Monday, October 31, 2011

Neuropsychology Abstract of the Day: Alzheimer's Disease Pharmacologic Strategies

New pharmacological strategies for treatment of Alzheimer's disease: focus on disease-modifying drugs
British Journal of Clinical Pharmacology. 2011 Oct 28;
Salomone S, Caraci F, Leggio GM, Fedotova J, Drago F


Current approved drug treatments for Alzheimer disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine. These drugs provide symptomatic relief but poorly affect the progression of the disease. Drug discovery has been directed, in the last ten years, to develop "disease-modifying drugs" hopefully able to counteract the progression of AD. Because in a chronic, slow progressing pathological process, such as AD, an early start of treatment enhances the chance of success, it is crucial to have biomarkers for early detection of AD-related brain dysfunction, usable before clinical onset. Reliable early biomarkers need therefore to be prospectively tested for predictive accuracy, with specific cutoff values validated in clinical practice. Disease-modifying drugs developed so far include drugs to reduce β amyloid (Aβ) production, drugs to prevent Aβ aggregation, drugs to promote Aβ clearance, drugs targeting tau phosphorylation and assembly, and other approaches. Unfortunately none of these drugs has demonstrated efficacy in phase 3 studies. The failure of clinical trials with disease-modifying drugs rises a number of questions, spanning from methodological flaws to fundamental understanding of AD patho-physiology and biology. Recently, new diagnostic criteria applicable to presymptomatic stages of AD have been published. These new criteria may impact drug development, such that future trials on disease-modifying drugs will include populations susceptible to AD, before clinical onset. Specific problems with completed trials and hopes with ongoing trials are discussed in this review.

PMID: 22035455 [PubMed - as supplied by publisher]

Sunday, October 30, 2011

Neuropsychology Abstract of the Day: MCI

Predictive value of APOE-ε4 allele for progression from MCI to AD-type dementia: A meta-analysis
Journal of Neurology Neurosurgery and Psychiatry. 2011 Oct; 82(10): 1149-1156.
Elias-Sonnenschein LS, Viechtbauer W, Ramakers IH, Verhey FR, Visser PJ


BACKGROUND: The identification of subjects with mild cognitive impairment (MCI) at high risk for Alzheimer's disease (AD) is important for prognosis and early intervention. The APOE-ε4 allele is the strongest known genetic risk factor for AD. The authors performed a meta-analysis to establish the predictive accuracy of the APOE-ε4 allele for progression from MCI to AD-type dementia.

METHODS: The authors included 35 prospective cohort studies of subjects with MCI, including 6095 subjects, of whom 1236 progressed to AD-type dementia after 2.9 years of follow-up. Pooled estimates of the OR, sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (LR+ and LR-) were obtained using random-effects models.

RESULTS: The OR for subjects with MCI who are carriers of APOE-ε4 allele to progress to AD-type dementia was 2.29 (95% CI 1.88 to 2.80), the sensitivity was 0.53 (95% CI 0.46 to 0.61), the specificity was 0.67 (95% CI 0.62 to 0.71), the PPV was 0.57 (95% CI 0.48 to 0.66), the NPV was 0.75 (95% CI 0.70 to 0.80), the LR+ was 1.60 (95% CI 1.48 to 1.72), and the LR- was 0.75 (95% CI 0.67 to 0.82). Meta-regression showed that sensitivity, specificity and NPV were dependent on age, APOE-ε4 allele background prevalence or follow-up length.

CONCLUSIONS: The APOE-ε4 allele is associated with a moderately increased risk for progression from MCI to AD-type dementia. The low sensitivity and PPV makes genotyping of limited value for predicting AD-type dementia in clinical practice. For trials aiming to prevent progression from MCI to AD-type dementia, APOE genotyping may be useful in selecting subjects with a higher risk for progression to AD-type dementia.

PMID: 21493755 [PubMed - indexed for MEDLINE]

Saturday, October 29, 2011

Neuropsychology Abstract of the Day: Amyloid

Nitration of tyrosine 10 critically enhances amyloid β aggregation and plaque formation
Neuron. 2011 Sep 8; 71(5): 833-844.
Kummer MP, Hermes M, Delekarte A, Hammerschmidt T, Kumar S, Terwel D, Walter J, Pape HC, König S, Roeber S, Jessen F, Klockgether T, Korte M, Heneka MT


Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation of the inducible nitric oxide synthase (NOS2) resulting in increased NO production. NO contributes to cell signaling by inducing posttranslational protein modifications. Under pathological conditions there is a shift from the signal transducing actions to the formation of protein tyrosine nitration by secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid β (Aβ) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Aβ). Nitration of Aβ accelerated its aggregation and was detected in the core of Aβ plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment with the NOS2 inhibitor L-NIL strongly decreased 3NTyr(10)-Aβ, overall Aβ deposition and cognitive dysfunction in APP/PS1 mice. Further, injection of 3NTyr(10)-Aβ into the brain of young APP/PS1 mice induced β-amyloidosis. This suggests a disease modifying role for NOS2 in AD and therefore represents a potential therapeutic target.

PMID: 21903077 [PubMed - indexed for MEDLINE]

Friday, October 28, 2011

Neuropsychology Abstract of the Day: Mild Cognitive Impairment

There have been a number of excellent papers published over the past month in a number of different journals on the topic of Mild Cognitive Impairment (MCI). Looking forward to reading this new paper:

An exploration of subgroups of mild cognitive impairment based on cognitive, neuropsychiatric and functional features: analysis of data from the national Alzheimer's coordinating center
American Journal of Geriatric Psychiatry. 2011 Nov; 19(11): 940-950.
Hanfelt JJ, Wuu J, Sollinger AB, Greenaway MC, Lah JJ, Levey AI, Goldstein FC


OBJECTIVES: : To empirically expand the existing subtypes of mild cognitive impairment (MCI) by incorporating information on neuropsychiatric and functional features, and to assess whether cerebrovascular disease (CVD) risk factors are associated with any of these subgroups.

DESIGN: : Latent class analysis using 1,655 patients with MCI.

SETTING: : Participants in the Uniform Data Set (UDS) from 29 National Institutes of Health-supported Alzheimer's Disease Centers.

PARTICIPANTS: : Patients with a consensus diagnosis of MCI from each center and with a Mini-Mental State Examination score of 22 or greater.

MEASUREMENTS: : UDS cognitive battery, Neuropsychiatric Inventory Questionnaire, and Functional Assessment Questionnaire administered at initial visit.

RESULTS: : Seven empirically based subgroups of MCI were identified: 1) minimally impaired (relative frequency, 12%); 2) amnestic only (16%); 3) amnestic with functional and neuropsychiatric features (16%); 4) amnestic multidomain (12%); 5) amnestic multidomain with functional and neuropsychiatric features (12%); 6) functional and neuropsychiatric features (15%); and 7) executive function and language impairments (18%). Two of these subgroups with functional and neuropsychiatric features were at least 3.8 times more likely than the minimally impaired subgroup to have a Rosen-Hachinski score of 4 or greater, an indicator of probable CVD.

CONCLUSIONS: : Findings suggest that there are several distinct phenotypes of MCI characterized by prominent cognitive features, prominent functional features, and neuropsychiatric features or a combination of all three. Subgroups with functional and neuropsychiatric features are significantly more likely to have CVD, which suggests that there may be distinct differences in disease etiology from the other phenotypes.

PMID: 22024618 [PubMed - in process]

Thursday, October 27, 2011

Neuropsychology Abstract of the Day: Pediatric Epilepsy and Memory Assessment

Everyday verbal memory and pediatric epilepsy
Epilepsy and Behavior. 2011 Jul; 21(3): 285-290.
Chapieski L, Evankovich K, Hiscock M, Collins R


This study addressed the reliability and validity of reports of everyday verbal memory with a sample of 132 pediatric patients with epilepsy. Each patient and one parent completed a questionnaire on everyday verbal memory comprising two scales assessing learning/retrieval and prospective memory. Each patient was also administered tests of memory, attention, and academic skills. Information about attention, mood, and academic performance was obtained from parent and teacher report, as well as self-report. Memory test scores were correlated with children's reports of learning and retrieval in everyday activities, but were not significantly associated with reports of prospective memory. Reports of everyday memory were found to be reliable and predictive of academic performance. Performance on tests of memory, conversely, was unrelated to reports of academic performance. Reports of everyday memory may, therefore, provide more useful information than tests when evaluating the effects of epilepsy and its treatments.

PMID: 21620770 [PubMed - indexed for MEDLINE]

Temporal Integration

A paper about temporal integration and the psychological present, available as a free download:

Wittmann, M. (2011). Moments in time. Frontiers in Integrative Neuroscience.
published: 18 October 2011
doi: 10.3389/fnint.2011.00066

Free download pdf

Wednesday, October 26, 2011

Book Review: "Kraken" by Wendy Williams

This post, and all others on BrainBlog, are written by Anthony Risser for his blog BrainBlog. The appearance of this entry, and others, on different websites, framed under different websites, or not at the BrainBlog URL do not have my permission. All rights retained.

Wendy Williams
Kraken: The curious, exciting, and slightly disturbing science of squid
NY: Abrams Image (2011)
ISBN 978-0-8109-8465-3

My guess is that, unlike biology students, many psychology students exposed to their first courses in biopsychology and neuroscience have little idea about cephalopods and their role played in our knowledge about the nervous system and behavior. (Hint: You are likely to have found squid in your textbook, in that diagram which shows the recording of electrical activity from a generic single neuron and its axon.)

Wendy Williams’ new book, Kraken, is a curious book that gives credit to the cephalopods and to the scientists who respect them and learn from them. It is a brief book with a nicely moving narrative. It is accessible to a general audience. It introduces the reader to a community of scientists (professional and amateur) who search for and study squid, cuttlefish, and octopus. People like Julie Taylor and Bill Gilly who work with the Humboldt squid. People like Bruce Andersen who teach neurosurgeons how to remove the single giant axon of Loligo pealei in a manner that will allow it to function for several hours after its removal. The book’s photographs are notably lo-tech; it is easy to imagine the subjects of the pictures posing for (or trying to avoid) the author’s pocket cam.

Collections of Loligo pealei offered up their giant axons to allow Alan Hodgkin and Andrew Huxley to appreciate the action potential and the movement of ions across the cell membrane. Nobel-award winning work that, though the author believes that cephalopods themselves deserve a Nobel for their overall contributions to medicine and science (not entirely tongue-in-cheek!).

Neuroscience is an important part of the story, but it certainly not the only part. Cephalopods have survived several mass extinctions on Earth and their story takes on many different elements. Simply advancing knowledge from mythology was an important part of cephalopod investigations in the 19th and early 20th centuries. The so-called ‘Monsters of the Deep’ are still part of B-movie plots, but we thrill more in the 21st century to their bioluminescence (which has been translated into a methodology to study functioning neurons), their response to their environment, their problem-solving abilities, and rises and falls in their numbers. Returning to the nervous system and behavior, the final pages of the book are a fascinating look at the intelligence of cephalopods or, more clearly, how could one determine the "intelligence" of animals other than humans. There are volumes and volumes available about this issue, but the coverage here is succinct and creative.

In all, a charming book.

Ahoy! A lagniappe for the curious: Many of the topics portrayed in the book (and other things about cephalopods) are available by others who have posted videos on YouTube. Like any salty 19th century seafarer, just search for cephalopods.

UC San Francisco-Pfizer Drug Development Partnership

From EurekaAlert:

UCSF-Pfizer partnership yields projects aimed at clinical trials
26 October 2011

Read the full article

An Award for Dr. Brenda Milner

From the Scientific American blog:

The 2011 Pearl Meister Greengard Prize: Honoring Dr. Brenda Milner for her pioneering work in cognitive neuroscience
By Jeanne Garbarino
October 26, 2011 |

Read the blog post about the award

Amyloid Precursor Protein Processing and Alzheimer’s Disease

An NIH Public Access Author Manuscript:

Richard J. O’Brien and Philip C. Wong
Amyloid Precursor Protein Processing and Alzheimer’s Disease
Published in final edited form as:
Annu Rev Neurosci. 2011 ; 34: 185–204. doi:10.1146/annurev-neuro-061010-113613.

Download the free-access pdf here

This looks like a fine overview of our current knowledge.

Neuropsychology Abstract of the Day: Visual Memory Assessment

Landscape test for assessing visual memory in Alzheimer's disease
Rev Neurol. 2011 Jul 1; 53(1): 1-7
Valls-Pedret C, Olives J, Bosch B, Caprile C, Castellví M, Molinuevo JL, Rami L


INTRODUCTION: Visual episodic memory is affected in the early phases of Alzheimer's disease (AD).

AIMS: To design a visual memory test free of any verbal content, to offer its normative values in the elderly population in Spain, to validate the test in a group of patients with mild AD and to determine its capacity to discriminate between subjects with AD and controls.

SUBJECTS AND METHODS: The study involved a sample of 263 subjects (137 controls and 126 patients with AD) over 50 years of age. The landscape test consists of a first part in which participants are shown 25 photographs of landscapes. Five minutes later, the previous 25 photos are shown again together with 25 new pictures, and the subject must recognise the ones that have already been seen. The statistical analysis was performed using the Student t test for independent measures, ANCOVA, linear regression, Pearson's correlation and the ROC curve.

RESULTS: In the control group, sex and schooling did not have any significant effect on the results, although differences were found between the youngest group (50-59 years) and the oldest age group (equal to or above 80 years). Findings show that there is a significant difference between the mean scores on the landscape test obtained by the two groups (control: 44.06 ± 3.2; AD: 34.25 ± 6.6; p < 0.001). The area under the curve from the landscape test was 0.904, with a sensitivity of 0.82 and a specificity of 0.85.

CONCLUSIONS: The landscapes test is a simple, sensitive and novel instrument for assessing visual memory in early AD.

PMID: 21678318 [PubMed - indexed for MEDLINE]

From the Wellcome Trust Blog

A good read from today, an entry at the Wellcome Trust blog:

Craters, blisters and Pringles: Do small irregularities on the brain surface give us clues about its functions?
26 October 2011
Read the blog post

This Week's All in the Mind from BBC Radio 4

This week's All in the Mind podcast from BBC Radio 4:

Visit the show's webpage to listen or to download the episode

From the webpage:

"How can a good night's sleep improve your memory? Why does the answer to a crossword clue suddenly appear first thing in the morning after a night's rest? In this week's programme Claudia Hammond talks to psychologist, Kimberly Fenn about what happens in the brain when we sleep and why it can significantly improve our memory. Hysteria or conversion disorder is surprisingly, not confined to medical history. Nearly 1 in 5 patients seen by neurologists will have symptoms like paralysis, fits or loss of vision which can't be explained neurologically. Claudia talks to neurologist, Mark Edwards and psychiatrist, Richard Kanaan about the history of conversion disorder, how common it is today, the best way to treat it and its complex causes. Also in the programme, Claudia meets the carers getting involved in mental health research and why their input is making a a difference to research projects exploring mental health across the country."

(Running length = 30 mins.)

Tuesday, October 25, 2011

Parliamentary Private Members' Debate on Medication Use in ADHD

A discussion about ADHD and medication was held today as a Private Members' Debate at Westminster. Set by Pat McFadden MP (pictured above), the debate includes response by the Minister of State, Department of Health.

Available for streaming at Parliament TV Go to the 25th of October, Westminster Hall at advance to 1330 hrs.

Background resource: The 2008 NICE guideline about ADHD.

Neuropsychology Abstract of the Day: Cortical Neuroanatomy of Neuropsychological Deficits

The cortical neuroanatomy of neuropsychological deficits in mild cognitive impairment and Alzheimer's disease: A surface-based morphometric analysis
Neuropsychologia. 2011 Oct 15;
Ahn HJ, Seo SW, Chin J, Suh MK, Lee BH, Kim ST, Im K, Lee JM, Lee JH, Heilman KM, Na DL


Patients with probable Alzheimer's disease (AD) and the amnesic form of mild cognitive impairment (aMCI) often demonstrate several types of neuropsychological deficits. These deficits are often related to cortical atrophy, induced by neuronal degradation. The purpose of this study is to investigate whether different anatomic patterns of cortical atrophy are associated with specific neuropsychological deficits. The participants were 170 patients with AD and 99 patients with aMCI. All participants underwent the Seoul Neuropsychological Screening Battery (SNSB), which includes tests that assess attention, language, visuospatial functions, verbal and visual memory, and frontal/executive functions. Cortical atrophy (thinning) was quantified by measuring the thickness of the cortical mantle across the entire brain using automated, three-dimensional magnetic resonance imaging. The relationship between cortical thickness and neuropsychological performance was analysed using stepwise multiple linear regression analyses. These analyses (corrected P<.001) showed that several specific brain regions with cortical thinning were associated with cognitive dysfunction including: digit span backward, verbal and picture recall, naming and fluency, drawing-copying, response inhibition and selective attention. Some of the other functions, however, were not associated with specific foci of cortical atrophy (digit span forward, the word reading portion of the Stroop test, word and picture recognition). Our study, involving a large sample of participants with aMCI and AD, provides support for the postulate that cortical thinning-atrophy in specific anatomic loci are pathological markers for specific forms of cognitive dysfunction.

PMID: 22019776 [PubMed - as supplied by publisher]

Monday, October 24, 2011

'What is Alzheimer's Disease" by thevisualmd

This new video about Alzheimer's disease is getting some coverage in the media today:

It comes from

View the video

Upcoming Event: Alzheimer's Seminar (White Plains, NY; 04 Nov 2011)

The Alzheimer’s Association Annual Research Seminar
Burke Rehabilitation Hospital
White Plains, NY

04 November 2011

Read news article


"The annual seminar focuses on the latest research as well as treatment options for the disease. Barry Jordan, M.D., Director of the ADAC and Director of the Memory Evaluation and Treatment Service (METS) at Burke, will speak on “Differential Diagnosis of Dementia.” According to Dr. Jordan, “This type of program is an important forum for researchers, families and the public to share information about the latest in Alzheimer’s research,” he said. “Burke is proud to have hosted this event for the past several years,” he added."


Alzheimer Disease Treatment

The current (October 2011) issue of the Canadian Journal of Psychiatry has free-download access to two review articles dealing with Alzheimer's disease. One deals with drug treatment, whilst the other addresses non-pharmacolgic treatments. An editiorial by Serge Gauthier (also a free download) introduces the issue.

Canadian Journal of Psychiatry

News from the FDA: Onfi tablets (clobazam) for Adjunctive Treatment in Lennox-Gastaut Syndrome

From the FDA:

For Immediate Release: Oct. 24, 2011

FDA approves Onfi to treat severe type of seizures

On Oct. 21, the U.S. Food and Drug Administration approved Onfi tablets (clobazam) for use as an adjunctive (add-on) treatment for seizures associated with Lennox-Gastaut syndrome in adults and children 2 years of age and older. As Onfi is intended to treat a disease or condition that affects fewer than 200,000 people in the United States, it was granted orphan drug designation by the FDA.

“Lennox-Gastaut syndrome is a severe form of epilepsy that causes debilitating seizures,” said Russell Katz, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “This is a difficult condition to treat, and it will be helpful to have an additional treatment option.”

Read the full release

Neuropsychology Abstract of the Day: A Leisurely Curiousity

Training-induced neural plasticity in golf novices
Journal of Neuroscience. 2011 Aug 31; 31(35): 12444-8.
Authors: Bezzola L, Mérillat S, Gaser C, Jäncke L


Previous neuroimaging studies in the field of motor learning have shown that learning a new skill induces specific changes of neural gray and white matter in human brain areas necessary to control the practiced task. Former longitudinal studies investigating motor skill learning have used strict training protocols with little ecological validity rather than physical leisure activities, although there are several retrospective and cross-sectional studies suggesting neuroprotective effects of physical leisure activities. In the present longitudinal MRI study, we used voxel-based morphometry to investigate training-induced gray matter changes in golf novices between the age of 40 and 60 years, an age period when an active life style is assumed to counteract cognitive decline. As a main result, we demonstrate that 40 h of golf practice, performed as a leisure activity with highly individual training protocols, are associated with gray matter increases in a task-relevant cortical network encompassing sensorimotor regions and areas belonging to the dorsal stream. A new and striking result is the relationship between training intensity (time needed to complete the 40 training hours) and structural changes observed in the parieto-occipital junction. Thus, we demonstrate that a physical leisure activity induces training-dependent changes in gray matter and assume that a strict and controlled training protocol is not mandatory for training-induced adaptations of gray matter.

PMID: 21880905 [PubMed - indexed for MEDLINE]

Sunday, October 23, 2011

Neuropsychology Abstract of the Day: Art and Neuroscience

Returning to a fav topic of mine, here is a new research study:

The right hemisphere in esthetic perception
Front Hum Neurosci. 2011;5:109
Bromberger B, Sternschein R, Widick P, Smith W, Chatterjee A


Little about the neuropsychology of art perception and evaluation is known. Most neuropsychological approaches to art have focused on art production and have been anecdotal and qualitative. The field is in desperate need of quantitative methods if it is to advance. Here, we combine a quantitative approach to the assessment of art with modern voxel-lesion-symptom-mapping methods to determine brain-behavior relationships in art perception. We hypothesized that perception of different attributes of art are likely to be disrupted by damage to different regions of the brain. Twenty participants with right hemisphere damage were given the Assessment of Art Attributes, which is designed to quantify judgments of descriptive attributes of visual art. Each participant rated 24 paintings on 6 conceptual attributes (depictive accuracy, abstractness, emotion, symbolism, realism, and animacy) and 6 perceptual attributes (depth, color temperature, color saturation, balance, stroke, and simplicity) and their interest in and preference for these paintings. Deviation scores were obtained for each brain-damaged participant for each attribute based on correlations with group average ratings from 30 age-matched healthy participants. Right hemisphere damage affected participants' judgments of abstractness, accuracy, and stroke quality. Damage to areas within different parts of the frontal parietal and lateral temporal cortices produced deviation in judgments in four of six conceptual attributes (abstractness, symbolism, realism, and animacy). Of the formal attributes, only depth was affected by inferior prefrontal damage. No areas of brain damage were associated with deviations in interestingness or preference judgments. The perception of conceptual and formal attributes in artwork may in part dissociate from each other and from evaluative judgments. More generally, this approach demonstrates the feasibility of quantitative approaches to the neuropsychology of art.

PMID: 22016728 [PubMed - in process]

Saturday, October 22, 2011

Celebrities with CNS Diseases: Glen Campbell

American cowboy singer, Glen Campbell, is touring the UK in a farewell tour. He has been diagnosed with Alzheimer's disease.

Here is a commentary from The Independent from the 21st of October:

"Letter from Simon Kelner: A poignant farewell to the Wichita Lineman"

UPDATE: A review of his performance, from The Telegraph: Read the article here.

Neuropsychology Abstract of the Day: Visuocognition

The Cambridge Car Memory Test: A task matched in format to the Cambridge Face Memory Test, with norms, reliability, sex differences, dissociations from face memory, and expertise effects
Behav Res Methods. 2011 Oct 20;
Dennett HW, McKone E, Tavashmi R, Hall A, Pidcock M, Edwards M, Duchaine B


Many research questions require a within-class object recognition task matched for general cognitive requirements with a face recognition task. If the object task also has high internal reliability, it can improve accuracy and power in group analyses (e.g., mean inversion effects for faces vs. objects), individual-difference studies (e.g., correlations between certain perceptual abilities and face/object recognition), and case studies in neuropsychology (e.g., whether a prosopagnosic shows a face-specific or object-general deficit). Here, we present such a task. Our Cambridge Car Memory Test (CCMT) was matched in format to the established Cambridge Face Memory Test, requiring recognition of exemplars across view and lighting change. We tested 153 young adults (93 female). Results showed high reliability (Cronbach's alpha = .84) and a range of scores suitable both for normal-range individual-difference studies and, potentially, for diagnosis of impairment. The mean for males was much higher than the mean for females. We demonstrate independence between face memory and car memory (dissociation based on sex, plus a modest correlation between the two), including where participants have high relative expertise with cars. We also show that expertise with real car makes and models of the era used in the test significantly predicts CCMT performance. Surprisingly, however, regression analyses imply that there is an effect of sex per se on the CCMT that is not attributable to a stereotypical male advantage in car expertise.

PMID: 22012343 [PubMed - as supplied by publisher]

Friday, October 21, 2011

WBUR Boston: Fade to Darkness: The Age of Alzheimer's

WBUR Boston has, this week, run a series of presentations about Alzheimer's disease. Here is the WBUR webpage that described their programming: WBUR Boston "Fade to Darkness" webpage

Neuropsychology Abstract of the Day: Methodology

Estimating Decision-Relevant Comparative Effects Using Instrumental Variables
Stat Biosci. 2011 Sep;3(1):6-27
Basu A


Instrumental variables methods (IV) are widely used in the health economics literature to adjust for hidden selection biases in observational studies when estimating treatment effects. Less attention has been paid in the applied literature to the proper use of IVs if treatment effects are heterogeneous across subjects. Such a heterogeneity in effects becomes an issue for IV estimators when individuals' self-selected choices of treatments are correlated with expected idiosyncratic gains or losses from treatments. We present an overview of the challenges that arise with IV estimators in the presence of effect heterogeneity and self-selection and compare conventional IV analysis with alternative approaches that use IVs to directly address these challenges. Using a Medicare sample of clinically localized breast cancer patients, we study the impact of breast-conserving surgery and radiation with mastectomy on 3-year survival rates. Our results reveal the traditional IV results may have masked important heterogeneity in treatment effects. In the context of these results, we discuss the advantages and limitations of conventional and alternative IV methods in estimating mean treatment-effect parameters, the role of heterogeneity in comparative effectiveness research and the implications for diffusion of technology.

PMID: 22010051 [PubMed - as supplied by publisher]

Thursday, October 20, 2011

Neuropsychology Abstract of the Day: A SenseCam Study

There is a growing research literature in neuropsychology examining the SenseCam, a relatively long-time Microsoft project.

Microsoft's research project: SenseCam

Here is another example:

The neural correlates of everyday recognition memory
Brain and Cognition. 2011 Aug;76(3):369-81
Milton F, Muhlert N, Butler CR, Benattayallah A, Zeman AZ


We used a novel automatic camera, SenseCam, to create a recognition memory test for real-life events. Adapting a 'Remember/Know' paradigm, we asked healthy undergraduates, who wore SenseCam for 2 days, in their everyday environments, to classify images as strongly or weakly remembered, strongly or weakly familiar or novel, while brain activation was recorded with functional MRI. Overlapping, widely distributed sets of brain regions were activated by recollected and familiar stimuli. Within the medial temporal lobes, 'Remember' responses specifically elicited greater activity in the right anterior and posterior parahippocampal gyrus than 'Know' responses. 'New' responses activated anterior parahippocampal regions. A parametric analysis, across correctly recognised items, revealed increasing activation in the right hippocampus and posterior parahippocampal gyrus (pPHG). This may reflect modulation of these regions by the degree of recollection or, alternatively, by increasing memory strength. Strong recollection elicited greater activity in the left posterior hippocampus/pPHG than weak recollection indicating that this region is specifically modulated by the degree of recollection.

PMID: 21561699 [PubMed - indexed for MEDLINE]

Animal Modelling of Testing Task Switching

This is an open-access, free-download article from the PLoS journal:

Caselli L, Chelazzi L (2011) Does the Macaque Monkey Provide a Good Model for Studying Human Executive Control? A Comparative Behavioral Study of Task Switching. PLoS ONE 6(6): e21489. doi:10.1371/journal.pone.0021489

Article pdf

Wednesday, October 19, 2011

SAGE Therapeutics

A report from Fierce BioTech:

Third Rock Ventures Launches SAGE Therapeutics to Address CNS Disorders with Critical Unmet Needs
Posted October 18, 2011


"Third Rock Ventures, LLC today announced the formation of SAGE Therapeutics. The company was launched with a $35 million Series A financing. SAGE's efforts focus on advancing a broad pipeline of new, critically needed treatments for some of the most disabling central nervous system (CNS) disorders such as schizophrenia, depression, pain and traumatic brain injury (TBI). SAGE Therapeutics is founded on a proprietary Positive and Negative Allosteric Modulator (PANAM) chemistry platform that will enable the rapid development of a novel class of allosteric receptor modulators. Steven Paul, M.D., the former executive vice president for science and technology and president of Lilly Research Laboratories and a former scientific director of the National Institute of Mental Health (NIMH) and Douglas Covey, Ph.D., professor of biochemistry at the Washington University School of Medicine, are founders of the company."


Read the full report

Tuesday, October 18, 2011

American Academy of Pediatrics New ADHD Clinical Practice Guideline

ADHD: Clinical Practice Guideline for the Diagnosis, Evaluation, and Treatment of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

American Academy of Pediatrics
pdf download

Upon release, the new guideline resulted in a good deal of commentary, analysis, and media coverage. Here is an example, from the Pharmalot blog: Read the blog entry here.

Monday, October 17, 2011

Neuropsychology Abstract of the Day: Perinatal Cortical Growth and its Cognitive Correlates

Perinatal cortical growth and childhood neurocognitive abilities
Neurology. 2011 Oct 12;
Rathbone R, Counsell SJ, Kapellou O, Dyet L, Kennea N, Hajnal J, Allsop JM, Cowan F, Edwards AD


OBJECTIVE:This observational cohort study addressed the hypothesis that after preterm delivery brain growth between 24 and 44 weeks postmenstrual age (PMA) is related to global neurocognitive ability in later childhood. METHODS:Growth rates for cerebral volume and cortical surface area were estimated in 82 infants without focal brain lesions born before 30 weeks PMA by using 217 magnetic resonance images obtained between 24 and 44 weeks PMA. Abilities were assessed at 2 years using the Griffiths Mental Development Scale and at 6 years using the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Developmental Neuropsychological Assessment (NEPSY), and the Movement Assessment Battery for Children (MABC). Analysis was by generalized least-squares regression. RESULTS:Mean test scores approximated population averages. Cortical growth was directly related to the Griffiths Developmental Quotient (DQ), the WPPSI-R full-scale IQ, and a NEPSY summary score but not the MABC score and in exploration of subtests to attention, planning, memory, language, and numeric and conceptual abilities but not motor skills. The mean (95% confidence interval) estimated reduction in cortical surface area at term corrected age associated with a 1 SD fall in test score was as follows: DQ 7.0 (5.8-8.5); IQ 6.0 (4.9-7.3); and NEPSY 9.1 (7.5-11.0) % · SD(-1). Total brain volume growth was not correlated with any test score. CONCLUSIONS:The rate of cerebral cortical growth between 24 and 44 weeks PMA predicts global ability in later childhood, particularly complex cognitive functions but not motor functions.

PMID: 21998316 [PubMed - as supplied by publisher]

Olfaction and Alzheimer's Disease

A new study has been funded to examine the use of olfactory testing in the earlier detection of Alzheimer's disease, one of my interests in neuropsychological assessment.

The study is being funded and run is Australia.

Here is a news report, from The Australian:

Research funding boost for Alzheimer's
October 17, 2011 12:00AM


"We are interested in developing a test that picks up Alzheimer's disease in the earliest stages, even before problems with cognition appear," he told The Australian. Adapting the strategy of the cardiac stress test that picks up heart disease in its early stages, Professor Schofield wants to see whether a smell test can identify people who later go on to develop Alzheimer's.

Participants in the trial would be asked to scratch, sniff and identify 20 smells embedded in a piece of paper, then they would be given a chemical in their left nostril that interfered with the part of the olfactory system affected by Alzheimer's. Patients would be given a further 20 smells to identify after the chemical was administered. If it proved successful, the test would cost just $35 and be much cheaper than imaging techniques used now to identify people in the pre-clinical stages of Alzheimer's, Professor Schofield said.


Read the full story

Australia Clinical Neuroscience Centre Opens

Melbourne Brain Centre opens
17:22 AEST Mon Oct 17 2011

Read the report

Sunday, October 16, 2011

BBC Radio 4 Brain Series

A press release from the BBC:

Radio 4 presents season of programmes on the brain
Date: 30.09.2011
Category: Radio 4
Starting on 7 November, BBC Radio 4 presents a new season of programmes about the brain.

The season includes: a major 10-part series about the history of the brain; an exploration of what the latest discoveries in neuroscience might mean for the way we live our lives; an interview with one of Britain's leading brain experts and the slaying of common myths about the brain and its workings; and a new radio science website.

The season starts with Dr Geoff Bunn's 10-part A History Of The Brain series which takes listeners on a journey through 5,000 years of our understanding of the most complex thing in the known universe. Moving from Neolithic times to the present day, Geoff journeys through the many and varied ideas about what the brain is for and how it fulfils its functions. This ground-breaking series, written and presented by Dr Geoff Bunn, can be heard on weekdays at 1.45pm starting on Monday 7 November, with an omnibus on Fridays at 9pm.

In a three-part series, Brain Culture: Neuroscience And Society, starting on Tuesday 15 November at 4pm, Matthew Taylor explores how new imaging techniques have produced some remarkable insights into the functioning of the brain. And he looks at how the findings of neuroscience might radically transform our understanding of the classroom, the courtroom and the cabinet office. With a potentially new understanding of how the mind works will we seek to teach, punish and rule people differently? The series continues on Tuesday 22 and 29 November, 4pm.

On Monday 7 November at 8pm, Hugh Levinson tells the story of the lobotomy procedure in The Lobotomists. Hugh asks what the procedure's popularity said about society's idea of mental health and about the nature of the scientific method itself.

On Tuesday 8 November at 9pm, Radio 4's psychologist Claudia Hammond makes it her mission to slay common myths about the brain and its workings in Mind Myths; everything from the fallacy that we use only 10 per cent of our brains to the idea that listening to Mozart makes children smarter.

This season follows Radio 4's bold commitment to science with a new science strand – The Life Scientific With Jim Al-Khalili – starting on Tuesday 11 October at 9am, and which gets inside the mind of leading neuroscientist, Colin Blakemore, on 8 November 2011.

A new website, The Science Explorer will offer a rich archive of Radio 4 programmes that explore the lives, the work and the inspiration of scientists featured in this autumn's science programming and the new science strand The Life Scientific. The archive will include episodes from series such as In Our Time, Material World, Desert Island Discs and The Reith Lectures.

Scientists to be featured include Sir Paul Nurse, Steven Pinker and Prof Jocelyn Bell Burnell, Prof John Sulston, Dr Geoff Bunn, Matthew Taylor and Prof Robert Winston.

Programmes from the brain season and The Life Scientific will be available via the Science Explorer site to listen again or to download as podcasts. Listeners will also be able find out more about the scientists, their big ideas and their work, starting with Prof Jim Al-Khalili on Monday, 3 October. The Science Explorer can be found at

BBC Radio 4 Publicity

Neuropsychology Abstract of the Day: Alzheimer's Disease

Amyloid-beta levels are significantly reduced and spatial memory defects are rescued in a novel neuroserpin-deficient Alzheimer's disease transgenic mouse model
J Neurochem. 2011 Sep; 118(5): 928-38
Authors: Fabbro S, Schaller K, Seeds NW


Amyloid-beta (Aβ) plaques are a hallmark of Alzheimer's disease. Several proteases including plasmin are thought to promote proteolytic cleavage and clearance of Aβ from brain. The activity of both plasmin and tissue plasminogen activator are reduced in Alzheimer's disease brain, while the tissue plasminogen activator inhibitor neuroserpin is up-regulated. Here, the relationship of tissue plasminogen activator and neuroserpin to Aβ levels is explored in mouse models. Aβ(1-42) peptide injected into the frontal cortex of tissue plasminogen activator knockout mice is slow to disappear compared to wildtype mice, whereas neuroserpin knockout mice show a rapid clearance of Aβ(1-42). The relationship of neuroserpin and tissue plasminogen activator to Aβ plaque formation was studied further by knocking-out neuroserpin in the human amyloid precursor protein-J20 transgenic mouse. Compared to the J20-transgenic mouse, the neuroserpin-deficient J20-transgenic mice have a dramatic reduction of Aβ peptides, fewer and smaller plaques, and more active tissue plasminogen activator associated with plaques. Furthermore, neuroserpin-deficient J20-transgenic mice have near normal performances in the Morris water maze, in contrast to the spatial memory defects seen in J20-transgenic mice. These results support the concept that neuroserpin inhibition of tissue plasminogen activator plays an important role both in the accumulation of brain amyloid plaques and loss of cognitive abilities.

PMID: 21689108 [PubMed - indexed for MEDLINE]

Saturday, October 15, 2011

Neuropsychology Abstract of the Day: Assessment in Alzheimer's Disease

The SIST-M: Predictive Validity of a Brief Structured Clinical Dementia Rating Interview
Alzheimer Disease and Associated Disorders. 2011 Oct 6;
Okereke OI, Pantoja-Galicia N, Copeland M, Hyman BT, Wanggaard T, Albert MS, Betensky RA, Blacker D


BACKGROUND:: We have previously established the reliability and cross-sectional validity of the SIST-M (Structured Interview and Scoring Tool-Massachusetts Alzheimer's Disease Research Center), a shortened version of an instrument shown to predict progression to Alzheimer disease (AD), even among persons with very mild cognitive impairment (vMCI). OBJECTIVE:: To test the predictive validity of the SIST-M. METHODS:: Participants were 342 community-dwelling, nondemented older adults in a longitudinal study. Baseline Clinical Dementia Rating (CDR) ratings were determined by either (1) clinician interviews or (2) a previously developed computer algorithm based on 60 questions (of a possible 131) extracted from clinician interviews. We developed age+sex+education-adjusted Cox proportional hazards models using CDR-sum-of-boxes (CDR-SB) as the predictor, where CDR-SB was determined by either a clinician interview or an algorithm; models were run for the full sample (n=342) and among those jointly classified as vMCI using clinician-based and algorithm-based CDR ratings (n=156). We directly compared predictive accuracy using time-dependent receiver operating characteristic (ROC) curves. RESULTS:: AD hazard ratios (HRs) were similar for clinician-based and algorithm-based CDR-SB: for a 1-point increment in CDR-SB, the respective HRs [95% confidence interval (CI)] were 3.1 (2.5, 3.9) and 2.8 (2.2, 3.5); among those with vMCI, the respective HRs (95% CI) were 2.2 (1.6, 3.2) and 2.1 (1.5, 3.0). Similarly high predictive accuracy was achieved: the concordance probability (weighted average of the area-under-the-ROC curves) over follow-up was 0.78 versus 0.76 using clinician-based versus algorithm-based CDR-SB. CONCLUSION:: CDR scores based on items from this shortened interview had high predictive ability for AD-comparable to that using a lengthy clinical interview.

PMID: 21986342 [PubMed - as supplied by publisher]

Friday, October 14, 2011

Neuropsychology Abstract of the Day: CERAD Assessment

Norms for CERAD Constructional Praxis Recall
Clinical Neuropsychol. 2011 Oct 13
Fillenbaum GG, Burchett BM, Unverzagt FW, Rexroth DF, Welsh-Bohmer K


Recall of the four-item constructional praxis measure was a later addition to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. Norms for this measure, based on cognitively intact African Americans age ≥70 (Indianapolis-Ibadan Dementia Project, N = 372), European American participants age ≥66 (Cache County Study of Memory, Health and Aging, N = 507), and European American CERAD clinic controls age ≥50 (N = 182), are presented here. Performance varied by site; by sex, education, and age (African Americans in Indianapolis); education and age (Cache County European Americans); and only age (CERAD European American controls). Performance declined with increased age, within age with less education, and was poorer for women. Means, standard deviations, and percentiles are presented separately for each sample.

PMID: 21992077 [PubMed - as supplied by publisher]

Reality Monitoring

The Brain Study blog published an interesting posting earlier in the week about this important contemporary issue in neuropsychology:

Brain Study posting about Reality Monitoring

A good read!

New Open-Access Journal: "Brain and Behavior"

A new online open-access journal:

Brain and Behavior
Volume 1, Issue 1
Table of Contents

From the website:

"With the launch of this open access, multidisciplinary journal, we offer a broad scientific community a forum for rapid publication of original contributions, covering all aspects of neurology, neuroscience, psychology, and psychiatry. By offering quality assurance through stringent peer review and delivering content quickly, broadly, and effectively, we aim for Brain and Behavior to become both your regular source for neurology, neuroscience, psychology and psychiatry research, as well as a platform by which you will offer your best science to the broadest community possible."

Thursday, October 13, 2011

Neuropsychology Abstract of the Day: Gaming and Executive Control in Older Adults

Space Fortress game training and executive control in older adults: A pilot intervention
Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2011 Oct 12;
Stern Y, Blumen HM, Rich LW, Richards A, Herzberg G, Gopher D


ABSTRACT We investigated the feasibility of using the Space Fortress (SF) game, a complex video game originally developed to study complex skill acquisition in young adults, to improve executive control processes in cognitively healthy older adults. The study protocol consisted of 36 one-hour game play sessions over 3 months with cognitive evaluations before and after, and a follow-up evaluation at 6 months. Sixty participants were randomized to one of three conditions: Emphasis Change (EC) - elders were instructed to concentrate on playing the entire game but place particular emphasis on a specific aspect of game play in each particular game; Active Control (AC) - game play with standard instructions; Passive Control (PC) - evaluation sessions without game play. Primary outcome measures were obtained from five tasks, presumably tapping executive control processes. A total of 54 older adults completed the study protocol. One measure of executive control, WAIS-III letter-number sequencing, showed improvement in performance from pre- to post-evaluations in the EC condition, but not in the other two conditions. These initial findings are modest but encouraging. Future SF interventions need to carefully consider increasing the duration and or the intensity of the intervention by providing at-home game training, reducing the motor demands of the game, and selecting appropriate outcome measures.

PMID: 21988726 [PubMed - as supplied by publisher]

Wednesday, October 12, 2011

Celebrities with CNS Diseases: Glen Campbell

Glen Campbell, a US cowboy-music entertainer was diagnosed with probable Alzheimer's disease earlier on 2011.

He and his spouse have appeared on a number of television and radio shows, including BBC's Today show.

Today, they appear on The Ellen Show, on US television.

Neuropsychology Abstract of the Day: Mirror Neurons

Brain regions with mirror properties: A meta-analysis of 125 human fMRI studies
Neuroscience Biobehavioral Rev. 2011 Jul 18. [Epub ahead of print]
Molenberghs P, Cunnington R, Mattingley JB.


Mirror neurons in macaque area F5 fire when an animal performs an action, such as a mouth or limb movement, and also when the animal passively observes an identical or similar action performed by another individual. Brain-imaging studies in humans conducted over the last 20 years have repeatedly attempted to reveal analogous brain regions with mirror properties in humans, with broad and often speculative claims about their functional significance across a range of cognitive domains, from language to social cognition. Despite such concerted efforts, the likely neural substrates of these mirror regions have remained controversial, and indeed the very existence of a distinct subcategory of human neurons with mirroring properties has been questioned. Here we used activation likelihood estimation (ALE), to provide a quantitative index of the consistency of patterns of fMRI activity measured in human studies of action observation and action execution. From an initial sample of more than 300 published works, data from 125 papers met our strict inclusion and exclusion criteria. The analysis revealed 14 separate clusters in which activation has been consistently attributed to brain regions with mirror properties, encompassing 9 different Brodmann areas. These clusters were located in areas purported to show mirroring properties in the macaque, such as the inferior parietal lobule, inferior frontal gyrus and the adjacent ventral premotor cortex, but surprisingly also in regions such as the primary visual cortex, cerebellum and parts of the limbic system. Our findings suggest a core network of human brain regions that possess mirror properties associated with action observation and execution, with additional areas recruited during tasks that engage non-motor functions, such as auditory, somatosensory and affective components.

Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

PMID: 21782846 [PubMed - as supplied by publisher]

Tuesday, October 11, 2011

Cognitive Rehabilitation in Traumatic Brain Injury (TBI)

Cognitive Rehabilitation Therapy for Traumatic Brain Injury: Evaluating the Evidence
Institute of Medicine
Released: 11 October 2011

For more information, click here

Cochrane Collaboration Supports Free Access to all Data from all Clinical Trials

The Cochrane Collaboration Supports Free Access to all Data from all Clinical Trials
05 October 2011

Read the full statement

Neuropsychology Abstract of the Day: fMRI Protocol for Intrinsic Alertness

Revealing the Functional Neuroanatomy of Intrinsic Alertness Using fMRI: Methodological Peculiarities
PLoS One. 2011; 6(9): e25453
Clemens B, Zvyagintsev M, Sack A, Heinecke A, Willmes K, Sturm W


Clinical observations and neuroimaging data revealed a right-hemisphere fronto-parietal-thalamic-brainstem network for intrinsic alertness, and additional left fronto-parietal activity during phasic alertness. The primary objective of this fMRI study was to map the functional neuroanatomy of intrinsic alertness as precisely as possible in healthy participants, using a novel assessment paradigm already employed in clinical settings. Both the paradigm and the experimental design were optimized to specifically assess intrinsic alertness, while at the same time controlling for sensory-motor processing. The present results suggest that the processing of intrinsic alertness is accompanied by increased activity within the brainstem, thalamus, anterior cingulate gyrus, right insula, and right parietal cortex. Additionally, we found increased activation in the left hemisphere around the middle frontal gyrus (BA 9), the insula, the supplementary motor area, and the cerebellum. Our results further suggest that rather minute aspects of the experimental design may induce aspects of phasic alertness, which in turn might lead to additional brain activation in left-frontal areas not normally involved in intrinsic alertness. Accordingly, left BA 9 activation may be related to co-activation of the phasic alertness network due to the switch between rest and task conditions functioning as an external warning cue triggering the phasic alertness network. Furthermore, activation of the intrinsic alertness network during fixation blocks due to enhanced expectancy shortly before the switch to the task block might, when subtracted from the task block, lead to diminished activation in the typical right hemisphere intrinsic alertness network. Thus, we cautiously suggest that - as a methodological artifact - left frontal activations might show up due to phasic alertness involvement and intrinsic alertness activations might be weakened due to contrasting with fixation blocks, when assessing the functional neuroanatomy of intrinsic alertness with a block design in fMRI studies.

PMID: 21984928 [PubMed - as supplied by publisher]

Monday, October 10, 2011

Neuropsychology Abstract of the Day: Alzheimer's Disease Progression

Model-based economic evaluation in Alzheimer's disease: a review of the methods available to model Alzheimer's disease progression
Value Health. 2011 Jul-Aug;14(5):621-30
Green C, Shearer J, Ritchie CW, Zajicek JP


OBJECTIVE: To consider the methods available to model Alzheimer's disease (AD) progression over time to inform on the structure and development of model-based evaluations, and the future direction of modelling methods in AD.

METHODS: A systematic search of the health care literature was undertaken to identify methods to model disease progression in AD. Modelling methods are presented in a descriptive review.

RESULTS: The literature search identified 42 studies presenting methods or applications of methods to model AD progression over time. The review identified 10 general modelling frameworks available to empirically model the progression of AD as part of a model-based evaluation. Seven of these general models are statistical models predicting progression of AD using a measure of cognitive function. The main concerns with models are on model structure, around the limited characterization of disease progression, and on the use of a limited number of health states to capture events related to disease progression over time. None of the available models have been able to present a comprehensive model of the natural history of AD.

CONCLUSIONS: Although helpful, there are serious limitations in the methods available to model progression of AD over time. Advances are needed to better model the progression of AD and the effects of the disease on peoples' lives. Recent evidence supports the need for a multivariable approach to the modelling of AD progression, and indicates that a latent variable analytic approach to characterising AD progression is a promising avenue for advances in the statistical development of modelling methods.

PMID: 21839398 [PubMed - indexed for MEDLINE]

Saturday, October 08, 2011

Neuropsychology Abstract of the Day: Parkinson's Disease

Executive functions in Parkinson's disease: Systematic review and meta-analysis
Movement Disorders. 2011 Oct 3;
Kudlicka A, Clare L, Hindle JV


Impairment of executive function (EF) is commonly reported as a feature of PD. However, the exact pattern of executive impairment remains unclear. Also, there is an ongoing discussion surrounding the definition and conceptualization of EF, which might affect the clarity of research evidence on cognition in PD. The aim of this systematic review was to describe the pattern of executive impairment in early-stage PD emerging from the research literature and to identify critical issues for improving consistency in this field. The PsychInfo, MEDLINE, Science Direct, CINAHL, and Cochrane Library databases were searched using the term "Parkinson's disease" combined with each of 14 cognitive abilities defined as representing aspects of EF. The review was limited to studies that investigated EF as the central variable in early-stage, nondemented PD patients. The review identified 33 studies of EF that were operationalized in terms of 30 abilities tested by 60 measures and variously interpreted. Many measures were used only once, so only a small part of the available research evidence could be synthesized in the meta-analysis. The meta-analysis was undertaken using data from five commonly used tests of EF drawn from 18 studies. This revealed consistent evidence for cognitive difficulties across all five EF tests. Research on EF in PD is characterized by a considerable lack of clarity with regard to measure selection and interpretation. The findings support the view that EF impairments are evident in PD. However, the clinical significance of the cognitive abnormalities reported has yet to be clarified. 2011 Movement Disorder Society.

PMID: 21971697 [PubMed - as supplied by publisher]

Friday, October 07, 2011

Neuropsychology Abstract of the Day: Cognition of Depressed Mood

Difficulties in disengaging attentional resources from self-generated thoughts moderate the link between dysphoria and maladaptive self-referential thinking
Cogn Emot. 2011 Oct 5;
Rochat L, Billieux J, Van der Linden M


Negative emotions increase self-focused attention, a core feature of depression and anxiety-related disorders. However, the cognitive mechanisms associated with the tendency to self-focus-and, conversely, with the ability to voluntarily disengage attentional resources from the self and direct them towards the external environment-remain poorly understood. Thus, this study aimed to examine whether a specific cognitive control mechanism that directs attention between self-generated thoughts and external information might moderate the relationship between dysphoria and maladaptive self-referential thinking. Results showed that dysphoria increases the frequency of rumination, self-blame, and catastrophising, especially for participants who have more difficulty in switching from self-generated thoughts to information provided by the environment. These results shed new light on the cognitive mechanisms underlying maladaptive self-referential thinking associated with dysphoria. More specifically, this specific cognitive mechanism might play a key role in the maintenance or amplification of a depressed mood.

PMID: 21972982 [PubMed - as supplied by publisher]

Thursday, October 06, 2011

Pharmalot Interview with Dr. Michael Rogawski About Reporting Data in Clinical Trials

A fine read from the Pharmalot blog:

All Trial Data Must Be Disclosed: Rogawski Explains
By Ed Silverman
October 5th, 2011 - 9:36 am

Read the full blog posting

Neuropsychology Abstract of the Day: Cognitive Intervention in Amnestic MCI and Mild Alzheimer's Disease

Effects of a 6-Month Cognitive Intervention on Brain Metabolism in Patients with Amnestic MCI and Mild Alzheimer's Disease.
Journal of Alzheimers Disease. 2011 Jan 1;26(0):337-48
Authors: Förster S, Buschert VC, Teipel SJ, Friese U, Buchholz HG, Drzezga A, Hampel H, Bartenstein P, Buerger K


The effect of cognitive intervention on brain metabolism in AD is largely unexplored. Therefore, we aimed to investigate cognitive parameters and 18FDG PET to test for effects of a cognitive intervention in patients with aMCI or mild AD. Patients with aMCI (N = 24) or mild AD (N = 15) were randomly assigned either to cognitive intervention groups (IGs), receiving weekly sessions of group-based multicomponent cognitive intervention, or active control groups (CGs), receiving pencil-paper exercises for self-study. We obtained resting-state FDG-PET scans and neuropsychological testing at baseline and after six-months. Normalized FDG-PET images were analyzed using voxel-based SPM5 approaches to determine longitudinal changes, group-by-time interactions and correlations with neuropsychological outcome parameters. Primary global cognitive outcome was determined by analyses of covariance with MMSE and ADAS-cog scores as dependent measures. Both, aMCI and AD subgroups of CGs showed widespread bilateral cortical declines in FDG uptake, while the AD subgroup of IGs showed discrete decline or rather no decline in case of the aMCI subgroup. Group by time analyses revealed strongest attenuation of metabolic decline in the aMCI subgroup of the IGs, involving left anterior temporal pole and anterior cingulate gyrus. However, correlation analyses revealed only weak non-significant associations between increased FDG uptake and improvement in primary or secondary outcome parameters. Concurrently, there was significant improvement in global cognitive status in the aMCI subgroup of the IGs. A six-month cognitive intervention imparted cognitive benefits in patients with aMCI, which were concurrent with an attenuated decline of glucose metabolism in cortical regions affected by neurodegenerative AD.

PMID: 21971473 [PubMed - in process]

Wednesday, October 05, 2011

Neuropsychology Abstract of the Day: Gait and Cognition

Slower gait, slower information processing and smaller prefrontal area in older adults
Age Ageing. 2011 Sep 28;
Rosano C, Studenski SA, Aizenstein HJ, Boudreau RM, Longstreth WT, Newman AB


BACKGROUND: slower gait in older adults is related to smaller volume of the prefrontal area (PFAv). The pathways underlying this association have not yet been explored. Understanding slowing gait could help improve function in older age. We examine whether the association between smaller PFAv and slower gait is explained by lower performance on numerous neuropsychological tests.Hypothesis: we hypothesise that slower information processing explains this association, while tests of language or memory will not. METHODS: data on brain imaging, neuropsychological tests (information processing speed, visuospatial attention, memory, language, mood) and time to walk 15 feet were obtained in 214 adults (73.3 years, 62% women) free from stroke and dementia. Covariates included central (white matter hyperintensities, vision) and peripheral contributors of gait (vibration sense, muscle strength, arthritis, body mass index), demographics (age, race, gender, education), as well as markers of prevalent vascular diseases (cardiovascular disease, diabetes and ankle arm index). RESULTS: in linear regression models, smaller PFAv was associated with slower time to walk independent of covariates. This association was no longer significant after adding information processing speed to the model. None of the other neuropsychological tests significantly attenuated this association. CONCLUSIONS: we conclude that smaller PFAv may contribute to slower gait through slower information processing. Future longitudinal studies are warranted to examine the casual relationship between focal brain atrophy with slowing in information processing and gait.

PMID: 21965414 [PubMed - as supplied by publisher]


Gait and cognition: The relationship between gait stability and variability with executive function in persons with and without dementia
Gait Posture. 2011 Oct 1;
Ijmker T, Lamoth CJ


Besides cognitive decline, dementia is characterized by gait changes and increased fall risk, also in early stages of the disease. The aim of this study was to investigate differences in the relationship between executive function and gait variability and stability during single task and dual task walking in persons with and without dementia. The study sample consisted of three groups: fifteen dementia patients (aged 75-87), fourteen healthy elderly (aged 75-85), and twelve relatively younger elderly (aged 55-70). Participants underwent neuropsychological testing and tests of single and dual task walking while wearing an accelerometer. Outcome measures include stride related measures such as mean and coefficient of variation of stride time, and dynamic measures regarding the magnitude, smoothness, predictability and local stability of trunk accelerations. Patients with dementia exhibited a significantly (p<.05) less variable, but more irregular trunk acceleration pattern than cognitively intact elderly on single and dual task walking. The walking pattern during dual tasking for the whole group became increasingly unstable, even though participants modified their gait pattern by slowing their walking speed, and decreasing the magnitude of trunk accelerations. Moderate to high correlations (r>.51) were found between executive tasks and gait parameters. In conclusion, these findings indicate that decreased executive function plays an important role in increased gait variability in dementia patients; a fact that should be considered when designing fall risk interventions for this population. Furthermore, results indicate that measures of gait variability and stability should be deemed worthwhile in the diagnosis of dementia.

PMID: 21964053 [PubMed - as supplied by publisher]

Tuesday, October 04, 2011

News from the FDA: FDA Outlines Plans for an Outside Network of Scientific Experts

A press release from the FDA:

FDA outlines plans for an outside network of scientific experts
Network will help quickly address regulatory concerns, broaden staff knowledge of new and emerging technologies

04 October 2011

"FDA’s Center for Devices and Radiological Health (CDRH) is soliciting comment on a plan to create a network of outside scientific experts who would provide staff with rapid access to specific specialized knowledge about emerging technology, as well as other topics. To further enrich this comment period, CDRH will also conduct a 12-week pilot of the network through Dec. 30, 2011.

"CDRH has a world-class scientific staff that includes scientists, engineers, and clinicians. Nevertheless, there are times when staff must turn to external sources to further enhance their scientific understanding, given the rapid advancements in certain scientific fields, the development of pioneering technologies and increasingly complex medical devices.

"The CDRH Network of Experts would allow CDRH staff to tap into a vetted network of scientists and engineers for detailed scientific information on topics related to medical devices.

"CDRH already uses outside experts for its advisory panels. But panel membership is limited to a pool of Special Government Employees who must be recruited and enrolled. The Center cannot be assured that an expert in an emerging technology will be available when that expertise is needed. Other traditional sources of external expertise, such as public workshops, conferences and literature may lag behind current research or may not be available when a scientific question arises at CDRH.

“Medical devices continue to become more diverse and complex. The CDRH Network of Experts will help us broaden our existing expertise and expose our staff to a variety of scientific viewpoints, especially on emerging technology,” said William Maisel, M.D., CDRH deputy center director and chief scientist.

"Members of the Network of Experts will not provide policy advice or opinions. Instead, network members will share their particular expertise on specific topics to help center staff form their own conclusions."

To read the full release click here.

Neuropsychology Abstract of the Day: "Cognitive and Behavioural Predictors of Survival in Alzheimer Disease"

Cognitive and behavioural predictors of survival in Alzheimer disease: Results from a sample of treated patients in a tertiary-referral memory clinic
Int J Geriatr Psychiatry. 2011 Sep 29;
Russ TC, Batty GD, Starr JM


OBJECTIVE: This study examined the influence of cognitive and non-cognitive factors at the time of diagnosis on the survival of patients with treated probable Alzheimer Disease (AD). METHODS: Consecutive patients seen at a regional, tertiary-referral clinic completed a battery of cognitive tests and assessments of activities of daily living and neuropsychiatric symptoms. These clinic data were linked with death certificate data for all individuals and survival from diagnosis was calculated. Cox regression models were constructed using the baseline covariates. RESULTS: The sample comprised 653 patients (459 women), mean age 77.1 years (SD 7.6, range 48-94 years), diagnosed with probable AD and treated with a cholinesterase inhibitor. In the survival analysis, age was a consistently significant predictor of survival with a gender-adjusted hazard ratio of 1.35 (95% CI 1.23, 1.48) for one standard deviation increase in age. Men were at greater risk of death than women (age-adjusted HR 1.44, 95% CI 1.19, 1.73). In a model adjusted for all study variables, Paired-Associate Learning (Cambridge Automated Neuropsychological Test Assessment Battery) and the psychotic factor of the Neuropsychiatric Inventory were significant predictors of survival. CONCLUSIONS: At diagnosis, in addition to the anticipated impact of age and gender, the presence of psychotic symptoms and poor performance on paired-associate learning are also indicators of poor prognosis. Copyright © 2011 John Wiley & Sons, Ltd.

PMID: 21956773 [PubMed - as supplied by publisher]

Monday, October 03, 2011

From Dana Smith's Brain Study Blog: "Amazing aging discoveries: It’s in the blood"

From Dana Smith's Brain Study blog:

Amazing aging discoveries: It’s in the blood
27 September 2011

"In a vote for coolest experiment of the year, scientists at Stanford University surgically created conjoined-twin mice of different age pairs to assess the impact of young versus old blood on the brain." - Introduction of the posting.

Read the blog post

The Nobel Prize for Medicine

From the CBC:

Montreal-born scientist dies before Nobel honour
Nobel committee unaware of recipient's recent death

CBC News
Posted: Oct 3, 2011 5:54 AM ET Last Updated: Oct 3, 2011 10:20 AM ET

"Montreal-born scientist Ralph Steinman was announced as the co-winner of the Nobel Prize for Medicine on Monday, but the news was immediately overshadowed by word of his death on Friday.

"Steinman and two other scientists were announced as winners of the Nobel in medicine. Nobel committee member Goran Hansson said the committee didn't know Steinman was dead when it chose him as a winner and was looking through its regulations.

"The Rockefeller University is delighted that the Nobel Foundation has recognized Ralph Steinman for his seminal discoveries concerning the body's immune responses," Rockefeller University president Marc Tessier-Lavigne said in a statement.

"But the news is bittersweet, as we also learned this morning from Ralph's family that he passed a few days ago after a long battle with cancer. Our thoughts are with Ralph's wife, children and family."

Read the full report

Neuropsychology Abstract of the Day: Simvastatin Clinical Trial in Alzheimer's Disease

A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease.
Neurology. 2011 Aug 9;77(6):556-63
Sano M, Bell KL, Galasko D, Galvin JE, Thomas RG, van Dyck CH, Aisen PS


BACKGROUND: Lowering cholesterol is associated with reduced CNS amyloid deposition and increased dietary cholesterol increases amyloid accumulation in animal studies. Epidemiologic data suggest that use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) may decrease the risk of Alzheimer disease (AD) and a single-site trial suggested possible benefit in cognition with statin treatment in AD, supporting the hypothesis that statin therapy is useful in the treatment of AD.

OBJECTIVE: To determine if the lipid-lowering agent simvastatin slows the progression of symptoms in AD.

METHODS: This randomized, double-blind, placebo-controlled trial of simvastatin was conducted in individuals with mild to moderate AD and normal lipid levels. Participants were randomly assigned to receive simvastatin, 20 mg/day, for 6 weeks then 40 mg per day for the remainder of 18 months or identical placebo. The primary outcome was the rate of change in the Alzheimer's Disease Assessment Scale-cognitive portion (ADAS-Cog). Secondary outcomes measured clinical global change, cognition, function, and behavior.

RESULTS: A total of 406 individuals were randomized: 204 to simvastatin and 202 to placebo. Simvastatin lowered lipid levels but had no effect on change in ADAS-Cog score or the secondary outcome measures. There was no evidence of increased adverse events with simvastatin treatment.

CONCLUSION: Simvastatin had no benefit on the progression of symptoms in individuals with mild to moderate AD despite significant lowering of cholesterol.

CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that simvastatin 40 mg/day does not slow decline on the ADAS-Cog.

PMID: 21795660 [PubMed - indexed for MEDLINE]

Sunday, October 02, 2011

Stop-Signal Task

The following paper is available as an open full-download from PLoS. It provides an interesting example of the use of stop-signal tasks in pursuing a better understanding of executive functioning and its neuroanatomical correlates:

Full publication

Rule-guided executive control of response inhibition: functional topography of the inferior frontal cortex.
PLoS One. 2011;6(6):e20840
Cai W, Leung HC


BACKGROUND: The human inferior frontal cortex (IFC) is a large heterogeneous structure with distinct cytoarchitectonic subdivisions and fiber connections. It has been found involved in a wide range of executive control processes from target detection, rule retrieval to response control. Since these processes are often being studied separately, the functional organization of executive control processes within the IFC remains unclear.

METHODOLOGY/PRINCIPAL FINDINGS: We conducted an fMRI study to examine the activities of the subdivisions of IFC during the presentation of a task cue (rule retrieval) and during the performance of a stop-signal task (requiring response generation and inhibition) in comparison to a not-stop task (requiring response generation but not inhibition). We utilized a mixed event-related and block design to separate brain activity in correspondence to transient control processes from rule-related and sustained control processes. We found differentiation in control processes within the IFC. Our findings reveal that the bilateral ventral-posterior IFC/anterior insula are more active on both successful and unsuccessful stop trials relative to not-stop trials, suggesting their potential role in the early stage of stopping such as triggering the stop process. Direct countermanding seems to be outside of the IFC. In contrast, the dorsal-posterior IFC/inferior frontal junction (IFJ) showed transient activity in correspondence to the infrequent presentation of the stop signal in both tasks and the left anterior IFC showed differential activity in response to the task cues. The IFC subdivisions also exhibited similar but distinct patterns of functional connectivity during response control.

CONCLUSIONS/SIGNIFICANCE: Our findings suggest that executive control processes are distributed across the IFC and that the different subdivisions of IFC may support different control operations through parallel cortico-cortical and cortico-striatal circuits.

PMID: 21673969 [PubMed - indexed for MEDLINE]

Neuropsychology Abstract of the Day: Traumatic Brain Injury

Are self-reported symptoms of executive dysfunction associated with objective executive function performance following mild to moderate traumatic brain injury?
Journal of Clinical and Experimental Neuropsychology. 2011 Jul;33(6):704-14
Schiehser DM, Delis DC, Filoteo JV, Delano-Wood L, Han SD, Jak AJ, Drake AI, Bondi MW


Background and objective: We examined the relationship between self-reported pre- and post-injury changes in executive dysfunction, apathy, disinhibition, and depression, and performance on neuropsychological tests of executive function, attention/processing speed, and memory in relation to mood levels and effort test performance in individuals in the early stages of recovery from mild to moderate traumatic brain injury (TBI). Method: Participants were 71 noncombat military personnel who were in a semiacute stage of recovery (<3 months post injury) from mild to moderate TBI. Pre- and post-TBI behaviors were assessed with the Frontal Systems Behavior Scale (FrSBe; Grace & Malloy, 2001 ) and correlated with levels of depressive symptoms, effort test performance, and performance on objective measures of attention, executive function, and memory. Results: Self-reported symptoms of executive dysfunction generally failed to predict performance on objective measures of executive function and memory, although they predicted poorer performance on measures of attention/processing speed. Instead, higher levels of depressive symptomatology best predicted poorer performance on measures of executive function and memory. However, the relationship between memory performance and TBI symptoms was no longer significant when effort performance was controlled. Conclusions: Our findings suggest that, among individuals in early recovery from mild to moderate TBI, self-reported depressive symptoms, rather than patients' cognitive complaints, are associated with objective executive function. However, self-reported cognitive complaints may be associated with objectively measured inattention and slow processing speed.

PMID: 21958432 [PubMed - in process]

Saturday, October 01, 2011

Neuropsychology Abstract of the Day: Aphasia Treatment

Intensity of Aphasia Therapy: Evidence and Efficacy.
Curr Neurol Neurosci Rep. 2011 Sep 30;
Cherney LR, Patterson JP, Raymer AM


Determining the optimal amount and intensity of treatment is essential to the design and implementation of any treatment program for aphasia. A growing body of evidence, both behavioral and biological, suggests that intensive therapy positively impacts outcomes. We update a systematic review of treatment studies that directly compares conditions of higher and lower intensity treatment for aphasia. We identify five studies published since 2006, review them for methodologic quality, and synthesize their findings with previous ones. For both acute and chronic aphasia, results at the language impairment and communication activity/participation levels tend to be more equivocal than previously demonstrated, with no clear differences between intensive and nonintensive treatment emerging across studies. Future research directions are discussed including research design, definitions of treatment intensity, and behavioral and biological measurement of short- and long-term changes following implementation of an intensive treatment.

PMID: 21960063 [PubMed - as supplied by publisher]