bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tube feeding in patients with dementia is associated with a longer palliative care unit stay
Authors: Zengin Hilal , Tasci Ilker 
Published: December 2021

AbstractBackgroundTube feeding (TF) was reported to alter the length of stay (LOS) in a palliative care unit (PCU) in patients with dementia. Admission of dementia patients to the PCU for many reasons including respite is tried to be kept as short as possible due to limited reimbursement in Turkey. Our past observations in our unit have suggested that patients with dementia on TF may be prone to a longer stay in the PCU. Therefore, our objective in this study was to explore the association of TF with the LOS in the PCU in patients with home discharge.MethodIn this single center study at a PCU of a tertiary training hospital, we retrospectively enrolled patients with dementia with a diagnosis on admission, between April 2017 and December 2020. Subjects with a history of intracranial surgery, brain tumors, hemiplegic stroke, hypoxic brain injury, and other neurodegenerative diseases were excluded. Very early (within 4 days) or extremely late (beyond 45 days of hospitalization) discharges were also excluded. The association between TF and LOS in the PCU was examined using logistic regression analysis.ResultThe study included 71 home discharges [mean (SD) age: 82.5 (7.0) years], females 58.1%]. Median (IQR) LOS was 15 (13.0) days (4‐44), and 45 patients (63.4%) were on TF. Median age, gender, and the ration of cancer, infectious etiology, renal failure, hypertension, diabetes mellitus, composite cardiovascular disease, sleep disturbance, depression symptoms, and pain (VAS≥1) were similar patients with and without TF. All patients on TF were bed‐bound and had more pressure ulcers (73.2% vs. 50%) compared to those without TF. Multivariate logistic regression analysis showed that controlling for study covariates TF on admission or TF placement in the PCU was independently associated with highest tertile of LOS in the PCU (OR:4.29, 95%CI: 1.03 ‐ 17.77, P=0.045, Nagelkerke R2=%28.5, Hosöer Lemeshow test p=0.643).ConclusionThe present study showed that, in patients with an established diagnosis of dementia, TF is common and independently associated with a longer length of PCU stay. Nevertheless, the study was underpowered and the results deserve confirmation in larger studies.
Longitudinal changes of phosphorylated tau 181 and neurofilament light chain in plasma and their associations with tau‐ and amyloid‐PET
Authors: Perneczky Robert , Schneider‐Axmann Thomas , Rauchmann Boris‐Stephan 
Published: December 2021

AbstractBackgroundTo explore if changes over time of plasma phosphorylated tau (p‐tau) 181 and neurofilament light chain (NfL) predict future tau and amyloid β(Aβ) PET load and cognitive performance.MethodEight hundred sixty‐five Alzheimer's Disease Neuroimaging Initiative (ADNI) participants were included. Using established AD cut‐points for the CSF concentrations of Aβ42, total‐tau and p‐tau 181, subjects were classified according to the National Institute on Aging‐Alzheimer’s Association research framework, grouping markers into those of Aβ deposition (A), tau pathology (T) and neurodegeneration (N). Analysis of variance was used to compare the plasma biomarker data between the ATN groups. The rate of change over time of p‐tau 181 and NfL was obtained from linear mixed effects models and compared between the ATN groups. Linear regression analysis was used to investigate the association of baseline plasma biomarker concentrations and rates of change with future PET tau and Aβ load and cognitive performance.ResultP‐tau 181 and NfL plasma concentrations increased along the AD spectrum, but only NfL showed greater rates of change in AD patients vs controls. Cognitive performance was associated cross‐sectionally with NfL in all sub‐groups, and with p‐tau 181 only in AD spectrum individuals. The baseline concentrations of both plasma markers, but only the rate of change of NfL, predicted future PET tau and Aβ load and cognitive performance.ConclusionP‐tau 181 and NfL in plasma show different trajectories over time within the same individuals. These biomarkers may therefore provide complementary information for AD diagnosis and prognosis in clinical routine and research settings.
Serum proBDNF availability predicts memory gains in the FINGER multimodal lifestyle intervention
Authors: Håkansson Krister , Goikolea Julen , Daniilidou Makrina , Gerenu Gorka , Ngandu Tiia , Solomon Alina , Kivipelto Miia , Sandebring‐Matton Anna 
Published: December 2021

AbstractBackgroundBrain‐derived neurotrophic factor (BDNF), including the mature form (mBDNF) and its precursor (proBDNF), has an important role in synaptogenesis, and is possibly also involved in pathophysiological mechanisms related to dementia. In this study we relate, for the first time, serum levels of both mBDNF and proBDNF with cognitive changes in elderly persons at risk of dementia during a multimodal life‐style intervention.MethodParticipants from the Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER) were included in the analysis. BDNF and proBDNF levels were measured in serum of a subsample of 151 participants, aged between 60 and 79 years, with high compliance to the intervention protocol. The multidomain intervention comprised a combination of lifestyle changes (diet, exercise, cognitive training, and vascular risk management) over 24 months. Cognitive assessments were performed at baseline, after 12 months and after 24 months. BDNF levels and changes in BDNF levels were related to changes in overall cognitive performance and to changes in three cognitive domains over the intervention period through multiple linear regression models.ResultWe found a positive association between proBDNF levels, and improved memory performance after the FINGER intervention. This association was especially strong for changes in complex memory performance (B=0.84, 95% confidence interval (CI): 0.42 – 1.26, p=0.0001), suggesting that proBDNF availability can serve as a powerful predictor of memory benefits from lifestyle changes of the type that were implemented in the FINGER study. In this respect, proBDNF outperformed mBDNF, where no associations to cognition was seen, and all other investigated predictors, including age, sex, education, and ApoE4 status. Average levels of mBDNF and proBDNF did not change during the course of the intervention, but participants with larger increases in their proBDNF levels also had larger gains in memory performance.ConclusionThese results suggest that circulating proBDNF is a key factor in the molecular processes underlying memory improvement.
Sphingosine 1‐phosphate (S1P) analogue FTY720 decreases ceramide levels and ameliorates memory performance in AD mice model
Authors: Luo Qian 
Published: December 2021

AbstractBackgroundNo effective therapeutic drugs were found for Alzheimer’s disease (AD), which focuses on amyloid plaques and neurofibrillary tangles in the past decades. Sphingolipid changes in AD patients and animals are getting more attention, especially the shift between ceramide and S1P in the brain, proposing an essential role in the amyloid‐β formation, neuroinflammation, and neuronal apoptosis in AD pathophysiology. Fingolimod (FTY720) is a drug that resembles sphingosine‐1‐phosphate (S1P) chemical structure and bioactivity. Therefore, we hypothesized that by increasing S1P signaling by means of FTY720, sphingolipid disbalance could be restored in the brain, and memory impairment observed in AD transgenic mouse models would be prevented.MethodTwo doses of FTY720 (0.1 mg/kg and 0.5 mg/kg daily) were given by oral gavage for 3 months to transgenic mouse models of AD on human apolipoprotein (APOE) APOE4 or APOE3 genetic background. During the drug administration, blood was withdrawn at different time points, and animals were challenged with behavioral tests for memory locomotion and anxiety. Brain was then collected for sphingolipids analysis by mass spectrometry and Aβ quantification.ResultSphingolipid analysis in the cortex showed that ceramide subsets elevated in AD mice. In the plasma, ceramides and sphingomyelins overall diminish in concentration over time. The behavioral tests analysis suggested that especially the low dose of FTY720 mildly prevented memory impairment in E4FAD and reduced anxiety behavior in APOE4 mice.ConclusionOn cerebral sphingolipids, Fingolimod shifted the pathway towards reducing ceramide, especially in the cortex. Our data are supportive of targeting the sphingolipid metabolism as a valid pathway for developing new therapeutic drugs for AD.
Good practice in dementia care
Authors: Borza Liana Rada 
Published: December 2021

AbstractBackgroundThe current presentation will focus on good practice principles underlying the psychogeriatric services in the NHS England, outlining the central role of the multidisciplinary mental health team in promoting active ageing by formulating person‐centred care plans based on psychosocial interventions and psychoeducation. The social worker will be illustrated as the main partner of the psychiatric team in improving the quality of life of the people with dementia by overcoming clinical risk and ensuring a safe environment for these vulnerable adults. The current talk will also explore the role of the occupational therapist in engaging a person with dementia in activities of daily living (ADLs), thus contributing to his or her wellbeing. Moreover, this presentation will help us to understand how to facilitate the autonomy of a person with dementia and how to perform an accurate mental capacity assessment.
Development of a dual Aβ‐tau vaccine for the prevention of Alzheimer’s disease
Authors: Barbour Robin M , Bard Frederique , Elmaarouf Abderrahman , Louie LeeAnn , Prill Heather , Thomas Kimberly , Kinney Gene G , Zago Wagner M 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is characterized by two pathological hallmarks, Aβ plaques and tau tangles. Several antibodies targeting Aβ plaques showed signs of slowing clinical decline in AD. Antibodies targeting tau epitopes and vaccines targeting either Aβ or tau are in earlier clinical development stages. Since Aβ and tau may act synergistically in the cause and/or progression of disease, targeting both concomitantly may lead to better efficacy for prevention of AD. Here we describe the development of our dual Aβ‐tau vaccine for AD aimed to clear pathogenic Aβ and block tau transmission.MethodA variety of linear immunogens containing both Aβ and tau peptides separated by various linkers and dendritic cell cleavage sites were screened in mice and guinea pigs for the generation of balanced titers to Aβ and tau. A subset was also evaluated in cynomolgus monkey. Animals were immunized intramuscularly with peptide‐conjugated immunogens formulated with an appropriate adjuvant. Bleeds were taken 1‐2 week after each injection. Serum titers were determined against Aβ and tau. Fresh frozen human AD or control brain sections were stained with sera from immunized and control animals. The neutralizing activity of immune sera was also assessed against soluble Ab oligomers. T‐cell reactivity was also investigated.ResultWe found dual vaccine constructs that provided balanced and immunogenic responses against Aβ and tau proteins. Immune sera bound avidly to Aβ plaques and tau tangles in human AD brain sections at concentrations expected to be achieved in CNS under in vivo conditions. Immune sera also inhibited the binding of soluble Aβ aggregates to hippocampal neurons. Immunogens did not elicit cytotoxic T‐cell responses to Aβ or tau.ConclusionWe developed dual vaccine constructs that induce optimally balanced titers against Aβ and tau in cynomolgus monkeys. Antibodies were immunoreactive to both Aβ plaques and neurofibrillary tau tangles in human AD brain sections and blocked the binding of soluble Aβ aggregates to neurons, without eliciting T‐cell responses to Aβor tau. These results support the development of a dual Aβ‐tau vaccine with the ability to target pathogenic Aβ and tau for the prevention of AD.
Is there a critical life stage to promote physical activity for preserving cognitive function? Results from a population‐based birth cohort
Authors: Feter Natan , Leite Jayne S , Rombaldi Airton 
Published: December 2021

AbstractBackgroundPhysical activity improves cognitive function across the life course, reducing the risk of all‐cause dementia in older ages. We aimed to identify the life course model that best describes the association between physical activity throughout life and cognitive performance at age 50.MethodAdults aged 50 participants of the National Child Development Survey (NCDS) were followed from birth (1958) to 2013. Physical activity was accessed using a self‐reported questionnaire in each wave. Participants were classified as physically active or inactive. Short‐term memory was assessed by word recall test while the executive function was assessed by letter cancelation and animal naming tests. Scores from both cognitive domains were reported as standard deviation (SD). The most appropriate life course model (critical, sensitive, or accumulation) to explain cognitive performance at age 50 was identified by partial F‐tests.ResultData from 4,103 adults were analyzed (53.8% women). At age 50, most participants were employees (74.3%), non‐smokers (80.3%), and overweight or obese (64.7%). Whilst 175 (4.0%) of participants were physically inactive at age 7, 44.9% practiced physical activity once a week or less at age 50. Physical activity at age 42 was defined as a critical period for better memory and executive function at age 50 in men. Among women, physical activity at age 23 was identified as a critical period for executive function while the sensitive model best explained the association between physical activity through the life course and memory at age 50. Women who were physically active at age 23 had a better executive function (1.13 [95%CI 1.06, 1.20] SD) than inactive counterparts. Better performance on memory test was observed in women physically active at age 7 (0.18 [95%CI: 0.02, 0.34] SD), 23 (0.11 [95%CI: 0.03, 0.18] SD) and 50 (0.08 [95%CI: 0.01, 0.15] SD). Physically active men at age 42 showed better performance in memory test (0.12 [95%CI: 0.03, 0.21] SD) and executive function (0.11 [95%CI: 0.04, 0.18] SD) than inactive respondents.ConclusionEarly childhood and adulthood for women and late‐adulthood for men were identified as important life stages to promote physical activity for preserving cognitive function at age 50.
Validation of dementia diagnostics toolbox using interactive iPad technology
Authors: Chandra Jay , Muthupalaniappan Siva , Shang Zisheng , Bose Soham , Deng Richard , Pecyna Eryk , Chen Alexander , Lin Raymond , Butts Dignity , Capo‐Battaglia Athena 
Published: December 2021

AbstractBackgroundConventional means for dementia diagnosis rely on qualitative tests usually administered after significant pathogenesis. Past studies suggest the utility of more quantitative analytical approaches such as handwriting/drawing tasks (Impedevo et al., 2018). Such tools would provide low‐cost, portable, and instantaneous quantitative diagnostics for more efficient patient screening. However, efforts to realize these methods have faced challenges such as low sample size, incomplete feature extraction, and lack of task diversity. We attempted to create a tablet application that uses pen‐tracking technology to surmount these challenges.MethodAs fine motor control provides fundamental markers of neurological health (Bisio et al., 2017; Thomas et al., 2017), rigorous statistical analysis of simple drawing tasks on a tablet permitted differentiation between neuronormative patients and dementia patients with high fidelity. We have started testing our data analysis pipeline with open access datasets: PaHaW (Drotár et al., 2016), Isuniba (Impedovo et al, 2013), ParkinsonHW (Isenkul et al., 2014). These datasets contain drawing data for healthy individuals and those with both dementia and other neurodegenerative diseases. They contain similar raw data that the in‐house iPad app collects. From that raw data, we extracted predictive features, including velocity, acceleration, jerk, curvature, and measures of variation.ResultWe have successfully created an iPad app that is able to record the dynamic handwriting process with an Apple Pencil. Our platform has the potential to generate more standardized datasets with improved documentation compared to existing archives. Patients trace complex figures such as spirals and infinity symbols at varying speeds over multiple trials. Additionally, the subjects are asked to remember and draw a shape that was presented to them at the beginning of the test. The app collects key data such as the position of the pen tip, velocity of pen movement, pen angle relative to the surface, and pressure exerted on the surface.ConclusionWe plan to deploy our in‐house iPad app in clinical trials to collect pen‐tracking data with which to facilitate differential diagnoses for neurodegenerative diseases afflicting Alzheimer’s and Parkinson’s patients. The validation of such a platform would improve upon existing diagnostic datasets and lower major barriers to dementia screening.
Reduced oral intake is the primary cause of referral of patients with dementia to the internists in Turkey
Authors: Kaya Seher , Tasci Ilker 
Published: December 2021

AbstractBackgroundDuring acute care admissions of dementia patients, an internist consultation is ordered in the first step due to the complexity of these patients. In this study, to determine what types of care are expected in the internal medicine wards, we examined the causes of referral of patients with dementia to an internal medicine clinic.MethodIn this single center study, we retrospectively enrolled patients with dementia who were consulted and admitted to the internal medicine clinic of tertiary care hospital between April 2018 and December 2020. The causes of admission were identified from the medical records. Patients consulted but not hospitalized were excluded. Patients with a history of neurodegenerative disorders other than Alzheimer’s dementia, vascular dementia, dementia with Lewy bodies and Parkinson’s dementia were excluded.ResultThe analysis included 71 patients [mean (SD) age: 85.0 (9.1) years, female 54.9%]). Lower education (<5 years, 87.3%), low estimated glomerular filtration rate (<60 ml/min, 84.5%), hypertension (80.3%), composite CVD (CAD, stroke or peripheral arterial disease, 56.3%), coronary heart disease (46.5%), diabetes mellitus (32.4%), stroke history (22.5%), anemia 45.1%, polypharmacy (>4 drugs, 39.4%), and overall multimorbidity (4 or more comorbidities, 70.4%) were prevalent. The most common cause of referral resulting hospitalization was reduced oral intake by 57.7%. Acute kidney failure (9.9%), glycemic disturbances (7.0%), blood pressure disturbances (2.8%), cancer related problems (2.8%), urinary infection (2.8%), and other disorders (2.8%). In 14.1% of patients the cause of neither referral nor admission was identified by the referring physician and the internist. Men vs. women (71.9 vs. 46.2%, p=0.029) and patients with BMI<30 vs. >30 (62.5% vs. 14.3%, p=0.037) were more frequently, whereas patients with diabetes vs. without diabetes (30.4 vs. 70.8, p=0.001), and composite CVD (47.5 vs. 71.0, p=0.047) were less frequently admitted with reduced oral intake.ConclusionThe present study showed reduced oral intake as the leading cause of admissions of dementia patients to the internal medicine ward. Given the well‐known complexity of these patients, this finding may justify the recent efforts by the international societies to increase the involvement of internists in the management of undernutrition in acute and chronic care.
Machine learning for neuropsychological assessment of Alzheimer’s disease and behavioral variant frontotemporal dementia
Authors: Matias‐Guiu Jordi A , García‐Gutiérrez Fernando , Pytel Vanesa , Hernández‐Lorenzo Laura , Delgado‐Álvarez Alfonso , Valles‐Salgado María , Delgado‐Alonso Cristina , Cabrera‐Martín María Nieves , Matias‐Guiu Jorge , Ayala José Luis 
Published: December 2021

AbstractBackgroundDiagnosis of Alzheimer’s disease and behavioral variant frontotemporal dementia is often challenging. In spite of comprehensive clinical and cognitive assessments, the use of biomarkers is usually needed. We aimed to develop machine learning based models for the diagnosis of AD and bvFTD using only cognitive testing. These techniques may allow selecting the most relevant tests for an optimized neuropsychological diagnosis.MethodWe included 329 participants: 171 patients with AD, 72 patients with bvFTD, and 87 healthy controls (HC). All patients met the current diagnostic criteria, had a neuroimaging compatible with FDG‐PET, and had at least two years of follow‐up confirming the diagnosis. A comprehensive neuropsychological protocol was performed. Evolutionary algorithms were developed, including NSGA‐II. F1‐score was calculated, as a measure of accuracy. Algorithms were developed for the following classification problems between AD vs FTD, AD vs HC, FTD vs HC, and AD/FTD vs HC.ResultsDifferentiation between FTD vs HC, AD vs HC and FTD/AD vs HC reached an F1 superior to 90%. Differentiation between FTD vs AD was slightly inferior (F1 80‐85%). Test selected by the NSGAII algorithm for AD vs FTD were as follows: Symbol Digit Modalities Test, Stroop test, Trail Making Test, Corsi blocks, and ACE‐III. For FTD vs HC, the algorithm selected Free and Cued Selective Reminding Test, Trail Making Test, Rey Figure (copy type), Boston Naming Test, and ACE. For AD vs HC, the following test was selected: Rey Figure, Trail Making Test, Corsi test, and verbal fluency.ConclusionsWe have developed a machine‐learning approach to perform feature selection and modeling of neuropsychological test scores, with a high level of discrimination between groups. Our study suggests the interest of applying machine learning for an optimized use of cognitive tests and to improve the interpretation of neuropsychological assessment. . These algorithms allow maximizing the diagnostic capacity, selecting the tests with best characteristics, and the automation, which may be useful for diagnosis.