The author has not supplied his declaration of competing interest.

The author has not supplied his declaration of competing interest.

Sexual minority youth are at increased risk for bullying and suicide, but they are heterogeneous in their sexual orientation dimensions (attraction, behavior and identity).

To compare the association of bullying and suicide parameters between (1) heterosexually identified students without same-sex attractions or behaviors (2) heterosexually identified students with same-sex attractions or behaviors and (3) non-heterosexually identified students.

The Quebec Youth Risk Behavior Survey was a self-report questionnaire given to 1852 students 14–18 years old.

The heterosexually identified students without same-sex attraction or behavior, and no bullying, was our reference group. When these students had bullying, the likelihood of suicidal ideation was double, but their likelihood of suicide attempts was the same. For non-heterosexually identified students, those with no bullying were twice as likely, and those with bullying were four times as likely to have suicidal ideation. When these students had no bullying, they were not more likely to have suicide attempts, but they were almost three times as likely when they had bullying. Heterosexually identified students with same-sex attraction or behavior were never more likely on any of the suicide measures.

This study was the first to show that adolescents with a non-heterosexual identity will have a disproportionately greater likelihood in their suicide parameters when subject to bullying, than heterosexually identified students with or without same-sex attraction or behavior, suggesting that these latter two dimensions were non-contributory to suicide risk. The significance of identity as a predictor of suicidal ideation and behavior will be discussed.

The authors have not supplied their declaration of competing interest.

Dual diagnosis (substance used disorders (SUD) and mental illness) represents 3% of general population. Among United States population, 42.3% of SUD patients have psychiatric troubles (without tobacco). Moreover, SUD can concern all psychoactive substances (PAS) or illicit PAS only named “dual disorder with drugs” (DDD).

A quantitative analysis of DDD data from January 2013 to July 2014 of two epidemiological tools has been performed: PMSI database (Programme Médicalisé des Systeme d’Information) hospital discharge data is made up of data providing medical information for all patients discharged in Paris public hospital system (AP–HP) and NOT'S is a vigilance database of spontaneous NOTifications of drug abuse and dependence. We propose a descriptive analysis of DDD in Paris metropolitan area.

With PMSI, 9.2% of SUD inpatients (n = 617) have DDD, with mean age of 46 years (62% of men). In comparison, NOT'S reports 36% of SUD with DDD (n = 302) with mean age of 39.5 years (68% of men). Suicide attempt is also listed and reach 23% of cases.

These two databases (Fig. 1) show the difficulty of DDD diagnosis with the discordance in results. DDD miss in PMSI database since addictovigilance database shows a first prevalence of DDD. Despite the high rates of DDD, the problem is often under diagnosed by clinicians practising. It is also important to promote the collaboration among health care workers (addictologist and psychiatrist) because these patients require intensive mental and substance abuse care.

The authors have not supplied their declaration of competing interest.

Novel psychoactive substances (NPS) use is progressively increasing year on year. A new group of phenethylamines sold as legal stimulants and hallucinogens is being reported increasingly since 2012. Within this group, 25I-NBOMe is an outstanding substance with powerful effects and high affinity with the serotonin 2a (5HT2a) receptor. Several toxicity cases have been reported so far.

To describe the presence of 25I-NBOMe and its characteristics in samples delivered to Energy Control from 2009 to 2015 in Spain.

Among the samples, 21,198 analyzed from august 2009 to august 2015 and only those samples containing 25I-NBOMe were studied (n = 56). Samples were analyzed by Energy Control, a Spanish harm-reduction NGO that offers users the possibility of analyzing the substances they intend to consume. Analysis was done by Gas Chromatography–Mass Spectrometry.

From 56 samples were 25I-NBOMe was found, 24 were bought as LSD (42.8%), 12 as 25I-NBOMe (21.4%), 4 as 25C-NBOMe (7.1%), 4 as 25I-NBOH (7.1%) and 12 as other substances (21.4%), gummy bears included. All samples were received from 2012 on, having the highest peak on 2013 (19 samples).

25I-NBOMe consumption represents an emerging issue with potential harmful effects, especially when the substance used is not the expected. Further pharmacokinetic, pharmacodynamic, clinical and epidemiological researches should be conducted to deepen knowledge about 25I-NBOMe and the management of its possible toxic effects. Physicians should be aware of NPS, their increasing use and the clinical differences between them.

The authors have not supplied their declaration of competing interest.

Prenatal smoking exposure is one of the most common insults during the fetal period prevalence varying from 5 to 19% in the European countries [1].

Prenatal smoking exposure increases the risk of psychiatric morbidity in the offspring, externalizing disorders in particular. However, less is known whether maternal smoking during pregnancy increases the risk for anxiety disorders [1].

To study the associations between maternal smoking during pregnancy and offspring psychiatric morbidity in early adulthood in a Finnish birth cohort study.

A prospective data collection from 10th gestational week (GW10) to early adulthood (n = 475, 37% from the original sample). Information on self-reported smoking during pregnancy was collected using questionnaires at GW10 and GW28. Offspring psychiatric diagnoses and clinically relevant symptoms were assessed using Development and Well-being Assessment (DAWBA)-interviews at age 18 to 20 years. Information on parental alcohol use, depressive mood, anxiety, and education level, as well as offspring's gender, education level, and birth weight were used as covariates.

Maternal smoking during pregnancy associated independently associated with PTSD (OR = 6.9, 95% CI 1.3–35.6, P = 0.021), and conduct disorder (OR = 2.7, 95% CI 1.02–6.9, P = 0.046) in a multivariate analysis after adjusting for other psychiatric diagnoses, offspring and parental variables (OR = 1.9, 95% CI 0.5–6.9, P = 0.359).

In addition to conduct problems, prenatal nicotine exposure may increase the offspring's risk for posttraumatic stress disorder (PTSD). This relationship may be explained, in part, by effects on nicotinic acetylcholine receptors and uteroplacental mechanisms [1].

The authors have not supplied their declaration of competing interest.

Regeneration processes are the new target in looking for biological markers of psychiatric disorders.

In this study, we considered the role of stem cells and factors responsible for their trafficking in panic disorder (PD).

A group of 30 patients with panic disorder was examined and compared with a group of 30 healthy volunteers. In peripheral blood we have analysed: the number of hematopoetic stem cells – HSC (Lin−/CD45+/CD34+) and HSC (Lin−/CD45+/AC133+), the number of very small embryonic – like stem cells – VSEL (Lin−/CD45−/CD34+) and VSEL (Lin−/CD45−/CD133+) and concentration of stromal derived factor-1 (SDF-1), sphingosine-1-phosphate (S1P), and some proteins of the complement cascade.

Peripheral blood concentration of HSCs (Lin−/CD45+/AC133+) was significantly lower in PD group compared to control group, before and after antidepressant treatment. Peripheral blood concentration of VSEL (Lin−/CD45−/CD133+) was significantly lower in PD group before treatment compared to concentration after treatment. In PD group concentrations of factors involved in stem cell trafficking were statistically significant lower in PD group (before and after treatment) compared to control group.

Examination of regeneration system seems to be useful in PD diagnostics.

The authors have not supplied their declaration of competing interest.

Multimorbidity (MM) refers to the coexistence of two or more chronic diseases in the same individual; it encompasses medical comorbidity (MC) and psychiatric comorbidity (PC). Hypothesis: MM is prevalent amongst in-patients suffering from affective disorders (AD) and also impacted on length of stay.

To determine the prevalence of MM and its impact on duration of hospitalization in AD admissions.

This cross-sectional study was conducted using secondary data taken from discharge records of 1056 adults admitted for AD to a Quebec-based facility, between 2006 and 2014. Distribution of AD cases: 47% depression, 53% bipolar disorders.

The prevalence rate of MM: 85%. PC was present in 70% of sample whereas MC was present in 62%. The median number of comorbid illnesses was 2.7 for each study subject. The rate of MM was not related to age or gender. Metabolic syndrome (54%), cardiovascular diseases and chronic pain syndrome (17%) were the most prevalent MC in both depressed and bipolar populations. Personality disorder (65%) was highest in the depression population, whereas substance misuse (55%) was the most prevalent PC in the bipolar subjects. A longer length of stay was correlated with MM. However, a logistic regression analysis indicated that duration of hospitalization was only correlated with MC.

The observation that MM is the norm, even in this relatively young population with AD. The results confirmed that MC prolongs hospital stay. These findings advocate strongly for integrated management of psychiatric and physical health problems in clinical practice.

The authors have not supplied their declaration of competing interest.

Bipolar I (B-I) is an important cause of morbidity and mortality in hospitalized patients. While B-I has been extensively studied in the past, the contemporary data for impact of B-I on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 1,80,681 were analyzed; 56.29% were female and 43.71% were male (P < 0.0001); 70.63% were white, 17.14% black and 12.23% of other race (P < 0.0001). Rate of hospitalization increased from 7469.65/million to 9375.27/million from 1998–2011. Overall mortality was 0.12% and mean cost of hospitalization was 19,821.50$. The in-hospital mortality increased from 0.13% to 0.16% (P < 0.0001) and mean cost of hospitalization increased from 12,091.31$ to 29,292.97$. Total yearly spending on B-I related admissions increased from $0.72 million/year to $2.16 billion/year.

While mortality has slightly increased from 1998 to 2011, the cost has significantly increased from $0.72 million/year to $2.16 billion/year, which leads to an estimated $1.46 billion/year additional burden to US health care system. In the era of cost conscious care, preventing B-I related Hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for B-I related hospitalization.

The authors have not supplied their declaration of competing interest.

Bipolar disorder varies with season: admissions for depression peak in winter and mania peak in summer. Sunlight presumably increases the risk of mania through suppression of melatonin. If so, we expect admissions for mania to vary in accordance with climate variations.

To investigate how climate and climate changes affects admissions for mania.

To identify which climate variables – sunshine, ultraviolet radiation, rain and snow cover – affect admissions for mania.

To examine whether year-to-year weather variation as well as long-term climate changes reflects the variation in number of admissions for mania.

This register-based nationwide cohort study covers all patients admitted for mania (ICD-10 code F31 or F30.0–F30.2) between 1995 and 2012 in Denmark. Climate data, obtained from the Danish Meteorological Institute, were merged with admission data and correlated using an Unobserved Component Model regression model.

In total, 8893 patients were admitted 24,313 times between 1995 and 2012: 6573 first-admissions and 17,740 readmissions. Linear regression shows significant association between admissions per day and hours of sunshine (P < 0.01) and ultraviolet radiation (UV) dose (P < 0.01). Average days with snow cover and rain were not significantly correlated with admissions. Analyses on year-to-year variation and long-term change are not yet available.

Admissions for mania are correlated with sunshine and UV, but not rain and snow cover. If more patients are admitted during very sunny summers compared with less sunny summers this implies a relation with light itself and not just season.

The authors have not supplied their declaration of competing interest.

There are often substantial delays before diagnosis and initiation of treatment in people bipolar disorder. Increased delays are a source of considerable morbidity among affected individuals.

To investigate the factors associated with delays to diagnosis and treatment in people with bipolar disorder.

Retrospective cohort study using electronic health record data from the South London and Maudsley NHS Foundation Trust (SLaM) from 1364 adults diagnosed with bipolar disorder. The following predictor variables were analysed in a multivariable Cox regression analysis on diagnostic delay and treatment delay from first presentation to SLaM: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder.

The median diagnostic delay was 62 days (interquartile range: 17–243) and median treatment delay was 31 days (4–122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18–3.06) and treatment delay (4.40, 3.63–5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33–0.41) and substance misuse disorders (0.44, 0.31–0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.

Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder, particularly those with alcohol/substance misuse disorders. These findings highlight a need to better identify the symptoms of bipolar disorder and offer appropriate treatment sooner in order to facilitate improved clinical outcomes. This may include the development of specialist early intervention services.

The authors have not supplied their declaration of competing interest.

Bipolar II (B-II) is an important cause of morbidity and mortality in hospitalized patients. While B-II has been extensively studied in the past, the contemporary data for impact of B-II on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 107,152 patients were analyzed; 62.61% were female and 31.39% were male (P < 0.0001); 78.19% were white, 11.44% black and 10.37% of other race (P < 0.0001). Rate of hospitalization increased from 866.87/million to 8156.03/million from 1998–2011. Overall mortality was 0.32% and mean cost of hospitalization was 19,447.89$. The in-hospital mortality increased from 0.00% to 0.07% (P < 0.0001) and mean cost of hospitalization increased from 7565.20$ to 26,511.95$. Total yearly spending on B-II related admissions have increased from $52.24 million/year to $1.6 billion/year.

While mortality has slightly increased from 1998 to 2011, the cost has significantly increased from $52.24 million/year to $1.6 billion/year, which leads to an estimated $1.55 billion/year additional burden to US health care system. In the era of cost conscious care, preventing B-II related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for B-II related hospitalization.

The authors have not supplied their declaration of competing interest.

Bipolar disorders (BD) are chronic and recurrent psychopathological conditions characterized by therapeutic failures (TFs), regardless of the initial choice of psychiatric medication with a high prevalence of adverse drug reactions (ADRs). Cytochrome P450(CYP)2D6 genetics has been recently suggested to have a role in the response to treatment and extra-pyramidal symptoms (EPS) across several psychiatric conditions.

To evaluate interindividual differences in CYP2D6 enzyme activities, TFs and ADRs rates in BDs patients.

To tailor psychiatric medication choice and dose based on pharmacogenetic test.

We analyzed 16 clinical relevant polymorphisms CYP2D6 genotype in Psychiatric Unit of Foggia using the InfinitiTM Analyzer; the Simpson Angus Scale (SAS) was used to measure drug-induced EPS and Brief Psychiatric Rating Scale-24 (BPRS-24) response to treatment.

Ten drug-resistant patients were consecutively enrolled, and six of these experience major ADR during therapy with worsening of symptoms before screening for CYP polymorphism: BM (*2A/*5 genotype, BPRS-24 T0: 63, T14: 51), SR (*2A/*4, BPRS-24 T0: 66, T14: 59), LT (*4/*17 BPRS-24 T0: 72, T14: 64), DC (*2A/*4A BPRS-24 T0: 69, T14: 54), AL (*2A/*2A, BPRS-24 T0: 72, T14: 64), PA (*2A/*2A BPRS-24 T0: 52, T14: 46).

According to the specific CYP2D6 polymorphism, we personalized patients’ treatment considering that poor and extensive metabolizers have different rates of ADR and responses to treatment. CYP2D6 genotype's knowledge is useful for the reduction of therapeutic attempt during patient clinical history, thus reducing admission time and costs, and to guide clinicians toward a better patient management.

The authors have not supplied their declaration of competing interest.

Bipolar unspecified (BP-U) is an important cause of morbidity and mortality in hospitalized patients. While BP-U has been extensively studied in the past, the contemporary data for impact of BP-U on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 711,147 patients were analyzed; 61.33% were female and 38.67% were male (P < 0.0001); 77.63% were white, 13.17% black and 9.2% of other race (P < 0.0001). Rate of hospitalization increased from 2,310.28/million to 74,908.88/million from 1998–2011. Overall mortality was 0.81% and mean cost of hospitalization was $25,152.02. The in-hospital mortality reduced from 1.24% to 0.97% (P < 0.0001) and mean cost of hospitalization increased from 11,308.05$ to 32,211.67$. Total yearly spending on BP-U related admissions have increased from $207 million/year to $19.15 billion/year.

While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $0.21 billion/year $19.15 billion/year, which leads to an estimated $18.94 billion/year additional burden to US health care system. In the era of cost conscious care, preventing BP-U related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for BP-U related hospitalization.

The authors have not supplied their declaration of competing interest.

Bipolar I most recent episode-manic (BP-I-M) is an important cause of morbidity and mortality in hospitalized patients. While BP-I-M has been extensively studied in the past, the contemporary data for impact of BP-I-M on cost of hospitalization are largely lacking.

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

A total of 10,875 patients were analyzed; 57.13% were female and 42.87% were male (P < 0.0001); 74.78% were white, 14.51% black and 10.71% of other race (P < 0.0001). Rate of hospitalization increased from 528.71/million to 588.76/million from 1998–2011. Overall mortality was 0.42% and mean cost of hospitalization was 22,215.77$. The in-hospital mortality increased from 0.37% to 0.82% (P < 0.0001) and mean cost of hospitalization increased from 10,580.54$ to 40,737.65$. Total spending on BP-I-M related admissions have increased from $44.24 million/year to $187.00 million/year.

While mortality has slightly decreased from 1998 to 2011, the cost has significantly increased from $44.24 million/year to $187.00 million/year, which leads to an estimated $ 142.76 million/year additional burden to US health care system from. In the era of cost conscious care, preventing BP-I-M related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for BP-I-M related hospitalization.

The authors have not supplied their declaration of competing interest.

Guanfacine extended release (GXR) is a non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD).

To separate efficacy and sedative treatment-emergent adverse events (TEAEs) associated with GXR in four randomized, controlled trials in children (6–12 years) and adolescents (13–17 years) with ADHD.

SPD503-301 (n = 345) and SPD503-304 (n = 324) were 8 and 9 week studies of fixed-dose GXR (≤ 4 mg/day). SPD503-312 (n = 314; adolescents only) and SPD503-316 (n = 338) were 10–13 week studies of dose-optimized GXR (1–7 mg/day).

In fixed-dose studies, pooled incidences of sedative TEAEs with GXR were highest at week 1 (GXR, 13.9–18.7%; placebo, 8.7%) and decreased to placebo levels at week 8 (0–1.4%; placebo, 0%). In contrast, proportions of responders (≥ 30% reduction from baseline in ADHD Rating Scale IV [ADHD-RS-IV] total score) increased from week 1 (GXR, 29.6–34.8%; placebo, 25.0%) through endpoint (GXR, 66.7–72.2%; placebo, 42.6%). Incidences of sedative TEAEs, but not proportions of responders, increased with GXR dosing. GXR was associated with a statistically significant reduction in ADHD-RS-IV total score from baseline to endpoint in patients without sedative TEAEs in both fixed-dose and dose-optimized studies (GXR versus placebo, effect size = 0.49 and 0.67, respectively; P < 0.001). GXR was associated with statistically significant improvements compared with placebo in both ADHD-RS-IV Hyperactivity/Impulsivity and Inattentiveness subscale scores (P < 0.001).

These data from pooled GXR clinical trials indicate that incident sedative TEAEs do not contribute to increased treatment response over time, and that sedation and symptomatic improvement are distinct effects of GXR.

The authors have not supplied their declaration of competing interest.

To evaluate the effect of comorbid psychiatric disorders (PD) on the association between childhood ADHD and suicidality and the effect of gender on the association between PDs and suicidality among adults with childhood ADHD.

Subjects were recruited from a birth cohort of all children born 1976–1982 remaining in Rochester, MN after five years of age. Participating subjects with research-identified childhood ADHD (n = 232; mean age 27.0 years; 72% men) and non-ADHD controls (n = 335; mean age 28.6 years; 63% men) were administered a structured psychiatric interview (MINI International Neuropsychiatric Interview) to assess suicidality and psychiatric comorbidities.

Compared to controls, ADHD cases were significantly more likely to meet criteria for suicidality [odds ratio (OR) = 2.7, 95% CI 1.7–4.5]. Although this association was not moderated by the presence of PDs (P = 0.63 for interaction effect), the association between ADHD and suicidality was partially mediated by the presence of PDs [OR decreased from 2.7 to 2.1 (95% CI 1.2–3.5)]. Among adults with childhood ADHD, there was no significant moderating effect of gender on the association between suicidality and PD (P = 0.26 for interaction effect). However, the odds of suicidality was 6.1 (95% CI, 2.3–15.9) times higher among males with both externalizing and internalizing PDs compared to males with no disorders; among females the corresponding odds ratio was 3.4 (95% CI, 0.7–16.6).

Childhood ADHD is significantly associated with adult suicidal risk. Among those with ADHD, associations between suicidality and comorbid psychiatric disorders are more apparent in men among those with comorbid externalizing and internalizing disorders.

The authors have not supplied their declaration of competing interest.

Methods for measuring cognitive reserve (CR) are limited and controversial. Dual task cost (DTC) paradigms, assessing links between gait and cognition, are increasingly regarded as robust measures of CR.

Here, we aimed to validate a simplified methodology for a DTC paradigm in healthy volunteers for application in clinical settings as a measurement of CR.

We tested if subtracting by 7's (cognitive task) while walking (motor task) induced a DTC in a sample of 39 healthy young adults. For the cognitive task, we recorded the number of correct and incorrect subtractions, as well as the latency between subtractions. Gait parameters were recorded on a tri-axial accelerometer fixed to the left ankle. Both tasks were performed separately (single task) and simultaneously (double task) to assess the DTC. A battery for neuropsychological assessment and questionnaires to assess quality of life and affective symptoms were also applied, to measure possible correlations with the DTC.

Subtracting 7's while walking caused significant changes in gait parameters and in cognitive task performance. A significant decrease in the autocorrelation of the accelerometer signal during the dual task was also found (DTC = 37.92 ± 7.56%; P < 0.0001). This measure has not been previously used and may be a more sensitive measure of the dual task induced disturbance of the gait periodic signal pattern. Correlations between DTC and quality of life, affective or cognitive measures were not significant.

Our study provides an effective, portable and non-intrusive DTC experimental protocol that can be easily applied in clinical settings.

The authors have not supplied their declaration of competing interest.

Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis. Many studies highlighted the possible deleterious effects of elevated cortisol on cognition, assuming a likely role of stressful events. Yet, very few studies actually examined these assumed links between life events, cortisol and cognition.

To examine associations between salivary cortisol, cognition and life events in a population of non-demented old individuals.

A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study involving 6733 Lausanne residents. Salivary cortisol samples (upon waking, 30 minutes after waking, at 11 am and at 8 pm) were obtained from 799 non-demented participants aged at least 60.

Life events, activities of daily life along with depressive symptoms were assessed using a standardized questionnaire. A comprehensive neuropsychological test battery was used to determine the Clinical Dementia Rating (CDR).

For multiple comparisons, P values were adjusted (P′) according to Holm-Bonferroni's method.

Cortisol at 11 am and cortisol area under the curve (AUC) were positively correlated with CDR sum of boxes (CDRSOB) scores (P′ = 0.035; Rho = 0.097 and P′ = 0.024; Rho = 0.110, respectively). The association between cortisol AUC and CDRSOB remained significant after controlling for age, sex, body mass index, education, smoking and depression (P = 0.001; β = 0.001; R2 change = 0.016).

The number and the total impact of life events were associated neither with cortisol nor with CDRSOB.

Elevated cortisol was associated with poorer cognitive functioning yet independently of life events. This suggests that the increased cortisol associated with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated.

The authors have not supplied their declaration of competing interest.

The authors have not supplied their declaration of competing interest.