ResearchPad - dementia https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Participant and informant memory-specific cognitive complaints predict future decline and incident dementia: Findings from the Sydney Memory and Ageing Study]]> https://www.researchpad.co/article/elastic_article_7842 Subjective Cognitive Complaints (SCCs) may represent one of the earliest stages of preclinical dementia. The objective of the present study was to extend previous work by our group to examine the relationship between participant-reported and informant-reported memory and non-memory SCCs, cognitive decline and incident dementia, over a six-year period. Participants were 873 community dwelling older adults (Mage = 78.65, SD = 4.79) without dementia and 843 informants (close friends or family) from the Sydney Memory and Ageing Study. Comprehensive neuropsychological testing and diagnostic assessments were carried out at baseline and biennially for six years. Linear mixed models and Cox proportional hazard models were performed to determine the association of SCCs, rate of cognitive decline and risk of incident dementia, controlling demographics and covariates of mood and personality. Participant and informant memory-specific SCCs were associated with rate of global cognitive decline; for individual cognitive domains, participant memory SCCs predicted decline for language, while informant memory SCCs predicted decline for executive function and memory. Odds of incident dementia were associated with baseline participant memory SCCs and informant memory and non-memory SCCs in partially adjusted models. In fully adjusted models, only informant SCCs were associated with increased risk of incident dementia. Self-reported memory-specific cognitive complaints are associated with decline in global cognition over 6-years and may be predictive of incident dementia, particularly if the individual is depressed or anxious and has increased neuroticism or decreased openness. Further, if and where possible, informants should be sought and asked to report on their perceptions of the individual’s memory ability and any memory-specific changes that they have noticed as these increase the index of diagnostic suspicion.

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<![CDATA[Pooling individual participant data from randomized controlled trials: Exploring potential loss of information]]> https://www.researchpad.co/article/elastic_article_7838 Pooling individual participant data to enable pooled analyses is often complicated by diversity in variables across available datasets. Therefore, recoding original variables is often necessary to build a pooled dataset. We aimed to quantify how much information is lost in this process and to what extent this jeopardizes validity of analyses results.MethodsData were derived from a platform that was developed to pool data from three randomized controlled trials on the effect of treatment of cardiovascular risk factors on cognitive decline or dementia. We quantified loss of information using the R-squared of linear regression models with pooled variables as a function of their original variable(s). In case the R-squared was below 0.8, we additionally explored the potential impact of loss of information for future analyses. We did this second step by comparing whether the Beta coefficient of the predictor differed more than 10% when adding original or recoded variables as a confounder in a linear regression model. In a simulation we randomly sampled numbers, recoded those < = 1000 to 0 and those >1000 to 1 and varied the range of the continuous variable, the ratio of recoded zeroes to recoded ones, or both, and again extracted the R-squared from linear models to quantify information loss.ResultsThe R-squared was below 0.8 for 8 out of 91 recoded variables. In 4 cases this had a substantial impact on the regression models, particularly when a continuous variable was recoded into a discrete variable. Our simulation showed that the least information is lost when the ratio of recoded zeroes to ones is 1:1.ConclusionsLarge, pooled datasets provide great opportunities, justifying the efforts for data harmonization. Still, caution is warranted when using recoded variables which variance is explained limitedly by their original variables as this may jeopardize the validity of study results. ]]> <![CDATA[MEDICATION DISCREPANCIES AND COMMUNICATION ERRORS DURING NURSING HOME INTAKE: A MIXED-METHODS ANALYSIS]]> https://www.researchpad.co/article/N7fec902e-1215-4860-a7a0-61676c13f908

Abstract

Older adults experience high medication discrepancy rates during transitions from inpatient to nursing home settings. Dosage changes and multiple prescribers increases the risk of inaccurate handoffs and creates challenges for medication reconciliation at nursing home intake. Our objectives were to 1) Characterize medication discrepancies occurring at nursing home intake and 2) Identify resident and medication related factors associated with medication discrepancies. Demographics, comorbidities, medications, discrepancy types and location were prospectively collected over 9-months. Chi-square tests were used to determine factors associated with discrepancies. A focus group of nurse practitioners, pharmacists, and administrators from four long-term care facilities was convened to discuss medication reconciliation challenges at resident intake. Thematic analysis was used to determine key themes. 22%, 12%, and 3% of residents experienced one, 2 to 5, or six or more discrepancies, respectively. The most prevalent discrepancies were omission (34%), frequency (20%), and therapeutic duplication (13%) occurring in analgesics, respiratory and genitourinary medications. 44% of discrepancies occurred between nursing homes and hospitals and 39% involved the community pharmacy. The most significant risk factors for discrepancies included age over 70, Charlson comorbidity indices over 7, readmission to nursing homes, or the prescribing of at least 17 medications. Staff faced challenges of delayed and/or inaccurate data, incompatible documentation forms and inefficient workflows for resolving discrepancies. Residents at greatest risk for medication discrepancies require additional attention during admission medication reconciliation to prevent errors. Nursing home intake and medication reconciliation workflow needs to be improved with data sharing technology to increase accuracy and efficiency.

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<![CDATA[A smartphone-based test for the assessment of attention deficits in delirium: A case-control diagnostic test accuracy study in older hospitalised patients]]> https://www.researchpad.co/article/N8fecd5fe-2073-4d74-805a-6132ddca5eea

Background

Delirium is a common and serious acute neuropsychiatric syndrome which is often missed in routine clinical care. Inattention is the core cognitive feature. Diagnostic test accuracy (including cut-points) of a smartphone Delirium App (DelApp) for assessing attention deficits was assessed in older hospital inpatients.

Methods

This was a case-control study of hospitalised patients aged ≥65 years with delirium (with or without pre-existing cognitive impairment), who were compared to patients with dementia without delirium, and patients without cognitive impairment. Reference standard delirium assessment, which included a neuropsychological test battery, was based on Diagnostic and Statistical Manual of Mental Disorders-5 criteria. A separate blinded assessor administered the DelApp arousal assessment (score 0–4) and attention task (0–6) yielding an overall score of 0 to 10 (lower scores indicate poorer performance). Analyses included receiver operating characteristic curves and sensitivity and specificity. Optimal cut-points for delirium detection were determined using Youden’s index.

Results

A total of 187 patients were recruited, mean age 83.8 (range 67–98) years, 152 (81%) women; n = 61 with delirium; n = 61 with dementia without delirium; and n = 65 without cognitive impairment. Patients with delirium performed poorly on the DelApp (median score = 4/10; inter-quartile range 3.0, 5.5) compared to patients with dementia (9.0; 5.5, 10.0) and those without cognitive impairment (10.0; 10.0, 10.0). Area under the curve for detecting delirium was 0.89 (95% Confidence Interval 0.84, 0.94). At an optimal cut-point of ≤8, sensitivity was 91.7% (84.7%, 98.7%) and specificity 74.2% (66.5%, 81.9%) for discriminating delirium from the other groups. Specificity was 68.3% (56.6%, 80.1%) for discriminating delirium from dementia (cut-point ≤6).

Conclusion

Patients with delirium (with or without pre-existing cognitive impairment) perform poorly on the DelApp compared to patients with dementia and those without cognitive impairment. A cut-point of ≤8/10 is suggested as having optimal sensitivity and specificity. The DelApp is a promising tool for assessment of attention deficits associated with delirium in older hospitalised adults, many of whom have prior cognitive impairment, and should be further validated in representative patient cohorts.

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<![CDATA[Mixed evidence for the relationship between periodontitis and Alzheimer’s disease: A bidirectional Mendelian randomization study]]> https://www.researchpad.co/article/N89b89fe7-2f39-423b-9f5f-6e2e7b2736b5

Recent experimental studies indicated that a periodontitis-causing bacterium might be a causal factor for Alzheimer’s disease (AD). We applied a two-sample Mendelian randomization (MR) approach to examine the potential causal relationship between chronic periodontitis and AD bidirectionally in the population of European ancestry. We used publicly available data of genome-wide association studies (GWAS) on periodontitis and AD. Five single-nucleotide polymorphisms (SNPs) were used as instrumental variables for periodontitis. For the MR analysis of periodontitis on risk of AD, the causal odds ratio (OR) and 95% confidence interval (CI) were derived from the GWAS of periodontitis (4,924 cases vs. 7,301 controls) and from the GWAS of AD (21,982 cases vs. 41,944 controls). Seven non-overlapping SNPs from another latest GWAS of periodontitis was used to validate the above association. Twenty SNPs were used as instrumental variables for AD. For the MR analysis of liability to AD on risk of periodontitis, the causal OR was derived from the GWAS of AD including 30,344 cases and 52,427 controls and from the GWAS of periodontitis consisted of 12,289 cases and 22,326 controls. We employed multiple methods of MR. Using the five SNPs as instruments of periodontitis, there was suggestive evidence of genetically predicted periodontitis being associated with a higher risk of AD (OR 1.10, 95% CI 1.02 to 1.19, P = 0.02). However, this association was not verified using the seven independent SNPs (OR 0.97, 95% CI 0.87 to 1.08, P = 0.59). There was no association of genetically predicted AD with the risk of periodontitis (OR 1.00, 95% CI 0.96 to 1.04, P = 0.85). In summary, we did not find convincing evidence to support periodontitis being a causal factor for the development of AD. There was also limited evidence to suggest genetic liability to AD being associated with the risk of periodontitis.

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<![CDATA[Dysregulation of multiple metabolic networks related to brain transmethylation and polyamine pathways in Alzheimer disease: A targeted metabolomic and transcriptomic study]]> https://www.researchpad.co/article/Nf62c48b8-7c01-44cc-9110-a611b974b3f9

Background

There is growing evidence that Alzheimer disease (AD) is a pervasive metabolic disorder with dysregulation in multiple biochemical pathways underlying its pathogenesis. Understanding how perturbations in metabolism are related to AD is critical to identifying novel targets for disease-modifying therapies. In this study, we test whether AD pathogenesis is associated with dysregulation in brain transmethylation and polyamine pathways.

Methods and findings

We first performed targeted and quantitative metabolomics assays using capillary electrophoresis-mass spectrometry (CE-MS) on brain samples from three groups in the Baltimore Longitudinal Study of Aging (BLSA) (AD: n = 17; Asymptomatic AD [ASY]: n = 13; Control [CN]: n = 13) (overall 37.2% female; mean age at death 86.118 ± 9.842 years) in regions both vulnerable and resistant to AD pathology. Using linear mixed-effects models within two primary brain regions (inferior temporal gyrus [ITG] and middle frontal gyrus [MFG]), we tested associations between brain tissue concentrations of 26 metabolites and the following primary outcomes: group differences, Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) (neuritic plaque burden), and Braak (neurofibrillary pathology) scores. We found significant alterations in concentrations of metabolites in AD relative to CN samples, as well as associations with severity of both CERAD and Braak, mainly in the ITG. These metabolites represented biochemical reactions in the (1) methionine cycle (choline: lower in AD, p = 0.003; S-adenosyl methionine: higher in AD, p = 0.005); (2) transsulfuration and glutathione synthesis (cysteine: higher in AD, p < 0.001; reduced glutathione [GSH]: higher in AD, p < 0.001); (3) polyamine synthesis/catabolism (spermidine: higher in AD, p = 0.004); (4) urea cycle (N-acetyl glutamate: lower in AD, p < 0.001); (5) glutamate-aspartate metabolism (N-acetyl aspartate: lower in AD, p = 0.002); and (6) neurotransmitter metabolism (gamma-amino-butyric acid: lower in AD, p < 0.001). Utilizing three Gene Expression Omnibus (GEO) datasets, we then examined mRNA expression levels of 71 genes encoding enzymes regulating key reactions within these pathways in the entorhinal cortex (ERC; AD: n = 25; CN: n = 52) and hippocampus (AD: n = 29; CN: n = 56). Complementing our metabolomics results, our transcriptomics analyses also revealed significant alterations in gene expression levels of key enzymatic regulators of biochemical reactions linked to transmethylation and polyamine metabolism. Our study has limitations: our metabolomics assays measured only a small proportion of all metabolites participating in the pathways we examined. Our study is also cross-sectional, limiting our ability to directly test how AD progression may impact changes in metabolite concentrations or differential-gene expression. Additionally, the relatively small number of brain tissue samples may have limited our power to detect alterations in all pathway-specific metabolites and their genetic regulators.

Conclusions

In this study, we observed broad dysregulation of transmethylation and polyamine synthesis/catabolism, including abnormalities in neurotransmitter signaling, urea cycle, aspartate-glutamate metabolism, and glutathione synthesis. Our results implicate alterations in cellular methylation potential and increased flux in the transmethylation pathways, increased demand on antioxidant defense mechanisms, perturbations in intermediate metabolism in the urea cycle and aspartate-glutamate pathways disrupting mitochondrial bioenergetics, increased polyamine biosynthesis and breakdown, as well as abnormalities in neurotransmitter metabolism that are related to AD.

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<![CDATA[Accelerated brain aging towards transcriptional inversion in a zebrafish model of the K115fs mutation of human PSEN2]]> https://www.researchpad.co/article/N35618ab8-cca5-47c4-ba7f-8d3941adbaaf

Background

The molecular changes involved in Alzheimer’s disease (AD) progression remain unclear since we cannot easily access antemortem human brains. Some non-mammalian vertebrates such as the zebrafish preserve AD-relevant transcript isoforms of the PRESENILIN genes lost from mice and rats. One example is PS2V, the alternative transcript isoform of the PSEN2 gene. PS2V is induced by hypoxia/oxidative stress and shows increased expression in late onset, sporadic AD brains. A unique, early onset familial AD mutation of PSEN2, K115fs, mimics the PS2V coding sequence suggesting that forced, early expression of PS2V-like isoforms may contribute to AD pathogenesis. Here we use zebrafish to model the K115fs mutation to investigate the effects of forced PS2V-like expression on the transcriptomes of young adult and aged adult brains.

Methods

We edited the zebrafish genome to model the K115fs mutation. To explore its effects at the molecular level, we analysed the brain transcriptome and proteome of young (6-month-old) and aged (24-month-old) wild type and heterozygous mutant female sibling zebrafish. Finally, we used gene co-expression network analysis (WGCNA) to compare molecular changes in the brains of these fish to human AD.

Results

Young heterozygous mutant fish show transcriptional changes suggesting accelerated brain aging and increased glucocorticoid signalling. These early changes precede a transcriptional ‘inversion’ that leads to glucocorticoid resistance and other likely pathological changes in aged heterozygous mutant fish. Notably, microglia-associated immune responses regulated by the ETS transcription factor family are altered in both our zebrafish mutant model and in human AD. The molecular changes we observe in aged heterozygous mutant fish occur without obvious histopathology and possibly in the absence of Aβ.

Conclusions

Our results suggest that forced expression of a PS2V-like isoform contributes to immune and stress responses favouring AD pathogenesis. This highlights the value of our zebrafish genetic model for exploring molecular mechanisms involved in AD pathogenesis.

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<![CDATA[Neuroimaging modality fusion in Alzheimer’s classification using convolutional neural networks]]> https://www.researchpad.co/article/N4bce0426-e39d-45a0-9dc9-42db4f6cba04

Automated methods for Alzheimer’s disease (AD) classification have the potential for great clinical benefits and may provide insight for combating the disease. Machine learning, and more specifically deep neural networks, have been shown to have great efficacy in this domain. These algorithms often use neurological imaging data such as MRI and FDG PET, but a comprehensive and balanced comparison of the MRI and amyloid PET modalities has not been performed. In order to accurately determine the relative strength of each imaging variant, this work performs a comparison study in the context of Alzheimer’s dementia classification using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset with identical neural network architectures. Furthermore, this work analyzes the benefits of using both modalities in a fusion setting and discusses how these data types may be leveraged in future AD studies using deep learning.

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<![CDATA[PREDICTORS OF CHANGES IN WELL-BEING AMONG THE INTEGRATED MEMORY CARE CLINIC CLIENTS]]> https://www.researchpad.co/article/N4de22c29-8fef-46a0-a4d1-e7711b5dda42

Abstract

The Integrated Memory Care Clinic (IMCC) at Emory Healthcare is a patient-centered medical home led by advanced practice registered nurses who seamlessly provide dementia care and primary care. This analysis explored predictors of significant changes in clients’ well-being and symptoms in clients’ first-year experience at the IMCC (N=42 caregivers, three assessments over nine months). The significant changes were decreases in caregivers’ distress regarding PLWDs’ delusions (Delusions-Distress) and PLWDs’ anxiety (Anxiety-Distress), and in PLWDs’ severity of delusions, depression, and total symptom severity. Mixed linear models were used to determine significant predictors among baseline sociodemographic characteristics that correlated significantly with outcomes that changed significantly over time. Caregivers not employed outside home had lower baseline Delusions-Distress (p=0.006) and slower decline in Delusions-Distress (p=0.015). The longer PLWD needed care, the lower baseline Delusions-Distress caregivers reported (p=0.023). Caregivers not living with their PLWD reported higher baseline Anxiety-Distress (p=0.016). Caregivers not employed outside home reported lower baseline Delusions-Severity for their PLWD (p=0.006). Caregivers not employed outside home reported PLWDs’ lower baseline depression severity (p=0.026). Older caregivers reported PLWDs’ lower baseline total symptom severity (p=0.002). Increase in caregiver’s age was associated with PLWDs’ higher total symptom severity (p=0.049). For PLWD with male caregivers, total baseline symptom severity was lower compared to PLWD with female caregivers (p=0.01). These findings highlight that PLWDs’ illness duration and caregivers’ employment status, living arrangement, age, and gender may determine their perception of their PLWDs’ symptoms. Clinicians may individualize caregiver education with the knowledge of such predictors.

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<![CDATA[Association of metformin, sulfonylurea and insulin use with brain structure and function and risk of dementia and Alzheimer’s disease: Pooled analysis from 5 cohorts]]> https://www.researchpad.co/article/5c70673cd5eed0c4847c6c7d

Objective

To determine whether classes of diabetes medications are associated with cognitive health and dementia risk, above and beyond their glycemic control properties.

Research design and methods

Findings were pooled from 5 population-based cohorts: the Framingham Heart Study, the Rotterdam Study, the Atherosclerosis Risk in Communities (ARIC) Study, the Aging Gene-Environment Susceptibility-Reykjavik Study (AGES) and the Sacramento Area Latino Study on Aging (SALSA). Differences between users and non-users of insulin, metformin and sulfonylurea were assessed in each cohort for cognitive and brain MRI measures using linear regression models, and cognitive decline and dementia/AD risk using mixed effect models and Cox regression analyses, respectively. Findings were then pooled using meta-analytic techniques, including 3,590 individuals with diabetes for the prospective analysis.

Results

After adjusting for potential confounders including indices of glycemic control, insulin use was associated with increased risk of new-onset dementia (pooled HR (95% CI) = 1.58 (1.18, 2.12);p = 0.002) and with a greater decline in global cognitive function (β = -0.014±0.007;p = 0.045). The associations with incident dementia remained similar after further adjustment for renal function and excluding persons with diabetes whose treatment was life-style change only. Insulin use was not related to cognitive function nor to brain MRI measures. No significant associations were found between metformin or sulfonylurea use and outcomes of brain function and structure. There was no evidence of significant between-study heterogeneity.

Conclusions

Despite its advantages in controlling glycemic dysregulation and preventing complications, insulin treatment may be associated with increased adverse cognitive outcomes possibly due to a greater risk of hypoglycemia.

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<![CDATA[Metal based donepezil analogues designed to inhibit human acetylcholinesterase for Alzheimer’s disease]]> https://www.researchpad.co/article/5c76fe06d5eed0c484e5b2cd

Among neurodegenerative disorders, Alzheimer’s disease (AD) is one of the most common disorders showing slow progressive cognitive decline. Targeting acetylcholinesterase (AChE) is one of the major strategies for AD therapeutics, as cholinergic pathways in the cerebral cortex and basal forebrain are compromised. Herein, we report the design of some copper and other metal based donepezil derivatives, employing density functional theory (DFT). All designed compounds are optimized at the B3LYP/SDD level of theory. Dipole moments, electronic energie, enthalpies, Gibbs free energies, and HOMO-LUMO gaps of these modified compounds are also investigated in the subsequent analysis. The molecules were then subjected to molecular docking analysis with AChE to study the molecular interactions broadly. Ensemble based docking and molecular dynamics (MD) simulations of the best candidates were also performed. Docking and MD simulation reveal that modified drugs are more potent than unmodified donepezil, where Trp86, Tyr337, Phe330 residues play some important roles in drug-receptor interactions. According to ensemble based docking, D9 shows greater binding affinity compared to the parent in most conformations obtained from protein data bank and MD simulation. In addition, it is observed that the π- π stacking with the residues of Trp86, Tyr337, Tyr341, Tyr124 and Trp286 may be required for strong ligand binding. Moreover, ADME/T analysis suggests that modified derivatives are less toxic and have improved pharmacokinetic properties than those of the parent drug. These results further confirm the ability of metal-directed drugs to bind simultaneously to the active sites of AChE and support them as potential candidates for the future treatment of Alzheimer’s disease.

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<![CDATA[Trans ε viniferin decreases amyloid deposits and inflammation in a mouse transgenic Alzheimer model]]> https://www.researchpad.co/article/5c76fe09d5eed0c484e5b330

As Alzheimer’s disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice. We report that trans ε-viniferin could go through the blood brain barrier, reduces size and density of amyloid deposits and decreases reactivity of astrocytes and microglia, after a weekly intraperitoneal injection at 10 mg/kg from 3 to 6 months of age.

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<![CDATA[Population-based dementia prediction model using Korean public health examination data: A cohort study]]> https://www.researchpad.co/article/5c6c7598d5eed0c4843cfefb

The early identification and prevention of dementia is important for reducing its worldwide burden and increasing individuals’ quality of life. Although several dementia prediction models have been developed, there remains a need for a practical and precise model targeted to middle-aged and Asian populations. Here, we used national Korean health examination data from adults (331,126 individuals, 40–69 years of age, mean age: 52 years) from 2002–2003 to predict the incidence of dementia after 10 years. We divided the dataset into two cohorts to develop and validate of our prediction model. Cox proportional hazards models were used to construct dementia prediction models for the total group and sex-specific subgroups. Receiver operating characteristics curves, C-statistics, calibration plots, and cumulative hazards were used to validate model performance. Discriminative accuracy as measured by C-statistics was 0.81 in the total group (95% confidence interval (CI) = 0.81 to 0.82), 0.81 in the male subgroup (CI = 0.80 to 0.82), and 0.81 in the female subgroup (CI = 0.80 to 0.82). Significant risk factors for dementia in the total group were age; female sex; underweight; current hypertension; comorbid psychiatric or neurological disorder; past medical history of cardiovascular disease, diabetes mellitus, or hypertension; current smoking; and no exercise. All identified risk factors were statistically significant in the sex-specific subgroups except for low body weight and current hypertension in the female subgroup. These results suggest that public health examination data can be effectively used to predict dementia and facilitate the early identification of dementia within a middle-aged Asian population.

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<![CDATA[The impact of dementia on hospital outcomes for elderly patients with sepsis: A population-based study]]> https://www.researchpad.co/article/5c75abe0d5eed0c484d07df2

Background

Prior studies have suggested that dementia adversely influences clinical outcomes and increases resource utilization in patients hospitalized for acute diseases. However, there is limited population-data information on the impact of dementia among elderly hospitalized patients with sepsis.

Methods

From the 2009–2011 National Hospital Discharge Database we identified hospitalizations in adults aged ≥65 years. Using ICD9-CM codes, we selected sepsis cases, divided them into two cohorts (with and without dementia) and compared both groups with respect to organ dysfunction, in-hospital mortality and the use of hospital resources. We estimated the impact of dementia on these primary endpoints through multivariate regression models.

Results

Of the 148 293 episodes of sepsis identified, 16 829 (11.3%) had diagnoses of dementia. Compared to their dementia-free counterparts, they were more predominantly female and older, had a lower burden of comorbidities and were more frequently admitted due to a principal diagnosis of sepsis. The dementia cohort showed a lower risk of organ dysfunction (adjusted OR: 0.84, 95% Confidence Interval [CI]: 0.81, 0.87) but higher in-hospital mortality (adjusted OR: 1.32, 95% [CI]: 1.27, 1.37). The impact of dementia on mortality was higher in the cases of younger age, without comorbidities and without organ dysfunction. The cases with dementia also had a lower length of stay (-3.87 days, 95% [CI]: -4.21, -3.54) and lower mean hospital costs (-3040€, 95% [CI]: -3279, -2800).

Conclusions

This nationwide population-based study shows that dementia is present in a substantial proportion of adults ≥65s hospitalized with sepsis, and while the condition does seem to come with a lower risk of organ dysfunction, it exerts a negative influence on in-hospital mortality and acts as an independent mortality predictor. Furthermore, it is significantly associated with shorter length of stay and lower hospital costs.

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<![CDATA[Validation of a simple sample preparation method for multielement analysis of bovine serum]]> https://www.researchpad.co/article/5c633931d5eed0c484ae61f2

Here we propose a single acid digestion (SAD) sample preparation method for ICP-MS analysis of animal serum samples to determine trace element contents. The method was evaluated in comparison with a commonly used procedure involving dilution of samples in an alkaline solution (AKD). In the SAD procedure, aliquots (1 mL) of bovine serum samples were treated at low temperature with a mixture of concentrated nitric acid and hydrogen peroxide. Trace elements (As, B, Ba, Cd, Co, Cr, Cu, Fe, Hg, Li, Mn, Mo, Ni, Pb, Sb, Se, Sr, U, and Zn) were directly determined by ICP-MS analysis of diluted solutions of samples. Both methods were sufficiently sensitive to enable quantification of most trace elements, with the exception of the AKD method for Cd, Hg and Pb. The quality of the data was verified by using certified reference material. Good results were obtained for the SAD procedure and all elements, but recoveries were unacceptable with the AKD procedure for Se (recovery: 57%), Cd (154%) and Fe (139%). Strong associations (R2>0.90, P = 0.000) between the data obtained by both methods were demonstrated for the elements considered. The proposed SAD sample preparation method produced satisfactory results for determining most toxic and essential trace elements targeted in monitoring studies.

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<![CDATA[Relationship between dementia and ankylosing spondylitis: A nationwide, population-based, retrospective longitudinal cohort study]]> https://www.researchpad.co/article/5c5ca317d5eed0c48441f12e

Among a variety of comorbidities of ankylosing spondylitis (AS), the association between dementia and AS by using an extensive dataset from the Korean National Health Insurance System was evaluated in this study. We extracted 15,547 newly diagnosed AS subjects among the entire Korean population and excluded wash-out patients (n = 162) and patients that were inappropriate for cohort match (n = 1192). Finally, 14,193 subjects were chosen as the AS group, and through 1:5 age- and sex-stratified matching, 70,965 subjects were chosen as the control group. We evaluated patient demographics, household incomes, and comorbidities, including hypertension, diabetes, and dyslipidemia. The prevalence of overall dementia (1.37%) and Alzheimer’s dementia (AD) (0.99%) in the AS group was significantly higher than in the control group (0.87% and 0.63%), respectively. The adjusted hazard ratio of the AS group for overall dementia (1.758) and AD (1.782) showed statistical significance also. On the other hand, the prevalence of vascular dementia did not differ significantly between the two groups. Subgroup analyses revealed the following risk factors for dementia in the AS group: male gender, greater than 65 years in age, fair income (household income greater than 20% of the median), urban residency, no diabetes, and no hypertension. From the nationwide, population-based, retrospective, longitudinal cohort study, AS patients showed a significantly higher prevalence of overall dementia and Alzheimer’s dementia. Comprehensive patient assessment using our subgroup analysis could help to prevent dementia in patients suffering from AS.

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<![CDATA[Elevated cellular cholesterol in Familial Alzheimer’s presenilin 1 mutation is associated with lipid raft localization of β-amyloid precursor protein]]> https://www.researchpad.co/article/5c79afead5eed0c4841e3a1a

Familial Alzheimer’s disease (FAD)-associated presenilin 1 (PS1) serves as a catalytic subunit of γ-secretase complex, which mediates the proteolytic liberation of β-amyloid (Aβ) from β-amyloid precursor protein (APP). In addition to its proteolytic role, PS1 is involved in non-proteolytic functions such as protein trafficking and ion channel regulation. Furthermore, postmortem AD brains as well as AD patients showed dysregulation of cholesterol metabolism. Since cholesterol has been implicated in regulating Aβ production, we investigated whether the FAD PS1-associated cholesterol elevation could influence APP processing. We found that in CHO cells stably expressing FAD-associated PS1 ΔE9, total cholesterol levels are elevated compared to cells expressing wild-type PS1. We also found that localization of APP in cholesterol-enriched lipid rafts is substantially increased in the mutant cells. Reducing the cholesterol levels by either methyl-β-cyclodextrin or an inhibitor of CYP51, an enzyme mediating the elevated cholesterol in PS1 ΔE9-expressing cells, significantly reduced lipid raft-associated APP. In contrast, exogenous cholesterol increased lipid raft-associated APP. These data suggest that in the FAD PS1 ΔE9 cells, the elevated cellular cholesterol level contributes to the altered APP processing by increasing APP localized in lipid rafts.

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<![CDATA[The temporal trend and distribution characteristics in mortality of Alzheimer's disease and other forms of dementia in China: Based on the National Mortality Surveillance System (NMS) from 2009 to 2015]]> https://www.researchpad.co/article/5c5ca2bad5eed0c48441e98d

Background

China is experiencing rapid age, which will lead to increasing burden of age-related diseases, such as Alzheimer disease and other forms of dementia.

Objectives

The aim of this study was to 1) Explore the temporal trend of mortality of Alzheimer disease (AD) and other forms of dementia in China and 2) Analyze its geographic variations and urban-rural differences and calculate the years of life lost (YLLs) from AD and other forms of dementia.

Data and methods

Data were extracted from the National Mortality Surveillance System (NMS). Age-standardized mortalities were calculated with the Western Grade 26 Standard Life List, and the YLLs were calculated using the DALY template provided by the WHO / World Bank global burden of disease (GBD) Working Group. The trends in crude and age-standardized mortality of AD and other forms of dementia were examined using Cochran-Armitage trend test.

Results

In China, the crude mortality from AD and other forms of dementia increased from 2009 to 2015, but the age-standardized mortality decreased. The YLLs of AD and other forms of dementia increased during the study period. The age-standardized mortality in the east was higher than those in the west and middle regions, and the age-standardized mortality in rural areas was higher than that in urban areas.

Conclusion

In China, the age-standardized mortality of AD and other forms of dementia decreased from 2009 to 2015. However, the disease burden from AD and other forms of dementia is becoming heavier due to increasing elderly population. Moreover, there were geographic variations and urban-rural differences in mortality of AD and other forms of dementia in China.

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<![CDATA[Who gets lost and why: A representative cross-sectional survey on sociodemographic and vestibular determinants of wayfinding strategies]]> https://www.researchpad.co/article/5c5b52bdd5eed0c4842bcf61

When we think of our family and friends, we probably know someone who is good at finding their way and someone else that easily gets lost. We still know little about the biological and environmental factors that influence our navigational ability. Here, we investigated the frequency and sociodemographic determinants of wayfinding and their association with vestibular function in a representative cross-sectional sample (N = 783) of the adult German-speaking population. Wayfinding was assessed using the Wayfinding Strategy Scale, a self-report scale that produces two scores for each participant representing to what degree they rely on route-based or orientation (map-based) strategies. We were interested in the following research questions: (1) the frequency and determinants of wayfinding strategies in a population-based representative sample, (2) the relationship between vestibular function and strategy choice and (3) how sociodemographic factors influence general wayfinding ability as measured using a combined score from both strategy scores. Our linear regression models showed that being male, having a higher education, higher age and lower regional urbanization increased orientation strategy scores. Vertigo/dizziness reduced the scores of both the orientation and the route strategies. Using a novel approach, we grouped participants by their combined strategy scores in a multinomial regression model, to see whether individuals prefer one strategy over the other. The majority of individuals reported using either both or no strategy, instead of preferring one strategy over the other. Young age and reduced vestibular function were indicative of using no strategy. In summary, wayfinding ability depends on both biological and environmental factors; all sociodemographic factors except income. Over a third of the population, predominantly under the age of 35, does not successfully use either strategy. This represents a change in our wayfinding skills, which may result from the technological advances in navigational aids over the last few decades.

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<![CDATA[Trazodone use and risk of dementia: A population-based cohort study]]> https://www.researchpad.co/article/5c63396bd5eed0c484ae66ce

Background

In vitro and animal studies have suggested that trazodone, a licensed antidepressant, may protect against dementia. However, no studies have been conducted to assess the effect of trazodone on dementia in humans. This electronic health records study assessed the association between trazodone use and the risk of developing dementia in clinical practice.

Methods and findings

The Health Improvement Network (THIN), an archive of anonymised medical and prescribing records from primary care practices in the United Kingdom, contains records of over 15 million patients. We assessed patients from THIN aged ≥50 years who received at least two consecutive prescriptions for an antidepressant between January 2000 and January 2017. We compared the risk of dementia among patients who were prescribed trazodone to that of patients with similar baseline characteristics prescribed other antidepressants, using a Cox regression model with 1:5 propensity score matching. Patients prescribed trazodone who met the inclusion criteria (n = 4,716; 59.2% female) were older (mean age 70.9 ± 13.1 versus 65.6 ± 11.4 years) and were more likely than those prescribed other antidepressants (n = 420,280; 59.7% female) to have cerebrovascular disease and use anxiolytic or antipsychotic drugs. After propensity score matching, 4,596 users of trazadone and 22,980 users of other antidepressants were analysed. The median time to dementia diagnosis for people prescribed trazodone was 1.8 years (interquartile range [IQR] = 0.5–5.0 years). Incidence of dementia among patients taking trazodone was higher than in matched users of other antidepressants (1.8 versus 1.1 per 100 person-years), with a hazard ratio (HR) of 1.80 (95% confidence interval [CI] 1.56–2.09; p < 0.001). However, our results do not suggest a causal association. When we restricted the control group to users of mirtazapine only in a sensitivity analysis, the findings were very similar to the results of the main analysis. The main limitation of our study is the possibility of indication bias, because people in the prodromal stage of dementia might be preferentially prescribed trazodone. Due to the observational nature of this study, we cannot rule out residual confounding.

Conclusions

In this study of UK population-based electronic health records, we found no association between trazodone use and a reduced risk of dementia compared with other antidepressants. These results suggest that the clinical use of trazodone is not associated with a reduced risk of dementia.

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