Hind A. Beydoun

Obesity and central obesity as risk factors for incident dementia and its subtypes: a systematic review and meta-analysis

While dementia affects 6–10% of persons 65 years or older, industrialized countries have witnessed an alarming rise in obesity. However, obesitys influence on dementia remains poorly understood. We conducted a systematic review and meta‐analysis. PUBMED search (1995–2007) resulted in 10 relevant prospective cohort studies of older adults (40–80 years at baseline) with end points being dementia and predictors including adiposity measures, such as body mass index (BMI) and waist circumference (WC). There was a significant U‐shaped association between BMI and dementia (P = 0.034), with dementia risk increased for obesity and underweight. Pooled odds ratios (OR) and 95% confidence intervals (CI) for underweight, overweight and obesity compared with normal weight in relation to incident dementia were: 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93, 2.18) respectively. Pooled ORs and 95% CI for obesity and incident Alzheimers disease (AD) and vascular dementia were 1.80 (1.00, 3.29) vs. 1.73 (0.47, 6.31) and were stronger in studies with long follow‐up (>10 years) and young baseline age (<60 years). Weight gain and high WC or skin‐fold thickness increased risks of dementia in all included studies. The meta‐analysis shows a moderate association between obesity and the risks for dementia and AD. Future studies are needed to understand optimal weight and biological mechanisms.

Physical and mental health outcomes of prenatal maternal stress in human and animal studies: a review of recent evidence

Prenatal maternal stress (PNMS) has been linked with adverse health outcomes in the offspring through experimental studies using animal models and epidemiological studies of human populations. The purpose of this review article is to establish a parallel between animal and human studies, while focusing on methodological issues and gaps in knowledge. The review examines the quality of recent evidence for prevailing PNMS theoretical models, namely the biopsychosocial model for adverse pregnancy outcomes and the fetal programming model for chronic diseases. The investigators used PubMed (2000-06) to identify recently published original articles in the English language literature. A total of 103 (60 human and 43 animal) studies were examined. Most human studies originated from developed countries, thus limiting generalisability to developing nations. Most animal studies were conducted on non-primates, rendering extrapolation of findings to pregnant women less straightforward. PNMS definition and measurement were heterogeneous across studies examining similar research questions, thus precluding the conduct of meta-analyses. In human studies, physical health outcomes were often restricted to birth complications while mental health outcomes included postnatal developmental disorders and psychiatric conditions in children, adolescents and adults. Diverse health outcomes were considered in animal studies, some being useful models for depression, schizophrenia or attention deficit hyperactivity disorder in human populations. The overall evidence is consistent with independent effects of PNMS on perinatal and postnatal outcomes. Intervention studies and large population-based cohort studies combining repeated multi-dimensional and standardised PNMS measurements with biomarkers of stress are needed to further understand PNMS aetiology and pathophysiology in human populations.

Intimate partner violence against adult women and its association with major depressive disorder, depressive symptoms and postpartum depression: a systematic review and meta-analysis.

To date, few systematic reviews of observational studies have been conducted to comprehensively evaluate the co-morbidity of intimate partner violence (IPV) and specific depression outcomes in women. In this systematic review and meta-analysis, we summarize the extant literature and estimate the magnitude of the association between IPV and key depressive outcomes (elevated depressive symptoms, diagnosed major depressive disorder and postpartum depression). PubMed (January 1, 1980-December 31, 2010) searches of English-language observational studies were conducted. Most of the selected 37 studies had cross-sectional population-based designs, focused on elevated depressive symptoms and were conducted in the United States. Most studies suggested moderate or strong positive associations between IPV and depression. Our meta-analysis suggested two to three-fold increased risk of major depressive disorder and 1.5-2-fold increased risk of elevated depressive symptoms and postpartum depression among women exposed to intimate partner violence relative to non-exposed women. A sizable proportion (9%-28%) of major depressive disorder, elevated depressive symptoms, and postpartum depression can be attributed to lifetime exposure to IPV. In an effort to reduce the burden of depression, continued research is recommended for evaluating IPV preventive strategies.

Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue

Purpose: Histopathology is the standard approach for tissue diagnostics and centerpiece of pathology. Although the current system provides prognostic information, there is need for molecular markers that enhance diagnosis and better predict clinical prognosis. The ability to localize disease-specific molecular changes in biopsy tissue would help improve critical pathology decision making. Direct profiling of proteins from tissue using matrix-assisted laser desorption/ionization imaging mass spectrometry has the potential to supplement morphology with underlying molecular detail. Experimental Design: A discovery set of 11 prostate cancer (PCa)–containing and 10 benign prostate tissue sections was evaluated for protein expression differences. A separate validation set of 54 tissue sections (23 PCa and 31 benign) was used to verify the results. Cryosectioning was done to yield tissue sections analyzed by a pathologist to determine tissue morphology and mirror sections for imaging mass spectrometry. Spectra were acquired and the intensity of signals was plotted as a function of the location within the tissue. Results: An expression profile was found that discriminates between PCa and normal tissue. The overexpression of a single ion at m/z 4,355 was able to discriminate cancer from uninvolved tissue. Tandem mass spectrometry identified this marker as a fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 (MEKK2). The ability of MEKK2 to discriminate tumor from normal cells was orthogonally confirmed. Conclusions: This study highlights the potential of this approach to uncover molecular detail that can be correlated with pathology decision making. In addition, the identification of MEKK2 shows the ability to discover proteins of relevance to PCa biology. (Clin Cancer Res 2009;15(17):5541–51)

Serum Antioxidant Status Is Associated with Metabolic Syndrome among U.S. Adults in Recent National Surveys

Potential antiinflammatory and antioxidant effects were recently ascribed to naturally occurring micronutrients. The extent and magnitudes of their differential effects on the metabolic syndrome (MetS) are still unknown. We examined the association between serum antioxidant status and MetS. NHANES 2001-2006 cross-sectional data among adults aged 20-85 y were analyzed (n = 3008-9099). MetS was defined with the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and also by elevated homeostatic model assessment insulin resistance (HOMA-IR), C-reactive protein (CRP) and hyperuricemia. Serum antioxidants included retinol, retinyl esters, carotenoids [α-carotene, β-carotene (cis+trans), β-cryptoxanthin, lutein+zeaxanthin, total lycopene], vitamin E, and vitamin C. MetS (NCEP ATP III) prevalence in U.S. adults was 32.0% among men and 29.5% among women. Adults with MetS had consistently lower serum carotenoid concentrations compared with those without MetS, even after controlling for total cholesterol and TG among other potential confounders. Vitamin E had no significant relationship with MetS in the full multiple logistic regression model, whereas retinol+retinyl esters were inversely related to MetS among men only. The latter were also inversely related to elevated CRP and positively associated with hyperuricemia. Vitamin C exhibited a similar pattern to serum carotenoids with an inverse linear association with MetS (binary), HOMA-IR, and hyperuricemia. Future intervention studies of dietary and lifestyle change must be conducted to assess the utility of modifying serum antioxidant concentrations, especially carotenoids, given their suboptimal levels among U.S. adults with MetS, for the prevention of type 2 diabetes and various cardiovascular endpoints.

Intimate partner violence as a risk factor for postpartum depression among Canadian women in the Maternity Experience Survey

PURPOSE Intimate partner violence is a worldwide public health concern that predominantly affects women of reproductive age. The purpose of this study was to evaluate the effect of exposure to intimate partner violence before, during, or after pregnancy on postpartum depression in a nationally representative sample of Canadian women. METHODS A cross-sectional analysis was performed with the use of data from the Maternity Experience Survey conducted by Statistics Canada in 2006. A population-based sample of 8542 women 15 years and older who delivered singleton live births was selected from all Canadian provinces and territories; of those, 6421 completed a computer-assisted telephone interview. Recent experiences with and threats of physical or sexual violence by an intimate partner were examined in relation to postpartum depression assessed through the Edinburgh Postpartum Depression Scale. RESULTS The prevalence of postpartum depression was 7.5% (95% confidence interval, 6.8-8.2). Controlling for confounders, odds of postpartum depression were significantly greater among women who reported partner violence in the past two years as opposed to those who did not (adjusted odds ratio, 1.61; 95% confidence interval, 1.06-2.45). CONCLUSIONS Intimate partner violence is positively associated with postpartum depression among Canadian women. Implications for healthcare practice are discussed.

Statins and serum cholesterol's associations with incident dementia and mild cognitive impairment

Background Statin use and serum cholesterol reduction have been proposed as preventions for dementia and mild cognitive impairment (MCI). Methods 1604 and 1345 eligible participants from the Baltimore Longitudinal Study of Aging (BLSA) were followed after age 50 for a median time of around 25 years, to examine the incidence of dementia (n=259) and MCI (n=138), respectively. Statin use (ever-use and time-dependent use), total cholesterol levels (TC; first visit and time-dependent), TC change trajectory from first visit and high-density lipoprotein (HDL-C):TC ratio (first visit and time-dependent) were the main exposures of interest. Cox proportional hazards models were used. Results Participants with incident dementia had a higher first-visit TC compared with participants who remained free of dementia and MCI, while first-visit TC was higher among statin ever-users compared with never-users (age-unadjusted associations). Statin users had a two- to threefold lower risk of developing dementia (HR=0.41; 95% CI 0.18 to 0.92), but not MCI, when considering time-dependent ‘statin use’ with propensity score model adjustment. This association remained significant independently of serum cholesterol exposures. An elevated first-visit TC was associated with reduced MCI risk (upper quartile (Q4) vs Q1: HR=0.51; 95% CI 0.29 to 0.90). Compared with the lowest quartile (Q1: 0.00–0.19), HDL-C:TC (time-dependent) in (Q2: 0.19–0.24) was associated with reduced MCI risk (HR=0.58; 95% CI 0.34 to 0.98). Among men only, TC decline from first visit was significantly associated with increased dementia risk (HR=4.21; 95% CI 1.28 to 13.85). Conclusions Statins may have multifactorial effects on dementia but not MCI risk. Future interventions may be warranted, and research should focus on optimal serum TC, HDL-C:TC ratio and TC change trajectories.

Serum Folate, Vitamin B-12, and Homocysteine and Their Association With Depressive Symptoms Among U.S. Adults

Objective: To examine, in a nationally representative sample of U.S. adults, the associations of serum folate, vitamin B-12, and total homocysteine (tHcy) levels with depressive symptoms. Several nutritional and physiological factors have been linked to depression in adults, including low folate and vitamin B-12 and elevated tHcy levels. Methods: Data on U.S. adults (age, 20–85 years; n = 2524) from the National Health and Nutrition Examination Survey during the period 2005 to 2006 were used. Depressive symptoms were measured with the Patient Health Questionnaire (PHQ), and elevated symptoms were defined as a PHQ total score of ≥10. Serum folate, vitamin B-12, and tHcy were mainly expressed as tertiles. Multiple ordinary least square (OLS), logistic, and zero-inflated Poisson regression models were conducted in the main analysis. Results: Overall, mean PHQ score was significantly higher among women compared with men. Elevated depressive symptoms (PHQ score of ≥10) were inversely associated with folate status, particularly among women (fully adjusted odds ratio [tertiles T3 versus T1] = 0.37; 95% confidence interval, 0.17–0.86), but not significantly related to tHcy or vitamin B-12. No interaction was noted between the three exposures in affecting depressive symptoms. In older adults (≥50 years) and both sexes combined, tHcy was positively associated with elevated depressive symptoms (fully adjusted odds ratio [tertiles T2 versus T1] = 3.01; 95% confidence interval, 1.01–9.03), although no significant dose-response relationship was found. Conclusions: Future interventions to improve mental health outcomes among U.S. adults should take into account dietary and other factors that would increase levels of serum folate. BH4 = tetrahydro biopterins; CNS = central nervous system; DSM = Diagnostic and Statistical Manual; MEC = Mobile Examination Center; MR = methylation reactions; NHANES = National Health and Nutrition Examination Surveys; OLS = ordinary least square; PHQ = Patient Health Questionnaire; PIR = Poverty Income Ratio; tHcy = total homocysteine; T = tertile.

Household crowding index: a correlate of socioeconomic status and inter-pregnancy spacing in an urban setting

Objectives: This paper examines the effect of household crowding on inter-pregnancy spacing and its association with socioeconomic indicators, among parous mothers delivered in an urban environment. Design: Cross sectional survey. Methods: Sociodemographic data were obtained on 2466 parous women delivering at eight hospitals in Greater Beirut over a one year period. Statistical methodology comprised Pearson χ2 test and logistic regression analysis. Main results: A significant inverse relation was observed between household crowding and socioeconomic status, defined as education and occupation of women and their spouses. Inter-pregnancy spacing increased with higher levels of crowding. Further analysis suggested that this positive association was confounded by maternal demographic characteristics. Conclusions: These data have shown that household crowding, a correlate of low parental socioeconomic status, is associated with longer birth intervals. This association, however, seems to be largely explained by maternal age and parity.

Serum Antioxidant Concentrations and Metabolic Syndrome Are Associated among U.S. Adolescents in Recent National Surveys

Specific micronutrients, including retinol, retinyl esters, carotenoids [α-carotene, β-carotene (cis+trans), β-cryptoxanthin, lutein+zeaxanthin, and total lycopene], vitamin E, and vitamin C have antiinflammatory and antioxidant effects, properties shown to reduce oxidative stress, a process that accompanies the pathogenesis of many chronic diseases. It is still largely unknown whether they are associated with the occurrence of metabolic syndrome (MetS) in the adolescent U.S. population. MetS was defined by the International Diabetes Federation (IDF) criteria. Other non-MetS outcomes relying on blood measurements were elevated HOMA-IR, C-reactive protein (CRP), and hyperuricemia. We tested associations between serum antioxidants and MetS outcomes among adolescents aged 12-19 y using cross-sectional data from NHANES 2001-2006 (n = 782-4285). IDF MetS prevalence was estimated at 7% among boys and 3% among girls. In adjusted models, adolescents with MetS had consistently lower carotenoid concentrations compared with their counterparts without MetS. Total carotenoids were also inversely related to HOMA-IR and CRP. Vitamin C was inversely related to uric acid level and MetS binary outcome. Retinol+retinyl esters exhibited an inverse relationship with CRP and a positive relationship with uric acid and HOMA-IR as well as MetS binary outcome. Vitamin E had no association with MetS, particularly after controlling for serum cholesterol and TG. In conclusion, among U.S. adolescents, serum carotenoid concentrations were inversely associated with MetS status, HOMA-IR, and CRP, whereas serum vitamin C was inversely related to MetS status and serum uric acid. Vitamin E had no consistent association with MetS, whereas retinol+retinyl esters had a positive relationship with HOMA-IR, uric acid, and MetS, while being inversely related to CRP. These associations need further study.