at doses of 12.5, 50, and 200 mg · kg(-1) BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv). At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg · kg(-1) BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

Screening for Alzheimer's Disease: Cognitive Impairment in Self-Referred and Memory Clinic-Referred Patients.

PubMed

Kirsebom, Bjørn-Eivind; Espenes, Ragna; Waterloo, Knut; Hessen, Erik; Johnsen, Stein Harald; Bråthen, Geir; Aarsland, Dag; Fladby, Tormod

2017-01-01

Cognitive assessment is essential in tracking disease progression in AD. Presently, cohorts including preclinical at-risk participants are recruited by different means, which may bias cognitive and clinical features. We compared recruitment strategies to levels of cognitive functioning. We investigate recruitment source biases in self-referred and memory clinic-referred patient cohorts to reveal potential differences in cognitive performance and demographics among at-risk participants. We included 431 participants 40-80 years old. Participants were classified as controls (n = 132) or symptom group (n = 299). The symptom group comprised of subjective cognitive decline (SCD, n = 163) and mild cognitive impairment (MCI, n = 136). We compared cognitive performance and demographics in memory clinic-referrals (n = 86) to self-referred participants responding to advertisements and news bulletins (n = 179). Participants recruited by other means were excluded from analysis (n = 34). At symptom group level, we found significant reductions in cognitive performance in memory clinic-referrals compared to self-referrals. However, here reductions were only found within the MCI group. We found no differences in cognitive performance due to recruitment within the SCD group. The MCI group was significantly impaired compared to controls on all measures. Significant reductions in learning, and executive functions were also found for the SCD group. Regardless of recruitment method, both the SCD and MCI groups showed reductions in cognitive performance compared to controls. We found differences in cognitive impairment for memory clinic-referrals compared to self-referrals only within the MCI group, SCD-cases being equally affected irrespective of referral type.

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment.

PubMed

Tran, Tammy T; Speck, Caroline L; Pisupati, Aparna; Gallagher, Michela; Bakker, Arnold

2017-01-01

Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. To assess the ApoE-4 contribution to increased hippocampal fMRI activation, patients with aMCI genotyped for ApoE-4 status and healthy age-matched control participants completed a high-resolution fMRI scan while performing a memory task designed to tax hippocampal subregion specific functions. Consistent with previous reports, patients with aMCI showed increased hippocampal activation in the left dentate gyrus/CA3 region of the hippocampus as well as memory task errors attributable to this subregion. However, this increased fMRI activation in the hippocampus did not differ between ApoE-4 carriers and ApoE-4 non-carriers and the proportion of memory errors attributable to dentate gyrus/CA3 function did not differ between ApoE-4 carriers and ApoE-4 non-carriers. These results indicate that increased fMRI activation of the hippocampus observed in patients with aMCI is independent of ApoE-4 status and that ApoE-4 does not contribute to the dysfunctional hippocampal activation or the memory errors attributable to this subregion in these patients.

Acute neuropsychological effects of MDMA and ethanol (co-)administration in healthy volunteers.

PubMed

Dumont, G J H; Wezenberg, E; Valkenberg, M M G J; de Jong, C A J; Buitelaar, J K; van Gerven, J M A; Verkes, R J

2008-04-01

In Western societies, a considerable percentage of young people expose themselves to 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy"). Commonly, ecstasy is used in combination with other substances, in particular alcohol (ethanol). MDMA induces both arousing as well as hallucinogenic effects, whereas ethanol is a general central nervous system depressant. The aim of the present study is to assess the acute effects of single and co-administration of MDMA and ethanol on executive, memory, psychomotor, visuomotor, visuospatial and attention function, as well as on subjective experience. We performed a four-way, double-blind, randomised, crossover, placebo-controlled study in 16 healthy volunteers (nine male, seven female) between the ages of 18-29. MDMA was given orally (100 mg) and blood alcohol concentration was maintained at 0.6 per thousand by an ethanol infusion regime. Co-administration of MDMA and ethanol was well tolerated and did not show greater impairment of performance compared to the single-drug conditions. Impaired memory function was consistently observed after all drug conditions, whereas impairment of psychomotor function and attention was less consistent across drug conditions. Co-administration of MDMA and ethanol did not exacerbate the effects of either drug alone. Although the impairment of performance by all drug conditions was relatively moderate, all induced significant impairment of cognitive function.

Memory, Cognition and the Endogenous Evoked Potentials of the Brain: the Estimation of the Disturbance of Cognitive Functions and Capacity of Working Memory Without the Psychological Testing.

PubMed

Gnezditskiy, V V; Korepina, O S; Chatskaya, A V; Klochkova, O I

2017-01-01

Cognition, cognitive and memory impairments is widely discussed in the literature, especially in the psycho physiological and the neurologic. In essence, this literature is dedicated to the psycho physiological tests, different scales. However, instrument neurophysiologic methods not so widely are used for these purposes. This review is dedicated to the instrument methods of neurophysiology, in particular to the endogenous evoked potentials method Р 300 (by characteristic latency 300 ms), in the estimation of cognitive functions and memory, to their special features dependent on age and to special features to their changes with the pathology. Method cognitive EP - Р 300 is the response of the brain, recorded under the conditions of the identification of the significant distinguishing stimulus, it facilitates the inspection of cognitive functions and memory in the healthy persons and patients with different manifestation of cognitive impairments. In the review it is shown on the basis of literature and our own data, that working (operative) memory and the capacity of the working memory it can be evaluated with the aid of the indices Р 300 within the normal subject and with the pathology. Testing with the estimation of working memory according to latent period of the peak Р 300 can be carried out and when conducting psychological testing is not possible for any reasons. Together with these cognitive EP are used for evidence pharmacotherapy of many neurotropic drugs.

Controlling memory impairment in elderly adults using virtual reality memory training: a randomized controlled pilot study.

PubMed

Optale, Gabriele; Urgesi, Cosimo; Busato, Valentina; Marin, Silvia; Piron, Lamberto; Priftis, Konstantinos; Gamberini, Luciano; Capodieci, Salvatore; Bordin, Adalberto

2010-05-01

Memory decline is a prevalent aspect of aging but may also be the first sign of cognitive pathology. Virtual reality (VR) using immersion and interaction may provide new approaches to the treatment of memory deficits in elderly individuals. The authors implemented a VR training intervention to try to lessen cognitive decline and improve memory functions. The authors randomly assigned 36 elderly residents of a rest care facility (median age 80 years) who were impaired on the Verbal Story Recall Test either to the experimental group (EG) or the control group (CG). The EG underwent 6 months of VR memory training (VRMT) that involved auditory stimulation and VR experiences in path finding. The initial training phase lasted 3 months (3 auditory and 3 VR sessions every 2 weeks), and there was a booster training phase during the following 3 months (1 auditory and 1 VR session per week). The CG underwent equivalent face-to-face training sessions using music therapy. Both groups participated in social and creative and assisted-mobility activities. Neuropsychological and functional evaluations were performed at baseline, after the initial training phase, and after the booster training phase. The EG showed significant improvements in memory tests, especially in long-term recall with an effect size of 0.7 and in several other aspects of cognition. In contrast, the CG showed progressive decline. The authors suggest that VRMT may improve memory function in elderly adults by enhancing focused attention.

Influence of anxiety symptoms on improvement of neurocognitive functions in patients with major depressive disorder: A 12-week, multicenter, randomized trial of tianeptine versus escitalopram, the CAMPION study.

PubMed

Yoo, Ikki; Woo, Jong-Min; Lee, Seung-Hwan; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Kim, Eui-Joong; Chung, Seockhoon; Ha, Jee Hyun; Jeon, Hong Jin

2015-10-01

Previous research has reported evidence that patients with major depressive disorder (MDD) show anxiety symptoms and neurocognitive impairments. However, the influence of anxiety on neurocognitive function in MDD patients during antidepressant treatment is unclear. MDD patients (n=164) completed a 12-week, multicenter, randomized trial assigned in a 1:1 ratio to either tianeptine or escitalopram. Changes of anxiety symptoms were assessed by the Hamilton Anxiety Rating Scale (HAM-A), and the Hamilton Depression Rating Scale (HAM-D), self-rated subjective cognitive impairment on memory and concentration, the Mini-Mental Status Examination (MMSE), Continuous Performance Test (CPT), Verbal Learning Test (VLT), and Raven's Progressive Matrices (RPM) were assessed every 4 weeks. During 12 weeks of treatment, decrease in the HAM-A score was significantly associated with improvement of subjective cognitive impairments on memory (p<0.001) and concentration (p<0.001), and objective measures on delayed memory (p=0.006) and reasoning ability (p=0.002), after adjusting for covariates such as baseline HAM-A scores, time, sex, age, education years and assigned medication using the Mixed effects and Generalized Estimated Equation model analysis. However, the other cognitive outcome variables, immediate memory, commission error, and MMSE, which showed significant improvement through 12-week study period, showed no significant association with improvement of anxiety. Improvement of anxiety symptoms was significantly associated with improvement in subjective and objective neurocognitive functions such as delayed memory and reasoning ability in elderly MDD patients during antidepressant treatment, but not significantly associated with improvement of immediate memory and commission error. ClinicalTrials.gov identifier NCT01309776. Copyright © 2015 Elsevier B.V. All rights reserved.

Centella asiatica increases hippocampal synaptic density and improves memory and executive function in aged mice.

PubMed

Gray, Nora E; Zweig, Jonathan A; Caruso, Maya; Martin, Marjoen D; Zhu, Jennifer Y; Quinn, Joseph F; Soumyanath, Amala

2018-06-19

Centella asiatica is a plant used for centuries to enhance memory. We have previously shown that a water extract of Centella asiatica (CAW) attenuates age-related spatial memory deficits in mice and improves neuronal health. Yet the effect of CAW on other cognitive domains remains unexplored as does its mechanism of improving age-related cognitive impairment. This study investigates the effects of CAW on a variety of cognitive tasks as well as on synaptic density and mitochondrial and antioxidant pathways. Twenty-month-old CB6F1 mice were treated with CAW (2 mg/ml) in their drinking water for 2 weeks prior to behavioral testing. Learning, memory, and executive function were assessed using the novel object recognition task (NORT), object location memory task (OLM), and odor discrimination reversal learning (ODRL) test. Tissue was collected for Golgi analysis of spine density as well as assessment of mitochondrial, antioxidant, and synaptic proteins. CAW improved performance in all behavioral tests suggesting effects on hippocampal and cortical dependent memory as well as on prefrontal cortex mediated executive function. There was also an increase in synaptic density in the treated animals, which was accompanied by increased expression of the antioxidant response gene NRF2 as well as the mitochondrial marker porin. These data show that CAW can increase synaptic density as well as antioxidant and mitochondrial proteins and improve multiple facets of age-related cognitive impairment. Because mitochondrial dysfunction and oxidative stress also accompany cognitive impairment in many pathological conditions this suggests a broad therapeutic utility of CAW. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex.

PubMed

Kunisawa, K; Nakashima, N; Nagao, M; Nomura, T; Kinoshita, S; Hiramatsu, M

2015-10-01

Betaine plays important roles that include acting as a methyl donor and converting homocysteine (Hcy) to methionine. Elevated plasma Hcy levels are known as hyperhomocysteinemia (HHcy) and contribute to impairments of learning and memory. Although it is commonly known that betaine plays an important role in Hcy metabolism, the effects of betaine on Hcy-induced memory impairment have not been investigated. Previously, we demonstrated the beneficial effects of betaine on acute stress and lipopolysaccharide-induced memory impairment. In the present study, we investigated whether betaine ameliorates Hcy-induced memory impairment and the underlying mechanisms of this putative effect. Mice were treated with Hcy (0.162mg/kg, s.c.) twice a day for nine days, and betaine (25mg/kg, s.c.) was administered 30min before the Hcy injections. The memory functions were evaluated using a spontaneous alternation performance test (Y-maze) at seven days and a step-down type passive avoidance test (SD) at nine and ten days after Hcy injection. We found that betaine suppressed the memory impairment induced by repeated Hcy injections. However, the blood concentrations of Hcy were significantly increased in the Hcy-treated mice immediately after the passive avoidance test, and betaine did not prevent this increase. Furthermore, Hcy induces redox stress in part by activating matrix metalloproteinase-9 (MMP-9), which leads to BBB dysfunction. Therefore, we tested whether betaine affected MMP-9 activity. Interestingly, treatment with betaine significantly inhibited Hcy-induced MMP-9 activity in the frontal cortex but not in the hippocampus after acute Hcy injection. These results suggest that the changes in MMP-9 activity after betaine treatment might have been partially responsible for the amelioration of the memory deficits and that MMP-9 might be a candidate therapeutic target for HHcy. Copyright © 2015 Elsevier B.V. All rights reserved.

Applying an Integrative Framework of Executive Function to Preschoolers With Specific Language Impairment.

PubMed

Kapa, Leah L; Plante, Elena; Doubleday, Kevin

2017-08-16

The first goal of this research was to compare verbal and nonverbal executive function abilities between preschoolers with and without specific language impairment (SLI). The second goal was to assess the group differences on 4 executive function components in order to determine if the components may be hierarchically related as suggested within a developmental integrative framework of executive function. This study included 26 4- and 5-year-olds diagnosed with SLI and 26 typically developing age- and sex-matched peers. Participants were tested on verbal and nonverbal measures of sustained selective attention, working memory, inhibition, and shifting. The SLI group performed worse compared with typically developing children on both verbal and nonverbal measures of sustained selective attention and working memory, the verbal inhibition task, and the nonverbal shifting task. Comparisons of standardized group differences between executive function measures revealed a linear increase with the following order: working memory, inhibition, shifting, and sustained selective attention. The pattern of results suggests that preschoolers with SLI have deficits in executive functioning compared with typical peers, and deficits are not limited to verbal tasks. A significant linear relationship between group differences across executive function components supports the possibility of a hierarchical relationship between executive function skills.

Cognitive deficit in patients with paranoid schizophrenia: Its clinical and laboratory correlates.

PubMed

Dorofeikova, Mariia; Neznanov, Nikolay; Petrova, Nataliia

2018-04-01

The aim of this study was to search for correlates of cognitive impairment in patients with paranoid schizophrenia among clinical, demographic, anamnestic and biochemical markers (NSE, S100B protein, BDNF, hs-CRP). Patients with paranoid schizophrenia (n=125) were examined using the Brief Assessment of Cognitive Function in Schizophrenia, the Rey-Osterrieth Complex Figure task, and a number of clinical scales including the Positive and Negative Syndrome Scale. The majority of patients demonstrated cognitive impairment. The type of impairment was highly heterogeneous and individual. Relationships were found between the degree of executive functioning and family history of mental illness; working memory and age of onset of schizophrenia; and visual memory and psychopathological symptomatology. Negative and affective symptoms were not significantly associated with cognitive functioning. Treatment with first generation antipsychotics was associated with a more frequent impairment of motor skills, and concomitant anticholinergic drugs, with reduced accuracy. Use of second-generation antipsychotics only was associated with better accuracy, working memory and speech fluency. Among the patients, 21.4% had signs of a systemic inflammatory response, indicating a possible role of inflammatory response in the development of schizophrenia. CRP, S100B and NSE levels reflected features of the course of illness and therapeutic response. Patients with lower concentrations of BDNF were characterized by lower processing speeds. Copyright © 2017 Elsevier B.V. All rights reserved.

Altered cognitive development in the siblings of individuals with schizophrenia

PubMed Central

Barch, Deanna M.; Cohen, Rachel; Csernansky, John

2014-01-01

The goal of the current study was to further investigate the late neurodevelopmental hypothesis of schizophrenia by examining cross-sectional, age-related changes in cognitive function among young adult: 1) siblings of individuals with schizophrenia (N = 66); (2) healthy control participants (N = 77); and (3) the siblings of healthy controls (N = 77). All subjects participated in a battery of tasks in four domains: 1) IQ; 2) working memory; 3) episodic memory; and 4) executive function. We found significant group differences in the relationships between age and performance in working memory and episodic memory, with similar patterns for executive function and verbal IQ. The siblings of individuals with schizophrenia showed impaired performance in working memory, episodic memory, and executive function. In addition, healthy controls and/or their siblings showed age-related improvements in all four cognitive domains, while the siblings of individuals with schizophrenia only showed this for verbal IQ. PMID:25485180

Altered cognitive development in the siblings of individuals with schizophrenia.

PubMed

Barch, Deanna M; Cohen, Rachel; Csernansky, John

2014-03-01

The goal of the current study was to further investigate the late neurodevelopmental hypothesis of schizophrenia by examining cross-sectional, age-related changes in cognitive function among young adult: 1) siblings of individuals with schizophrenia (N = 66); (2) healthy control participants (N = 77); and (3) the siblings of healthy controls (N = 77). All subjects participated in a battery of tasks in four domains: 1) IQ; 2) working memory; 3) episodic memory; and 4) executive function. We found significant group differences in the relationships between age and performance in working memory and episodic memory, with similar patterns for executive function and verbal IQ. The siblings of individuals with schizophrenia showed impaired performance in working memory, episodic memory, and executive function. In addition, healthy controls and/or their siblings showed age-related improvements in all four cognitive domains, while the siblings of individuals with schizophrenia only showed this for verbal IQ.

Piracetam improves children's memory after general anaesthesia.

PubMed

Fesenko, Ułbołgan A

2009-01-01

Surgery and anaesthesia may account for postoperative complications including cognitive impairment. The purpose of the study was to assess the influence of general anaesthetics on children's memory and effectiveness of piracetam for prevention of postoperative cognitive dysfunction. The study included patients receiving different kinds of anaesthesia for various surgical procedures, randomly allocated to two groups. According to immediate postoperative treatment, the study group received intravenous piracetam 30 mg kg(-1) and the control group--placebo. The cognitive functions were examined preoperatively and within 10 consecutive postoperative days using the ten-word memory test. The study group consisted of 123 children, the control one--of 127. Declines in memory indexes were observed in all anaesthetized patients. The most injured function was long-term memory. The intravenous administration of piracetam improved this cognitive function. The study results confirm that general anaesthesia affects the memory function in children. Piracetam is effective for prevention of postoperative cognitive dysfunction after anaesthesia.

Changes in cognitive function and brain glucose metabolism in elderly women with subjective memory impairment: a 24-month prospective pilot study.

PubMed

Jeong, H S; Park, J S; Song, I U; Chung, Y A; Rhie, S J

2017-01-01

Subjective memory impairment (SMI) may precede mild cognitive impairment (MCI) stage and would offer an earlier therapeutic opportunity than MCI would. However, it is not clear whether complaints of forgetfulness are truly reflective of objective memory dysfunction or of impairments in other cognitive domains. The aim of this current longitudinal study was to investigate changes in various cognitive functions and in regional cerebral metabolic rate of glucose (rCMRglc) among elderly women with SMI. Clinical evaluation, comprehensive neuropsychological test, and 18 F-fluoro-2-deoxyglucose positron emission tomography scans were conducted on 24 women with SMI at the baseline and 24-month follow-up. Changes in the cognitive domain scores and rCMRglc were assessed, and the relationships between them were analyzed. All participants stayed in SMI all the way till the follow-up, not converted to MCI or dementia. A significant reduction in executive function was found (mean difference in z-score: -0.21, P = 0.02) without changes in other cognitive domains. Declines in rCMRglc were detected in the left superior temporal gyrus, right posterior cingulate gyrus, left parahippocampal gyrus, right lingual gyrus, and right angular gyrus. The change in executive function had a positive correlation with the percent change of rCMRglc in the right posterior cingulate gyrus (β = 0.43, P = 0.02). Our findings suggest that elderly women with SMI symptoms should be carefully monitored for declines in executive function and related brain glucose metabolism over time. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Social Resources That Preserve Functional Independence After Memory Loss

DTIC Science & Technology

2015-05-01

20, 471 (May, 2005). 3. A. M. Jette, Toward a common language for function, disability, and health. Physical therapy 86, 726 (May, 2006). 4. R. D...impairment. We found strong associations between decreased cognitive functioning and incident ADL and IADL limitations. Physical activity may help to...ADL limitations among those with cognitive impairments. We also found that physical activity is associated with lower risk of future nursing home

Pre-training administration of tianeptine, but not propranolol, protects hippocampus-dependent memory from being impaired by predator stress.

PubMed

Campbell, Adam M; Park, Collin R; Zoladz, Phillip R; Muñoz, Carmen; Fleshner, Monika; Diamond, David M

2008-02-01

Extensive research has shown that the antidepressant tianeptine blocks the adverse effects of chronic stress on hippocampal functioning. The current series of experiments extended this area of investigation by examining the influence of tianeptine on acute stress-induced impairments of spatial (hippocampus-dependent) memory. Tianeptine (10 mg/kg, ip) administered to adult male rats before, but not after, water maze training blocked the amnestic effects of predator stress (occurring between training and retrieval) on memory. The protective effects of tianeptine on memory occurred in rats which had extensive pre-stress training, as well as in rats which had only a single day of training. Tianeptine blocked stress effects on memory without altering the stress-induced increase in corticosterone levels. Propranolol, a beta-adrenergic receptor antagonist (5 and 10 mg/kg, ip), in contrast, did not block stress-induced amnesia. These findings indicate that treatment with tianeptine, unlike propanolol, provides an effective means with which to block the adverse effects of stress on cognitive functions of the hippocampus.

Patterns of drug use and the influence of gender on self-reports of memory ability in ecstasy users: a web-based study.

PubMed

Rodgers, J; Buchanan, T; Scholey, A B; Heffernan, T M; Ling, J; Parrott, A C

2003-12-01

Research indicates that the use of recreational drugs, including MDMA ('ecstasy') can result in impairments in cognitive functioning. Recent evidence, based on accounts of 'on drug' effects and cortical binding ratios suggests that women may be more susceptible to the effects of MDMA; however, no research has explored whether there are differences in the long-term behavioural sequelae of the drug between men and women. In addition, little is known about the profile of functioning of the 'typical' user. The present investigation accessed a large sample of recreational drug users, using the Internet, to obtain self-reports of memory functioning with a view to exploring any differences in self-reported ability amongst male and female users, and the level of difficulty reported by the 'typical' ecstasy user. A web site (www.drugresearch.org.uk) was developed and used for data collection. Prospective memory ability was assessed using the Prospective Memory Questionnaire. Self-report of day-to-day memory performance was investigated using the Everyday Memory Questionnaire. The UEL Drug Questionnaire assessed the use of other substances. The number of mistakes made while completing the questionnaires was also taken as an objective measure of performance errors. Findings, based on datasets submitted from 763 respondents, indicate no differences in self-reports of functioning between male and female participants. An overall dissociation between the effects of cannabis and ecstasy on self-reported memory functioning and on the likelihood of making an error during the completion of the questionnaire was found. Typical ecstasy users were found to report significantly more difficulties in long-term prospective memory and to make more completion errors than users of other substances and drug naive controls. Whilst taking into account the fact that participants were recruited via the World Wide Web and that a number of stringent exclusion criteria were applied to the data, a number of conclusions can be drawn. Recreational drug users perceive their memory ability to be impaired compared to non-users. The type of memory difficulties reported varies depending upon the drug of choice. These difficulties are exacerbated in ecstasy users. Individuals reporting average levels of use of ecstasy are more likely to report memory problems than non-ecstasy drug users or drug free individuals. The deleterious effects of ecstasy are therefore not restricted to heavy or chronic users. No gender differences were detected, suggesting that there may be a dissociation between cognitive impairment and cortical binding worthy of further exploration.

Rhinal and Dorsolateral Prefrontal Cortex Lesions Produce Selective Impairments in Object and Spatial Learning and Memory in Canines

PubMed Central

Christie, Lori-Ann; Saunders, Richard C.; Kowalska, Danuta, M.; MacKay, William A.; Head, Elizabeth; Cotman, Carl W.; Milgram, Norton W.

2014-01-01

To examine the effects of rhinal and dorsolateral prefrontal cortex lesions on object and spatial recognition memory in canines, we used a protocol in which both an object (delayed non-matching to sample, or DNMS) and a spatial (delayed non-matching to position or DNMP) recognition task were administered daily. The tasks used similar procedures such that only the type of stimulus information to be remembered differed. Rhinal cortex (RC) lesions produced a selective deficit on the DNMS task, both in retention of the task rules at short delays and in object recognition memory. By contrast, performance on the DNMP task remained intact at both short and long delay intervals in RC animals. Subjects who received dorsolateral prefrontal cortex (dlPFC) lesions were impaired on a spatial task at a short, 5-sec delay, suggesting disrupted retention of the general task rules, however, this impairment was transient; long-term spatial memory performance was unaffected in dlPFC subjects. The present results provide support for the involvement of the RC in object, but not visuospatial, processing and recognition memory, whereas the dlPFC appears to mediate retention of a non-matching rule. These findings support theories of functional specialization within the medial temporal lobe and frontal cortex and suggest that rhinal and dorsolateral prefrontal cortices in canines are functionally similar to analogous regions in other mammals. PMID:18792072

Memory, language, and ageing.

PubMed Central

Burke, D M; Mackay, D G

1997-01-01

This overview provides both theoretical and empirical reasons for emphasizing practice and familiar skills as a practical strategy for enhancing cognitive functioning in old age. Our review of empirical research on age-related changes in memory and language reveals a consistent pattern of spared and impaired abilities in normal old age. Relatively preserved in old age is memory performance involving highly practised skills and familiar information, including factual, semantic and autobiographical information. Relatively impaired in old age is memory performance that requires the formation of new connections, for example, recall of recent autobiographical experiences, new facts or the source of newly acquired facts. This pattern of impaired new learning versus preserved old learning cuts across distinctions between semantic memory, episodic memory, explicit memory and perhaps also implicit memory. However, familiar verbal information is not completely preserved when accessed on the output side rather than the input side: aspects of language production, namely word finding and spelling, exhibit significant age-related declines. This emerging pattern of preserved and impaired abilities presents a fundamental challenge for theories of cognitive ageing, which must explain why some aspects of language and memory are more vulnerable to the effects of ageing than others. Information-universal theories, involving mechanisms such as general slowing that are independent of the type or structure of the information being processed, require additional mechanisms to account for this pattern of cognitive aging. Information-specific theories, where the type or structure of the postulated memory units can influence the effects of cognitive ageing, are able to account for this emerging pattern, but in some cases require further development to account for comprehensive cognitive changes such as general slowing. PMID:9460069

Neuroinflammatory Dynamics Underlie Memory Impairments after Repeated Social Defeat

PubMed Central

McKim, Daniel B.; Niraula, Anzela; Tarr, Andrew J.; Wohleb, Eric S.

2016-01-01

Repeated social defeat (RSD) is a murine stressor that recapitulates key physiological, immunological, and behavioral alterations observed in humans exposed to chronic psychosocial stress. Psychosocial stress promotes prolonged behavioral adaptations that are associated with neuroinflammatory signaling and impaired neuroplasticity. Here, we show that RSD promoted hippocampal neuroinflammatory activation that was characterized by proinflammatory gene expression and by microglia activation and monocyte trafficking that was particularly pronounced within the caudal extent of the hippocampus. Because the hippocampus is a key area involved in neuroplasticity, behavior, and cognition, we hypothesize that stress-induced neuroinflammation impairs hippocampal neurogenesis and promotes cognitive and affective behavioral deficits. We show here that RSD caused transient impairments in spatial memory recall that resolved within 28 d. In assessment of neurogenesis, the number of proliferating neural progenitor cells (NPCs) and the number of young, developing neurons were not affected initially after RSD. Nonetheless, the neuronal differentiation of NPCs that proliferated during RSD was significantly impaired when examined 10 and 28 d later. In addition, social avoidance, a measure of depressive-like behavior associated with caudal hippocampal circuitry, persisted 28 d after RSD. Treatment with minocycline during RSD prevented both microglia activation and monocyte recruitment. Inhibition of this neuroinflammatory activation in turn prevented impairments in spatial memory after RSD but did not prevent deficits in neurogenesis nor did it prevent the persistence of social avoidance behavior. These findings show that neuroinflammatory activation after psychosocial stress impairs spatial memory performance independent of deficits in neurogenesis and social avoidance. SIGNIFICANCE STATEMENT Repeated exposure to stress alters the homeostatic environment of the brain, giving rise to various cognitive and mood disorders that impair everyday functioning and overall quality of life. The brain, previously thought of as an immune-privileged organ, is now known to communicate extensively with the peripheral immune system. This brain–body communication plays a significant role in various stress-induced inflammatory conditions, also characterized by psychological impairments. Findings from this study implicate neuroimmune activation rather than impaired neurogenesis in stress-induced cognitive deficits. This idea opens up possibilities for novel immune interventions in the treatment of cognitive and mood disturbances, while also adding to the complexity surrounding the functional implications of adult neurogenesis. PMID:26937001

B vitamins influence vascular cognitive impairment

USDA-ARS?s Scientific Manuscript database

As the number of elderly in the USA and globally continues to increase, age-related neurological disorders, such as Alzheimer's disease and vascular dementia, are a growing concern. The loss of memory, emotional changes, and impairments in general cognitive functioning frequently result in social is...

Intermittent fasting uncovers and rescues cognitive phenotypes in PTEN neuronal haploinsufficient mice.

PubMed

Cabral-Costa, J V; Andreotti, D Z; Mello, N P; Scavone, C; Camandola, S; Kawamoto, E M

2018-06-05

Phosphatase and tensin homolog (PTEN) is an important protein with key modulatory functions in cell growth and survival. PTEN is crucial during embryogenesis and plays a key role in the central nervous system (CNS), where it directly modulates neuronal development and synaptic plasticity. Loss of PTEN signaling function is associated with cognitive deficits and synaptic plasticity impairment. Accordingly, Pten mutations have a strong link with autism spectrum disorder. In this study, neuronal Pten haploinsufficient male mice were subjected to a long-term environmental intervention - intermittent fasting (IF) - and then evaluated for alterations in exploratory, anxiety and learning and memory behaviors. Although no significant effects on spatial memory were observed, mutant mice showed impaired contextual fear memory in the passive avoidance test - an outcome that was effectively rescued by IF. In this study, we demonstrated that IF modulation, in addition to its rescue of the memory deficit, was also required to uncover behavioral phenotypes otherwise hidden in this neuronal Pten haploinsufficiency model.

Cognitive Dysfunction in Patients with Renal Failure Requiring Hemodialysis

PubMed Central

Thimmaiah, Rohini; Murthy, K. Krishna; Pinto, Denzil

2012-01-01

Background and Objectives: Renal failure patients show significant impairment on measures of attention and memory, and consistently perform significantly better on neuropsychological measures of memory and attention, approximately 24 hours after hemodialysis treatment. The objectives are to determine the cognitive dysfunction in patients with renal failure requiring hemodialysis. Materials and Methods: A total of 60 subjects comprising of 30 renal failure patients and 30 controls were recruited. The sample was matched for age, sex, and socioeconomic status. The tools used were the Standardized Mini-Mental State Examination and the Brief Cognitive Rating Scale. Results: The patients showed high cognitive dysfunction in the pre-dialysis group, in all the five dimensions (concentration, recent memory, past memory, orientation and functioning, and self-care), and the least in the 24-hour post dialysis group. This difference was found to be statistically significant (P=0.001). Conclusion: Patients with renal failure exhibited pronounced cognitive impairment and these functions significantly improved after the introduction of hemodialysis. PMID:23439613

Categorical spatial memory in patients with mild cognitive impairment and Alzheimer dementia: positional versus object-location recall.

PubMed

Kessels, Roy P C; Rijken, Stefan; Joosten-Weyn Banningh, Liesbeth W A; Van Schuylenborgh-VAN Es, Nelleke; Olde Rikkert, Marcel G M

2010-01-01

Memory for object locations, as part of spatial memory function, has rarely been studied in patients with Alzheimer dementia (AD), while studies in patients with Mild Cognitive Impairment (MCI) patients are lacking altogether. The present study examined categorical spatial memory function using the Location Learning Test (LLT) in MCI patients (n = 30), AD patients (n = 30), and healthy controls (n = 40). Two scoring methods were compared, aimed at disentangling positional recall (location irrespective of object identity) and object-location binding. The results showed that AD patients performed worse than the MCI patients on the LLT, both on recall of positional information and on recall of the locations of different objects. In addition, both measures could validly discriminate between AD and MCI patients. These findings are in agreement with the notion that visual cued-recall tests may have better diagnostic value than traditional (verbal) free-recall tests in the assessment of patients with suspected MCI or AD.

Biflorin Ameliorates Memory Impairments Induced by Cholinergic Blockade in Mice

PubMed Central

Jeon, Se Jin; Kim, Boseong; Ryu, Byeol; Kim, Eunji; Lee, Sunhee; Jang, Dae Sik; Ryu, Jong Hoon

2017-01-01

To examine the effect of biflorin, a component of Syzygium aromaticum, on memory deficit, we introduced a scopolamine-induced cognitive deficit mouse model. A single administration of biflorin increased latency time in the passive avoidance task, ameliorated alternation behavior in the Y-maze, and increased exploration time in the Morris water maze task, indicating the improvement of cognitive behaviors against cholinergic dysfunction. The biflorin-induced reverse of latency in the scopolamine-treated group was attenuated by MK-801, an NMDA receptor antagonist. Biflorin also enhanced cognitive function in a naïve mouse model. To understand the mechanism of biflorin for memory amelioration, we performed Western blot. Biflorin increased the activation of protein kinase C-ζ and its downstream signaling molecules in the hippocampus. These results suggest that biflorin ameliorates drug-induced memory impairment by modulation of protein kinase C-ζ signaling in mice, implying that biflorin could function as a possible therapeutic agent for the treatment of cognitive problems. PMID:27829270

PTSD symptom severity relates to cognitive and psycho-social dysfunctioning – a study with Congolese refugees in Uganda

PubMed Central

Ainamani, Herbert E.; Elbert, Thomas; Olema, David K.; Hecker, Tobias

2017-01-01

ABSTRACT Background: In the ongoing conflict in the Democratic Republic of the Congo (DRC), civilians have been heavily exposed to traumatic stressors. Traumatizing experiences cumulatively heighten the risk for trauma-related disorders, and with it affect cognitive and psycho-social functioning. Objectives: We aimed at investigating the association between trauma-related disorders and cognitive and psycho-social functioning and hypothesized that PTSD symptom severity would negatively correlate with executive functioning, working memory and psycho-social functioning in everyday life. Method: In total, 323 Congolese refugees (mean age: 31.3 years) who arrived in the Ugandan Nakivale refugee settlement after January 2012 were assessed regarding their exposure to traumatic events, PTSD symptom severity (posttraumatic symptom scale interview), executive functioning (Tower of London), working memory performance (Corsi block tapping task) and psycho-social dysfunctioning (Luo functioning scale). Results: Hierarchical regression analyses indicated a significant negative association between PTSD symptom severity and working memory (β = –0.32, p < 0.001), as well as executive functions (β = –0.19, p = 0.003). Furthermore, the impairment of psycho-social functioning in everyday life was positively related with PTSD symptom severity (β = 0.70, p < 0.001), and negatively with executive functioning (β = –0.15, p = 0.003). However, working memory performance was not significantly related to psycho-social dysfunctioning (β = 0.09, p > 0.05). Conclusion: Trauma survivors not only suffer from the core PTSD symptoms but also from impaired cognitive functioning. PTSD symptom severity seems furthermore to be related to impaired psycho-social functioning. Our findings suggest that trauma-related mental health problems may heighten the risk for poverty and lack of prospect and further aggravate the consequences of war and conflict. PMID:28326164

The Extent of Working Memory Deficits Associated with Williams Syndrome: Exploration of Verbal and Spatial Domains and Executively Controlled Processes

ERIC Educational Resources Information Center

Rhodes, Sinead M.; Riby, Deborah M.; Fraser, Emma; Campbell, Lorna Elise

2011-01-01

The present study investigated verbal and spatial working memory (WM) functioning in individuals with the neuro-developmental disorder Williams syndrome (WS) using WM component tasks. While there is strong evidence of WM impairments in WS, previous research has focused on short-term memory and has neglected assessment of executive components of…

Individual Differences in Young Children's Suggestibility: Relations to Event Memory, Language Abilities, Working Memory, and Executive Functioning

ERIC Educational Resources Information Center

Roebers, C.M.; Schneider, W.

2005-01-01

In this paper, two empirical studies are presented in which an attempt was made to explain individual differences in two different aspects of 4-year-olds' suggestibility, that is, their ability to resist false suggestions and memory impairments due to prior misinformation. As sources of individual differences cognitive skills along the information…

Effect of harmane, an endogenous β-carboline, on learning and memory in rats.

PubMed

Celikyurt, Ipek Komsuoglu; Utkan, Tijen; Gocmez, Semil Selcen; Hudson, Alan; Aricioglu, Feyza

2013-01-01

Our aim was to investigate the effects of acute harmane administration upon learning and memory performance of rats using the three-panel runway paradigm and passive avoidance test. Male rats received harmane (2.5, 5, and 7.5mg/kg, i.p.) or saline 30 min. before each session of experiments. In the three panel runway paradigm, harmane did not affect the number of errors and latency in reference memory. The effect of harmane on the errors of working memory was significantly higher following the doses of 5mg/kg and 7.5mg/kg. The latency was changed significantly at only 7.5mg/kg in comparison to control group. Animals were given pre-training injection of harmane in the passive avoidance test in order to determine the learning function. Harmane treatment decreased the retention latency significantly and dose dependently, which indicates an impairment in learning. In this study, harmane impaired working memory in three panel runway test and learning in passive avoidance test. As an endogenous bioactive molecule, harmane might have a critical role in the modulation of learning and memory functions. Copyright © 2012 Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

Wener, Sarah E; Archibald, Lisa MD

2011-01-01

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

The emotional harbinger effect: poor context memory for cues that previously predicted something arousing.

PubMed

Mather, Mara; Knight, Marisa

2008-12-01

A key function of memory is to use past experience to predict when something important might happen next. Indeed, cues that previously predicted arousing events (emotional harbingers) garner more attention than other cues. However, the current series of five experiments demonstrates that people have poorer memory for the context of emotional harbinger cues than of neutral harbinger cues. Participants first learned that some harbinger cues (neutral tones or faces) predicted emotionally arousing pictures and others predicted neutral pictures. Then they studied associations between the harbinger cues and new contextual details. They were worse at remembering associations with emotional harbingers than with neutral harbingers. Memory was impaired not only for the association between emotional harbingers and nearby digits, but also for contextual details that overlapped with or were intrinsic to the emotional harbingers. However, new cues that were inherently emotionally arousing did not yield the same memory impairments as the emotional harbingers. Thus, emotional harbinger cues seem to suffer more from proactive interference than do neutral harbinger cues, impairing formation of new associations with cues that previously predicted something arousing. 2008 APA, all rights reserved

Phospholipase A₂: the key to reversing long-term memory impairment in a gastropod model of aging.

PubMed

Watson, Shawn N; Wright, Natasha; Hermann, Petra M; Wildering, Willem C

2013-02-01

Memory failure associated with changes in neuronal circuit functions rather than cell death is a common feature of normal aging in diverse animal species. The (neuro)biological foundations of this phenomenon are not well understood although oxidative stress, particularly in the guise of lipid peroxidation, is suspected to play a key role. Using an invertebrate model system of age-associated memory impairment that supports direct correlation between behavioral deficits and changes in the underlying neural substrate, we show that inhibition of phospholipase A(2) (PLA(2)) abolishes both long-term memory (LTM) and neural defects observed in senescent subjects and subjects exposed to experimental oxidative stress. Using a combination of behavioral assessments and electrophysiological techniques, we provide evidence for a close link between lipid peroxidation, provocation of phospholipase A(2)-dependent free fatty acid release, decline of neuronal excitability, and age-related long-term memory impairments. This supports the view that these processes suspend rather than irreversibly extinguish the aging nervous system's intrinsic capacity for plasticity. Copyright © 2013 Elsevier Inc. All rights reserved.

Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe): development and validation.

PubMed

Viswanath, Biju; Harihara, Shashidhara N; Nahar, Abhinav; Phutane, Vivek Haridas; Taksal, Aarati; Thirthalli, Jagadisha; Gangadhar, Bangalore N

2013-06-01

The use of electroconvulsive therapy (ECT) in treatment of psychiatric disorders is associated with adverse cognitive effects. There is a need to develop a short assessment tool of cognitive functions during the course of ECT. This study aimed at developing and validating a short, sensitive battery to assess cognitive deficits associated with ECT in India. Battery for ECT Related Cognitive Deficits (B4ECT-ReCoDe), a brief cognitive battery (20-30 min) to assess verbal, visual, working and autobiographic memory, sustained attention, psychomotor speed and subjective memory impairment, was administered to 30 in-patients receiving bilateral ECT, one day after the 1st, 3rd and 6th ECT. Data was analysed using repeated measures analysis of variance and Pearson's correlation. Significant deficits were found in verbal, visual and autobiographic memory, psychomotor speed. Subjective experience of memory loss correlated positively with verbal memory impairment. B4ECT-ReCoDe, a brief, sensitive measure of cognitive impairments associated with ECT can be used in routine clinical practice. Copyright © 2013 Elsevier B.V. All rights reserved.

The emotional harbinger effect: Poor context memory for cues that previously predicted something arousing

PubMed Central

Mather, Mara; Knight, Marisa

2009-01-01

A key function of memory is to use past experience to predict when something important might happen next. Indeed, cues that previously predicted arousing events (emotional harbingers) garner more attention than other cues. However, the current series of five experiments demonstrates that people have poorer memory for the context of emotional harbinger cues than of neutral harbinger cues. Participants first learned that some harbinger cues (neutral tones or faces) predicted emotionally arousing pictures and others predicted neutral pictures. Then they studied associations between the harbinger cues and new contextual details. They were worse at remembering associations with emotional harbingers than with neutral harbingers. Memory was impaired not only for the association between emotional harbingers and nearby digits but also for contextual details that overlapped with or were intrinsic to the emotional harbingers. However, new cues that were inherently emotionally arousing did not yield the same memory impairments as the emotional harbingers. Thus, emotional harbinger cues seem to suffer more from proactive interference than do neutral harbinger cues, impairing formation of new associations with cues that previously predicted something arousing. PMID:19102596

The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat.

PubMed

Kanoski, Scott E; Zhang, Yanshu; Zheng, Wei; Davidson, Terry L

2010-01-01

Cognitive impairment and Alzheimer's disease are linked with intake of a Western diet, characterized by high levels of saturated fats and simple carbohydrates. In rats, these dietary components have been shown to disrupt hippocampal-dependent learning and memory processes, particularly those involving spatial memory. Using a rat model, the present research assessed the degree to which consumption of a high-energy (HE) diet, similar to those found in modern Western cultures, produces a selective impairment in hippocampal function as opposed to a more global cognitive disruption. Learning and memory performance was examined following 90-day consumption of an HE-diet in three nonspatial discrimination learning problems that differed with respect to their dependence on the integrity of the hippocampus. The results showed that consumption of the HE-diet impaired performance in a hippocampal-dependent feature negative discrimination problem relative to chow-fed controls, whereas performance was spared on two discrimination problems that do not rely on the hippocampus. To explore the mechanism whereby consuming HE-diets impairs cognitive function, we investigated the effect of HE-diets on the integrity of the blood-brain barrier (BBB). We found that HE-diet consumption produced a decrease in mRNA expression of tight junction proteins, particularly Claudin-5 and -12, in the choroid plexus and the BBB. Consequently, an increased blood-to-brain permeability of sodium fluorescein was observed in the hippocampus, but not in the striatum and prefrontal cortex following HE-diet access. These results indicate that hippocampal function may be particularly vulnerable to disruption by HE-diets, and this disruption may be related to impaired BBB integrity.

Neuropsychological function and cerebral glucose utilization in isolated memory impairment and Alzheimer's disease.

PubMed

Berent, S; Giordani, B; Foster, N; Minoshima, S; Lajiness-O'Neill, R; Koeppe, R; Kuhl, D E

1999-01-01

We hypothesized that 20 patients with isolated memory impairment (IMI) would demonstrate [18F]-2-fluoro-2-deoxy-D-glucose utilization and a progression of neuropsychological symptoms consistent with Alzheimer's disease (AD). IMI subjects performed similarly to AD in recall and verbal fluency, but comparable to normal subjects in other areas of cognitive functioning. A positron emission tomography (PET) diagnostic index based on parietal Z-scores categorized IMI patients into normal and abnormal metabolic patterns. Ten of the original 20 IMI patients (50%) reflected PET AD abnormalities. Clinical information was available for IMI patients at three-year follow-up. Ten (50%) had converted to AD, three were found to have pseudodementia and the seven remained IMI. Of the 10 IMI patients with an originally normal PET index, three (30%) were diagnosed with AD at three years. Of the 10 with an abnormal index originally, seven (70%) converted to AD. The finding that memory deficit in IMI was as pronounced as that in AD patients is consistent with the notion that memory is an initial symptom of AD. A substantial number of the IMI patients reflected regional hypometabolism similar to AD, suggesting that IMI is likely an early stage in progressive dementia. A large percentage of IMI patients converted clinically to AD within three years of initial study, though we observed impaired memory functioning well before a clinical diagnosis of AD could be made. In addition to potential clinical utility, IMI and PET represent an opportunity to study dementia in relation to brain chemistry at a time when brain pathology is in the process of development.