Machine Learning Approaches for Dementia Detection Through Speech and Gait Analysis: A Systematic Literature Review.

Background: Dementia is a general term for several progressive neurodegenerative disorders including Alzheimer's disease. Timely and accurate detection is crucial for early intervention. Advancements in artificial intelligence present significant potential for using machine learning to aid in early detection. Objective: Summarize the state-of-the-art machine learning-based approaches for dementia prediction, focusing on non-invasive methods, as the burden on the patients is lower. Specifically, the analysis of gait and speech performance can offer insights into cognitive health through clinically cost-effective screening methods. Methods: A systematic literature review was conducted following the PRISMA protocol (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The search was performed on three electronic databases (Scopus, Web of Science, and PubMed) to identify the relevant studies published between 2017 to 2022. A total of 40 papers were selected for review. Results: The most common machine learning methods employed were support vector machine followed by deep learning. Studies suggested the use of multimodal approaches as they can provide comprehensive and better prediction performance. Deep learning application in gait studies is still in the early stages as few studies have applied it. Moreover, including features of whole body movement contribute to better classification accuracy. Regarding speech studies, the combination of different parameters (acoustic, linguistic, cognitive testing) produced better results. Conclusions: The review highlights the potential of machine learning, particularly non-invasive approaches, in the early prediction of dementia. The comparable prediction accuracies of manual and automatic speech analysis indicate an imminent fully automated approach for dementia detection.

Molecular insights into the fine-tuning of pH-dependent ArsR-mediated regulation of the SabA adhesin in Helicobacter pylori.

Adaptation to variations in pH is crucial for the ability of Helicobacter pylori to persist in the human stomach. The acid responsive two-component system ArsRS, constitutes the global regulon that responds to acidic conditions, but molecular details of how transcription is affected by the ArsR response regulator remains poorly understood. Using a combination of DNA-binding studies, in vitro transcription assays, and H. pylori mutants, we demonstrate that phosphorylated ArsR (ArsR-P) forms an active protein complex that binds DNA with high specificity in order to affect transcription. Our data showed that DNA topology is key for DNA binding. We found that AT-rich DNA sequences direct ArsR-P to specific sites and that DNA-bending proteins are important for the effect of ArsR-P on transcription regulation. The repression of sabA transcription is mediated by ArsR-P with the support of Hup and is affected by simple sequence repeats located upstream of the sabA promoter. Here stochastic events clearly contribute to the fine-tuning of pH-dependent gene regulation. Our results reveal important molecular aspects for how ArsR-P acts to repress transcription in response to acidic conditions. Such transcriptional control likely mediates shifts in bacterial positioning in the gastric mucus layer.

Adaptation of a guided low-intensity behavioral activation intervention for people with dementia in Sweden: a qualitative study exploring the needs and preferences of key stakeholders.

BACKGROUND: Despite depression being prevalent in people with dementia, contributing to negative health outcomes and placing increased burden on individuals and family members, access to psychological interventions is limited. A potential solution is guided low-intensity behavioral activation, supported by informal caregivers and guided by healthcare professionals. However, it is necessary to adapt interventions to meet the needs and preferences of key stakeholders to enhance acceptability and relevance. Study objectives were to: (1) explore needs and preferences concerning the content and delivery model of the guided low-intensity behavioral activation intervention; and (2) adapt the intervention to ensure cultural appropriateness, relevancy, and acceptability to people with dementia and their caregivers in Sweden. METHODS: Semi-structured interviews and focus group discussions were conducted with key stakeholders, including healthcare professionals (n = 18), community stakeholders (n = 7), people with dementia (n = 8), and informal caregivers (n = 19). A draft of the written low-intensity behavioral activation intervention and a description of the proposed intervention delivery model were provided to participants. Open-ended questions explored the perceived relevance of the intervention, alongside needs and preferences concerning content and delivery. A manifest content analysis approach was adopted. RESULTS: Content analysis resulted in three categories: Content, Delivery procedures, and Illness trajectory. Results highlighted a need to consider the intervention Content via increased cultural adaptation to the Swedish context, and increasing the inclusiveness of intervention content. Delivery procedures were identified as needing to be flexible given the unpredictable nature of caring for people with dementia, with the provision of additional guidance to informal caregivers supporting the intervention. Illness trajectory was viewed as essential to consider, with the intervention regarded as suitable for those early in the dementia trajectory, alongside a need to reduce workbook text to minimize burden given dementia symptomology. CONCLUSIONS: The intervention and proposed delivery model were generally well received by all stakeholders. We were able to identify key adaptations to enhance cultural appropriateness, relevancy, and acceptability for a currently neglected population. Results will inform a feasibility study to explore the feasibility and acceptability of the intervention and study procedures to inform the design of a future superiority randomized controlled trial. TRIAL REGISTRATION/PROTOCOL: Not applicable.

Healthcare and community stakeholders' perceptions of barriers and facilitators to implementing a behavioral activation intervention for people with dementia and depression: a qualitative study using Normalization Process Theory.

BACKGROUND: Depression is commonly experienced by people with dementia, and associated with lower quality of life and functional decline. However, access to evidence-based psychological interventions for people with dementia and depression is limited. One potential solution is guided low-intensity behavioral activation. Following the new Medical Research Council Framework, considering factors such as potential barriers and facilitators to implementation is recommended during the development of new interventions. Aims of this study were to: (1) develop an understanding of existing healthcare and community support in the Swedish context for people with dementia and their informal caregivers; and (2) identify barriers and facilitators to intervention uptake informed by Normalization Process Theory. METHODS: Semi-structured interviews and focus groups were held with healthcare (n = 18) and community (n = 7) stakeholders working with people with dementia and/or informal caregivers. Interview questions were informed by Normalization Process Theory. Data was analysed utilizing a two-step deductive analysis approach using the Normalization Process Theory coding manual, with inductive categories applied to data related to the main mechanisms of the theory, but not captured by its sub-constructs. RESULTS: Twelve deductive and three inductive categories related to three Normalization Process Theory primary mechanisms (Coherence, Cognitive Participation, and Collective Action) were identified. Identified barriers to intervention uptake included: (1) additional burden for informal caregivers; (2) lack of appropriate workforce to provide guidance; (3) lack of time and financial resources; (4) people with dementia not recognising their diagnosis of dementia and/or a need for support; and (5) stigma. Identified facilitators to intervention uptake included: (1) intervention has potential to fill a large psychological treatment gap in Sweden; (2) objectives and potential benefits understood and agreed by most stakeholders; and (3) some healthcare professionals recognized their potential role in providing intervention guidance. CONCLUSIONS: Several barriers and facilitators for future implementation, specific to the intervention, individuals and families, as well as professionals, were identified during intervention development. Barriers were mapped into evidence-based implementation strategies, which will be adopted to overcome identified barriers. A feasibility study further examining implementation potential, acceptability and feasibility, alongside clinical, methodological, and procedural uncertainties associated with the intervention will be conducted. TRIAL REGISTRATION: Not applicable.

Effectiveness, acceptability, and completeness and quality of intervention reporting of psychological interventions for people with dementia or mild cognitive impairment: protocol for a mixed-methods systematic review.

INTRODUCTION: Mental health difficulties such as anxiety and depression have negative impacts on psychological well-being and are common in people with dementia and mild cognitive impairment. However, access to psychological treatments is limited. This mixed-method systematic review will: (1) examine the effectiveness of psychological interventions to improve mental health and psychological well-being in people with dementia or mild cognitive impairment; (2) examine the effectiveness of these psychological interventions to improve mental health and psychological well-being in informal caregivers; (3) examine potential clinical and methodological moderators associated with effectiveness; (4) explore factors associated with the acceptability of psychological interventions from the perspective of key stakeholders; and (5) examine the completeness and quality of intervention reporting. METHODS AND ANALYSIS: Electronic databases (ASSIA, CENTRAL, CINAHL, EMBASE, PsycINFO and MEDLINE) will be systematically searched and supplemented with expert contact, reference and citation checking, and grey literature searches. If possible, we will conduct a meta-analysis to examine the overall effectiveness of psychological interventions to improve mental health and psychological well-being in people with dementia or mild cognitive impairment and their informal caregivers; and examine potential clinical and methodological moderators associated with effectiveness. We will conduct a deductive framework synthesis, informed by the theoretical framework of acceptability, to explore factors associated with the acceptability of psychological interventions from the perspective of key stakeholders. In accordance with Joanna Briggs Institute guidance, we will adopt a convergent segregated approach to data synthesis and integration of quantitative and qualitative findings. We will examine the completeness and quality of intervention reporting according to the Template for Intervention Description and Replication checklist and guide. ETHICS AND DISSEMINATION: No primary data will be collected, and therefore, ethical approval is not required. Results will be disseminated through a peer-reviewed publication, academic conferences, and plain language summaries. PROSPERO REGISTRATION NUMBER: CRD42023400514.

Prediction of conversion to dementia disorders based on timed up and go dual-task test verbal and motor outcomes: a five-year prospective memory-clinic-based study.

BACKGROUND: While assessment tools can increase the detection of cognitive impairment, there is currently insufficient evidence regarding clinical outcomes based on screening for cognitive impairment in older adults. METHODS: The study purpose was to investigate whether Timed Up and Go dual-task test (TUGdt) results, based on TUG combined with two different verbal tasks (name different animals, TUGdt-NA, and recite months in reverse order, TUGdt-MB), predicted dementia incidence over a period of five years among patients (N = 186, mean = 70.7 years; 45.7% female) diagnosed with Subjective Cognitive Impairment (SCI) and Mild Cognitive Impairment (MCI) following assessment at two memory clinics. Associations between TUG parameters and dementia incidence were examined in Cox regression models. RESULTS: During follow-up time (median (range) 3.7 (0.1-6.1) years) 98 participants converted to dementia. Novel findings indicated that the TUGdt parameter words/time, after adjustment for age, gender, and education, can be used for the prediction of conversion to dementia in participants with SCI or MCI over a period of five years. Among the TUG-related parameters investigated, words/time showed the best predictive capacity, while time scores of TUG and TUGdt as well as TUGdt cost did not produce significant predictive results. Results further showed that the step parameter step length during TUGdt predicts conversion to dementia before adjustment for age, gender, and education. Optimal TUGdt cutoffs for predicting dementia at 2- and 4-year follow-up based on words/time were calculated. The sensitivity of the TUGdt cutoffs was high at 2-year follow-up: TUGdt-NA words/time, 0.79; TUGdt-MB words/time, 0.71; reducing respectively to 0.64 and 0.65 at 4-year follow-up. CONCLUSIONS: TUGdt words/time parameters have potential as cost-efficient tools for conversion-to-dementia risk assessment, useful for research and clinical purposes. These parameters may be able to bridge the gap of insufficient evidence for such clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05893524: https://www. CLINICALTRIALS: gov/study/NCT05893524?id=NCT05893524&rank=1 .

Dual-Task Interference of Gait Parameters During Different Conditions of the Timed Up-and-Go Test Performed by Community-Dwelling Older Adults.

The Timed Up-and-Go (TUG) test has been combined with different verbal/cognitive tasks (i.e., TUG dual task [TUGdt]) as a form of motor-cognitive testing. However, it is still unclear how different TUGdt conditions affect gait among older adults. Thirty community-dwelling older adults, with mean age of 73 years, participated in the study. Data were collected using marker-free video recordings. Gait parameters were extracted using a semiautomatic deep learning system. Comparisons of execution time and gait parameter outcomes were made under TUG and three types of TUGdt test conditions: TUGdt-naming animals, TUGdt-months backwards, and TUGdt-serial 7s. Statistical analyses were based on mean values of the gait parameters for each participant and TUG condition, including TUGdt gait cost, that is, the relative difference between TUGdt and TUG. All the investigated TUGdt conditions resulted in varying degrees of gait parameter changes. Under TUGdt conditions, participants took shorter and slower steps, with TUGdt-serial 7s causing the largest interference.

Neuromuscular Controller Models for Quantifying Standing Balance in Older People: A Systematic Review.

Objective quantification of the balancing mechanisms in humans is strongly needed in health care of older people, yet is largely missing among current clinical balance assessment methods. Hence, the main goal of this literature review is to identify methods that have the potential to meet that need. We searched in the PubMed and IEEE Xplore databases using predefined criteria, screened 1064 articles, and systematically reviewed and categorized methods from 73 studies that deal with identification of neuromuscular controller models of human upright standing from empirical data. These studies were then analyzed with the particular aim to understand to what degree such methods would be useful solutions for assessing the balance of older individuals aged above 60 years. The 16 studies that included an older subject population were especially examined with this in mind. The majority of the reviewed articles focused on research questions related to the general function of human balance control rather than clinical applicability. Further efforts need to be made to adapt these methods for more accessible and mobile technologies and to ensure that the outcomes are valid for balance assessment of a general older population.

ppGpp, the General Stress Response Alarmone, Is Required for the Expression of the α-Hemolysin Toxin in the Uropathogenic Escherichia coli Isolate, J96.

ppGpp is an intracellular sensor that, in response to different types of stress, coordinates the rearrangement of the gene expression pattern of bacteria to promote adaptation and survival to new environmental conditions. First described to modulate metabolic adaptive responses, ppGpp modulates the expression of genes belonging to very diverse functional categories. In Escherichia coli, ppGpp regulates the expression of cellular factors that are important during urinary tract infections. Here, we characterize the role of this alarmone in the regulation of the hlyCABDII operon of the UPEC isolate J96, encoding the toxin α-hemolysin that induces cytotoxicity during infection of bladder epithelial cells. ppGpp is required for the expression of the α-hemolysin encoded in hlyCABDII by stimulating its transcriptional expression. Prototrophy suppressor mutations in a ppGpp-deficient strain restore the α-hemolysin expression from this operon to wild-type levels, confirming the requirement of ppGpp for its expression. ppGpp stimulates hlyCABDII expression independently of RpoS, RfaH, Zur, and H-NS. The expression of hlyCABDII is promoted at 37 °C and at low osmolarity. ppGpp is required for the thermoregulation but not for the osmoregulation of the hlyCABDII operon. Studies in both commensal and UPEC isolates demonstrate that no UPEC specific factor is strictly required for the ppGpp-mediated regulation described. Our data further support the role of ppGpp participating in the coordinated regulation of the expression of bacterial factors required during infection.

Sarcopenia and malnutrition in relation to mortality in hospitalised patients in geriatric care - predictive validity of updated diagnoses.

BACKGROUND AND AIM: The definition of sarcopenia was recently updated by the European Working Group on Sarcopenia (EWGSOP2), and consensus criteria for the diagnosis of malnutrition have been presented by the Global Leadership Initiative on Malnutrition (GLIM). The aim of this study was to investigate prevalence and mortality related to categorisation of patients according to these definitions in a geriatric hospital setting. METHOD: Fifty-six consecutive geriatric inpatients (84y (SD 7.3), 68% women) underwent test of handgrip strength (HGS) and five-rise chair stand test (5CST). Muscle mass and fat free mass (FFM) were evaluated by Dual X-ray Absorptiometry (DXA). Calf circumference (CC) was recorded. Probable sarcopenia was defined, according to EWGSOP2, as low HGS (<27/16 kg for men/women) and/or 5CST >15 s; sarcopenia was confirmed when coupled with low appendicular skeletal muscle index (ASMI <7.0 and <5.5 kg/m2 (m/w)). Malnutrition was defined according to GLIM as weight loss >5% (past 6 mo); BMI <20/22 kg/m2 (<70/>70y); and FFM-index <17/15 kg/m2 (m/w) combined with reduced food intake and/or disease burden/inflammatory condition. Alternatively, CC <31 cm was used as a proxy for low muscle mass for both sarcopenia and malnutrition. One- and two-year mortality was registered. RESULTS: All participants displayed probable sarcopenia; 46% and 20% were sarcopenic depending on whether muscle mass was estimated by DXA or CC. Malnutrition according to the GLIM criteria was prevalent in 64% or 60% (muscle mass by DXA or CC, respectively). Nine in ten with sarcopenia were also malnourished. Twenty-six participants (46%) died within two years. Sarcopenia defined by CC <31 cm, but not by DXA, was associated with increased mortality; e.g. 2-y mortality HR was 3.19 (95% CI 1.31-7.75). Similarly, malnutrition according to GLIM related to increased 1-y mortality (HR 4.83, 95% CI 1.04-22.39) when DXA was used for muscle mass estimation. All of the participants with CC <31 cm were categorised as both sarcopenic and malnourished. CONCLUSION: In this small set of well-characterised geriatric inpatients all displayed probable sarcopenia. Prevalence of sarcopenia (EWGSOP2) and malnutrition (GLIM) was 20-46% and 60-64%, respectively. Both conditions related to mortality. CC <31 cm hold promises to be an acceptable alternative for DXA as a proxy for low muscle mass.

Extraction of gait parameters from marker-free video recordings of Timed Up-and-Go tests: Validity, inter- and intra-rater reliability.

BACKGROUND: We study dual-task performance with marker-free video recordings of Timed Up-and-Go tests (TUG) and TUG combined with a cognitive/verbal task (TUG dual-task, TUGdt). RESEARCH QUESTION: Can gait parameters be accurately estimated from video-recorded TUG tests by a new semi-automatic method aided by a technique for human 2D pose estimation based on deep learning? METHODS: Thirty persons aged 60-85 years participated in the study, conducted in a laboratory environment. Data were collected by two synchronous video-cameras and a marker-based optoelectronic motion capture system as gold standard, to evaluate the gait parameters step length (SL), step width (SW), step duration (SD), single-stance duration (SSD) and double-stance duration (DSD). For reliability evaluations, data processing aided by a deep neural network model, involved three raters who conducted three repetitions of identifying anatomical keypoints in recordings of one randomly selected step from each of the participants. Validity was analysed using 95 % confidence intervals (CI) and p-values for method differences and Bland-Altman plots with limits of agreement. Inter- and intra-rater reliability were calculated as intraclass correlation coefficients (ICC) and standard errors of measurement. Smallest detectable change was calculated for inter-rater reliability. RESULTS: Mean ddifferences between video and the motion capture system data for SW, DSD, and SSD were significant (p < 0.001). However, mean differences for all parameters were small (-6.4%-13.0% of motion capture system) indicating good validity. Concerning reliability, almost all 95 % CI of the ICC estimates exceeded 0.90, indicating excellent reliability. Only inter-rater reliability for SW (95 % CI = 0.892;0.973) and one rater's intra-rater reliability for SSD (95 % CI = 0.793;0.951) were lower, but still showed good to excellent reliability. SIGNIFICANCE: The presented method for extraction of gait parameters from video appears suitable for valid and reliable quantification of gait. This opens up for analyses that may contribute to the knowledge of cognitive-motor interference in dual-task testing.

Adapting a guided low-intensity behavioural activation intervention for people with dementia and depression in the Swedish healthcare context (INVOLVERA): a study protocol using codesign and participatory action research.

INTRODUCTION: Dementia is a worldwide health concern with incident rates continuing to increase. While depression prevalence is high in people with dementia and psychological interventions such as cognitive behavioural therapy (CBT) are effective, access to psychological interventions remains limited. Reliance on traditional CBT for people with dementia and depression may present difficulties given it is a complex psychological approach, costly to deliver, and professional training time is lengthy. An alternative approach is behavioural activation (BA), a simpler psychological intervention for depression. The present study seeks to work with people with dementia, informal caregivers, community stakeholders, and healthcare professionals, to adapt a guided low-intensity BA intervention for people with dementia and depression, while maximising implementation potential within the Swedish healthcare context. METHODS AND ANALYSIS: A mixed methods study using codesign, principles from participatory action research (PAR) and normalisation process theory to facilitate the cultural relevance, appropriateness and implementation potential of the intervention. The study will consist of four iterative PAR phases, using focus groups with healthcare professionals and community stakeholders, and semi-structured interviews with people with dementia and informal caregivers. A content analysis approach will be adopted to analyse the transcribed focus groups and semi-structured interviews recordings. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the Declaration of Helsinki and data handled according to General Data Protection Regulation. Written informed consent will be obtained from all study participants. In accordance with the Swedish Health and Medical Services Act, capacity to consent will be examined by a member of the research team. Ethical approval has been obtained from the Swedish Ethical Review Authority (Dnr: 2020-05542 and Dnr: 2021-00925). Findings will be published in an open access peer-reviewed journal, presented at academic conferences, and disseminated among lay and healthcare professional audiences.

Timed "Up & Go" Dual-Task Tests: Age- and Sex-Specific Reference Values and Test-Retest Reliability in Cognitively Healthy Controls.

OBJECTIVE: The purpose of the study was to establish reference values for the Uppsala-Dalarna Dementia and Gait (UDDGait) Timed "Up & Go" dual-task (TUGdt) test variables in cognitively healthy adults and to assess these variables' test-retest reliability. METHODS: For reference values, 166 participants were recruited with approximately equal numbers and proportions of women and men in the age groups 50 to 59, 60 to 69, 70 to 79, and 80+ years (mean age = 70 years, age range = 50-91 years, 51% women). For reliability testing, 43 individuals (mean age = 69 years, age range = 50-89 years, 51% women) were recruited. Two dt tests were carried out: TUGdt naming animals and TUGdt months backward, representing 8 test variables: time scores, costs (the relative difference between single-task and dt time scores), "number of animals," "number of months," "animals/10 seconds ," and "months/10 seconds ." Reference ranges for the variables were established by quantile regression in age- and sex-specific groups. For reliability, intraclass correlation coefficients (ICCs), standard error of measurement, minimal detectable change, and Bland-Altman plots were used. RESULTS: Reference values for the TUGdt test variables are presented for the 2.5th and 97.5th percentiles. The reliability of TUGdt time scores was excellent (ICCs between 0.85 and 0.86). "Number of animals" and "animals/10 seconds" as well as "months/10 seconds" showed fair to good levels of reliability (ICCs between 0.45 and 0.58), whereas the reliability for both cost measures and "number of months" was poor (ICCs between 0.34 and 0.39). CONCLUSION: Normative reference values, potentially useful for clinical and research purposes, were presented in 4 age- and sex-specific groups from 50 years and older. Reliability for the test variables varied between poor and excellent, the lower estimates partly explained by some variables being the ratio of 2 other variables. In UDDGait, TUGdt tests are intended for diagnostic and predictive purposes, for which these tests are promising and require further investigations. IMPACT: Normative reference values and test-retest reliability results for the UDDGait TUGdt test variables were presented. These results should be useful for both clinical and research purposes.

Women with Fibromyalgia Prefer Resistance Exercise with Heavy Loads-A Randomized Crossover Pilot Study.

Fibromyalgia (FM) is a chronic pain condition associated with impaired muscle strength and exercise-induced pain. Physical exercise has been highlighted, by international clinical guidelines and stakeholders, as an essential component of rehabilitation in FM. Exposure to pain during exercise is generally correlated with elevated lactate levels and, additionally, is one known reason for persons with FM to avoid physical exercise and activity. A crossover design was used to test and evaluate an approach consisting of resistance exercise with heavy loads and a low number of repetitions among ten women with FM. The participants were consecutively recruited to test and perform exercise with two different resistance levels (A = light/moderate load, and B = heavy load) in a randomized crossover trial using an AB/BA setting. Results showed that the heavy load exercise session was experienced as more positive than the light/moderate load exercise session and that lower lactate levels followed exercise with heavier weight loads. This is promising and indicates that the approach of heavy weight loads and accustomed repetitions is accepted in FM and has the potential to attenuate hesitation to exercise due to exercise-induced pain. However, these effects need to be further investigated in more extensive studies.

High Monocyte Count and Expression of S100A9 and S100A12 in Peripheral Blood Mononuclear Cells Are Associated with Poor Outcome in Patients with Metastatic Prostate Cancer.

Increasing evidence indicates calcium-binding S100 protein involvement in inflammation and tumor progression. In this prospective study, we evaluated the mRNA levels of two members of this family, S100A9 and S100A12, in peripheral blood mononuclear cells (PBMCs) in a cohort of 121 prostate cancer patients using RT-PCR. Furthermore, monocyte count was determined by flow cytometry. By stratifying patients into different risk groups, according to TNM stage, Gleason score and PSA concentration at diagnosis, expression of S100A9 and S100A12 was found to be significantly higher in patients with metastases compared to patients without clinically detectable metastases. In line with this, we observed that the protein levels of S100A9 and S100A12 in plasma were higher in patients with advanced disease. Importantly, in patients with metastases at diagnosis, high monocyte count and high levels of S100A9 and S100A12 were significantly associated with short progression free survival (PFS) after androgen deprivation therapy (ADT). High monocyte count and S100A9 levels were also associated with short cancer-specific survival, with monocyte count providing independent prognostic information. These findings indicate that circulating levels of monocytes, as well as S100A9 and S100A12, could be biomarkers for metastatic prostate cancer associated with particularly poor prognosis.

Dual-Task Tests Predict Conversion to Dementia-A Prospective Memory-Clinic-Based Cohort Study.

The aim of this study was to investigate whether Timed Up-and-Go (TUG) dual-task (TUGdt) tests predict dementia incidence among patients with subjective or mild cognitive impairment (SCI; MCI). Other study objectives were to determine whether TUGdt improves dementia prediction compared to a) demographic characteristics and standard cognitive tests alone; and b) TUG and Verbal Fluency performed separately. Patients (n = 172, age range 39-91 years, 78 women) with SCI or MCI performed TUGdt tests, including 1) naming animals and 2) reciting months backwards, and clinical cognitive tests at baseline. Diagnoses were identified at follow-up after 2.5 years. Logistic regression was used to predict dementia incidence, receiver operating characteristic (ROC) curves and c-statistics for predictive capacity. Analyses were stratified by age and gender. At follow-up, 51 patients had developed dementia. The TUGdt result "animals/10 s" was associated with dementia incidence (standardized odds ratio (OR) = 4.06, 95% confidence interval (CI) 2.28-7.23, p < 0.001), more so among patients under the median age of 72 years (standardized OR = 19.4, 95% CI 3.53-106.17, p < 0.001). TUGdt "animals/10 s" improved dementia prediction compared to demographic characteristics and standard tests alone (c-statistics 0.88 to 0.94) and single-task tests (c-statistics 0.86 to 0.89), but only in the younger patient group. TUGdt has the potential to become a useful tool for dementia prediction.

Levels of mannose-binding lectin (MBL) associates with sepsis-related in-hospital mortality in women.

BACKGROUND: Mannose-binding lectin (MBL) mediates the innate immune response either through direct opsonisation of microorganisms or through activation of the complement system. There are conflicting data whether MBL deficiency leads to increased susceptibility to infections or not. The aim of this study was to determine if low levels of mannose-binding lectin (MBL) predict sepsis development, sepsis severity and outcome from severe sepsis or septic shock. METHOD: Patients aged 18 years or more with documented sepsis within 24 h after admission to the intensive care unit were included if they had participated in a health survey and donated blood samples prior to the sepsis event. A subset of these patients had stored plasma also from the acute phase. Two matched referents free of known sepsis were selected for each case. Plasma levels MBL were determined in stored samples from health surveys (baseline) and from ICU admission (acute phase). The association between MBL and sepsis, sepsis severity and in-hospital mortality were determined with 1300 ng/mL as cut-off for low levels. RESULTS: We identified 148 patients (61.5% women) with a first-time sepsis event 6.5 years (median with IQR 7.7) after participation in a health survey, of which 122 also had samples from the acute septic phase. Both high MBL levels in the acute phase (odds ratio [95% confidence interval]) (2.84 [1.20-6.26]), and an increase in MBL levels from baseline to the acute phase (3.76 [1.21-11.72]) were associated with increased risk for in-hospital death in women, but not in men (0.47 [0.11-2.06]). Baseline MBL levels did not predict future sepsis, sepsis severity or in-hospital mortality. CONCLUSIONS: An increase from baseline to the acute phase as well as high levels in the acute phase associated with an unfavourable outcome in women.