A place to ramble on about neurology and neuroscience.
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Risk in complex genetics: “All models are wrong but some are useful” No comments yet

Abstract

Although genome-wide association studies (GWAS) have proven remarkably effective at identifying reliably associated genetic variants, the biology underlying these discoveries is rarely immediately apparent and in most cases seems bound to require extensive fine mapping and functional analysis before it is revealed. In this context, it is logical and appropriate to try to interrogate available genetic data for biological insights. However, because such efforts invariably depend upon mathematical modeling, misperceptions can easily arise if the relevant mathematical properties are overlooked or forgotten. In this report, we will examine these mathematical issues, highlight some of the more common misconceptions, and hopefully help to clarify the somewhat blurry distinction between biology and mathematics that can so easily undermine and obscure the value of GWAS discoveries. Ann Neurol 2012;

Dietary fat types and 4-year cognitive change in community-dwelling older women No comments yet

Abstract

Objective:

A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders.

Methods:

Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake.

Results:

Higher SFA intake was associated with worse global cognitive (p for linear trend = 0.008) and verbal memory (p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04–2.58) for global cognition and 1.65 (1.04–2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p for linear trend < 0.001) and verbal memory (p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31–0.88]) and verbal memory (0.56 [0.34–0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive trajectory.

Interpretation:

Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging. ANN NEUROL 2012;

Whistleblower Suit Involving Alzheimer’s Grant to ProceedWhistleblower Suit Involving Alzheimer’s Grant to Proceed No comments yet

Federal appeals court rules that the lower court failed to consider expert testimony and that 'genuine issues of material fact remain.'
Medscape Medical News

More Patients, More Revenue, but Less Rush. How?More Patients, More Revenue, but Less Rush. How? No comments yet

Doctors may think the only way to increase revenue is to add services, do more marketing, and change their practice. But there are ways to make more money by adapting what you're already doing. Here's how.
Medscape Business of Medicine

Lifetime Prevalence of Sleepwalking Almost 30%Lifetime Prevalence of Sleepwalking Almost 30% No comments yet

Use of hypnotic sleeping medications doesn't significantly increase risk for sleepwalking, but comorbid major depression, obsessive-compulsive disorder, or alcohol abuse does.
Medscape Medical News

Multiple loci influencing hippocampal degeneration identified by genome scan No comments yet

Abstract

Objective: Large genome-wide association studies (GWAS) have identified many novel genes influencing Alzheimer disease (AD) risk, but most of the genetic variance remains une×plained. We conducted a two-stage GWAS for AD-related quantitative measures of hippocampal volume (HV), total cerebral volume (TCV), and white matter hyperintensities (WMH).

Methods: Brain MRI measures of HV, TCV and WMH were obtained from 981 Caucasian and 419 African American AD cases and their cognitively normal siblings in the MIRAGE Study, and from 168 AD cases, 336 individuals with mild cognitive impairment and 188 controls in the ADNI Study. A GWAS for each trait was conducted in the two Caucasian datasets in stage 1. Results from the two datasets were combined by meta analysis. In stage 2, one SNP from each region that was nominally significant in each dataset (p<0.05) and strongly associated in both datasets (p<1.0×10-5) was evaluated in the African American dataset.

Results: Twenty-two markers (14 for HV, 3 for TCV, and 5 for WMH) from distinct regions met criteria for evaluation in stage 2. Novel genome-wide significant associations (p<5.0×10-8) were attained for HV with SNPs in the APOE, F5/SELP, LHFP and GCFC2 gene regions. All of these associations were supported by evidence in each dataset. Associations with different SNPs in the same gene (p<1×10-5 in Caucasians and p<2.2×10-4 in African Americans) were also observed for PICALM with HV, SYNPR with TCV and TTC27 with WMH.

Interpretation: Our study demonstrates the efficacy of endophenotypes for broadening our understanding of the genetic basis of AD. ANN NEUROL 2012

Media & Book Reviews: App review: Neuro Toolkit No comments yet

Teaching Video NeuroImages: Asymptomatic subclavian-carotid double steal phenomenon due to innominate artery stenosis No comments yet

Teaching NeuroImages: Intracranial optic nerve enlargement in infantile Krabbe disease No comments yet

Effects of fetal antiepileptic drug exposure: Outcomes at age 4.5 years No comments yet

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