Short-term Memory Deficits Research Articles

Clinical Aspects of Alzheimer Disease

The clinical diagnosis of Alzheimer disease (AD) has been well established, but there is a widespread misunderstanding about the relationship between dementia (a syndrome) and AD (a cause of dementia). AD is the most common etiology that causes dementia in mid- and late life. The prototypical clinical presentation is that of a gradually worsening problem with learning new information, that is, a short-term memory deficit, accompanied by cognitive impairment in other domains, including language, spatial cognition, and executive functioning, as well as changes in personality and behavior. A key element of the diagnosis of dementia is that daily functioning is impaired. The concept of mild cognitive impairment (MCI) as the earliest symptomatic presentation of a dementing illness is now widely accepted. MCI due to AD typically presents with isolated problems with learning and memory without substantial loss of ability to function in daily life. Less common variants of AD are now recognized and include a disorder in which spatial and visual cognitive dysfunction occurs or in which word-finding problems predominate at the onset of symptoms. Although AD as a cause of dementia is the most common among etiologies, AD often co-occurs with other neurodegenerative diseases and with cerebrovascular disease. The presence of multietiology dementia in which AD is a contributor is particularly common in the eighth decade of life and beyond. This review contains 1 figure, 3 tables, and 28 references Keywords: Alzheimer disease, cognitive impairment, dementia, mild cognitive impairment

Clinical Aspects of Alzheimer Disease

The clinical diagnosis of Alzheimer disease (AD) has been well established, but there is a widespread misunderstanding about the relationship between dementia (a syndrome) and AD (a cause of dementia). AD is the most common etiology that causes dementia in mid- and late life. The prototypical clinical presentation is that of a gradually worsening problem with learning new information, that is, a short-term memory deficit, accompanied by cognitive impairment in other domains, including language, spatial cognition, and executive functioning, as well as changes in personality and behavior. A key element of the diagnosis of dementia is that daily functioning is impaired. The concept of mild cognitive impairment (MCI) as the earliest symptomatic presentation of a dementing illness is now widely accepted. MCI due to AD typically presents with isolated problems with learning and memory without substantial loss of ability to function in daily life. Less common variants of AD are now recognized and include a disorder in which spatial and visual cognitive dysfunction occurs or in which word-finding problems predominate at the onset of symptoms. Although AD as a cause of dementia is the most common among etiologies, AD often co-occurs with other neurodegenerative diseases and with cerebrovascular disease. The presence of multietiology dementia in which AD is a contributor is particularly common in the eighth decade of life and beyond. This review contains 1 figure, 3 tables, and 28 references Keywords: Alzheimer disease, cognitive impairment, dementia, mild cognitive impairment

Distinct contributions of GluA1-containing AMPA receptors of different hippocampal subfields to salience processing, memory and impulse control

Schizophrenia is associated with a broad range of severe and currently pharmacoresistant cognitive deficits. Prior evidence suggests that hypofunction of AMPA-type glutamate receptors (AMPARs) containing the subunit GLUA1, encoded by GRIA1, might be causally related to impairments of selective attention and memory in this disorder, at least in some patients. In order to clarify the roles of GluA1 in distinct cell populations, we investigated behavioural consequences of selective Gria1-knockout in excitatory neurons of subdivisions of the prefrontal cortex and the hippocampus, assessing sustained attention, impulsivity, cognitive flexibility, anxiety, sociability, hyperactivity, and various forms of short-term memory in mice. We found that virally induced reduction of GluA1 across multiple hippocampal subfields impaired spatial working memory. Transgene-mediated ablation of GluA1 from excitatory cells of CA2 impaired short-term memory for conspecifics and objects. Gria1 knockout in CA3 pyramidal cells caused mild impairments of object-related and spatial short-term memory, but appeared to partially increase social interaction and sustained attention and to reduce motor impulsivity. Our data suggest that reduced hippocampal GluA1 expression—as seen in some patients with schizophrenia—may be a central cause particularly for several short-term memory deficits. However, as impulse control and sustained attention actually appeared to improve with GluA1 ablation in CA3, strategies of enhancement of AMPAR signalling likely require a fine balance to be therapeutically effective across the broad symptom spectrum of schizophrenia.

The sGC stimulator BAY-747 and activator runcaciguat can enhance memory in vivo via differential hippocampal plasticity mechanisms

Soluble guanylate cyclase (sGC) requires a heme-group bound in order to produce cGMP, a second messenger involved in memory formation, while heme-free sGC is inactive. Two compound classes can increase sGC activity: sGC stimulators acting on heme-bound sGC, and sGC activators acting on heme-free sGC. In this rodent study, we investigated the potential of the novel brain-penetrant sGC stimulator BAY-747 and sGC activator runcaciguat to enhance long-term memory and attenuate short-term memory deficits induced by the NOS-inhibitor L-NAME. Furthermore, hippocampal plasticity mechanisms were investigated. In vivo, oral administration of BAY-747 and runcaciguat to male Wistar rats enhanced memory acquisition in the object location task (OLT), while only BAY-747 reversed L-NAME induced memory impairments in the OLT. Ex vivo, both BAY-747 and runcaciguat enhanced hippocampal GluA1-containing AMPA receptor (AMPAR) trafficking in a chemical LTP model for memory acquisition using acute mouse hippocampal slices. In vivo only runcaciguat acted on the glutamatergic AMPAR system in hippocampal memory acquisition processes, while for BAY-747 the effects on the neurotrophic system were more pronounced as measured in male mice using western blot. Altogether this study shows that sGC stimulators and activators have potential as cognition enhancers, while the underlying plasticity mechanisms may determine disease-specific effectiveness.

Acetylcholine deficiency disrupts extratelencephalic projection neurons in the prefrontal cortex in a mouse model of Alzheimer\u2019s disease

Short-term memory deficits have been associated with prefrontal cortex (PFC) dysfunction in Alzheimer’s disease (AD) and AD mouse models. Extratelencephalic projection (ET) neurons in the PFC play a key role in short-term working memory, but the mechanism between ET neuronal dysfunction in the PFC and short-term memory impairment in AD is not well understood. Here, using fiber photometry and optogenetics, we found reduced neural activity in the ET neurons in the medial prefrontal cortex (mPFC) of the 5×FAD mouse model led to object recognition memory (ORM) deficits. Activation of ET neurons in the mPFC of 5×FAD mice rescued ORM impairment, and inhibition of ET neurons in the mPFC of wild type mice impaired ORM expression. ET neurons in the mPFC that project to supramammillary nucleus were necessary for ORM expression. Viral tracing and in vivo recording revealed that mPFC ET neurons received fewer cholinergic inputs from the basal forebrain in 5×FAD mice. Furthermore, activation of cholinergic fibers in the mPFC rescued ORM deficits in 5×FAD mice, while acetylcholine deficiency reduced the response of ET neurons in the mPFC to familiar objects. Taken together, our results revealed a neural mechanism behind ORM impairment in 5×FAD mice.

Glucosylceramide synthase inhibition reduces ganglioside GM3 accumulation, alleviates amyloid neuropathology, and stabilizes remote contextual memory in a mouse model of Alzheimer\u2019s disease

BackgroundGangliosides are highly enriched in the brain and are critical for its normal development and function. However, in some rare neurometabolic diseases, a deficiency in lysosomal ganglioside hydrolysis is pathogenic and leads to early-onset neurodegeneration, neuroinflammation, demyelination, and dementia. Increasing evidence also suggests that more subtle ganglioside accumulation contributes to the pathogenesis of more common neurological disorders including Alzheimer’s disease (AD). Notably, ganglioside GM3 levels are elevated in the brains of AD patients and in several mouse models of AD, and plasma GM3 levels positively correlate with disease severity in AD patients.MethodsTg2576 AD model mice were fed chow formulated with a small molecule inhibitor of glucosylceramide synthase (GCSi) to determine whether reducing glycosphingolipid synthesis affected aberrant GM3 accumulation, amyloid burden, and disease manifestations in cognitive impairment. GM3 was measured with LC-MS, amyloid burden with ELISA and amyloid red staining, and memory was assessed using the contextual fear chamber test.ResultsGCSi mitigated soluble Aβ42 accumulation in the brains of AD model mice when treatment was started prophylactically. Remarkably, GCSi treatment also reduced soluble Aβ42 levels and amyloid plaque burden in aged (i.e., 70 weeks old) AD mice with preexisting neuropathology. Our analysis of contextual memory in Tg2576 mice showed that impairments in remote (cortical-dependent) memory consolidation preceded deficits in short-term (hippocampal-dependent) contextual memory, which was consistent with soluble Aβ42 accumulation occurring more rapidly in the cortex of AD mice compared to the hippocampus. Notably, GCSi treatment significantly stabilized remote memory consolidation in AD mice—especially in mice with enhanced cognitive training. This finding was consistent with GCSi treatment lowering aberrant GM3 accumulation in the cortex of AD mice.ConclusionsCollectively, our results indicate that glycosphingolipids regulated by GCS are important modulators of Aβ neuropathology and that glycosphingolipid homeostasis plays a critical role in the consolidation of remote memories.

Effects of Prenatal Nicotine, THC, or Co-Exposure on Cognitive Behaviors in Adolescent Male and Female Rats.

Although there has been a decrease in the prevalence of tobacco smoking, exposure to nicotine during pregnancy remains a substantial problem worldwide. Further, given the recent escalation in e-cigarette use and legalization of cannabis, it has become essential to understand the effects of nicotine and cannabinoid co-exposure during early developmental stages. We systematically examined the effects of nicotine and/or THC prenatal exposure on cognitive behaviors in male and female offspring. Dams were exposed to nicotine vape or vehicle, and oral edible THC or vehicle, throughout pregnancy. Adolescent offspring were then tested in the prepulse inhibition test, novel object recognition task, and novelty suppressed feeding task. At birth, pups from mothers exposed to nicotine vape or oral THC exhibited reduced body weight, compared to control pups. Prenatal nicotine vape exposure resulted in a decreased baseline startle reactivity in adolescent male and female rats, and in females, enhanced sensorimotor gating in the prepulse inhibition test. Prenatal nicotine and THC co-exposure resulted in significant deficits in the prepulse inhibition test in males. Deficits in short-term memory were also found in males prenatally exposed to THC, either alone or with nicotine co-exposure, and in females exposed to THC alone. Finally, in males, a modest increase in anxiety-associated behaviors was found with THC or nicotine exposure in the latency to approach a novel palatable food. These studies demonstrate differential effects of prenatal exposure to e-cigarette nicotine vape and/or edible THC on cognitive function, with differing effects within male and female groups. These studies demonstrate an impact of nicotine, THC, or co-exposure during early developmental stages in utero on behavioral outcomes in adolescence. These findings have important translational implications given the continued use of nicotine and THC containing products by pregnant women worldwide, which can be applied to support healthcare and policy efforts restricting nicotine and THC use during pregnancy.

Exploring Cognitive Impairment in Patients With Bilateral Capsular Genu Lesions

The authors investigated for presence of cognitive impairment after occurrence of bilateral lesions of the genu of the internal capsule (GIC). Clinical and neuropsychological features of unilateral GIC lesions have previously been studied, but the cognitive profile of bilateral lesions of the GIC has not been fully explored. An investigation was conducted of neurocognitive deficits and computerized tomography MRI findings among 4,200 stroke patients with bilateral GIC involvement who were admitted to the hospital between January 2010 and October 2018. Eight patients with bilateral lesions of the capsular genu were identified and their data analyzed. Overall, behavioral and cognitive dysfunction were characterized by impairment of frontal, memory, and executive functions. Attention and abstraction were present among all eight patients (100%); apathy, abulia, and executive dysfunctions, among seven (87.5%); global mental dysfunction and planning deficits, among six (75.0%); short-term verbal memory deficits and language dysfunctions, among five (62.5%); long-term verbal memory deficits, among four (50.0%); and spatial memory deficits, reading, writing, counting dysfunctions, and anarthria, among two (25.0%). Four of the patients (50.0%) without a history of cognitive disorder showed severe mental deterioration compatible with the clinical picture of dementia. A clinical picture of dementia was still present in these patients 6 months after stroke. Bilateral lesions of the capsular genu appearing either simultaneously or at different times were significantly associated with executive dysfunctions.

Cognitive difficulties in people with systemic sclerosis: a qualitative study.

This study used a qualitative approach to explore how people with SSc experience cognitive changes and how cognitive difficulties impact their functioning. Four 90-min focus groups of adults with SSc and self-reported changes in cognition were recruited from a SSc research registry and targeted social media. A focus group guide elicited information from participants via open-ended questions. Content analysis was conducted using grounded theory methodology. There were 20 participants (mean age = 55.5 (11.4) years) comprising 16 (80%) females, 14 (70%) Caucasians, and 11 (55%) people with diffuse cutaneous SSc. Study themes included cognitive difficulties as part of daily life experience, impact of cognitive difficulties on daily life functioning, coping strategies and information seeking. Participants used different terms to describe their experience of cognitive difficulties, and most encountered deficits in short-term memory, language difficulties, decreased executive function, difficulties with concentration and focus, and slow processing speed. Participants expressed frustration with their cognitive difficulties and used coping strategies to lessen their impact. Participants were uncertain about the causes and wanted to understand factors contributing to cognitive difficulties as well as how to manage them. Participants with SSc reported cognitive difficulties that had a substantial negative impact on their lives. Improved understanding of cognitive changes could subsequently facilitate development of relevant therapeutic interventions or educational programmes for symptom self-management to reduce impact of cognitive difficulties in people with SSc.

REPEATED COLLECTION OF VAGINAL SMEAR CAUSES STRESS IN MICE

Women are more likely to be misdiagnosed in many neuropsychiatric disorders than men. One of the possible underlying reasons for this disparity may be more frequent use of male mice than female mice in neuroscience studies. With the increasing realization of the shortcomings of this approach in understanding the neurobiological basis of these disorders, many funding agencies mandate the inclusion of both male and female subjects in study design. As the behaviors vary with the stage of the estrous cycle, the collection of vaginal smears to identify the estrous stage becomes a widely used procedure. Here we tested whether vaginal smear collection causes similar effects to that of stress by evaluating an increase in depression-like behavior and impairment in memory. Vaginal smear was collected from Swiss albino mice twice a day for 10 days. In order to test depression-like behavior tail suspension, sucrose preference and splash tests were conducted. Novel object recognition and novel object location tests were performed 1 hour and 24 hours after training to evaluate short-and long-term memory respectively. The female mice whose vaginal smears were collected demonstrated increased behavioral despair and anhedonia. Vaginal smear group showed deficits in both short-term and long-term memory when compared to the control group. Our results indicate that the collection of vaginal smear not only increased depression-like behaviors in mice, but also impaired short-term and long-term memory, indicating that the procedure of vaginal smear collection was stressful. We recommend to consider other ways of estrous cycle staging when studying behavior.

Donepezil-loaded PLGA-b-PEG Nanoparticles Enhance the Learning and Memory Function of Beta-Amyloid Rat Model of Alzheimer’s Disease

Our aim is to reduce the side effects and increase the efficiency of donepezil by formulating donepezil-loaded poly(lactic-co-glycolic acid)-block-poly(ethylene glycol) nanoparticles (NPs) directly targeting amyloid beta (Aβ) fibrils in the brain and evaluate behavioral changes in this fibril model of AD. AD model was developed by intracerebroventricular injection of pre-aggregated β25-35 fibrils. Rats were intravenously administered either solvent, donepezil-loaded NPs (15µg/kg) or free donepezil (1mg/kg) 3 times for a week except for naïve controls. The effect of treatments on anxiety, motor functions, and cognitive functions was tested by elevated plus maze, locomotor activity, novel object recognition, and Morris's water maze tests, respectively. Accumulation of Aβ25-35 fibrils in brain sections was confirmed. Anxiety-like behavior was observed in the Aβ Alzheimer and free donepezil treatment groups while donepezil-loaded NP treatment showed hypo-anxiety-like behavior. Donepezil-loaded NPs were successful in treatment of short-term memory deficit better than free donepezil injection. In Morris's water maze, both donepezil-loaded NPs and free donepezil groups found the platform in shorter time compared to Aβ Alzheimer group. In locomotor activity test, both donepezil treated groups moved less than the Aβ Alzheimer group and naïve controls. After the pharmacological experiments, acetylcholinesterase activity was determined and showed an increase in Aβ Alzheimer group compared to controls. Donepezil-loaded NPs inhibited the acetylcholinesterase activity more efficiently than the free donepezil group. Targeting with donepezil-loaded PLGA-b-PEG-NPs increases efficiency, helps to inhibit acetylcholinesterase activity more substantially, improves cognitive decline due to its longer duration of action and destabilizing effect on amyloid fibrils.

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

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

Transdiagnostic neurocognitive deficits in patients with type 2 diabetes mellitus, major depressive disorder, bipolar disorder, and schizophrenia: A 1-year follow-up study

BackgroundNeurocognition impairments are critical factors in patients with major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ), and also in those with somatic diseases such as type 2 diabetes mellitus (T2DM). Intriguingly, these severe mental illnesses are associated with an increased co-occurrence of diabetes (direct comorbidity). This study sought to investigate the neurocognition and social functioning across T2DM, MDD, BD, and SZ using a transdiagnostic and longitudinal approach. MethodsA total of 165 participants, including 30 with SZ, 42 with BD, 35 with MDD, 30 with T2DM, and 28 healthy controls (HC), were assessed twice at a 1-year interval using a comprehensive, integrated test battery on neuropsychological and social functioning. ResultsCommon neurocognitive impairments in somatic and psychiatric disorders were identified, including deficits in short-term memory and cognitive reserve (p < 0.01, η²p=0.08–0.31). Social functioning impairments were observed in almost all the disorders (p < 0.0001; η²p=0.29–0.49). Transdiagnostic deficits remained stable across the 1-year follow-up (p < 0.001; η²p=0.13–0.43) and could accurately differentiate individuals with somatic and psychiatric disorders (χ² = 48.0, p < 0.0001). LimitationsThe initial sample size was small, and high experimental mortality was observed after follow-up for one year. ConclusionsThis longitudinal study provides evidence of some possible overlap in neurocognition deficits across somatic and psychiatric diagnostic categories, such as T2DM, MDD, BD, and SZ, which have high comorbidity. This overlap may be a result of shared genetic and environmental etiological factors. The findings open promising avenues for research on transdiagnostic phenotypes of neurocognition in these disorders, in addition to their biological bases.

Investigating the prevalence of cognitive impairment in mild and moderate COVID‐19 patients two months post‐discharge: Associations with physical fitness and respiratory function

BackgroundThe aim of our study was to investigate the prevalence and associations of cognitive impairment in previously COVID‐19 patients 2 months after discharge.MethodOur study included previously hospitalized, consecutive COVID‐19 patients with mild to moderate disease, followed up 2 months post discharge at a tertiary hospital’s outpatient clinic during May 2021. Exclusion criteria included intensive care unit admission, intubation, or a history of neurodegenerative disease and stroke prior to COVID‐19. Prior to inclusion, eligible patients had provided written informed consent. The full battery of measurements in our study included demographics, medical and family history, anthropometrics, the 6‐minute walk test (6MWT), the Borg Dyspnea Scale, spirometry, the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), the Short Form 36 health Survey (SF‐36), the Montreal Cognitive Assessment (MoCA) and the Symptom Checklist 90‐R (SLC90‐R), reactive oxygen metabolites (dROMs) and plasma antioxidant capacity (PAT test; FRAS5, Parma, Italy). Cognitive impairment was considered on a MoCA cutoff ≤24. Data are presented as mean ±SD or Frequencies (%). Correlations between continuous data were assessed via the Spearman’s Rho correlation coefficient, whereas associations were assessed via multiple linear regression (MLR) models. For all tests, a p‐value <0.05 was considered statistically significant.ResultsA total of 32 subjects were included in the study (35 Male, 17 Female; Mean age of 61.6±9.4). A total of 56.2% presented with cognitive decline (CD) as indicated by a MoCA score <24. Principal component analysis revealed that short‐term memory impairments and multidomain impairment without short‐term memory deficits were the predominant patterns of cognitive impairment. MoCA score correlated with age (ρ=‐0.513, p=0.003), waist circumference (ρ=‐0.388, p=0.028) waist to hip ratio (ρ=‐0.361, p=0.042) and SpO2 during 6MWT (1st, 4th and 6th minute; p<0.05). MLR indicated that after adjusting for age and gender, SpO2 at the 6th minute of the 6MWT was independently associated with MoCA score (Beta=0.579, p‐value=0.001).ConclusionOur findings indicated that among 32 outpatient clinic subjects, 56.2% presented with cognitive decline. The associations with oxygen saturation and physical condition as detected by the 6MWT may indicate overlap with post‐COVID‐19 fatigue and warrants further investigation.

Fatty acid‐binding protein 3 knockout mice exhibit astrocyte‐mediated neuroinflammation and cognitive impairment

Fatty acid-binding protein 3 (FABP3) levels in the human cerebrospinal fluid elevate at early phases of Alzheimer's disease (AD), which is associated with reduced FABP3 levels in the brain and the onset of cognitive deterioration. However, it is unclear if reduced FABP3 levels in the brain can attribute to AD-like symptoms and pathology. The cognitive function of FABP3 knockout (KO) and wildtype (WT) mice (15-week-old females) has been assessed using a battery of behavioural assessment tools, and the brain cytokines were subsequently assessed. Astrocytes were isolated from FABP3 KO and WT mice and cell metabolism and genes associated with metabolism and cytokines were examined. FABP3 KO mice displayed deficits in short-term spatial memory (Fig 1A, 1B) and working memory (Fig 1C), which is associated with elevated IL-1β and TNF-α levels in the brain (Fig 1D). A significant decrease in glucose cellular uptake (Fig 2A) and metabolism (Fig 2B) and increase in fatty acid oxidation (Fig 2C) was demonstrated in FABP3 KO in relative to WT astrocytes. Genes responsible for fatty acid oxidation (carnitine palmitoyltransferase 1A) and transport (CD36) are upregulated in FABP3KO astrocytes (Fig 2D). In addition, IL-1β and TNFα mRNA in FABP3KO astrocytes increases by 3-fold and 4-fold, respectively (Fig 2D). This study demonstrates for the first time that FABP3 genetic knockout modifies astrocyte activities, which leads to AD-like pathology in mouse including elevated pro-inflammatory cytokine levels in the brain and cognitive dysfunction.

LGI1 antibody encephalitis: acute treatment comparisons and outcome

ObjectiveTo compare acute treatment responses and long-term outcome in leucine-rich glioma-inactivated 1 (LGI1) antibody encephalitis.MethodsRetrospective case series of 118 patients with LGI1 antibody encephalitis evaluated at Mayo Clinic across all...

Effects of Importin α1/KPNA1 deletion and adolescent social isolation stress on psychiatric disorder-associated behaviors in mice.

Importin α1/KPNA1 is a member of the Importin α family widely present in the mammalian brain and has been characterized as a regulator of neuronal differentiation, synaptic functionality, and anxiety-like behavior. In humans, a de novo mutation of the KPNA1 (human Importin α5) gene has been linked with schizophrenia; however, the precise roles of KPNA1 in disorder-related behaviors are still unknown. Moreover, as recent studies have highlighted the importance of gene-environment interactions in the development of psychiatric disorders, we investigated the effects of Kpna1 deletion and social isolation stress, a paradigm that models social stress factors found in human patients, on psychiatric disorder-related behaviors in mice. Through assessment in a behavioral battery, we found that Kpna1 knockout resulted in the following behavioral phenotype: (1) decreased anxiety-like behavior in an elevated plus maze test, (2) short term memory deficits in novel object recognition test (3) impaired sensorimotor gating in a prepulse inhibition test. Importantly, exposure to social isolation stress resulted in additional behavioral abnormalities where isolated Kpna1 knockout mice exhibited: (1) impaired aversive learning and/or memory in the inhibitory avoidance test, as well as (2) increased depression-like behavior in the forced swim test. Furthermore, we investigated whether mice showed alterations in plasma levels of stress-associated signal molecules (corticosterone, cytokines, hormones, receptors), and found that Kpna1 knockout significantly altered levels of corticosterone and LIX (CXCL5). Moreover, significant decreases in the level of prolactin were found in all groups except for group-housed wild type mice. Our findings demonstrate that Kpna1 deletion can trigger widespread behavioral abnormalities associated with psychiatric disorders, some of which were further exacerbated by exposure to adolescent social isolation. The use of Kpna1 knockout mice as a model for psychiatric disorders may show promise for further investigation of gene-environment interactions involved in the pathogenesis of psychiatric disorders.

Difficulties in diagnosing atypical variants of Alzheimer’s disease

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

Using an invertebrate model to investigate the mechanisms of short-term memory deficits induced by food deprivation

Although prolonged food deprivation is known to cause memory deficits, the underlying mechanisms are only partially understood. In this study, we began to investigate the cellular substrates of food deprivation-induced memory impairments in the invertebrate Aplysia. Following a single trial of noxious stimuli, Aplysia concurrently express short-term sensitization (an elementary form of learning in which withdrawal reflexes are enhanced) and short-term feeding suppression for at least 15 min. Cellular correlates of sensitization and feeding suppression include increased excitability of the tail sensory neurons (TSNs) controlling the withdrawal reflexes, and decreased excitability of feeding decision-making neuron B51, respectively. Recently, 14 days of food deprivation (14DFD) was reported to break the co-expression of sensitization and feeding suppression in Aplysia without health deterioration. Specifically, under 14DFD, sensitization was completely prevented while feeding suppression was present albeit attenuated. This study explored the cellular mechanisms underlying the absent sensitization and reduced feeding suppression under 14DFD. A reduced preparation was used to evaluate the short-term cellular modifications induced by delivering an aversive training protocol in vitro. TSN excitability failed to increase following in vitro training under 14DFD, suggesting that the lack of sensitization may be a consequence of the fact that TSN excitability failed to increase. B51 excitability also failed to decrease following in vitro training, indicating that additional neurons may contribute to the conserved albeit reduced feeding suppression in 14DFD animals. This study lays the foundations for the future use of the Aplysia model system to investigate the mechanisms underlying the memory impairments induced by prolonged food deprivation.

Are Different Types of Learning Disorder Associated With Distinct Cognitive Functioning Profiles?

Introduction: DSM-5 presented a revised conceptualization of specific learning disorders (LD). Contrary to former versions, the various types of LD—i.e., mathematics disorder, reading disorder, and writing disorder—are not treated as distinct diagnostic entities but are integrated into one single LD category. In support of this new classification, it has been argued that the various types of LD overlap to a great extent in their cognitive functioning profiles and therefore do not exhibit a distinct set of cognitive causes. In contrast, ICD-11 still adheres to the idea of discrete categories and thus follows the specificity hypothesis of LD. Using latent profile analysis (LPA), we therefore tested the specificity of cognitive strengths and weaknesses in children with different types of LD. Secondly, we aimed at examining the extent to which observed LD characteristics (type and severity of LD as well as IQ-achievement discrepancy) were consistent with the membership of a given latent profile.Method: 302 German third-graders (134 girls; IQ ≥ 85; Mage = 111.05 months; SD = 5.76) with single or comorbid types of LD in the domains of mathematics, reading, and spelling completed a wide range of domain-specific and domain-general cognitive functioning measures.Results: Five qualitative distinct profiles of cognitive strengths and weaknesses were identified. Profile 1 (23% of the sample) showed Comprehensive Cognitive Deficits, performing low in all measures except for naming speed, language, and inhibition. Profile 2 (21%) included children with a Double Deficit in Phonological Awareness and Phonological Short-term Memory. Profile 3 (20%) was characterized by a Double Deficit of Phonological Awareness and Naming Speed. Profile 4 (19%) included children with a Single Deficit in Attention, and profile 5 (17%) consisted of children without any cognitive deficits. Moreover, type and severity of LD as well as IQ-achievement discrepancy discriminated between the profiles, which is in line with the specificity hypothesis of LD.Discussion: Overall, the finding of specific associations between the LD types and the identified cognitive profiles supports the ICD-11 classification of LD. Yet, those inferences may not be valid for an individual child but need to be examined through comprehensive diagnostic.