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)

Saturday, January 12, 2008

Hippocampus: Mind Hacks Catches A Taxi

The excellent neuroblog, Mind Hacks, has a post today that includes discussion about a program of research examining the hippocampal structures of professional navigators (e.g., taxi drivers) - research with fascinating neuropsychological results.

The Mind Hacks post can be read at: post.

A link to a .pdf of one of these publications can be found at: London Taxi Drivers and Bus Drivers: A Structural MRI and Neuropsychological Analysis. I am off to read this paper right now, which was published in 2006 in the journal Hippocampus.

Thursday, January 10, 2008

Obit: Dr. Paul MacLean

From The New York Times:

Paul MacLean, 94, Neuroscientist Who Devised ‘Triune Brain’ Theory, Dies
Published: January 10, 2008

Dr. Paul D. MacLean, a neuroscientist and psychiatrist who developed the intriguing theory of the “triune brain” to explain its evolution and to try to reconcile rational human behavior with its more primal and violent side, died on Dec. 26 in Potomac, Md. He was 94.

Dr. MacLean’s death was confirmed by his family.

In the late 1940s, while he was a young researcher at Yale, Dr. MacLean became interested in the brain’s control of emotion and behavior. After initial studies of brain activity in epileptic patients, he turned to cats, monkeys and other models, using electrodes to stimulate different parts of the brain in conscious animals. He then recorded the animals’ responses and, in the 1950s, began to trace individual behaviors like aggression and sexual arousal to their physiological sources.

Dr. MacLean (pronounced mac-LANE) termed the brain’s center of emotions the limbic system, and described an area that includes structures called the hippocampus and amygdala. Developing observations made by Dr. James W. Papez of Cornell, he proposed that the limbic system had evolved in early mammals to control fight-or-flight responses and react to both emotionally pleasurable and painful sensations. The concept is now broadly accepted in neuroscience.

Dr. MacLean said that the idea of the limbic system leads to a recognition that its presence “represents the history of the evolution of mammals and their distinctive family way of life.”

In the 1960s, Dr. MacLean enlarged his theory to address the human brain’s overall structure and divided its evolution into three parts, an idea that he termed the triune brain. In addition to identifying the limbic system, he pointed to a more primitive brain called the R-complex, related to reptiles, which controls basic functions like muscle movement and breathing. The third part, the neocortex, controls speech and reasoning and is the most recent evolutionary arrival.

In Dr. MacLean’s theory, all three systems remain in place and in frequent competition; indeed, their conflicts help explain extremes in human behavior.

In the 1970s and ’80s, aspects of Dr. MacLean’s model were popularized by the astronomer Carl Sagan and the novelist Arthur Koestler.

[ ... Read the full obit ... ]

Wednesday, January 09, 2008

"Sleeping sickness” (Human African Trypanosomiasis)

From yesterday's New York Times:

Jump-Start on Slow Trek to Treatment for a Disease
Published: January 8, 2008

Last month, the Bill and Melinda Gates Foundation donated $19 million to the Drugs for Neglected Diseases Initiative to further one of its goals: finding a new drug for African sleeping sickness.

Not that $19 million will come close to doing that. Even if a miracle cure is found, it will take lab work and clinical trials that could easily cost $100 million to prove it is really a miracle and not the Vioxx of the African savannah.

But the gift spotlights just how tricky the search for new treatments can be when the disease is fearsome but nearly forgotten because its victims are poor and obscure.

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

Voxel-Based Lesion-Symptom Mapping

Today's abstract included mention of voxel-based lesion-symptom mapping. Here is a .pdf publication that outlines the technique: paper.

Musical Alzheimer's Tribute: Victoria, British Columbia

From the Times-Columnist:

Symphony starts the year with 'bigger bag of tricks'

PREVIEW What: Victoria Symphony with clarinetist Simon Aldrich When and Where: 7:30 p.m., Jan. 5 at the Mary Winspear Centre in Sidney; 2:30 p.m., Jan. 6 and 8 p.m., Jan. 7 at the Royal Theatre Tickets: For the Sidney concert, tickets are $26/29, available at the box office (656-0275). For the Victoria concerts, tickets are $13.50 to $27.25, available at the box office (385-6515). For more information, visit:

Sarah Petrescu , Times Colonist
Published: Thursday, January 03, 2008

When Victoria Symphony Maestra Tania Miller and her team plan a season of concerts, they are driven by the artists, pieces and instruments they want to shine the spotlight on.

This year, Miller wanted to highlight a wind instrument. She chose contemporary composer John Adams's piece Gnarly Buttons, "a phenomenally challenging, funky piece," she says, and recruited Montreal clarinetist Simon Aldrich to tackle it.
"He's incredibly talented and has worked with Tim many times," Miller says, referring to guest conductor Timothy Vernon.

Vernon will conduct the orchestra's first concerts of 2008 in Sidney and Victoria this week. They feature the debut of new concertmaster Terence Tam and a 200th-anniversary performance of Ludwig van Beethoven's Symphony No. 5.

Aldrich performed Gnarly Buttons with Vernon six years ago in London, Ont., where he grew up. Vernon is music director and principal conductor of Orchestra London, in addition to his role as artistic director of Pacific Opera Victoria.

"It's one of my favourite pieces, very eclectic," says Aldrich, 42. "I feel connected to it on many levels."

Part of that connection, Aldrich says, comes from the way Adams shared his inspiration for the piece: His father's battle with Alzheimer's disease.

"It's his most biographical piece, a tribute to his father," Aldrich says. "John Adams, as a clarinetist, wrote it to be difficult to play -- and it is."

In his note about the piece, Adams writes about how his father taught him to play clarinet. When his father fell victim to Alzheimer's he became obsessed with his clarinets. Convinced someone was trying to break into their New Hampshire home to steal them, he hid them in the laundry hamper. Not long after, Adams's mother sent the instruments to him, where they collected dust until long after his father's death. Adams was nearing 50 when he composed this piece, his first for clarinet.

"The three movements are very different," Aldrich says. "The first has that Benny Goodman and Mozart influence [favourites of the elder Adams]."

The second movement, Hoe-down (Mad Cow), calls for banjo and has a western feel.

"Adams premiered the piece at the height of Mad Cow in England, so there's a bitter twist there," Aldrich says.

The third movement, Put Your Loving Arms Around Me, reflects the degenerating effects of Alzheimer's.

Aldrich says contemporary music makes up a large part of his career as a solo clarinetist. He splits his time between solo work and playing with the Montreal Metropolitan Orchestra.

"The clarinet repertoire picks up in the contemporary period and includes a lot of elements like jazz and extended techniques," Aldrich says. "This is why contemporary composers like to write for the clarinet; it can go from the range of a flute down to an organ. We have a bigger bag of tricks."

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

Neuropsychology Abstract of the Day: Parietal Function

Haramati S, Soroker N, Dudai Y, & Levy DA. The posterior parietal cortex in recognition memory: A neuropsychological study. Neuropsychologia. 2007 Nov 29 [Epub ahead of print]

Department of Neurobiology, Weizmann Institute of Science, P.O. Box 26, Rehovot 76100, Israel.

Several recent functional neuroimaging studies have reported robust bilateral activation (L>R) in lateral posterior parietal cortex and precuneus during recognition memory retrieval tasks. It has not yet been determined what cognitive processes are represented by those activations. In order to examine whether parietal lobe-based processes are necessary for basic episodic recognition abilities, we tested a group of 17 first-incident CVA patients whose cortical damage included (but was not limited to) extensive unilateral posterior parietal lesions. These patients performed a series of tasks that yielded parietal activations in previous fMRI studies: yes/no recognition judgments on visual words and on colored object pictures and identifiable environmental sounds. We found that patients with left hemisphere lesions were not impaired compared to controls in any of the tasks. Patients with right hemisphere lesions were not significantly impaired in memory for visual words, but were impaired in recognition of object pictures and sounds. Two lesion-behavior analyses - area-based correlations and voxel-based lesion symptom mapping (VLSM) - indicate that these impairments resulted from extra-parietal damage, specifically to frontal and lateral temporal areas. These findings suggest that extensive parietal damage does not impair recognition performance. We suggest that parietal activations recorded during recognition memory tasks might reflect peri-retrieval processes, such as the storage of retrieved memoranda in a working memory buffer for further cognitive processing.

PMID: 18178228 [PubMed - as supplied by publisher]

Sunday, January 06, 2008

Neuropsychology Abstract of the Day: Parkinson's Disease

Bohnen NI, Kuwabara H, Constantine GM, Mathis CA, & Moore RY. Grooved pegboard test as a biomarker of nigrostriatal denervation in Parkinson's disease. Neuroscience Letters. 2007 September 13; 424(3): 185-189.

Department of Radiology, University of Michigan, Ann Arbor, MI 48109-0028, USA.

Recent pharmacotherapy trials in Parkinson's disease (PD) using dopaminergic neuroimaging as outcome parameter failed to show significant relationships between imaging and clinical results. One possible explanation is that there is a non-linear relationship between striatal denervation and motor performance reflecting a statistical "floor" effect in the imaging data with advanced disease. Both the motor manifestations and the striatal dopamine denervation of idiopathic PD, however, are typically asymmetric and more meaningful associations may be found by comparing data from the least denervated striatum with motor performance in the corresponding body side. PD patients (n=28) underwent [11C]beta-CFT dopamine transporter (DAT) positron emission tomography (PET) and grooved pegboard testing. Voxel-based analysis of DAT PET and bimanual pegboard scores demonstrated significant correlation clusters within the bilateral striata (P LT 0.001). However, findings were most prominent in the least denervated striatum. There was a significant inverse correlation between pegboard scores of the least affected arm and DAT binding of the least denervated striatum (Rs=-0.69, P LT 0.0001) but no significant correlation between pegboard scores of the clinically most affected arm and DAT binding of the most denervated striatum (Rs=-0.15, ns). These data indicate that the robustness of the grooved pegboard test as a biomarker for nigrostriatal denervation in PD mainly reflects the relationship between test performance of the clinically least affected limb and the least denervated striatum. These findings indicate that there is both a statistical "floor" and "ceiling" effect for the most affected striatal and body sides that must be considered when employing imaging as an outcome measure in clinical trials in PD.

PMID: 17714864 [PubMed - indexed for MEDLINE]

Tuesday, January 01, 2008

Neuropsychology Abstract of the Day: Cognitive Function in 95-Year-Olds

Börjesson-Hanson A, Gustafson D, & Skoog I. Five-year mortality in relation to dementia and cognitive function in 95-year-olds. Neurology. 2007 Nov 27; 69(22): 2069-2075.

Neuropsychiatric Epidemiology Unit, Psychiatry Section, Institute of Neuroscience and Physiology, Sahlgrenska Academy at Göteborg University, Sweden.

BACKGROUND: Dementia is a known predictor of mortality, but most studies include small numbers of participants above age 90. The influence of dementia or cognition on mortality in this age group is therefore uncertain. OBJECTIVE: To examine 5-year mortality in relation to dementia and cognitive performance at age 95. METHODS: A population sample of 338 individuals examined at age 95 was followed to age 100. Dementia was diagnosed according to DSM-III-R criteria. Cognitive function was measured using the Mini-Mental State Examination (MMSE). Information on severe physical disorders was obtained from the Swedish Hospital Discharge Register, and date of death from the Swedish Population Register. RESULTS: Five-year mortality was higher in 95-year-olds with dementia than in 95-year-olds without dementia (96% vs 73%; p < 0.0001), even when adjusting for severe physical disorders. A Cox regression analysis with calculation of population attributable risk (PAR), calculated from adjusted relative risks, showed that mortality was predicted by dementia (PAR 42%), cardiac disease (PAR 17%), cancer (PAR 6%), and male sex (PAR 7%), but not by stroke. Among the subjects without dementia, cognitive performance measured using the MMSE (n = 133 with complete tests; 81% of the subjects without dementia) predicted mortality. For each point increase in the MMSE, mortality decreased by 13%. CONCLUSIONS: In 95-year-olds, dementia, as well as cognitive performance in the subjects without dementia, influences mortality. When controlling for other severe medical conditions we found dementia to be the leading cause of deaths among the oldest old. The reason why dementia and cognitive function predict life expectancy requires further elucidation.

PMID: 18040013 [PubMed - indexed for MEDLINE]