Short-term Memory Deficits Research Articles

The role of ADAM17 in cerebrovascular and cognitive function in the APP/PS1 mouse model of Alzheimer's disease.

The disintegrin and metalloproteinase 17 (ADAM17) exhibits α-secretase activity, whereby it can prevent the production of neurotoxic amyloid precursor protein-α (APP). ADAM17 is abundantly expressed in vascular endothelial cells and may act to regulate vascular homeostatic responses, including vasomotor function, vascular wall morphology, and formation of new blood vessels. The role of vascular ADAM17 in neurodegenerative diseases remains poorly understood. Here, we hypothesized that cerebrovascular ADAM17 plays a role in the pathogenesis of Alzheimer's disease (AD). We found that 9-10 months old APP/PS1 mice with b-amyloid accumulation and short-term memory and cognitive deficits display a markedly reduced expression of ADAM17 in cerebral microvessels. Systemic delivery and adeno-associated virus (AAV)-mediated re-expression of ADAM17 in APP/PS1 mice improved cognitive functioning, without affecting b-amyloid plaque density. In isolated and pressurized cerebral arteries of APP/PS1 mice the endothelium-dependent dilation to acetylcholine was significantly reduced, whereas the vascular smooth muscle-dependent dilation to the nitric oxide donor, sodium nitroprusside was maintained when compared to WT mice. The impaired endothelium-dependent vasodilation of cerebral arteries in APP/PS1 mice was restored to normal level by ADAM17 re-expression. The cerebral artery biomechanical properties (wall stress and elasticity) and microvascular network density was not affected by ADAM17 re-expression in the APP/PS1 mice. Additionally, proteomic analysis identified several differentially expressed molecules involved in AD neurodegeneration and neuronal repair mechanisms that were reversed by ADAM17 re-expression. Thus, we propose that a reduced ADAM17 expression in cerebral microvessels impairs vasodilator function, which may contribute to the development of cognitive dysfunction in APP/PS1 mice, and that ADAM17 can potentially be targeted for therapeutic intervention in AD.

A Comparative Study of the Impact of NO-Related Agents on MK-801- or Scopolamine-Induced Cognitive Impairments in the Morris Water Maze

Learning and memory deficits accompany numerous brain dysfunctions, including schizophrenia and Alzheimer's disease (AD), and many studies point to the role of nitric oxide (NO) in these processes. The present investigations constitute the follow-up of our previous research, in which we investigated the activity of NO releasers and a selective inhibitor of neuronal NO synthase (nNOS) to prevent short-term memory deficits in novel object recognition and T-maze. Here, the ability of the compounds to prevent the induction of long-term memory deficits by MK-801 or scopolamine administration was investigated. The Morris Water Maze test, a reliable and valid test of spatial learning and memory, was used, in which escape latency in the acquisition phase and nine different parameters in the retention phase were measured. A fast NO releaser (spermine NONOate), a slow NO releaser (DETA NONOate), and a nNOS inhibitor, N(ω)-propyl-L-arginine (NPLA), were used. The compounds were administered i.p. at a dose range of 0.05-0.5 mg/kg. All compounds prevented learning deficits in the acquisition phase and reversed reference memory deficits in the retention phase of the scopolamine-treated mice. Spermine NONOate was the least effective. In contrast, the drugs poorly antagonised MK-801-induced deficits, and only the administration of DETA NONOate induced some improvements in the retention trial.

Abstract TMP112: CD133+Exosome Treatment Improves Neuro-cognitive And Cardiac Function After Stroke In Female Adult Type 2 Diabetic Mice

Background: Cardiac complications post-stroke are common, and diabetes exacerbates post-stroke cardiac injury. In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improve neuro-cognitive and cardiac function in female type 2 diabetes mellitus (T2DM) mice subjected to ischemic stroke. Methods: Female, adult non-DM and T2DM mice were randomized to: 1) Non-DM (n=6), 2) Non-DM-stroke (n=15), 3) T2DM (n=8), 4) T2DM-stroke (n=12) and 5) T2DM-stroke+Exo (n=13). CD133+Exo (20μg/200μl PBS, i.v.) was administered 3 days after stroke. Evaluation of neurological function (mNSS, adhesive removal test), cognitive function (novel object recognition (NOR) test, odor test) and cardiac function (echocardiography) was performed, and mice were sacrificed at 28 days after stroke. Results: Stroke induces severe neurological deficits and significant short-term and long-term memory deficits which were worse in T2DM mice compared to non-DM mice. CD133+Exo treatment in T2DM-stroke mice significantly improves neurological function and cognitive outcome indicated by improved discrimination index in NOR test and odor test compared to control T2DM-stroke mice. T2DM-stroke induces significant cardiac dysfunction indicated by reduced left ventricular ejection fraction (LVEF) and shortening fraction (LVSF) compared to T2DM-control and non-DM-stroke mice. CD133+Exo treatment significantly improves LVEF, LVSF and heart rate and reduces left ventricular dimension compared to T2DM-stroke mice. T2DM-stroke mice exhibit significantly increased cardiomyocyte hypertrophy, cardiac fibrosis and inflammation compared to T2DM-control and non-DM-stroke mice. Treatment of T2DM-stroke with CD133+Exo significantly reduced cardiomyocyte hypertrophy, cardiac fibrosis and inflammation compared to T2DM-stroke mice. T2DM-stroke increases while CD133+Exo treatment reduces expression of serum inflammatory factors such as MMP-2, DKK-1, CRP, VCAM, CXCL5 and Cystatin-C. Conclusions: In T2DM-stroke mice, CD133+Exo treatment significantly improves neurological, cognitive, and cardiac function, and reduces cardiac pathological remodeling compared to T2DM-stroke control mice.

Abstract TMP77: Iga+ B Cells Are Recruited To The Brain After Intracerebral Hemorrhage

Introduction: There is ample evidence of a B cell response in human stroke patients, and evidence that long-term cognitive decline is linked to ongoing B cell activation in ischemic stroke models in mice. However, the role of B cells in hemorrhagic stroke, particularly at late timepoints, is unknown. Methods: Intracerebral hemorrhage (ICH) was induced in 12-week male C57BL/6 mice by collagenase (or saline for sham controls) injection into the striatum. Mice were perfused 2, 4, or 8 weeks post-ICH or sham, ipsilateral and contralateral hemispheres were harvested and B cell counts analyzed by flow cytometry. Motor deficits were measured via grid walk test and short-term memory was tested by Y maze at 1, 2, 4, 8, 12, and 16 weeks post-ICH or sham. B cell repertoire analysis was conducted by PCR amplification and molecular cloning of B cells in 8 week post-ICH or naïve brain tissue, followed by Sanger sequencing and comparison to the IMGT database. Results: B cells are robustly recruited to the ipsilateral hemisphere as early as 2 weeks post-ICH (2439 +/- 987 cells; n=5) and persist at 8 weeks (14,162 +/- 12,103 cells, n=4). At 2 and 4 weeks a small fraction of B cells in the ipsilateral hemisphere are IgA+ (2 weeks=14.0% +/- 6.8%, n=5; 4 weeks=13.3% +/- 4.6%, n=3). Interestingly, by 8 weeks post-ICH this proportion significantly increased in ICH (41.3% +/- 22.8, n=6) but not sham controls (12.0% +/- 11.8%, n=5). While our work has demonstrated no significant motor deficit after 2 weeks post-ICH, preliminary data suggests a cognitive short-term memory deficit starting 16 weeks post-ICH. Furthermore, we have found that post-ICH brain-infiltrating IgA+ B cells are somatically hypermutated and show diverse V gene usage. Conclusion: Our findings suggest that ICH induces a robust, delayed IgA+ B cell response within the affected brain hemisphere, underscoring the need to better understand how B cells shape post-stroke inflammation and recovery, particularly at late timepoints.

Relationship Between Cannabis Use and Immediate, Delayed, and Working Memory Performance Among Older Adults.

Cannabis is increasingly accessible and use is increasing rapidly among older adults as laws change and cannabis becomes more frequently prescribed in healthcare settings. Past research identified cognitive effects of cannabis use among adolescents and young adults that can persist for several weeks after intoxication, though little is known about how these effects generalize to older adults. Participants (N = 1348) were drawn from the Health and Retirement Study (HRS) and were categorized as current occasional users (up to once/week in the past year, n = 36), current frequent users (once per week or more in the past year, n = 92), past users (n = 334), and non-users (n = 886). Participant ages ranged from 50 to 98 (M = 67.25, SD = 10.68). Uncontrolled, one-way ANOVAs and controlled ANCOVAs were used to examine between-group differences on immediate and delayed wordlist memory and working memory (serial sevens). When controlling for age, gender, education, and minority status, current frequent users demonstrated significantly worse immediate memory performance compared to past and non-users. However, this difference could have been the result of acute, residual effects of past-month cannabis use among current users. In controlled analyses, there were no differences between groups on delayed or working memory. Findings indicate that greater than weekly cannabis use may result in attentional and short-term memory deficits. Further, these effects may be mitigated by sustained abstinence. Limitations including sample size and measures of cannabis use warrant future studies to replicate and build upon these findings.

Dietary choline metabolite TMAO impairs cognitive function and induces hippocampal synaptic plasticity declining through the mTOR/P70S6K/4EBP1 pathway.

Mild cognitive impairment (MCI) is an intermediate state between "healthy" and "dementia", which affects memory and cognitive function. Timely intervention and treatment of MCI can effectively prevent it from developing into an incurable neurodegenerative disease. Lifestyle factors, such as dietary habits, were highlighted as risk factors for MCI. The effect of a high-choline diet on cognitive function is contentious. In this study, we focus our attention on the choline metabolite trimethylamine-oxide (TMAO), an acknowledged pathogenic molecule of cardiovascular disease (CVD). With recent studies indicating that TMAO also plays a potential role in the central nervous system (CNS), we aim to explore the effect of TMAO on synaptic plasticity in the hippocampus, the basic structure of studying and memory. Using various hippocampal-dependent spatial references or working memory-related behavioral texts, we found that TMAO treatment caused both long-term memory (LTM) and short-term memory (STM) deficits in vivo. Simultaneously, the plasm and whole brain levels of choline and TMAO were measured by employing liquid phase mass spectrometry (LC/MS). Furthermore, the effects of TMAO on the hippocampus were further explored by applying Nissl staining and transmission electron microscopy (TEM). Moreover, the expression of synaptic plasticity-related proteins, including synaptophysin (SYN), postsynaptic density protein95 (PSD95), and N-methyl-aspartate receptor (NMDAR), was examined by western blotting and immunohistochemical (IHC). The results showed that TMAO treatment contributes to neuron loss, synapse ultrastructure alteration, and synaptic plasticity impairments. In mechanism, the mammalian target of rapamycin (mTOR) regulates synaptic function, and the activation of the mTOR signaling pathway was observed in TMAO groups. In conclusion, this study confirmed that the choline metabolite TMAO can induce hippocampal-dependent learning and memory ability impairment with synaptic plasticity deficits by activating the mTOR signaling pathway. The effects of choline metabolites on cognitive function may provide a theoretical basis for establishing the daily reference intakes (DRIs) of choline.

Carotid Body Resection Prevents Short-Term Spatial Memory Decline in Prediabetic Rats Without Changing Insulin Signaling in the Hippocampus and Prefrontal Cortex.

Individuals who develop type 2 diabetes (T2D) at an early age are at higher risk of developing neurodegenerative disorders such as Alzheimer's and Parkinson's disease. A shared dysfunctional characteristic between T2D and these neurodegenerative disorders is insulin resistance. Recently, it was shown that prediabetes animals and patients exhibited increased carotid body (CB) activity. Moreover, these organs are deeply involved in the development of metabolic diseases, since upon abolishment of their activity via carotid sinus nerve (CSN) resection, several dysmetabolic features of T2D were reverted. Herein, we investigated if CSN resection may also prevent cognitive impairment associated with brain insulin resistance. We explored a diet-induced prediabetes animal model where Wistar rats are kept in a high fat-high sucrose (HFHSu) diet for 20weeks. We evaluated CSN resection effects on behavioral parameters and on insulin signaling-related proteins levels, in the prefrontal cortex and the hippocampus. HFHSu animals exhibited impaired short-term memory evaluated by the y-maze test. Remarkably, CSN resection prevented the development of this phenotype. HFHSu diet or CSN resection did not promote significant alterations in insulin signaling-associated proteins levels. Our findings suggest that CBs modulation might have a role in preventing short-term spatial memory deficits associated with peripheral dysmetabolic states.

Restoring Age-Related Cognitive Decline through Environmental Enrichment: A Transcriptomic Approach

Cognitive decline is one of the greatest health threats of old age and the maintenance of optimal brain function across a lifespan remains a big challenge. The hippocampus is considered particularly vulnerable but there is cross-species consensus that its functional integrity benefits from the early and continuous exercise of demanding physical, social and mental activities, also referred to as environmental enrichment (EE). Here, we investigated the extent to which late-onset EE can improve the already-impaired cognitive abilities of lifelong deprived C57BL/6 mice and how it affects gene expression in the hippocampus. To this end, 5- and 24-month-old mice housed in standard cages (5mSC and 24mSC) and 24-month-old mice exposed to EE in the last 2 months of their life (24mEE) were subjected to a Barnes maze task followed by next-generation RNA sequencing of the hippocampal tissue. Our analyses showed that late-onset EE was able to restore deficits in spatial learning and short-term memory in 24-month-old mice. These positive cognitive effects were reflected by specific changes in the hippocampal transcriptome, where late-onset EE affected transcription much more than age (24mSC vs. 24mEE: 1311 DEGs, 24mSC vs. 5mSC: 860 DEGs). Remarkably, a small intersection of 72 age-related DEGs was counter-regulated by late-onset EE. Of these, Bcl3, Cttnbp2, Diexf, Esr2, Grb10, Il4ra, Inhba, Rras2, Rps6ka1 and Socs3 appear to be particularly relevant as key regulators involved in dendritic spine plasticity and in age-relevant molecular signaling cascades mediating senescence, insulin resistance, apoptosis and tissue regeneration. In summary, our observations suggest that the brains of aged mice in standard cage housing preserve a considerable degree of plasticity. Switching them to EE proved to be a promising and non-pharmacological intervention against cognitive decline.

Posterior cortical atrophy in logopenic progressive aphasia: A case report

Posterior Cortical Atrophy (PCA) and Logopenic progressive aphasia (LPA) are nonamnestic variants of Alzheimer's disease (AD). Language deficits are a hallmark of LPA but not PCA. Studies have revealed the presence of language deficits in PCA similar to LPA, however it has not been a consistent observation. Only alexia and agraphia are the language deficits listed in the latest consensus criteria for classification of PCA. In this case report we present the clinical, cognitive-linguistic, and neuroimaging features of a patient presenting with an unusual overlap of LPA-PCA. Although the diagnostic characteristics for LPA is fulfilled, the probable progression of the disease to exhibit most of the characteristics similar to PCA is highlighted. Thus, it contributes to the notion of a continuum between the two atypical variants of AD. The possibility of patients with PCA to exhibit language deficits with the progression of the disease similar to that of LPA that primarily involves the phonological short-term memory deficits is emphasized. The need to not undermine the language deficits irrespective of the stage of the disease in PCA is weighed upon for a better identification and management via speech-language intervention programs.

Short term memory in aphasia: effects of modality and relationship with Western Aphasia Battery-R performance

ABSTRACT Background Producing and comprehending language requires maintenance of linguistic units in short term memory (STM). While there is evidence of verbal STM impairments in persons with aphasia (PWA), there are unresolved questions about other aspects of STM in aphasia, particularly the role of input and output modalities on STM performance. This includes the extent to which visual STM abilities are impaired in PWA and if the modality of eliciting responses (verbal versus pointing) influences STM performance. A better understanding of the relationship between STM performance and clinical language assessments of PWA will inform test interpretation. Aims This study investigated three questions about short term memory (STM) performance in post-stroke aphasia: 1) whether visual STM is impaired in PWA given that a common neural network subserves encoding-recall of both verbal and visual STM, 2) whether the response modality (verbal vs pointing) impacts STM score, 3) the relationship between STM and language performance, specifically on the Western Aphasia Battery-Revised (WAB-R). Methods & Procedures Verbal and visuo-spatial performance on a STM battery was compared between 45 PWA and a representative neurotypical sample (N=40). For PWA, individual performance across STM subtasks was examined to identify dissociations and correlated with language performance on the WAB-R. Outcomes & Results PWA scored lower than neurotypical controls on verbal but not visual STM tasks. At the individual level, about one-half of PWA were impaired on the three verbal STM tasks, and one-third had dissociations among the three verbal STM tasks. There was no effect of response modality (verbal versus pointing) on verbal STM performance. There was a strong association between verbal STM and individual subtests of the WAB-R. In general, the relative phonological and semantic demands of the task (e.g. repetition) influenced the association strength with digit recall versus picture recall scores. Conclusions Verbal STM deficits are: 1) more prevalent than visual-spatial STM deficits in PWA, 2) strongly associated with WAB-R performance in a pattern that is consistent with the phonological and semantic demands of the tasks. The clinical implications of this study are that it is crucial to assess STM performance in PWA and examine its potential impact on language assessments. Further, a verbal or pointing response modality can be used for STM measurement without negatively impacting the score (unless there are clear motoric contra-indications). This study provides performance data for a set of aphasia-friendly STM tasks that can serve as future reference.

Integrating Verbal Short-Term Memory Into the Assessment and Treatment of Aphasia

Purpose:Verbal short-term memory (STM) impairment is ubiquitous in people with aphasia, and its severity generally parallels the severity of word processing impairment. In language-based models of STM, verbal STM arises from the activation and maintenance of linguistic representations. Measures of verbal STM can provide insight into the nature of language processing deficits in aphasia and should be a component of comprehensive assessment and treatment plans. Although verbal STM impairment in aphasia is widely studied in the research community, inclusion of verbal STM assessment and treatment in clinical practice remains limited.Method:This tutorial presents a description of language-based models of verbal STM and factors that contribute to performance in verbal STM tasks. We outline a model of verbal STM assessment and intervention that considers two levels of linguistic processing deficits (i.e., semantic vs. phonological), temporal variability in performance and access to representations (activation transmission vs. maintenance), and the effects of memory load. This tutorial presents a practical framework for the integration of measures of verbal STM in both assessment and treatment. Case studies are included to facilitate learning.Conclusions:This tutorial provides clinicians with the theoretical background and practical framework for integration of verbal STM in both treatment and assessment. While the assessment and treatment of verbal STM deficits in aphasia is in the beginning stages of implementation in the clinical setting, it offers a promising avenue for aphasia rehabilitation.

Zinc supplement reverses short-term memory deficit in sodium benzoate-induced neurotoxicity in male Wistar rats by enhancing anti-oxidative capacity via Nrf 2 up-regulation

Sodium benzoate (SB) is a commonly-used food preservative, with a controversial report to its neurological benefit and toxicity. Zinc (Zn) is a trace element that plays a crucial role in memory, inflammation and oxidative stress. This study was to investigate the effect of SB on rat cognition and memory and the possible modulatory effect of Zn supplement. Twenty four male Wistar rats were divided into four groups of six animals each. Animals in groups 1–4 were treated with normal saline 1 ml/kg, SB 200 mg/kg, zinc sulphate 10 ml/kg and SB 200 mg/kg + zinc sulphate 10 ml/kg/day daily respectively for three weeks. After treatment, the animals were subjected to different behavioural tests, and then sacrificed. Their blood samples were collected for catalase(CAT), superoxide dismutase(SOD) and interleukin-1B(IL-1B) assay. Brain samples were also collected for nuclear factor-erythroid-related factor 2(Nrf2), and acetylcholinesterase (AchE) mRNA gene expression. The serum levels of CAT and SOD were (p < 0.0001; p < 0.0001) reduced in the SB only-treated group compared to the other groups. Nrf2 gene expression was totally shut down in the SB only-treated group but, up-regulated in the Zn-treated groups (p < 0.0001). The serum level of IL-1B was higher in the SB only-treated group compared to the other groups. SB-treated group spent longer time in the close arm (p = <0.0001), shorter time in the open arm (p = <0.0001) and had higher anxiety index (p = 0.0045) than the Zn-treated groups. Conclusively, Zinc improves memory deficit, has anxiolytic, anti-oxidant and anti-inflammatory properties.

Choroid plexus-CSF-targeted antioxidant therapy protects the brain from toxicity of cancer chemotherapy

For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemotherapy-related cognitive impairment (CRCI). We discovered that the chemotherapy methotrexate (MTX) adversely affects oxidative metabolism of non-cancerous choroid plexus (ChP) cells and the cerebrospinal fluid (CSF). We used a ChP-targeted adeno-associated viral (AAV) vector approach in mice to augment CSF levels of the secreted antioxidant SOD3. AAV-SOD3 gene therapy increased oxidative defense capacity of the CSF and prevented MTX-induced lipid peroxidation in the hippocampus. Furthermore, this gene therapy prevented anxiety and deficits in short-term learning and memory caused by MTX. MTX-induced oxidative damage to cultured human cortical neurons and analyses of CSF samples from MTX-treated lymphoma patients demonstrated that MTX diminishes antioxidant capacity of patient CSF. Collectively, our findings motivate the advancement of ChP- and CSF-targeted anti-oxidative prophylactic measures to relieve CRCI.

A-161 Neuropsychological Findings and Atypical Motoric Features Associated with Hashimoto Encephalopathy in a 52-year-old Male

Abstract Objective: Hashimoto encephalopathy (HE) is a rare neurological condition with pathophysiology associated with elevated autoimmune anti-thyroid antibodies. The condition, associated with Hashimoto’s thyroiditis, is found more commonly in women. Clinical presentations of HE vary significantly, with cognitive deficit and generalized seizures as the most prominent manifestations. While there is robust literature illustrating HE in female populations, literature on HE in male patients, particularly with dominant motoric features, remains limited. Methods: A 52-year-old, right-handed, Caucasian male presented for evaluation reporting difficulties with short-term memory, word-finding, disorientation, and motor deficits. The patient exhibited significant motor symptoms including myotonia, micrographia, fasciculations and paresthesias, phantosmia, and myoclonic jerking, beginning in 2017 with progressive decline. Relevant medical history includes Hashimoto thyroiditis (2021), focal temporal EEG abnormalities (2021), dystonia (2021), and migraines. Prior to presenting concerns, the patient was otherwise generally healthy. Neuroimaging (MRI) revealed increased signal intensity in the subcortical white matter of the right frontal lobe. He was dependent in several instrumental activities of daily living. Results: His premorbid baseline was estimated to be in the average range. His neurocognitive profile was marked by mild impairments in immediate and delayed verbal memory and recognition paradigms, whereas he demonstrated moderate impairments in processing speed and motor functioning. Conculsion: Taken together, his neurocognitive profile, clinical history, and functional independence are consistent with the clinical presentation of HE. His cognitive deficits and epileptiform activity are consistent with prominent manifestations of HE, whereas his pronounced motoric features are seemingly aberrant in HE. Furthermore, post-steroidal treatment revealed increased cognitive proficiency on a single mental status examination.

Understanding the multidimensional cognitive deficits of logopenic variant primary progressive aphasia.

The logopenic variant of primary progressive aphasia is characterized by early deficits in language production and phonological short-term memory, attributed to left-lateralized temporoparietal, inferior parietal and posterior temporal neurodegeneration. Despite patients primarily complaining of language difficulties, emerging evidence points to performance deficits in non-linguistic domains. Temporoparietal cortex, and functional brain networks anchored to this region, are implicated as putative neural substrates of non-linguistic cognitive deficits in logopenic variant primary progressive aphasia, suggesting that degeneration of a shared set of brain regions may result in co-occurring linguistic and non-linguistic dysfunction early in the disease course. Here, we provide a Review aimed at broadening the understanding of logopenic variant primary progressive aphasia beyond the lens of an exclusive language disorder. By considering behavioural and neuroimaging research on non-linguistic dysfunction in logopenic variant primary progressive aphasia, we propose that a significant portion of multidimensional cognitive features can be explained by degeneration of temporal/inferior parietal cortices and connected regions. Drawing on insights from normative cognitive neuroscience, we propose that these regions underpin a combination of domain-general and domain-selective cognitive processes, whose disruption results in multifaceted cognitive deficits including aphasia. This account explains the common emergence of linguistic and non-linguistic cognitive difficulties in logopenic variant primary progressive aphasia, and predicts phenotypic diversification associated with progression of pathology in posterior neocortex.

Impact of High Fat Consumption on Neurological Functions after Traumatic Brain Injury in Rats.

Traumatic brain injury (TBI) and obesity are two common conditions in modern society; both can impair neuronal integrity and neurological function. However, it is unclear whether the coexistence of both conditions will worsen outcomes. Therefore, in a rat model, we aimed to investigate whether the coexistence of TBI and a high-fat diet (HFD) has an additive effect, leading to more severe neurological impairments, and whether they are related to changes in brain protein markers of oxidative stress, inflammation, and synaptic plasticity. Sprague-Dawley rats (female, ∼250 g) were divided into HFD (43% fat) and diet (CD) (17% fat) groups for 6 weeks. Within each dietary group, half underwent a TBI by a weight-drop device, and the other half underwent sham surgery. Short-term memory and sensory function were measured at 24 h, 1 week, 3 weeks, and 6 weeks post-TBI. Brain tissues were harvested at 24 h and 6 weeks post-TBI, and markers of oxidative stress, apoptosis, inflammation, and synaptic plasticity were measured via immunostaining and Western blotting. In rats without TBI, HFD increased the pre-synaptic protein synaptophysin. In rats with TBI, HFD resulted in worsened sensory and memory function, an increase in activated macrophages, and a decrease in the endogenous antioxidant manganese superoxide dismutase (MnSOD). Our findings suggest that the additive effect of HFD and TBI worsens short term memory and sensation deficits, and may be driven by enhanced oxidative stress and inflammation.

Habilidades cognitivas de idosos institucionalizados com sintomas depressivos

ABSTRACT Objective To determine the level of association between depressive symptoms and cognitive abilities of institutionalized older adults. Methods This is a cross-sectional study that enrolled 69 older adults, living in a long-term care facility. Investigation of depressive symptoms in all individuals was performed using the geriatric depression scale. Cognitive verbal fluency, digit span forward (DSF) and backward (DSB) tests, and two-minute stationary gait, sit-to-stand test, and six-minute walk test were performed to assess their association with depressive symptoms. Results Depressive symptoms were identified in 35 individuals. Worse cognition and physical performances were associated with the presence of depressive symptoms – Mini-Mental State Examination [t (61) = 2.36; p &lt; 0.05] and Stationary gait test of two minutes [t (53) = 3.12; p &lt; 0.05]. Short-term memory and working memory tests presented worse results in individuals with depressive symptoms (DSF: U = 402.00; p &lt; 0.05 e DSB: U = 341,00; p &lt; 0.05). Older adults with scores below normal in DSF were 5 times more likely to exhibit depressive symptoms. Conclusion The importance of physical, cognitive and social intervention strategies in long-term care facilities for the older adults is highlighted, in order to privilege autonomy. Notably, there is an association between deficits in short-term memory and the presence of depressive symptoms in older adults. Therefore, prospective studies are suggested to investigate the cause-effect relationship of this association with the institutionalization of older adults.

Auditory Verb Generation Performance Patterns Dissociate Variants of Primary Progressive Aphasia.

Primary progressive aphasia (PPA) is a clinical syndrome in which patients progressively lose speech and language abilities. Three variants are recognized: logopenic (lvPPA), associated with phonology and/or short-term verbal memory deficits accompanied by left temporo-parietal atrophy; semantic (svPPA), associated with semantic deficits and anterior temporal lobe (ATL) atrophy; non-fluent (nfvPPA) associated with grammar and/or speech-motor deficits and inferior frontal gyrus (IFG) atrophy. Here, we set out to investigate whether the three variants of PPA can be dissociated based on error patterns in a single language task. We recruited 21 lvPPA, 28 svPPA, and 24 nfvPPA patients, together with 31 healthy controls, and analyzed their performance on an auditory noun-to-verb generation task, which requires auditory analysis of the input, access to and selection of relevant lexical and semantic knowledge, as well as preparation and execution of speech. Task accuracy differed across the three variants and controls, with lvPPA and nfvPPA having the lowest and highest accuracy, respectively. Critically, machine learning analysis of the different error types yielded above-chance classification of patients into their corresponding group. An analysis of the error types revealed clear variant-specific effects: lvPPA patients produced the highest percentage of “not-a-verb” responses and the highest number of semantically related nouns (production of baseball instead of throw to noun ball); in contrast, svPPA patients produced the highest percentage of “unrelated verb” responses and the highest number of light verbs (production of take instead of throw to noun ball). Taken together, our findings indicate that error patterns in an auditory verb generation task are associated with the breakdown of different neurocognitive mechanisms across PPA variants. Specifically, they corroborate the link between temporo-parietal regions with lexical processing, as well as ATL with semantic processes. These findings illustrate how the analysis of pattern of responses can help PPA phenotyping and heighten diagnostic sensitivity, while providing insights on the neural correlates of different components of language.

Assessment of Hippocampal Cell Death and Memory Deficits in Rats Following Neonatal Stress

Objective: Neonatal stress (NS) has harmful effects on the hippocampal neurons of rat neonates. It has been reported to enhance neuronal cell death and impair memory behaviors. The researchers conducted this study in order to assess NS’s effects on hippocampal apoptosis and memory deficits in rat neonates’ hippocampus. Methods: Three groups of male Wistar rat neonates exposed to NS; rat neonates reared with 1 hour neonatal isolation (NI) for 8 consecutive days (P2-P9), rat neonates exposed to febrile seizure (FS) at day 10 (P10) and rat neonates reared with both NI plus FS (NI-FS). Control group was reared normally. Novel object recognition test (NORT) carried out to evaluate the effects of NI, FS and NI-FS on memory deficits. At day 22 (P22), Terminal deoxynucleotidyl transferase- mediated dUTP nick end labeling (TUNEL) assay was done. Results: NORT demonstrated that rat neonates exposed to NI-FS had short-term and long-term memory deficits (P&lt;0.01 and P&lt;0.001). Rat neonates experienced NI had long-term memory deficits (P&lt;0.05). TUNEL assay results showed that NI-FS increased the count of hippocampal apoptotic neurons in Cornu Ammonis 1 (CA1), Cornu Ammonis 3 (CA3) and dentate gyrus (DG) subfields (P&lt;0.001, P&lt;0.001 and P&lt;0.001). Also, NI increased the count of hippocampal TUNEL positive cells in CA3 and DG subfields (P&lt;0.05 and P&lt;0.01). In addition, FS increased the count of hippocampal apoptotic neurons in DG subfield (P&lt;0.05). Conclusion: The present results showed that NS exerted apoptotic effect and induced memory deficits in the hippocampus of rat neonate.

The Percentages of Cognitive Skills Deficits among Chinese Children with Developmental Dyslexia: A Systematic Review and Meta-Analysis.

The current study was conducted to examine the percentages of cognitive skills deficits among Chinese children with developmental dyslexia. Via a systematic review, we collated twenty-two available studies on the proportion of cognitive skills deficits, including phonological awareness, rapid automatized naming, morphological awareness, orthographic knowledge, short-term memory and working memory, and visual and motor skills deficits, among Chinese children with developmental dyslexia. The results of a meta-analysis showed that the rapid automatized naming deficits are the core deficit of developmental dyslexia among Chinese children, with a pooled percentage of 44%. This is followed by orthographic knowledge deficits (43%), phonological awareness deficits (41%), morphological awareness deficits (40%), visual and motor skills deficits (33%), and short-term memory and working memory deficits (25%). At the same time, we compared the proportions of different locations, ages, standards and control groups.