Tuesday, March 30, 2010

Neuropsychology Abstract of the Day: Stretch!

Kashdan TB, & Rottenberg J. Psychological flexibility as a fundamental aspect of health. Clinical Psychology Review. 2010 Mar 12.

Traditionally, positive emotions and thoughts, strengths, and the satisfaction of basic psychological needs for belonging, competence, and autonomy have been seen as the cornerstones of psychological health. Without disputing their importance, these foci fail to capture many of the fluctuating, conflicting forces that are readily apparent when people navigate the environment and social world. In this paper, we review literature to offer evidence for the prominence of psychological flexibility in understanding psychological health. Thus far, the importance of psychological flexibility has been obscured by the isolation and disconnection of research conducted on this topic. Psychological flexibility spans a wide range of human abilities to: recognize and adapt to various situational demands; shift mindsets or behavioral repertoires when these strategies compromise personal or social functioning; maintain balance among important life domains; and be aware, open, and committed to behaviors that are congruent with deeply held values. In many forms of psychopathology, these flexibility processes are absent. In hopes of creating a more coherent understanding, we synthesize work in emotion regulation, mindfulness and acceptance, social and personality psychology, and neuropsychology. Basic research findings provide insight into the nature, correlates, and consequences of psychological flexibility and applied research provides details on promising interventions. Throughout, we emphasize dynamic approaches that might capture this fluid construct in the real-world.

PMID: 20347514 [PubMed - as supplied by publisher]

Monday, March 29, 2010

In the Wide World: Halifax, Nova Scotia

The Novel Tech Ethics research team at Dalhousie University, where today's Neuropsychology Abstract of the Day originated:

Novel Tech Ethics website

From the homepage:
"The Novel Tech Ethics research team led by Françoise Baylis and based at Dalhousie University, focuses on novel technologies that promise transformation. These technologies challenge us to explore the social, political, and cultural understandings of the self, and to reexamine our ethical obligations to others, including those with whom we will not co-exist.

"Currently, the Novel Tech Ethics research team has a particular focus on neural, genetic, and reproductive technologies. Grant-funded projects in these areas address the concerns of the individual, the community and the species. Academic exchanges, public discussion and debate contribute to our understanding of these issues and also help to inform public policy."

Among other features at the website, podcasts of presentations for their 2009 conference, BrainMatters: New Directions in Neuro Ethics, are available on this page:
Conference Podcasts

Neuropsychology Abstract of the Day: Cognitive Enhancement

Outram SM. The use of methylphenidate among students: The future of enhancement? Journal of Medical Ethics. 2010 Apr, 36(4), 198-202.

Novel Tech Ethics, Dalhousie University, 1234 LeMarchant Street, Halifax NS B3H 3P7, Canada.

During the past few years considerable debate has arisen within academic journals with respect to the use of smart drugs or cognitive enhancement pharmaceuticals. The following paper seeks to examine the foundations of this cognitive enhancement debate using the example of methylphenidate use among college students. The argument taken is that much of the enhancement debate rests upon inflated assumptions about the ability of such drugs to enhance and over-estimations of either the size of the current market for such drugs or the rise in popularity as drugs for enhancing cognitive abilities. This article provides an overview of the empirical evidence that methylphenidate has the ability to significantly improve cognitive abilities in healthy individuals, and examines whether the presumed uptake of the drug is either as socially significant as implied or growing to the extent that it requires urgent regulatory attention. In addition, it reviews the evidence of side-effects for the use of methylphenidate which may be an influential factor in whether an individual decides to use such drugs. The primary conclusions are that neither drug efficacy, nor the benefit-to-risk balance, nor indicators of current or growing demand provide sufficient evidence that methylphenidate is a suitable example of a cognitive enhancer with mass appeal. In light of these empirically based conclusions, the article discusses why methylphenidate might have become seen as a smart drug or cognitive enhancer.

PMID: 20338928 [PubMed - in process]

Sunday, March 28, 2010

Chronic Disease and Using the Internet for Information

Last week, the Pew Internet & American Life Project released a report about individuals with chronic diseases and their use of the Internet to obtain and share information. The report is available at the link below:

Pew Report on Chronic Disease and the Internet

From the summary:
"The deck is stacked against people living with chronic disease. They are disproportionately offline. They often have complicated health issues, not easily solved by the addition of even the best, most reliable, medical advice.

"And yet, those who are online have a trump card. They have each other. This survey finds that having a chronic disease increases the probability that an internet user will share what they know and learn from their peers. They unearth nuggets of information. They blog. They participate in online discussions. And they just keep going. "

Multiple Sclerosis (MS): The SURPASS Clinical Trial

Study Evaluating Rebif, Copaxone, and Tysabri for Active Multiple Sclerosis (SURPASS): Description

Corporate press release


Neuropsychology Abstract of the Day: fMRI Tablet Touchscreen

Tam F, Churchill NW, Strother SC, & Graham SJ. A new tablet for writing and drawing during functional MRI.
Human Brain Mapping. 2010 Mar 24.

Writing and drawing are understudied with fMRI, partly for lack of a device that approximates these behaviors well while supporting task feedback and quantitative behavioral logging in the confines of the magnet. Consequently, we developed a tablet based on touchscreen technology that is accurate, reliable, relatively inexpensive, and fMRI compatible. After confirming fMRI compatibility, we conducted preliminary fMRI experiments examining the neural correlates of a widely used pen-and-paper neuropsychological assessment, the trail making test. In two subjects, we found left hemisphere frontal lobe activations similar to the major results of a previous group study, and we also noted individual differences mostly in the right hemisphere. These results demonstrate the utility of the new tablet for adaptations of pen-and-paper tests and suggest possible uses of the tablet for longitudinal, within-subjects studies of disease or therapy. We also discuss using the tablet for several other types of tests requiring many, continuous, or two-dimensional responses that were previously very difficult to perform during fMRI. Hum Brain Mapp, 2010. (c) 2010 Wiley-Liss, Inc.

PMID: 20336688 [PubMed - as supplied by publisher]

Brain Evolution: Colin Blakemore

From today's Observer:

Colin Blakemore: how the human brain got bigger by accident and not through evolution
Oxford neurobiologist Colin Blakemore tells Robin McKie why he thinks a mutation in the human brain 200,000 years ago suddenly made us a super-intelligent species

Robin McKie
28 March 2010
The Observer

Read the article

Saturday, March 27, 2010

Neuropsychology Abstract of the Day: Temporal Encoding

Bueti D, Bahrami B, Walsh V, & Rees G. Encoding of temporal probabilities in the human brain. Journal of Neuroscience. 2010 Mar 24, 30(12), 4343-4352.

Anticipating the timing of future events is a necessary precursor to preparing actions and allocating resources to sensory processing. This requires elapsed time to be represented in the brain and used to predict the temporal probability of upcoming events. While neuropsychological, imaging, magnetic stimulation studies, and single-unit recordings implicate the role of higher parietal and motor-related areas in temporal estimation, the role of earlier, purely sensory structures remains more controversial. Here we demonstrate that the temporal probability of expected visual events is encoded not by a single area but by a wide network that importantly includes neuronal populations at the very earliest cortical stages of visual processing. Moreover, we show that activity in those areas changes dynamically in a manner that closely accords with temporal expectations.

PMID: 20335470 [PubMed - in process]

Saturday, March 20, 2010

Traumatic Brain Injury: New CDC Report

Several days ago, the CDC released a report entitled, "Traumatic Brain Injury in the United States: Emergency Department Visits, Hospitalizations, and Deaths, 2002-2006" - available as a .pdf (and .doc) download.

Download the report

C-SPAN Video Library: Carl Zimmer's Soul Made Flesh

C-SPAN Video Library: Carl Zimmer's "Soul Made Flesh: The Discovery of the Brain":

Watch the Talk

From 23 February 2004, "Carl Zimmer talked about his book, Soul Made Flesh: The Discovery of the Brain--and How it Changed the World, published by The Free Press. The book examined the way the brain has been perceived throughout history."

Neuropsychology Abstract of the Day: Alzheimer's Drugs in Clinical Practice

Santoro A, Siviero P, Minicuci N, Bellavista E, Mishto M, Olivieri F, Marchegiani F, Chiamenti AM, Benussi L, Ghidoni R,
Nacmias B, Bagnoli S, Ginestroni A, Scarpino O, Feraco E, Gianni W, Cruciani G, Paganelli R, Di Iorio A, Scognamiglio
M, Grimaldi LM, Gabelli C, Sorbi S, Binetti G, Crepaldi G, & Franceschi C. Effects of donepezil, galantamine and rivastigmine in 938 italian patients with Alzheimer's disease: A prospective, observational study. CNS Drugs. 2010 Feb 1; 24(2): 163-176. doi: 10.2165/11310960-000000000-00000.

Department of Experimental Pathology, University of Bologna, Via S. Giacomo 12, Bologna, Italy.

Acetylcholinesterase inhibitors (AChEIs) have been used to improve cognitive status and disability in patients with mild to moderate Alzheimer's disease (AD). However, while the efficacy of AChEIs (i.e. how they act in randomized controlled trials) in this setting is widely accepted, their effectiveness (i.e. how they behave in the real world) remains controversial. To compare the effects of three AChEIs, donepezil (Aricept), galantamine (Reminyl) and rivastigmine (Exelon), in an Italian national, prospective, observational study representative of the 'real world' clinical practice of AChEI treatment for AD. 938 patients with mild to moderate AD collected within the framework of the Italian National Cronos Project (CP), involving several UVAs (AD Evaluation Units) spread over the entire national territory, who were receiving donepezil, galantamine or rivastigmine were followed for 36 weeks by measuring: (i) function, as determined by the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales; (ii) cognition, as measured by the Mini-Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) [primary outcome measures]; and (iii) behaviour, as measured on the Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR) scale. Moreover, all patients were genotyped for apolipoprotein E (apoE) genetic variants. No statistically significant improvement in the primary outcome measures (MMSE and ADAS-Cog) was observed with drug therapy at 36 weeks, at which point all groups had lost, on average, 1 point on the MMSE and gained 2-3 points on the ADAS-Cog scale compared with baseline. On the secondary outcome measures at week 36, all treatment groups showed a significant worsening on the ADL and IADL scales compared with baseline, while on the NPI scale there were no significant differences from baseline except for the galantamine-treated group which worsened significantly. Moreover, patients receiving galantamine worsened significantly compared with the donepezil-treated group on the IADL scale. ApoE epsilon4 allele did not influence the effect of drug therapy. Over a 36-week follow-up period, no significant difference in the effects of donepezil, galantamine and rivastigmine on a variety of functional and cognitive parameters was observed in a large number of apoE-genotyped patients with mild to moderate AD recruited within the framework of a national project representative of the scenario usually encountered in actual clinical practice in Italy. The limitations (possibility of administration of lower drug doses than are used in clinical trials, relatively short follow-up period and the lack of randomization) and strengths (large number of patients, concomitant observation of the three drugs and the number of parameters assessed, including apoE genotype) of the present study are acknowledged. Our type of naturalistic study should complement clinical trials because 'real world' practice operates in the face of the numerous variables (e.g. health status and co-morbidities) associated with a complex disease such as AD in elderly people.

PMID: 20088621 [PubMed - indexed for MEDLINE]

Thursday, March 18, 2010

MindHacks Brings Neuropsychology to Parliament

An interesting post at MindHacks about their presentation for the All-Party Parliamentary Group on Scientific Research in Learning and Education:

Lords, Ladies, and Video Games

The posting also provides a link to the presentation's PowerPoint file.


"Beauty and the Brain" Walters Art Museum

Here is the website for the "Beauty and the Brain" exhibit discussed in the previous posting:

Walters Art Museum

Beauty and the Brain

A good read from The Dana Foundation Blog:

Gazing with New Eyes


Sunday, March 14, 2010

Neuropsychology Abstract of the Day: Alzheimer's Progression Rates

Doody RS, Pavlik V, Massman P, Rountree S, Darby E, & Chan W. Predicting progression of Alzheimer's disease. Alzheimers Res Ther. 2010 Feb 23; 2(1):2. [Epub ahead of print]

Alzheimer's Disease and Memory Disorders Center, Baylor College of Medicine, 6501 Fannin Street, NB302, Houston, TX 77030, USA.

ABSTRACT: INTRODUCTION: Clinicians need to predict prognosis of Alzheimer's disease (AD), and researchers need models of progression to develop biomarkers and clinical trials designs. We tested a calculated initial progression rate to see whether it predicted performance on cognition, function and behavior over time, and to see whether it predicted survival. METHODS: We used standardized approaches to assess baseline characteristics and to estimate disease duration, and calculated the initial (pre-progression) rate in 597 AD patients followed for up to 15 years. We designated slow, intermediate and rapidly progressing groups. Using mixed effects regression analysis, we examined the predictive value of a pre-progression group for longitudinal performance on standardized measures. We used Cox survival analysis to compare survival time by progression group. RESULTS: Patients in the slow and intermediate groups maintained better performance on the cognitive (ADAScog and VSAT), global (CDR-SB) and complex activities of daily living measures (IADL) (P values < 0.001 slow versus fast; P values < 0.003 to 0.03 intermediate versus fast). Interaction terms indicated that slopes of ADAScog and PSMS change for the slow group were smaller than for the fast group, and that rates of change on the ADAScog were also slower for the intermediate group, but that CDR-SB rates increased in this group relative to the fast group. Slow progressors survived longer than fast progressors (P = 0.024). CONCLUSIONS: A simple, calculated progression rate at the initial visit gives reliable information regarding performance over time on cognition, global performance and activities of daily living. The slowest progression group also survives longer. This baseline measure should be considered in the design of long duration Alzheimer's disease clinical trials.

PMID: 20178566 [PubMed - as supplied by publisher]

Saturday, March 13, 2010

Neuropsychology Abstract of the Day: Subjective Memory Complaints

Elfgren C, Gustafson L, Vestberg S, & Passant U. Subjective memory complaints, neuropsychological performance and psychiatric variables in memory clinic attendees: A 3-year follow-up study. Archives of Gerontology and Geriatrics. 2010 Mar 6. [Epub ahead of print]

Department of Geriatric Psychiatry, Clinical Sciences, Lund University Hospital, SE-221 85 Lund, Sweden.

The aims were to evaluate the cognitive performance and clinical diagnosis in patients (<75 years) seeking help for subjective memory complaints, to determine the prevalence of certain psychiatric symptoms and to conduct follow-up examinations. At baseline 41% showed normal cognitive performance (subjective memory impairment; SMI), 37% fulfilled criteria for mild cognitive impairment (MCI) and 22% were classified as dementia. There were significant associations between the three groups and experiences of psychosocial stress and feelings of anxiety. The proportion of psychosocial stress was significantly higher in SMI vs. MCI and SMI vs. dementia. Feelings of anxiety were significantly higher in SMI vs. MCI. At the 3-year follow-up, 88% of the SMI patients remained stable SMI and 60% of the MCI patients remained stable. There was a significant reduction of psychosocial stress and moderate reduction of feelings of anxiety among the SMI patients. The findings indicate that the risk of patients with SMI developing dementia is small within a 3-year span. We propose that subjective memory complaints might be influenced by the presence of psychosocial stress and feelings of anxiety disturbing the memory processes and interfering with the patients' evaluation of their memory function. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PMID: 20211500 [PubMed - as supplied by publisher]

Friday, March 12, 2010

Pain Research

From King's College London:

Innovative Partnership for Pain Research
10 Mar 2010, PR 48/10
"King’s has partnered with Pfizer to create an open innovation laboratory for pain research. As part of the partnership, a small team of Pfizer scientists will be based at the Wolfson Centre for Age-Related Diseases to conduct research in pain biology."

read the full article

Upcoming Event: Computers and Medical Practice (London, 17 March 2010)

From the King's College London website:

Seminar: The computer as the third actor in the clinical consultation
17 Mar 2010, 12:45-13:45, 6th Floor Seminar Room, Capital House, Guy's Campus

Speaker: Dr Simon de Lusignan
Speaker institution: St George's University of London

Full information

Neuropsychology Abstract of the Day: Aging and MCI Screening

Today's recommended read deals with an important neuropsychological assessment issue in the domain of aging and the potential to identify the presence of cognitive problems that might (emphasis on "might" - such findings in a screen are not definitive) be part of the onset of a dementing disease process. The issue has implications, as well, for applications in CNS clinical trials.

Scharre DW, Chang SI, Murden RA, Lamb J, Beversdorf DQ, Kataki M, Nagaraja HN, & Bornstein RA. Self-administered Gerocognitive Examination (SAGE): A Brief Cognitive Assessment Instrument for Mild Cognitive Impairment (MCI) and Early Dementia. Alzheimer Disease and Associate Disorders. 2010 January/March; 24(1), 64-71.

OBJECTIVES: To develop a self-administered cognitive assessment instrument to facilitate the screening of mild cognitive impairment (MCI) and early dementia and determine its association with gold standard clinical assessments including neuropsychologic evaluation. METHODS: Adults aged above 59 years with sufficient vision and English literacy were recruited from geriatric and memory disorder clinics, educational talks, independent living facilities, senior centers, and memory screens. After Self-administered Gerocognitive Examination (SAGE) screening, subjects were randomly selected to complete a clinical evaluation, neurologic examination, neuropsychologic battery, functional assessment, and mini-mental state examination (MMSE). Subjects were identified as dementia, MCI, or normal based on standard clinical criteria and neuropsychologic testing. RESULTS: Two hundred fifty-four participants took the SAGE screen and 63 subjects completed the extensive evaluation (21 normal, 21 MCI, and 21 dementia subjects). Spearman rank correlation between SAGE and neuropsychologic battery was 0.84 (0.76 for MMSE). SAGE receiver operating characteristics on the basis of clinical diagnosis showed 95% specificity (90% for MMSE) and 79% sensitivity (71% for MMSE) in detecting those with cognitive impairment from normal subjects. CONCLUSIONS: This study suggests that SAGE is a reliable instrument for detecting cognitive impairment and compares favorably with the MMSE. The self-administered feature may promote cognitive testing by busy clinicians prompting earlier diagnosis and treatment.

PMID: 20220323 [PubMed - as supplied by publisher]

Interpersonal Impact and Infection Avoidance

The British Psychological Society's Research Digest blog has an interesting posting today about how we respond socially to reminders about infectious disease:

Reminder of disease primes the body and mind to repel other people

Thursday, March 11, 2010

Neuropsychology Abstract of the Day: TBI Clinical Trials

Today's recommended reading addresses proposed efficacy measures for use in clinical trials related to traumatic brain injury (TBI):

Bagiella E, Novack TA, Ansel B, Diaz-Arrastia R, Dikmen S, Hart T, & Temkin N. Measuring Outcome in Traumatic Brain Injury Treatment Trials: Recommendations From the Traumatic Brain Injury Clinical Trials Network. Journal of Head Trauma Rehabilitation. 2010.

BACKGROUND: Traumatic brain injury (TBI) involves several aspects of a patient's condition, including physical, mental, emotional, cognitive, social, and functional changes. Therefore, a clinical trial with individuals with TBI should consider outcome measures that reflect their global status. METHODS: We present the work of the National Institute of Child Health and Development-sponsored Traumatic Brain Injury Clinical Trials Network Outcome Measures subcommittee and its choice of outcome measures for a phase III clinical trial of patients with complicated mild to severe TBI. RESULTS: On the basis of theoretical and practical considerations, the subcommittee recommended the adoption of a core of 9 measures that cover 2 different areas of recovery: functional and cognitive. These measures are the Extended Glasgow Outcome Scale; the Controlled Oral Word Association Test; the Trail Making Test, Parts A and B; the California Verbal Learning Test-II; the Wechsler Adult Intelligence Scale-III Digit Span subtest; the Wechsler Adult Intelligence Scale-III Processing Speed Index; and the Stroop Color-Word Matching Test, Parts 1 and 2. CONCLUSIONS: The statistical methods proposed to analyze these measures using a global test procedure, along with research and methodological and regulatory issues involved with the use of multiple outcomes in a clinical trial, are discussed.

PMID: 20216459 [PubMed - as supplied by publisher]

Wednesday, March 10, 2010

Neuropsychology Abstract of the Day: The New Wechsler Scales

Today's recommended reading deals with a very important issue in neuropsychological assessment:

Loring DW, & Bauer RM. Testing the limits: cautions and concerns regarding the new Wechsler IQ and Memory scales. Neurology, 2010, 74(8), 685-690.

Department of Neurology, Emory University, 101 Woodruff Circle, Suite 6000, Atlanta, GA, USA. 30322

The Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (WMS) are 2 of the most common psychological tests used in clinical care and research in neurology. Newly revised versions of both instruments (WAIS-IV and WMS-IV) have recently been published and are increasingly being adopted by the neuropsychology community. There have been significant changes in the structure and content of both scales, leading to the potential for inaccurate patient classification if algorithms developed using their predecessors are employed. There are presently insufficient clinical data in neurologic populations to insure their appropriate application to neuropsychological evaluations. We provide a perspective on these important new neuropsychological instruments, comment on the pressures to adopt these tests in the absence of an appropriate evidence base supporting their incremental validity, and describe the potential negative impact on both patient care and continuing research applications.

PMID: 20177123 [PubMed - in process]

Tuesday, March 09, 2010

Assistive Aid for Persons with Memory Deficits

A Little Black Box to Jog Failing Memory
The New York Times
Published: March 8, 2010
"Researchers have tested the Sensecam, which contains a digital camera and an accelerometer, as an aid to people with Alzheimer’s disease and other memory disorders."

Read the full article

Monday, March 08, 2010

Alzheimer's Disease: A-beta and Immune System

Old Enemy Might Help to Prevent Alzheimer’s
The New York Times
Published: March 8, 2010

"Harvard researchers are taking a new look at beta amyloid, which was thought to be a chief villain in Alzheimer’s whose function was that of a waste product in the brain."

Read the full article

In the Wide World: Norwegian Neuropsychological Society

The Norwegian Neuropsychological Society/Norsk Nevropsykologisk Forening:


From the homepage:

"The Norwegian Neuropsychological Society (NNS) was formed in 1996 and professor Hallgrim Kløve was elected as NNA’s first chair. The aims of the Association are to promote neuropsychology in Norway, stimulate exchange of national and international communication among neuropsychologists, and stimulate development in neuropsychology as well as to provide information both internally and toward the public.

"The NNS is an interest organisation that has its member base in the Norwegian Psychological Association. The regulations of the NNS comply with the regulations of the Norwegian Psychological Association. From 2007 we have formally been approved as an associated interest group with the Norwegian Psychological Association."

Now, you can follow them on Twitter, too.

Friday, March 05, 2010

Developmental Neuropsychology: The Infant Brain on BBC Radio 4

Available from BBC Radio 4:

In Our Time: The Infant Brain: Listen Here.

Description, from the BBC source link:

Melvyn Bragg and guests Usha Goswami, Annette Karmiloff-Smith and Denis Mareschal discuss what new research reveals about the infant brain.

For obvious reasons, what happens in the minds of very young, pre-verbal children is elusive. But over the last century, the psychology of early childhood has become a major subject of study.

Some scientists and researchers have argued that children develop skills only gradually, others that many of our mental attributes are innate.

Sigmund Freud concluded that infants didn't differentiate themselves from their environment.

The pioneering Swiss child psychologist Jean Piaget thought babies' perception of the world began as a 'blooming, buzzing confusion' of colour, light and sound, before they developed a more sophisticated worldview, first through the senses and later through symbol.

More recent scholars such as the leading American theoretical linguist Noam Chomsky have argued that the fundamentals of language are there from birth. Chomsky has famously argued that all humans have an innate, universally applicable grammar.

Over the last ten to twenty years, new research has shed fresh light on important aspects of the infant brain which have long been shrouded in mystery or mired in dispute, from the way we start to learn to speak to the earliest understanding that other people have their own minds.


Usha Goswami, Professor of Education at the University of Cambridge and Director of its Centre for Neuroscience in Education

Annette Karmiloff-Smith, Professorial Research Fellow at the Centre for Brain and Cognitive Development at the Department of Psychological Sciences, Birkbeck College, University of London

Denis Mareschal, Professor of Psychology at the Centre for Brain and Cognitive Development at Birkbeck College, University of London.

Wednesday, March 03, 2010

Alzheimer Disease: Dimebon Results, Part II

From The New York Times:

Hopes for Alzheimer’s Drug Are Dashed
Published: March 4, 2010

"The drug, called Dimebon, failed in its first late-stage clinical trial, dealing a blow to patients with Alzheimer’s and the companies developing the treatment, Medivation and Pfizer."

Read the full article

Alzheimer Disease: Dimebon Results

A press release from earlier today by Pfizer:

Pfizer And Medivation Announce Results From Two Phase 3 Studies In Dimebon (latrepirdine) Alzheimer’s Disease Clinical Development Program

"About the CONNECTION Study

"CONNECTION is a Phase 3, multi-national, double-blind, placebo-controlled safety and efficacy trial involving 598 patients with mild-to-moderate AD at 63 sites in North America, Europe, and South America. Patients had a mean age of 74.4 years and a mean score of 17.7 on the Mini-Mental State Examination (MMSE) upon entry into the study. More than 40 percent of the patients enrolled were in the United States. In the study, patients were randomized to one of three treatment groups, receiving dimebon 20 mg three times a day (TID), dimebon 5 mg TID, or placebo TID for six months. The 5 mg arm was included in the study to help define the effective dose range for dimebon treatment.

"No statistically significant improvements for the 20 mg TID group relative to placebo were achieved on the co-primary endpoints. One primary endpoint evaluated the effect of dimebon on cognition, as measured by the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), and showed that dimebon-treated patients achieved a 0.1 point difference from patients receiving placebo (p=0.86). Neither group was significantly changed from baseline. The other primary endpoint evaluated the effect of dimebon on independently-rated global function over the course of the six-month trial, as measured by the Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus; p=0.81). According to the CIBIC-plus scale, 64.9 percent of the patients treated with dimebon 20 mg TID showed improvement or no change at Week 26 compared to 65.4 percent of placebo-treated patients. Results for the dimebon 5 mg dose were similar to the dimebon 20 mg and placebo, although they were numerically lower.

"The 20 mg TID dimebon-treated patients also showed no statistically significant differences compared to placebo on the secondary efficacy endpoints. After six months of treatment, patients treated with dimebon showed a 0.4 point difference from patients taking placebo on activities of daily living (p=0.61), as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL). Neither group was significantly changed from baseline. The dimebon-treated group showed a 1.6 point improvement on behavior compared to placebo (p=0.17), as measured by the Neuropsychiatric Inventory (NPI). Compared to baseline, each group was improved, but this change was only significant for the dimebon group. On the Mini Mental State Examination (MMSE), another measure of cognition, both groups improved significantly over baseline (dimebon 0.7; placebo 1.2). The difference favoring placebo was not significant (p=0.10). Results for the dimebon 5 mg dose were similar to dimebon 20 mg and placebo, although they were numerically lower. Dimebon, 20 mg orally three-times daily, was well tolerated in the study. The number of patients with at least one adverse event was similar in the dimebon 20 mg and placebo groups (72.0% vs. 74.2%, respectively). The most frequently reported adverse events (>5%) in patients in the 20 mg dimebon group occurring more commonly than in the placebo group included somnolence (11.0% vs. 10.1%), dry mouth (8.5% vs. 6.6%), headache (9.5% vs. 5.6%), dizziness (7.5% vs. 5.1%), constipation (5.5% vs. 3.5%), cough (7.5% vs. 3.5%) and depression (6.0% vs. 3.5%). Similar rates of adverse events were observed for the 5 mg TID group. No clinically significant findings were noted in assessment of vital signs, clinical laboratories or on electrocardiography (ECG)."

Read the full release


Alzheimer’s Association statement on negative Phase III trial results for latrepirdine (Dimebon)
03 March 2010

Read the statement


From ABC News:

Pfizer Alzheimer's Drug Dimebon Fails in Study
Late Stage Trials Show No Effect But Drug May Still Have a Future
ABC News Medical Unit
March 03, 2010
"Dimebon, a once-promising new Alzheimer's drug from Pfizer Inc., may be no more effective than a placebo at treating the disease, according to late-stage clinical data released by the company Wednesday."

Read the full article

Event: Take Your Brain to Lunch (Philadelphia)

A program from the University of Pennsylvania:

Take Your Brain to Lunch
"Everything from education to warfare comes down to the workings of the human mind, and now the mind itself is being understood in terms of the brain. Come hear about the different ways that Penn Arts and Sciences faculty are studying this amazing three-pound organ and the insights it is offering on diverse human problems.

"Martha Farah, Annenberg Professor of Natural Sciences in the Department of Psychology and Director of Penn's new Center for Neuroscience & Society, will lead conversations with Penn faculty members about the brain. So take your brain to lunch and enjoy some food for thought!

All lectures are from 12:00 p.m. - 1:30 p.m.
Light refreshments will be provided."

For dates and topics, please see the UPenn webpage for the program

Tuesday, March 02, 2010

Neuropsychology Abstract of the Day: Alzheimer Drug Development

Today's recommended article to read; abstract from PubMed:

Bergmans BA & De Strooper B. gamma-secretases: From cell biology to therapeutic strategies. Lancet Neurology. 2010 Feb; 9(2 ): 215-226.

Department of Molecular and Developmental Genetics, VIB, Leuven, Belgium; Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium.

Presenilins form the catalytic part of the gamma-secretases, protein complexes that are responsible for the intramembranous cleavage of transmembrane proteins. The presenilins are involved in several biological functions, but are best known for their role in the generation of the beta-amyloid (Abeta) peptide in Alzheimer's disease and are therefore thought to be important drug targets for this disorder. Mutations in the presenilin genes cause early-onset familial Alzheimer's disease, but mutation carriers have substantial phenotypic heterogeneity. Recent evidence implicating presenilin mutations in non-Alzheimer's dementias, including frontotemporal dementia and Lewy body dementia, warrants further investigation. An increased understanding of the diversity of the molecular cell biology of the gamma-secretase complex and the effects of clinical mutations in the presenilin genes might help pave the way for improved development of drugs that are designed to target gamma-secretase enzymatic activity in Alzheimer's disease and potentially in other neurological diseases. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID: 20129170 [PubMed - indexed for MEDLINE]