Efficacy of Ginkgo biloba extract EGb 761(®) in dementia with behavioural and psychological symptoms: A systematic review.

To review current evidence of efficacy of Ginkgo biloba extract EGb 761(®) in dementia with behavioural and psychological symptoms (BPSD). Randomized, placebo-controlled trials assessing the effects of EGb 761(®) in dementia patients with BPSD were included if the diagnosis was made in accordance with internationally accepted criteria, the treatment period was at least 22 weeks, outcome measures covered BPSD and at least two of the following domains of assessment, i.e. cognition, activities of daily living and clinical global assessment, and methodological quality was adequate. An analysis of covariance (ANCOVA) model was used to calculate the pooled effect estimates and to compare effects of EGb 761(®) and placebo; furthermore, combined risk differences of response rates were calculated. Four published trials were identified, involving altogether 1,628 outpatients with mild to moderate dementia. Least-square mean differences for change from baseline in cognition, BPSD (including caregiver distress rating), activities of daily living, clinical global impression, and quality of life favoured EGb 761(®) (P < 0.001 for all comparisons). The pooled analyses provide evidence of efficacy of EGb 761(®) at a daily dose of 240 mg in the treatment of out-patients suffering from Alzheimer's, vascular or mixed dementia with BPSD

Proxy-to-proxy calibration: Increasing the temporal resolution of quantitative climate reconstructions

High-resolution paleoclimate reconstructions are often restricted by the difficulties of sampling geologic archives in great detail and the analytical costs of processing large numbers of samples. Using sediments from Lake Braya Sø, Greenland, we introduce a new method that provides a quantitative high-resolution paleoclimate record by combining measurements of the alkenone unsaturation index ([Image: see text]) with non-destructive scanning reflectance spectroscopic measurements in the visible range (VIS-RS). The proxy-to-proxy (PTP) method exploits two distinct calibrations: the in situ calibration of [Image: see text] to lake water temperature and the calibration of scanning VIS-RS data to down core [Image: see text] data. Using this approach, we produced a quantitative temperature record that is longer and has 5 times higher sampling resolution than the original [Image: see text] time series, thereby allowing detection of temperature variability in frequency bands characteristic of the AMO over the past 7,000 years

Treatment effects of Ginkgo biloba extract EGb 761® on the spectrum of behavioral and psychological symptoms of dementia: meta-analysis of randomized controlled trials.

ABSTRACTBackground:In randomized controlled trials, Ginkgo biloba extract EGb 761® has been found to be effective in the treatment of behavioral and psychological symptoms of dementia (BPSD). To assess the effects of EGb 761® on specific BPSD, we analyzed data from all randomized, placebo-controlled, at least 20-week, trials of EGb 761® enrolling patients with dementia (probable Alzheimer's disease (AD), probable vascular dementia or probable AD with cerebrovascular disease) who had clinically significant BPSD (Neuropsychiatric Inventory (NPI) total score at least 6). Data were pooled and joint analyses of NPI single item composite and caregiver distress scores were performed by meta-analysis with a fixed effects model. Four trials involving 1628 patients (EGb 761®, 814; placebo, 814) were identified; treatment duration was 22 or 24 weeks; the daily dose of EGb 761® was 240 mg in all trials. Pooled analyses including data from the full analysis sets of all trials (EGb 761®, 796 patients; placebo, 802 patients) revealed significant superiority of EGb 761® over placebo in total scores and 10 single symptom scores. Regarding caregiver distress scores, EGb 761®-treated patients improved significantly more than those receiving placebo in all symptoms except delusions, hallucinations, and elation/euphoria. The benefit of EGb 761® mainly consists of improvement in symptoms present at baseline, but the incidence of some symptoms was also decreased. Twenty two- to twenty four-week treatment with Ginkgo biloba extract EGb 761® improved BPSD (except psychotic-like features) and caregiver distress caused by such symptoms

Life events, salivary cortisol, and cognitive performance in nondemented subjects: a population-based study.

Older people are particularly exposed to stressful events, known to activate the hypothalamus-pituitary-adrenal axis resulting in increased cortisol levels. High cortisol has been associated with deleterious effects on cognition. We hypothesized that stressful life events could increase cortisol secretion leading to cognitive impairment. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a longitudinal population-based study among Lausanne residents. Salivary cortisol samples were obtained from 796 nondemented subjects aged at least 65. A neuropsychological battery was used to assess cognitive performance and determine the Clinical Dementia Rating Sum of Boxes (CDRSOB). Lifetime life events and their subjective impact were assessed using a validated questionnaire. The total impact of life events was associated neither with cortisol area under the curve (AUC) nor with CDRSOB nor with any cognitive domain performance. The CDRSOB was associated with the cortisol AUC, controlling for age, sex, body mass index, education and depressive symptoms (p = 0.003; B = 0.686 [0.240; 1.333]; r = 0.114). This association between CDRSOB and the cortisol AUC remained significant after controlling for life events total impact (p = 0.040; B = 0.591 [0.027; 1.155]; r = 0.106). These findings do not support the hypothesis that stressful life events increase cortisol secretion leading to cognitive impairment. The association of higher cortisol levels with poorer cognition might be not a mere reflection of stressful events but rather explained by other factors, yet to be elucidated

Instruments to Assess Depressive Symptoms and Spiritual Distress Investigate Different Dimensions

Objective: Although affective and spiritual states may share some common clinical features, the precise nature of the relationship between depression and spirituality is still unclear. We tested the hypothesis that two instruments that measure depressive symptoms and spiritual distress describe similar dimensions. Methods: Patients admitted to geriatric rehabilitation (N = 185; mean age 81.3 ± 6.9 years) had depressive symptoms assessed with the 15-item Geriatric Depression Scale (GDS-15) and spiritual distress evaluated with the Spiritual Distress Assessment Tool (SDAT). Results: A principal components analysis pooling GDS-15 and SDAT resulted in a 6-factor solution, with only one factor shared by both dimensions. Conclusions: Depressive symptoms and spiritual distress measured by the two instruments appeared only moderately correlated and corresponded to distinct dimensions

Personality, Cortisol, and Cognition in Non-demented Elderly Subjects: Results from a Population-Based Study.

Certain personality traits, in particular higher neuroticism, have been associated, on one hand, with elevated cortisol levels, and on the other hand, with poorer cognitive performance. At the same time, several studies highlighted the association between high cortisol and poor cognitive functioning. Here, we hypothesized that increased cortisol may be associated with poorer cognition and with certain personality traits (mainly high neuroticism), and that personality might explain the association between cortisol and cognition. A cross-sectional analysis was conducted using data from Colaus/PsyColaus, a population-based study involving residents of Lausanne, Switzerland. Salivary cortisol samples (upon waking, 30 min after waking, at 11 am and at 8 pm) along with cognitive and personality measures were obtained from 643 non-demented participants aged at least 65. Personality traits were assessed using the NEO Five-Factor Inventory (NEO-FFI). We examined the links between the cortisol Area under the Curve (AUC), the Clinical Dementia Rating Sum of Boxes (CDRSOB) and the NEO-FFI scores. No association was found between personality traits and the CDRSOB or the MMSE score, controlling for age, sex, depression, education and BMI. However, the executive functioning domain z-score was negatively associated with agreeableness (p = 0.005; slope = -0.107 [-0.181; -0.033]) and openness (p = 0.029; slope = -0.081 [-0.154; -0.008]) after controlling for age, sex, depression, education and BMI. The CDRSOB score was positively associated with the cortisol AUC after controlling for age, sex, BMI, education and depression, (p = 0.003; slope = 0.686 [0.240; 1.333]). This association remained significant after controlling for personality traits and for the interaction between personality traits and the cortisol AUC (p = 0.006; slope = 0.792 [0.233; 1.352]. High agreeableness and openness might be associated with poorer executive performance in later life. Increased cortisol may be associated with both specific personality traits (high extraversion, low openness) and worse cognitive performance. Increased salivary cortisol does not mediate the relationship between personality traits and cognitive impairment

The effect of neoadjuvant therapy on PD-L1 expression and CD8+lymphocyte density in non-small cell lung cancer.

PD-L1 expression is the routine clinical biomarker for the selection of patients to receive immunotherapy in non-small cell lung cancer (NSCLC). However, the application and best timing of immunotherapy in the resectable setting is still under investigation. We aimed to study the effect of chemotherapy on PD-L1 expression and tumor infiltrating lymphocytes (TILs), which is to date still poorly understood. Our retrospective, single-centre neoadjuvant cohort comprised 96 consecutive patients with NSCLC resected 2000-2016 after neoadjuvant therapy, including paired diagnostic chemo-naïve specimens in 53 cases. A biologically matched surgical cohort of 114 primary resected cases was included. PD-L1 expression, CD8 + TILs density and tertiary lymphoid structures were assessed on whole slides and correlated with clinico-pathological characteristics and survival. Seven/53 and 12/53 cases had lower respectively higher PD-L1 expressions after neoadjuvant therapy. Most cases (n = 34) showed no changes in PD-L1 expression, the majority of these harboring PD-L1 < 1% in both samples (21/34 [61.8%]). Although CD8 + TILs density was significantly higher after chemotherapy (p = 0.031) in resections compared to diagnostic biopsies, this might be due to sampling and statistical bias. No difference in PD-L1 expression or CD8 + TILs density was detected when comparing the neoadjuvant and surgical cohort. In univariable analyses, higher CD8 + TILs density, higher numbers of tertiary lymphoid structures but not PD-L1 expression were significantly associated with longer survival. Increased PD-L1 expression after neoadjuvant chemotherapy was not significantly associated with shorter 5-year survival, but the number of cases was very low. In multivariable analysis, only pT category and age remained independent prognostic factors. In summary, PD-L1 expression was mostly unchanged after neoadjuvant chemotherapy compared to diagnostic biopsies. The sample size of cases with changed PD-L1 expression was too small to draw conclusions on any prognostic value

Does physical exercise improve ADL capacities in people over 65 years with moderate or severe dementia hospitalized in an acute psychiatric setting? A multisite randomized clinical trial.

Several studies on the effect of physical exercise on activities of daily living (ADL) for people with dementia exist; yet, data concerning the specific context of acute psychiatric hospitals remain scant. This study measured the effect of a physical exercise program on ADL scores in patients with moderate to severe dementia hospitalized in an acute psychiatric ward. A multicenter clinical trial was conducted in five Swiss and Belgian psychiatric hospitals. Participants were randomly allocated to either an experimental group (EG) or a control group (CG). Members of the EG received 20 physical exercise sessions (strengthening, balance, and walking) over a four-week period while members of the CG participated in social interaction sessions of equivalent duration and frequency, but without physical exercise. The effect of exercise on ADL was measured by comparing scores of the Barthel Index and the Functional Independence Measure in the EG and CG before and after the intervention, and two weeks later. Hundred and sixty patients completed the program. Characteristics of participants of both groups were similar at the inception of the study. The mean ADL score of EG decreased slightly over time, whereas that of the CG significantly decreased compared to initial scores. Overall differences between groups were not significant; however, significant differences were found for mobility-related items. ADL scores in elderly with moderate to severe dementia deteriorate during acute psychiatric hospitalization. An exercise program delays the loss of mobility but does not have a significant impact on overall ADL scores