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1.  Symptoms and Risk Factors for Stroke in a Community-Based Observational Sample in Viet Nam 
Background
Viet Nam is experiencing a health transition from infectious to chronic disease. Data on cardiovascular diseases, including strokes, are limited.
Methods
Data were randomly collected from six communities in Da Nang, Viet Nam, on participant demographics, medical history, blood pressure, anthropometrics and health behavior using World Health Organization (WHO) guidelines. Stroke symptoms were collected by self-report with the standardized Questionnaire for Verifying Stroke Free Status. Multivariate logistic regression was used to identify factors associated with the presence of stroke symptoms.
Results
1,621 adults were examined with a mean age of 52.0 years (± 12.5 years), of which 56.1% were women. 27.3% of the participants were found to have hypertension, 26.2% used tobacco, and 16.1% were overweight. More than two-thirds of the participants with hypertension were unaware of their condition. Almost one fourth of the participants were identified by the questionnaire as previously experiencing at least one stroke symptom. Age, rural residence, and education were associated with the presence of stroke symptoms. Models adjusted for demographics found hypertension, high cholesterol, reported severe chest pain, former smoking, and being overweight to be associated with a higher prevalence of stroke symptoms.
Conclusions
The high frequency of stroke symptoms in Da Nang calls for further evaluation and interventions to reduce hypertension and other risk factors for chronic disease.
doi:10.1016/j.jegh.2012.06.001
PMCID: PMC3607634  PMID: 23538875
stroke; symptoms; Viet Nam; community-based; risk factors
2.  Leukocyte telomere length and age at menopause 
Epidemiology (Cambridge, Mass.)  2014;25(1):139-146.
Background
Telomere length is a marker of cellular aging that varies by the individual, is inherited, and is highly correlated across somatic cell types within persons. Inter-individual telomere length variability may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age.
Methods
We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women aged 65 years or older. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions.
Results
For every one kilobase (kb) increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval= 1.3 to 19.0). There was no association in 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (−0.4 to 15.5).
Conclusions
Women with the longest leukocyte telomere length underwent menopause three years later than those with the shortest leukocyte telomere length. If artifactual, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause.
doi:10.1097/EDE.0000000000000017
PMCID: PMC3926311  PMID: 24213145
3.  Caregiver perceptions of child nutritional status in Magallanes, Chile 
Background
We aimed to identify risk factors for childhood overweight and obesity and the accuracy of caregivers’ perceptions of their child’s nutritional status in the Magallanes region, Patagonia, Chile.
Methods
Heights and weights of children attending day care centers and elementary schools were collected and caregivers completed questionnaires regarding their child’s health and behavior. The child’s nutritional status was diagnosed using the 2006 WHO Child Growth Standards (for children under age 6) and the CDC 2000 Growth Charts (for children age 6 and older). Logistic regression was used to evaluate factors related to childhood overweight/obesity and weight underestimation by caregivers of overweight or obese children.
Results
Of the 795 children included in the study, 247 (31.1%) were overweight and 223 (28.1%) were obese. Risk factors for overweight/obesity included younger age and being perceived to eat more than normal by the caregiver. Caregivers were less likely to underestimate their child’s weight if the child was older or if the caregiver believed the child ate more than a normal amount.
Conclusions
There is a high prevalence of overweight and obesity among children in Magallanes and the majority of caregivers underestimate the extent of the problem in their children.
doi:10.1016/j.orcp.2012.10.003
PMCID: PMC3929963  PMID: 24548582
Nutrition; Overweight; Children; Chile
4.  Mid- and Late-Life Obesity: Risk of Dementia in the Cardiovascular Health Cognition Study 
Archives of neurology  2009;66(3):336-342.
Objectives
To evaluate associations between mid- and late-life obesity and risk of dementia.
Design
Prospective cohort followed 5.4 years from 1992/4 through 1999.
Setting
Community-dwelling sample in four US sites recruited from Medicare eligibility files.
Participants
2,798 adults without dementia, mean age 74.7 years, 59.1% women, participating in the Cardiovascular Health Cognition Study completing a magnetic resonance image, measured for height and weight at baseline (late-life) and self-reporting weight at age 50 (mid-life). Body mass index (BMI) was calculated at both times.
Main Outcome Measures
Dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) classified by a multidisciplinary committee using standardized criteria.
Results
Classification resulted in 480 persons with incident dementia, 245 with AD (no VaD) and 213 with VaD (with or without AD). In evaluations of mid-life obesity, an increased risk of dementia was found for obese (BMI >30) compared to normal (BMI 20-25) persons adjusted for demographics (HR: 1.39, 95% CI: 1.03-1.87) and for caradiovascularl risk factors (HR: 1.36, 95% CI: 0.94-1.95). The risk estimates reversed in assessments of late-life BMI. Underweight persons (BMI < 20) had an increased risk of dementia (HR: 1.62, 95% CI: 1.02-2.64) while being overweight (BMI 25-30) was not associated (HR: 0.92, 95% CI: 0.72-1.18) and being obese reduced the risk of dementia (HR: 0.63, 95% CI: 0.44-0.91) compared to those with normal BMI.
Conclusions
These results help explain the “obesity paradox” as differences in dementia risk over time are consistent with physical changes in the trajectory toward disability.
doi:10.1001/archneurol.2008.582
PMCID: PMC3513375  PMID: 19273752
5.  Leukocyte Telomere Length and Mortality in the Cardiovascular Health Study 
Background.
Leukocyte telomere length (LTL) is related to diseases of aging, but studies of mortality have been inconsistent.
Methods.
We evaluated LTL in relation to total mortality and specific cause of death in 1,136 participants of the Cardiovascular Health Study who provided blood samples in 1992–1993 and survived through 1997–1998. LTL was measured by Southern blots of the terminal restriction fragments. Cause of death was classified by a committee of physicians reviewing death certificates, medical records, and informant interviews.
Results.
A total of 468 (41.2%) deaths occurred over 6.1 years of follow-up in participants with mean age of 73.9 years (SD 4.7), 65.4% female, and 14.8% African American. Although increased age and male gender were associated with shorter LTLs, African Americans had significantly longer LTLs independent of age and sex (p < .001). Adjusted for age, sex, and race, persons with the shortest quartile of LTL were 60% more likely to die during follow-up than those within the longest quartile (hazard ratio: 1.61, 95% confidence interval: 1.22–2.12, p = .001). The association remained after adjustment for cardiovascular disease risk factors. Evaluations of cause of death found LTL to be related to deaths due to an infectious disease etiology (hazard ratio: 2.80, 95% confidence interval: 1.32–5.94, p = .007), whereas a borderline association was found for cardiac deaths (hazard ratio: 1.82, 95% confidence interval: 0.95–3.49, p = .07) in adjusted models. Risk estimates for deaths due to cancer, dementia, and ischemic stroke were not significant.
Conclusion.
These data weakly corroborate prior findings of associations between LTL and mortality in the elderly.
doi:10.1093/gerona/glq224
PMCID: PMC3055278  PMID: 21289018
Telomere; Mortality; Cause of death; Cardiovascular disease; Heart failure
6.  Antihypertensive drugs decrease risk of Alzheimer disease 
Neurology  2013;81(10):896-903.
Objectives:
The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI).
Methods:
Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders.
Results:
Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31–0.82), 0.31 in ARB (95% CI 0.14–0.68), 0.50 in ACE-I (95% CI 0.29–0.83), 0.62 in CCB (95% CI 0.35–1.09), and 0.58 in BB (95% CI 0.36–0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20–0.73).
Conclusions:
Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.
doi:10.1212/WNL.0b013e3182a35228
PMCID: PMC3885216  PMID: 23911756
7.  Associations between total serum GGT activity and metabolic risk: MESA 
Biomarkers in medicine  2013;7(5):709-721.
Aim
To evaluate associations between total serum GGT activity, metabolic risk factors and prevalent metabolic disease in MESA.
Patients & methods
Continuous associations between GGT and fasting blood glucose (FBG), fasting insulin, HbA1c and Homeostasis Model Assessment Index of Insulin Resistance (HOMA–IR) were evaluated in the entire MESA cohort and in metabolic disease subgroups using linear regression models incrementally adjusted for age, gender, site, race, lifestyle, traditional risk factors and medications. Cross-sectional odds of prevalent impaired FBG, metabolic syndrome and Type 2 diabetes were calculated for GGT quintiles in the entire cohort and in subgroups defined by age (< or ≥65 years) and ethnicity.
Results
In multivariable models, significant associations were present between GGT activity and FBG, fasting insulin, HbA1c and HOMA–IR, with the interaction between GGT and BMI affecting the association between GGT and HOMA–IR as well as the association between BMI and HOMA–IR (p < 0.0001). Adjusted odds ratios (95% CIs) of prevalent impaired FBG, metabolic syndrome and Type 2 diabetes for quintile 5 versus 1 in the entire cohort were 2.4 (1.7–3.5), 3.3 (2.5–4.5) and 2.8 (1.8–4.4), respectively (p < 0.0001). GGT associations weakened with age. The significance of linear trends for increased prevalent metabolic disease by increasing GGT quintile varied by ethnicity.
Conclusion
GGT is strongly associated with both cardiovascular and metabolic risk factors, including prevalent metabolic disease, in the MESA cohort.
doi:10.2217/bmm.13.71
PMCID: PMC4106917  PMID: 24044563
γ-glutamyltransferase; GGT; glutathione; metabolic syndrome; oxidative stress; Type 2 diabetes
8.  Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease 
Escott-Price, Valentina | Bellenguez, Céline | Wang, Li-San | Choi, Seung-Hoan | Harold, Denise | Jones, Lesley | Holmans, Peter | Gerrish, Amy | Vedernikov, Alexey | Richards, Alexander | DeStefano, Anita L. | Lambert, Jean-Charles | Ibrahim-Verbaas, Carla A. | Naj, Adam C. | Sims, Rebecca | Jun, Gyungah | Bis, Joshua C. | Beecham, Gary W. | Grenier-Boley, Benjamin | Russo, Giancarlo | Thornton-Wells, Tricia A. | Denning, Nicola | Smith, Albert V. | Chouraki, Vincent | Thomas, Charlene | Ikram, M. Arfan | Zelenika, Diana | Vardarajan, Badri N. | Kamatani, Yoichiro | Lin, Chiao-Feng | Schmidt, Helena | Kunkle, Brian | Dunstan, Melanie L. | Vronskaya, Maria | Johnson, Andrew D. | Ruiz, Agustin | Bihoreau, Marie-Thérèse | Reitz, Christiane | Pasquier, Florence | Hollingworth, Paul | Hanon, Olivier | Fitzpatrick, Annette L. | Buxbaum, Joseph D. | Campion, Dominique | Crane, Paul K. | Baldwin, Clinton | Becker, Tim | Gudnason, Vilmundur | Cruchaga, Carlos | Craig, David | Amin, Najaf | Berr, Claudine | Lopez, Oscar L. | De Jager, Philip L. | Deramecourt, Vincent | Johnston, Janet A. | Evans, Denis | Lovestone, Simon | Letenneur, Luc | Hernández, Isabel | Rubinsztein, David C. | Eiriksdottir, Gudny | Sleegers, Kristel | Goate, Alison M. | Fiévet, Nathalie | Huentelman, Matthew J. | Gill, Michael | Brown, Kristelle | Kamboh, M. Ilyas | Keller, Lina | Barberger-Gateau, Pascale | McGuinness, Bernadette | Larson, Eric B. | Myers, Amanda J. | Dufouil, Carole | Todd, Stephen | Wallon, David | Love, Seth | Rogaeva, Ekaterina | Gallacher, John | George-Hyslop, Peter St | Clarimon, Jordi | Lleo, Alberto | Bayer, Anthony | Tsuang, Debby W. | Yu, Lei | Tsolaki, Magda | Bossù, Paola | Spalletta, Gianfranco | Proitsi, Petra | Collinge, John | Sorbi, Sandro | Garcia, Florentino Sanchez | Fox, Nick C. | Hardy, John | Naranjo, Maria Candida Deniz | Bosco, Paolo | Clarke, Robert | Brayne, Carol | Galimberti, Daniela | Scarpini, Elio | Bonuccelli, Ubaldo | Mancuso, Michelangelo | Siciliano, Gabriele | Moebus, Susanne | Mecocci, Patrizia | Zompo, Maria Del | Maier, Wolfgang | Hampel, Harald | Pilotto, Alberto | Frank-García, Ana | Panza, Francesco | Solfrizzi, Vincenzo | Caffarra, Paolo | Nacmias, Benedetta | Perry, William | Mayhaus, Manuel | Lannfelt, Lars | Hakonarson, Hakon | Pichler, Sabrina | Carrasquillo, Minerva M. | Ingelsson, Martin | Beekly, Duane | Alvarez, Victoria | Zou, Fanggeng | Valladares, Otto | Younkin, Steven G. | Coto, Eliecer | Hamilton-Nelson, Kara L. | Gu, Wei | Razquin, Cristina | Pastor, Pau | Mateo, Ignacio | Owen, Michael J. | Faber, Kelley M. | Jonsson, Palmi V. | Combarros, Onofre | O'Donovan, Michael C. | Cantwell, Laura B. | Soininen, Hilkka | Blacker, Deborah | Mead, Simon | Mosley, Thomas H. | Bennett, David A. | Harris, Tamara B. | Fratiglioni, Laura | Holmes, Clive | de Bruijn, Renee F. A. G. | Passmore, Peter | Montine, Thomas J. | Bettens, Karolien | Rotter, Jerome I. | Brice, Alexis | Morgan, Kevin | Foroud, Tatiana M. | Kukull, Walter A. | Hannequin, Didier | Powell, John F. | Nalls, Michael A. | Ritchie, Karen | Lunetta, Kathryn L. | Kauwe, John S. K. | Boerwinkle, Eric | Riemenschneider, Matthias | Boada, Mercè | Hiltunen, Mikko | Martin, Eden R. | Schmidt, Reinhold | Rujescu, Dan | Dartigues, Jean-François | Mayeux, Richard | Tzourio, Christophe | Hofman, Albert | Nöthen, Markus M. | Graff, Caroline | Psaty, Bruce M. | Haines, Jonathan L. | Lathrop, Mark | Pericak-Vance, Margaret A. | Launer, Lenore J. | Van Broeckhoven, Christine | Farrer, Lindsay A. | van Duijn, Cornelia M. | Ramirez, Alfredo | Seshadri, Sudha | Schellenberg, Gerard D. | Amouyel, Philippe | Williams, Julie
PLoS ONE  2014;9(6):e94661.
Background
Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
Principal Findings
In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4×10−6) and 14 (IGHV1-67 p = 7.9×10−8) which indexed novel susceptibility loci.
Significance
The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
doi:10.1371/journal.pone.0094661
PMCID: PMC4055488  PMID: 24922517
9.  Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease 
Lambert, Jean-Charles | Ibrahim-Verbaas, Carla A | Harold, Denise | Naj, Adam C | Sims, Rebecca | Bellenguez, Céline | Jun, Gyungah | DeStefano, Anita L | Bis, Joshua C | Beecham, Gary W | Grenier-Boley, Benjamin | Russo, Giancarlo | Thornton-Wells, Tricia A | Jones, Nicola | Smith, Albert V | Chouraki, Vincent | Thomas, Charlene | Ikram, M Arfan | Zelenika, Diana | Vardarajan, Badri N | Kamatani, Yoichiro | Lin, Chiao-Feng | Gerrish, Amy | Schmidt, Helena | Kunkle, Brian | Dunstan, Melanie L | Ruiz, Agustin | Bihoreau, Marie-Thérèse | Choi, Seung-Hoan | Reitz, Christiane | Pasquier, Florence | Hollingworth, Paul | Ramirez, Alfredo | Hanon, Olivier | Fitzpatrick, Annette L | Buxbaum, Joseph D | Campion, Dominique | Crane, Paul K | Baldwin, Clinton | Becker, Tim | Gudnason, Vilmundur | Cruchaga, Carlos | Craig, David | Amin, Najaf | Berr, Claudine | Lopez, Oscar L | De Jager, Philip L | Deramecourt, Vincent | Johnston, Janet A | Evans, Denis | Lovestone, Simon | Letenneur, Luc | Morón, Francisco J | Rubinsztein, David C | Eiriksdottir, Gudny | Sleegers, Kristel | Goate, Alison M | Fiévet, Nathalie | Huentelman, Matthew J | Gill, Michael | Brown, Kristelle | Kamboh, M Ilyas | Keller, Lina | Barberger-Gateau, Pascale | McGuinness, Bernadette | Larson, Eric B | Green, Robert | Myers, Amanda J | Dufouil, Carole | Todd, Stephen | Wallon, David | Love, Seth | Rogaeva, Ekaterina | Gallacher, John | St George-Hyslop, Peter | Clarimon, Jordi | Lleo, Alberto | Bayer, Anthony | Tsuang, Debby W | Yu, Lei | Tsolaki, Magda | Bossù, Paola | Spalletta, Gianfranco | Proitsi, Petroula | Collinge, John | Sorbi, Sandro | Sanchez-Garcia, Florentino | Fox, Nick C | Hardy, John | Deniz Naranjo, Maria Candida | Bosco, Paolo | Clarke, Robert | Brayne, Carol | Galimberti, Daniela | Mancuso, Michelangelo | Matthews, Fiona | Moebus, Susanne | Mecocci, Patrizia | Zompo, Maria Del | Maier, Wolfgang | Hampel, Harald | Pilotto, Alberto | Bullido, Maria | Panza, Francesco | Caffarra, Paolo | Nacmias, Benedetta | Gilbert, John R | Mayhaus, Manuel | Lannfelt, Lars | Hakonarson, Hakon | Pichler, Sabrina | Carrasquillo, Minerva M | Ingelsson, Martin | Beekly, Duane | Alvarez, Victoria | Zou, Fanggeng | Valladares, Otto | Younkin, Steven G | Coto, Eliecer | Hamilton-Nelson, Kara L | Gu, Wei | Razquin, Cristina | Pastor, Pau | Mateo, Ignacio | Owen, Michael J | Faber, Kelley M | Jonsson, Palmi V | Combarros, Onofre | O’Donovan, Michael C | Cantwell, Laura B | Soininen, Hilkka | Blacker, Deborah | Mead, Simon | Mosley, Thomas H | Bennett, David A | Harris, Tamara B | Fratiglioni, Laura | Holmes, Clive | de Bruijn, Renee F A G | Passmore, Peter | Montine, Thomas J | Bettens, Karolien | Rotter, Jerome I | Brice, Alexis | Morgan, Kevin | Foroud, Tatiana M | Kukull, Walter A | Hannequin, Didier | Powell, John F | Nalls, Michael A | Ritchie, Karen | Lunetta, Kathryn L | Kauwe, John S K | Boerwinkle, Eric | Riemenschneider, Matthias | Boada, Mercè | Hiltunen, Mikko | Martin, Eden R | Schmidt, Reinhold | Rujescu, Dan | Wang, Li-san | Dartigues, Jean-François | Mayeux, Richard | Tzourio, Christophe | Hofman, Albert | Nöthen, Markus M | Graff, Caroline | Psaty, Bruce M | Jones, Lesley | Haines, Jonathan L | Holmans, Peter A | Lathrop, Mark | Pericak-Vance, Margaret A | Launer, Lenore J | Farrer, Lindsay A | van Duijn, Cornelia M | Van Broeckhoven, Christine | Moskvina, Valentina | Seshadri, Sudha | Williams, Julie | Schellenberg, Gerard D | Amouyel, Philippe
Nature genetics  2013;45(12):1452-1458.
Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease.
doi:10.1038/ng.2802
PMCID: PMC3896259  PMID: 24162737
10.  Low Social Support Is Associated With Shorter Leukocyte Telomere Length in Late Life: Multi-Ethnic Study of Atherosclerosis (MESA) 
Psychosomatic medicine  2013;75(2):10.1097/PSY.0b013e31828233bf.
Objective
The primary goal was to test the hypothesis that limited social support (SS) is related to shorter leukocyte telomere length (LTL), particularly in an older adult population.
Methods
Cross-sectional analyses were performed on 948 participants at Exam 1 of the Multi-Ethnic Study of Atherosclerosis (MESA), ages 45–84 years (18.4% White, 53.1% Hispanics, and 28.5% African-American). LTL was determined using qPCR and social support was measured with the ENRICHD social support inventory.
Results
Across the entire sample, SS was not associated with LTL (p = .87) after adjusting for demographic (age, gender, race/ethnicity, socioeconomic status), age X gender, age X race, health (body mass index, diabetes, pulse pressure), and lifestyle factors (smoking, physical activity, diet), however the interaction term Age (dichotomized) X SS was significant, p = .001. Stratification by age group revealed a positive association between SS (score range: 5–25) and LTL in the older (65–84 years) B(SE) = .005(.002), p = .007, but not younger participants (45–64 years), p = .12, after adjusting for covariates.
Conclusions
These results from a racially/ethnically diverse community sample of men and women provide initial evidence that low SS is associated with shorter LTL in adults aged 65 and older and is consistent with the hypothesis that social environment may contribute to rates of cellular aging, particularly in late life.
doi:10.1097/PSY.0b013e31828233bf
PMCID: PMC3881963  PMID: 23370895
telomere length; social support; cellular aging; loneliness; isolation; older adults
11.  The Epidemiology of Sleep Quality and Consumption of Stimulant Beverages among Patagonian Chilean College Students 
Sleep Disorders  2013;2013:910104.
Objectives. (1) To assess sleep patterns and parameters of sleep quality among Chilean college students and (2) to evaluate the extent to which stimulant beverage use and other lifestyle characteristics are associated with poor sleep quality. Methods. A cross-sectional study was conducted among college students in Patagonia, Chile. Students were asked to complete a self-administered questionnaire to provide information about lifestyle and demographic characteristics. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality. In addition, students underwent a physical examination to collect anthropometric measurements. Results. More than half of students (51.8%) exhibited poor sleep quality. Approximately 45% of study participants reported sleeping six hours or less per night and 9.8% used medications for sleep. In multivariate analysis, current smokers had significantly greater daytime dysfunction due to sleepiness and were more likely to use sleep medicines. Students who reported consumption of any stimulant beverage were 1.81 times as likely to have poor sleep quality compared with those who did not consume stimulant beverages (OR:1.81, 95% CI:1.21–2.00). Conclusions. Poor sleep quality is prevalent among Chilean college students, and stimulant beverage consumption was associated with the increased odds of poor sleep quality in this sample.
doi:10.1155/2013/910104
PMCID: PMC3671558  PMID: 23766919
12.  Telomere-associated polymorphisms correlate with cardiovascular disease mortality in Caucasian women: The Cardiovascular Health Study 
Leukocyte telomere length (LTL) is linked to cardiovascular disease (CVD); however, it is unclear if LTL has an etiologic role in CVD. To gain insight into the LTL and CVD relationship, a cohort study of CVD mortality and single nucleotide polymorphisms (SNPs) in OBFC1 and TERC, genes related to LTL, was conducted among 3271 Caucasian participants ages ≥65 years enrolled 1989–1990 in the Cardiovascular Health Study. Leukocyte DNA was genotyped for SNPs in OBFC1 (rs4387287 and rs9419958) and TERC (rs3772190) that were previously associated with LTL through genome-wide association studies. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). The OBFC1 SNPs were in linkage disequilibrium (r2=0.99), and both SNPs were similarly associated with CVD mortality in women. For women, there was a decreased risk of CVD death associated with the minor allele (rs4387287), HR=0.7; 95% CI: 0.5–0.9 (CC vs. AC) and HR=0.5; 95% CI: 0.20–1.4 (CC vs. AA) (p-trend <0.01). For men there was no association, HR=1.0; 95% CI: 0.7–1.3 (CC vs. AC) and HR=1.7; 95% CI: 0.8–3.6 (CC vs. AA) (p-trend=0.64). These findings support the hypothesis that telomere biology and associated genes may play a role in CVD-related death, particularly among women.
doi:10.1016/j.mad.2012.03.002
PMCID: PMC3391009  PMID: 22449406
13.  Contribution of Multiple Chronic Conditions to Universal Health Outcomes 
OBJECTIVES
To determine the relative effect of five chronic conditions on four representative universal health outcomes.
DESIGN
Cross-sectional.
SETTING
Cardiovascular Health Study.
PARTICIPANTS
Five thousand two hundred and ninety-eight community-living participants aged 65 and older.
MEASUREMENTS
Multiple regression and Cox models were used to determine the effect of heart failure (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression, and cognitive impairment on self-rated health, 12 basic and instrumental activities of daily living (ADLs and IADLs), six-item symptom burden scale, and death.
RESULTS
Each condition adversely affected self-rated health (P<.001) and ADLs and IADLs (P<.001). For example, persons with HF performed 0.70 ± 0.08 fewer ADLs and IADLs than those without; persons with depression and persons with cognitive impairment performed 0.59 ± 0.04 and 0.58 ± 0.06 fewer activities, respectively, than those without these conditions. Depression, HF, COPD, and osteoarthritis were associated with 1.18 ± 0.04, 0.40 ± 0.08, 0.40 ± 0.05, and 0.57 ± 0.03 more symptoms, respectively, in individuals with these conditions than in those without. HF (hazard ratio (HR) = 2.84, 95% confidence interval (CI) = 1.97–4.10), COPD (2.62, 95% CI = 1.94–3.53), cognitive impairment (2.05, 95% CI = 1.47–2.85), and depression (1.47, 95% CI = 1.08–2.01) were each associated with death within 2 years. Several paired combinations of conditions had synergistic effects on ADLs and IADLs. For example, individuals with HF plus depression performed 2.0 fewer activities than persons with neither condition, versus the 1.3 fewer activities expected from adding the effects of the two conditions together.
CONCLUSION
Universal health outcomes may provide a common metric for measuring the effects of multiple conditions and their treatments. The varying effects of the conditions across universal outcomes could inform care priorities.
doi:10.1111/j.1532-5415.2011.03573.x
PMCID: PMC3622699  PMID: 21883118
multiple chronic conditions; patient-reported outcomes; universal health outcomes
14.  Leukocyte Telomere Length Is Associated With Noninvasively Measured Age-Related Disease: The Cardiovascular Health Study 
Background.
Most studies of leukocyte telomere length (LTL) focus on diagnosed disease in one system. A more encompassing depiction of health is disease burden, defined here as the sum of noninvasively measured markers of structure or function in different organ systems. We determined if (a) shorter LTL is associated with greater age-related disease burden and (b) shorter LTL is less strongly associated with disease in individual systems or diagnosed chronic conditions (cardiovascular disease, stroke, pulmonary disease, diabetes, kidney disease, arthritis, or depression).
Methods.
LTL was measured by Southern blots of terminal restriction fragment length. Age-related disease was measured noninvasively and included carotid intima–media thickness, lung vital capacity, white matter grade, cystatin-C, and fasting glucose; each graded 0 (best tertile), 1 (middle tertile), or 2 (worst tertile) and summed (0 to 10) to estimate disease burden. Of 419 participants randomly selected for LTL measurement, 236 had disease burden assessed (mean [SD] age 74.2 [4.9] years, 42.4% male, 86.8% white, and 13.2% black).
Results.
Mean (SD) LTL was 6,312 (615) bp, and disease score was 4.7 (2.1) points. An SD higher disease score (β [SE] = −132 [47] bp, p < .01), age (β [SE] = −107 [46], p = .02) or carotid thickness (β [SE] = −95 [40] bp, p = .02) was associated with shorter LTL, but diagnosed conditions or number of conditions were not associated with LTL. Disease score attenuated the effect of age on LTL by 35%.
Conclusion.
LTL was associated with a characterization of age-related disease burden across multiple physiologic systems, which was comparable to, but independent of, its association with age.
doi:10.1093/gerona/glr173
PMCID: PMC3309872  PMID: 21934123
Leukocyte telomere length; Disease burden; Noninvasive measurements; Aging
15.  Gender Differences in Tea, Coffee, and Cognitive Decline in the Elderly: The Cardiovascular Health Study 
Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually by an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.
doi:10.3233/JAD-2011-110431
PMCID: PMC3577072  PMID: 21841254
Caffeine; coffee; cognition; tea
16.  Double burden: a cross-sectional survey assessing factors associated with underweight and overweight status in Danang, Vietnam 
BMC Public Health  2013;13:35.
Background
Many low- to middle-income countries are faced with an increasing prevalence of overweight/obesity while that for underweight remains high, a duality termed “double burden”; both are key risk factors for chronic diseases. This cross-sectional study assesses the prevalence and factors for underweight and overweight/obesity among adults in Danang, Vietnam, using WHO standard and suggested Asian-specific BMI cut-offs.
Methods
In 2010, 1713 residents age ≥35 years from 900 households in 6 of 56 urban, rural and mixed urban–rural communes in Danang were selected using multistage-cluster sampling methodology to participate; 1621 qualified adults enrolled. Participants completed a health survey based on WHO STEPwise Approach to Chronic Disease Risk Factor Surveillance and additional questions on chest pain and stroke symptoms. Anthropometric and other measurements were conducted. Relative risk regression was used to identify independent risk factors for underweight or overweight/obesity according to WHO standard cut-offs and suggested Asian-specific cut-offs (<18.5 kg/m2 or 23–27.49 kg/m2; and ≥27.5 kg/m2).
Results
We observed 12.4% prevalence of underweight and 16.0% for overweight/obesity using WHO standard. The prevalence of overweight/obesity doubled (33.7%) when Asian-specific cut-offs were applied. For both definitions, rural communes had the highest prevalence of underweight while urban communes had the highest prevalence of overweight/obesity. Being underweight was associated with less urbanization. Factors independently associated with being underweight included older age, rural living, current smoking, and lower systolic pressure. Factors independently associated with Asian-specific BMI definition for being overweight/obese included older age, urbanization, higher systolic pressure, and diabetes. Age was not an independent factor with WHO standard cut-offs; however, myocarial infarction and diabetes showed strong associations.
Conclusions
The double burden of underweight and overweight/obesity observed in Danang is consistent with patterns found for large cities in Vietnam that are undergoing rapid economic growth and urbanization of lifestyle. Factors independently associated with underweight and overweight/obesity status by WHO standard and Asian-specific definitions include urbanization and modifiable lifestyle factors. Further studies are needed to define ethnic specific BMI cut-offs for Vietnam and to explore strategies to reduce the rising prevalence of overweight/obesity.
doi:10.1186/1471-2458-13-35
PMCID: PMC3671199  PMID: 23316727
17.  A prospective cohort study of stroke characteristics, care, and mortality in a hospital stroke registry in Vietnam 
BMC Neurology  2012;12:150.
Background
As low and middle-income countries such as Vietnam experience the health transition from infectious to chronic diseases, the morbidity and mortality from stroke will rise. In line with the recommendation of the Institute of Medicine’s report on “Promoting Cardiovascular Health in the Developing World” to “improve local data”, we sought to investigate patient characteristics and clinical predictors of mortality among stroke inpatients at Da Nang Hospital in Vietnam.
Methods
A stroke registry was developed and implemented at Da Nang Hospital utilizing the World Health Organization’s Stroke STEPS instrument for data collection.
Results
754 patients were hospitalized for stroke from March 2010 through February 2011 and admitted to either the intensive care unit or cardiology ward. Mean age was 65 years, and 39% were female. Nearly 50% of strokes were hemorrhagic. At 28-day follow-up, 51.0% of patients with hemorrhagic stroke died whereas 20.3% of patients with ischemic stroke died. A number of factors were independently associated with 28-day mortality; the two strongest independent predictors were depressed level of consciousness on presentation and hemorrhagic stroke type. While virtually all patients completed a CT during the admission, evidence-based processes of care such as anti-thrombotic therapy and carotid ultrasound for ischemic stroke patients were underutilized.
Conclusions
This cohort study highlights the high mortality due in part to the large proportion of hemorrhagic strokes in Vietnam. Lack of hypertension awareness and standards of care exacerbated clinical outcomes. Numerous opportunities for simple, inexpensive interventions to improve outcomes or reduce recurrent stroke have been identified.
doi:10.1186/1471-2377-12-150
PMCID: PMC3563478  PMID: 23199098
Hemorrhage; Ischemia; Mortality; Risk factors; Stroke
18.  Association of HSP70 and its co-chaperones with Alzheimer’s Disease 
The heat shock protein (HSP) 70 family has been implicated in the pathology of Alzheimer’s disease (AD). In this study, we examined common genetic variations in the 80 genes encoding HSP70 and its co-chaperones. We conducted a study in a series of 462 patients and 5238 unaffected participants derived from the Rotterdam Study, a population-based study including 7983 persons aged 55 years and older. We genotyped a total of 12,053 Single Nucleotide Polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. Replication was performed in two independent cohort studies, the Framingham Heart study (FHS; N=806) and Cardiovascular Health Study (CHS; N=2150). When adjusting for multiple testing, we found a small but consistent, though not significant effect of rs12118313 located 32kb from PFDN2, with an OR of 1.19 (p-value from meta-analysis =0.003). However this SNP was in the intron of another gene, suggesting it is unlikely this SNP reflects the effect of PFDN2. In a formal pathway analysis we found nominally significant evidence for an association of BAG, DNAJA and prefoldin with AD. These findings corroborate with those of a study of 2032 AD patients and 5328 controls, in which several members of the prefoldin family showed evidence for association to AD. Our study did not reveal evidence for a genetic variant if the HSP70 family with a major effect on AD. However, our findings of the single SNP analysis and pathway analysis suggest that multiple genetic variants in prefoldin are associated with AD.
doi:10.3233/JAD-2011-101560
PMCID: PMC3483142  PMID: 21403392
Heat-Shock Proteins; Alzheimer Disease; prefoldin; Genetic Association Studies
19.  Genome-wide meta-analysis points to CTC1 and ZNF676 as genes regulating telomere homeostasis in humans 
Human Molecular Genetics  2012;21(24):5385-5394.
Leukocyte telomere length (LTL) is associated with a number of common age-related diseases and is a heritable trait. Previous genome-wide association studies (GWASs) identified two loci on chromosomes 3q26.2 (TERC) and 10q24.33 (OBFC1) that are associated with the inter-individual LTL variation. We performed a meta-analysis of 9190 individuals from six independent GWAS and validated our findings in 2226 individuals from four additional studies. We confirmed previously reported associations with OBFC1 (rs9419958 P = 9.1 × 10−11) and with the telomerase RNA component TERC (rs1317082, P = 1.1 × 10−8). We also identified two novel genomic regions associated with LTL variation that map near a conserved telomere maintenance complex component 1 (CTC1; rs3027234, P = 3.6 × 10−8) on chromosome17p13.1 and zinc finger protein 676 (ZNF676; rs412658, P = 3.3 × 10−8) on 19p12. The minor allele of rs3027234 was associated with both shorter LTL and lower expression of CTC1. Our findings are consistent with the recent observations that point mutations in CTC1 cause short telomeres in both Arabidopsis and humans affected by a rare Mendelian syndrome. Overall, our results provide novel insights into the genetic architecture of inter-individual LTL variation in the general population.
doi:10.1093/hmg/dds382
PMCID: PMC3510758  PMID: 23001564
20.  Genital Tract Infections, Bacterial Vaginosis, HIV, and Reproductive Health Issues among Lima-Based Clandestine Female Sex Workers 
Sociodemographic and behavioral characteristics of 212 Peruvian female sex workers (FSWs) were analyzed. The association between genital tract infections (GTIs) and risk factors by multivariate analysis was evaluated. Eighty-eight percent of FSWs were diagnosed with at least one GTI (HSV-2 80.1%, BV 44.8%, candidiasis 9.9%, syphilis seropositivity 9.4%, Trichomonas vaginalis 2.4%, HIV seropositivity 2.4%). Reported condom use with clients was nearly universal (98.3%), but infrequent with husband/regular partners (7.3%). In multivariate analysis BV was negatively associated with more consistent condom use (PRR = 0.63, 95% CI, 0.42–0.96). Many had not visited a Sexually Transmitted Infection (STI) clinic or been tested for HIV in the past year (40.6%, 47.1%, resp.). Nonclient contraceptive use was low (57%) and induced abortion was common (68%). High GTI burden and abortions suggest that a services-access gap persists among marginalized FSWs. Continued health outreach programs and integrating family planning and reproductive health services into existing STI clinic services are recommended.
doi:10.1155/2012/739624
PMCID: PMC3395213  PMID: 22811592
21.  Comparing Years of Healthy Life, Measured in 16 Ways, for Normal Weight and Overweight Older Adults 
Journal of Obesity  2012;2012:894894.
Introduction. The traditional definitions of overweight and obesity are not age specific, even though the relationship of weight to mortality is different for older adults. Effects of adiposity on aspects of health beside mortality have not been well investigated. Methods. We calculated the number of years of healthy life (YHL) in the 10 years after baseline, for 5,747 older adults. YHL was defined in 16 different ways. We compared Normal and Overweight persons, classified either by body mass index (BMI) or by waist circumference (WC). Findings. YHL for Normal and Overweight persons differed significantly in 25% of the comparisons, of which half favored the Overweight. Measures of physical health favored Normal weight, while measures of mental health and quality of life favored Overweight. Overweight was less favorable when defined by WC than by BMI. Obese persons usually had worse outcomes. Discussion. Overweight older adults averaged as many years of life and years of healthy life as those of Normal weight. There may be no outcome based reason to distinguish Normal from Overweight for older adults. Conclusion. The “Overweight paradox” appears to hold for nonmortality outcomes. New adiposity standards are needed for older adults, possibly different by race and sex.
doi:10.1155/2012/894894
PMCID: PMC3388309  PMID: 22778920
22.  Phenotype harmonization and cross-study collaboration in GWAS consortia: the GENEVA experience 
Genetic epidemiology  2011;35(3):159-173.
Genome-wide association study (GWAS) consortia and collaborations formed to detect genetic loci for common phenotypes or investigate gene-environment (G*E) interactions are increasingly common. While these consortia effectively increase sample size, phenotype heterogeneity across studies represents a major obstacle that limits successful identification of these associations. Investigators are faced with the challenge of how to harmonize previously collected phenotype data obtained using different data collection instruments which cover topics in varying degrees of detail and over diverse time frames. This process has not been described in detail. We describe here some of the strategies and pitfalls associated with combining phenotype data from varying studies. Using the Gene Environment Association Studies (GENEVA) multi-site GWAS consortium as an example, this paper provides an illustration to guide GWAS consortia through the process of phenotype harmonization and describes key issues that arise when sharing data across disparate studies. GENEVA is unusual in the diversity of disease endpoints and so the issues it faces as its participating studies share data will be informative for many collaborations. Phenotype harmonization requires identifying common phenotypes, determining the feasibility of cross-study analysis for each, preparing common definitions, and applying appropriate algorithms. Other issues to be considered include genotyping timeframes, coordination of parallel efforts by other collaborative groups, analytic approaches, and imputation of genotype data. GENEVA's harmonization efforts and policy of promoting data sharing and collaboration, not only within GENEVA but also with outside collaborations, can provide important guidance to ongoing and new consortia.
doi:10.1002/gepi.20564
PMCID: PMC3055921  PMID: 21284036
phenotype; harmonization; genome-wide association studies; GENEVA; consortia
23.  Cognition and the Risk of Hospitalization for Serious Falls in the Elderly: Results From the Cardiovascular Health Study 
Background.
Many elderly adults fall every year, sometimes resulting in serious injury and hospitalization. Although impaired cognition is a risk factor for injurious falls, little is known about cognitive decline above the threshold of impairment and risk of serious falls in community-dwelling seniors.
Methods.
In total, 702 of 5,356 older adults participating in the Cardiovascular Health Study experienced an injurious fall between 1990 and 2005, as indicated by hospitalization records. General cognition was measured annually with the Modified Mini-Mental State Examination and processing speed with the Digit Symbol Substitution Test. The Cox regression model was used to calculate hazard ratio and 95% confidence interval with and without time-dependent covariates and adjusted for known risk factors.
Results.
Participants with slightly decreased Digit Symbol Substitution Test scores were at increased risk for a serious fall (hazard ratio = 1.58, 95% confidence interval = 1.15–2.17). The risk continued to increase with each quartile decrease in Digit Symbol Substitution Test score. Participants without prevalent cardiovascular disease at baseline and decreased Modified Mini-Mental State Examination scores (80–89) had a 45% increased risk for a serious fall and those at high risk for dementia (<80) were at twice the risk as participants scoring above 90 (hazard ratio = 2.16, 95% confidence interval = 1.60–2.91).
Conclusions.
Both decreased general cognition and decreased processing speed appear to be potential risk factors for serious falls in the elderly. When assessing the risk of serious falls in elderly patients, clinicians should consider usual factors like gait instability and sensory impairment as well as less obvious ones such as cardiovascular disease and cognitive function in nondemented adults.
doi:10.1093/gerona/glq115
PMCID: PMC2954237  PMID: 20584769
Elderly; Falls; Cognition; Epidemiology
24.  Common variants in ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer’s disease 
Hollingworth, Paul | Harold, Denise | Sims, Rebecca | Gerrish, Amy | Lambert, Jean-Charles | Carrasquillo, Minerva M | Abraham, Richard | Hamshere, Marian L | Pahwa, Jaspreet Singh | Moskvina, Valentina | Dowzell, Kimberley | Jones, Nicola | Stretton, Alexandra | Thomas, Charlene | Richards, Alex | Ivanov, Dobril | Widdowson, Caroline | Chapman, Jade | Lovestone, Simon | Powell, John | Proitsi, Petroula | Lupton, Michelle K | Brayne, Carol | Rubinsztein, David C | Gill, Michael | Lawlor, Brian | Lynch, Aoibhinn | Brown, Kristelle S | Passmore, Peter A | Craig, David | McGuinness, Bernadette | Todd, Stephen | Holmes, Clive | Mann, David | Smith, A David | Beaumont, Helen | Warden, Donald | Wilcock, Gordon | Love, Seth | Kehoe, Patrick G | Hooper, Nigel M | Vardy, Emma R. L. C. | Hardy, John | Mead, Simon | Fox, Nick C | Rossor, Martin | Collinge, John | Maier, Wolfgang | Jessen, Frank | Schürmann, Britta | Rüther, Eckart | Heun, Reiner | Kölsch, Heike | van den Bussche, Hendrik | Heuser, Isabella | Kornhuber, Johannes | Wiltfang, Jens | Dichgans, Martin | Frölich, Lutz | Hampel, Harald | Hüll, Michael | Gallacher, John | Rujescu, Dan | Giegling, Ina | Goate, Alison M | Kauwe, John S K | Cruchaga, Carlos | Nowotny, Petra | Morris, John C | Mayo, Kevin | Sleegers, Kristel | Bettens, Karolien | Engelborghs, Sebastiaan | De Deyn, Peter P | Van Broeckhoven, Christine | Livingston, Gill | Bass, Nicholas J | Gurling, Hugh | McQuillin, Andrew | Gwilliam, Rhian | Deloukas, Panagiotis | Al-Chalabi, Ammar | Shaw, Christopher E | Tsolaki, Magda | Singleton, Andrew B | Guerreiro, Rita | Mühleisen, Thomas W | Nöthen, Markus M | Moebus, Susanne | Jöckel, Karl-Heinz | Klopp, Norman | Wichmann, H-Erich | Pankratz, V Shane | Sando, Sigrid B | Aasly, Jan O | Barcikowska, Maria | Wszolek, Zbigniew K | Dickson, Dennis W | Graff-Radford, Neill R | Petersen, Ronald C | van Duijn, Cornelia M | Breteler, Monique MB | Ikram, M Arfan | DeStefano, Anita L | Fitzpatrick, Annette L | Lopez, Oscar | Launer, Lenore J | Seshadri, Sudha | Berr, Claudine | Campion, Dominique | Epelbaum, Jacques | Dartigues, Jean-François | Tzourio, Christophe | Alpérovitch, Annick | Lathrop, Mark | Feulner, Thomas M | Friedrich, Patricia | Riehle, Caterina | Krawczak, Michael | Schreiber, Stefan | Mayhaus, Manuel | Nicolhaus, S | Wagenpfeil, Stefan | Steinberg, Stacy | Stefansson, Hreinn | Stefansson, Kari | Snædal, Jon | Björnsson, Sigurbjörn | Jonsson, Palmi V. | Chouraki, Vincent | Genier-Boley, Benjamin | Hiltunen, Mikko | Soininen, Hilkka | Combarros, Onofre | Zelenika, Diana | Delepine, Marc | Bullido, Maria J | Pasquier, Florence | Mateo, Ignacio | Frank-Garcia, Ana | Porcellini, Elisa | Hanon, Olivier | Coto, Eliecer | Alvarez, Victoria | Bosco, Paolo | Siciliano, Gabriele | Mancuso, Michelangelo | Panza, Francesco | Solfrizzi, Vincenzo | Nacmias, Benedetta | Sorbi, Sandro | Bossù, Paola | Piccardi, Paola | Arosio, Beatrice | Annoni, Giorgio | Seripa, Davide | Pilotto, Alberto | Scarpini, Elio | Galimberti, Daniela | Brice, Alexis | Hannequin, Didier | Licastro, Federico | Jones, Lesley | Holmans, Peter A | Jonsson, Thorlakur | Riemenschneider, Matthias | Morgan, Kevin | Younkin, Steven G | Owen, Michael J | O’Donovan, Michael | Amouyel, Philippe | Williams, Julie
Nature genetics  2011;43(5):429-435.
We sought to identify new susceptibility loci for Alzheimer’s disease (AD) through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer’s Disease Genetic Consortium (ADGC). First, we undertook a combined analysis of four genome-wide association datasets (Stage 1) and identified 10 novel variants with P≤1×10−5. These were tested for association in an independent sample (Stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (Stage 3). Meta-analyses of all data provide compelling evidence that ABCA7 (meta-P 4.5×10−17; including ADGC meta-P=5.0×10−21) and the MS4A gene cluster (rs610932, meta-P=1.8×10−14; including ADGC meta-P=1.2×10−16; rs670139, meta-P=1.4×10−9; including ADGC meta-P=1.1×10−10) are novel susceptibility loci for AD. Second, we observed independent evidence for association for three suggestive loci reported by the ADGC GWAS, which when combined shows genome-wide significance: CD2AP (GERAD+ P=8.0×10−4; including ADGC meta-P=8.6×10−9), CD33 (GERAD+ P=2.2×10−4; including ADGC meta-P=1.6×10−9) and EPHA1 (GERAD+ P=3.4×10−4; including ADGC meta-P=6.0×10−10). These findings support five novel susceptibility genes for AD.
doi:10.1038/ng.803
PMCID: PMC3084173  PMID: 21460840
25.  Ginkgo biloba and risk of cancer: Secondary Analysis of the Ginkgo Evaluation of Memory (GEM) Study 
Purpose
Evidence from in vitro and in vivo studies suggests that Ginkgo biloba has cancer chemopreventive properties, but epidemiological evidence is sparse. We analyzed cancer as a secondary endpoint in the Ginkgo Evaluation of Memory (GEM) Study, the largest randomized, double-blind, placebo-controlled clinical trial of Ginkgo supplementation to date.
Methods
A total of 3,069 GEM participants 75+ years of age were randomized to twice-daily doses of either 120mg Ginkgo extract (EGb 761) or placebo and followed for a median 6.1 years. We identified hospitalizations for invasive cancer by reviewing hospital admission and discharge records for all reported hospitalizations over follow-up. Using an intention-to-treat approach, we compared the risk of cancer hospitalization between participants assigned to treatment and those assigned to placebo.
Results
During the intervention, there were 148 cancer hospitalizations in the placebo group and 162 in the EGb 761 group (Hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.87–1.36; p=0.46). Among the site-specific cancers analyzed, we observed an increased risk of breast (HR, 2.15; 95% CI, 0.97–4.80; p=0.06) and colorectal (HR, 1.62; 95% CI, 0.92–2.87; p=0.10) cancer, and a reduced risk of prostate cancer (HR, 0.71; 95% CI, 0.43–1.17; p=0.18).
Conclusions
Overall, these results do not support the hypothesis that regular use of Ginkgo biloba reduces the risk of cancer.
doi:10.1002/pds.1979
PMCID: PMC2917376  PMID: 20582906
Ginkgo biloba; randomized controlled trial; breast cancer; prostate cancer; complimentary and alternative medicine

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