BrainBlog

BrainBlog

Sunday, December 31, 2006

Music of the Hemispheres













Interesting piece in today's New York Times about music and the brain and work by Daniel Levitin [link].

Curious neuro readers are directed to some classical papers by Macdonald Critchley on this topic.



Saturday, December 30, 2006

Dr. Arthur L. Benton, Neuropsychologist
















Dr. Arthur L. Benton, Neuropsychologist
1909-2006



Obituary printed in the Iowa City Press-Citizen:

Friday, December 29, 2006
Arthur Benton, 97

Arthur Benton, beloved husband of the late Rita, died December 27, 2006 from complications of emphysema, in Glenview, Illinois. Loving father of Raymond Benton (Nina), Abigail Sivan (Milton Harris), and Daniel Benton (Nancy Hauserman). Devoted grandfather of Jeffrey Benton, Ori Sivan (Claudia Regojo), and Ofer Sivan (Amber Neville). Fond brother-in-law of Joan Rogers.

He was born October 16, 1909 in New York City. Dr. Benton received his B.A. and M.A. degrees from Oberlin College and his Ph.D. in Psychology from Columbia University in 1935. He acquired his training as a psychologist at the Payne Whitney Psychiatric Clinic of New York Hospital. Early in 1941, Benton volunteered for service in the U.S. Navy and was commissioned as a lieutenant in the medical department. His active duty lasted until 1945, followed by many years of service in the U. S. Navy Reserve, retiring at the rank of Captain.

In 1946, Benton accepted an appointment as associate professor of Psychology at the University of Louisville. In 1948, he moved to the University of Iowa, as professor and director of graduate training in clinical psychology. In 1958 he became professor of psychology and neurology, retiring in 1978, at which time the Benton Laboratory of Neuropsychology in the Division of Behavioral Neurology was dedicated. At Iowa he supervised 46 doctoral dissertations and 24 master's theses.

He was president of the American Orthopsychiatric Association (1965), the International Neuropsycholo-gical Society (1970), and secretary-general of the Research Group on Aphasia of the World Federation of Neurology (1971-78). He held appointments as visiting scientist or scholar at the University of Milan (1964), the Neurosurgical Clinic, Hospital Sainte-Anne, Paris (1968), the Hebrew University Medical School, Jerusalem (1969), the Free University of Amsterdam (1971), the University of Helsinki (1974), the Tokyo Metropolitan Institute of Gerontology (1974), the University of Melbourne (1977), L'Ecole des Hautes Etudes, Paris (1979), the University of Victoria, British Columbia (1980), the University of Minnesota Medical School (1980), and the University of Michigan (1986). He received honorary doctorates from Cornell College (1978) and the University of Rome (1990).

His awards include the Distinguished Professional Contribution Award from the American Psychological Association (1978), the Distinguished Service and Outstanding Contribution Award of the American Board of Professional Psychology (1985), the Outstanding Scientific Contribution of the International Neuropsychological Society (1981), the Samuel Torrey Orton Award of the Orton Dyslexia Society (1982), and the Distinguished Clinical Neuropsychological Award of the National Academy of Neuropsychology (1989). In 1992 he received the Gold Medal Award for Life Achievement in the Application of Psychology from the American Psychological Foundation. The citation for this award reads in part: "For lifetime contributions that include pioneering clinical studies of brain-behavior relations. He introduced novel and objective psychological assessment techniques that expanded our understanding of the difficulties manifested by neurologically compromised patients. He broadened the applications of psychology and in the process opened up a new field of study and practice, clinical neuropsychology."

Internment private. A memorial service will be scheduled later. In lieu of flowers, donations to: Arthur Benton-Manfred Meier Neuropsychology Fund, c/o American Psychological Foundation, 750 First Street N.E., Washington, DC 20002-4242.

Dr. Arthur L. Benton, Neuropsychologist


risser_1985_DrBenton
Originally uploaded by rissera.















Dr. Arthur L. Benton, Neuropsychologist
1909-2006

Friday, December 29, 2006

Alzheimer Disease: Centenary Theme Issue of Brain

The November 2006 issue [link] of the journal, Brain, celebrates the centenary of Dr. Alois Alzheimer and his case report.

Among the issue's papers are a half-dozen ones with full-content free-access, including a good historical review and an overview of treatment.

Thursday, December 28, 2006

Malnutrition

Today's New York Times has an article about malnutrition.

Two forms of malnutrition of global importance are marasmus and kwashiorkor. I often discuss them and their cognitive consequences whenever I write about developmental neuropsychology.

Here is the Times article:

Malnutrition Is Cheating Its Survivors, and Africa’s Future
By MICHAEL WINES
December 28, 2006
The New York Times

SHIMIDER, Ethiopia — In this corrugated land of mahogany mountains and tan, parched valleys, it is hard to tell which is the greater scandal: the thousands of children malnutrition kills, or the thousands more it allows to survive.

Malnutrition still kills here, though Ethiopia’s infamous famines are in abeyance. In Wag Hamra alone, the northern area that includes Shimider, at least 10,000 children under age 5 died last year, thousands of them from malnutrition-related causes.

Yet almost half of Ethiopia’s children are malnourished, and most do not die. Some suffer a different fate. Robbed of vital nutrients as children, they grow up stunted and sickly, weaklings in a land that still runs on manual labor. Some become intellectually stunted adults, shorn of as many as 15 I.Q. points, unable to learn or even to concentrate, inclined to drop out of school early.

There are many children like this in the villages around Shimider. Nearly 6 in 10 are stunted; 10-year-olds can fail to top an adult’s belt buckle. They are frequently sick: diarrhea, chronic coughs and worse are standard for toddlers here. Most disquieting, teachers say, many of the 775 children at Shimider Primary are below-average pupils — often well below.

“They fall asleep,” said Eteafraw Baro, a third-grade teacher at the school. “Their minds are slow, and they don’t grasp what you teach them, and they’re always behind in class.”

Their hunger is neither a temporary inconvenience nor a quick death sentence. Rather, it is a chronic, lifelong, irreversible handicap that scuttles their futures and cripples Ethiopia’s hopes to join the developed world.

“It is a barrier to improving our way of life,” said Dr. Girma Akalu, perhaps the nation’s leading nutrition expert. Ethiopia’s problem is sub-Saharan Africa’s curse. Five million African children under age 5 died last year — 40 percent of deaths worldwide — and malnutrition was a major contributor to half of those deaths. Sub-Saharan children under 5 died not only at 22 times the rate of children in wealthy nations, but also at twice the rate for the entire developing world.

But below the Sahara, 33 million more children under 5 are living with malnutrition. In United Nations surveys from 1995 to 2003, nearly half of sub-Saharan children under 5 were stunted or wasted, markers of malnutrition and harbingers of physical and mental problems.

The world mostly mourns the dead, not the survivors. Intellectual stunting is seldom obvious until it is too late.

Bleak as that may sound, the outlook for malnourished children in sub-Saharan Africa is better than in decades, thanks to an awakening to the issue — by selected governments, anyway.

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

Wednesday, December 27, 2006

The Game Brain

There is a front-page article in today's New York Times concerning the current state of mental-gymnastic services:

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

(A very catchy lead sentence for the article!)

Friday, December 22, 2006

FDA Approves Cool-Cap

An FDA press release:


FOR IMMEDIATE RELEASE
P06-211
December 20, 2006


Media Inquiries: Karen Riley, 301-827-6242
Consumer Inquiries: 888-INFO-FDA


FDA Approves Novel Device That Prevents or Reduces Brain Damage in Infants

The Food and Drug Administration (FDA) today approved a first-of-a-kind medical device for the treatment of babies born with moderate to severe hypoxic-ischemic encephalopathy (HIE), a potentially fatal injury to the brain caused by low levels of oxygen.  The Olympic Cool-Cap system is designed to prevent or reduce damage to the brains of these patients by keeping the head cool while the body is maintained at a slightly below-normal temperature.  The Cool-Cap is manufactured by Olympic Medical Corporation, a subsidiary of Natus Medical Incorporated of San Carlos, Calif.

“This approval brings new hope to parents of the approximately 5,000-9,000 babies each year who are born in the United States with moderate to severe hypoxic-ischemic encephalopathy,” said Dr. Daniel Schultz, director of FDA’s Center for Devices and Radiological Health.  “Until now, there has been no effective treatment for these infants other than supportive care.  Up to 20 percent of them died, and 25 percent suffered permanent disability because of neurological deficits.”

The Olympic Cool-Cap treats the patient by maintaining a steady flow of water at a selected cool temperature through a cap covering the infant’s head. The system, which consists of a cooling unit, a control unit, temperature probes and a water-filled cap, was found safe and effective in a study with 234 infants with moderate to severe HIE.  At 18 months of age, there were fewer deaths and fewer severe cases of neurodevelopmental disability in the cooled group compared with the control group.

As conditions of the approval, Olympic Medical Corporation will set up a patient registry to collect information on device usage and to track treatment outcomes; organize a training and certification process for all operators of the device; and restrict use of the device to patients who meet the eligibility criteria defined by the original study.

Thursday, December 21, 2006

Early Diagnosis of Alzheimer Disease and FDDNP

From today's New York Times:

New Chemical Is Said to Provide Early Sign of Alzheimer’s Disease
By REUTERS
The New York Times
Published: December 21, 2006


chem
Originally uploaded by rissera.


A chemical designed by doctors in Los Angeles could give earlier signals of Alzheimer’s disease and provide a new way to test treatments, a study has shown.

Currently, the only way to diagnose the disease is to remove brain tissue or to perform an autopsy.

The new study, to be published today in the New England Journal of Medicine, is by doctors at the University of California, Los Angeles, and is part of a larger quest to find a better method to diagnose the condition using tracers that can be detected with a positron emission tomography, or PET, scan.

The new chemical, called FDDNP, attaches to abnormal clumps of proteins called amyloid plaques and nerve cell tangles that develop in Alzheimer’s sufferers and inhibit messages being processed by the brain.

In the study, Dr. Gary Small and his colleagues discovered that the chemical allowed doctors to pick out which of 83 volunteers had Alzheimer’s, which had mild memory problems and which were functioning normally for their age.

It was 98 percent accurate in determining the difference between Alzheimer’s and mild cognitive impairment, which surpassed the 87 percent success rate for a PET scan test that measured sugar metabolism in the brain, and the 62 percent accuracy rate when doctors used a magnetic resonance imaging.

The FDDNP signal can be seen in people years before they develop Alzheimer’s disease, Dr. Small said.

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

Wednesday, December 20, 2006

Neuropsychology Abstract of the Day: Alzheimer Disease

Atchison TB, Massman PJ, & Doody RS. Baseline cognitive function predicts rate of decline in basic-care abilities of individuals with dementia of the Alzheimer's type. Archives of Clinical Neuropsychology. 2006 Dec 13; [Epub ahead of print].

Department of Psychology, Sociology, and Social Work, West Texas A&M University, Box 60296, Canyon, TX 79016-0001, United States.

Decline in basic self-care abilities is an important risk factor for institutionalization in individuals with dementia. The ability to predict such decline would be of clinical importance in working with families of dementia patients. Research has suggested that cognitive decline may precede loss of functional capacity. This paper utilized a large sample of probable Alzheimer's disease patients (N=150) who were evaluated longitudinally to assess the pattern of neuropsychological functioning predictive of rapid decline in self-care. The findings indicated that despite initial equality of Lawton Physical Self-Maintenance (PSM) scores, patients showing rapid decline of PSM function displayed significantly more impaired performance on neuropsychological measures at diagnosis. They also exhibited a statistically significant difference in the pattern of scores from patients who remained stable. The pattern of the rapid declining group included more severe impairment in visual spatial skills, processing speed, and concept formation. Difficulties in using individual patients' cognitive profiles to make predictions about future rate of PSM decline are discussed.

PMID: 17174522 [PubMed - as supplied by publisher]

More on the ACTIVE Study

From an NIH press release:

EMBARGOED FOR RELEASE
Tuesday, December 19, 2006
4:00 PM ET

NIA CONTACT:
Susan Farrer
or Linda Joy
301- 496-1752

NINR CONTACT:
Lanny Newman
301-496-0209

Mental Exercise Helps Maintain Some Seniors’ Thinking Skills

Certain mental exercises can offset some of the expected decline in older adults' thinking skills and show promise for maintaining cognitive abilities needed to do everyday tasks such as shopping, making meals and handling finances, according to a new study. The research, funded by the National Institutes of Health (NIH) and published in the Dec. 20, 2006, Journal of the American Medical Association, showed that some of the benefits of short-term cognitive training persisted for as long as five years.

The Advanced Cognitive Training for Independent and Vital Elderly, or ACTIVE, Study is the first randomized, controlled trial to demonstrate long-lasting, positive effects of brief cognitive training in older adults. However, testing indicated that the training did not improve the participants’ ability to tackle everyday tasks, and more research is needed to translate the findings from the laboratory into interventions that prove effective at home.

The ACTIVE trial was funded by the National Institute on Aging (NIA) and the National Institute of Nursing Research (NINR), both components of NIH. Sherry L. Willis, Ph.D., of Pennsylvania State University in State College, Pa., and co-authors report the findings on behalf of ACTIVE investigators at the study’s six sites: Hebrew SeniorLife, Boston; Indiana University School of Medicine, Indianapolis; Johns Hopkins University, Baltimore; Pennsylvania State University; University of Alabama at Birmingham; and University of Florida, Gainesville (in collaboration with Wayne State University, Detroit), and the data coordinating center at the New England Research Institutes, Watertown, Mass.

“This large trial found that community-dwelling seniors who received cognitive training had less of a decline in certain thinking skills than their peers who did not have training. The study addresses a very important hypothesis — that interventions can be designed to maintain cognitive function,” says NIA Director Richard J. Hodes, M.D. “The challenge now is to further examine these interventions and others to see how they can be employed in real-world settings.”

“Cognitive decline is known to precede loss of functional ability in older adults. It affects everyday activities such as driving or following instructions on a medicine bottle,” says NINR Director Patricia A. Grady, Ph.D., R.N. “Research to identify effective ways of delaying this decline is important because it may help individuals, and our aging citizenry, maintain greater independence as they grow older.”

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

FDA Approves Invega (Paliperidone)

An FDA Press Release:

FOR IMMEDIATE RELEASE
P06-208
December 20, 2006
Media Inquiries: Press Office, 301-827-6242
Consumer Inquiries: 888-INFO-FDA

FDA Approves New Drug for Schizophrenia

The Food and Drug Administration (FDA) today approved Invega (paliperidone) extended-release tablets for the treatment of schizophrenia. Paliperidone is a new molecular entity, which means this medication contains an active substance that has never before been approved for marketing in any form in the United States. Paliperidone is the principal active metabolite of risperidone, a marketed drug for treating schizophrenia.

"Schizophrenia can be a devastating illness requiring lifelong medication and professional counseling," said Douglas Throckmorton, MD, Deputy Director of FDA's Center for Drug Evaluation and Research. "Today's approval adds to the treatment options for patients with this condition."

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

Monday, December 18, 2006

Your Busy Brain, While You Sleep: Way Better Than TiVo!

This is one of the more interesting research studies that I've read about over the past couple of months. Please open up the link to the full article to read all about it:

From today's New York Times:

In Memory-Bank ‘Dialogue,’ the Brain Is Talking to Itself

By NICHOLAS WADE
The New York Times
December 18, 2006

New recordings of electrical activity in the brain may explain a major part of its function, including how it consolidates daily memories, why it needs to dream and how it constructs models of the world to guide behavior.

The recordings capture dialogue between the hippocampus, where initial memories of the day’s events are formed, and the neocortex, the sheet of neurons on the outer surface of the brain that mediates conscious thought and contains long-term memories.

Such a dialogue had been thought to exist, but no one had been able to eavesdrop on it successfully. The new insight has emerged from recordings of rat brains but is likely to occur in much the same way in the human brain, which has analogous structures and the same basic principles of operation.

The finding, reported on the Web site of the journal Nature Neuroscience by Daoyun Ji and Matthew A. Wilson, researchers at the Massachusetts Institute of Technology, showed that during nondreaming sleep, the neurons of both the hippocampus and the neocortex replayed memories — in repeated simultaneous bursts of electrical activity — of a task the rat learned the previous day.

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

Here is the Nature Neuroscience abstract: link

Friday, December 01, 2006

Around the Globe: Iran Alzheimer Association

Alzheimer programming in Iran:

http://www.alzheimer.ir/

(Available in Farsi and in English).

-
Anthony H. Risser | |

Abstract of the Day: Agitation in Alzheimer Disease

Zuidema SU, Derksen E, Verhey FR, & Koopmans RT. (2006). Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia. International Journal of Geriatric Psychiatry,

Kalorama, Beek-Ubbergen, The Netherlands.

OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms of dementia patients in Dutch nursing homes. METHODS: Cross-sectional study in a large sample of 1322 demented patients living in 59 dementia special care units (SCUs) in The Netherlands. Symptoms were observed by licensed vocational nurses during regular care-giving in a 2-week observational period prior to assessment. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory- Nursing home version (NPI-NH; frequency X severity score >/= 4) and the Cohen-Mansfield Agitation Inventory (CMAI; symptoms occurring at least once a week). RESULTS: More than 80% of these patients suffered from at least one clinically significant symptom, as defined with the NPI-NH frequency X severity score >/= 4. Measured with the NPH-NH agitation/aggression, apathy and irritability were the most frequently observed behaviors, with prevalences of 30-35%. Using the CMAI, 85% of the patients showed at least one symptom of agitation, of which general restlessness was observed most frequently (44%). Other frequently observed symptoms with prevalence rates of 30% were cursing or verbal aggression, constant request for attention, negativism, repetitious sentences, mannerisms, pacing, and complaining. Physically aggressive symptoms such as hitting, kicking, biting occurred less often (less than 13%). CONCLUSIONS: Prevalence rates of neuropsychiatric symptoms in Dutch nursing home patients with dementia residing in SCUs are high, especially agitation and apathy. Insight into the prevalence rates of individual symptoms in patients with dementia has important practical consequences for the accurate planning of staff allotment and stresses the need for patient oriented care. Copyright (c) 2006 John Wiley & Sons, Ltd.

PMID: 17136713 [PubMed - as supplied by publisher]

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Anthony H. Risser | |

Thursday, November 30, 2006

A Holiday Stocking Stuffer

Just in time for gift-giving, Dana Press released earlier this month a paperback version of its 2003 resource on family-friendly brain health. A quick look at the 2006 release shows a very impressive resource about the healthy and disordered nervous system - as well as a CD-ROM of material. Nicely illustrated and written for a broad general audience:

The Dana Guide to Brain Health: A Practical Family Reference from Medical Experts by Floyd E. Bloom, M. Flint Beal, & David J. Kupfer. 2006 paperback version: Amazon link

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Anthony H. Risser | |

Monday, November 27, 2006

Caregivers of Persons with Dementia

From an NIH press release:

Novel Program Enhances Dementia Caregivers’ Quality of Life

EMBARGOED FOR RELEASE
Monday, November 20, 2006
5:00 p.m. ET

NIA Media Contacts:
Susan Farrer or Linda Joy
301-496-1752
nianews3@mail.nih.gov

NINR Media Contact:
Lanny Newman
301-496-0209
newmanl@mail.nih.gov

A multifaceted, personalized intervention can significantly improve the quality of life for caregivers of people with dementia, new research published Nov. 21, 2006, in Annals of Internal Medicine has found. The study, Resources for Enhancing Alzheimer’s Caregiver Health II (REACH II), is the first randomized, controlled trial to look systematically at the effectiveness of a multi-component caregiver intervention provided to ethnically diverse populations. Follow-up studies, the researchers suggest, should examine how the intervention might be used in communities through the nation’s existing network of health and aging services.

REACH II was funded by the National Institute on Aging (NIA) and the National Institute of Nursing Research (NINR), both components of the National Institutes of Health (NIH). The research was conducted at five sites nationwide — the University of Alabama (Birmingham and Tuscaloosa), Thomas Jefferson University (Philadelphia), the University of Tennessee (Memphis), the University of Miami (Fla.) and Stanford University (Palo Alto, Calif.). The University of Pittsburgh served as the coordinating center, and Pittsburgh’s Richard Schulz, Ph.D., was corresponding author for the study.

“Family members and friends provide most of the care for millions of people with dementia who live at home, often facing challenges that can seriously compromise their own quality of life,” notes NIA Director Richard J. Hodes, M.D. “REACH II tells us that a well-designed, tailored intervention can make a positive, meaningful difference in caregivers’ lives.”

“This important research demonstrates that the intervention can readily benefit the diverse communities of caretakers who provide care to individuals with Alzheimer’s disease,” adds NINR Director Dr. Patricia A. Grady. “It also underscores the substantial cost that caregivers face — financially, physically, spiritually and emotionally — and helps to illustrate why caregiving research is a priority for NINR and NIA.”

The REACH II study included 642 individuals, more than 200 each of Hispanic, white and African American caregivers of persons with dementia. The caregivers within each ethnic/racial group were randomly assigned to either an intervention or a control group.

Trained project staff visited the caregivers in the intervention group at home nine times, talked with them during three half-hour telephone calls, and offered five structured telephone support sessions. The strategies included information sharing, instruction, role playing, problem solving, skills training, stress-management techniques and telephone support groups. Those in the control group received a packet of dementia education materials and two brief “check-in” telephone calls. Spanish-language services and materials were offered to the Spanish-speaking caregivers in Miami, Palo Alto and Philadelphia.

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

-
Anthony H. Risser | |

Spindle Neurons

From the CBC:

Humpback whales share brain cells with humans
Last Updated: Monday, November 27, 2006 | 1:12 PM ET
CBC News

Humpback whales have joined an exclusive evolutionary club alongside humans, gorillas and dolphins, thanks to the discovery of a particular type of brain cell in the large aquatic mammals.

The brains of humpback whales contain spindle neurons, a kind of brain cell found in the cerebral cortex in large primates like humans and gorillas, according to a study published online on Monday.

Patrick R. Hof and Estel Van der Gucht of the Department of Neuroscience at Mount Sinai School of Medicine in New York published their findings in The Anatomical Record, the official journal of the American Association of Anatomists.

The authors found humpback whales not only had spindle neurons in the same area of the cortex where they are found in hominids, but also in other parts of their brain.

Named for their long, spindle-shaped bodies, spindle neurons are a complex and not completely understood cellular structure found in the brains of larger primates and cetaceans, the group of marine mammals that includes whales and dolphins.

They are thought to be involved in cognitive processes such as learning, remembering and recognizing, and are affected by conditions like Alzheimer's disease, autism and schizophrenia. In humans, they occur in the part of the brain thought to control speech, social organization and empathy.

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

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Anthony H. Risser | |

Sunday, November 26, 2006

Abstract of the Day: Assessing Neurocognitive Toxicity in Animal Models

Bertaina-Anglade V, Enjuanes E, Morillon D, & Drieu la Rochelle C. (2006). The object recognition task in rats and mice: A simple and rapid model in safety pharmacology to detect amnesic properties of a new chemical entity. J Pharmacol Toxicol Methods, 54(2), 99-105.

Preclinical Pharmacology Department, Biotrial, 7-9 rue JL Bertrand, 35000 Rennes, France.

INTRODUCTION: The aim of the present study was to evaluate the potential usefulness of the object recognition learning paradigm to detect the potential amnesic properties of a new drug for use in the characterisation of its safety pharmacology profile. METHODS AND RESULTS: In the first experiment, the time-dependent decay of object recognition memory was characterised in Sprague-Dawley rats and C57Bl/6J mice. Under our experimental conditions, it takes between 3 and 4 post-training hours for the rats and between 1 and 2 post-training hours for the mice to forget the respective value of the objects. In the second experiment, the effects of scopolamine (0.03-1 mg/kg) were investigated in both rats and mice when administered 30 min prior to training in the object recognition task. Memory retention was tested 2 h after training in rats and 1 h after training in mice. Scopolamine impairs the object recognition memory at doses of 0.1, 0.3, and 1 mg/kg in rats and at doses of 0.3 and 1 mg/kg in mice. In the last experiment, effects of two benzodiazepines (alprazolam and diazepam) were assessed in the mouse model of object recognition task. Diazepam and alprazolam were intraperitoneally administered 30 min prior to training and memory retention was tested 10 min and 1 h after training. At 0.2 mg/kg, both benzodiazepines impair object recognition memory when testing is performed 1 h after training. However, when testing is performed 10 min after training, both benzodiazepines at 0.2 mg/kg failed to disrupt memory processes. DISCUSSION: Taken together, these results show that the object recognition task can easily be performed in rats and mice for safety pharmacology studies related to CNS function. Because of the ageing population and the increasing number of drugs prescribed to elderly patients, it becomes important to evaluate the potential side effects of a new chemical entity on memory function during evaluation of its safety profile. The object recognition task, which is simple, rapid, and reliable, should be of great use in safety pharmacology to detect amnesic properties of new compounds.

PMID: 16750402 [PubMed - indexed for MEDLINE]

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Anthony H. Risser | |

Wednesday, November 22, 2006

Abstract of the Day: Quality of Life (QOL) Measurement in Epilepsy

von Lehe M, Lutz M, Kral T, Schramm J, Elger CE, & Clusmann H. Correlation of health-related quality of life after surgery for mesial temporal lobe epilepsy with two seizure outcome scales. Epilepsy and Behavior 2006 Aug; 9(1): 73-82.

Department of Neurosurgery, University Clinic Bonn, Bonn, Germany.

PURPOSE: The objective of this study was to correlate health-related quality of life (HRQOL) after surgery for mesial temporal lobe epilepsy, as revealed by a postoperative screening tool, to different modalities of seizure outcome classification (Engel, International League Against Epilepsy (ILAE)). METHOD: One hundred twenty-eight of one hundred forty consecutive patients returned a HRQOL questionnaire at a mean of 36 months after selective amygdalohippocampectomy. Patients answered in two ways: with an absolute estimation (values 1-4) and with a self-rated relative change (-1, 0, +1) after surgery. RESULTS: Eighty patients were seizure- and aura-free (63.3% ILAE 1), 16 continued to have auras (12.5% ILAE 2), and 13 experienced 1-3 seizure days per year after surgery (10.2% ILAE 3). Ninety-two patients were classified seizure-free (71.9% Engel I), and 17 had two or fewer seizures per year (13.3% Engel II). Of 110 patients in ILAE 1-3, 100 (91%) stated good or even very good postoperative HRQOL, and 99 (90.0%) reported improvements in HRQOL. Only 9 of the remaining 18 (50%) reported good or very good HRQOL after surgery (P=0.01). Corresponding results were obtained with Engel classes I and II, suggesting a trend toward ILAE 1-3 and Engel I and II as overall satisfactory outcomes. A more detailed HRQOL assessment yielded lowest scores in the cognitive domain, and a significant correlation of self-rated changes in cognitive functioning with seizure control (P=0.01). Changes in physical capabilities and mood were significantly better with satisfactory seizure outcome (P=0.006 and P<0.001, respectively), whereas the social aspects were not significantly dependent on seizure outcome (P=0.06). CONCLUSION: Correlation of HRQOL and seizure control suggested that ILAE 1-3 and Engel I and II most likely represent overall satisfactory outcome. Subdomain analyses revealed cognitive abilities as the most critical feature associated with seizure control, whereas social aspects remained mainly stable.

PMID: 16730476 [PubMed - indexed for MEDLINE]

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Anthony H. Risser | |

Tuesday, November 14, 2006

Dr. Sandra Witelson in the News!

From today's New York Times:

A Hands-On Approach to Studying the Brain, Even Einstein’s
By SIOBHAN ROBERTS
Published: November 14, 2006

HAMILTON, Ontario — Standing in her vaultlike walk-in refrigerator, Sandra F. Witelson pries open a white plastic tub that looks like an ice cream container.

There, soaking in diluted formaldehyde, is a gleaming vanilla-colored brain: the curvy landscape of hills and valleys (the gyri and sulci) that channeled the thoughts of the late mathematician Donald Coxeter, known as the man who saved geometry from near extinction in the 20th century.

“His brain is amazingly plump,” Dr. Witelson says. She ought to know.

Here at McMaster University, where she is a neuroscientist with the Michael G. DeGroote School of Medicine, Dr. Witelson has a collection of 125 brains. They are all from Canadians: business people, professionals, homemakers, and blue- and white-collar workers.

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

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Anthony H. Risser | |

Monday, October 23, 2006

Self-portraits of an Artist with Dementia

From The New York Times:

Self-Portraits Chronicle a Descent Into Alzheimer’s
By DENISE GRADY
The New York Times
Published: October 24, 2006

When he learned in 1995 that he had Alzheimer’s disease, William Utermohlen, an American artist in London, responded in characteristic fashion.

“From that moment on, he began to try to understand it by painting himself,” said his wife, Patricia Utermohlen, a professor of art history.

Mr. Utermohlen’s self-portraits are being exhibited through Friday at the New York Academy of Medicine in Manhattan, by the Alzheimer’s Association.

The paintings starkly reveal the artist’s descent into dementia, as his world began to tilt, perspectives flattened and details melted away. His wife and his doctors said he seemed aware at times that technical flaws had crept into his work, but he could not figure out how to correct them.

“The spatial sense kept slipping, and I think he knew,” Professor Utermohlen said. A psychoanalyst wrote that the paintings depicted sadness, anxiety, resignation and feelings of feebleness and shame.

Dr. Bruce Miller, a neurologist at the University of California, San Francisco, who studies artistic creativity in people with brain diseases, said some patients could still produce powerful work.

“Alzheimer’s affects the right parietal lobe in particular, which is important for visualizing something internally and then putting it onto a canvas,” Dr. Miller said. “The art becomes more abstract, the images are blurrier and vague, more surrealistic. Sometimes there’s use of beautiful, subtle color.”

Mr. Utermohlen, 73, is now in a nursing home. He no longer paints.

[ ... Read the full article, with slide show ... ]

~

From the website of The New York Academy of Medicine:

Art Exhibition: The Later Works of William Utermohlen

Location: The New York Academy of Medicine, Presidents Gallery

In 1995, the artist William Utermohlen was diagnosed with Alzheimer’s disease. It was then he embarked on a series of self-portraits that poignantly and powerfully depict his journey living with the disease. This exhibition showcases these later works where one can see the artist’s attempts to stay connected to the world around him while he loses the ability to communicate in other ways. His work remains a testimony to the creative and human spirit that resides in all people living with dementia. The exhibition is being hosted by the Alzheimer’s Association, New York City Chapter, and supported by Myriad Pharmaceuticals, Inc. A companion evening lecture event—Portraits & Promises in Alzheimer’s Disease—will be held on October 25, 2006.

The exhibition is free to the public and open daily from 9:00 AM to 5:00 PM from Sunday, October 22, to Friday, October 27, 2006.

For more information and to register contact Donald Morcone (212)822-7272, dmorcone@nyam.org

~

Anthony H. Risser | |

Saturday, October 21, 2006

FDA: Alzheimer Disease, Aricept (donepezil hydrochloride)

From the FDA last week:

FDA Approves Expanded Use of Treatment for Patients With Severe Alzheimer's Disease
FOR IMMEDIATE RELEASE
P06-168
October 13, 2006

Media Inquiries:
Susan Cruzan, 301-827-6242
Consumer Inquiries:
888-INFO-FDA

The Food and Drug Administration (FDA) today approved Aricept (donepezil hydrochloride) for the treatment of severe dementia in patients with Alzheimer's Disease.

Aricept was previously approved for the treatment of mild to moderate dementia of the Alzheimer's type.  It now becomes the first product approved for the treatment of all degrees of severity of the disease.

 "Alzheimer's Disease is a devastating, age-associated brain disorder that affects an estimated 4.5 million Americans -- and, as our population grows older, this number is expected to multiply," said Dr. Steven Galson, director of the Center for Drug Evaluation and Research. "Today's approval makes available another treatment for those with severe dementia."

FDA approved Aricept to treat patients with mild to moderate Alzheimer's Disease ten years ago after two clinical trials demonstrated that patients receiving the drug performed better than patients who received placebo. Today's approval is based on two additional randomized, placebo-controlled, 24-week clinical studies conducted in Sweden and Japan in more than 500 patients with severe Alzheimer's Disease.

In these studies, the effectiveness of treatment with Aricept was determined by evaluating the patients' cognitive functions such as memory, language, orientation and attention, as well as their overall functioning. The results showed that patients on Aricept performed better on both measures compared to placebo.

Aricept is manufactured by Eisai Inc., Teaneck, N.J.

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Anthony H. Risser | |

Brain Fiction

In the past two years there have been quite a number of fictional works dealing with the brain and its disorders.

I just found a new entry to that niche area of fiction in one of my neighborhood bookstores this afternoon: The Echo Maker by Richard Powers (FSG Press). The condition, Capgras. The dedication page, a quote by Luria.

Powers has done some remarkable fiction with the intertwine of Glenn Gould's recordings of Bach's Goldberg Variations and DNA in the massive The Gold Bug Variations and with medical science, artificial intelligence, and virtual reality in other works.

Thursday, October 19, 2006

Alzheimer Disease: New Clinical Trial Foci

From an NIH press release from 18 October 2006: 

New Alzheimer’s Clinical Trials To Be Undertaken by NIA Nationwide Consortium

The Alzheimer’s Disease Cooperative Study (ADCS), a federally-established consortium conducting clinical trials on Alzheimer’s disease (AD), will receive $52 million over six years to conduct several new trials, the National Institutes of Health (NIH) announced today. The award is a cooperative agreement between the NIH’s National Institute on Aging (NIA) and the University of California, San Diego (UCSD), which coordinates the consortium of nearly 70 sites in the United States and Canada.

The purpose of the award is to test drugs for their effectiveness in slowing down the progression or treating the symptoms of AD, as well as to investigate new methods for conducting dementia research. Specifically, researchers will focus on possible therapies aimed at affecting the beta amyloid peptide and the tau protein, both involved in the development of AD.

“We have learned a great deal from basic and observational research about how Alzheimer’s and other neurodegenerative diseases develop,” says Richard J. Hodes, M.D., Director of the NIA. “The consortium’s work will translate this knowledge in clinical trials of interventions that target the mechanisms underlying Alzheimer’s disease.”

Among the new studies to be undertaken are:


Docosahexaenoic Acid (DHA) — This trial will examine whether treatment with DHA, an omega-3 fatty acid found in fish, will slow decline in AD. Observational studies associate high fish consumption with reduced risk of AD in people, and studies in mouse models of AD show that dietary DHA reduces brain levels of beta amyloid, oxidative damage associated with beta amyloid, and neurotoxicity.


Intravenous Immunoglobulin (IVIg) — There is increased interest in passive immunization strategies against AD. IVIg contains naturally-occurring antibodies against beta amyloid, and preliminary studies have shown that IVIg may improve cognition. In addition, research has demonstrated that IVIg increased levels of anti-beta amyloid antibodies in plasma and promoted clearance of beta amyloid from cerebrospinal fluid. The new ADCS trial will more definitively demonstrate whether IVIg is useful clinically for treating AD.

Lithium — The biological activity of lithium, which has been shown in animal models to block abnormal changes in tau, has created interest in lithium as a novel treatment for AD. ADCS investigators will undertake a pilot biomarker study to see whether the drug can lower tau and beta amyloid levels in cerebrospinal fluid and be safely tolerated in older AD patients.

Home-Based Assessment — Older individuals, particularly the very elderly, may have physical, social and health limitations that make it difficult for them to take part in research trials. This study, conducted in people aged 75 and older, will examine the use of mail-in questionnaires, automated telephone technology and computerized data collection to assess cognitive, functional, and other factors in the home environment to see how home-based assessments might be used in primary prevention trials. Such an approach could significantly reduce the cost and increase the feasibility of participation in these long-term, costly clinical trials.



These projects join ongoing ADCS trials testing whether statins and high-dose folate/B6/B12 supplements can slow the clinical signs of AD, as well as a study of valproate to determine whether this drug can either slow decline or help delay the agitation and psychosis that often emerge in AD patients.

Leon Thal, M.D., chair of the Department of Neurosciences at the UCSD School of Medicine and principal investigator of the ADCS, notes that the selection of compounds for testing was enhanced by seeking ideas from the biotechnology sector as well as from individual investigators and the consortium’s members. “We have been able to bring together a larger universe of people studying therapies for Alzheimer’s, and I think this group of studies reflects new thinking in how to approach the disease,” he says.

This ADCS consortium was first established in 1991 as an infrastructure of leading researchers to carry out clinical trials for promising new therapies for AD. Investigators have tested such compounds as vitamin E, the anti-Parkinson’s disease drug selegiline, estrogen, anti-inflammatories and donepezil for their potential in slowing down or preventing cognitive impairment and/or dementia. Recently, positive but limited effects have been shown in slowing the development of dementia with donepezil.

To date, approximately 4,600 people have participated in the ADCS studies. Neil Buckholtz, Ph.D., who leads the federal government’s partnership with the consortium as chief of the Dementias of Aging Branch of the NIA, recognized the efforts of the study participants and their families. “Participating in research takes time and dedication, and the efforts of the participants and their families stand out,” Buckholtz notes. “We are deeply grateful for their help in finding new and better ways to treat and prevent Alzheimer’s disease.” As the new round of trials gets underway, stepped up public participation will be essential for their success, Buckholtz says, and he urges the public to learn more about how to take part in such research. (See information, below)

Alzheimer’s disease affects an estimated 4.5 million people in the U.S. It increases dramatically with age, affecting approximately 40-50 percent of people age 85 and older. The numbers of people with AD are expected to rise dramatically with the aging of the population over the next few decades.

The NIA, one of 27 institutes and centers at the NIH, is part of the U.S. Department of Health and Human Services. It leads the federal effort to support and conduct basic, clinical, and social and behavioral studies on aging generally and AD specifically. NIA supports the Alzheimer’s Disease Education and Referral (ADEAR) Center, which provides information on clinical studies and other research to the public, health professionals, and the media. ADEAR can be contacted toll-free at 1-800-438-4380 or by viewing www.nia.nih.gov/alzheimers.

As the studies mentioned above move forward, more information will be available at the ADEAR website about participation. NIA invites the public to sign up for e-mail alerts, which will let subscribers know when trials begin recruitment and generally when new information about AD is available.

A list of the 35 primary ADCS sites appears on the NIA website at website.

The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih.gov.

Sleep Deprivation and Learning

From the Science website:

Asleep at the Memory Wheel

By Greg Miller
ScienceNOW Daily News

18 October 2006

ATLANTA, GEORGIA--Going a night without sleep may cause your hippocampus to go on strike. A new study has caught this crucial memory-encoding brain region slacking off in college students the day after they've pulled an all-nighter. The study is one of the first to investigate how sleep deprivation interferes with memory mechanisms in the human brain.

Neuroscientist Matthew Walker of Harvard University and his colleagues paid 10 undergraduate students to forgo a night's sleep. The next day, the students viewed a series of 30 words, and two days later--after having two nights to catch up on their sleep--the students returned to the lab and took a test to see how well they remembered the words they'd seen.

The students recalled about 40% fewer words overall than a group of 10 students who had slept normally, Walker reported here yesterday at the annual meeting of the Society for Neuroscience. But the researchers also found that the emotional content of the words made a big difference in what people remembered. Previous studies have found that both positive and negative emotions bolster memory, but in the current study, negatively charged words (such as cancer or jail) seemed to penetrate the sleep-deprived brain more deeply than positive ones (such as happy or sunshine). Indeed, sleep-deprived students were only 19% worse than their well-rested counterparts at remembering negative words, but 59% worse
for positive words. Walker suspects the difference may reflect an evolutionary safeguard against forgetting potential threats.

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

Tuesday, September 26, 2006

The Brain that Squeaked

From today's New York TImes:

Atlas Squeaked: A Complete Map of the Brain of a Mouse
By NICHOLAS WADE
Published: September 26, 2006
The New York Times

Scientists have gained a new window for peering into the brain, courtesy of a $41 million project financed by Paul G. Allen, the co-founder of Microsoft.

The project is an electronic atlas that shows which genes are switched on in neurons throughout the brain of a mouse.

Instead of looking at one gene at a time in one or a few neurons, researchers can now study all the brain genes systematically. And instead of having to visualize each gene experimentally, everything is available online. “I am using it all the time,” said Catherine Dulac, who studies mouse behavior at Harvard. “It’s an extraordinary resource.”

Marc Tessier-Lavigne, an expert on neuronal signaling and vice president for research at Genentech, said he would put the new brain atlas “on a par with the human genome project.” Both are members of the scientific advisory board overseeing the project.

Thomas M. Jessel, a neuroscientist at Columbia University, said after looking at the atlas that it was of high quality and would complement other available brain maps.

“It is likely to be the standard source for the next few years” for people interested in the pattern of gene activation in the brain,” Professor Jessel said.

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

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Anthony H. Risser | |

Abstract of the Day: Alzheimer Disease Drug Treatments

Brinton RD & Wang JM (2006). Therapeutic potential of neurogenesis for prevention and recovery from Alzheimer's disease: allopregnanolone as a proof of concept neurogenic agent. Curr Alzheimer Res., 3(3), 185-190.

Department of Molecular Pharmacology and Toxicology and Program in Neuroscience, Pharmaceutical Science Center, 1985 Zonal Avenue, University of Southern California, Los Angeles, CA 90033, USA.

A major challenge not yet addressed by current therapeutic interventions for Alzheimer's disease (AD) is the regeneration of lost neurons and neural circuitry to restore cognitive function. Therapies that lead to cessation of the degenerative process still leave the brain riddled with deteriorated neural circuits and reduced neuron number. The discovery of neurogenesis in the adult brain and the regenerative potential of neural stem cells holds the promise for restoration of neural populations and regeneration of neural circuits necessary for cerebral function. While the regenerative potential of neural stem cells is great, so too is the challenge of delivering neural stem cells to the brain. Basic science analyses and human trials indicate that constituents of microenvironments within the brain determine the neurogenic potential, phenotypic differentiation of neural stem cells and magnitude of the neural stem cell pool. Multiple analyses have documented that dentate neurogenesis is regulated by multiple growth factors which are abundant during development and which dramatically decline with age. While the cause(s) of age-associated decline in neurogenesis remains to be fully determined, loss in growth factors, FGF-2, IGF-1 and VEGF, in the microenvironment of the subgranular zone (SGZ) are prime contributors to the reduced neurogenic potential. The decline in dentate neurogenesis can be observed as early as middle age. In the aged and AD brain, both the pool of neural stem cells and their proliferative potential are markedly diminished. In parallel, the level of potential regenerative factors is diminished in the brains of Alzheimer's patients compared to age-matched controls. Our efforts have been directed towards discovery and development of small, blood brain barrier penetrant molecules to promote endogenous proliferation of neural stem cells within the brain. These endeavors have led to the discovery that the neurosteroid alloprognanolone (APalpha) is a potent and highly efficacious proliferative agent in vitro and in vivo of both rodent and human neural stem cells. Results of our in vitro studies coupled with our more recent analyses in the triple transgenic mouse model of AD suggest that APalpha is a promising strategy for promoting neurogenesis in the aged brain and potentially for restoration of neuronal populations in brains recovering from neurodegenerative disease or injury. A brief overview of issues impacting the therapeutic potential of neurogenesis and the factors used to promote neurogenesis in the aging and degenerating brain is presented. Also included is a review of our current research into the neurogenic potential of the small molecule, blood brain barrier penetrating, neurosteroid allopregnanolone (APalpha).

PMID: 16842093 [PubMed - indexed for MEDLINE]

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Anthony H. Risser | |

Sunday, September 17, 2006

Beck Gets a Lasker

From today's Philadelphia Inquirer:

Penn psychiatrist to be honored today
Aaron T. Beck will receive the prestigious Lasker Award for his pioneering work in cognitive therapy.
By Josh Goldstein
Inquirer Staff Writer
17 September 2006

In the 1960s, University of Pennsylvania psychiatrist Aaron T. Beck began to develop the theories and practice of a new branch of psychoanalysis known as cognitive therapy.

Beck's more than 40 years of pioneering work at Penn is being honored today with the prestigious Albert Lasker Award for Clinical Medical Research.

The Lasker awards are given annually for "stunning" achievements in basic and clinical research in medicine. The awards are often likened to Nobel Prizes and come with a $100,000 honorarium.

Cognitive therapy, which treats mental problems including depression, anxiety disorders and phobias, is based on the premise that thoughts, feelings and actions are interwoven. Patients are taught to identify their negative, sometimes irrational patterns of thought and replace them with more realistic, helpful ones.

Beck's development of cognitive therapy "is one of the most important advances - if not the most important advance - in the treatment" of depression and other anxiety disorders in the last 50 years, said Joseph L. Goldstein, a 1985 Nobel laureate for medicine and chairman of the jury of researchers who selected the latest Lasker winners.

"This was really quite an unexpected, but very much appreciated, honor," Beck said.

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

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Anthony H. Risser | |

Friday, September 08, 2006

Abstract of the Day: Alzheimer Disease

Pavlik VN, Doody RS, Massman PJ, & Chan W. (2006). Influence of premorbid IQ and education on progression of Alzheimer's Disease. Dementia, Geriatrics, & Cognitive Disorders,22(4), 367-377. [Epub ahead of print]

Department of Family and Community Medicine, Baylor College of Medicine, Houston, Tex., USA.

Background: Lower education is associated with a higher risk of developing Alzheimer's disease (AD). Years of education and measures of general intellectual function (IQ) are highly correlated. It is important to determine whether there is a relationship between education and AD outcomes that is independent of IQ. Objective: To test the hypothesis that premorbid IQ is a stronger predictor of cognitive decline, global progression, and overall survival, than education in patients with AD. Methods: The study included 478 probable AD patients (322 women and 156 men, mean age 74.5 years) followed in a large AD referral center for a mean of 3.2 years. Eligible participants had a baseline estimate of premorbid IQ using the American version of the Nelson Adult Reading Test (AMNART) and at least one follow-up visit with complete neuropsychological assessment. We used random effects linear regression analysis, and Cox proportional hazards analysis to determine whether or not education and/or premorbid IQ were independently associated with cognitive decline, global progression of AD, and survival. Results: When the baseline AMNART score was included in regression models along with education and other demographic variables, AMNART score, but not education, was associated with a higher baseline score and slower rate of decline in MMSE and ADAS-Cog scores, and the Clinical Dementia Rating sum of boxes score. Neither higher premorbid IQ nor higher education was associated with longer survival. Conclusions: We conclude that a baseline AMNART score is a better predictor of cognitive change in AD than education, but neither variable is associated with survival after diagnosis. Copyright (c) 2006 S. Karger AG, Basel.

PMID: 16954693 [PubMed - as supplied by publisher]

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Anthony H. Risser | |

Thursday, September 07, 2006

Knockout Mice are the Bomb!

From an NIH press release from earlier today:

NIH Launches Knockout Mouse Project
Genome-Wide Public Resource Will Provide New Mouse Models for Understanding Human Disease


The National Institutes of Health (NIH) today awarded a set of cooperative agreements, totaling up to $52 million over five years, to launch the Knockout Mouse Project. The goal of this program is to build a comprehensive and publicly available resource of knockout mutations in the mouse genome. The knockout mice produced from this resource will be extremely useful for the study of human disease.

The NIH Knockout Mouse Project will work closely with other large-scale efforts to produce knockouts that are underway in Canada, called the North American Conditional Mouse Mutagenesis Project (NorCOMM), and in Europe, called the European Conditional Mouse Mutagenesis Program (EUCOMM). The objective of all these programs is to create a mutation in each of the approximately 20,000 protein-coding genes in the mouse genome.

“Knockout mice are powerful tools for exploring the function of genes and creating animal models of human disease. By enabling more researchers to study these knockouts, this trans-NIH initiative will accelerate our efforts to translate basic research findings into new strategies for improving human health,” said NIH Director Elias A. Zerhouni, M.D. “It is exciting that so many components of NIH have joined together to support this project, and that the NIH Knockout Mouse Project will be working hand-in-hand with other international efforts. This is scientific teamwork at its best.”

Knockout mice are lines of mice in which specific genes have been completely disrupted, or “knocked out.” Systematic disruption of each of the 20,000 genes in the mouse genome will allow researchers to determine the role of each gene in normal physiology and development. Even more importantly, researchers will use knockout mice to develop better models of inherited human diseases such as cancer, heart disease, neurological disorders, diabetes and obesity. Recent advances in recombinant DNA technologies, as well as completion of the mouse genome sequence, now make this project feasible.

NIH today awarded five-year cooperative agreements totaling up to $47.2 million to two groups for the creation of the knockout mice lines. Recipients of those awards are Regeneron Pharmaceuticals, Inc., in Tarrytown, N.Y., and a collaborative team from Children’s Hospital Oakland Research Institute (CHORI) in Oakland, Calif.; the School of Veterinary Medicine, University of California, Davis (UC Davis); and the Wellcome Trust Sanger Institute in Hinxton, England.

In addition, NIH awarded another five-year cooperative agreement totaling $2.5 million to the Jackson Laboratory in Bar Harbor, Maine for the establishment of a NIH Knockout Mouse Project data coordination center. Finally, NIH awarded cooperative agreements to the University of Pennsylvania in Philadelphia and to the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto to improve the efficiency of methods for creating knockout lines. Those agreements total about $2.5 million and run for three and two years, respectively.

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

NIH Knockout Mouse Project website
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Anthony H. Risser | |

Wednesday, September 06, 2006

p16-Ink4a

From The New York Times:
Gene Found to Switch Off Stem Cells During Aging
By NICHOLAS WADE

Published: September 6, 2006

Biologists have uncovered a deep link between lifespan and cancer in the form of a gene that switches off stem cells as a person ages.

The critical gene, already well known for its role in suppressing tumors, seems to mediate a profound balance between life and death. It weighs the generation of new replacement cells, required for continued life, against the risk of death from cancer, which is the inevitable outcome of letting cells divide. To offset the increasing risk of cancer as a person ages, the gene gradually reduces the ability of stem cells to proliferate.

The new finding, reported by three groups of researchers online Wednesday in Nature, was made in a special breed of mice that lack the pivotal gene, but is thought likely to apply to people as well.

The finding indicates that many of the degenerative diseases of aging are caused by an active shutting down of the stem cells that renew the body’s various tissues, and are not just a passive disintegration of tissues under life’s daily wear and tear, as is often assumed.

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

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Anthony H. Risser | |

Tuesday, August 22, 2006

Somatization Disorder

From today's New York Times:

Doctors Give Hope to Patients With Long Histories of Unexplained Symptoms
By DAN HURLEY
22 August 2006

People with a long history of medically unexplained symptoms — aches, pains, fatigue, dizziness and other complaints for which doctors can find no physical cause — might finally find relief.

Two new studies by researchers who specialize in the baffling condition called somatization syndrome, estimated to affect up to 3 percent of adults, suggest that the quest for a physical explanation may take on a destructive life of its own. Instead, those with the syndrome should focus on practical strategies to regain normal function and relieve symptoms, the researchers say.

One study, by German scientists, sought to explain why the doctors’ reassurances were generally ineffective with such patients. The researchers played taped comments by a doctor about a hypothetical patient for two groups of participants, people who had the syndrome and people who did not. Those with somatization syndrome were three times as likely to believe incorrectly that in the course of the comments the doctor had said the symptom had a worrisome physical cause.

The findings, in the August issue of the online journal Public Library of Science Medicine, offer at least a partial explanation for why patients often go from doctor to doctor and take test after test in a fruitless search for answers: repeated reassurances are simply not being understood.

A second study, by New Jersey researchers, provides the first published evidence of an effective clinical treatment. The study, in the July 24 issue of The Archives of Internal Medicine, found that patients benefited from 10 sessions of cognitive behavioral therapy specifically organized to help relieve their stress and increase emotional awareness and to get them to become more socially active and think differently about their symptoms.

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

Wednesday, August 09, 2006

Abstract of the Day: Rater Training and the NIH Stroke Scale (NIHSS)

Josephson SA, Hills NK, & Johnston SC (2006). NIH Stroke Scale reliability in ratings from a large sample of clinicians.. Cerebrovascular Disorders,, 22(5-6), 389-395

Objective: The NIH Stroke Scale (NIHSS) is widely used in stroke clinical care and trials. Certification in its use, most commonly through rating of video vignettes, is routinely required. To investigate the reliability of the NIHSS in a representative sample of raters, we examined the results of the most frequently used certification examination. Methods: At the invitation of the National Stroke Association, we analyzed the results of all raters who completed one of two multiple patient videotaped certification examinations from 1998 to 2004. Total scores for each vignette were calculated and ratings were compared based on percentile of responses and modified kappa scores. Results: There were 7,405 unique raters with 38,148 individual NIHSS item responses; median scores for each vignette ranged from 0 to 31. Total NIHSS scores varied widely between raters; scoring for 7 of the 11 patients (64%) had a four or more point difference in NIHSS score from the 5th to 95th percentile. The aphasia (kappa = 0.60) and facial palsy (0.65) items on the test contributed most to the variance in the total NIHSS score. Nurses agreed with the most common response on scoring more frequently than physicians (p < 0.0001). Taking the certification examination multiple times did not improve agreement. Conclusions: In a large diverse sample of clinicians, inter-rater reliability for individual elements of the NIHSS on videotaped vignettes was generally good, but overall scoring was inconsistent and could impact clinical trial results. Whether additional training, modification of examination elements, or clearer definitions for scoring could improve reliability requires further study. Copyright (c) 2006 S. Karger AG, Basel.

PMID: 16888381 [PubMed - as supplied by publisher]

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Anthony H. Risser | |

Sunday, July 30, 2006

Abstract of the Day: Of Time and the River

Takahashi T. Time-estimation error following Weber-Fechner law may explain subadditive time-discounting.. Medical Hypotheses. 2006 Jul 25; [Epub ahead of print]

Department of Cognitive and Behavioral Science, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.

Impulsivity in drug addicts have been associated with impatience in intertemporal choice, i.e., high degrees to which delayed rewards are discounted, indicating the importance of reducing the degree of discounting in drug addicts. Intertemporal choice (delay discounting) has been attracting attention in neuropsychopharmacology and behavioral neuroeconomics. Recently, behavioral economists have reported that impatience/impulsivity in intertemporal choice is increased if a delay period is presented as a sum of divided time-blocks, which is referred to as subadditive discounting (i.e., "total patience" over the delay period is larger than the "sum of patience" over divided delay periods). This finding implies that abstinent drug addicts may more readily relapse into addiction if an abstinence period is presented as a series of shorter abstinent periods, rather than a single block of a long abstinence period. Therefore, understanding of neuropsychological processing underlying subadditive discounting is important for establishing medical treatments of drug addiction, although to date, no study has addressed this question. In this study, we propose that time-estimation following Weber-Fechner law, formerly introduced for explaining hyperbolic discounting, may also explain subadditive discounting. Our present hypothesis also predicts that possibility of relapse into drug dependence can be decreased by helping abstinent patients to perceive time-duration of an abstinence/withdrawal period precisely.

PMID: 16872753 [PubMed - as supplied by publisher]

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Anthony H. Risser | |

Sunday, July 23, 2006

Upcoming Event: Zurich, 26-30 July 2006

International Neuropsychological Society (INS) mid-year conference taking place this week in Zurich, Switzerland. Visit the conference website for more information: website.

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Anthony H. Risser | |

Saturday, July 15, 2006

Virginia Apgar!

Most everyone reading this will have had a closer degree of connection with Virginia Apgar than they know. Who is Virginia Apgar, you ask? When born, most of you will have received an Apgar Score in the delivery room. She created it. Did you know?... (grin)




From an NIH press release on the 13th of July:

Papers of Virginia Apgar Added to National Library of Medicine's Profiles in Science Web Site

Bethesda, Maryland - The National Library of Medicine's Profiles in Science Web site has been enriched by the addition of the papers of Virginia Apgar, M.D., creator of the widely used Apgar Score to evaluate newborns. The Library has collaborated with the Mount Holyoke College Archives and Special Collections to digitize her papers and make them widely available. This brings to 18 the number of notable scientists who have personal and professional records included in Profiles. The site is at http://www.profiles.nlm.nih.gov.

In 1949, faced with unacceptably high newborn mortality rates in her hospital's maternity ward, Virginia Apgar (1909-1974), an anesthesiologist, set out to ensure that newborns in distress got the prompt attention they needed. Using the same signs anesthesiologists monitored during and after surgery - heart rate, respiration, reflex irritability, muscle tone, and color - she developed a simple, rapid method for assessing the medical condition of newborn babies. Quickly adopted by obstetric teams, her method (now known as the Apgar Score) reduced infant mortality and laid the foundations of neonatology.

"Dr. Apgar brought enormous intelligence and energy to everything she did. Her newborn scoring method put neonatology on a firm scientific basis, and she made substantial contributions to anesthesiology and the study of birth defects. I personally found her a memorable and inspiring teacher," said Donald A. B. Lindberg, M.D., Director of the National Library of Medicine.

Born on June 7, 1909, in Westfield, New Jersey, Apgar attended Mount Holyoke College, and then received her M.D. from the Columbia University College of Physicians and Surgeons in 1933. Although she completed a two-year surgical internship at New York's Presbyterian Hospital, her mentor there discouraged her from pursuing a surgical career, noting that women surgeons rarely achieved financial success. Instead he recommended that she enter anesthesiology, then a new medical specialty. Apgar subsequently trained with anesthesiology pioneer Ralph Waters at the University of Wisconsin, and in 1938 returned to Presbyterian Hospital as the director of a new Division of Anesthesia. She transformed the anesthesia service during the next decade, establishing an anesthesiology education program and replacing nurse-anesthetists with physicians.

In 1949, Apgar was appointed a full professor of anesthesiology and she stepped down as director of the Division of Anesthesia. Free of administrative duties, she continued to teach and devoted more time to research in obstetrical anesthesia. Within three years, she developed the Apgar scoring method, and started using score data from thousands of infants to assess the results of obstetric practices, types of maternal pain relief, and effects of resuscitation.

Apgar was a legendary clinical teacher, well known for her fierce dedication to patients of all ages. She kept basic resuscitation equipment with her at all times, both on and off duty, explaining, "Nobody, but nobody is going to stop breathing on me!"

[ .. Read the full release ... ]
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Anthony H. Risser | |

Monday, July 10, 2006

New Books from The Dana Center

I received a couple of new books on neuroethics from The Dana Center. The first one I started to read is Mind Wars: Brain Research and National Defense by bioethicist Jonathan D. Moreno, Ph.D. It's been a fascinating read so far.

The cover blurb points to coverage of how neuroscience may influence warfare and the ethical and policy issues that are likely to be confronted.

I'm curious as to what arguments and points will emerge in Moreno's presentation!

The other book is Hard Science, Hard Choices: Facts, Ethics, and Policies Guiding Brain Science Today by Sandra J. Ackerman.

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Anthony H. Risser | |

Saturday, July 08, 2006

Media: Hemispherectomy in The New Yorker

Last week's issue of The New Yorker (03 July 2006) included an excellent Annals of Medicine essay on hemispherectomy, The Deepest Cut, written by Christine Kenneally. She follows the lives of two individuals, Lacy and Christina, and provides a succinct overview to the indications for this operative procedure and its outcomes.
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Anthony H. Risser | |

Wednesday, July 05, 2006

Abstract of the Day: Alzheimer Disease

Cummings JL, McRae T, & Zhang R. (2006). Effects of donepezil on neuropsychiatric symptoms in patients with dementia and severe behavioral disorders. American Journal of Geriatric Psychiatry, 14(7), 605-612.

Departments of Neurology and Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, California (JLC); and Pfizer, Inc., New York, New York (TM, RZ).

Objective: The objective of this study was to conduct exploratory analyses of data pertaining to the efficacy of donepezil treatment of patients with severe behavioral disturbances. Preliminary studies suggest that cholinesterase inhibitors, including donepezil, may reduce behavioral disturbances in patients with Alzheimer disease (AD). Most patients included in clinical trials have had low levels of psychopathology at baseline, and the effect of cholinesterase inhibitors on patients with more severe behavioral disturbances is unknown. The authors report the effects of donepezil on behavioral disturbances in patients with relatively severe psychopathology at baseline. Methods: This is a hypothesis-driven secondary analysis of a three-phase study involving donepezil and sertraline. In phase 1, psychotropic agents were withdrawn; in phase 2, patients were treated in an open-label fashion with donepezil for 8 weeks; and in phase 3, patients on donepezil were randomized to receive placebo or sertraline for an additional 12 weeks. The data set analyzed is comprised of the patient population treated with donepezil (without sertraline) for 20 weeks. One hundred twenty patients were included in the analyses. Mean age was 76 years, average Mini-Mental State Examination Score was 18, and mean Neuropsychiatric Inventory (NPI) total score was 30. Primary efficacy assessments were the NPI, the Clinical Global Impression-Improvement, and the Clinical Global Impression-Severity scales. Secondary measures included the Behavioral Pathology in Alzheimer's Disease Rating Scale, The Hamilton Depression Rating Scale, and the Alzheimer's Disease Functional Assessment and Change Scale. Results: Excellent concurrent validity was noted between the NPI and the Behavioral Pathology in Alzheimer's Disease Rating Scale. The total score of the NPI was significantly reduced over the 20 weeks of therapy with donepezil. Sixty-two percent of patients had at least a 30% reduction in the total NPI score (significantly greater than the number with no meaningful response). Likewise, more patients had total or partial resolution of depression and delusions than those who had no meaningful change. Factor analysis of baseline NPI data revealed five factors, including a psychosis factor, an agitation factor, mood factor, frontal lobe function factor, and appetite and eating disorders factor. Clinically meaningful treatment effect sizes were notable for the delusion factor (0.340) and the mood factor (0.39). There were significant correlations between the Clinical Global Impression-Improvement and reductions in mood and agitation scores. Conclusion: The results of these analyses suggest that donepezil reduces behavioral symptoms, particularly mood disturbances and delusions, in patients with AD with relatively severe psychopathology.

PMID: 16816014 [PubMed - in process]
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Anthony H. Risser | |

Parkinson Disease

From an NIH press release on 04 July 2006:

Dopamine Drug Leads to New Neurons and Recovery of Function in Rat Model of Parkinson's Disease

In preliminary results, researchers have shown that a drug which mimics the effects of the nerve-signaling chemical dopamine causes new neurons to develop in the part of the brain where cells are lost in Parkinson's disease (PD). The drug also led to long-lasting recovery of function in an animal model of PD. The findings may lead to new ways of treating PD and other neurodegenerative diseases. The study was funded in part by the NIH's National Institute of Neurological Disorders and Stroke (NINDS).

The study suggests that drugs which affect dopamine D3 receptors might trigger new neurons to grow in humans with the disease. Some of these drugs are commonly used to treat PD. The finding also suggests a way to develop new treatments for PD. The results appear in the July 5, 2006, issue of The Journal of Neuroscience.

[snip]

The new study, conducted by Christopher Eckman, Ph.D., and Jackalina Van Kampen, Ph.D., at the Mayo Clinic College of Medicine in Jacksonville, Florida, focused on a second possible way to restore function — prompting stem cells that normally remain dormant in the adult brain to develop into neurons. While most researchers previously believed the adult brain could not develop new neurons, recent studies have shown that the brain contains stem cells and that new neurons can develop in some regions. Studies by Dr. Van Kampen and others also have shown that drugs which affect dopamine D3 receptors can trigger development of new neurons (a process called neurogenesis) in the brains of adult rats. Until now, however, no one had shown that the newly developed neurons could connect with other parts of the brain and restore function.

"This is the first study to show that endogenous neurogenesis [development of new neurons from cells already in the brain] can lead to recovery of function in an animal model of Parkinson's disease," says Dr. Eckman.

[ ... Read the full release ... ]
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Anthony H. Risser | |

Monday, July 03, 2006

Pushing Alzheimer Research Forward

Zach Lynch of Brain Waves points to a recent Op-Ed piece in The Washington Post by the CEO of Wyeth, Robert Essner:

Read the post, with a link to the piece

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Anthony H. Risser | |

Ants!

From the Canadian Broadcasting Corporation (CBC):
Ants walk using internal distance clock: Study
Last Updated Fri, 30 Jun 2006 15:43:19 EDT
CBC News

Desert ants have an internal pedometer that measures how far they've marched, researchers have found.

Foraging Sahara Desert ants wander when searching for food, but take a relatively straight path when heading back to their nests.

To do so, the ants need to judge directions and distances when travelling over flat, sandy terrain without landmarks. Scent trails used by other species won't work because the odours fade in the hot desert.

[...continues...]

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

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Anthony H. Risser | |

Thursday, June 29, 2006

Meningitis

From The New York Times:
City Tackles Meningitis in Brooklyn
By RICHARD PÉREZ-PEÑA
The New York Times
29 June 2006

City health officials yesterday announced a novel assault on a large meningitis outbreak in Brooklyn, seeking to vaccinate thousands of drug users and others in and around Bedford-Stuyvesant against the bacterium that has sickened 23 people and killed eight of them.

That group of cases, over the past seven months, "is one of the largest outbreaks of meningitis described in the U.S. literature in the last couple of decades," said Health Commissioner Thomas R. Frieden. And the department's response, a mass vaccination for meningococcal meningitis, made possible by a new, more effective vaccine, appears to be the first in the city's history, he said.

[ ... Read the full article ... ]
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Anthony H. Risser | |