BrainBlog

BrainBlog

Sunday, November 23, 2008

Cognition: Giving Wayfinding Directions

The British Psychological Society's (BPS) Research Digest blog has an interesting post about a study that concerns itself with giving route directions: link

Saturday, November 22, 2008

Neuropsychology Abstract of the Day: Neurodegeneration in Alzheimer Disease

de Jong LW, van der Hiele K, Veer IM, Houwing JJ, Westendorp RG, Bollen EL, de Bruin PW, Middelkoop HA, van Buchem MA, & van der Grond J. Strongly reduced volumes of putamen and thalamus in Alzheimer's disease: An MRI study. Brain. 2008 Nov 20.

Department of Radiology, Section Neuropsychology of the Department of Neurology, Department of Medical Statistics, Department of Geriatrics and Department of Neurology of the Leiden University Medical Center, Leiden, The Netherlands.

Atrophy is regarded a sensitive marker of neurodegenerative pathology. In addition to confirming the well-known presence of decreased global grey matter and hippocampal volumes in Alzheimer's disease, this study investigated whether deep grey matter structure also suffer degeneration in Alzheimer's disease, and whether such degeneration is associated with cognitive deterioration. In this cross-sectional correlation study, two groups were compared on volumes of seven subcortical regions: 70 memory complainers (MCs) and 69 subjects diagnosed with probable Alzheimer's disease. Using 3T 3D T1 MR images, volumes of nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen and thalamus were automatically calculated by the FMRIB's Integrated Registration and Segmentation Tool (FIRST)-algorithm FMRIB's Software Library (FSL). Subsequently, the volumes of the different regions were correlated with cognitive test results. In addition to finding the expected association between hippocampal atrophy and cognitive decline in Alzheimer's disease, volumes of putamen and thalamus were significantly reduced in patients diagnosed with probable Alzheimer's disease. We also found that the decrease in volume correlated linearly with impaired global cognitive performance. These findings strongly suggest that, beside neo-cortical atrophy, deep grey matter structures in Alzheimer's disease suffer atrophy as well and that degenerative processes in the putamen and thalamus, like the hippocampus, may contribute to cognitive decline in Alzheimer's disease.

PMID: 19022861 [PubMed - as supplied by publisher]

Tuesday, November 18, 2008

The GEM Study

From an NIH press release earlier today:

Ginkgo Evaluation of Memory (GEM) Study Fails To Show Benefit in Preventing Dementia in the Elderly

The dietary supplement Ginkgo biloba was found to be ineffective in reducing the development of dementia and Alzheimer's disease in older people, according to a study published in the Journal of the American Medical Association1. Researchers led by Stephen T. DeKosky, M.D., formerly of the University of Pittsburgh, vice president and dean of the School of Medicine at the University of Virginia in Charlottesville, conducted the trial known as the Ginkgo Evaluation of Memory (GEM) study at four clinical sites over the course of 8 years. GEM is the largest clinical trial ever to evaluate ginkgo's effect on the occurrence of dementia.

This research was co-funded by five components of the National Institutes of Health (NIH): National Center for Complementary and Alternative Medicine (NCCAM); National Institute on Aging (NIA); National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke, and the Office of Dietary Supplements.

"We have made enormous progress in understanding the basic mechanisms involved in Alzheimer's disease, and we continue to pursue a vigorous program to translate what we know into the development and testing of new potential therapies for this devastating disease," said Richard Hodes, M.D., director of the NIA. "However, it is disappointing that the dietary supplement tested in this study had no effect in preventing Alzheimer's disease."

GEM enrolled 3,069 participants age 75 or older with normal cognition or mild cognitive impairment. Those with dementia were excluded from participation. After extensive medical and neuropsychological screening, participants were randomly assigned to receive twice-daily doses of either 120 milligrams of ginkgo extract or an identical-appearing placebo. The 240 milligrams daily dose of ginkgo was selected based on current dosage recommendations and prior clinical studies indicating possible effectiveness at this dose. The products used in the study were supplied by Schwabe Pharmaceuticals, a German company.

"According to the 2007 National Health Interview Survey, ginkgo is one of the top 10 natural products used by Americans," said Richard L. Nahin, Ph.D., M.P.H., acting director of the Division of Extramural Research at NCCAM. "It is important to conduct studies and build the scientific evidence base regarding botanical supplements through rigorous research, such as the GEM trial."

The study was conducted primarily to determine if ginkgo would decrease the incidence of all types of dementia and, more specifically, reduce the incidence of Alzheimer's disease. Secondarily, the study evaluated ginkgo for its effects on overall cognitive decline, functional disability, incidence of cardiovascular disease and stroke, and total mortality. The primary endpoint was the diagnosis of dementia as determined by an expert panel of clinicians using standard criteria for diagnosis. The patients with a diagnosis of dementia underwent magnetic resonance imaging scans to determine their dementia type.

"The results of this study confirm the importance of randomized trials in the development of new therapies for dementia and Alzheimer's disease and in determining therapeutic benefit not only for conventional therapies but also complementary therapies like ginkgo," said Dr. DeKosky, principal investigator on the GEM study. "If older patients are considering using ginkgo for preventing dementia, I urge them to speak with their health care providers about the results of this study and work together to create the best treatment plan."

Study participants were followed for an average of approximately 6 years (maximum of just over 7 years). During the study, 523 participants were diagnosed with dementia, 246 in the placebo group and 277 in the ginkgo group. Thus, ginkgo showed no overall effect for reducing all types of dementia or Alzheimer's disease. In addition, in analyzing safety data, the GEM study did not find significant adverse effects from ginkgo, in particular there was no evidence for increased bleeding risk in persons taking ginkgo.

Cognitive status was known for more than 93 percent of all participants at the end of the trial and 60 percent of active participants were taking their assigned study medication. There was no difference in adherence to taking medication between the ginkgo group and the placebo group.

"While this study revealed that ginkgo does not have an effect on reducing dementia in the study populationit does provide us with important information about how to design and conduct large dementia prevention trials in older adults" said Dr. Jeff Williamson, a geriatrician and principal investigator of the GEM Clinical Coordinating Center at Wake Forest University. "Future analyses will provide us with additional information on ginkgo's possible effects on cardiovascular disease, cancer, depression and other age-related conditions. We are especially grateful to the more than 3,000 older adults who dedicated many hours to helping us answer the important questions addressed by GEMS."

The GEM results will prove useful in determining how many participants are needed in future trials to provide clinically significant measures on outcomes such as occurrence of dementia. Future analysis of this study may also identify subgroups of these participants who may be at greater risk for developing dementia.

Data analysis for the trial was overseen by the University of Washington, Seattle and the four GEM institutions that participated in this study were

University of Pittsburgh
Wake Forest University, Winston-Salem, N.C.
Johns Hopkins University, Baltimore, Md.
University of California, Davis

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


The GEM website: link

Monday, November 10, 2008

Neuropsychology Abstract of the Day: Aging and Cognition

Pratt LA, Weeks JD, & Goulding MR. Measures of cognitive functioning in the 1994-2000 Second Longitudinal Study of Aging. National Health Statistics Reports. 2008 Jul 7; (2): 1-15.

US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Health Statistics, Hyattsville, MD 20782, USA.

OBJECTIVES: This report describes in detail the measures of cognitive functioning administered in the Second Longitudinal Study of Aging (LSOA II) and proposes a three-category cognitive impairment variable for analysts' use that is derived from the individual measures. METHODS: LSOA II self-respondents completed an 11-question cognitive functioning measure based on the Telephone Interview of Cognitive Status (TICS) instrument. Proxy respondents answered nine questions drawn from the short Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Using cut points provided in the literature as a guide, a single three-level categorical measure of cognitive impairment was created: probable, possible, and no cognitive impairment. RESULTS: The cognitive functioning measures administered in LSOA II retain many of the favorable psychometric properties of the original TICS and IQCODE. The constructed cognitive impairment (CI) variable demonstrates good construct validity, and prevalence rates are generally consistent with those from other published studies. CONCLUSIONS: The categorical CI variable is easy to use and interpret and allows analysts the option of combining self- and proxy-respondent data in investigations of associations between CI and health outcomes, including continuing independence, progressive impairment, health care utilization patterns, and mortality.

PMID: 18839800 [PubMed - indexed for MEDLINE]

Sunday, November 02, 2008

Upcoming Event: 15-19 November 2008, Washington, D.C.

"Neuroscience 2008" --- The 38th annual meeting of the Society for Neuroscience, is scheduled for 15-19 November 2008 in Washington, D.C.

The location is the Walter E. Washington Convention Center.

Conference website.

Wednesday, October 15, 2008

Neuropsychology Abstract of the Day: Alzheimer's Disease Drug Development

Becker RE & Greig NH. Alzheimer's disease drug development in 2008 and beyond: Problems and opportunities. Current Alzheimer Research. 2008 Aug; 5(4): 346-357.

Drug Design & Development Section, Laboratory of Neurosciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.

Recently, a number of Alzheimer's disease (AD) multi-center clinical trials (CT) have failed to provide statistically significant evidence of drug efficacy. To test for possible design or execution flaws we analyzed in detail CTs for two failed drugs that were strongly supported by preclinical evidence and by proven CT AD efficacy for other drugs in their class. Studies of the failed commercial trials suggest that methodological flaws may contribute to the failures and that these flaws lurk within current drug development practices ready to impact other AD drug development [1]. To identify and counter risks we considered the relevance to AD drug development of the following factors: (1) effective dosing of the drug product, (2) reliable evaluations of research subjects, (3) effective implementation of quality controls over data at research sites, (4) resources for practitioners to effectively use CT results in patient care, (5) effective disease modeling, (6) effective research designs. New drugs currently under development for AD address a variety of specific mechanistic targets. Mechanistic targets provide AD drug development opportunities to escape from many of the factors that currently undermine AD clinical pharmacology, especially the problems of inaccuracy and imprecision associated with using rated outcomes. In this paper we conclude that many of the current problems encountered in AD drug development can be avoided by changing practices. Current problems with human errors in clinical trials make it difficult to differentiate drugs that fail to evidence efficacy from apparent failures due to Type II errors. This uncertainty and the lack of publication of negative data impede researchers' abilities to improve methodologies in clinical pharmacology and to develop a sound body of knowledge about drug actions. We consider the identification of molecular targets as offering further opportunities for overcoming current failures in drug development.

PMID: 18690832 [PubMed - indexed for MEDLINE]

Download the full article: Link

Aging Research

A press release from the NIH earlier today:

NIA and McKnight Brain Research Foundation Join Forces to Support Cognitive Aging Research

The Research Partnership in Cognitive Aging is a newly launched public-private effort to support current and emerging research on age-related changes in the brain and cognition. Jointly funded by the National Institute on Aging (NIA), one of the National Institutes of Health (NIH), and the McKnight Brain Research Foundation, through the Foundation for the National Institutes of Health (FNIH), this effort is expected to award an estimated $20 million in research grants over the next five years. The research partnership is aimed at expanding understanding of how we think, learn and remember with age and at developing interventions to maintain cognitive health as we grow older.


Read the full release

Tuesday, October 14, 2008

Neuropsychology Abstract of the Day: Patient-Reported Outcome Measurement for Fatigue

Christodoulou C, Junghaenel DU, Dewalt DA, Rothrock N, & Stone AA. Cognitive interviewing in the evaluation of fatigue items: Results from the patient-reported outcomes measurement information system (PROMIS). Quality of Life Research. 2008 Oct 12. [Epub ahead of print]

Department of Neurology, HSC T12-028, Stony Brook University, Stony Brook, NY, 11794-8121.

OBJECTIVES: Cognitive Interviewing (CI) is a technique increasingly used to obtain respondent feedback on potential items during questionnaire development. No standard guidelines exist by which to incorporate CI feedback in deciding to retain, revise, or eliminate potential items. We used CI in developing fatigue items for the National Institutes of Health (NIH) Patient-Reported Outcomes Measurement Information System (PROMIS) Roadmap initiative. Our aims were to describe the CI process, formally evaluate the utility of decisions made on the basis of CI, and offer suggestions for future research. METHODS: Participants were 22 patients with a diverse range of chronic health conditions. During CI, each participant provided feedback on a series of items. We then reviewed the CI data and decided whether to retain, revise, or eliminate each potential item. Following this, we developed or adopted three quantitative methods to compare retained versus eliminated items. RESULTS: Retained items raised fewer serious concerns, were less likely to be viewed as non-applicable, and were less likely to display problems with clarity or to make incorrect assumptions about respondents. CONCLUSIONS: CI was useful in developing the PROMIS fatigue items and the methods used to judge CI for the present item set may be useful for future investigations.

PMID: 18850327 [PubMed - as supplied by publisher]

===

Additional information about "cognitive interviewing" may be found here: link

Election Day in Canada

Today is election day in Canada. Vote!

Here is a discussion of one of the health care issues in Canada: a shortage in the number of physicians:

From The CBC:

Why MDs are scarce and what can be done about it
Read the article

Internet Use Good For Brain Circuitry, As Well As For The WWW

From The BBC:

Internet use 'good for the brain'
Read the full article

[snip]

Lead researcher Professor Gary Small said: "The study results are encouraging, that emerging computerized technologies may have physiological effects and potential benefits for middle-aged and older adults.

"Internet searching engages complicated brain activity, which may help exercise and improve brain function."

The latest study was based on 24 volunteers aged between 55 and 76. Half were experienced internet users, the rest were not.

Each volunteer underwent a brain scan while performing web searches and book-reading tasks.

Both types of task produced evidence of significant activity in regions of the brain controlling language, reading, memory and visual abilities.

However, the web search task produced significant additional activity in separate areas of the brain which control decision-making and complex reasoning - but only in those who were experienced web users.

The researchers said that compared with simple reading, the internet's wealth of choices requires that people make decisions about what to click on in order to get the relevant information.

[snip]

Tuesday, October 07, 2008

Neuropsychology Abstract of the Day

Tinetti ME, McAvay GJ, Fried TR, Allore HG, Salmon JC, Foody JM, Bianco L, Ginter S, & Fraenkel L. Health outcome priorities among competing cardiovascular, fall injury, and medication-related symptom outcomes. Journal of the American Geriatrics Society. 2008 Aug; 56(8): 1409-1416. Epub 2008 Jul 24.

Department of Internal Medicine and Epidemiology, New Haven, Connecticut 06504, USA.

OBJECTIVES: To determine the priority that older adults with coexisting hypertension and fall risk give to optimizing cardiovascular outcomes versus fall- and medication symptom-related outcomes. DESIGN: Interview. SETTING: Community. PARTICIPANTS: One hundred twenty-three cognitively intact persons aged 70 and older with hypertension and fall risk. MEASUREMENTS: Discrete choice task was used to elicit the relative importance placed on reducing the risk of three outcomes: cardiovascular events, serious fall injuries, and medication symptoms. Risk estimates with and without antihypertensive medications were obtained from the literature. Participants chose between 11 pairs of options that displayed lower risks for one or two outcomes and a higher risk for the other outcome(s), versus the reverse. Results were used to calculate relative importance scores for the three outcomes. These scores, which sum to 100, reflect the relative priority participants placed on the difference between the risk estimates of each outcome. RESULTS: Sixty-two participants (50.4%) placed greater importance on reducing risk of cardiovascular events than reducing risk of the combination of fall injuries and medication symptoms; 61 participants did the converse. A lower percentage of participants with chronic obstructive pulmonary disease (P=.02), unsteadiness (P=.02), functional dependency (P=.04), lower cognition (P=.02) and depressive symptoms (P=.03) prioritized cardiovascular outcomes over fall injuries and medication symptoms than did participants without these characteristics. CONCLUSION: Interindividual variability in the face of competing outcomes supports individualizing decision-making to individual priorities. In the current example, this may mean forgoing antihypertensive medications or compromising on blood pressure reduction for some individuals.

Tuesday, September 30, 2008

Upcoming Event: 06 October 2008, Stockholm

From the Nobel Prize website:

Announcement of the Nobel Prize in Physiology or Medicine

The names of the year's Nobel Laureates in Physiology or Medicine are announced during a press conference at the Nobel Forum, Karolinska Institutet in Stockholm. The announcement is webcast live here at Nobelprize.org!

The 2008 Nobel Prize in Physiology or Medicine will be announced on Monday, October 6, 11:30 a.m. CET (at the earliest).

Biotech: Link Medicine and Neurodegenerative Disorders

From a company press release:

September 30, 2008

Media Contact:
Greg Kelley, Feinstein Kean Healthcare
(+++) +++-++++

Link Medicine Completes $40 million Series C Financing to Accelerate Development of First Disease-Modifying Treatments for Neurodegenerative Disorders

Co-led by Clarus Ventures and SV Life Sciences,the Financing will Advance Preclinical and Clinical Programs

CAMBRIDGE, Mass. - Link Medicine Corporation, a privately held biotechnology company advancing novel approaches for the treatment of neurodegenerative diseases, announced today that it has obtained $40 million of Series C equity financing to help move its lead preclinical programs into human clinical testing. The round was funded by two leading biotechnology investors - Clarus Ventures and SV Life Sciences.

Link Medicine, founded in March 2005, is focused on developing the first disease-modifying therapies for the treatment of several neurodegenerative diseases - including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS). The company is pursuing innovative approaches to target a common feature of these disorders - the buildup in nerve cells of incorrectly folded, aggregated and ultimately neurotoxic proteins.

Link Medicine's development programs build on groundbreaking discoveries made in the laboratory of Link Medicine's Chief Scientific Officer Peter T. Lansbury, Jr., Ph.D., a professor of neurology at Harvard Medical School, and Director of the Morris K. Udall Research Center of Excellence in Parkinson's Disease at Brigham and Women's Hospital. Dr. Lansbury is a leader in the scientific understanding of protein misfolding and aggregation in neurodegeneration.

"Despite advances in our understanding how these conditions progress, Alzheimer's disease and Parkinson's disease continue to exert a devastating toll on patients and their families," said Adam J. Rosenberg, Link Medicine's Chief Executive Officer. "Link Medicine was established to bring sharp focus to the most pressing need these patients face - for therapies not only designed to alleviate disease symptoms, but to modify the course of the disease. The strong backing of Clarus Ventures and SV Life Sciences both validates the progress we have made to date, and accelerates our path to the clinic."

Michael Ross, Managing Partner of SV Life Sciences, said: "The company's scientific platform is unique because of its potential applicability across a wide spectrum of conditions, including more prevalent conditions like Alzheimer's and Parkinson's, and a wide range of orphan indications where protein misfolding and aggregation play a critical role."

Nick Galakatos, Managing Director of Clarus Ventures added: "The approach taken by Link to modify the course of neurodegenerative disease is a novel way to tackle Alzheimer's disease and related disorders. It is particularly attractive because it can be potentially used as a monotherapy, or as a complementary combination with other medicines."

As of the closing of the Series C financing, the Link Medicine Board of Directors is comprised of the following members:

Nick Galakatos, Managing Director, Clarus Ventures
David Guyer, Venture Partner, SV Life Sciences
Peter Lansbury, Chief Scientific Officer
Adam Rosenberg, Chief Executive Officer
Michael Ross, Managing Partner, SV Life Sciences
Edward Scolnick, Director of Psychiatry Initiative at the Broad Institute


About Link Medicine

Link Medicine is advancing disease-modifying technologies targeted at Alzheimer's, Parkinson's and other neurodegenerative diseases where current symptomatic therapies are limited in efficacy or duration, and at orphan indications which lack any meaningful symptomatic treatments. Link was founded by Chief Scientific Officer Peter T. Lansbury, Jr., a leading neuroscience researcher from Harvard Medical School and Brigham & Women's Hospital with a focus on protein misfolding and aggregation in neurodegeneration. The founding investment in Link was made by Edward I. Rudman, a prominent Boston-based business executive and philanthropist, who previously served as Chairman of the Board of Trustees of Beth Israel Hospital in Boston. Link has raised a total of $56.5 million in equity financings to date. Major investors include Clarus Ventures, SV Life Sciences, Endurance Investments Limited, Biogen Idec New Ventures, and private individuals. Link is based in Cambridge, MA.

Neuropsychology Abstract of the Day: Cross-Cultural Distance Continuing Education for Physicians

Llambí L, Margolis A, Toews J, Dapueto J, Esteves E, Martínez E, Forster T, López A, & Lockyer J. Distance education for physicians: Adaptation of a Canadian experience to Uruguay. Journal of Continuing Education for Health Professionals. 2008 Spring; 28(2): 79-85.

EviMed, Montevideo, Uruguay.

INTRODUCTION: The production of online high-quality continuing professional development is a complex process that demands familiarity with effective program and content design. Collaboration and sharing across nations would appear to be a reasonable way to improve quality, increase access, and reduce costs. METHODS: In this case report, the process of adapting and modifying a course to improve the management of Alzheimer's disease developed for the Canadian context for use in Uruguay is described. RESULTS: Both quantitative and qualitative data on the process are shown. The original course was developed by the University of Calgary in the 1990s, and taught initially face to face and later online. The adaptation included using a distance education system developed and widely used in Uruguay, called eviDoctor. DISCUSSION: The key aspects of transforming this course from one country to another with different resources, health care systems, culture, and language are analyzed. Problems encountered are described, as well as their possible solutions.

Thursday, September 25, 2008

Neuropsychology Abstract of the Day: Post-operative Pain, Cognition, and PCA Techniques

Benzion Beilin; Dan Hoofien; Ravit Poran; Inbal Gral; Galina Grinevich; Berta Butin; Eduard Mayburd; & Yehuda Shavit. Comparison of two patient-controlled analgesia techniques on neuropsychological functioning in the immediate postoperative period. Journal of Clinical and Experimental Neuropsychology, Volume 30, Issue 6, August 2008, 674-682.

Pain may contribute to cognitive decline, which is a common complication in the early postoperative period. We compared the effects of two common pain management techniques, intravenous patient-controlled analgesia (PCA-IV) and patient-controlled epidural analgesia (PCEA), on cognitive functioning in the immediate postoperative period. Patients hospitalized for elective surgery were randomly assigned to one of the treatment groups (30 patients per group). A battery of objective, standardized neuropsychological tests was administered preoperatively and 24 hours after surgery. Pain intensity was also evaluated. Nonoperated volunteers served as controls. Patients of the PCA-IV group exhibited significantly higher pain scores than did patients of the PCEA group. PCA-IV patients exhibited significant deterioration in the postoperative period in all the neuropsychological measures, while the PCEA patients exhibited significant deterioration only in one cognitive index, compared to controls.

Keywords: Cognitive function; Local anaesthetics; Opiates; PCA-IV; PCEA; Postoperative pain

Monday, September 22, 2008

Upcoming Event: NYC, 22-25 October 2008

The annual meeting of the National Academy of Neuropsychology (NAN) occurs next month in midtown Manhattan. Here is the conference's webpage: Link

Brain Banks

From the CBC:

Brain banks: Crucial for research, clamouring for donors
Last Updated: Monday, September 22, 2008 | 7:56 AM ET
By Gloria Troyer
CBC News
Read the full article

[snip]

Brain banks. The work they do is not widely publicized — most people who consider signing donor cards think along the lines of organs such as the hearts and kidneys for transplant — but it's crucial for many researchers trying to understand the causes and characteristics of myriad diseases.

"Brain donations and brain banks are absolutely essential to neurological and psychiatric research," says Dr. Margaret Fahnestock, professor of neuroscience in the department of psychiatry and behavioural neurosciences at McMaster University in Hamilton.

"One of the main reasons is that there are few to no good cellular or animal models of most neuropsychiatric conditions — schizophrenia and autism, for example," she says. "This is because we currently have a poor understanding of the cellular and molecular basis of most neuropsychiatric disorders."

Fahnestock says that in light of the lack of good experimental models, one of the best ways to make progress in understanding these disorders — and thereby to make progress in prevention or therapy — is to compare the chemistry and structure of normal and abnormal human brains.

"Thus, the generosity of donors of both normal and abnormal brains is critical to our research effort," she says.

[snip]

Neuropsychology Abstract of the Day: Epilepsy

Frings L, Wagner K, Maiwald T, Carius A, Schinkel A, Lehmann C, & Schulze-Bonhage A. Early detection of behavioral side effects of antiepileptic treatment using handheld computers. Epilepsy and Behavior. 2008 Aug; 13(2) :402-406.

Epilepsy Center, University Hospital of Freiburg, Freiburg, Germany.

OBJECTIVE: Treatment-emergent side effects are frequent events, particularly during the uptitration of antiepileptic drugs. So far, monitoring of such adverse events in outpatients has often been limited to intervals of weeks or months. We here report the application of a new device for temporally fine-grained assessment of objective well-being and cognitive performance using personal digital assistants (PDAs). METHODS: Twenty adult patients with epilepsy participated in this pilot study. Ten received add-on treatment with levetiracetam. Ten patients with constant medication served as a control group. Differences between groups with respect to self-rated cognitive condition, psychophysical condition, aggressiveness, and cognitive test performance in a concentration test assessed three times daily (morning, early afternoon, and evening), over the course of 6 days, were analyzed. RESULTS: Levetiracetam-treated patients manifested an early augmentation of self-rated aggressiveness, which increased in intensity over the course of days. Aggressiveness reached a maximum in the early afternoon across days. There were no major changes in cognitive performance, except for an increase in morning performance in the control group. CONCLUSIONS: This study demonstrates the feasibility of a new method of ambulatory assessment of behavioral and cognitive data during titration of antiepileptic drugs. Significant changes in aggressiveness under add-on treatment with levetiracetam were found to be dependent on the time of assessment during the day. These results suggest that PDA-based ambulatory monitoring of patients with epilepsy may be a promising tool for early detection of drug-related side effects and, thus, may constitute a significant improvement in patient care.

Sunday, September 21, 2008

World Alzheimer's Day

Today is World Alzheimer's Day.

Quality Assurance in Clinical Trials

Public release date: 21-Sep-2008

American Society for Therapeutic Radiology and Oncology

Quality assurance programs improve clinical trials

Boston – Quality assurance programs like the one at the Quality Assurance Review Center (QARC) in Worcester, Mass., strengthen the quality of clinical trials, including cooperative groups conducting National Cancer Institute-supported clinical trials, thereby improving the standard of care in cancer patients, according to a study presented September 21, 2008, at the American Society for Therapeutic Radiology and Oncology's 50th Annual Meeting in Boston.

The Quality Assurance Program, provided by QARC at the University of Massachusetts Medical School, was founded in 1980. The program's services include site credentialing to ensure that those looking to conduct clinical trials have the expertise, equipment and tools necessary to properly participate in research trials. The Quality Assurance Program also establishes benchmarks to monitor the ongoing trials and provide feedback to the physicians conducting the trials. This monitoring helps ensure that patients get the best treatments possible while making certain that the data obtained from the trials are valid and statistically significant.

From 2003 to present, QARC performed reviews on radiation therapy protocols for 6,449 patients enrolled in NCI-supported clinical trials. Cases are reviewed prior to or very early in the radiation therapy course, so that modifications in treatment can be implemented to make the treatment compliant with the study requirements. This study shows that this improved the overall quality of the clinical trial and its potential outcomes.

"Clinical trials are one the most important tools that the cancer research community has to evaluate treatments and protocols in an effort to cure cancer" T.J. FitzGerald, M.D., a study author and a radiation oncologist at QARC, said. "This study shows that a quality assurance program, like ours at QARC, can help cancer researchers conduct better clinical trials. This in turn helps patients get the best treatments possible, while recording the data in a way to help other cancer patients and further help the cancer community better understand what treatments work best."

Saturday, September 20, 2008

Neurology Podcast

A new podcast weekly:

http://www.aan.com/rss/?event=feed&channel=1

Obit: Robert Katzman

Dr. Robert Katzman dies at 82; neuroscientist identified Alzheimer's disease as a 'major killer'
By Thomas H. Maugh II, Los Angeles Times Staff Writer
Los Angeles Times
September 20, 2008
Link

Dr. Robert Katzman, the UC San Diego neuroscientist who pushed Alzheimer's disease into the public consciousness as a "major killer" and who co-founded the activist Alzheimer's Assn., died Tuesday at his home in La Jolla after a long illness. He was 82.

Katzman played a major role in making San Diego one of the major centers for Alzheimer's research in the United States, if not the world, bringing prominent neuroscientists and major funding to a program that had been virtually nonexistent before his arrival in 1984.

"His pioneering and, really, revolutionary work in Alzheimer's disease for more than three decades paved the way for clinical trials of potential treatments to delay the onset or progression of the disease being done today," said neuroscientist David Salmon of UC San Diego.

Alzheimer's was first described in 1906 by the Bavarian psychiatrist Dr. Alois Alzheimer. But it was considered to be a rare form of senile dementia that occurred primarily in patients younger than 65.

During the 1960s, Katzman studied many dementia patients, especially the elderly, and concluded that they had Alzheimer's.

In a seminal 1976 editorial in the journal Archives of Neurology, Katzman concluded that senile dementia was not a normal part of the aging process, as had been believed, but that it was a disease -- in fact, Alzheimer's disease.

Extrapolating from estimates of the prevalence of dementia, he concluded that Alzheimer's was the fourth leading cause of death in the United States, trailing only heart disease, cancer and stroke.

Katzman's efforts increased the number of Alzheimer's cases many-fold and challenged the long-held idea that growing old was the primary cause of dementia, sociologist Patrick Fox of UC San Francisco wrote in the Milbank Quarterly. These ideas provided the ammunition "to define the disease as a major social and health problem and to mobilize the resources to address the defined problem," he wrote.

Funding for Alzheimer's research grew from $5 million in 1980 to $647 million in 2005.

In 1977, Katzman and his close colleague Dr. Robert D. Terry of UC San Diego organized the first national conference on Alzheimer's disease, triggering a boom in research. In 1981, he and his colleagues formed the Alzheimer's Disease and Related Disorders Assn. -- later renamed the Alzheimer's Assn. -- which has become a major source of private funding for research and an advocate for patients.

Robert Katzman was born Nov. 29, 1925, in Denver, the son of a physician. He served in the Navy during World War II as an electronic technician's mate, then enrolled in the University of Chicago. There, he became interested in the chemistry of the brain, but because there were no classes on the topic, he enrolled in Harvard Medical School, earning his degree in 1953.

After a residency at Columbia-Presbyterian Medical Center in New York, he joined the faculty of the Albert Einstein College of Medicine in New York, where he spent 30 years before finishing his career at La Jolla.

Although his research focused on brain chemistry, his interests were diverse. He began studying brain electrolytes and experimental models of brain swelling, then moved on to study the cerebrospinal fluid that surrounds the brain.

In 1984, he was recruited as chairman of the department of neurosciences at UC San Diego. That year, he wrote the grant proposal that resulted in the creation of the university's Alzheimer's Disease Research Center, one of only five such centers in the country.

At San Diego, he led a pioneering study in China that showed that higher education delays the onset of Alzheimer's disease. Another study also found that a higher brain capacity enabled the brain to fight off the disease longer.

Katzman officially retired in 2002 but continued to participate in research and case conferences at the university hospital.

He is survived by his wife of 61 years, the former Nancy Bernstein; two sons, David of Brooklyn, N.Y., and Daniel of Clayton, Calif.; and a grandson.

===


Also, here is the UCSD Obit: Dr. Robert Katzman,
Pioneering Alzheimer’s Disease Expert, Dies

University of Pennsylvania Neuroscience Initiative

A press release from the University of Pennsylvania:


Penn Announces $50 Million Penn Integrates Knowledge Neurosciences Initiative
September 18, 2008

PHILADELPHIA –- The University of Pennsylvania will make a major investment in neuroscience, the interdisciplinary study of brain/behavior relationships and nervous-system diseases, with a $50 million contribution from Penn’s Health System to endow five new Penn Integrates Knowledge (PIK) professorships.

A portion of this contribution will supply start-up funds for each PIK professorship in neuroscience and will support interdisciplinary neuroscience initiatives involving the School of Medicine and other schools of the University.

The announcement was made by Penn President Amy Gutmann and Provost Ronald Daniels.

“This landmark contribution by the Health System represents an extraordinary commitment toward strengthening Penn’s academic programs.” Gutmann said. “With our commitment to integrating knowledge and our formidable teaching and research capacity in medicine and the neural and behavioral sciences, Penn can drive progress in the path-breaking fields of brain science.

“This $50 million contribution, coupled with Penn’s collaborative cross-school team approach, helps empower Penn to develop the knowledge needed to improve our understanding of the neural basis of behavior, including human cognition and emotion and ultimately to improve the health and well being of people around the globe.”

The $50 million adds to the Health System’s existing funding for new centers and institutes, support toward the construction of a new research building and aggressive faculty recruitment efforts in the School of Medicine.

PIK professorships, a University-wide initiative launched by Gutmann in 2005, are awarded to exceptional faculty members whose research and teaching exemplify the integration of knowledge across fields of study.

This new $50 million Penn Integrates Knowledge Neuroscience Initiative is in addition to several significant neuroscience initiatives currently underway or planned at Penn including:

• Eighteen faculty positions in the neurosciences added since 2006.

• Dedicated neuroscience facilities in the Fisher Translational Research Center intended to accelerate the conversion of cutting-edge research into new therapies and treatments and funded by a recent $50 million gift from Anne and Jerome Fisher.

• A new Neural and Behavioral Sciences Building in the School of Arts and Sciences designed to integrate research and education in psychology, biology and cognitive sciences.

• Enhanced facilities for Penn’s Center for Cognitive Neuroscience and Center for Functional Neuroimaging. Penn has been a world leader in neuroscience research and training since 1953 when it founded the Mahoney Institute of Neurological Sciences, the nation’s first university-wide institute devoted exclusively to neuroscience research.

“We are confident,” Daniels said, “that the new Penn Integrates Knowledge Neuroscience Initiative will allow Penn to continue to lead the life-sciences revolution by empowering our world-class faculty and investigators to take giant strides toward improving the health and well being of people around the globe.”

Penn supports one of the world’s leading neuroscience research communities: 182 faculty from 32 departments across six schools, a pioneering undergraduate program in Biological Basis of Behavior and a Neuroscience Graduate Group that fosters the next generation of neuroscientists.

Friday, September 19, 2008

Upcoming Event: 16 October 2008, Morgantown, West Virginia

For Immediate Release
Contact: Jenni Brewer

August 26, 2008

...

PIONEERING NEUROSCIENCES INSTITUTE SETS DATE FOR DEDICATION OF NEW FACILITY AND FIRST-EVER INTERNATIONAL FORUM ON MEMORY AND MEMORY DISORDERS

ON OCTOBER 16 WORLD-RENOWNED SCIENTISTS WILL CONVENE TO SHARE CUTTING EDGE RESEARCH ON ALZHEIMER'S DISEASE, MEMORY AND AGING

Morgantown, W.Va. - On October 16th, 2008, the new $30 million
Blanchette Rockefeller Neurosciences Institute (BRNI) located on the
campus on West Virginia University and founded in honor of U.S. Senator Jay Rockefeller's mother, will play host to prominent international scientists who are advancing research on Alzheimer's disease and other memory disorders. The first-ever International Forum on Memory and Memory Disorders will highlight the work of nine celebrated scientists whose research have led to breakthrough advances for the aging brain, Alzheimer's disease, and patients suffering from memory loss and memory disorders. The next day, on October 17, BRNI will open its doors to the public and further continue the Institute's research, which started nearly nine years ago. The approximately 78,000 square foot three-level building will provide state-of-the-art laboratory space and support research activities for nearly a hundred scientists and researchers.

"Even before the doors have opened, BRNI has undertaken ground-breaking
research into the treatment for Alzheimer's and other neurological
disorders. Now, for the first time ever, the best and brightest minds
in our country, and from around the world, will gather to discuss the
state of memory and memory disorders research and have a place to carry
on their important work," said Sen. Rockefeller. "I know the heartbreak
that comes with having someone you love slowly fade from Alzheimer's.
BRNI's opening is a great day for not only West Virginia, but for all
families across the globe that will benefit from its important work."

The prestigious list of scientists chosen to share their research is an
international mix of experts from Switzerland, to Harvard Medical
School, to West Virginia University and includes:

Professor Floyd Bloom, Professor Emeritus and Chairman of Neuropharmacology, The Scripps Institute, Professor Andrew Matus, Director, Emeritus Neurobiology, Friedrich Miescher Institute, Novartis Research Foundation, Switzerland, Professor Howard Eichenbaum, Director, Center for Memory, Boston University, Professor Tracy Shors, Department of Psychology, Center for Collaborative Neuroscience, Rutgers University, Dr. Daniel Alkon, Scientific Director, Blanchette Rockefeller Neurosciences Institute at West Virginia University, Professor Rudi Tanzi, Director, Genetics and Aging Unit, Harvard Medical School, Professor Sangram Sisodia, Director, Center for Brain Disease, University of Chicago, Professor James Stevenson, Chairman, Department
of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine and Professor Carol Barnes, Director, Evelyn F. McKnight Brain Institute, The University of Arizona.

"Because of the dedication of Sen. Rockefeller and his passion for finding a cure for Alzheimer's, this magnificent facility and its outstanding world-renowned scientists can work everyday to unlock the
causes and treatments for this troubling disease," said Dr. Daniel
Alkon, Scientific Director at BRNI. "BRNI's hosting of the International Forum on Memory and Memory Disorders will shine a global spotlight on our own work and contribute to the progress we are making in finding a cure for Alzheimer's disease and new undiscovered treatments for memory disorders."

The only non-profit independent institution in the world dedicated to the study of human memory and memory disorders, BRNI was established by Rockefeller in 1999 in honor of his mother, Blanchette, who was afflicted by Alzheimer's disease. The Institute's scientific exploration of memory and memory disorders has led to recent discoveries with a drug - Bryostatin - shown to create new connections in the brain, among other revolutionary findings. BRNI's work expands and advances the scientific research of memory and memory disorders for the purposes of prevention, diagnosis and treatment, with the goal of moving research out of the laboratory and into the hands of physicians and patients.

For more information on the Blanchette Rockefeller
Neurosciences Institute or to register to attend the International
Forum, visit www.brni.org .

Self-Navigating Wheelchair

From the website, MedGadget::

A Wheelchair with Ears and Brain
http://www.medgadget.com/archives/2008/09/a_wheelchair_with_ears_and_brain.html

Thursday, September 18, 2008

Neuropsychology Abstract of the Day: Pain Assessment

Jensen MP, Mardekian J, Lakshminarayanan M, & Boye ME. Validity of 24-h recall ratings of pain severity: Biasing effects of "Peak" and "End" pain. Pain. 2008 Jul 15; 137(2): 422-427.

Department of Rehabilitation Medicine, Box 356490, University of Washington School of Medicine, Seattle, WA 98195-6490, USA.

Despite the frequent use of pain recall ratings in clinical research, there remains doubt about the ability of individuals to accurately recall their pain. In particular, previous research indicates the possibility that the most pain experienced during a recall period and the most recent pain experienced (known as peak and end effects, respectively) might bias recall ratings. The current study used data from a published clinical trial to determine the relative validity of a 24-h recall rating of average post-operative pain and the nature and extent of any biasing influence of peak and end effects on nine separate 24-h recall ratings. The results supported a statistically significant but small biasing influence of both peak and end pain. Also, the influence of peak pain was stronger than that of end pain. However, the biasing impact of both peak and end pain together was very small, suggesting that 24-h recall ratings are adequately valid indicants of average pain for patients participating in post-surgery clinical pain trials.

Friday, August 29, 2008

Neuropsychology Abstract of the Day: Parkinson's Disease and Olfaction

Landis BN & Burkhard PR. Phantosmias and Parkinson disease. Archives of Neurology. 2008 Sep; 65(9): 1237-1239.

BACKGROUND: Impaired olfaction is a common, nonmotor manifestation of Parkinson disease (PD). However, to our knowledge, qualitative olfactory disturbances, such as odor distortions, have not been extensively reported in this condition. OBJECTIVE: To describe 2 patients who reported positive olfactory symptoms preceding typical PD, which were consistent with olfactory hallucinations (phantosmias) in the absence of major smell deficit. DESIGN: Case series. SETTING: University hospital. Patients We describe 2 patients, both seen in 2007, who reported pleasant olfactory hallucinations for several years. MAIN OUTCOME MEASURES: Iodine I 123-labeled ioflupane single-photon emission computed tomography and olfactometric testing results. RESULTS: The (123)I-labeled ioflupane single-photon emission computed tomography showed reduced radiotracer uptake in both striatum more marked in the putamen and on the left side in patient 1 and reduced radiotracer uptake in both putamen more marked on the right side in patient 2. Olfactometric testing showed mild hyposmia in patient 1 and normal function in patient 2. The disappearance of the phantosmias in both patients coincided with the development of typical PD. CONCLUSION: We propose phantosmia as a new premotor manifestation of PD and suggest that qualitative abnormalities of olfaction, rather than the typical smell loss demonstrated in this condition, should be more carefully examined in the prodromal phase of PD

Saturday, July 26, 2008

Current Event: International Conference on Alzheimer's Disease (ICAD) 2008, Chicago IL

The Alzheimer's Association ICAD 2008 conference begins today and continues through the 31st of July. The conference takes place in Chicago at McCormick Place.

Details available at the conference website: ICAD website.

Friday, July 11, 2008

Neuropsychology Abstract of the Day: Verbal Fluency and MCI

Nutter-Upham KE, Saykin AJ, Rabin LA, Roth RM, Wishart HA, Pare N, Flashman LA. Verbal fluency performance in amnestic MCI and older adults with cognitive complaints. Archives of Clinical Neuropsychology. 2008 May; 23(3): 229-241.

Neuropsychology Program, Department of Psychiatry, Dartmouth Medical School/DHMC, Lebanon, NH, USA.

Verbal fluency tests are employed regularly during neuropsychological assessments of older adults, and deficits are a common finding in patients with Alzheimer's disease (AD). Little extant research, however, has investigated verbal fluency ability and subtypes in preclinical stages of neurodegenerative disease. We examined verbal fluency performance in 107 older adults with amnestic mild cognitive impairment (MCI, n=37), cognitive complaints (CC, n=37) despite intact neuropsychological functioning, and demographically matched healthy controls (HC, n=33). Participants completed fluency tasks with letter, semantic category, and semantic switching constraints. Both phonemic and semantic fluency were statistically (but not clinically) reduced in amnestic MCI relative to cognitively intact older adults, indicating subtle changes in the quality of the semantic store and retrieval slowing. Investigation of the underlying constructs of verbal fluency yielded two factors: Switching (including switching and shifting tasks) and Production (including letter, category, and action naming tasks), and both factors discriminated MCI from HC albeit to different degrees. Correlational findings further suggested that all fluency tasks involved executive control to some degree, while those with an added executive component (i.e., switching and shifting) were less dependent on semantic knowledge. Overall, our findings highlight the importance of including multiple verbal fluency tests in assessment batteries targeting preclinical dementia populations and suggest that individual fluency tasks may tap specific cognitive processes.

Tuesday, July 08, 2008

New Online Dementia Resources from UCSF

The University of California, San Francisco (UCSF) Memory and Aging Center has recently revised their website and has launched a YouTube channel dedicated to educating patients, caregivers, and health professionals about neurodegenerative diseases and the dementias. The Center has also launched a Facebook webpage.

The website can be examined at UCSF website.

The YouTube channel - the first one I've heard of dedicated to these topics - can be found at YouTube channel link.

As noted by a UCSF contact:

"Through the YouTube channel, we also hope to support the caregiver and the caregiver’s loved ones to help them cope with these illnesses.

"The channel features UCSF’s renowned clinical-researchers discussing disease characteristics – which are often subtle and not well known, even among members of the medical community. Personal stories of patients and family members are also featured, together with practical advice and coping strategies from healthcare professionals."

The “Defeat Dementia” Facebook group to help support patients, their families, friends, caregivers and others can be found at: link.

Monday, June 02, 2008

Alzheimer's Disease

On the New York Times website:

Earlier diagnosis giving Alzheimer's a new voice
By THE ASSOCIATED PRESS
Published: June 2, 2008
Filed at 4:26 p.m. ET

"WASHINGTON (AP) -- Don Hayen has a handy way of deflecting the instant pity that comes when he reveals his Alzheimer's disease: "But I haven't lost my keys all day," he quickly jokes. Hayen is part of a growing new movement in Alzheimer's: Patients diagnosed early enough to still be articulate and demand better care and better research.

They are giving a voice to a disease whose victims until now have remained largely silent, and powerless.

It's a shift with big ramifications."

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

Sunday, May 25, 2008

Three Brainy General-Readership Books

Just finished reading three excellent books with neuro themes, one a work of fiction and the other two are narrative accounts:

"Still Alice" by Lisa Genova (available in paperback by iUniverse Press), is a very accurate dramatic fictional account of early-onset Alzheimer's disease.

"Insomniac" by Gayle Greene is a great account of the world of insomnia, from the vantage point of individuals living with sleep disorders (including the author) and from the vantage point of the clinical researchers who study the condition and who work on drug development and other facets of diagnosis, understanding, and treatment.

Finally, "Can't Remember What I Forgot" by Sue Halpern, self described as a "behind-the-scenes foray into the world of cutting-edge memory research." It lives up to that description and does so in a very readable manner.

"Insomniac" is published by the University of California Press and "Can't Remember ..." is published by Harmony Books.


Today, I am reading "Netherland" by Joseph O'Neill, published by Pantheon,, which was released about a week ago to critical acclaim. No neuro themes, but a compellingly good read.

Analysis of the Neurotechnology Industry

The Ultimate Cure
by David Ewing Duncan
CondeNast Portfolio
May 2008

"The neurotech industry is engaged in a $2 trillion race to fix your brain. Many players will fail, but the payoff will be huge for those who succeed."

[snip]

"Neurotech’s returns are already enormous. In 2006, the industry brought in more than $120 billion—about $101 billion from drugs and the rest from neurodevices ($4.5 billion) and neurodiagnostics ($15 billion)—up 10 percent from the previous year, reports NeuroInsights, a market research and investment advisory firm. But industry analysts insist that this figure hardly begins to suggest the potential. For Alzheimer’s, a disease currently without an effective treatment for about 4.5 million sufferers in the U.S., 40 companies—including behemoths like Eli Lilly, GlaxoSmithKline, and Wyeth, as well as Targacept and a gaggle of similar upstarts—are testing 48 new drugs in human trials in a quest for the Prozac of dementia. The push has brought many small to midsize biotech firms together in partnerships with larger pharmaceutical companies to pursue everything from pain-control compounds derived from chili peppers to an antistroke medicine developed from vampire-bat saliva. There is so much activity in neurotech that last fall it got its own index, NERV, on the Nasdaq, tracking the performance of 30 leading brain companies based in the United States. Analysts estimate that the sector should continue to grow by about 10 percent a year, which would produce a brain-industrial complex worth more than $300 billion in the next 10 years."

[snip]

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

Saturday, May 24, 2008

Military Traumatic Brain Injury and Rehabilitation

An interesting feature article in tomorrow's New York Times Sunday Magazine:

The Sergeant Lost Within
By DANIEL BERGNER
Published: May 25, 2008

"Roadside bombs have caused hundreds of dire brain injuries to soldiers in Iraq. One of them is Shurvon Phillip, and a team of specialists has worked avidly trying to reach him."

A good deal of the article deals with the Rehabilitation Institute of Chicago (RIC).

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

Friday, May 02, 2008

The Game Brain

Yep - another fine New York Times interview about neuro gymnastics:

Boomers, Exercise Your Brains, or Else You’ll...Uh...
By KATIE HAFNER
Published: May 3, 2008

"The fear of a decaying brain has inspired a mini-industry of products from dietary supplements to computer games."

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

Thursday, May 01, 2008

Upcoming Event: American Pain Society, 8-10 May 2008, Tampa Florida

The annual meeting of the APS takes place next week in Florida. Visit the conference homepage for details: Link.

From the conference homepage:

Conference Purpose and Objectives

"The 27th Annual Scientific Meeting of the American Pain Society will offer current information about the diagnosis, treatment, and management of acute pain, chronic cancer and noncancer pain, and recurrent pain. In-depth workshops are planned and are designed to enhance research or clinical skills pertinent to the management of pain; they will feature content appropriate for professionals at several experience levels.

"Each year the APS Scientific Program Committee carefully reviews attendees’ evaluations in order to organize a scientific program which addresses a broad range of topics related to pain research and treatment.

"Designed for a diverse group of scientists, pain clinicians, and other professionals, the 27th Annual Scientific Meeting features a prominent faculty presenting basic, translational, and clinical research advancements.

Interact with cutting-edge researchers.

Translate scientific discoveries into clinical practice.

Network with your colleagues.

Hear from policy makers about issues that directly affect you.

Raise questions, debate the implications, plan follow-up studies, and discuss results.

Discuss your own research and clinical observations.

Meet with poster presenters to learn about their thinking and future research directions.

Visit more than 150 booths that feature products and services specifically designed for multidisciplinary leaders who study and treat pain."

Saturday, April 12, 2008

I ...... Mac

In tomorrow's New York Times Sunday Magazine:

Total Recall
By GARY MARCUS
Published: April 13, 2008

"How much would you pay to have a small memory chip implanted in your brain if that chip would double the capacity of your short-term memory? Or guarantee that you would never again forget a face or a name?"

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

Current Event: American Academy of Neurology (AAN) Annual Conference, Chicago

The AAN conference takes place this week. Look for some interesting reports of dementia pharmaceutical clinical trials.

Visit the conference website: [Link].

Sunday, April 06, 2008

Neuropsychology Abstract of the Day: Parkinson's Disease and Olfaction

Kranick SM, & Duda JE. Olfactory dysfunction in Parkinson's disease. Neurosignals. 2008; 16(1): 35-40.

Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.

Prior to the onset of the cardinal motor features of idiopathic Parkinson's disease (PD), other manifestations of neurodegeneration such as olfactory dysfunction are often apparent. Characterizing these potential biomarkers of preclinical PD is particularly important in identifying individuals who will go on to develop disabling symptoms, and thus be good candidates for new neuroprotective strategies. As shown by the Braak neuropathologic staging of PD, the olfactory system is among the first neuronal populations to display Lewy body pathology. Clinically, loss of smell can be easily tested in the office using several validated techniques and is often helpful to the physician in distinguishing idiopathic PD from other forms of parkinsonism. Recent findings have indicated that a decline in olfaction may be observed in selected at-risk patients, which has significant implications for identifying potential study populations. Ongoing studies of olfactory dysfunction may also reveal potential for use as a medication-independent biomarker of disease progression in addition to use as a biomarker for the diagnosis of PD.

Publication Types: Review

PMID: 18097158 [PubMed - indexed for MEDLINE]

Saturday, April 05, 2008

Neuropsychology Abstract of the Day: Parkinson's Disease

Pagonabarraga J, Kulisevsky J, Llebaria G, García-Sánchez C, Pascual-Sedano B, & Gironell A. Parkinson's disease-cognitive rating scale: A new cognitive scale specific for Parkinson's disease. Movement Disorders. 2008 Mar 31 [Epub ahead of print].

Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Autonomous University of Barcelona, and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Spain.

Cognitive defects associated with cortical pathology may be a marker of dementia in Parkinson's disease (PD). There is a need to improve the diagnostic criteria of PD dementia (PDD) and to clarify the cognitive impairment patterns associated with PD. Current neuropsychological batteries designed for PD are focused on fronto-subcortical deficits but are not sensitive for cortical dysfunction. We developed a new scale, the Parkinson's Disease-Cognitive Rating Scale (PD-CRS), that was designed to cover the full spectrum of cognitive defects associated with PD. We prospectively studied 92 PD patients [30 cognitively intact (CogInt), 30 mild cognitive impairment (MCI), 32 PDD] and 61 matched controls who completed the PD-CRS and neuropsychological tests assessing the cognitive domains included in the PD-CRS. Acceptability, construct validity, reliability, and the discriminative properties of the PD-CRS were examined. The PD-CRS included items assessing fronto-subcortical defects and items assessing cortical dysfunction. Construct validity, test-retest and inter-rater reliability of PD-CRS total scores showed an intraclass correlation coefficient >0.70. The PD-CRS showed an excellent test accuracy to diagnose PDD (sensitivity 94%, specificity 94%). The PD-CRS total scores and confrontation naming item scores-assessing "cortical" dysfunction-independently differentiated PDD from non-demented PD. Alternating verbal fluency and delayed verbal memory independently differentiated the MCI group from both controls and CogInt. The PD-CRS appeared to be a reliable and valid PD-specific battery that accurately diagnosed PDD and detected subtle fronto-subcortical deficits. Performance on the PD-CRS showed that PDD is characterized by the addition of cortical dysfunction upon a predominant and progressive fronto-subcortical impairment. (c) 2008 Movement Disorder Society.

PMID: 18381647 [PubMed - as supplied by publisher]

Thursday, March 27, 2008

Neuropsychology Abstract of the Day: Frontotemporal Dementia

Wittenberg D, Possin KL, Rascovsky K, Rankin KP, Miller BL, & Kramer JH. The Early Neuropsychological and Behavioral Characteristics of Frontotemporal Dementia. Neuropsychological Review. 2008 Feb 29 [Epub ahead of print]

Memory and Aging Center, University of California—San Francisco Medical Center, San Francisco, CA, USA.

Frontotemporal lobar degeneration (FTLD) represent a constellation of disorders that may be overlooked or misdiagnosed, despite being fairly common presenile neurodegenerative diseases. Although the cognitive disorder can be difficult to document, particularly early in the dementia course, neuropsychological evaluation can assist in the diagnosis. Neuropsychologists are in an excellent position to draw from related disciplines like personality theory and social psychology to better assess the types of changes that characterize the prodromal and early phases of the disease. This review summarizes the current state of the field in the diagnosis of FTLD and discusses the emerging role of neuropsychology in elucidating the brain organization of complex processes including empathy, behavioral control and inhibition, reward systems, appetitive behaviors, emotional regulation, and goal-orientation. As this review underscores, frontotemporal dementia remains a powerful model for studying brain-behavior relationships.

PMID: 18311522 [PubMed - as supplied by publisher]

Wednesday, March 19, 2008

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

Bondi MW, Jak AJ, Delano-Wood L, Jacobson MW, Delis DC, & Salmon DP. Neuropsychological Contributions to the Early Identification of Alzheimer's Disease. Neuropsychological Review. 2008 Mar 18.

A wealth of evidence demonstrates that a prodromal period of Alzheimer's disease (AD) exists for some years prior to the appearance of significant cognitive and functional declines required for the clinical diagnosis. This prodromal period of decline is characterized by a number of different neuropsychological and brain changes, and reliable identification of individuals prior to the development of significant clinical symptoms remains a top priority of research. In this review we provide an overview of those neuropsychological changes. In particular, we examine specific domains of cognition that appear to be negatively affected during the prodromal period of AD, and we review newer analytic strategies designed to examine cognitive asymmetries or discrepancies between higher-order cognitive functions versus fundamental skills. Finally, we provide a critical examination of the clinical concept of Mild Cognitive Impairment and offer suggestions for an increased focus on the impact of cerebrovascular disease (CVD) and CVD risk during the prodromal period of AD.

PMID: 18347989 [PubMed - as supplied by publisher]

Tuesday, March 18, 2008

Pediatric Brain Tumors

From today's New York Times:

A Daring Treatment, a Little Girl’s Survival
By DENISE GRADY
Published: March 18, 2008

Melanie Joy McDaniel is a study subject but also a reminder of how medical research can change lives.

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

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
By ALEX BERENSON
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

Memory

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 (http://www.nimh.nih.gov/science-news/2007/faster-acting-antidepressants-closer-to-becoming-a-reality.shtml) 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.

Objectives:

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
By DENISE GRADY
Published: February 5, 2008

[snip]

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.

[snip]

[ ... 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

[snip]

"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."

[snip]

[ ... 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]

Tuesday, January 22, 2008

Alzheimer's Disease: Sarah Polley's Movie, Away From Her

In continued postings here about Away From Her, I note that Julie Christie and Sarah Polley have just been nominated in Academy Award categories Best Actress and Best Adapted Screenplay, respectively.

The screenplay was adapted from a short story written by Alice Munro.

Wednesday, January 16, 2008

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

Fleisher AS, Sun S, Taylor C, Ward CP, Gamst AC, Petersen RC, Jack CR, Aisen PS, & Thal LJ. Volumetric MRI vs clinical predictors of Alzheimer disease in mild cognitive impairment. Neurology. 2008 Jan 15; 70(3): 191-199.

OBJECTIVE: To compare volumetric MRI of whole brain and medial temporal lobe structures to clinical measures for predicting progression from amnestic mild cognitive impairment (MCI) to Alzheimer disease (AD). METHODS: Baseline MRI scans from 129 subjects with amnestic MCI were obtained from participants in the Alzheimer's Disease Cooperative Study group's randomized, placebo-controlled clinical drug trial of donepezil, vitamin E, or placebo. Measures of whole brain, ventricular, hippocampal, and entorhinal cortex volumes were acquired. Participants were followed with clinical and cognitive evaluations until formal criteria for AD were met, or completion of 36 months of follow-up. Logistic regression modeling was done to assess the predictive value of all MRI measures, risk factors such as APOE genotype, age, family history of AD, education, sex, and cognitive test scores for progression to AD. Least angle regression modeling was used to determine which variables would produce an optimal predictive model, and whether adding MRI measures to a model with only clinical measures would improve predictive accuracy. RESULTS: Of the four MRI measures evaluated, only ventricular volumes and hippocampal volumes were predictive of progression to AD. Maximal predictive accuracy using only MRI measures was obtained by hippocampal volumes by themselves (60.4%). When clinical variables were added to the model, the predictive accuracy increased to 78.8%. Use of MRI measures did not improve predictive accuracy beyond that obtained by cognitive measures alone. APOE status, MRI, or demographic variables were not necessary for the optimal predictive model. This optimal model included the Delayed 10-word list recall, New York University Delayed Paragraph Recall, and the Alzheimer's Disease Assessment Scale-Cognitive Subscale total score. CONCLUSION: In moderate stages of amnestic mild cognitive impairment, common cognitive tests provide better predictive accuracy than measures of whole brain, ventricular, entorhinal cortex, or hippocampal volumes for assessing progression to Alzheimer disease.

PMID: 18195264 [PubMed - in process]

Tuesday, January 15, 2008

Occupational Therapy (OT)

Today's Science Times section of The New York Times has a good feature article about the daily work of an Occupational Therapist working with patients who have sustained severe traumatic brain injuries.

Link to full text of article

Neuropsychology Abstract of the Day: Stroke Rehab Outcome Assessment

Salter KL, Teasell RW, Foley NC, & Jutai JW. Outcome assessment in randomized controlled trials of stroke rehabilitation. American Journal of Physical Medicine and Rehabilitation. 2007 Dec ;86(12): 1007-1012.

Department of Physical Medicine and Rehabilitation, St. Joseph's Healthcare London, London, Canada.

The lack of a unified approach to outcome assessment in stroke rehabilitation limits our ability to interpret evidence provided by randomized controlled trials (RCTs). The purpose of this review was to identify outcomes and assessment tools reported in RCTs of stroke rehabilitation interventions as a first step toward consistent assessment of outcomes. Given that the validity of research is linked to reliability and validity of measurement, the relationship between the use of previously developed outcome measures and the methodological quality of RCTs was explored.Electronic literature searches identified RCTs examining stroke rehabilitation therapies from 1968 to 2005. The Physiotherapy Evidence Database (PEDro) scale was used to assess methodological quality. Cited outcomes were recorded and assessment tools identified as previously published or study specific. Four hundred ninety-one RCTs cited the assessment of 1447 outcomes using 489 measurement tools. Two hundred fifty-four of these were previously published, and 235 were study specific. A core of 30 frequently cited tools was identified. The use of previously published assessment tools to evaluate primary study outcomes was associated with higher PEDro scores.Significant heterogeneity in outcome assessment was demonstrated, although a core of 30 frequently cited tools could be identified. Appropriate evaluation and selection of outcome measures would enhance the methodological quality of randomized controlled trials.

PMID: 17912137 [PubMed - indexed for MEDLINE]

Monday, January 14, 2008

Alzheimer's Disease: Sarah Polley's Movie, Away From Her

In continued postings here about Away From Her, I note that yesterday Julie Christie won a Golden Globe award as Best Actress for her performance in the movie.

Golden Globe Winners

Neuropsychology Abstract of the Day: Desires for Caffeine

Okay, sitting in a coffeehouse right now, how could I not choose this abstract!




West O, & Roderique-Davies G. Development and initial validation of a caffeine craving questionnaire. Journal of Psychopharmacology. 2008 Jan; 22(1):80-91.

Department of Psychology, HaSS, University of Glamorgan, Pontypridd, CF37 1DL, UK.

Craving for caffeine has received little empirical attention, despite considerable research into the potential for caffeine dependence. The main aim of this study was to develop, and initially validate, a multi-item, multidimensional instrument to measure cravings for caffeine. Participants were 189 caffeine consumers who completed the Questionnaire of Caffeine Cravings, which was based on the Questionnaire of Smoking Urges (QSU), in one of five naturally occurring periods of abstinence; 1-15 min; 16-120 mins; 3-7 h; 12-48 h and +48 h. Exploratory factor analysis suggested a three-factor solution best described the data; Factor 1 reflected strong desires, intentions and positive reinforcement; Factor 2 reflected mild/general positive and negative reinforcement and Factor 3 reflected functional/mood-based negative reinforcement. Significantly higher Factor 1 and Factor 2 scores were recorded for high frequency users; significantly higher Factor 1 and Factor 3 scores were recorded as a function of increased levels of dependence. Duration of abstinence did not significantly effect cravings across all three factors. Regression analyses suggested level of dependence best predicted both current cravings and frequency of daily use. These findings suggest caffeine cravings may be conceptualized multidimensionally and further validates the use of multidimensional, multi-item instruments. Cravings for caffeine may manifest and be detected across varying levels of dependence and, frequency of use and independently of duration of abstinence.

PMID: 18187535 [PubMed - in process]


(photo by anthony risser, copyright 2008, philadelphia)