Objectively Assessed Weight Change and All-Cause Mortality among Community-Dwelling Older People.

Later life changes in body weight may be associated with an increased risk of mortality in older adults. The objective of this study was to examine whether weight change over four years was associated with a 17-year mortality risk in older adults. Participants were 1664 community-dwelling adults aged ≥65 years in the longitudinal Enquete de Sante' Psychologique-Risques, Incidence et Traitement (ESPRIT) study. Outcomes were all-cause mortality, cardiovascular disease (CVD) and cancer mortality. Weight change was defined as difference between weight at baseline and 4 years, categorised into: weight stable (±<5% weight change), weight loss (≥5%) and weight gain (≥5%). Association between weight change and mortality risk was evaluated using Cox proportional hazards models. Over 17 years of follow-up (median 15 years), 565 participants died. Compared to stable weight participants, those with ≥ 5% weight loss had an increased risk of all-cause mortality (HR: 1.24, 95% CI: 1.00−1.56, p = 0.05) and CVD mortality (HR: 1.53, 95% CI: 1.10−2.14, p = 0.01), but not cancer mortality (HR: 0.83, 95% CI: 0.50−1.39, p = 0.49). Weight gain of ≥5% was not associated with increased mortality (HR: 1.05, 95% CI: 0.76−1.45, p = 0.74). Weight monitoring in older adults could help identify weight loss at its early stages to better target interventions to maintain nutritional reserve and prevent premature mortality.

Aromatase (CYP19A1) gene variants, sex steroid levels, and late-life depression.

BACKGROUND: Sex differences in psychiatric disorders are common and could involve sex steroids. Aromatase, the product of the CYP19A1 gene, is the key enzyme in the conversion of androgen to estrogen. Whether CYP19A1 variants could be associated with depression differently in men and women has not been examined. METHODS: This population-based study included 405 men and 602 women aged ≥65 years. A clinical level of depression (DEP) was defined as having a score ≥16 on the Center for Epidemiology Studies Depression scale or a diagnosis of current major depression based on the Mini-International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) spanning the CYP19A1 gene were genotyped and circulating levels of estradiol and testosterone were determined. Multivariable analyses were adjusted for age, body mass index, ischemic pathologies, cognitive impairment, and anxiety. RESULTS: Five SNPs were associated with DEP in women specifically and this varied according to a history of major depression (p-values .01 to .0005). Three SNPs were associated with an increased risk of late-life DEP in women without a history of major depression, while two SNPs were associated with a decreased DEP risk in women with a history of major depression and were also associated with higher estradiol levels. CONCLUSIONS: Variants of the CYP19A1 gene appear to be susceptibility factors for late-life depression in a sex-specific manner. The polymorphisms decreasing the risk of recurrent depression in postmenopausal women also influence estradiol levels.

Determinants of cognitive performance and decline in 20 diverse ethno-regional groups: A COSMIC collaboration cohort study.

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.

Investigating the epigenetic profile of the inflammatory gene IL-6 in late-life depression.

BACKGROUND: It is well established that there is a link between inflammation and depression, with several studies reporting increased circulating levels of the pro-inflammatory cytokine, interleukin-6 (IL6), in depressed individuals. Peripheral epigenetic marks, including DNA methylation, hold promise as biomarkers for a range of complex conditions, with potential to inform diagnosis and tailor interventions. The aim of this study was to determine whether individuals with depression display differential methylation of the IL6 gene promoter compared to individuals without depression. METHODS: The ESPRIT study of later life neuropsychiatric disorders used a random sampling framework to select non-institutionalised participants aged ≥65 years and over living in the Montpellier region of France. Major depressive disorder (MDD) was assessed using the Mini International Neuropsychiatric Interview (MINI) according to DSM-IV criteria. High levels of depressive symptoms were defined as a score of ≥16 on the Centre for Epidemiologic Studies Depression Scale (CES-D). IL6 promoter DNA methylation was measured on a sub-sample of 380 participants who provided buccal samples. RESULTS: Individuals with depression (current MDD or high depressive symptoms) had lower IL6 methylation levels at one of the four sites investigated, however the effect size was small (∆ 2.4%, SE 0.009, p = 0.006). Interestingly, antidepressant use was independently associated with higher IL-6 methylation at the same site (∆ 4.6%, SE 0.019, p = 0.015). In multivariate linear regression analyses adjusting for covariates, including sex and smoking status, these associations remained. There was no effect modification when considering IL6 genotype. CONCLUSION: This study presents evidence that IL6 methylation may be a marker of depression status in older individuals, however further work is now needed to replicate these findings and to assess the association with inflammatory status of individuals.

Modifiable Risk Factors for Prevention of Dementia in Midlife, Late Life and the Oldest-Old: Validation of the LIBRA Index.

BACKGROUND: Recently, the LIfestyle for BRAin health (LIBRA) index was developed to assess an individual's prevention potential for dementia. OBJECTIVE: We investigated the predictive validity of the LIBRA index for incident dementia in midlife, late life, and the oldest-old. METHODS: 9,387 non-demented individuals were recruited from the European population-based DESCRIPA study. An individual's LIBRA index was calculated solely based on modifiable risk factors: depression, diabetes, physical activity, hypertension, obesity, smoking, hypercholesterolemia, coronary heart disease, and mild/moderate alcohol use. Cox regression was used to test the predictive validity of LIBRA for dementia at follow-up (mean 7.2 y, range 1-16). RESULTS: In midlife (55-69 y, n = 3,256) and late life (70-79 y, n = 4,320), the risk for dementia increased with higher LIBRA scores. Individuals in the intermediate- and high-risk groups had a higher risk of dementia than those in the low-risk group. In the oldest-old (80-97 y, n = 1,811), higher LIBRA scores did not increase the risk for dementia. CONCLUSION: LIBRA might be a useful tool to identify individuals for primary prevention interventions of dementia in midlife, and maybe in late life, but not in the oldest-old.

Mean arterial pressure change associated with cerebral blood flow in healthy older adults.

We investigate over a 12-year period the association between regional cerebral blood flow (CBF) and cardiovascular risk factors in a prospective cohort of healthy older adults (81.96 ± 3.82 year-old) from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) study. Cardiovascular risk factors were measured over 12 years, and gray matter CBF was measured at the end of the study from high-resolution magnetic resonance imaging using arterial spin labeling. The association between cardiovascular risk factors, their long-term change, and CBF was assessed using multivariate linear regression models. Women were observed to have higher CBF than men (p < 0.05). Increased mean arterial pressure (MAP) over the 12-year period was correlated with a low cerebral blood flow (p < 0.05, R(2) = 0.21), whereas no association was detected between CBF and MAP at the time of imaging. High levels of glycemia tended to be associated with low cerebral blood flow values (p < 0.05). Age, alcohol consumption, smoking status, body mass index, history of cardiovascular disease, and hypertension were not associated with CBF. Our main result suggests that change in MAP is the most significant predictor of future CBF in older adults.

Target risk factors for dementia prevention: a systematic review and Delphi consensus study on the evidence from observational studies.

OBJECTIVE: Dementia has a multifactorial etiology, but the importance of individual health and lifestyle related risk factors is often uncertain or based on few studies. The goal of this paper is to identify the major modifiable risk factors for dementia as a first step in developing an effective preventive strategy and promoting healthy late life cognitive functioning. METHODS: A mixed-method approach combined findings from a systematic literature review and a Delphi consensus study. The literature search was conducted in PubMed and updated an earlier review by the United States National Institutes of Health from 2010. We reviewed the available evidence from observational epidemiological studies. The online Delphi study asked eight international experts to rank and weigh each risk factor for its importance for dementia prevention. RESULTS: Out of 3127 abstracts, 291 were included in the review. There was good agreement between modifiable risk factors identified in the literature review and risk factors named spontaneously by experts. After triangulation of both methods and re-weighting by experts, strongest support was found for depression, (midlife) hypertension, physical inactivity, diabetes, (midlife) obesity, hyperlipidemia, and smoking, while more research is needed for coronary heart disease, renal dysfunction, diet, and cognitive activity. CONCLUSIONS: Findings provide good support for several somatic and lifestyle factors and will be used to inform the design of a new multicenter trial into dementia prevention.

Malnutrition and retinal vascular caliber in the elderly: the POLA study.

PURPOSE: The pathway linking late-life malnutrition to greater risk of cardiovascular disease is unclear. Microcirulatory changes assessed by retinal vascular caliber have been linked with increased risk of stroke and coronary heart disease. The purpose of this study was to examine whether retinal vascular calibers are associated with malnutrition in elderly subjects free of cardiovascular diseases. METHODS: This was a cross-sectional analysis of a community-dwelling cohort comprising 1145 individuals aged 60 years and older. Retinal vascular caliber was measured from fundus photographs using a semiautomated, standardized imaging software. Malnutrition was assessed using body mass index (BMI) < 18.5 kg/m(2) and biomarkers of protein malnutrition: plasma albumin and transthyretin. RESULTS: In a multivariate model controlling for cardiovascular risk factors, retinal venular caliber was related to BMI (P = 0.0002) with an increased mean caliber for individuals with obesity and for those with low BMI. After multivariate adjustment for age, sex, hypertension, smoking, high-density lipoprotein (HDL) cholesterol, glomerular filtration rate and BMI, lower levels of albumin or transthyretin were associated with larger retinal venular caliber (P = 0.026 and P = 0.0018, respectively), that remain significant when adjusting for CRP (P = 0.040 and P = 0.0060, respectively) or orosomucoid (P = 0.034 and P = 0.0020, respectively). The relationships between retinal arteriolar caliber and BMI, albumin and transthyretin did not reach significance (P = 0.14, P = 0.12, and P = 0.15, respectively). CONCLUSIONS: Protein malnutrition was identified as an additional factor associated with retinal venular dilatation beyond inflammation. This suggests that early microvascular changes may be one of the underlying mechanisms of increased risk of cardiovascular disease observed in elderly subjects suffering from malnutrition.

Estrogen receptor polymorphisms and incident dementia: the prospective 3C study.

BACKGROUND: Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors. METHODS: The association between five ESR α (ESR1) and ß (ESR2) polymorphisms with 7-year dementia incidence was examined among 6959 older men and women from the Three City Study using multivariate-adjusted Cox regression models with delayed entry. Gender, the apolipoprotein E (APOE) ε4 allele, and hormone treatment were considered as potential effect modifiers of this association. RESULTS: Among women, the CC genotype of ESR1rs2234693 was specifically associated with a small increased risk of AD (adjusted hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.03-2.28, P = .03). However, women with this genotype had a substantially increased risk of AD associated with the APOE ε4 allele (adjusted HR: 3.24, 95% CI: 1.81-5.79 for women rs2234693 CC; compared with HR: 1.87, 95% CI: 1.37-2.56 for all women). There was also evidence of a nominally significant interaction between the ESR1 and ESR2 polymorphisms on the risk of all dementias (P = .04). Hormone treatment did not modify these associations, and there were no significant associations in men. CONCLUSIONS: Although there was only weak support for a gender-specific association between the common ESR1rs2234693 polymorphism and AD, this polymorphism may act as an effect modifier, modifying the association between an ESR2 polymorphism and dementia, as well as the risk of AD associated with the APOE ε4 allele.

Brain volumes in late life: gender, hormone treatment, and estrogen receptor variants.

Structural imaging studies suggest gender differences in brain volumes; however, whether hormone treatment (HT) can protect against age-related structural changes remains unknown, and no prior neuroimaging study has investigated potential interactions between HT and estrogen receptor (ESR) polymorphisms. Magnetic resonance imaging was used to measure gray and white matter, hippocampal volume, corpus callosum, cerebrospinal fluid (CSF), total intracranial volume (ICV) and white matter lesions (WML) in 582 non-demented older adults. In multivariable analysis, when compared to women who had never used HT, men and women currently on treatment, but not past users, had significantly smaller ratios of gray matter to ICV and increased atrophy (CSF/ICV ratio). Hippocampal and white matter volume as well as the corpus callosum area were not significantly different across groups. ESR2 variants were not significantly associated with brain measures, but women with the ESR1 rs2234693 C allele had significantly smaller WML. Furthermore this association was modified by HT use. Our results do not support a beneficial effect of HT on brain volumes in older women, but suggest the potential involvement of ESR1 in WML.

Hypnotics and mortality in an elderly general population: a 12-year prospective study.

BACKGROUND: Hypnotics are widely used by the elderly, and their impact on mortality remains controversial. The inconsistent findings could be due to methodological limitations, notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use, for example, insomnia symptoms and excessive daytime sleepiness, depression and anxiety. Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders and sleep complaints. METHODS: Analyses were carried out on 6,696 participants aged 65 years or older randomly recruited from three French cities and free of dementia at baseline. Adjusted Cox proportional hazards models with delayed entry, and age of the participants as the time scale, were used to determine the association between hypnotic use and 12-year survival. RESULTS: At baseline, 21.7% of the participants regularly used at least one hypnotic. During follow-up, 1,307 persons died, 480 from cancer and 344 from cardiovascular disease. Analyses adjusted for study center, age and gender showed a significantly greater risk of all-cause and cardiovascular-related mortality with hypnotics, particularly benzodiazepines, and this increased with the number of hypnotics used. None of these associations were significant in models adjusting for sociodemographic and lifestyle characteristics, chronic disorders including cardiovascular pathologies, sleep and psychiatric disorders. Results remained unchanged when duration of past hypnotic intake or persistent versus intermittent use during follow-up were taken into account. CONCLUSIONS: When controlling for a large range of potential confounders, the risk of mortality was not significantly associated with hypnotic use regardless of the type and duration. Underlying psychiatric disorders appear to be the principal confounders of the observed association.

Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women.

A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23-2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12-1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05-1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.

Measuring resilience in adult women using the 10-items Connor-Davidson Resilience Scale (CD-RISC). Role of trauma exposure and anxiety disorders.

PURPOSE: Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience. METHODS: We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory). RESULTS: Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21-0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44-7.01]). CONCLUSION: Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a "vaccination" effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations.

Hormone treatment, estrogen receptor polymorphisms and mortality: a prospective cohort study.

BACKGROUND: The association between hormone treatment (HT) and mortality remains controversial. This study aimed to determine whether the risk of mortality associated with HT use varies depending on the specific characteristics of treatment and genetic variability in terms of the estrogen receptor. METHODOLOGY/PRINCIPAL FINDINGS: A prospective, population-based study of 5135 women aged 65 years and older who were recruited from three cities in France and followed over six years. Detailed information related to HT use was obtained and five estrogen receptor polymorphisms were genotyped. The total follow-up was 25,436 person-years and during this time 352 women died. Cancer (36.4%) and cardiovascular disease (19.3%) were the major causes of death. Cox proportional hazards models adjusted for age, education, centre, living situation, comorbidity, depression, physical and mental incapacities, indicated no significant association between HT and mortality, regardless of the type or duration of treatment, or the age at initiation. However, the association between HT and all-cause or cancer-related mortality varied across women, with significant interactions identified with three estrogen receptor polymorphisms (p-values = 0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1 rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI: 0.18-0.97), while in stark contrast, those homozygous for the T allele had a significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23-8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572. CONCLUSIONS/SIGNIFICANCE: The risk of mortality was not associated with HT duration, type or age at initiation. It was however not equal across all women, with some women appearing genetically more vulnerable to the effects of HT in terms of their estrogen receptor genotype. These findings, if confirmed in another independent study, may help explain the differential susceptibility of women to the beneficial or adverse effects of HT.

Estrogen receptor alpha gene variants and major depressive episodes.

BACKGROUND: Despite evidence of estrogen's mood-enhancing effects, the association between estrogen receptor (ER) gene variants and lifetime major depression has been insufficiently studied. METHODS: 3987 community-dwelling women aged 65years and over were recruited in France as part of the Three City Study. Current and past major depressive disorders (MDD) were diagnosed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. The association between two common estrogen receptor alpha (ESR1) polymorphisms with lifetime MDD was examined using adjusted logistic regression models, taking into account the age at first depressive episode and the recurrence of depression. RESULTS: Women homozygous for the variant G allele of ESR1 rs9340799 had a 1.6-fold increased risk of MDD across their lifetime compared with women who were homozygous for the A allele (p=0.009). There was a similar non-significant trend for the C allele of rs2234693 being associated with an increased risk (p=0.09). Polytomous regression analysis further indicated that the GG genotype of rs9340799 was specifically associated with an increased risk of recurrent depressive episodes, regardless of the age at first onset of depression relative to the menopause. LIMITATIONS: The duration and severity of depressive episodes was not considered in the analysis. CONCLUSIONS: This is the first study to examine the association between ESR1 gene variants and lifetime MDD. Our findings indicate a significant association between common variants and the risk of recurrent depressive episodes. This suggests that certain depressed women could be most responsive to hormone-based treatment.

Oestrogen receptor polymorphisms and late-life depression.

BACKGROUND: Evidence suggests a role for oestrogen in depression but the involvement of oestrogen receptor polymorphisms remains unknown. AIMS: To determine the association between oestrogen receptor polymorphisms and late-life depression and the modifying effect of hormone treatment. METHOD: Depression was assessed using the Mini-International Neuropsychiatric Interview, according to DSM-IV criteria and the Centre for Epidemiologic Studies - Depression Scale. The association between oestrogen receptor α and ß (ER-α and ER-ß) polymorphisms with severe depression was examined in 6017 community-dwelling elderly people using multivariate logistic regression. RESULTS: In women, the ER-α rs2234693 and rs9340799 polymorphisms were significantly associated with the risk of late-life depression. The A allele of ER-ß rs1256049 increased the risk of depression, but only for non-current users of hormone treatment. In men, only the ER-ß rs4986938 polymorphism showed a weak association with depression risk. CONCLUSIONS: Oestrogen receptor polymorphisms are associated with severe late-life depression risk in women only.

Alternative Healthy Eating Index and mortality over 18 y of follow-up: results from the Whitehall II cohort.

BACKGROUND: Indexes of diet quality have been shown to be associated with decreased risk of mortality in several countries. It remains unclear if the Alternative Healthy Eating Index (AHEI), designed to provide dietary guidelines to combat major chronic diseases, is related to mortality risk. OBJECTIVE: We aimed to examine the association between adherence to the AHEI and cause-specific mortality over 18 y of follow-up in a British working population. DESIGN: Analyses are based on 7319 participants (mean age: 49.5 y; range: 39-63 y; 30.3% women) from the Whitehall II Study. Cox proportional hazards regression models were performed to analyze associations of the AHEI (scored on the basis of intake of 9 components: vegetables, fruit, nuts and soy, white or red meat, trans fat, polyunsaturated or saturated fat, fiber, multivitamin use, and alcohol) with mortality risk. RESULTS: After potential confounders were controlled for, participants in the top compared with the bottom third of the AHEI score showed 25% lower all-cause mortality [hazard ratio (HR): 0.76; 95% CI: 0.61, 0.95] and >40% lower mortality from cardiovascular disease (CVD; HR: 0.58; 95% CI: 0.37, 0.91). Consumption of nuts and soy and moderate alcohol intake appeared to be the most important independent contributors to decreased mortality risk. The AHEI was not associated with cancer mortality or noncancer/non-CVD mortality. CONCLUSION: Our findings suggest that the encouragement of adherence to the AHEI dietary recommendations constitutes a valid and clear public health recommendation that would decrease the risk of premature death from CVD.

Estrogen receptor gene variants are associated with anxiety disorders in older women.

BACKGROUND: Estrogen is thought to play a key role in anxiety, but it remains unknown whether genetic variants in the estrogen receptors (ERs) can influence the risk of anxiety. This study investigated whether ESR1 and ESR2 gene variants were associated with specific anxiety disorders in postmenopausal women and evaluated the potential modifying effect of hormone treatment (HT) on these associations. METHODS: One thousand and ninety-two community-dwelling women aged 65 years and older were recruited as part of the ESPRIT Study in Montpellier, France. Anxiety was assessed using the Mini-International Neuropsychiatry Interview (MINI), according to DSM-IV criteria. Two ESR1 and three ESR2 polymorphisms were genotyped. RESULTS: The most common anxiety disorders were phobia (14.2%) and generalised anxiety disorder (GAD, 8%). The A allele of ESR2 rs1256049 was associated with an increased risk of GAD [OR: 2.06, 95% CI: 1.09-3.87], while both ESR1 polymorphisms were specifically associated with phobia. The C allele of ESR1 rs2234693 decreased the risk of phobia by 42% [95% CI: 0.41-0.83], and this remained significant even after Bonferroni correction. The G allele of ESR1 rs9340799 was associated with a 31% decreased phobia risk [95% CI: 0.49-0.96]. There was also evidence of a significant gene-environment interaction, where only women who were currently using HT had a reduced risk of phobia with these ESR1 gene variants. CONCLUSIONS: This study confirms earlier findings of an association between ESR1 and global anxiety in older women, however these associations varied depending on the anxiety syndrome and the use of HT. The results also suggest that the ESR2 may contribute to the genetic vulnerability to GAD, but these findings require further confirmation.

Metabolic syndrome, its components, and mortality in the elderly.

CONTEXT AND OBJECTIVE: The metabolic syndrome (MetS) has been shown to predict mortality in the middle-aged, but less is known on the impact of MetS and its components on mortality risk in the elderly. Our objectives were 1) to examine the association of MetS with the risk of all-cause and cause-specific mortality in a French elderly community-dweller cohort and 2) to determine the main components driving these associations. PARTICIPANTS AND METHODS: Prospective analyses were carried out on 7118 men and women aged 65 yr and over from the Three-City cohort. Association between MetS (defined using the National Cholesterol Education Program Adult Treatment Panel III criteria) and mortality risk over the 7-yr follow-up was assessed using Cox proportional hazards models. RESULTS: After adjusting for sociodemographic variables, health behaviors, and health status, a 50% increased risk for all-cause mortality was observed in participants with MetS at baseline compared with those without, with a hazard ratio of 1.54 [95% confidence interval (CI) = 1.24-1.92]. Elevated fasting blood glucose, high triglycerides, and low high-density lipoprotein cholesterol were the major contributors to this association, acting synergistically on mortality risk. For coronary heart disease mortality and cancer mortality, the hazard ratios associated with MetS were 2.21 (95% CI = 1.07-4.55) and 1.49 (95% CI = 1.04-2.14), respectively. CONCLUSIONS: By showing that an elevated fasting blood glucose potentiates the excess mortality risk associated with lipid abnormality, our study supports the status of MetS as a risk factor for mortality in the elderly. Our findings emphasize the importance of MetS screening and managing dyslipidemia and hyperglycemia in older persons in general practice.

A prospective study of hormone therapy and depression in community-dwelling elderly women: the Three City Study.

BACKGROUND: The potential benefits of hormone therapy (HT) in treating depressed postmenopausal women are controversial, and data on depression (re)emergence in the context of HT discontinuation are lacking. OBJECTIVE: To determine whether HT is associated with a modified risk of new-onset depressive symptoms in elderly women. METHOD: Current depressive symptomatology was evaluated in 4,069 community-dwelling postmenopausal women aged 65 years and over who were randomly recruited from 3 French cities between 1999 and 2001. Depressive symptomatology was assessed using the Center for Epidemiologic Studies-Depression Scale at baseline and as part of the 2- and 4-year follow-up. RESULTS: Over the follow-up period, multivariate logistic regression analyses adjusted for sociodemographic variables, measures of physical health, and cognitive impairment failed to find a significant association between HT at baseline and the incidence of depressive symptoms. However further analysis indicated an increased risk of incident depressive symptoms for women using transdermal estradiol treatment combined with synthetic progestin specifically (odds ratio [OR] = 1.59; 95% CI, 1.01-2.50; P = .046). In addition, while women taking HT continuously over the 4-year follow-up did not show an increased risk of depressive symptoms, women who stopped their treatment early after study inclusion, had a significantly higher risk (OR = 2.63; 95% CI, 1.52-4.55; P = .0005). CONCLUSIONS: Hormone therapy was not associated with a protective effect against the emergence of depressive symptoms in elderly postmenopausal women. However, discontinuing treatment could increase the risk of depressive symptoms. Data on the appropriate management of depression in the context of HT discontinuation among postmenopausal women require further investigation.