Search

Background: The Learning Ratio (LR) is a novel learning score that has shown improved utility over other learning metrics in detecting Alzheimer's disease (AD) across multiple memory tasks. However, its utility on the Consortium to Establish a Registry for Alzheimer's Disease Word List Memory Test (CERAD WLMT), a widely used list learning measure sensitive to decline in neurodegenerative disease, is unknown. The goal of the current study was to determine the utility of LR on the CERAD WLMT in differentiating between diagnostic (MiNCD vs MaNCD) and etiologic groups (VaD vs AD) in a veteran sample. Methods: Raw learning slope (RLS) and LR scores were examined in 168 veterans diagnosed with major neurocognitive disorder (MaNCD), mild neurocognitive disorder (MiNCD), or normal aging following neuropsychological evaluation. Patients with MaNCD were further classified by suspected etiology (i.e. microvascular disease vs AD). Results: Whereas RLS scores were not significantly different between MiNCD and MaNCD, LR scores were significantly different between all diagnostic groups ( p ' s < .05). Those with AD had lower LR scores and RLS scores compared to those with VaD ( p ' s < .05). LR classification accuracy was acceptable for MiNCD (AUC = .76), excellent for MaNCD (AUC = .86) and VaD (AUC = .81), and outstanding for AD (AUC = .91). Optimal cutoff scores for WLMT LR were derived from Youden's index. Conclusion: Results support the use of LR scores over RLS when interpreting the CERAD WLMT and highlight the clinical utility of LR in differentiating between diagnostic groups and identifying suspected etiology.

Objective: Cognitive dispersion indexes intraindividual variability in performance across a battery of neuropsychological tests. Measures of dispersion show promise as markers of cognitive dyscontrol and everyday functioning difficulties; however, they have limited practical applicability due to a lack of normative data. This study aimed to develop and evaluate normed scores for cognitive dispersion among older adults., Method: We analyzed data from 4,283 cognitively normal participants aged ≥50 years from the Uniform Data Set (UDS) 3.0. We describe methods for calculating intraindividual standard deviation (ISD) and coefficient of variation (CoV), as well as associated unadjusted scaled scores and demographically adjusted z-scores. We also examined the ability of ISD and CoV scores to differentiate between cognitively normal individuals (n = 4,283) and those with cognitive impairment due to Lewy body disease (n = 282)., Results: We generated normative tables to map raw ISD and CoV scores onto a normal distribution of scaled scores. Cognitive dispersion indices were associated with age, education, and race/ethnicity but not sex. Regression equations were used to develop a freely accessible Excel calculator for deriving demographically adjusted normed scores for ISD and CoV. All measures of dispersion demonstrated excellent diagnostic utility when evaluated by the area under the curve produced from receiver operating characteristic curves., Conclusions: Results of this study provide evidence for the clinical utility of sample-based and demographically adjusted normative standards for cognitive dispersion on the UDS 3.0. These standards can be used to guide interpretation of intraindividual variability among older adults in clinical and research settings., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Introduction: Serial position effects (SPEs) have shown promise as predictors of future cognitive decline and conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD), even when accounting for total learning and memory scores. However, conflicting results have been found in the literature, which may be at least partially related to the many ways in which SPEs are calculated. The current study aimed to address the discrepancies in the literature by examining whether one method of analyzing SPEs is more sensitive at distinguishing those with and without psychometrically defined MCI., Method: 86 older adult participants (57 healthy comparison, 29 MCI) completed the California Verbal Learning Test, Third Edition (CVLT3) and the Rey Auditory Verbal Learning Test (RAVLT), along with measures assessing multiple cognitive domains. Each participant completed two visits, between 3 and 9 days apart, with a different memory measure administered on each day. The standard scoring approach and the regional scoring approach to calculating SPEs were compared., Results: Results showed that, when significant differences were found, SPEs were always reduced in the MCI group compared to the healthy comparison group when using regional scoring; however, results were not as consistent when using standard scoring. Further, lower primacy than recency scores were only consistently seen in the MCI group when using the RAVLT but not the CVLT3. ROC analyses showed that only regional scoring of SPEs from delayed recall of the RAVLT and the CVLT3 accurately discriminated between those with and without MCI., Conclusion: Regional scoring of SPEs may be more sensitive at identifying subtle cognitive decline compared to standard scoring. However, the specific measure that is used to analyze SPEs can impact the interpretation of findings.

Objective: To examine predictors of informant-reported everyday functioning in mild cognitive impairment (MCI) and relations between everyday function and conversion to dementia., Methods: Informants of participants (n = 2614) with mild cognitive impairment (MCI) were administered the Functional Activities Questionnaire (FAQ). Changes in dimensions of functional ability as determined by an exploratory factor analysis (EFA) were examined over 3 years and participant predictors of change were examined using multilevel modeling (MLM)., Results: The FAQ consisted of 3 factors, multistep, finance, and memory/orientation daily tasks. Impairment in memory/orientation tasks was significantly higher than impairment in multistep tasks. Worse functioning was associated with greater depression, worse memory, worse speed/EF, higher years of education and identifying as White. There was variability in some of these associations with different FAQ factors. Impairments in financial and memory/orientation daily tasks predicted follow-up conversion to dementia., Conclusions: Depression, speed/EF, and memory are consistently associated with domains of everyday functioning. Race, education, and age may be more variability associated with everyday functioning. Specific attention should be paid to subtle declines in the financial and memory/orientation domains as they may uniquely predict future dementia development. Depression may be a modifiable risk factor associated with functional impairment over time.

The Digit Span test is a widely used working memory measure. However, when using standardized scoring procedures, previous studies have demonstrated inconsistent relationships between Digit Span subtests and working memory measures frequently used in cognitive psychology experiments. Partial scoring involves awarding credit for all digits recalled in the correct serial location, whereas traditional scoring involves only awarding credit for a trial if all digits are recalled in the correct serial location. The current study compared the traditional all-or-nothing scoring method and the partial scoring method on Digit Span with other working memory measures and with measures of general fluid intelligence. The results showed that when differences were found, partial scoring was associated with stronger relationships with Digit Span Backwards but weaker relationships with Digit Span Forward and Sequencing compared with traditional scoring. These results support previous findings identifying differences between the Digit Span subtests and the utility of examining traditional scoring procedures.

Anxiety sensitivity is a transdiagnostic risk factor for internalizing psychopathology in children and adults. Several factor analytic studies have examined the factor structure of anxiety sensitivity in children, adolescents, and adults. However, to date, no studies have specifically examined the factor structure of the Anxiety Sensitivity Index-3 in older adults. The purpose of the current study was to compare the fit of a correlated three-factor, higher-order, and bifactor model of the Anxiety Sensitivity Index-3 (ASI-3) in a sample of older adults. Participants were 856 older adults aged 60-94 recruited through Qualtrics Panels. Confirmatory factor analyses demonstrated good model fit for the bifactor model and the higher-order model and adequate fit for the correlated three-factor model. These results suggests that the ASI-3 is a valid tool assessing anxiety sensitivity in older adults. Limitations and future directions are discussed., Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00736-9., Competing Interests: Conflict of interestThe authors report there are no competing interests to declare., (© The Author(s), under exclusive licence to Springer Nature B.V. 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Objective: Although there is an abundance of research on stand-alone and embedded performance validity tests and stand-alone symptom validity tests (SVTs), less emphasis has been placed on embedded SVTs. The goal of the current study was to examine the ability of embedded indicators within the Patient Competency Rating Scale (PCRS) to separately detect invalid cognitive and/or emotional/affective symptom responding., Method: Participants included 299 veterans assessed in a VA medical center epilepsy monitoring unit from 2013-2017 (mean age = 48.8 years, SD  = 13.5 years). Two SVT composites were created; self-reported cognitive symptom validity (SVT-C) and self-reported emotional/affective symptom validity (SVT-E). Groups were compared on PCRS total and index scores (i.e., cognitive, activities of daily living, emotional, and interpersonal competencies) using ANOVAs. Receiver operating characteristic (ROC) curve analyses assessed the classification accuracy of the PCRS total and index scores for SVT-C and SVT-E., Results: In ANOVAs, SVT-C was significantly associated with all PCRS indices, while SVT-E was only significantly associated with the PCRS total, emotional, and interpersonal competency indices. Although the PCRS-T ≤ 90 had the strongest classification of SVT-C and SVT-E (specificities: .90, sensitivities: .44 to .50), PCRS index scores showed suggestive evidence of domain specificity, with PCRS-ADL ≤22, PCRS-C ≤ 20, and PCRS-CADL ≤45 best classifying SVT-C (specificities: .92, sensitivities: .33) and the PCRS-E ≤ 18 best classifying the SVT-E group (specificity: .93, sensitivity: .40)., Conclusion: Results suggest the PCRS may be used to obtain clinically useful information while including embedded indicators that can assess cognitive and/or emotional/affective symptom invalidity.

Objective: While previous studies have described psychiatric profiles in patients with psychogenic non-epileptic seizures (PNES) and epileptic seizures (ES), a well-matched comparison between males and females has been lacking. To address this shortcoming, the present study sought to explore sex differences between male and female Veterans with ES and PNES in terms of psychiatric diagnoses, trauma histories, and psychiatric treatment., Methods: A male Veteran sample (PNES n = 87, ES n = 28) was identified matching age and seizure diagnosis with our previously-gathered female Veteran sample (PNES n = 90, ES n = 28). Retrospective chart review was used to obtain demographic, psychiatric, and seizure-related variables. Group differences between PNES and ES were first assessed among males followed by differences between males and females., Results: Males with PNES were more likely to receive psychiatric treatment (82.6 % vs. 60.7 %, p = 0.017), be prescribed more psychotropics (1.6 vs. 0.9, p = 0.003), and more likely to have childhood physical abuse (27.9 % vs. 3.6 %, p = 0.007) than those with ES. Compared to PNES, males with ES presented to the epilepsy monitoring unit (EMU) significantly later (12.8 years vs. 6.1 years, p = 0.009), and were prescribed more anti-seizure medications (ASMs) previously (2.1 vs. 0.8, p = 0.009) and currently (1.6 vs. 1.0, p = 0.001). Between males and females with PNES, females evidenced more depression (76.7 % vs. 26.3 %, p < 0.001), borderline personality disorder (18.9 % vs. 4.7 %, p = 0.004), suicidality (65.6 % vs. 33.7 %, p < 0.001), and childhood sexual abuse (37.8 % vs. 11.6 %, p < 0.001), while males had higher rates of substance use disorders (37.2 % vs. 8.9 %, p < 0.001)., Significance: A greater psychiatric burden is seen among females compared to males with PNES, especially diagnoses of borderline personality disorder and depression. Higher rates of suicidality and inpatient psychiatric hospitalization may warrant particular consideration in screening and intervention efforts among female Veterans with PNES., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Verbal memory is a predictor of later functional deficits. However, it is unclear if a specific aspect of immediate free-recall is driving this relationship. Serial position effects (i.e., relationship between a word's placement on a word-list and its likelihood of being recalled) have been shown to predict conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD). The goal of this study was to determine if serial position effects predict functioning 10-year postbaseline when controlling for demographic variables and total cognitive scores., Method: Data from 2,802 participants in the Advanced Cognitive Training for Independent and Vital Elderly trial were examined to predict subjective (i.e., Minimum Data Set Home Care questionnaire subscales) and performance-based (i.e., Observed Tasks of Daily Living and Everyday Problems Test) functioning 10-year postbaseline. Multilevel modeling was used to examine the association between functioning 10-year postbaseline and scores at baseline., Results: Primacy performance demonstrated the most consistent associations with overall subjective and performance-based functioning measures 10-year postbaseline. Specifically, higher primacy performance was associated with less decline in subjective and performance-based functioning over time, particularly when primacy was analyzed from the Rey Auditory Verbal Learning Test. Fewer associations were found between middle and recency scores with subjective and performance-based functioning measures., Conclusion: The present study suggests that serial position effects predict future subjective and performance-based functional changes, beyond demographic information and global cognition. The study adds to a growing literature about the relative importance of primacy, especially in the prediction of functional changes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The greatest risk factor for developing Alzheimer's disease (AD) is increasing age. Understanding the changes that occur in aging that make an aged brain more susceptible to developing AD could result in novel therapeutic targets. In order to better understand these changes, the current study utilized mice harboring a regulatable mutant P301L human tau transgene (rTg(TauP301L)4510), in which P301L tau expression can be turned off or on by the addition or removal of doxycycline in the drinking water. This regulatable expression allowed for assessment of aging independent of prolonged mutant tau expression. Our results suggest that P301L expression in aged mice enhances memory deficits in the Morris water maze task. These behavioral changes may be due to enhanced late-stage tau pathology, as evidenced by immunoblotting and exacerbated hippocampal dysregulation of glutamate release and uptake measured by the microelectrode array technique. We additionally observed changes in proteins important for the regulation of glutamate and tau phosphorylation that may mediate these age-related changes. Thus, age and P301L tau interact to exacerbate tau-induced detrimental alterations in aged animals.

Introduction: The use of virtual reality (VR) technology has been suggested as a method to increase ecological validity in neuropsychological assessments. Although validity has been a focus in VR research, little attention has been paid to other psychometric properties such as test-retest reliability and practice effects. Practice effects are common on traditional neuropsychological tests and can be impacted by novelty. Because VR is not widely used it was expected that participants would demonstrate higher practice effects on VR as compared to paper-and-pencil testing., Method: To compare test-retest reliability and practice effects in VR and traditional paper-and-pencil testing, the Virtual Environment Grocery Store (VEGS) and California Verbal Learning Test - Second Edition (CVLT-II) were used in healthy adults (n = 44). Participants received follow-up testing approximately 2 weeks after the initial visit., Results: Significant practice effects of similar magnitude were seen on memory scores (i.e., total learning, long-delay free recall, and long-delay cued recall) on the VEGS and the CVLT-II. The VEGS and CVLT-II memory scores also demonstrated strong test-retest reliability ( r 's > .71). Lastly, total learning scores ( d = .32) and long-delay cued recall ( d = .70) scores were significantly higher on the CVLT-II compared to the VEGS ( p 's < .01)., Conclusions: Results suggested similar test-retest reliability and practice effects of the VEGS and CVLT-II, although the VEGS has the benefit of being an immersive technology that simulates an everyday activity. The study replicated past findings that the VEGS is more difficult than the CVLT-II which may be a useful property for clinical assessment.

Objectives: Projections from the United States Census Bureau suggest that the African American population may be the fastest growing race over the next 30 years and that they may be at the highest risk for developing dementia later in life. Various social factors have been shown to be associated with cognitive function and health outcomes. The present study aims to evaluate the relationship between social engagement and cognitive decline in a cohort of older African American adults., Methods: We utilized multilevel modeling to examine the association between cognitive decline and social engagement in a sample of 617 older African American adults., Results: Social activity was associated with global cognition, perceptual speed, perceptual orientation, and episodic memory over time. Loneliness was associated with better semantic memory performance over time. Perceived discrimination was associated with better semantic memory performance over time. Larger social network was associated with worse perceptual speed scores over time., Conclusions: Although our findings on loneliness and perceived discrimination over time were inconsistent with prior research, our findings on social activity and social network size over time were consistent with past literature and are thought to be due to positive social interactions providing a catalyst for cognitively stimulating activities. These results suggest that interventions designed to preserve cognition in African American older adults should incorporate adequate social activity. Furthermore, to maximize effectiveness, interventions should not necessarily focus on just expanding one's social network., (© 2020 John Wiley & Sons Ltd.)

The coronavirus disease pandemic has brought a new urgency for the development and deployment of web-based applications which complement, and offer alternatives to, traditional one-on-one consultations and pencil-and-paper (PaP) based assessments that currently dominate clinical research. We have recently developed a web-based application that can be used for the self-administered collection of patient demographics, self-rated health, depression and anxiety, and cognition as part of a single platform. In this study we report the findings from a study with 155 cognitively healthy older adults who received established PaP versions, as well as our novel computerized measures of self-rated health, depression and anxiety, and cognition. Moderate to high correlations were observed between PaP and web- based measures of self-rated health (r = 0.77), depression and anxiety (r = 0.72), and preclinical Alzheimer's disease cognitive composite (PACC) (r = .61). Test-retest correlations were variable with high correlations for a measure of processing speed and a measure of delayed episodic memory. Taken together, these data support the feasibility and validity of utilization of this novel web-based platform as a new alternative for collecting patient demographics and the assessment of self-rated health, depression and anxiety, and cognition in the elderly., Competing Interests: The authors have declared that no competing interests exist.

Objective: Serial position effects (SPEs) on list learning tasks refer to the relationship between a word's placement on the list and its likelihood of being recalled. Typically, adults recall more words from the beginning (primacy) and end (recency) of the list compared to the middle of the list. These effects can be affected by neurological disease such that SPEs have been shown to be related to both current and future cognitive decline. This review aimed to summarize existing research on SPEs in individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Method: A systematic review of SPEs in MCI and AD was conducted., Results: Despite inconsistencies in the number of items included on word list tasks analyzing SPEs and inconsistencies in how researchers have defined and analyzed SPEs, SPEs have demonstrated the ability to predict future cognitive decline, at times above and beyond traditional memory score performance. In addition, individuals with MCI and AD show similar SPE patterns of reduced primacy and intact recency, with primacy being more reduced in AD, whereas individuals with vascular dementia demonstrate a reversed SPE pattern., Conclusion: The analysis of SPEs has demonstrated some utility as a marker of cognitive impairment associated with MCI, AD, and other dementias; however, research is limited by the multiple ways in which SPEs are defined and analyzed. Future research is discussed, including the need for increased data accessibility in order to quantitatively summarize previous research on SPEs in relation to MCI and AD. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objective : Previous studies analyzing the factor structure of the Rey Auditory Verbal Learning Test (RAVLT) have been limited in the number of scores included in the analysis. Often, they lacked inclusion of process scores that have been shown to add predictive value in identifying future cognitive decline. Therefore, the goal of the current study was to determine the factor structure of the RAVLT utilizing factor scores including serial position effects, repetitions, and intrusion errors, and to examine if the factor structure for older adults is similar to that found in the entire lifespan sample. Method : Exploratory factor analysis (EFA) was conducted on 718 participants (age 16-85 years) from the Nathan Kline Institute (NKI)-Rockland project. Confirmatory factor analyses (CFA) of a reduced model of the EFA was conducted on the entire sample and an older (ages 55-85 years; n  = 265) and a younger (less than 55 years of age; n  = 453) subsample. Results : EFA indicated three factors: Memory, Attention/Learning, and Inaccurate Memory (i.e., repetitions and intrusions). CFA of a reduced model indicated adequate fit in the entire sample and older subsample, and good fit in the younger subsample. Conclusion : The present study examined the factor structure of the RAVLT in a large lifespan sample utilizing a larger set of RAVLT scores than have been examined in prior studies, including total scores and process scores. The same factors were identified in the entire lifespan sample and the younger and older adult subsamples, although similar to previous studies, measures of model fit were less robust in the older adult subsample. These results provide additional support for the error scores (e.g., intrusions and repetitions) as separable from other aspects of learning and memory.

Background: Gait-related changes in older adulthood may be related to changes in cognition (e.g., executive functioning), and recent work suggests that different self-reported measures of sleep may be tied to contrasting aspects of executive functioning. However, the relationship between these self-reported sleep measures and gait domains has not been explored. Such an investigation would be useful in helping to determine which older adults might exhibit changes in gait as well as experience other gait-associated changes (e.g., increased fall risk)., Objective: To examine associations between different aspects of self-reported sleep and gait domains in a sample of cognitively healthy older adults., Method: A total of 423 older adults (mean age 69.9 years, range 50-92) completed self-report measures of sleep quality, daytime sleepiness, and sleep-related distress. The participants also completed an objective, electronic measure of both single-task and dual-task gait (i.e., GAITRite). Principal component analyses were used to elucidate the solution for each gait condition, and multiple linear regression was used to examine the contributions of sleep measures to variability in gait performance., Results: A 5-component solution of the single-task condition and a 4-component solution of the dual-task condition were identified. Multiple linear regressions revealed that a poorer sleep quality was associated with greater single-task and dual-task asymmetry. Greater daytime sleepiness was associated with increased dual-task gait variability and postural control. After controlling for the effects of other facets of sleep, sleep-related distress was not associated with any gait domain., Conclusions: Among cognitively healthy older adults,sleep quality and daytime sleepiness, but not sleep-related distress, are associated with aspects of gait. Patients who report these symptoms should be assessed and monitored for possible changes in gait., (© 2019 S. Karger AG, Basel.)

Objective: The aim of this study was to examine neuropsychiatric symptom (NPS) factor severity progression over time in empirically derived (ED) mild cognitive impairment (MCI) subtypes., Methods: Participants in the Alzheimer's Disease Neuroimaging Initiative study diagnosed with MCI by Alzheimer's Disease Neuroimaging Initiative protocol using conventional clinical (CC) criteria (n = 788) were reclassified using cluster analysis as amnestic, dysnomic, dysexecutive MCI, or cluster-derived normal (CC-Normal) using empirical criteria. Cognitively normal (CN) participants (n = 207) were also identified. The Neuropsychiatric Inventory-Questionnaire (NPI-Q) was administered from baseline through 48-month follow-up. Exploratory factor analysis was completed to determine the NPI-Q factor structure at 6-month follow-up. Multilevel modeling was used to determine NPI-Q symptom severity factor and apathy symptom progression over time by cognitive subtype., Results: The exploratory factor analysis revealed that the NPI-Q consisted of 2 factors: hyperactivity/agitation and mood symptoms. Using clinical and empirical criteria, all MCI groups were identified as having more severe hyperactivity/agitation symptoms than CN participants. However, only the amnestic MCI group identified using empirical criteria showed an increase in symptom severity over time relative to CN participants. Mood factor and apathy symptoms were found to be more severe in dysexecutive and amnestic groups in both models. Similarly, both models identified a significant worsening of mood and apathy symptoms over time for dysexecutive and amnestic groups relative to CN participants., Conclusions: This study provides further support that empirical criteria aid in examining the progression of clinical characteristics associated with MCI. Further, it helps to identify which MCI subtypes may be at higher risk for NPS progression., (© 2018 John Wiley & Sons, Ltd.)

Objective: To examine associations between pedometer-assessed daily steps and several domains of cognitive functioning in cognitive healthy older adults., Method: A total of 582 cognitively healthy older adults enrolled in a longitudinal aging study completed the Uniform Data Set (UDS) neuropsychological battery ( n = 374) or the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; n = 208) and were asked to wear a pedometer for 1 week., Results: Bivariate correlations revealed associations between average daily steps and attention, executive functioning, language, and memory on one or both cognitive batteries. Multiple regression analyses controlling for demographic, health, and mobility variables demonstrated a significant relationship between average daily steps and the executive functioning composite of the UDS battery and average daily steps and the attention index of the RBANS battery. Both of these composites include measures of processing speed and, therefore, the most robust link between daily steps and cognition may be its association with processing speed., Conclusions: Step counts as measured by a pedometer, a simple and inexpensive measure of daily physical activity, are robustly associated with aspects of cognition. As pedometer-based interventions have shown success in increasing daily physical activity in older adults, a greater number of future studies should consider measuring cognitive outcomes of these interventions. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Hyperexcitability of the hippocampus is a commonly observed phenomenon in the years preceding a diagnosis of Alzheimer's disease (AD). Our previous work suggests a dysregulation in glutamate neurotransmission may mediate this hyperexcitability, and glutamate dysregulation correlates with cognitive deficits in the rTg(TauP301L)4510 mouse model of AD. To determine whether improving glutamate regulation would attenuate cognitive deficits and AD-related pathology, TauP301L mice were treated with riluzole (~ 12.5 mg/kg/day p.o.), an FDA-approved drug for amyotrophic lateral sclerosis that lowers extracellular glutamate levels. Riluzole-treated TauP301L mice exhibited improved performance in the water radial arm maze and the Morris water maze, associated with a decrease in glutamate release and an increase in glutamate uptake in the dentate gyrus, cornu ammonis 3 (CA3), and cornu ammonis 1 (CA1) regions of the hippocampus. Riluzole also attenuated the TauP301L-mediated increase in hippocampal vesicular glutamate transporter 1, which packages glutamate into vesicles and influences glutamate release; and the TauP301L-mediated decrease in hippocampal glutamate transporter 1, the major transporter responsible for removing glutamate from the extracellular space. The TauP301L-mediated reduction in PSD-95 expression, a marker of excitatory synapses in the hippocampus, was also rescued by riluzole. Riluzole treatment reduced total levels of tau, as well as the pathological phosphorylation and conformational changes in tau associated with the P301L mutation. These findings open new opportunities for the development of clinically applicable therapeutic approaches to regulate glutamate in vulnerable circuits for those at risk for the development of AD., (© 2015 International Society for Neurochemistry.)

The Morris water maze (MWM) is a commonly used task to assess hippocampal-dependent spatial learning and memory in transgenic mouse models of disease, including neurocognitive disorders such as Alzheimer's disease. However, the background strain of the mouse model used can have a substantial effect on the observed behavioral phenotype, with some strains exhibiting superior learning ability relative to others. To ensure differences between transgene negative and transgene positive mice can be detected, identification of a training procedure sensitive to the background strain is essential. Failure to tailor the MWM protocol to the background strain of the mouse model may lead to under- or over- training, thereby masking group differences in probe trials. Here, a MWM protocol tailored for use with the F1 FVB/N x 129S6 background is described. This is a frequently used background strain to study the age-dependent effects of mutant P301L tau (rTg(TauP301L)4510 mice) on the memory deficits associated with Alzheimer's disease. Also described is a strategy to re-optimize, as dictated by the particular testing environment utilized.

Alzheimer's disease (AD) is the most common form of dementia in individuals over 65 years of age and is characterized by accumulation of beta-amyloid (Aβ) and tau. Both Aβ and tau alter synaptic plasticity, leading to synapse loss, neural network dysfunction, and eventually neuron loss. However, the exact mechanism by which these proteins cause neurodegeneration is still not clear. A growing body of evidence suggests perturbations in the glutamatergic tripartite synapse, comprised of a presynaptic terminal, a postsynaptic spine, and an astrocytic process, may underlie the pathogenic mechanisms of AD. Glutamate is the primary excitatory neurotransmitter in the brain and plays an important role in learning and memory, but alterations in glutamatergic signaling can lead to excitotoxicity. This review discusses the ways in which both beta-amyloid (Aβ) and tau act alone and in concert to perturb synaptic functioning of the tripartite synapse, including alterations in glutamate release, astrocytic uptake, and receptor signaling. Particular emphasis is given to the role of N-methyl-D-aspartate (NMDA) as a possible convergence point for Aβ and tau toxicity.

Clinical experience has shown that examinees performing the Grooved Pegboard Test frequently have difficulty maintaining the manualized right-to-left placement direction with their left hand. To date, no empirical study has examined this phenomenon. The purpose of this study was to investigate whether left-hand peg placement direction (right-to-left vs. left-to-right) influences performance on this standardized test of fine motor speed and dexterity. The participants were 66 male and female student volunteers aged 18 to 58 years old. None of the participants had a history of neurologic disease/trauma or conditions that would affect motor functioning of the right and left upper extremities. Data were analyzed using a two-way mixed-design analysis of covariance. Results revealed a significant main effect for gender, F(1, 62) = 5.638, p = .021. Of primary interest was the main effect for placement direction, which was not significant, F(1, 62) = 0.108, p = .744. No significant interaction was observed, F(1, 62) = 0.002, p = .964.

Transgenic mice expressing mutations in tau have yielded essential discoveries for Alzheimer's disease. One of the most commonly used tau mouse models is the tet-off Tg(tauP301L)4510 model that expresses P301L human tau driven by the calcium-calmodulin kinase IIα (CaMKIIα) promoter system. Tau expression in this model is regulatable, allowing for suppression of mutant tau expression until adulthood and prevention of possible developmental alterations resulting from P301L tau expression during development. Here, we compared the effect and sample sizes needed for three learning and memory tasks in mice with adult-onset P301L tau expression. Our findings indicate that the Incremental Repeated Acquisition (IRA) and trace fear conditioning tasks, neither of which have previously been published with these mice, were highly sensitive to P301L tau expression, whereas the Morris water maze, the most commonly used task with this model, was the least sensitive. Memory deficits were observed at a time when tau pathology was subtle and prior to readily detectable neuronal loss. Thus, we provide essential information (effect and sample sizes needed) for establishing experimental designs at a time point when memory deficits are likely to go undetected if inadequate sample sizes are used. Our work also suggests the tet-off Tg4510 model provides a way to avoid mutant tau expression during the perinatal and early postnatal stages, thereby preventing possible developmental alterations unrelated to Alzheimer's disease., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The Cognistat is a widely used screening instrument for the assessment of higher cerebral functioning. This study investigated the effects of gender and age on a specific item from the metric sequence of the Cognistat Judgment subtest. Participants consisted of 110 cognitively intact volunteers (45 males, 65 females). Results showed that females responded with 1-point answers, as defined by the manual, significantly more often than those who responded with a manual-defined 2-point response. Males responded with a 2-point answer with a significantly greater frequency than they responded with 1-point responses. The data indicate that a gender correction for females should be made to the Judgment subtest of the Cognistat.