BrainBlog

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 Abstract 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 specifi...

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 Abstract 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 ...

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 Abstract 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 inh...

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 Abstract 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...

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

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

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 ...

From EurekaAlert: UCSF-Pfizer partnership yields projects aimed at clinical trials 26 October 2011 Read the full article

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

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.

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 Abstract 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 performe...

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 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...

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 .

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 Abstract 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 at...

This new video about Alzheimer's disease is getting some coverage in the media today: It comes from TheVisualMD.com View the video

The Alzheimer’s Association Annual Research Seminar Burke Rehabilitation Hospital White Plains, NY 04 November 2011 Read news article [snippet] "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." [snippet]

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

From the FDA: FDA NEWS RELEASE 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

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 Abstract 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 ...