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1.  Hypnotics and mortality in an elderly general population: a 12-year prospective study 
BMC Medicine  2013;11:212.
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.
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.
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.
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.
PMCID: PMC3849429  PMID: 24070457
Cohort studies; Elderly; Hypnotics; Mortality; Sleep disorders
2.  Oestrogen receptor polymorphisms and late-life depression 
The British Journal of Psychiatry  2011;199(2):126-131.
Evidence suggests a role for estrogen in depression but the involvement of estrogen receptor (ER) polymorphisms remains unknown.
To determine the association between ER polymorphisms and late-life depression and the modifying effect of hormone treatment (HT).
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 ER-α and ER-β polymorphisms with severe depression was examined in 6017 community-dwelling elderly using multivariate logistic regression.
In women, the ER-α rs2234693 and rs9340799 polymorphisms were significantly associated with the risk of late-life depression. The A allele of ER-β rs1256049 increased the risk of depression, but only for non-current users of HT. In men, only the ER-β rs4986938 polymorphism showed a weak association with depression risk.
ER polymorphisms are associated with severe late-life depression risk in women only.
PMCID: PMC3623726  PMID: 21804148
Age Factors; Aged; Aged, 80 and over; Alleles; Depressive Disorder, Major; epidemiology; genetics; Effect Modifier, Epidemiologic; Estrogen Replacement Therapy; Female; Gene Frequency; Genetic Predisposition to Disease; epidemiology; Genotype; Humans; Logistic Models; Longitudinal Studies; Male; Multivariate Analysis; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Postmenopause; psychology; Psychiatric Status Rating Scales; Receptors, Estrogen; genetics
3.  Measuring Resilience in Adult Women Using the 10-Items Connor-Davidson Resilience Scale (CD-RISC). Role of Trauma Exposure and Anxiety Disorders 
PLoS ONE  2012;7(6):e39879.
Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience.
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).
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]).
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.
PMCID: PMC3387225  PMID: 22768152
4.  Hormone Treatment, Estrogen Receptor Polymorphisms and Mortality: A Prospective Cohort Study 
PLoS ONE  2012;7(3):e34112.
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.
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.
PMCID: PMC3311587  PMID: 22457817
5.  Long-term post-operative cognitive decline in the elderly: the effects of anesthesia type, apolipoprotein E genotype, and clinical antecedents 
Journal of Alzheimer's Disease  2010;22 Suppl 3:105-113.
Cognitive dysfunction in the elderly commonly observed following anesthesia has been attributed to age-related neuronal changes exacerbated by pharmacotoxic effects. However, the extent to which these changes may persist following recovery from surgery is still largely unknown. This study investigates the long-term effects of anesthesia on cognitive functioning after orthopedic surgery in 270 elderly patients over the age of 65 who completed a computerized cognitive battery before and 8 days, 4 and 13 months after surgery. Their performance was compared to that of 310 elderly controls who completed the same neuro-psychiatric evaluation at baseline and one-year interval. Multivariate analyses adjusted for socio-demographic variables, depressive symptomatology, vascular pathology as well as baseline cognitive performance. We found early and transient post-operative decline in reaction time and constructional praxis. With regard to long-term changes we observed improvement compared to controls in most verbal tasks (probably due to learning effects). On the other hand, a clear dissociation effect was observed for several areas of visuospatial functioning which persisted up to the 13-month follow-up. This specific pattern of visuospatial deficit was found to be independent of apolipoprotein E genotype and closely resembles what has recently been termed vascular mild cognitive impairment, in turn associated with subtle sub-cortical vascular changes. The observation of only minor differences between persons operated by general and regional anesthesia makes it difficult to attribute these changes directly to the anesthetic agents themselves, suggesting that cognitive dysfunction may be attributable at least in part to peri-operative conditions, notably stress and glucocorticoid exposure.
PMCID: PMC3078520  PMID: 20858969
Aged; Aged, 80 and over; Anesthesia; adverse effects; Anesthesia, Conduction; adverse effects; Anesthesia, General; adverse effects; Apolipoproteins E; genetics; Arthroplasty, Replacement; Attention; physiology; Choice Behavior; physiology; Cognition; physiology; Cognition Disorders; etiology; genetics; psychology; Female; Humans; Language; Male; Memory; physiology; Mental Processes; physiology; Neuropsychological Tests; Postoperative Complications; genetics; psychology; Questionnaires; Socioeconomic Factors; Space Perception; physiology; Visual Perception; physiology; Anesthesia; Apolipoprotein E; Mild cognitive impairment; Post-operative cognitive decline
6.  A prospective study of hormone therapy and depression in community-dwelling elderly women: the Three City Study 
The Journal of Clinical Psychiatry  2010;71(12):1673-1679.
The potential benefits of hormone therapy in treating depressed postmenopausal women are controversial and data on depression (re)emergence in the context of HT discontinuation are lacking.
To determine whether hormone therapy is associated with a modified risk of new onset of depressive symptoms in elderly women.
Current depressive symptomatology was evaluated in 4069 community-dwelling postmenopausal women aged 65 years and over, randomly recruited from three French cities. Depressive symptomatology was assessed using the Centre for Epidemiologic Studies Depression Scale at baseline and as part of the 2- and 4-year follow-up.
Over the follow-up period, multivariate logistic regression analyses adjusted for socio-demographic 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 specifically transdermal estradiol treatment combined with synthetic progestin (OR=1.59, 95%CI 1.01–2.50, p=0.046). In addition, while women taking hormone therapy continuously over the 4-year follow-up did not show an increased risk of depressive symptoms, women who stopped their treatment early after inclusion, had a significantly higher risk (OR= 2.63 95%CI 1.52–4.55, p=0.0005).
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 hormone therapy discontinuation among postmenopausal women requires further investigation.
PMCID: PMC3078521  PMID: 20816026
Administration, Cutaneous; Aged; Aged, 80 and over; Depression; chemically induced; diagnosis; epidemiology; etiology; Drug Therapy, Combination; Estradiol; administration & dosage; adverse effects; Estrogen Replacement Therapy; adverse effects; methods; Estrogens; administration & dosage; adverse effects; Female; Follow-Up Studies; France; epidemiology; Humans; Incidence; Logistic Models; Medication Adherence; psychology; statistics & numerical data; Multivariate Analysis; Odds Ratio; Postmenopause; Progesterone Congeners; administration & dosage; adverse effects; Prospective Studies; Risk Factors; Depression, estradiol, postmenopausal, progestogen, transdermal
7.  Characteristics of hormone therapy, cognitive function, and dementia: the prospective 3C Study 
Neurology  2009;73(21):1729-1737.
To examine the association between hormone therapy (HT) and cognitive performance or dementia, focusing on the duration and type of treatment used, as well as the timing of initiation of HT in relation to the menopause.
Women 65 years and older were recruited in France as part of the Three City Study. At baseline and 2 and 4 year follow-up, women were administered a short cognitive test battery and a clinical diagnosis of dementia was made. Detailed information was also gathered relating to current and past HT use. Analysis was adjusted for a number of socio-demographic, behavioural, physical and mental health variables, as well as Apolipoprotein ε4 (Apoe-ε4).
Among 3130 naturally postmenopausal women, current HT users performed significantly better than never users on verbal fluency, working memory and psychomotor speed. These associations varied according to the type of treatment and a longer duration of HT appeared to be more beneficial. However, initiation of HT close to the menopause was not associated with better cognition. HT did not significantly reduce dementia risk over 4 years but current treatment diminished the negative effect associated with Apoe-ε4.
Current HT was associated with better performance in certain cognitive domains but these associations are dependent on the duration and type of treatment used. We found no evidence that HT needs to be initiated close to the menopause to have a beneficial effect on cognitive function in later life. Current HT may decrease the risk of dementia associated with the Apoe-ε4 allele.
PMCID: PMC2993903  PMID: 19933973
Aged; Aged, 80 and over; Apolipoproteins E; genetics; Cognition Disorders; drug therapy; etiology; genetics; Cohort Studies; Dementia; complications; genetics; Estrogen Replacement Therapy; methods; Female; Humans; Logistic Models; Neuropsychological Tests; Retrospective Studies
8.  Lifetime hormonal factors may predict late-life depression in women 
International Psychogeriatrics / Ipa  2008;20(6):1203-1218.
Fluctuating hormone levels are known to influence a woman’s mood and well-being. This study aimed to determine whether lifetime hormonal markers are associated with late-life depression symptoms among elderly community-dwelling women.
Detailed reproductive histories of 1013 women aged 65 years and over were obtained using questionnaires and depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale. Multivariate logistic regression models were generated to determine whether any lifetime endogenous or exogenous hormonal factors were associated with late-life depression.
The prevalence of depressive symptoms was 17%. Age at menopause was associated with depressive symptoms, but only among women with a lower education level. For these women, an earlier age at menopause increased their risk of late-life depression (linear effect, OR=0.95, 95%CI: 0.91–0.99). The odds of late-life depression were also increased for women who were past (OR=1.6, 95%CI: 1.1–2.5), but not current hormonal replacement users. On the other hand, long-term oral contraceptive use (≥10 years) was protective against depression (OR=0.3, 95%CI: 0.1–0.9). These associations remained significant even after extensive adjustment for a range of potential confounding factors, including socio-demographic factors, mental and physical incapacities, antidepressant use and past depression. The other factors examined, including age at first menses, parity, age at childbirth and surgical menopause, were not associated with late-life depressive symptoms.
Lifetime hormonal factors that are significantly associated with depression symptoms in later life have been identified. Further work is needed to determine how potential hormonal interventions could be used in the treatment of late-life depression in certain sub-groups of women.
PMCID: PMC2612035  PMID: 18533067

Results 1-8 (8)