Marios K. Georgakis

Comorbidity of Cognitive Impairment and Late-Life Depression Increase Mortality: Results From a Cohort of Community-Dwelling Elderly Individuals in Rural Greece.

Objective: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece. Methods: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders. Results: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI. Conclusion: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.

Albuminuria in Association with Cognitive Function and Dementia: A Systematic Review and Meta-Analysis

Cerebral microvascular disease is considered to contribute to cognitive dysfunction. We opted to explore whether albuminuria, a marker of systemic microangiopathy, is associated with cognitive impairment, dementia, and cognitive function.

Circulating adiponectin levels in relation to carotid atherosclerotic plaque presence, ischemic stroke risk, and mortality: A systematic review and meta-analyses

BACKGROUND Low circulating levels of adiponectin, an anti-inflammatory and vasculoprotective adipokine, are associated with obesity, type 2 diabetes, and atherosclerotic disease. Presence of unstable plaques in the carotid artery is a known etiological factor causing ischemic strokes. Herein, we systematically reviewed the association between circulating adiponectin and progression of carotid atherosclerotic disease, particularly evaluating the occurrence of (1) carotid atherosclerotic plaques, (2) ischemic stroke, and (3) mortality in subjects who suffered a previous ischemic stroke. METHODS Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The effect size and 95% confidence intervals (CIs) of the individual studies were pooled using fixed-effect or random-effect models. The quality of the eligible studies was evaluated using the Newcastle-Ottawa quality assessment scale. Sensitivity, subgroup, and meta-regression analyses were performed to address the impact of various risk factors on the association between adiponectin and ischemic stroke risk. RESULTS Twelve studies fulfilled the inclusion criteria for 3 independent meta-analyses. The association of increasing circulating adiponectin levels (5μg/mL-increment) with presence of carotid plaque was not conclusive (n=327; OR: 1.07; 95% CI: 0.85-1.35; 2 studies), whereas high adiponectin levels showed a significant 8% increase in risk of ischemic stroke (n=13,683; 7 studies), with a more sizable association observed among men compared to women. HDL was observed to have a marginal effect on the association between adiponectin and ischemic stroke, while other evaluated parameters were not found to be effect modifiers. A non-significant association of adiponectin with mortality was yielded (n=663; OR: 2.58; 95% CI: 0.69-9.62; 3 studies). Although no publication bias was evident, there was significant between-study heterogeneity in most analyses. CONCLUSION It appears that the direction of the relationship between adiponectin and carotid atherosclerotic plaque presence is dependent on the duration, severity, and nature of the underlying disease, while increased adiponectin levels were associated with an increase in risk for ischemic stroke. Lastly, the results from the mortality meta-analysis remain inconclusive. Future properly designed studies are necessary to further elucidate the role of adiponectin on atherosclerotic plaque development, and its related outcomes.

Blood Pressure and All-Cause Mortality by Level of Cognitive Function in the Elderly: Results From a Population-Based Study in Rural Greece.

This study aimed to investigate whether the effect of blood pressure (BP) on mortality differs by levels of cognitive function. The associations of brachial systolic BP, diastolic BP, mean arterial pressure (MAP), and pulse pressure with all‐cause mortality were prospectively explored (follow‐up 7.0±2.2 years) in 660 community‐dwelling individuals (≥60 years) using adjusted Cox models, stratified by cognitive impairment (Mini‐Mental State Examination [MMSE] <24). No association between brachial BP variables and mortality was shown for the total sample in quartiles analysis; however, MAP in the highest quartile, compared with the second, was associated with mortality (hazard ratio, 1.85; 95% confidence intervals, 1.09–3.12) among cognitively impaired individuals. The fractional‐polynomials approach for BP confirmed this finding and further showed, solely in the MMSE <24 subcohort, U‐shaped trends of MAP and systolic BP, with increased mortality risk in extremely low or high values; no such pattern was evident for patients with MMSE ≥24. Elderly individuals with cognitive impairment might be more susceptible to the detrimental effects of low and elevated MAP and systolic BP.

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US: Incidence variation in neuroblastoma

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern–Eastern Europe (SEE), including – for the first time – the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM‐ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age‐adjusted incidence rates (AIR) were calculated for 1,859 childhood (0–14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990–2016), and were compared to those of SEER/US (N = 3,166; 1990–2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one‐third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1–4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male‐to‐female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.

Malignant central nervous system tumors among adolescents and young adults (15‐39 years old) in 14 Southern‐Eastern European registries and the US Surveillance, Epidemiology, and End Results program: Mortality and survival patterns

Unique features and worse outcomes have been reported for cancers among adolescents and young adults (AYAs; 15‐39 years old). The aim of this study was to explore the mortality and survival patterns of malignant central nervous system (CNS) tumors among AYAs in Southern‐Eastern Europe (SEE) in comparison with the US Surveillance, Epidemiology, and End Results (SEER) program.

Mortality and survival patterns of childhood lymphomas: geographic and age-specific patterns in Southern-Eastern European and SEER/US registration data.

Childhood (0‐14 years) lymphomas, nowadays, present a highly curable malignancy compared with other types of cancer. We used readily available cancer registration data to assess mortality and survival disparities among children residing in Southern‐Eastern European (SEE) countries and those in the United States. Average age‐standardized mortality rates and time trends of Hodgkin (HL) and non‐Hodgkin (NHL; including Burkitt [BL]) lymphomas in 14 SEE cancer registries (1990‐2014) and the Surveillance, Epidemiology, and End Results Program (SEER, United States; 1990‐2012) were calculated. Survival patterns in a total of 8918 cases distinguishing also BL were assessed through Kaplan‐Meier curves and multivariate Cox regression models. Variable, rather decreasing, mortality trends were noted among SEE. Rates were overall higher than that in SEER (1.02/106), which presented a sizeable (−4.8%, P = .0001) annual change. Additionally, remarkable survival improvements were manifested in SEER (10 years: 96%, 86%, and 90% for HL, NHL, and BL, respectively), whereas diverse, still lower, rates were noted in SEE. Non‐HL was associated with a poorer outcome and an amphi‐directional age‐specific pattern; specifically, prognosis was inferior in children younger than 5 years than in those who are 10 to 14 years old from SEE (hazard ratio 1.58, 95% confidence interval 1.28‐1.96) and superior in children who are 5 to 9 years old from SEER/United States (hazard ratio 0.63, 95% confidence interval 0.46‐0.88) than in those who are 10 to 14 years old. In conclusion, higher SEE lymphoma mortality rates than those in SEER, but overall decreasing trends, were found. Despite significant survival gains among developed countries, there are still substantial geographic, disease subtype‐specific, and age‐specific outcome disparities pointing to persisting gaps in the implementation of new treatment modalities and indicating further research needs.

Albuminuria and Cerebral Small Vessel Disease: A Systematic Review and Meta-Analysis

To determine whether albuminuria, a marker of systemic endothelial dysfunction, is associated with cerebral small vessel disease (SVD).

Validation of TICS for detection of dementia and mild cognitive impairment among individuals characterized by low levels of education or illiteracy: a population-based study in rural Greece

Abstract Objective: The efficacy of the most widely used tests for dementia screening is limited in populations characterized by low levels of education. This study aimed to validate the face-to-face administered Telephone Interview for Cognitive Status (TICS) for detection of dementia and mild cognitive impairment (MCI) in a population-based sample of community dwelling individuals characterized by low levels of education or illiteracy in rural Greece. Methods: The translated Greek version of TICS was administered through face-to-face interview in 133 elderly residents of Velestino of low educational level (<12 years). We assessed its internal consistency and test–retest reliability, its correlation with sociodemographic parameters, and its discriminant ability for cognitive impairment and dementia, as defined by a brief neurological evaluation, including assessment of cognitive status and level of independence. Results: TICS was characterized by adequate internal consistency (Cronbach’s α: .72) and very high test–retest reliability (intra-class correlation coefficient: .93); it was positively correlated with age and educational years. MCI and dementia were diagnosed in 18 and 10.5% of the population, respectively. Its discriminant ability for detection of dementia was high (Area under the curve, AUC: .85), with a sensitivity and specificity of 86 and 82%, respectively, at a cut-off point of 24/25. TICS did not perform well in differentiating MCI from cognitively normal individuals though (AUC: .67). Conclusion: The directly administered TICS questionnaire provides an easily applicable and brief option for detection of dementia in populations of low educational level and might be useful in the context of both clinical and research purposes.

Effect of Oestrogen Exposure, Obesity, Exercise and Diet on Breast Cancer Risk

Intense research efforts have been devoted to the exploration of breast cancer risk factors aiming at subsequent use in the development of prevention strategies. Age at menarche/menopause and childbearing patterns are proxies of exposure to endogenous oestrogens; circulating hormone levels, depending also on the use of exogenous oestrogens, are involved in the causation of the disease due to proliferative effects on breast epithelial tissue. Several modifiable lifestyle-related risk factors have been identified including obesity, alcohol consumption and physical inactivity, which increase breast cancer risk, especially in postmenopausal women, by up to 40%. Findings regarding the effect of diet remain inconclusive, apart from the established linear association of alcohol consumption with breast cancer risk. Exploration of specific components and the impact of these factors on disease outcome remains also to be established.