Monday, November 28, 2005

Primary Progressive Aphasia (PPA): Want to Learn More?

Northwestern University's Cognitive Neurology and Alzheimer's Disease Center has a helpful overview of PPA online here:
PPA Handbook.
Anthony H. Risser | |

Primary Progressive Aphasia (PPA)

From an NIH press release from earlier today:
Study Links Progressive Aphasia Syndrome to Prion Gene

Most people with a rare type of dementia called primary progressive aphasia (PPA) have a specific combination of prion gene variants, a new study shows. The study is the first to link the prion protein gene to this disorder. It was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health (NIH), and appears in the December 2005 issue of the Annals of Neurology.

The researchers, led by James A. Mastrianni, M.D., Ph.D., of the University of Chicago, also looked at the prion protein gene in people with Alzheimer's disease and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) and did not find any association with specific gene variants in those disorders.

PPA is classified as a type of frontotemporal dementia because of the pattern of brain degeneration it causes. The primary symptoms of the disease are problems speaking or understanding speech, and these problems gradually get worse over time. People with PPA also may develop difficulty with math. Most other functions remain normal for at least two years after the language symptoms appear, but the disease may eventually cause other changes, such as problems with memory, reasoning, and spatial abilities. While PPA sometimes runs in families, it has never before been linked to variations in a specific gene.

Unlike the abnormal disease-causing prions linked to Creutzfeldt-Jakob disease (CJD) and other so-called "prion diseases", the normal prion protein is found in everyone. The gene that codes for the normal protein has several common variants. One variant of the gene codes for an amino acid called methionine at a point called codon 129, while another version codes for the amino acid valine at codon 129. These variants appear to influence disease susceptibility and symptoms in CJD and other prion diseases, probably because they determine how the prion protein folds. Proteins' folded shapes affect how well they can function. Some protein shapes also interfere with normal cellular processes.

People normally have two copies of every gene. In the new study, Dr. Mastrianni and his colleagues found that almost 85 percent of the people with PPA who took part in this study had one copy of the prion gene coding for the methionine variant and the other coding for valine. "The association between this gene combination and the disease is really dramatic," he says. However, not all people with the two gene variants develop PPA. Therefore the prion gene is probably not the primary cause of the disease, he adds.

The researchers think that the methionine/valine combination leaves people susceptible to PPA in ways that are not yet understood. Previous studies have suggested that normal prion proteins carry out a variety of functions, from cellular delivery of copper to cell signaling and even triggering or preventing cell death. The proteins may work either better or worse depending on which gene variants people inherit. Any of the proteins' normal activities could be important in the chain of events that leads to PPA.

“This is a new case where prion genes are linked to a neurological disorder, and it suggests that we need to learn more about the normal function of prions in the nervous system in order to better understand their role in disease,” says Michael Nunn, Ph.D., the NIH neurology institute’s program director for this study.
[ ... Read the full release ... ]
Anthony H. Risser | |

Thursday, November 24, 2005

Human-Computer Interfaces and Facial Cognition

The N=1: Population of One blog discusses and points to an upcoming academic workshop about HCI and cognitive factors related to faces: Read the post.
Anthony H. Risser | |

Tuesday, November 22, 2005

Abstract of the Day: Donepezil (Aricept) and Alzheimer Disease

Csernansky JG, Wang L, Miller JP, Galvin JE, & Morris JC. Neuroanatomical predictors of response to donepezil therapy in patients with dementia. Archives of Neurology. 2005 Nov; 62(11): 1718-1722.

Alzheimer's Disease Research Center, and Department of Psychiatry, Washington University School of Medicine, St Louis, MO 63110, USA.

BACKGROUND: Patients with dementia of the Alzheimer type (DAT) respond variably to treatment with acetylcholinesterase inhibitors. OBJECTIVE: To determine whether measures of hippocampal volume and shape predict the response to donepezil in patients with DAT. DESIGN: T1-weighted, magnetic resonance images were obtained from patients with DAT, who subsequently underwent treatment with donepezil. Brain-mapping algorithms were used to quantify hippocampal volume and shape, and growth curves were used to estimate clinical outcome. SETTING: A referral outpatient center specializing in treatment of dementia. PATIENTS: Thirty-seven patients with very mild or mild DAT received donepezil therapy for up to 4 weeks before magnetic resonance imaging and for 24 to 96 weeks after magnetic resonance imaging. INTERVENTION: Donepezil, 10 mg/d. MAIN OUTCOME MEASURE: Rate of change in the cognitive portion of the Alzheimer's Disease Assessment Scale total scores. RESULTS: Smaller hippocampal volume and inward variation of the lateral and inferomedial portions of the hippocampal surface were correlated with a poorer response to donepezil therapy. CONCLUSIONS: Measures of hippocampal volume and surface variation can be used to predict the response of patients with DAT to the acetylcholinesterase inhibitor donepezil.

PMID: 16286546 [PubMed - in process]
Anthony H. Risser
| |

Abstract of the Day: Verbal Fluency Testing and Multiple Sclerosis (MS)

Henry JD, Beatty WW. Verbal fluency deficits in multiple sclerosis. Neuropsychologia. 2005 Nov 14; [Epub ahead of print]

School of Psychology, University of New South Wales, Sydney, NSW, Australia.

A quantitative review of 35 studies with 3673 participants was conducted to estimate and compare the magnitude of deficits upon tests of phonemic and semantic fluency for participants with multiple sclerosis (MS) relative to healthy controls. Participants with MS were substantially but similarly impaired on tests of phonemic and semantic fluency. These deficits were larger than deficits on measures of verbal intelligence, confrontation naming and another widely used measure of executive functioning, the Wisconsin Card Sorting Test, but were of a comparable or smaller magnitude relative to deficits on the oral version of the Symbol Digit Modalities Test (SDMT). This is consistent with other research suggesting that measures of verbal fluency and the SDMT may be amongst the most sensitive neuropsychological measures to cognitive impairment in MS. Increased neurological disability and a chronic progressive (as opposed to a relapsing remitting) disease course were associated with larger deficits on tests of phonemic and semantic fluency. However, it is suggested that this latter finding is attributable to the distinct clinical features of chronic progressive and relapsing remitting sub-types. Thus, patients who follow a chronic progressive course tend to be older, have an increased duration of illness and experience greater neurological disability. Once these variables were controlled for, differences between the two sub-types were substantially attenuated.

PMID: 16293271 [PubMed - as supplied by publisher]
Anthony H. Risser | |

Friday, November 18, 2005

Business World: Biogen Idec, Elan, & Tysabri (Natalizumab)

From the AP:

Elan Shares Jump As Tysabri to Get Review
Published: November 18, 2005
Filed at 12:52 p.m. ET

DUBLIN, Ireland (AP) -- Shares in Irish drug maker Elan Corp. PLC jumped Friday after U.S. regulators announced they would accelerate their review of a key suspended drug, Tysabri.

On the Irish Stock Exchange in Dublin, Elan shares rose 4.4 percent to close at 9.24 euros ($10.81) amid renewed optimism about the multiple sclerosis-fighting drug. Elan is developing Tysabri in conjunction with Cambridge, Massachusetts-based Biogen Idec Inc.

The U.S. Food and Drug Administration said Thursday night it had granted Tysabri ''priority review'' status, which means that a decision on whether the drug can return to the U.S. market will be made within six months instead of the standard 10.

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

In The Weeklies: Pharmacotherapy in Older Adults

In the current issue of the British Medical Journal:

Jennifer Glass, Krista L Lanctôt, Nathan Herrmann, Beth A Sproule, & Usoa E Busto. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. British Medical Journal;  2005; 331: 1169. [doi:10.1136/bmj.38623.768588.47]

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

Thursday, November 17, 2005

Wednesday, November 16, 2005

Abstract of the Day: Neuropsychology Tracking in Epilepsy Care

Lutz MT & Helmstaedter C. EpiTrack: Tracking cognitive side effects of medication on attention and executive functions in patients with epilepsy. Epilepsy and Behavior, 2005 Oct 30; [Epub ahead of print].

Department of Epileptology, University of Bonn, Bonn, Germany.

RATIONALE: Achievement of maximum seizure control with preservation or even improvement of patient's cognitive capabilities is the major aim of epilepsy therapy. EpiTrack is a brief screening tool for the tracking of cognitive side effects of antiepileptic drugs. Test selection was based on recent studies on the effects of topiramate on cognition and retrospective inspection of results from patients with antiepileptic drug (AED) side effects. METHODS: The 15-minute screening tool comprises six subtests: the Trail-Making Test (parts A and B), a test of response inhibition, digit span backward, written word fluency, and a maze test. These tests were standardized in 220 healthy subjects, 100 of whom were reevaluated after 5.3 months to obtain information on reliability and practice effects. Criterion validity was determined by correlation to other neuropsychological measures. For a first clinical evaluation, the impact of epilepsy (seizures) and medication on EpiTrack scores was evaluated cross-sectionally in 184 consecutive inpatients with chronic epilepsy. RESULTS: According to the normative data, we developed an easy scoring scheme assigning test scores on a 7-point scale. The EpiTrack is suitable for patients between 18 and 60 years of age. Age corrections were included for patients between 40 and 60 years. EpiTrack scores on subtests for both controls and patients were submitted to principal component analysis. VARIMAX rotation yielded a two-factor solution (verbal/visuo-spatial) that accounted for 63.8% of the total variance in controls. In the patient group, only one factor emerged accounting for 54.7% of variance. EpiTrack correlates with global scores of attention (r=0.85) and language (r=0.67) (P's<0.001). At a cutoff score of 25, only 2.7% of the controls were classified as impaired, while impairment was indicated in 48.4% of the patients. The score is sensitive to monthly frequency of complex partial seizures and to number of AEDs. It shows negative cognitive effects of valproate and topiramate given in mono/polytherapy. CONCLUSION: EpiTrack is a promising 15-minute screening tool for the detection and tracking of cognitive side effects of AEDs and adverse effects of seizures in patients with epilepsy. Future application will show its value in prospective follow-up studies on AED side effects.

PMID: 16266826 [PubMed - as supplied by publisher]
Anthony H. Risser | |

PubMed Goes RSS

Save a couple of steps and a little time in your lit searches by making use of the new RSS feed options on PubMed. Details are provided from the homepage.
Anthony H. Risser | |

The Amateur Pharmacists

From The New York Times:
Young, Assured and Playing Pharmacist to Friends
Published: November 16, 2005
The New York Times


For a sizable group of people in their 20's and 30's, deciding on their own what drugs to take - in particular, stimulants, antidepressants and other psychiatric medications - is becoming the norm. Confident of their abilities and often skeptical of psychiatrists' expertise, they choose to rely on their own research and each other's experience in treating problems like depression, fatigue, anxiety or a lack of concentration. A medical degree, in their view, is useful, but not essential, and certainly not sufficient.

They trade unused prescription drugs, get medications without prescriptions from the Internet and, in some cases, lie to doctors to obtain medications that in their judgment they need.
[ ... Read the full article ... ]
Anthony H. Risser | |

Tuesday, November 15, 2005

Fibril Structure and Alzheimer Disease

From a Salk Institute for Biological Studies press release:
Released: Fri 11-Nov-2005, 08:55 ET 
Embargo expired: Mon 14-Nov-2005, 17:00 ET 
3-D Structure of Alzheimer's Disease Filament Shows How It Zips Up Peptides

Newswise — Researchers have solved the three dimensional structure of the long thread-like fibers that fill the brains of Alzheimer's disease patients. The structure reveals the proteins that make up the fibrils lock onto each other much like a zipper on a jacket. This advance, reported in the Nov. 14th early online edition of Proceedings of the National Academy of Sciences (PNAS), helps illuminate the molecular roots of Alzheimer's and possibly other degenerative diseases of the brain.

“Now that we understand at an atomic level how these fibrils form, it might help researchers develop a biomarker test to diagnose Alzheimer's disease at an early stage, as well as drugs to treat it,” says the study's lead investigator, Salk Institute for Biological Studies scientist Roland Riek, Ph.D., who collaborated with researchers at the University of Lausanne and Roche pharmaceuticals, both in Switzerland

As a result of the study, Riek and his colleagues may now understand how a potential Alzheimer's disease medication now in clinical trials in Europe reacts to the fibril. The drug binds to the end of the fibril chain of beta amyloid proteins, halting their lethal accumulation, an early step in the formation of the amyloid plaque deposits that are a hallmark of Alzheimer's.


The research team of the Salk Institute in collaboration with the University of Lausanne and Roche, developed new research techniques to determine the 3D structure that mimics the most common type of fibrils found in patients with the disease.

They discovered that beta amyloid proteins (peptides) that make up these fibrils attach to each other on one end with an ever-growing property.

“From this structure we can nicely see what happens physically, where the fibril forms a template on which to bind other amyloid peptides in an inter-collated way,” Riek says. “The way these peptides lock on to each other is like a zipper on a jacket.” Due to the ever-growing property the zipper binds more and more loose peptides together to produce dense “plaque” filaments that may be toxic to the functioning of brain nerve cells.
Anthony H. Risser | |

Blogger/Blogspot Dysfunctional Once Again

Friday, November 04, 2005

Hippocampus and Early-Life Memories

The November issue of The APA Monitor includes a short piece about a recent talk by Dr. Lynn Nadel discussing advances in research related to the hippocampus and memory:

Why we can't remember when...
The hippocampus's role in memory may help explain why we cannot remember our early childhood, and why stress affects our memory later in life.
APA Monitor
November 2005
Print version: page 36
[ ... Read the article ... ]
Anthony H. Risser | |

Tuesday, November 01, 2005