Effects of APOE on brain white matter microstructure in healthy adults

Posted on November 5, 2012 by Maurice Preter MD

Articles

Effects of APOE on brain white matter microstructure in healthy adults

Lars T. Westlye, PhD,

Ivar Reinvang, PhD,

Helge Rootwelt, PhD and

Thomas Espeseth, PhD

+ Author Affiliations

From the Department of Psychology (L.T.W., I.R.), Center for the Study of Human Cognition, University of Oslo, Oslo; Centre for Advanced Study (L.T.W., I.R., T.E.), Oslo; and Department of Medical Biochemistry (H.R.), Division of Mental Health and Addiction (T.E.), Oslo University Hospital, Oslo, Norway.

Correspondence & reprint requests to Dr. Westlye : l.t.westlye@psykologi.uio.no.

View Complete Disclosures

Abstract

Objectives: APOE is related to cholesterol transport and clearance and brain white matter (WM) properties involving myelin, of which cholesterol is a major component. Diffusion tensor imaging enables in vivo investigations of brain WM, and could increase our understanding of the pathways leading to Alzheimer disease. The main objective was to investigate the association between APOE and diffusion tensor imaging–derived indices of WM microstructure.

Methods: Healthy participants were assessed on a range of neuropsychological measures, genotyped, and underwent MRI. A total of 203 volunteers (aged 21.1–69.9 years, mean = 47.6, SD = 14.9) with APOE genotypes ϵ2/ϵ3 (n = 30), ϵ3/ϵ3 (n = 113), and ϵ3/ϵ4 (n = 60) were included.

Results: There were widespread increases in mean and radial diffusion in carriers of the ϵ3/ϵ4 alleles compared with ϵ3/ϵ3 with medium to strong effect sizes (Cohen’s d = 0.77–0.79). No interactions between genotype and age were observed, indicating relatively stable differences from early adulthood. The results were independent of presence of dementia in close family. We also observed increased mean and radial diffusion and decreased fractional anisotropy in carriers of the ϵ2/ϵ3 alleles compared with ϵ3/ϵ3 carriers. No significant differences were found between ϵ2/ϵ3 and ϵ3/ϵ4.

Conclusions: APOE affects microstructural properties of the brain WM from early adulthood, but the specific allelic effects do not directly reflect the associated risk of developing Alzheimer disease. The role of APOE in cholesterol transport, the high density of cholesterol in myelin, and the specific effects on radial diffusivity support a putative functional role of APOE in modulating myelin-related processes in the brain.

Footnotes

Study funding: Supported by the Research Council of Norway (grant 204966/F20 to L.T.W., grant 177458/V50 to T.E., and grant 154313/V50 to I.R.) and the Centre for Advanced Study at the Norwegian Academy of Sciences and Letters (I.R., T.E., and L.T.W.). The funding organizations had no role in the design or conduct of the study; in the collection, analysis, or interpretation of the data; or in the preparation, review, or approval of the manuscript.

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Football players’ mortality from Alzheimer disease and Lou Gehrig’s is 4 times higher

Posted on November 5, 2012 by Maurice Preter MD

Another dent in the tired old tale of the role of (Mendelian) heredity in neuropsychiatry. More good stuff published in Neurology this week to follow.

Articles

Neurodegenerative causes of death among retired National Football League players

Everett J. Lehman, MS,

Misty J. Hein, PhD,

Sherry L. Baron, MD and

Christine M. Gersic

+ Author Affiliations

From the Centers for Disease Control and Prevention, The National Institute for Occupational Safety and Health, Division of Surveillance, Hazard Evaluations and Field Studies, Cincinnati, OH.

Correspondence & reprint requests to Mr. Lehman: elehman@cdc.gov

View Complete Disclosures

Abstract

Objective: To analyze neurodegenerative causes of death, specifically Alzheimer disease (AD), Parkinson disease, and amyotrophic lateral sclerosis (ALS), among a cohort of professional football players.

Methods: This was a cohort mortality study of 3,439 National Football League players with at least 5 pension-credited playing seasons from 1959 to 1988. Vital status was ascertained through 2007. For analysis purposes, players were placed into 2 strata based on characteristics of position played: nonspeed players (linemen) and speed players (all other positions except punter/kicker). External comparisons with the US population used standardized mortality ratios (SMRs); internal comparisons between speed and nonspeed player positions used standardized rate ratios (SRRs).

Results: Overall player mortality compared with that of the US population was reduced (SMR 0.53, 95% confidence interval [CI] 0.48−0.59). Neurodegenerative mortality was increased using both underlying cause of death rate files (SMR 2.83, 95% CI 1.36−5.21) and multiple cause of death (MCOD) rate files (SMR 3.26, 95% CI 1.90−5.22). Of the neurodegenerative causes, results were elevated (using MCOD rates) for both ALS (SMR 4.31, 95% CI 1.73−8.87) and AD (SMR 3.86, 95% CI 1.55−7.95). In internal analysis (using MCOD rates), higher neurodegenerative mortality was observed among players in speed positions compared with players in nonspeed positions (SRR 3.29, 95% CI 0.92−11.7).

Conclusions: The neurodegenerative mortality of this cohort is 3 times higher than that of the general US population; that for 2 of the major neurodegenerative subcategories, AD and ALS, is 4 times higher. These results are consistent with recent studies that suggest an increased risk of neurodegenerative disease among football players.

Footnotes

Study funding: Supported by the Intramural Research Program of the National Institute for Occupational Safety and Health. The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the National Institute for Occupational Safety and Health. The sponsor reviewed and approved final submission but did not have a role in design and conduct of the study, in the collection, analysis, and interpretation of the data, or in the preparation of the manuscript.

Received April 24, 2012.

Accepted July 9, 2012.

Copyright © 2012 by AAN Enterprises, Inc.

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Inflammation is the common link among the leading causes of death.

Posted on November 4, 2012 by Maurice Preter MD

Psychosom Med. 2010 May;724:365-9. Epub 2010 Apr 21.

Stress, food, and inflammation: psychoneuroimmunology and nutrition at the cutting edge.
Kiecolt-Glaser JK. Department of Psychiatry, The Ohio State Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, Ohio 43210-1228, USA. Janice.Kiecolt-Glaser@osumc.edu

Abstract
Inflammation is the common link among the leading causes of death. Mechanistic studies have shown how various dietary components can modulate key pathways to inflammation, including sympathetic activity, oxidative stress, transcription factor nuclear factor-kappaB activation, and proinflammatory cytokine production. Behavioral studies have demonstrated that stressful events and depression can also influence inflammation through these same processes. If the joint contributions of diet and behavior to inflammation were simply additive, they would be important. However, several far more intriguing interactive possibilities are discussed: stress influences food choices; stress can enhance maladaptive metabolic responses to unhealthy meals; and diet can affect mood as well as proinflammatory responses to stressors. Furthermore, because the vagus nerve innervates tissues involved in the digestion, absorption, and metabolism of nutrients, vagal activation can directly and profoundly influence metabolic responses to food, as well as inflammation; in turn, both depression and stress have well-documented negative effects on vagal activation, contributing to the lively interplay between the brain and the gut. As one example, omega-3 fatty acid intake can boost mood and vagal tone, dampen nuclear factor-kappaB activation and responses to endotoxin, and modulate the magnitude of inflammatory responses to stressors. A better understanding of how stressors, negative emotions, and unhealthy meals work together to enhance inflammation will benefit behavioral and nutritional research, as well as the broader biomedical community.PMID: 20410248 [PubMed – indexed for MEDLINE] PMCID: PMC2868080Free PMC Article

via Stress, food, and inflammation: psychoneuroimm… [Psychosom Med. 2010] – PubMed – NCBI.

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Americans’ suicide rates up since economic crisis began | Reuters

Posted on November 4, 2012 by Maurice Preter MD

Suicide rates in the United States have risen sharply since the economic crisis took hold in 2007 and political leaders should do more to protect Americans’ mental health during tough times, researchers said on Monday.

via Americans’ suicide rates up since economic crisis began | Reuters.

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What Changes in Survival Rates Tell Us About U.S. Health Care – The Commonwealth Fund

Posted on November 4, 2012 by Maurice Preter MD

Even as health care spending per capita has increased in the U.S. over the last three decades, the nation has fallen behind 12 other wealthy nations in 15-year survival for men and women at ages 45 and 65.

By 2005, 15-year survival rates for 45-year-old white women in the U.S. were lower than in all comparison countries; these rates had not even surpassed 1975 survival rates for Swiss, Swedish, Dutch, or Japanese women.

U.S. white men ages 45 and 65 experienced declines in their rankings in 15-year survival rates among the comparison countries, but they were not as dramatic as the declines in rankings for women.

While smoking and obesity are two important behavior-related risk factors, they do not explain the nation’s deteriorating performance. Prevalence of obesity in the U.S. has grown more slowly in the U.S. than in other nations, and smoking prevalence has declined more rapidly.

via What Changes in Survival Rates Tell Us About U.S. Health Care – The Commonwealth Fund.

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