BrainBlog

Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose Study of the Oral γ-Secretase Inhibitor BMS-708163 (Avagacestat): Tolerability Profile, Pharmacokinetic Parameters, and Pharmacodynamic Markers Clin Ther. 2012 Feb 28; Tong G, Wang JS, Sverdlov O, Huang SP, Slemmon R, Croop R, Castaneda L, Gu H, Wong O, Li H, Berman RM, Smith C, Albright CF, Dockens RC Abstract BACKGROUND: γ-Secretase inhibitors (GSIs) are being investigated for their potential to modify the progression of Alzheimer disease based on their ability to regulate amyloid-β (Aβ) accumulation. BMS-708163 (avagacestat) is an oral GSI designed for selective inhibition of Aβ synthesis currently in development for the treatment of mild to moderate and predementia AD. In addition to the desired effect on Aβ synthesis, GSIs affect Notch processing, which is thought to mediate some toxic adverse effects reported with this drug class. Avagacestat produced up to 190-fold greater selectivity for Aβ synth...

Effects of Practice on the Wechsler Adult Intelligence Scale-IV Across 3- and 6-Month Intervals Clinical Neuropsychologist. 2012 Feb 21; Estevis E, Basso MR, Combs D Abstract A total of 54 participants (age M = 20.9; education M = 14.9; initial Full Scale IQ M = 111.6) were administered the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV ) at baseline and again either 3 or 6 months later. Scores on the Full Scale IQ, Verbal Comprehension, Working Memory, Perceptual Reasoning, Processing Speed, and General Ability Indices improved approximately 7, 5, 4, 5, 9, and 6 points, respectively, and increases were similar regardless of whether the re-examination occurred over 3- or 6-month intervals. Reliable change indices (RCI) were computed using the simple difference and bivariate regression methods, providing estimated base rates of change across time. The regression method provided more accurate estimates of reliable change than did the simple difference between baseline and fol...

Impaired Cognitive Function and Hippocampal Neurogenesis Following Cancer Chemotherapy Clin Cancer Res . 2012 Feb 14; Christie LA, Acharya MM, Parihar VK, Nguyen A, Martirosian V, Limoli CL Abstract PURPOSE: A substantial proportion of breast cancer survivors report significant, long-lasting impairments in cognitive function, often referred to as "chemobrain." Advances in detection and treatment mean that many more patients are surviving long-term following diagnosis of invasive breast cancer. Thus, it is important to define the types, extent and persistence of cognitive impairments following treatment with cytotoxic cancer drugs. EXPERIMENTAL DESIGN: We examined the effects of chronic treatment with two agents commonly used in breast cancer patients, cyclophosphamide and doxorubicin (Adriamycin). Athymic nude rats were given 50mg/kg cyclophosphamide, 2mg/kg doxorubicin or saline injections once per week for 4 weeks. A novel place recognition task and contextual and cued fear...

Intraneuronally Injected Amyloid Beta Inhibits Long-Term Potentiation In Rat Hippocampal Slices J Neurophysiol. 2012 Feb 15; Nomura I, Takechi H, Kato N Abstract Extracellular accumulation of amyloid beta (Aβ) is a hallmark of Alzheimer's disease (AD). It has been reported that extracellular perfusion of Aβ inhibits long-term potentiation (LTP), which is strongly related to memory in animal models. However, it has recently been proposed that intracellular Aβ may be the first pathological change to occur in AD. Here, we have investigated the effect on LTP of intracellular injection of Aβ (Aβ(1-40), Aβ(1-42)) into hippocampal pyramidal cells using patch clamp technique. We found that injection of 1 nM Aβ(1-42) completely blocked LTP and extracellular perfusion of a p38 MAPK inhibitor or a metabotropic glutamate receptor blocker reversed these blocking effects on LTP. Furthermore, we have examined the effects of different concentrations of Aβ(1-40) and Aβ(1-42) on LTP and showed that...

Visualizing long-term memory formation in two neurons of the Drosophila brain Science. 2012 Feb 10;335(6069):678-85 Chen CC, Wu JK, Lin HW, Pai TP, Fu TF, Wu CL, Tully T, Chiang AS Abstract Long-term memory (LTM) depends on the synthesis of new proteins. Using a temperature-sensitive ribosome-inactivating toxin to acutely inhibit protein synthesis, we screened individual neurons making new proteins after olfactory associative conditioning in Drosophila. Surprisingly, LTM was impaired after inhibiting protein synthesis in two dorsal-anterior-lateral (DAL) neurons but not in the mushroom body (MB), which is considered the adult learning and memory center. Using a photoconvertible fluorescent protein KAEDE to report de novo protein synthesis, we have directly visualized cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)-dependent transcriptional activation of calcium/calmodulin-dependent protein kinase II and period genes in the DAL neurons after spaced but not...

The Columbia-Suicide Severity Rating Scale: initial validity and internal consistency findings from three multisite studies with adolescents and adults. American Journal of Psychiatry. 2011 Dec;168(12):1266-77. Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin GA, Greenhill L, Shen S, Mann JJ. Abstract Research on suicide prevention and interventions requires a standard method for assessing both suicidal ideation and behavior to identify those at risk and to track treatment response. The Columbia-Suicide Severity Rating Scale (C-SSRS) was designed to quantify the severity of suicidal ideation and behavior. The authors examined the psychometric properties of the scale. The C-SSRS's validity relative to other measures of suicidal ideation and behavior and the internal consistency of its intensity of ideation subscale were analyzed in three multisite studies: a treatment study of adolescent suicide attempters (N=124); a medication efficacy trial wit...

A randomized controlled trial of a cognitive rehabilitation intervention for persons with multiple sclerosis Clin Rehabil . 2012 Feb 2; Stuifbergen AK, Becker H, Perez F, Morison J, Kullberg V, Todd A Abstract Objective: To explore the feasibility and effects of a computer-assisted cognitive rehabilitation intervention - Memory, Attention, and Problem Solving Skills for Persons with Multiple Sclerosis (MAPSS-MS) - for persons with multiple sclerosis on cognitive performance, memory strategy use, self-efficacy for control of symptoms and neuropsychological competence in activities of daily living (ADL).Design: A randomized controlled single-blinded trial with treatment and wait list control groups.Setting: Southwestern United States.Subjects: Convenience sample of 61 persons (34 treatment, 27 wait list control) with multiple sclerosis (mean age 47.9 years, SD 8.8).Intervention: The eight-week MAPSS-MS intervention program included two components: (a) eight weekly group sessions focused ...

Brain development of very preterm and very low-birthweight children in childhood and adolescence: A meta-analysis Developmental Medicine and Child Neurology. 2012 Jan 28; de Kieviet JF, Zoetebier L, van Elburg RM, Vermeulen RJ, Oosterlaan J Abstract Aim  The aim of this article was to clarify the impact and consequences of very preterm birth (born PMID: 22283622 [PubMed - as supplied by publisher]

Odor identification deficits identify Parkinson's disease patients with poor cognitive performance Movement Disorders. 2011 Sep;26(11):2045-50 Damholdt MF, Borghammer P, Larsen L, Ostergaard K Abstract Olfactory dysfunction is a prodromal and prevalent nonmotor symptom of Parkinson's disease. Unlike olfactory dysfunction in Alzheimer's disease, it is believed to be unrelated to cognitive impairment. However, recent research has implicated cholinergic denervation in Parkinson's disease hyposmia and linked it to verbal memory. This research hypothesized that severe odor identification deficits may identify patients with Parkinson's disease at risk for cognitive impairment. The current study tested this hypothesis by comparing 24 functionally anosmic, nondemented patients with Parkinson's disease and 39 nonanosmic, nondemented patients with Parkinson's disease with 29 healthy control participants on composite scores of memory, processing speed, executive functi...

Exergaming and older adult cognition a cluster randomized clinical trial Am J Prev Med. 2012 Feb;42(2):109-19 Anderson-Hanley C, Arciero PJ, Brickman AM, Nimon JP, Okuma N, Westen SC, Merz ME, Pence BD, Woods JA, Kramer AF, Zimmerman EA Abstract BACKGROUND: Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or "exergames" may elicit greater participation. PURPOSE: To test the following hypotheses: (1) stationary cycling with virtual reality tours ("cybercycle") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain improvement; and (3) brain-derived neurotrophic growth factor (BDNF) will increase. DESIGN: Multi-site cluster randomized clinical trial (RCT) of the impact of 3 months of cybercycling versus traditional exercise, on cognitive function i...

Errorless learning in cognitive rehabilitation: A critical review Neuropsychological Rehabilatation. 2012 Jan 16; Middleton EL, Schwartz MF Abstract Cognitive rehabilitation research is increasingly exploring errorless learning interventions, which prioritise the avoidance of errors during treatment. The errorless learning approach was originally developed for patients with severe anterograde amnesia, who were deemed to be at particular risk for error learning. Errorless learning has since been investigated in other memory-impaired populations (e.g., Alzheimer's disease) and acquired aphasia. In typical errorless training, target information is presented to the participant for study or immediate reproduction, a method that prevents participants from attempting to retrieve target information from long-term memory (i.e., retrieval practice). However, assuring error elimination by preventing difficult (and error-permitting) retrieval practice is a potential major drawback of the error...

This looks like a great contribution. I am looking forward to reading it. Age group and sex differences in performance on a computerized neurocognitive battery in children age 8-21 Neuropsychology. 2012 Jan 16; Gur RC, Richard J, Calkins ME, Chiavacci R, Hansen JA, Bilker WB, Loughead J, Connolly JJ, Qiu H, Mentch FD, Abou-Sleiman PM, Hakonarson H, Gur RE Abstract Objective: Examine age group effects and sex differences by applying a comprehensive computerized battery of identical behavioral measures linked to brain systems in youths that were already genotyped. Such information is needed to incorporate behavioral data as neuropsychological "biomarkers" in large-scale genomic studies. Method: We developed and applied a brief computerized neurocognitive battery that provides measures of performance accuracy and response time for executive-control, episodic memory, complex cognition, social cognition, and sensorimotor speed domains. We tested a population-based sample of 3,500...

N-backer: An auditory n-back task with automatic scoring of spoken responses Behav Res Methods. 2011 Sep;43(3):888-96 Monk AF, Jackson D, Nielsen D, Jefferies E, Olivier P Abstract The n-back task is commonly used to load working memory (WM) in dual-task and neuroimaging experiments. However, it typically involves visual presentation and buttonpress responses, making it unsuitable for combination with primary tasks that involve vision and action, such as sequential object use and other tasks of daily living. The N-backer software presented here will automatically present and score auditory-verbal n-back sequences utilising the standard speech synthesis and recognition facilities that come with Microsoft Windows. Data are presented from an experiment in which 12 student participants carried out three tasks from the Naturalistic Action Test (NAT) while their attention was divided between the primary task and a continuous auditory-verbal 2-back secondary task. The participants' 2-bac...

Landmark sequencing and route knowledge: An fMRI study Cortex. 2011 Dec 16; Nemmi F, Piras F, Péran P, Incoccia C, Sabatini U, Guariglia C Abstract INTRODUCTION: The ability to navigate in a familiar environment mainly relies on route knowledge, that is, a mental representation of relevant locations along a way, sequenced according to a navigational goal. Despite the clear ecological validity of this issue, route navigation and route knowledge have been scarcely investigated and little is known about the neural and cognitive bases of this navigational strategy. Using functional magnetic resonance imaging (fMRI) we tested the validity of the predictions based on the main cognitive models of spatial knowledge acquisition about route-based navigation. METHODS: An order judgment task was used with two conditions (route and activity). Subjects were required to detect potential mismatches between a current sensory input and expectations deriving from route and activity knowledge. RESULTS: A...

Rehabilitation targeted at everyday communication: can we change the talk of people with aphasia and their significant others within conversation? Archives of Physical Medicine and Rehabilation . 2012 Jan;93(1 Suppl):S70-6 Wilkinson R, Wielaert S Abstract OBJECTIVE: To investigate whether aphasia therapy can change the talk of speakers with aphasia and/or their significant others within conversation. DESIGN: Small number of intervention studies targeting conversations involving speakers with aphasia are reviewed. All are single case studies. SETTING: Key assessment in the studies was an audio or video recording of 1 or more conversations between the dyad, usually made in the home setting. Intervention in these studies took place in the participants' home or another setting, such as a therapy room. PARTICIPANTS: In all of the studies reviewed, the participants consisted of a person with aphasia (PWA) and a significant other, usually the PWA's spouse. INTERVENTIONS: In all studie...

Subjective Cognitive Complaints of Older Adults at the Population Level: An Item Response Theory Analysis Alzheimers Disease and Associated Disorders. 2011 Dec 20; Snitz BE, Yu L, Crane PK, Chang CC, Hughes TF, Ganguli M Abstract Subjective cognitive complaints (SCCs) are increasingly a focus in studies on prodromal Alzheimer disease (AD) and risk for dementia. Little is known about the optimal approach to measure SCCs. We used item response theory (IRT) to examine the characteristics of 24 SCC items in a sample of 3495 older adults pooled from 4 community-based studies. We investigated the potential advantages of IRT scoring over conventional scoring on the basis of participants' item response patterns. Items most likely endorsed by individuals low in SCC severity relate to word retrieval and general subjective memory decline. Items likely endorsed only by individuals high in SCC severity relate to nonepisodic memory changes, such as decline in comprehension, judgment and executi...

Measuring Alzheimer disease progression with transition probabilities: Estimates from NACC-UDS Curr Alzheimer Res. 2011 Nov 28; Spackman DE, Kadiyala S, Neumann PJ, Veenstra DL, Sullivan SD Abstract Objectives: Estimate the probabilities, for Alzheimer's disease (AD) patients, of transitioning between stages of disease severity (mild, moderate, severe, dead) and care settings (community, institutional). Methods: Data were compiled by the National Alzheimer Coordinating Center. The main analyses were limited to 3,852 patients who were >50 years old, diagnosed with possible/probable AD and had at least two center visits. A multinomial logistic model accounting for patient and center level correlation was used to calculate transition probabilities between stages of the Clinical Dementia Rating (CDR). Separately we calculated the probabilities of being institutionalized based on CDR stage. Both analyses controlled for baseline age, time between visits, sex, marital status, whether ...

The cognitive impact of antiepileptic drugs Ther Adv Neurol Disord. 2011 Nov; 4(6): 385-407 Eddy CM, Rickards HE, Cavanna AE Abstract Effective treatment of epilepsy depends on medication compliance across a lifetime, and studies indicate that drug tolerability is a significant limiting factor in medication maintenance. Available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. On the other hand, some agents may serve to enhance cognitive function. In this review paper, we highlight the range of effects on cognition linked to a variety of newer and older AEDs, encompassing key alterations in both specific executive abilities and broader neuropsychological functions. Importantly, the data reviewed suggest that the effects exerted by an AED could vary depending on both patient characteristics and drug-related variables. However, there are considerable difficulties in evaluating the available evid...

Role of Neuropsychologists in the Evaluation and Management of Sport-related Concussion: An Inter-Organization Position Statement Clin Neuropsychol. 2011 Nov; 25(8): 1289-1294 Echemendia RJ, Iverson GL, McCrea M, Broshek DK, Gioia GA, Sautter SW, Macciocchi SN, Barr WB Abstract Over the past 20 years, clinical neuropsychologists have been at the forefront of both scientific and clinical initiatives aimed at developing evidence-based approaches to the evaluation and management of sport-related concussion. These efforts have directly impacted current policy on strategies for injury assessment and return-to-play by athletes after concussion. Many states are considering legislation requiring (a) education of athletes, parents, coaches, and school/organization officials on the recognition, evaluation, and management of sport-related concussions; (b) removal from play of any youth athlete that is suspected of having sustained a concussion; and (c) not allowing the student to return to parti...

Balkanizing the primate orbitofrontal cortex: distinct subregions for comparing and contrasting values Annals of the New York Academy of Science. 2011 Dec; 1239(1): 1-13 Rudebeck PH, Murray EA Abstract The primate orbitofrontal cortex (OFC) is often treated as a single entity, but architectonic and connectional neuroanatomy indicate that it has distinguishable parts. Nevertheless, few studies have attempted to dissociate the functions of its subregions. Here we review findings from recent neuropsychological and neurophysiological studies that do so. The lateral OFC seems to be important for learning, representing, and updating specific object-reward associations. The medial OFC seems to be important for value comparisons and choosing among objects on that basis. Rather than viewing this dissociation of function in terms of learning versus choosing, however, we suggest that it reflects the distinction between contrasts and comparisons: differences versus similarities. Making use of high...