An exploratory research report on brain mineralization in postoperative delirium and cognitive decline.

Delirium is a severe postoperative complication associated with poor overall and especially neurocognitive prognosis. Altered brain mineralization is found in neurodegenerative disorders but has not been studied in postoperative delirium and postoperative cognitive decline. We hypothesized that mineralization-related hypointensity in susceptibility-weighted magnetic resonance imaging (SWI) is associated with postoperative delirium and cognitive decline. In an exploratory, hypothesis-generating study, we analysed a subsample of cognitively healthy patients ≥65 years who underwent SWI before (N = 65) and 3 months after surgery (N = 33). We measured relative SWI intensities in the basal ganglia, hippocampus and posterior basal forebrain cholinergic system (pBFCS). A post hoc analysis of two pBFCS subregions (Ch4, Ch4p) was conducted. Patients were screened for delirium until the seventh postoperative day. Cognitive testing was performed before and 3 months after surgery. Fourteen patients developed delirium. After adjustment for age, sex, preoperative cognition and region volume, only pBFCS hypointensity was associated with delirium (regression coefficient [90% CI]: B = -15.3 [-31.6; -0.8]). After adjustments for surgery duration, age, sex and region volume, perioperative change in relative SWI intensities of the pBFCS was associated with cognitive decline 3 months after surgery at a trend level (B = 6.8 [-0.9; 14.1]), which was probably driven by a stronger association in subregion Ch4p (B = 9.3 [2.3; 16.2]). Brain mineralization, particularly in the cerebral cholinergic system, could be a pathomechanism in postoperative delirium and cognitive decline. Evidence from our studies is limited because of the small sample and a SWI dataset unfit for iron quantification, and the analyses presented here should be considered exploratory.

The Association of Plasma Leptin, Soluble Leptin Receptor and Total and High-Molecular Weight Adiponectin With the Risk of Perioperative Neurocognitive Disorders.

BACKGROUND: Perioperative neurocognitive disorders (NCD) are poorly characterized in terms of their risk factor profiles. Leptin and adiponectin are adipose-tissue-derived hormones with a role in inflammation and atherosclerosis whose function in perioperative NCD is unclear. Here, we used a cohort of older adults to examine the association of preoperative plasma concentrations of these biomarkers with the risk of perioperative NCD. METHODS: Prospective analysis of 768 participants aged ≥ 65 years of the BioCog study. Blood was collected before surgery for measurement of plasma total and high-molecular-weight (hmw) adiponectin, leptin, and soluble leptin receptor (sOB-R). The free leptin index (FLI, leptin:sOB-R) was calculated. Postoperative delirium (POD) was assessed twice daily until postoperative day 7/discharge. Five hundred twenty-six patients (68.5%) returned for 3-month follow-up and provided data on postoperative cognitive dysfunction (POCD). POCD was defined as a decline on six neuropsychological tests that exceeded that of a nonsurgical control group. Logistic regression analyses examined the associations of each exposure with POD and POCD risk, in separate models adjusted for age, sex, fasting, surgery type, and body mass index (BMI). RESULTS: Of 768 patients, 152 (19.8%) developed POD. Of 526 attendants of the follow-up, 54 (10.3%) had developed POCD. Leptin, sOB-R, and total and hmw adiponectin were each not associated with POD. For POCD, we observed reduced risk in patients in FLI quartile 4 compared with quartile 1 (odds ratio, 0.26; 95% CI 0.08, 0.89). Sensitivity analyses for the outcome POD revealed statistically significant interaction terms of sOB-R and total adiponectin with obesity (BMI≥30kg/m2 versus BMI<30kg/m2). For the outcome POCD, a higher sOB-R was associated with an increased risk in the obese subgroup (odds ratio, 4.00; 95% CI 1.01, 15.86). CONCLUSIONS: We did not find consistent evidence for the role of leptin, its receptor, and total and hmw adiponectin in POD and POCD risk. Future research should be used to support or refute our findings and to fully characterize any differences in the associations of these hormones with POD/POCD between obese and nonobese individuals.

Incidence of Parkinson's disease in Germany based on prevalence data from 70 million patients of the statutory health insurance.

BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and nonmotor system manifestations and psychiatric symptoms. The aim of this study was to estimate the age- and sex-specific incidence of PD in Germany using an illness-death model and a corresponding partial differential equation (PDE) based on prevalence and mortality data. METHODS: Based on a PDE that describes the dynamics in an illness-death model, the age- and sex-specific incidence of PD in Germany was estimated using published prevalence and mortality rates. Prevalence rates were provided by the Central Institute for Statutory Health Insurance (Zi) for the period from 2010 to 2019. Parkinson's related mortality was estimated based on comparable population data from Norway. Bootstrapping was used for incidence estimation (median of 5000 samples) and to obtain 95% confidence intervals to interpret the accuracy of the incidence estimation. RESULTS: Men had higher incidences of PD than women at all ages. The highest incidences (median of 5000 bootstrap samples) for both groups were estimated for the age of 85 years with an incidence of 538.49 per 100,000 person-years (py) in men and 284.09 per 100,000 py in women, with an increasing width of bootstrapping 95% CIs showing greater uncertainty in the estimation at older ages. CONCLUSION: The illness-death model and the corresponding PDE, which describes changes in prevalence as a function of mortality and incidence, can be used to estimate the incidence of PD as a chronic disease. As overestimation of incidence is less likely with this method, we found incidence rates of Parkinson's disease that are suitable for further analyses with a lower risk of bias.

Structural disconnectivity in postoperative delirium: A perioperative two-center cohort study in older patients.

BACKGROUND: Structural disconnectivity was found to precede dementia. Global white matter abnormalities might also be associated with postoperative delirium (POD). METHODS: We recruited older patients (≥65 years) without dementia that were scheduled for major surgery. Diffusion kurtosis imaging metrics were obtained preoperatively, after 3 and 12 months postoperatively. We calculated fractional anisotropy (FA), mean diffusivity (MD), mean kurtosis (MK), and free water (FW). A structured and validated delirium assessment was performed twice daily. RESULTS: Of 325 patients, 53 patients developed POD (16.3%). Preoperative global MD (standardized beta 0.27 [95% confidence interval [CI] 0.21-0.32] p < 0.001) was higher in patients with POD. Preoperative global MK (-0.07 [95% CI -0.11 to (-0.04)] p < 0.001) and FA (0.07 [95% CI -0.10 to (-0.04)] p < 0.001) were lower. When correcting for baseline diffusion, postoperative MD was lower after 3 months (0.05 [95% CI -0.08 to (-0.03)] p < 0.001; n = 183) and higher after 12 months (0.28 [95% CI 0.20-0.35] p < 0.001; n = 45) among patients with POD. DISCUSSION: Preoperative structural disconnectivity was associated with POD. POD might lead to white matter depletion 3 and 12 months after surgery.

The Thalamus in Perioperative Neurocognitive Disorders.

Thalamus function and structure are known predictors of individual differences in the risk of age-related neurocognitive disorders (NCD), such as dementia. However, to date, little is known about their role in the perioperative setting. Here, we provide a narrative review of brain-imaging studies of preoperative and postoperative thalamus scanning parameters associated with risks of developing perioperative NCD, such as postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) during the postoperative phase. These findings are discussed in light of the concept of reserve capacity.

Metabolic syndrome and the risk of postoperative delirium and postoperative cognitive dysfunction: a multi-centre cohort study.

BACKGROUND: Metabolic syndrome and its components are risk factors for cognitive impairment, but their contribution to perioperative neurocognitive disorders is unknown. We examined their associations with the risk of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in older patients. METHODS: In 765 male and female participants aged ≥65 years, we measured preoperative metabolic parameters and screened for POD for 7 days or until discharge. POCD was defined through comparison of cognitive change on six neuropsychological tests with non-surgical controls. Multiple logistic regression analyses examined the association of metabolic parameters with risk of POD and POCD with adjustment for age, sex, and surgery type. RESULTS: A total of 149 patients (19.5% of 765) developed POD and 53 (10.1% of 520 attendees) had POCD at 3 months. Patients with metabolic syndrome were at 1.85-fold higher risk of POD (95% confidence interval [CI] 1.26-2.70). Each 1 mM higher high-density lipoprotein cholesterol (HDL-C) was associated with a 0.47-fold lower POD risk (95% CI 0.30-0.74). Each 1 kg m-2 higher body mass index (BMI) was associated with a 1.09-fold higher POCD risk (95% CI 1.02- 1.16). CONCLUSIONS: Older surgical patients with metabolic syndrome were at increased risk of POD. Only reduced HDL-C was significantly associated with POD. For POCD, a higher preoperative BMI was identified as a risk factor. These findings add to mounting evidence of a distinct epidemiology of POD and POCD. Screening programmes taking advantage of HDL-C and BMI measurements and of metabolic interventions in reducing perioperative neurocognitive disorders should be evaluated. CLINICAL TRIAL REGISTRATION: NCT02265263.

Presurgical Thalamus Volume in Postoperative Delirium: A Longitudinal Observational Cohort Study in Older Patients.

BACKGROUND: Previous studies suggest a role of the thalamus in cognitive function, while others implicate it as a central effect site of anesthetics. Yet, its role in postoperative neurocognition in the aging brain remains uncertain. We used presurgical thalamic volume as a functional indicator and determined its association with postoperative delirium (POD). METHODS: For this study, 301 older adults (aged ≥65) without dementia and scheduled for surgery were enrolled. Before surgery, participants underwent magnetic resonance imaging (MRI). Thalamus volume was segmented using Freesurfer (Version 5.3.). Participants were screened for POD twice a day until discharge or for a maximum of 7 days. POD was defined as a positive screening on ≥1 of 4 validated instruments: Richmond Agitation Sedation Scale (RASS), Nursing Delirium Screening Scale (Nu-DESC), Confusion Assessment Method (CAM), and Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) score. A logistic regression associated thalamus volume with POD with adjustment for age, global brain atrophy, and physical status according to the American Society of Anesthesiologists (ASA) classification. RESULTS: In this cohort, 44 participants (14.6%) were diagnosed with POD. Independently of age, global brain atrophy, and physical status score, a higher preoperative thalamus volume was associated with a reduced odds of POD (odds ratio per 1-cm3 increment; 0.73 [95% confidence interval (CI), 0.58-0.92]; P = .008). CONCLUSIONS: A larger thalamus volume was associated with reduced odds of POD. Thus, the thalamus marks a region of interest in POD in the aging brain. These findings may help to understand the neuronal basis of POD.

Methodology of measuring postoperative cognitive dysfunction: a systematic review.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is an adverse outcome that impacts patients' quality of life. Its diagnosis relies on formal cognitive testing performed before and after surgery. The substantial heterogeneity in methodology limits comparability and meta-analysis of studies. This systematic review critically appraises the methodology of studies on POCD published since the 1995 Consensus Statement and aims to provide guidance to future authors by providing recommendations that may improve comparability between future studies. METHODS: This systematic review of literature published between 1995 and 2019 included studies that used baseline cognitive testing and a structured cognitive test battery, and had a minimal follow-up of 1 month. For cohorts with multiple publications, data from the primary publication were supplemented with available data from later follow-up studies. RESULTS: A total of 274 unique studies were included in the analysis. In the included studies, 259 different cognitive tests were used. Studies varied considerably in timing of assessment, follow-up duration, definition of POCD, and use of control groups. Of the 274 included studies, 70 reported POCD as a dichotomous outcome at 1 to <3 months, with a pooled incidence of 2998/10 335 patients (29.0%). CONCLUSIONS: We found an overwhelming heterogeneity in methodology used to study POCD since the publication of the 1995 Consensus Statement. Future authors could improve study quality and comparability through optimal timing of assessment, the use of commonly used cognitive tests including the Consensus Statement 'core battery', application of appropriate cut-offs and diagnostic rules, and detailed reporting of the methods used. PROSPERO REGISTRY NUMBER: CRD42016039293.

Contribution of IQ in young adulthood to the associations of education and occupation with cognitive ability in older age.

BACKGROUND: Studies suggest that a higher education and occupation are each associated with a higher late-life cognitive ability, but their inter-relationships in their association with cognitive ability and the contribution of peak IQ in young adulthood ('pre-morbid IQ') often remain unclear. METHODS: Cross-sectional analysis of 623 participants aged ≥65 years of the BioCog study. Education was coded according to the International Standard Classification of Education (ISCED; range 1 to 6). Occupation was coded as 'semi/unskilled', 'skilled manual', 'skilled non-manual', 'managerial', 'professional'. A summary score of global ability ('g') was constructed from six cognitive tests. Pre-morbid IQ was estimated from vocabulary. The Geriatric Depression Scale assessed symptoms of depression. Age- and sex-adjusted analyses of covariance were performed. RESULTS: Education (partial eta2 0.076; p < 0.001) and occupation (partial eta2 = 0.037; p < 0.001) were each significantly associated with g. For education, the association was attenuated but remained statistically significant when pre-morbid IQ was controlled for (partial eta2 0.036; p < 0.001) and was unchanged with additional adjustment for depression (partial eta2 0.037; p < 0.001). For occupation, the association with g was no longer significant when pre-morbid IQ (partial eta2 = 0.015; p = 0.06) and depression (partial eta2 = 0.011; p = 0.18) were entered as covariates in separate steps. When education and occupation were entered concurrently into the fully adjusted model, only education was independently associated with g (partial eta2 0.030; p < 0.001; occupation, p = 0.93). CONCLUSION: While a higher education and a higher occupation were each associated with a higher late-life cognitive ability, only for education some unique contribution to cognitive ability remained over and above its relationship with pre-morbid IQ, depression, and occupation. Further research is needed to address whether a longer time spent in education may promote late-life cognitive ability.

Treatment and Mortality of Hemophagocytic Lymphohistiocytosis in Adult Critically Ill Patients: A Systematic Review With Pooled Analysis.

OBJECTIVES: Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients. DATA SOURCES: MEDLINE database (PubMed) at October 20, 2019. STUDY SELECTION: Studies and case series of patients greater than or equal to 18 years old, of whom at least one had to be diagnosed with hemophagocytic lymphohistiocytosis and admitted to an ICU. DATA EXTRACTION: Source data of studies and case series were summarized and analyzed on an individual basis. Multivariable logistic regression analysis was performed adjusting for age, sex, and trigger groups. Each single treatment agent was entered as a dichotomous variable to determine treatments associated with survival, regardless if given alone or in combination. DATA SYNTHESIS: In total, 661 patients from 65 studies and case series were included. Overall mortality was 57.8%. Infections were the most frequent trigger (49.9%), followed by malignancies (28.0%), autoimmune diseases (12.1%), unknown triggers (9.4%), and drugs (0.6%). Treatment with IV immunoglobulins was associated with improved survival (odds ratio, 0.548; 95% CI, 0.337-0.891; p = 0.015), while treatment with cyclosporine was associated with increased risk of death (odds ratio, 7.571; 95% CI, 3.702-15.483; p < 0.001). Considering different trigger groups separately, same results occurred only for infection-triggered hemophagocytic lymphohistiocytosis. No information was available on disease severity and other confounding factors. CONCLUSIONS: Mortality of hemophagocytic lymphohistiocytosis in the ICU is high. Most common triggers were infections. Results of survival analyses may be biased by treatment indication and disease severity. Future studies prospectively investigating treatment tailored to critically ill hemophagocytic lymphohistiocytosis patients are highly warranted.

Cognitive Impairment Is Associated with Absolute Intraoperative Frontal α-Band Power but Not with Baseline α-Band Power: A Pilot Study.

BACKGROUND: Cognitive abilities decline with aging, leading to a higher risk for the development of postoperative delirium or postoperative neurocognitive disorders after general anesthesia. Since frontal α-band power is known to be highly correlated with cognitive function in general, we hypothesized that preoperative cognitive impairment is associated with lower baseline and intraoperative frontal α-band power in older adults. METHODS: Patients aged ≥65 years undergoing elective surgery were included in this prospective observational study. Cognitive function was assessed on the day before surgery using six age-sensitive cognitive tests. Scores on those tests were entered into a principal component analysis to calculate a composite "g score" of global cognitive ability. Patient groups were dichotomized into a lower cognitive group (LC) reaching the lower 1/3 of "g scores" and a normal cognitive group (NC) consisting of the upper 2/3 of "g scores." Continuous pre- and intraoperative frontal electroencephalograms (EEGs) were recorded. EEG spectra were analyzed at baseline, before start of anesthesia medication, and during a stable intraoperative period. Significant differences in band power between the NC and LC groups were computed by using a frequency domain (δ 0.5-3 Hz, θ 4-7 Hz, α 8-12 Hz, ß 13-30 Hz)-based bootstrapping algorithm. RESULTS: Of 38 included patients (mean age 72 years), 24 patients were in the NC group, and 14 patients had lower cognitive abilities (LC). Intraoperative α-band power was significantly reduced in the LC group compared to the NC group (NC -1.6 [-4.48/1.17] dB vs. LC -6.0 [-9.02/-2.64] dB), and intraoperative α-band power was positively correlated with "g score" (Spearman correlation: r = 0.381; p = 0.018). Baseline EEG power did not show any associations with "g." CONCLUSIONS: Preoperative cognitive impairment in older adults is associated with intraoperative absolute frontal α-band power, but not baseline α-band power.

Associations of the metabolic syndrome and its components with cognitive impairment in older adults.

BACKGROUND: The metabolic syndrome (MetS) is an established cardiovascular risk factor. Here, we investigated its role in cognitive impairment. METHODS: Baseline data from 202 participants (aged 65 to 87 years) of the BioCog study were used. All were free of clinical dementia (MMSE≥24/30). Cognitive impairment was defined as the lowest tertile of a cognitive summary score. Multiple logistic regression analyses examined associations of body mass index (BMI), triglycerides (TG), high-density lipoprotein (HDL-C), glucose and glycated hemoglobin A1c (HbA1c) levels with the odds of cognitive impairment. MetS was defined as ≥3 of its 5 components obesity (BMI ≥ 30 kg/m2), elevated TG (TG ≥1.7 mmol/L), reduced HDL-C (males: < 1.0 mmol/L; females: < 1.3 mmol/L), elevated glucose (glucose ≥5.5 mmol/L and/or diagnosed diabetes) and elevated blood pressure (history of hypertension). Analyses controlled for age, sex and smoking history. RESULTS: Lower HDL-C was significantly associated with a higher odds of cognitive impairment (OR 2.70 per 1 mmol/L reduction; 95% CI 1.25, 5.56; p = 0.011), whereas BMI, TG, glucose and HbA1c were not (all p > 0.05). Results for HDL-C were similar when HDL-C, glucose, BMI and TG were entered into a single model (OR 2.56 per 1 mmol/L reduction, 95% CI 1.09, 5.88, p = 0.031) and when cerebrovascular disease and coronary heart disease were additionally controlled for (OR 2.56 per 1 mmol/L reduction, 95% CI 1.06, 6.25, p = 0.036). Among the 5 MetS components, participants with elevated TG were at 2-fold increased odds of impairment (OR 2.09, 95% CI 1.08, 4.05, p = 0.028) including when the remaining 4 MetS components were entered (OR 2.23, 95% CI 1.07, 4.65, p = 0.033), but the finding was no longer statistically significant when cerebrovascular disease and coronary heart disease were additionally controlled for (p = 0.11). Presence of MetS and of obesity, reduced HDL-C, elevated glucose or elevated blood pressure were not significantly associated with impairment (all p > 0.05). CONCLUSION: Our findings support low HDL-C as an independent risk marker of cognitive impairment in older age. The need for research into mediatory and confounding factors, and re-evaluation of traditional cut-off points is highlighted. TRIAL REGISTRATION: The study was registered on 15th October 2014 at clinicaltrials.gov ( NCT02265263 ).

Diabetes, but Not Hypertension and Obesity, Is Associated with Postoperative Cognitive Dysfunction.

BACKGROUND/AIMS: Older people undergoing surgery are at risk of developing postoperative cognitive dysfunction (POCD), but little is known of risk factors predisposing patients to POCD. Our objective was to estimate the risk of POCD associated with exposure to preoperative diabetes, hypertension, and obesity. METHODS: Original data from 3 randomised controlled trials (OCTOPUS, DECS, SuDoCo) were obtained for secondary analysis on diabetes, hypertension, baseline blood pressure, obesity (BMI ≥30 kg/m2), and BMI as risk factors for POCD in multiple logistic regression models. Risk estimates were pooled across the 3 studies. RESULTS: Analyses totalled 1,034 patients. POCD occurred in 5.2% of patients in DECS, in 9.4% in SuDoCo, and in 32.1% of patients in OCTOPUS. After adjustment for age, sex, surgery type, randomisation, obesity, and hypertension, diabetes was associated with a 1.84-fold increased risk of POCD (OR 1.84; 95% CI 1.14, 2.97; p = 0.01). Obesity, BMI, hypertension, and baseline blood pressure were each not associated with POCD in fully adjusted models (all p > 0.05). CONCLUSION: Diabetes, but not obesity or hypertension, is associated with increased POCD risk. Consideration of diabetes status may be helpful for risk assessment of surgical patients.

Obesity and post-operative cognitive dysfunction: a systematic review and meta-analysis.

BACKGROUND: Post-operative cognitive dysfunction, a condition distinct from post-operative delirium (POD), occurs frequently after surgery, and is related to dementia and premature death. Obesity increases the risk of late-life cognitive impairment, but little is known about its role in post-operative cognitive dysfunction. We conducted a systematic review and meta-analysis of studies on the association between obesity and risk of post-operative cognitive dysfunction. METHODS: PubMed and the Cochrane Library were systematically searched. Studies were included if they had prospective designs, reported on human adults undergoing surgery, if cognitive function was measured pre- and post-surgery, if obesity, body mass index (BMI) and/or body weight were ascertained, and if associations with post-operative cognitive dysfunction were reported as relative risks or odds ratios. Underweight, weight loss, and post-operative delirium were not considered. RESULTS: Inclusion criteria were met by six articles. Samples totaled 1432 older patients (mean age ≥62 years) who were followed up for 24 h to 12 months after surgery. Analysis of studies with obesity defined as a categorical measure found a non-significantly higher risk of post-operative cognitive dysfunction among persons with BMI > 30 kg/m(2) versus ≤30 kg/m(2) (relative risk 1.27; 95% confidence interval 0.95, 1.70; p = 0.10). No such associations were found for studies that analysed BMI or body weight continuously as predictors of post-operative cognitive dysfunction (relative risk 0.98 per kg/m(2) ; 95% confidence interval 0.93, 1.03, p = 0.45; relative risk 0.99 per kg; 95% confidence interval 0.89, 1.09; p = 0.83, respectively). CONCLUSIONS: Few studies have addressed the topic, and the results of these studies provide only limited support for an increased risk of post-operative cognitive dysfunction in patients who are obese. Further large-scale, prospective investigations are necessary for clarification. Copyright © 2016 John Wiley & Sons, Ltd.

The Impact of Personality Factors and Preceding User Comments on the Processing of Research Findings on Deep Brain Stimulation: A Randomized Controlled Experiment in a Simulated Online Forum.

BACKGROUND: Laypeople frequently discuss medical research findings on Web-based platforms, but little is known about whether they grasp the tentativeness that is inherent in these findings. Potential influential factors involved in understanding medical tentativeness have hardly been assessed to date. OBJECTIVE: The research presented here aimed to examine the effects of personality factors and of other users' previous contributions in a Web-based forum on laypeople's understanding of the tentativeness of medical research findings, using the example of research on deep brain stimulation. METHODS: We presented 70 university students with an online news article that reported findings on applying deep brain stimulation as a novel therapeutic method for depression, which participants were unfamiliar with. In a randomized controlled experiment, we manipulated the forum such that the article was either accompanied by user comments that addressed the issue of tentativeness, by comments that did not address this issue, or the article was accompanied by no comments at all. Participants were instructed to write their own individual user comments. Their scientific literacy, epistemological beliefs, and academic self-efficacy were measured. The outcomes measured were perceived tentativeness and tentativeness addressed in the participants' own comments. RESULTS: More sophisticated epistemological beliefs enhanced the perception of tentativeness (standardized ß=.26, P=.034). Greater scientific literacy (stand. ß=.25, P=.025) and greater academic self-efficacy (stand. ß=.31, P=.007) were both predictors of a more extensive discussion of tentativeness in participants' comments. When forum posts presented in the experiment addressed the issue of tentativeness, participants' subsequent behavior tended to be consistent with what they had read in the forum, F2,63=3.66; P=.049, ηp(2)=.092. CONCLUSIONS: Students' understanding of the tentativeness of research findings on deep brain stimulation in an online forum is influenced by a number of character traits and by the previous comments that were contributed to the forum by other users. There is potential for targeted modification of traits such as scientific literacy, epistemological beliefs, and academic self-efficacy to foster critical thinking in laypeople who take part in online discussions of medical research findings.

The impact of epistemological beliefs and cognitive ability on recall and critical evaluation of scientific information.

Scientific research findings are frequently picked up by the mainstream media, but it is largely unclear which factors have an impact on laypeople's processing of the presented scientific information. In this study, we investigated the influence of cognitive and metacognitive inter-individual differences on recall and on critical evaluation of new scientific information that was presented in a journalistic article. Sixty-three participants (80 % female; mean age 24.1 ± 3.3 years) read a newspaper article reporting research findings on a recently developed and yet unproven treatment for depression. We found that more sophisticated, domain-specific epistemological beliefs and a higher cognitive ability were independently associated with better recall of content from the article. Additionally, participants with more sophisticated epistemological beliefs displayed a more critical evaluation of the article. Cognitive ability was unrelated to critical evaluation and to epistemological beliefs. There were also no interaction effects of cognitive ability and epistemological beliefs on recall or on critical evaluation. Based on our preliminary findings and previous evidence of epistemological beliefs as a modifiable feature, we discuss this inter-individual characteristic as a potential target for the promotion of better understanding of scientific topics by the general public.

Cardiovascular risk factors and cognitive decline in older people with type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this work was to assess the role of well-established cardiovascular risk factors in the late-life cognitive decline of patients with type 2 diabetes. METHODS: Data from 831 participants (aged 60-75 years) attending the 4 year follow-up of the Edinburgh Type 2 Diabetes Study (ET2DS) were used. Smoking history (pack-years), BP, HbA1c, plasma glucose and cholesterol were determined at baseline clinics (single time measurements) and/or from serial data recorded on a clinical management database from diagnosis until recruitment ('historical' data). Principal component analysis derived a factor, g, of general ability from seven cognitive tests. Linear regression models of follow-up g were adjusted for baseline g to represent 4 year cognitive change. 'Accelerated late-life cognitive decline' was defined as scoring in the lowest tertile of '4 year cognitive change' regression scores. Analyses controlled for age and sex. RESULTS: A baseline history of moderate/heavy smoking (≥ 10 pack-years) and a 1% increased historical HbA1c (equivalent to an increase by 11 mmol/mol) predicted a 64% (OR 1.64; 95% CI 1.14, 2.34; p = 0.007) and 21% (OR 1.21; 95% CI 1.00, 1.45; p = 0.046) increased risk of accelerated cognitive decline, respectively. When treated as continuous measures, higher pack-years, historical HbA1c and historical BP emerged as significant independent predictors of 4 year decline in g (standardised ß range -0.07 to -0.14; all p ≤ 0.05). CONCLUSIONS/INTERPRETATION: Increased smoking and poorer glycaemic control (with relatively weaker findings for BP) during the life-course were independently associated with accelerated late-life cognitive decline. Where possible, evaluation is warranted of these risk factors as targets for intervention to reduce the burden of cognitive impairment in diabetes.

N-terminal pro-brain natriuretic peptide and risk of cardiovascular events in older patients with type 2 diabetes: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with traditional cardiovascular risk factors and incident cardiovascular events in older people with type 2 diabetes. METHODS: In the prospective phase of the Edinburgh Type 2 Diabetes Study, 1066 men and women aged 60 to 75 years with type 2 diabetes mellitus were followed for 4 years; 112 participants had an incident cardiovascular event. At baseline, cardiovascular risk factors, pre-existing cardiovascular disease and levels of NT-proBNP were evaluated. RESULTS: Raised plasma NT-proBNP levels were associated with these classical cardiovascular risk factors: increased duration of diabetes, use of insulin, raised BMI, reduced HDL-cholesterol, reduced renal function and use of lipid-lowering and anti-hypertensive medication (all p < 0.05). In the prospective analysis, NT-proBNP was strongly associated with subsequent risk of all cardiovascular disease events (HR per one SD increase in NT-proBNP 1.39; 95% CI 1.10, 1.75), independent of cardiovascular risk factors traditionally used to predict vascular events. NT-proBNP was also independently associated with incident coronary artery disease events (1.48, 95% CI 1.10, 1.98). The addition of NT-proBNP to multivariate models improved the C-index by 0.019 for the 'hard' cardiac endpoint (fatal and non-fatal myocardial infarction). CONCLUSIONS/INTERPRETATION: In older people with type 2 diabetes, NT-proBNP is associated with the development of coronary and cerebrovascular events, independent of a wide range of other vascular and metabolic risk factors, and may prove a useful addition to current vascular risk scores in diabetes populations.

Perioperative Levels of IL8 and IL18, but not IL6, are Associated with Nucleus Basalis Magnocellularis Atrophy Three Months after Surgery.

Past studies have observed that brain atrophy may accelerate after surgical procedures. Furthermore, an association of systemic inflammation with neurodegeneration has been described. We hypothesize that postoperative interleukin (IL) levels in circulation as well as the perioperative change in interleukin levels are associated with increased postoperative atrophy in the Nucleus basalis magnocellularis (of Meynert, NBM) which is the major source of cortical acetylcholine. We analyzed data from the BioCog cohort which included patients ≥ 65 years presenting for elective major surgery (≥ 60min). Blood samples were taken before surgery and on the first postoperative day. Magnetic resonance imaging of the brain and neuropsychological assessments were conducted before surgery and after three months follow-up. We used linear regression analysis to determine the association of three interleukins (IL6, IL8 and IL18) with NBM atrophy (in % volume change from baseline before surgery to follow-up), as well as to examine the associations of NBM atrophy and volume with postoperative cognitive ability and perioperative cognitive change. Receiver-operating curves were used to determine the prognostic value of preoperative interleukin levels. For IL8 (N = 97) and IL18 (N = 217), but not IL6 (N = 240), we observed significant associations of higher postoperative IL levels at the first postoperative day with higher NBM atrophy at three months after surgery. Subsequent analyses suggested that in both IL8 and IL18, this association was driven by a more general association of chronically elevated IL levels and NBM atrophy, reflected by preoperative IL concentrations, rather than IL response to surgery, measured as the difference between pre- and postoperative IL concentrations. At follow-up, NBM volume was positively associated with the level of cognitive performance, but NBM atrophy was not significantly related to perioperative cognitive change. Prognostic value of preoperative IL concentrations for NBM atrophy was low. Our results suggest that an association of postoperative interleukin levels with NBM atrophy is driven by preoperatively elevated interleukins due to pre-existing inflammation, rather than perioperative change in interleukin levels in response to surgery and anesthesia. The BioCog study has been registered at clinicaltrials.gov on Oct 15, 2014 (NCT02265263).

Preoperative thalamus volume is not associated with preoperative cognitive impairment (preCI) or postoperative cognitive dysfunction (POCD).

A growing body of literature suggests the important role of the thalamus in cognition and neurodegenerative diseases. This study aims to elucidate whether the preoperative thalamic volume is associated with preoperative cognitive impairment (preCI) and whether it is predictive for postoperative cognitive dysfunction at 3 months (POCD). We enrolled 301 patients aged 65 or older and without signs of dementia who were undergoing elective surgery. Magnetic resonance imaging was conducted prior to surgery. Freesurfer (version 5.3.) was used to automatically segment the thalamus volume. A neuropsychological test battery was administered before surgery and at a 3 month follow-up. It included the computerized tests Paired Associate Learning (PAL), Verbal Recognition Memory (VRM), Spatial Span Length (SSP), Simple Reaction Time (SRT), the pen-and-paper Trail-Making-Test (TMT) and the manual Grooved Pegboard Test (GPT). Using a reliable change index, preCI and POCD were defined as total Z-score > 1.96 (sum score over all tests) and/or Z-scores > 1.96 in ≥ 2 individual cognitive test parameters. For statistical analyses, multivariable logistic regression models were applied. Age, sex and intracranial volume were covariates in the models. Of 301 patients who received a presurgical neuropsychological testing and MRI, 34 (11.3%) had preCI. 89 patients (29.5%) were lost to follow-up. The remaining 212 patients received a follow-up cognitive test after 3 months, of whom 25 (8.3%) presented with POCD. Independently of age, sex and intracranial volume, neither preCI (OR per cm3 increment 0.81 [95% CI 0.60-1.07] p = 0.14) nor POCD (OR 1.02 per cm3 increment [95% CI 0.75-1.40] p = 0.87) were statistically significantly associated with patients' preoperative thalamus volume. In this cohort we could not show an association of presurgical thalamus volume with preCI or POCD.Clinical Trial Number: NCT02265263 ( https://clinicaltrials.gov/ct2/show/results/NCT02265263 ).