Wednesday, October 15, 2008

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

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

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

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

PMID: 18690832 [PubMed - indexed for MEDLINE]

Download the full article: Link

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Aging Research

A press release from the NIH earlier today:

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

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


Read the full release

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Tuesday, October 14, 2008

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

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

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

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

PMID: 18850327 [PubMed - as supplied by publisher]

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

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Election Day in Canada

Today is election day in Canada. Vote!

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

From The CBC:

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

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

From The BBC:

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

[snip]

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

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

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

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

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

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

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

[snip]

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Tuesday, October 07, 2008

Neuropsychology Abstract of the Day

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

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

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

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