10-year trajectories of depressive symptoms and risk of dementia: a population-based study.

BACKGROUND: Late-life depressive symptoms have been extensively studied for their relationship with incident dementia, but have been typically assessed at a single timepoint. Such an approach neglects the course of depression, which, given its remitting and relapsing nature, might provide further insights into the complex association of depression with dementia. We therefore repeatedly measured depressive symptoms in a population of adults over a decade to study the subsequent risk of dementia. METHODS: Our study was embedded in the Rotterdam Study, a population-based study of adults aged 55 years or older in Rotterdam (Netherlands), ongoing since 1990. The cohort is monitored continuously for major events by data linkage between the study database and general practitioners. We examined a cohort of participants who were free from dementia, but had data for depressive symptoms from at least one examination round in 1993-95, 1997-99, or 2002-04. We assessed depressive symptoms with the validated Dutch version of the Center for Epidemiology Depression Scale (CES-D) and the Hospital Anxiety and Depression Scale-Depression. We used these data to identify 11-year trajectories of depressive symptoms by latent class trajectory modelling. We screened participants for dementia at each examination round and followed up participants for 10 years for incident dementia by latent trajectory from the third examination round to 2014. We calculated hazard ratios (HR) for dementia by assigned trajectory using two Cox proportional hazards models (model 1 adjusted for age and sex only, and model 2 adjusted additionally for APOEɛ4 carrier status, educational level, body-mass index, smoking, alcohol consumption, cognitive score, use of antidepressants, and prevalent disease status at baseline). We repeated the analyses censoring for incident stroke, restricting to Alzheimer's disease as an outcome, and accounting for mortality as a competing risk for dementia. FINDINGS: From 1993-2004, we obtained data for depressive symptoms from at least one examination round for 3325 participants (median age: 74·88 years [IQR 70·62-80·06], 1995 [60%] women). We identified five trajectories of depressive symptoms in these 3325 individuals, characterised by maintained low CES-D scores (low; 2441 [73%]); moderately high starting scores but then remitting (decreasing; 369 [11%]); low starting scores, increasing, then remitting (remitting; 170 [5%]); low starting scores that steadily increased (increasing; 255 [8%]); and maintained high scores (high; 90 [3%]). During 26 330 person-years, 434 participants developed incident dementia. Only the trajectory with increasing depressive symptoms was associated with a higher risk of dementia compared with the low depressive symptom trajectory, using model 2 (HR 1·42, 95% CI 1·05-1·94; p=0·024). Additionally, only the increasing trajectory was associated with a higher risk of dementia compared with the low trajectory after censoring for incident stroke (1·58, 1·15-2·16; p=0·0041), restricting to Alzheimer's disease as an outcome (1·44, 1·03-2·02; p=0·034), and accounting for mortality as a competing risk (1·45, 1·06-1·97; p=0·019). INTERPRETATION: Risk of dementia differed with different courses of depression, which could not be captured by a single assessment of depressive symptoms. The higher risk of dementia only in the increasing trajectory suggests depression might be a prodrome of dementia. FUNDING: Erasmus Medical Center; ZonMw; the Netherlands Ministry of Education Culture and Science; and the Netherlands Ministry for Health, Welfare and Sports.

Genetic diversity is a predictor of mortality in humans.

BACKGROUND: It has been well-established, both by population genetics theory and direct observation in many organisms, that increased genetic diversity provides a survival advantage. However, given the limitations of both sample size and genome-wide metrics, this hypothesis has not been comprehensively tested in human populations. Moreover, the presence of numerous segregating small effect alleles that influence traits that directly impact health directly raises the question as to whether global measures of genomic variation are themselves associated with human health and disease. RESULTS: We performed a meta-analysis of 17 cohorts followed prospectively, with a combined sample size of 46,716 individuals, including a total of 15,234 deaths. We find a significant association between increased heterozygosity and survival (P = 0.03). We estimate that within a single population, every standard deviation of heterozygosity an individual has over the mean decreases that person's risk of death by 1.57%. CONCLUSIONS: This effect was consistent between European and African ancestry cohorts, men and women, and major causes of death (cancer and cardiovascular disease), demonstrating the broad positive impact of genomic diversity on human survival.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium.

OBJECTIVES: To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. DESIGN: Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. PARTICIPANTS: Current, former and never smokers of European ancestry aged ≥16 years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). PRIMARY OUTCOME MEASURES: Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. RESULTS: The analytic sample included up to 58 176 never smokers, 37 428 former smokers and 32 028 current smokers (total N=127 632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. CONCLUSIONS: Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Association between circulating adiponectin levels and polycystic ovarian syndrome.

BACKGROUND: Low adiponectin levels in polycystic ovarian syndrome (PCOS) have been largely attributed to obesity which is common among these patients. In addition, evidence also suggests that low adiponectin in PCOS may be related to insulin resistance (IR) in these women. However, studies on the role of adiponectin in younger and lean patients are limited. Therefore, the aim of the present study was to examine the association of adiponectin levels in young and lean women with PCOS. METHODS: A case-control study was conducted at the Dow University of Health Sciences, Karachi, Pakistan. Cases were 75 patients of PCOS with Body Mass Index (BMI) &23 aged 16-35 years and 75 healthy age and BMI matched controls were selected from family and friends of the cases. Demographic details, family history and past medical history were obtained through interview by a physician. Anthropometric measurements included weight and height of the participants. Fasting glucose, total cholesterol, high-density lipoprotein (HDL), insulin, adiponectin, and androgen levels were determined. IR was calculated using homeostasis model assessment for insulin resistance (HOMA-IR). Logistic regression models were used to assess the association between adiponectin and PCOS after adjusting for co-variates. RESULTS: On multivariable analysis, PCOS cases were 3.2 times more likely to have low adiponectin level (OR = 3.2, 95% CI 1.49-6.90, p-value 0.003) compared to the controls after adjustment for age, BMI, family history, marital status, total cholesterol, HDL level and IR. Females with a family history of PCOS were significantly more likely to have lower adiponectin (OR = 3.32, 95% CI 1.27-8.67, p-value 0.014) compared to those who did not have a family history of PCOS. The associations of IR and family history with low adiponectin level also remained statistically significant after adjustments for covariates. CONCLUSION: Serum adiponectin levels are independently associated with PCOS and are only partly explained by IR. Adiponectin level may serve as a potential independent biomarker for diagnosis of PCOS in young and lean women with fewer symptoms, or women with a family history of PCOS.

Water-pipe smoking and albuminuria: new dog with old tricks.

Water-pipe (WP) smoking is on rise worldwide for the past few years, particularly among younger individuals. Growing evidence indicates that WP smoking is as harmful as cigarette smoking. To date, most of the research has focused on acute health effects of WP smoking, and evidence remains limited when it comes to chronic health effects in relation to long-term WP smoking. Therefore, the aim of this study was to examine the association between WP smoking and albuminuria in apparently healthy individuals. This analysis was conducted on data of a population-based cross-sectional study--the Urban Rural Chronic Diseases Study (URCDS). The study sample was recruited from three sites in Pakistan. Trained nurses carried out individual interviews and obtained the information on demographics, lifestyle factors, and past and current medical history. Measurements of complete blood count, lipid profile, fasting glucose level, and 24-hour albuminuria were also made by using blood and urine samples. Albumin excretion was classified into three categories using standard cut-offs: normal excretion, high-normal excretion and microalbuminuria. Multiple logistic regression models were used to examine the relationship between WP smoking and albuminuria. The final analysis included data from 1,626 health individuals, of which 829 (51.0%) were males and 797 (49.0%) females. Of 1,626 individuals, 267 (16.4%) were current WP smokers and 1,359 (83.6%) were non-WP smokers. WP smoking was significantly associated with high-normal albuminuria (OR  =  2.33, 95% CI 1.68-3.22, p-value <0.001) and microalbuminuria (OR  =  1.75, 95% CI 1.18-2.58, p-value 0.005) after adjustment for age, sex, BMI, social class, hypertension, and diabetes mellitus. WP smoking was significantly associated with high-normal albuminuria and microalbuminuria when analysis was stratified on hypertension and diabetes mellitus categories. WP smoking has a strong association with albuminuria in apparently healthy individuals. More research is warranted to evaluate the temporality of this association between WP smoking and albuminuria.

Water-pipe smoking and metabolic syndrome: a population-based study.

Water-pipe (WP) smoking has significantly increased in the last decade worldwide. Compelling evidence suggests that the toxicants in WP smoke are similar to that of cigarette smoke. The WP smoking in a single session could have acute harmful health effects even worse than cigarette smoking. However, there is no evidence as such on long term WP smoking and its impact on chronic health conditions particularly cardiovascular and metabolic conditions. Therefore, we conducted this study to investigate the relationship between WP smoking and metabolic syndrome (MetS). This was a cross-sectional study carried out in Punjab province of Pakistan using the baseline data of a population-based study--Urban Rural Chronic Diseases Study (URCDS). Information was collected by trained nurses regarding the socio-demographic profile, lifestyle factors including WP smoking, current and past illnesses. A blood sample was obtained for measurement of complete blood count, lipid profile and fasting glucose level. MetS was ascertained by using the International Diabetic Federation's criteria. We carried out multiple logistic regressions to investigate the association between WP smoking and MetS. Final sample included 2,032 individuals--of those 325 (16.0%) were current WP smokers. Age adjusted-prevalence of MetS was significantly higher among current WP smokers (33.1%) compared with non-smokers (14.8%). Water-pipe smokers were three times more likely to have MetS (OR 3.21, 95% CI 2.38-4.33) compared with non-smokers after adjustment for age, sex and social class. WP smokers were significantly more likely to have hypertriglyceridemia (OR 1.63, 95% CI 1.25-2.10), hyperglycaemia (OR 1.82, 95% CI 1.37-2.41), Hypertension (OR 1.95, 95% CI 1.51-2.51) and abdominal obesity (OR 1.93, 95% CI 1.52-2.45). However, there were no significant differences in HDL level between WP smokers and non-smokers. This study suggests that WP smoking has a significant positive (harmful) relationship with MetS and its components.

Areca nut chewing and systemic inflammation: evidence of a common pathway for systemic diseases.

BACKGROUND: Areca nut, the seed of fruit of an oriental palm, known as Areca catechu, is commonly chewed in many countries. Diabetes, hypertension, cardiovascular diseases, oropharyngeal and oesophageal cancers have been associated with areca nut chewing and the mechanism by which areca nut chewing increases the risk of systemic diseases remains elusive. We hypothesize that systemic inflammation may be elevated among areca nut users, which is linked with many systemic diseases. Therefore, this present study was conducted to examine the systemic inflammation among areca nut chewers and healthy controls. METHODS: This was an observational cross sectional study carried out on areca nut chewers and healthy individuals in Karachi, Pakistan. Participants were selected from a region of the city by invitation request sent from door to door. Information was collected regarding the socio-demographic profile and the pattern of use, and a blood sample was obtained to measure the level of C-reactive protein (CRP). We carried out multiple logistic regressions to investigate the association between socio-demographic profile, areca nut chewing and CRP levels. RESULTS: We carried out final analysis on 1112 individuals of which 556 were areca nut chewers and 556 were the age, gender and area matched controls. Areca nut chewers had a significantly higher proportion of men (15.1%, n = 84) who had an elevated CRP (>10 mg/dl) as compared to controls (5.2%, n = 29). Multivariate analyses showed that areca nut chewers had significantly higher odds of an elevated CRP (OR = 3.23, 95% CI 2.08-5.02, p value <0.001) as compared to controls. Increase in amount of areca nut consumption had a significant dose-response relationship with systemic inflammation (p for trend <0.001). Further analysis revealed that areca nut chewers with tobacco additives were two times more likely to have an elevated CRP as compared to raw areca nut users. These associations remained unchanged after adjustments for age, BMI and years of full time education. CONCLUSIONS: Areca nut chewing has a significant association with systemic inflammation. Further work is required to confirm that systemic inflammation is the main pathway by which areca nut use increases the risk of systemic diseases.

Neutrophil lymphocyte ratio as a measure of systemic inflammation in prevalent chronic diseases in Asian population.

BACKGROUND: Preliminary evidence has suggested the role of inflammation in development and prognosis of cardiovascular diseases and cancers. Most of the prognostic studies failed to account for the effects of co-morbid conditions as these might have raised the systemic inflammation. We used neutrophil lymphocyte ratio (NLR) as a measure of systemic inflammation and investigated its association with prevalent chronic conditions. METHODS: Present study is a cross sectional study conducted on population of Karachi, Pakistan. A detailed questionnaire about the demographic details of all subjects was filled and an informed consent obtained for blood sampling. Multinomial regression analyses were carried out to investigate the relationship between NLR and prevalent chronic conditions. RESULTS: 1070 apparently healthy individuals participated in the study. Proportion of individuals with hypertension was higher in middle and highest tertile of NLR as compared to the lowest tertile (18.2% & 16.1% compared to 11.8%). Individuals with hypertension were 43% (RRR = 1.43, 95% CI 0.94-2.20) and 66% (RRR = 1.69, 95% CI 1.09-2.54) more likely to be in the middle and highest tertile of NLR respectively compared to the baseline group. Similarly, individuals with diabetes mellitus were 53% (RRR = 1.53, 95% CI 0.93-2.51) and 65% (RRR = 1.65, 95% CI 1.01-2.71) more likely to be in the middle or highest tertile of NLR as compared to the baseline NLR group. CONCLUSIONS: Systemic inflammation measured by NLR has a significant association with prevalent chronic conditions. Future research is needed to investigate this relationship with longitudinal data to establish the temporal association between these variables.