bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring physical parameters from wearable sensors for detection of cognitive decline in routine care
Authors: Goerss Doreen , Amaefule Chimezie O. , Kowe Antonia , Köhler Stefanie , Teipel Stefan J. 
Published: December 2021

AbstractBackgroundWearable sensors offer the chance to measure activity and vital signs continuously and unobtrusively in elderly people living in domesticity or stationary care. To derive meaningful features from raw data and transform sensor data into clinically relevant information it is necessary to develop efficient algorithms and validate the results, e.g. with synchronized observational data. Only then sensor data bear the potential to detect functional changes or specific behaviors that are linked to Alzheimer’s disease and allow the complementation of the diagnostic process with sensor data.MethodInternational data point to a potential role of serious games applications to detect early signs of cognitive decline. Along this line a study of the DZNE uses a comprehensive memory paradigm examining age sensitive decline in a citizen science study performed with digital platforms. Complementary approaches include non‐intrusive assessment of everyday behaviour. We performed several studies to examine the feasibility and potential of mobile sensors in detection of challenging behaviors, spatial disorientation and gait changes to classify people with MCI or dementia and detect situations with need for help.ResultIn a study with dementia‐patients that were wearing mobile sensors continuously over several weeks, we could show that multimodal sensors can be applied long‐term in the setting of PwD living in stationary care. Accelerometry can be used to detect behavioral patterns in dementia patients. We extended the set of sensor data with vital signs (e.g. heart rate, electrodermal activity) and indoor tracking to detect spatial disorientation in an ongoing wayfinding study to classify MCI /dementia based on sensor data.ConclusionMobile sensors will be omnipresent in the following years. With complex algorithms we were able to derive features that allow information about crucial personal conditions with respect to mental health. Digital markers including sensor data won’t be a stand‐alone diagnostic tool and need to be embedded in an innovative diagnostic pathway.
An item response theory approach to clinical diagnosis of MCI and dementia: Illustrations from ADNI and NACC data
Authors: Kiselica Andrew M , Benge Jared 
Published: December 2021

AbstractBackgroundDiagnostic labels, such as cognitively normal, mild cognitive impairment, and dementia rely on application of several different criteria and are often based at least in part on subjective clinical judgments. These factors may lead to heterogeneity in diagnostic practices across datasets. A modern psychometric technique known as item response theory (IRT) can be used to take information from many different markers of an underlying spectrum (e.g., cognitive impairment) and evaluate how diagnostic labels perform across datasets when shared items are used.MethodIn this poster, we illustrate how IRT might be used to evaluate how diagnostic labels function across two major databases of older adults that include cognitive data and diagnostic labels, the National Alzheimer’s Coordinating Center Uniform Data Set (n = 6,042) and the Alzheimer’s Disease Neuroimaging Initiative (n = 513).ResultTaking an IRT driven Cochran‐Mantel‐Haenzel approach revealed no significant differential item functioning for the diagnostic labels among individuals from the Alzheimer’s Disease Neuroimaging Initiative and National Alzheimer’s Coordinating Center databases (Figure 2; X2
=11.79, p < .001, Class AA item characterization).ConclusionThe current study demonstrated how IRT scoring approaches outline similarities in cognitive functioning across a group of measures, despite being diagnosed under different criteria across studies. Findings illustrate a manner of evaluating if diagnostic labels are applied correctly across participants. The utility of this approach will be tempered by the ability to identify underlying unidimensional constructs across studies, although multi‐dimensional IRT approaches have been developed.
Masitinib in mild to moderate Alzheimer’s disease: Results from study AB09004
Authors: Dubois Bruno , Hermine Olivier ,   the AB09004 study group
Published: December 2021

AbstractBackgroundMasitinib is a small molecule drug targeting KIT, LYN, FYN and CSF1R. Proof‐of‐concept that masitinib slowed cognitive decline in Alzheimer's disease (AD) was previously demonstrated [doi:10.1186/alzrt75; doi:10.3233/JAD‐200466]. Study AB09004 assessed oral masitinib administered as an add‐on therapy to standard care for the treatment of mild to moderate AD.MethodPhase 2B/3 study AB09004 comprised two independent, double‐blinded, placebo‐controlled, sub‐studies: masitinib at 4.5mg/kg/day versus placebo (randomized 1:1), and a titrated masitinib dose of 6.0 mg/kg/day versus matched placebo (randomized 2:1). Eligible patients that had a clinical diagnosis of AD with baseline mini‐mental state examination (MMSE) score ≥12–≤25, and had received a stable dose of cholinesterase inhibitor (donepezil, rivastigmine or galantamine) and/or memantine for ≥6 months, were treated for 24 weeks. Primary endpoint was overall change from baseline at week‐24 (analysis of covariance model) in the Alzheimer's Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog) or the Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS‐ADL) score. The study was successful if a significant improvement was reached on either ADAS‐Cog or ADCS‐ADL at a 2.5% level of statistical significance, in either sub‐study.ResultMasitinib (4.5mg/kg/day) (n=182, median (age=73 years, MMSE=19, ADCS‐ADL=55.0, ADAS‐Cog=25.5)) showed significant benefit over placebo (n=176, median (age=73 years, MMSE=19, ADCS‐ADL=53.5, ADAS‐Cog=24.8)) with a least‐squares mean difference in ADAS‐Cog from baseline (δCog) of ‐1.46 versus 0.69, respectively, and corresponding least‐squares mean difference between groups (ΔCog) of ‐2.15 (97.5%CI[‐3.48,‐0.81]);p=0.0003. All ADAS‐Cog sensitivity analyses were convergent with the primary outcome, including the conservative jump‐to‐reference approach with ΔCog of ‐1.89 (95%CI[‐3.06,‐0.72];p=0.0016). Considering ADCS‐ADL, δADL was 1.01 for masitinib (4.5mg/kg/day) versus ‐0.81 for placebo, with a ΔADL of 1.82 (97.5%CI[‐0.15,3.79]);p=0.038. Safety was consistent with the known profile for masitinib. The proportion of patients presenting at least one adverse event (AE) or severe AE was respectively, 87.0% and 26.5% for masitinib (4.5mg/kg/day, n=185) versus 77.5% and 19.3% for placebo (pooled, n=280). Efficacy results from the titrated masitinib 6.0 mg/kg/day sub‐study were inconclusive and no new safety signal was observed.ConclusionMasitinib (4.5mg/kg/day), a tyrosine kinase inhibitor targeting mast cell and microglia activity, may provide a new treatment option for mild to moderate AD.
Fully automated immunoassays for measuring beta‐amyloid peptide (1‐42) and total tau in cerebral spinal fluid
Authors: Kozo Daniel R 
Published: December 2021

AbstractBackgroundBeta‐amyloid1‐42 (Aβ42) and tau protein are cerebral spinal fluid (CSF) biomarkers for progression to AD. The sensitivity requirements for Aβ42 and total tau assays are in the pg/mL range, a challenge for any methodology. The use of these biomarkers for clinical purposes requires assays that can reliably deliver accurate and reproducible results.MethodNew prototype immunoassays for Aβ42 and total tau on a fully automated clinical analyzer [Siemens Healthineers ADVIA Centaur® XPT Immunoassay System] are under development to enable routine testing of AD biomarkers in clinical laboratories. Each assay uses an antigen/antibody sandwich format and chemiluminescence detection. Standard curves from 0 to 4000 pg/mL and 0 to 6500 pg/mL were generated for the Aβ42 and Tau assays, respectively. Synthetic Aβ42 and recombinant tau‐441 were spiked into an immunodepleted (ID) CSF pool and tested. Precision was evaluated over 6 days by testing a CSF pool and buffer controls on two analyzers. Functional sensitivity was estimated using the precision data. Clinical utility was evaluated by testing 30 clinical CSF samples from subjects with and without AD.ResultRecoveries of spiked Aβ42 from CSF ranged from ‐13% to +0.7% over 113 to 3179 pg/mL. Recoveries of spiked tau‐441 from CSF ranged from ‐11% to +13% over 35 to 3826 pg/mL. The repeatability and within‐laboratory precision of the Aβ42 assay ranged from 1.3% to 8.6% and 1.9% to 9.9%, respectively, over 107 to 2005 pg/mL. The repeatability and within‐laboratory precision of the total tau assay ranged from 1.2% to 10.8% and 1.6% to 12.5%, respectively, over 108 to 3300 pg/mL. The functional sensitivities of the Aβ42 and total tau assays were estimated to be < 200 pg/mL and < 80 pg/mL, respectively. Using ROC analysis, a ratio of Aβ42 and total tau results was able to differentiate AD from non‐AD subjects with 90% sensitivity and 95% specificity (AUC 0.95).ConclusionWhen finalized, the fully automated Aβ42 and total tau assays will have performance characteristics suitable for routine use in a clinical laboratory. The performance of the assays in combination with automation will make testing for these important biomarkers more reliable and routine.
Repeated intravenous infusion of autologous adipose‐derived stem cells improves cognitive function
Authors: Shigematsu Kazuo , Ishii Kazunari , Tahara Kenichi , Komori Naoyuki , Yamagishi Hisakazu 
Published: December 2021

AbstractBackgroundStem cell therapy has emerged as a promising treatment for neurodegenerative diseases caused by the accumulation of abnormal proteins. We have administered repeated infusions of autologous adipose‐derived stem cells (ADSCs) to 39 patients with amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), Parkinson's disease (PD), multisystem atrophy (MSA) (including spinocerebellar degeneration (SCD)), and Alzheimer's disease. A total of 182 infusions have been administered, and not a single side effect has been observed. In this study, we evaluated cognitive function in 9 patients with cognitive impairment after administration.MethodThis treatment was conducted after registration with the Japanese Ministry of Health, Labour and Welfare, with the consent of the patient, approval of the Ethics Committee, and approval of the Specific Review Board for Regenerative Medicine. Stem cells were harvested from the patient's own abdominal subcutaneous adipose tissue and cultured in serum‐free medium. 5.0x10^7 to 1.2x10^8 stem cells were administered intravenously 5 or 6 times at approximately a‐month intervals. The evaluation was performed by neurologist's examinations, caregiver's interview and Montreal cognitive assessment (MoCA). Amyloid PET scans were performed before and after the treatment in three patients with Alzheimer's disease.ResultMoCA scores averaged 10.3 points before administration and 19.6 points after 5 infusions of ADSC, and there were no cases of deterioration among the 9 patients evaluated. Not only did the overall score improve, but the clock drawing visibly improved. Improvement was also observed in medical examinations and caregiver interviews. Amyloid PET scan in one case showed a decrease in brain amyloid deposition. Three patients had associated parkinsonism but showed significant improvement when assessed by Unified Prkinson's Disease Rating Scale (UPDRS). We confirmed that the administered stem cells were CD10 (neprilysin, an amyloid‐degrading enzyme) positive.ConclusionImprovement in cognitive function was observed after 5 doses of ADSCs infusion. No side effects were observed, confirming that this treatment is repeatable and safe. The mechanism may be amyloid removal by neprilysin, but since parkinsonism is also improved, multiple factors are considered, including neuronal regeneration and repair, improvement of blood flow, anti‐inflammatory effects, and removal of multiple abnormal proteins and deposits, such as alpha‐synuclein in Parkinson's disease.
Irregular sleep wake rhythm disorder (ISWRD) signs and symptoms reported directly from patients with dementia and caregivers
Authors: Pokrzywinski Robin , Abel Cristina , Lenderking William R , Yardley Jane , Cheng Jocelyn , Moline Margaret 
Published: December 2021

AbstractBackgroundSleep‐wake disturbances appear early in the course of Alzheimer’s disease (AD) and other dementias and are not uncommonly associated with disruption in circadian rhythms, such as Irregular Sleep‐Wake Rhythm Disorder (ISWRD; ICD‐10 code G47‐23). ISWRD is also associated with behavioural and functional symptoms. The objective of this study (E2006‐A001‐111; NCT04300569) was to identify signs and symptoms of ISWRD important to patients and caregivers of patients with dementia and ISWRD. The data informed a novel questionnaire, filling a measurement gap as no questionnaires specific to ISWRD in the AD population are available.MethodThis cross‐sectional, qualitative, non‐interventional, telephone study interviewed patients and their caregivers. Caregivers were interviewed apart from the patient; patients were interviewed with caregivers present. All participants were from the US; data were collected in English and Spanish. Interview transcripts were analysed using ATLAS.ti software.Result15 patient/caregiver dyads and 5 caregiver‐only subjects were interviewed. For the patient group (n=20; 5 not interviewed), mean age was 79.0 (8.3)y and 75% were male. For the caregiver group (n=20), mean age was 67.5 (14.5)y and 20% were male. Both caregivers and patients noted fragmented nighttime and daytime sleep‐wake patterns, but also reported functional consequences of ISWRD. Nighttime examples included waking, wandering, and refusing to go back to sleep. Daytime examples included falling asleep at inappropriate places; appearing sleepy; losing concentration due to sleepiness; sleepiness interfering with personal care and leisure activities; needing to postpone, change, or avoid activities due to sleepiness; adverse emotional impacts, and sundowning. Few differences in terms, or their meaning, were identified between language of data collection. Based on the differing quality of patient and caregiver reports, the potential for patient anosognosia, and the ability of caregivers to observe signs and behaviours, the data suggested a caregiver‐completed observer‐reported outcome (ObsRO) measure is most appropriate for ISWRD evaluation.ConclusionConcepts reported by patients and caregivers uncovered ISWRD observations and functional consequences appropriate for a novel ObsRO measure that can be used in future studies of ISWRD. Support: Eisai Inc.
Reproductive factors and the risk of incident dementia: Results from the UK Biobank
Authors: Gong Jessica , Harris Katie , Peters Sanne , Woodward Mark 
Published: December 2021

AbstractBackgroundAge‐standardised prevalence and deaths for dementia have been reported to be higher in women compared with men. The role of female‐specific endocrine and reproductive events in modulating dementia risk needs to be further clarified to explain some of these sex disparities.MethodThe UK Biobank recruited over 500,000 middle‐aged women and men. After 11.3 years, 3,701 (45% women) incident dementia occurred. Cox proportional hazard regressions estimated hazard ratios (HRs) for reproductive factors and hormone use with dementia in women; number of children in both sexes.ResultAdjusted HRs (95% CI) for dementia were 1.20 (1.08, 1.35) for menarche at <12, 1.24 (1.10, 1.39) at ≥15, compared to 13 years; 1.29 (1.12, 1.49) for menopause at <47 compared to 50 years; 1.13 (1.01, 1.27) for hysterectomy; 0.80 (0.72, 0.90) for use of oral contraceptive pills, and 1.56 (1.40, 1.73) for hormone replacement therapy. The number of children and dementia risk were similarly associated for women and men.ConclusionHormonal transition and reproductive experiences were associated with women’s dementia risk, although the biological factors associated with childbearing are unlikely to account for the risk variation in women.
Association between ambient temperature and dementia‐related hospital admissions in England
Authors: Gong Jessica , Part Cherie , Hajat Shakoor 
Published: December 2021

AbstractBackgroundThe impacts of a changing climate on dementia burdens have not been widely explored, despite the increasing pressures associated with dementia on the public health and social care systems. This study explores the association between ambient temperature and the dementia‐related emergency hospital admission, using the national hospital inpatient dataset for England. We also examine important modifiers of the heat‐risk, including separate results for each Government region of the country.MethodsDaily counts of emergency admissions with a primary diagnosis of dementia (ICD codes F00‐F03) and daily ambient temperature data from Met Office land surface stations were obtained for the period 2000‐2009 in England. Poisson regression was used to detect short‐term associations between daily mean temperature and daily counts of dementia admissions, adjusting for overdispersion and day‐of‐week effects, and including spline functions to model any underlying trends and seasonal patterns in the series. Distributed lag non‐linear models employing cross‐basis functions were used to characterise the exposure‐response relationship, at both national and regional levels at different lags of temperature; a 7‐day lag structure was used to explore potential delayed effects of temperature on the week leading up to admission. The modifying effects of age‐group, urban/rural residence, and quintiles of area‐level deprivation were also examined.ResultThere was some suggestion of seasonality in dementia admissions, with numbers peaking in the summer and winter months each year. After seasonal adjustment, there was an increase in the risk of dementia‐related hospital admission associated with high temperature, with adverse effects becoming apparent once daily mean temperatures rose above 15.0°C. At the national level, we estimated an approximately 10% increase in the risk of dementia admission for every 5°C increase in temperature above 15.0°C. When disaggregated by regions, the risk was highest in London. Separate results by age‐group, deprivation and urban/rural residence will be presented.ConclusionThe findings are likely to have important public health implications for priority settings, such as for hospital emergency department planning during hot seasons. The dangers of heat‐induced symptoms among dementia sufferers can be anticipated by caregivers whenever hot weather is forecast.
Telehealth outreach programming in the Pacific island of Guam: Providing access to dementia care support services during the COVID‐19 pandemic
Authors: Twaddle Iain K. B. , Hattori‐Uchima Margaret Perez , Orallo Rhoda Gaba , Gutierrez Nikolas Jude 
Published: December 2021

AbstractBackgroundThe COVID‐19 pandemic has led to heightened levels of isolation and loneliness for millions of individuals and families worldwide, resulting in adverse health and mental health outcomes. Persons with dementia and their family caregivers are particularly vulnerable due to the deleterious impact of social isolation on both dementia symptoms and caregiver burden. One of the greatest challenges for dementia patients has been accessing dementia care services during COVID‐19 lockdowns. In the Pacific island of Guam, the pandemic quickly led to the closure of senior centers, adult day care centers, family caregiver support programs, and other social services for older adults and their families in March 2020. As a result, persons with dementia suddenly found themselves isolated at home and dependent upon family members to provide round‐the‐clock care. This presentation will describe the development of an innovative telehealth outreach program that was launched in Guam in the summer of 2020, three months after the first COVID‐19 case had appeared on the island. The program was designed to provide improved access to social support and specialized community services for persons with dementia and their family caregivers. There are four components: (1) virtual family caregiver support groups where participants can share the stresses and challenges of caring for a loved one with dementia with others who are going through similar experiences; (2) virtual presentation and consultation sessions led by dementia care specialists from the community providing easy access to dementia care information and services; (3) 24/7 family caregiver support networks through mobile messaging apps to mitigate social isolation and ensure the availability of support in times of crisis; and (4) telehealth family counseling for persons with dementia and their family members employing narrative approaches that embrace the oral storytelling traditions of Pacific island cultures. The community response has been strong with approximately 50‐60 family caregivers and persons with dementia participating in the program monthly. Project outcomes suggest that telehealth outreach services represent an effective and sustainable approach to connecting persons living with dementia and their family caregivers to community resources during times of isolation.