Tuesday, February 26, 2008

Neuropsychology Abstract of the Day: Mild Cognitive Impairment (MCI)

Karas G, Sluimer J, Goekoop R, van der Flier W, Rombouts S, Vrenken H, Scheltens P, Fox N, & Barkhof F. Amnestic Mild Cognitive Impairment: Structural MR Imaging Findings Predictive of Conversion to Alzheimer Disease. American Journal of Neuroradiology. 2008 Feb 22 [Epub ahead of print].

Department of Diagnostic Radiology, Image Analysis Center, Alzheimer Center, and Department of Clinical Neurology, VU University Medical Center, Amsterdam, the Netherlands; Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, London, UK; Department of Physics and Medical Technology, Alzheimer Center, VU University Medical Center and Leiden Institute for Brain and Cognition, Leiden, the Netherlands; Department of Psychology, Leiden University, Leiden, the Netherlands; and Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands.

BACKGROUND AND PURPOSE: Mild cognitive impairment (MCI) is considered by many to be a prodromal phase of Alzheimer disease (AD). We used voxel-based morphometry (VBM) to find out whether structural differences on MR imaging could offer insight into the development of clinical AD in patients with amnestic MCI at 3-year follow-up. MATERIALS AND METHODS: Twenty-four amnestic patients with MCI were included. After 3 years, 46% had progressed to AD (n = 11; age, 72.7 +/- 4.8 years; women/men, 8/3). For 13 patients (age, 72.4 +/- 8.6 years; women/men, 10/3), the diagnosis remained MCI. Baseline MR imaging at 1.5T included a coronal heavily T1-weighted 3D gradient-echo sequence. Localized gray matter differences were assessed with VBM. RESULTS: The converters had less gray matter volume in medial (including the hippocampus) and lateral temporal lobe, parietal lobe, and lateral temporal lobe structures. After correction for age, sex, total gray matter volume, and neuropsychological evaluation, left-sided atrophy remained statistically significant. Specifically, converters had more left parietal atrophy (angular gyrus and inferior parietal lobule) and left lateral temporal lobe atrophy (superior and middle temporal gyrus) than stable patients with MCI. CONCLUSION: By studying 2 MCI populations, converters versus nonconverters, we found atrophy beyond the medial temporal lobe to be characteristic of patients with MCI who will progress to dementia. Atrophy of structures such as the left lateral temporal lobe and left parietal cortex may independently predict conversion.

PMID: 18296551 [PubMed - as supplied by publisher]

Monday, February 25, 2008

Neuroscience in the New Yorker: Numbers and Approximations

From this week's New Yorker:

Numbers Guy
Are our brains wired for math?
by Jim Holt
March 3, 2008

[ ... Read the full article ... ]

Drug Development: Glutamate and Schizophrenia

From Sunday's New York Times:

Daring to Think Differently About Schizophrenia
Published: February 24, 2008

"A new drug aimed at treating schizophrenia turns its focus away from dopamine and instead on the effects of glutamate, another powerful neurotransmitter."

[ ... Read the article ... ]

Saturday, February 23, 2008

Neuropsychology Abstract of the Day: Schizophrenia Clinical Trials

Hill SK, Sweeney JA, Hamer RM, Keefe RS, Perkins DO, Gu H, McEvoy JP, & Lieberman JA. Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia. Journal of the International Neuropsychological Society. 2008 Mar; 14(2): 209-221.

Center for Cognitive Medicine, Department of Psychiatry, University of Illinois at Chicago, Chicago, Illinois.

Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n = 367) and 12-week (n = 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes. (JINS, 2008, 14, 209-221.)Presented in part at the annual International Neuropsychology Society meeting in Portland, OR, February 2007; and the 2007 International Congress for Schizophrenia Research in Colorado Springs, CO.

PMID: 18282319 [PubMed - in process]

Thursday, February 21, 2008


A press release rom the NIH:

Genetic Tags Reveal Secrets of Memories’ Staying Power in Mice

A better understanding of how memory works is emerging from a newfound ability to link a learning experience in a mouse to consequent changes in the inner workings of its neurons. Researchers, supported in part by the National Institutes of Health's National Institute of Mental Health (NIMH), have developed a way to pinpoint the specific cellular components that sustain a specific memory in genetically-engineered mice.

"Remarkably, this research demonstrates a way to untangle precisely which cells and connections are activated by a particular memory," said NIMH Director Thomas Insel, M.D. "We are actually learning the molecular basis of learning and memory."

For a memory to last long-term, the neural connections holding it need to be strengthened by incorporating new proteins triggered by the learning. Yet, it's been a mystery how these new proteins — born deep inside a neuron — end up becoming part of the specific connections in far-off neuronal extensions that encode that memory.

By tracing the destinations of such migrating proteins, the researchers located the neural connections, called synapses, holding a specific fear memory. In the process, they discovered these synapses are distinguished by telltale molecular tags that enable them to capture the memory-sustaining proteins.

Mark Mayford, Ph.D., and Naoki Matsuo, Ph.D., of the Scripps Research Institute, report on their findings in the February 22, 2008 issue of the journal Science.

The Scripps researchers have been applying their new technique in a series of studies that focus on progressively finer details of the molecular machinery of memory.

"Inside neurons involved in a specific memory, we're tracing molecules activated by that learning to see how it ultimately changes neural connections," explained Mayford.

In a study published in the August 31, 2007 Science, Mayford and colleagues showed the same neurons activated by a learning experience are also activated when that memory is retrieved. The more neurons involved in the learning, the stronger the memory.

The researchers determined this by genetically engineering a strain of mice with traceable neurons in the brain's fear center, called the amygdala. Inserted genes caused activated neurons to glow red when the animals learned to fear situations where they received shocks, in a process known as fear conditioning — and to glow green when the memory was later retrieved. The researchers then chemically prevented further expression of those neurons, so that resulting neural and behavioral changes could be confidently attributed to that learning experience at a later time. The study revealed which circuits and neurons were involved in the specific learning experience.

In the new study, Mayford and Matsuo adapted this approach to discover how fear learning works at a deeper level — inside neurons of the brain's memory hub, called the hippocampus.

Evidence suggested that proteins called AMPA receptors ( strengthen memories by becoming part of the synapses encoding them. To identify these synapses, the researchers genetically engineered a strain of mice to express AMPA receptors traceable by a green glow. After fear conditioning had triggered new AMPA receptors deep in the neuron's nucleus, they chemically suppressed any further expression of the proteins. This allowed time for the receptors to migrate to their appointed synapses. Hours later, green fluorescence revealed the fate of the specific AMPA receptors born in response to the learning.

As expected, the newly synthesized AMPA receptors had traveled and become part of only certain hippocampus synapses — presumably the ones holding the memory. Synaptic connections are made onto small nubs on the neuron called spines. These spines come in three different shapes called thin, stubby and mushroom. While little was known about the function of these differently shaped spines, the fact that they are altered in various forms of mental retardation, like Fragile-X syndrome, suggests a critical importance in mental function.

The researchers discovered the synapses that received the AMPA receptors with memory were limited to the mushroom type. The mushroom spines also figured prominently in the same neurons when the fear conditioning was reversed by repeatedly exposing the animals to the feared situation without getting shocked — a procedure called extinction learning. This indicated that the same neurons activated when a fear is learned are also activated when it is lost. The surge in mushroom spine capture of the receptors appeared within hours of learning and was gone after a few days, but appeared to be critical for cementing the memory.

[ ... Read the full press release ... ]

Tuesday, February 05, 2008

Upcoming Event: Univ. of Minnesota, 08 February 2008

2008 Center for Bioethics Seminar Series

“Ethics and Public Health Emergencies: How Should We Prepare for Pandemic Flu?”
Friday, February 8, 2008
12:15–1:30 pm, 3-100 Mayo, University of Minnesota Campus

Presented by
Debra DeBruin, PhD
Director of Education and Assistant Professor, Center for Bioethics; Department of Medicine
University of Minnesota Medical School

Dr. DeBruin has served as a health policy fellow for the United States Senate, and worked as a
consultant to the National Academy of Science’s Institute of Medicine and the National Bioethics Advisory Commission. She has also been a member of a number of working groups relevant to public health, including the Minnesota Privacy and Security Project Solutions Workgroup, the Minnesota Privacy and Security Project Legal Workgroup, the Minnesota Center for Healthcare Ethics’ Pandemic Influenza Ethics Work Group, and the State of Minnesota Department of Administration’s Work Group on Genetic Information. Currently, she is leading a team from the University of Minnesota Center for Bioethics along with the Minnesota Center for Health Care Ethics to provide guidance to the Minnesota Department of Health on ethical issues in pandemic planning. In addition to her work in public health policy, she teaches and conducts research in the ethics of research.

Seminars are free and open to the public. Refreshments will be provided.


Following this seminar, participants will be able to:
1) Identify ethical issues that arise in the context of a public health emergency such as influenza pandemic.
2) Discuss moral considerations relating to the allocation of scarce resources.
3) Consider strategies for devising and implementing an ethical framework in pandemic planning.

Continuing Medical Education Credit (CME) Available

The University of Minnesota designates this educational activity for a maximum of 1 AMA PRA Category 1
Credit ™. Physicians should only claim credit commensurate with the extent of their participation in the activity.
The University of Minnesota is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Pre-registration is preferred if you are attending for CME credit. Please call 612-624-8478 to pre-register.
Registration will also be available on site.

Current Event: International Neuropsychological Society (INS) Meeting, Hawaii

36th Annual International Neuropsychological Society (INS) Meeting

February 6, 2008 to February 9, 2008
Waikoloa, Hawaii, USA
Hilton Waikoloa Village

Meeting webpage

Neuropsychology Abstract of the Day: Aphasia

Baldo JV, Klostermann EC, & Dronkers NF. It's either a cook or a baker: Patients with conduction aphasia get the gist but lose the trace. Brain and Language. 2008 Feb 1 [Epub ahead of print]

VA Northern California Health Care System, Center for Aphasia and Related Disorders, 150 Muir Road (126s), Martinez, CA 94553, USA.

Patients with conduction aphasia have been characterized as having a short-term memory deficit that leads to relative difficulty on span and repetition tasks. It has also been observed that these same patients often get the gist of what is said to them, even if they are unable to repeat the information verbatim. To study this phenomenon experimentally, patients with conduction aphasia and left hemisphere-injured controls were tested on a repetition recognition task that required them to listen to a sentence and immediately point to one of three sentences that matched it. On some trials, the distractor sentences contained substituted words that were semantically-related to the target, and on other trials, the distractor sentences contained semantically-distinct words. Patients with conduction aphasia and controls performed well on the latter condition, when distractors were semantically-distinct. However, when the distractor sentences were semantically-related, the patients with conduction aphasia were impaired at identifying the target sentence, suggesting that these patients could not rely on the verbatim trace. To further understand these results, we also tested elderly controls on the same task, except that a delay was introduced between study and test. Like the patients with conduction aphasia, the elderly controls were worse at identifying target sentences when there were semantically-related distractors. Taken together, these results suggest that patients with conduction aphasia rely on non-phonologic cues, such as lexical-semantics, to support their short-term memory, just as normal participants must do in long-term memory tasks when the phonological trace is no longer present.

PMID: 18243294 [PubMed - as supplied by publisher]

Progressive Inflammatory Neuropathy (PIN) - Post 2

From today's New York Times:

A Medical Mystery Unfolds in Minnesota
Published: February 5, 2008


By then, November 2007, other cases had begun to turn up. Ultimately, there were 12 — 6 men and 6 women, ranging in age from 21 to 51. Doctors and the plant owner, realizing they had an outbreak on their hands, had already called in the Minnesota Department of Health, which, in turn, sought help from the federal Centers for Disease Control and Prevention.

Though the outbreak seemed small, the investigation took on urgency because the disease was serious, and health officials worried that it might indicate a new risk to other workers in meatpacking.

“It is important to characterize this because it appears to be a new syndrome, and we don’t truly know how many people may be affected throughout the U.S. or even the world,” said Dr. Jennifer McQuiston, a veterinarian from the disease centers.

In early November, Dr. Aaron DeVries, a health department epidemiologist, visited the plant and combed through medical records. The disease bore no resemblance to mad cow disease or to trichinosis, the notorious parasite infection that comes from eating raw or undercooked pork. Nor did it spread person to person — the workers’ relatives were unaffected — or pose any threat to people who ate pork.

A survey of the workers confirmed what the plant’s nurses had suspected: those who got sick were employed at or near the “head table,” where workers cut the meat off severed hog heads.


[ ... Read the full article ... ]

Friday, February 01, 2008

Progressive Inflammatory Neuropathy (PIN)

From the CDC's Morbidity and Mortality Weekly Report (MMWR) on 31 January 2008:

Investigation of Progressive Inflammatory Neuropathy Among Swine Slaughterhouse Workers --- Minnesota, 2007---2008


"This report summarizes an ongoing investigation of PIN, a syndrome that appears to be associated with swine slaughterhouse workers who process pig heads. Several clinical and laboratory features of this illness and the distinctive epidemiology associated with patients appear unique. Pigs slaughtered at plant A have passed inspection by the U.S. Department of Agriculture Food Safety and Inspection Service, and the investigation has not identified any foodborne risk to the general population.

"The investigation in Minnesota indicates that PIN appears associated with having worked at the head table, where a compressed-air device was used to extract pig brains. In the process of blowing compressed air into the pig skull, brain material might have been splattered or even aerosolized, and workers might have been exposed through inhalation or contact with mucous membranes. One hypothesis for development of PIN is that worker exposure to aerosolized pig neural protein might have induced an autoimmune-mediated peripheral neuropathy (1,2). Additional investigation of the characteristics and causes of PIN is under way.

"Whether compressed-air devices are being used for pig-brain extraction in other slaughterhouses or processing facilities, in the United States or internationally, is unknown. Clinicians should provide CDC with information regarding swine slaughterhouse workers who might have illnesses similar to PIN, including patients with peripheral neuropathy, myelopathy, or features of both. Clinicians who identify such patients should report the cases to their state health department and contact CDC at 770-488-7100."


[ ... Read the full report ... ]

Neuropsychology Abstract of the Day: Mild Cognitive Impairment (MCI)

Unverzagt FW, Sujuan Gao , Lane KA, Callahan C, Ogunniyi A, Baiyewu O, Gureje O, Hall KS, & Hendrie HC. Mild cognitive dysfunction: An epidemiological perspective with an emphasis on African Americans. Geriatrics Psychiatry & Neurology. 2007 Dec; 20(4): 215-226.

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.

This review begins with a historical accounting of the evolution of the concept of mild cognitive dysfunction, including nomenclature and criteria from Kral to Petersen. A critical analysis of the main elements relating to assessment and diagnosis of mild cognitive dysfunction is provided. Methodological limitations in design, measurement, and characterization, especially as they relate to older African Americans, are identified. Data from a 15-year longitudinal study of community-dwelling African Americans in Indianapolis, Indiana, indicate a 23% prevalence of all-cause mild cognitive dysfunction, with approximately 25% progressing to dementia in 2 years and another 25% reverting to normal cognition in the same interval. Factors contributing to this longitudinal variability in outcomes are reviewed, including the role of medical health factors. The review closes with suggestions for next steps in the epidemiological research of mild cognitive impairment.

PMID: 18004008 [PubMed - indexed for MEDLINE]