bluuebunny/crossref_metadata_2025_split huggingface dataset:
The estimation of the global prevalence of dementia from 1990‐2019 and forecasted prevalence through 2050: An analysis for the Global Burden of Disease (GBD) study 2019
Authors: Nichols Emma , Vos Theo 
Published: December 2021

AbstractBackgroundGiven projected increases in population growth and population aging, the number of people with dementia is expected to increase in the future. Characterizing the distribution and magnitude of the anticipated growth is critical for public health planning and prioritization of resources. This study aimed to improve on prior forecasts of dementia prevalence by producing country‐level estimates and by incorporating information on trends in dementia risk factors.MethodDementia prevalence from 1990‐2019 was estimated using meta‐analytic techniques. We then forecasted dementia prevalence attributable to the three risk factors included in the Global Burden of Disease (GBD) study (BMI, fasting plasma glucose, and smoking), using relative risks and forecasted risk factor prevalence to predict future risk‐attributable prevalence. Finally, using linear regression models with other dementia risk factors included as predictors, we forecasted dementia prevalence not attributable to GBD risks. To assess the relative contribution of changes in prevalence, population growth and population aging, we conducted decomposition analysis.ResultWe estimated the number of people with dementia would increase from an estimated 57.4 (50.4 to 65.1) million cases globally in 2019 to an estimated 152.8 (130.8 to 175.6) million cases in 2050. There was geographic heterogeneity in projected increases, with the highest increases observed in eastern sub‐Saharan Africa and North Africa and the Middle East. Despite large increases in the number of projected dementia cases, age‐standardized rates remained largely stable. Decomposition analysis suggested that projected increases in cases could largely be attributed to population growth and aging, although the relative importance of these two factors varied by world region.ConclusionThe number of individuals with dementia is expected to grow, due largely to population growth and population aging. However, heterogeneity in expected rates of growth was observed across countries, and the country‐level estimates from this study can be used to inform policy decisions around funding for research and public health planning efforts at the national and international levels. Multifaceted approaches, including scaling up interventions to address modifiable risk factors and investing in research on etiologic disease mechanisms, will be critical in addressing expected increases in the number of individuals affected by dementia.
Differential correlation of white matter hyperintensity with Alzheimer’s pathology within A/T groups
Authors: Alban Sierra , Choupan Jeiran , Ringman John M. , Toga Arthur W. , Chui Helena C. , Sepehrband Farshid 
Published: December 2021

AbstractBackgroundWhite Matter Hyperintensities (WMH) of brain MRI have been linked to cerebral amyloid angiopathy, a hallmark of Alzheimer’s Disease (AD). Particular biomarkers, such as Florbetapir and Flotaucipir PET measures of β‐amyloid and neurofibrillary tangles, respectively, have been utilized to quantify AD pathology (A/T). Here we investigated WMH association with AD pathology across A/T groups.MethodImaging was gathered from ADNI (N=286, 137 male). Participants were stratified based on A/T. For Aβ classification, amyloid PET SUVR data was analyzed. Flortaucipir SUVR PET in metatemporal regions was used (Jack et al. 2017). The cutoffs used to categorize A+ and T+ were any values above 1.25 and 0.79 respectively. A deep convolutional neural network was used for mapping WMH in MRI (Sepehrband et al., 2020). Regression and Pearson correlation analysis were used to assess the association and correlation between WMH and amyloidosis (controlling for age, sex, education and scanner manufacturer).ResultWMH volume was positively correlated with amyloidosis (Figure 1A; r=0.28, p=6e‐7). We observed a significant effect of the WMH volume on global amyloid SUVR (F(1, 309) = 7.95, p = 0.008). WMH volume of participants with Amyloid (A+) or Tau (T+) pathology was higher than controls (A‐/T‐) (Figure 1B). WMH volume of AD participants(A+/T+) was significantly higher than controls (A‐/T‐) (p = 0.007, Cohen’s d = 0.4). A+/T‐ participants had higher WMH than control (p = 0.002, Cohen’s d = 0.5).We observed significant positive correlation between WMH and amyloid in the A+/T‐ group (r=0.36, p=0.0008) (Figure 1C). A marginal positive correlation was observed among A‐/T+ participants (r=0.58, p=0.0498), and a positive non‐significant correlation among the A+/T+ group (r=0.23, p=0.09). We observed neither a correlation nor an association between WMH and Tau uptake (Figure 1D: correlation p=0.25; association p=0.4).ConclusionIncreased global flortaucipir uptake was associated with an increase in overall WMH volume. The strongest relationship between WMH and amyloid accumulation was when neurodegeneration was not present (A+/T‐). These findings are consistent with autopsy studies showing correlations between cerebral amyloid angiopathy and WMH. The combination of significant WMH and a positive amyloid PET scan raises possibility of underlying amyloid angiopathy.
CSF total tau/α‐synuclein ratio improved the diagnostic performance for Alzheimer’s disease as an indicator of tau phosphorylation
Authors: Kang Min Ju , Shim Kyu Hwan , Suh Jeewon , Pyun Jung Min , Ryoo Nayoung , Park Young Ho , Youn Young Chul , Jang Jae‐Won , Jeong Jee Hyang , Park Kyung Won , Choi Seong Hye , Suk Kyoungho , Lee Ho‐Won , Ko Pan‐Woo , Lee Chan‐Nyoung , Lim Tae Sung , An Seong Soo , Kim Sangyun 
Published: December 2021

AbstractBackgroundRecently, several studies suggested potential involvements of α‐synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α‐synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α‐synuclein could be an additional supported biomarker in AD diagnosis.MethodIn this cross‐sectional study, CSF samples of 71 early‐onset AD, 34 late‐onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson’s disease, and 32 healthy control (HC) were collected. CSF amyloid‐β1‐42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in‐house ELISA kit was developed to quantify α‐synuclein. The cognitive assessments and amyloid‐PET imaging were also performed.ResultCSF α‐synuclein manifested a tendency to increase in AD and to decreased in Parkinson’s disease compared to HC. The equilibrium states of total tau and α‐synuclein concentrations were changed significantly in AD, and the ratio of total tau/α‐synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid‐β1‐42/phosphorylated tau181 had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid‐β1‐42 and amyloid‐PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non‐Alzheimer's disease pathophysiology, all A‐T+N+ patients with N/αS+ were reintegrated into AD.ConclusionThe high correlation of α‐synuclein with tau and the elevated N/αS in AD supported the involvement of α‐synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α‐synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.
Prevalence of mild behavioral impairment: A systematic review and meta‐analysis
Authors: Pan Yining , Shea Yat Fung , Li Siwen , Chen Ruijun , Mak Henry , Chiu Patrick Ka‐Chun , Chu Leung‐Wing , Song You‐Qiang 
Published: December 2021

AbstractBackgroundMild behavioral impairment (MBI) is a neurobehavioral syndrome characterized by later life emergent neuropsychiatric symptoms (NPS). There has not been any systematic review or meta‐analysis on the prevalence of MBI. Main aim of the study is to calculate the pooled prevalence of MBI.MethodA search of the literature on MBI in mild cognitive impairment (MCI), cognitively normal (CN), and subjective cognitive impairment (SCI) and cognitively normal but at risk (CN‐AR) subjects published between 1 January 2003 and 28 September 2020 was conducted. Meta‐analysis using a random effects model was performed to determine the pooled estimate of the prevalence of MBI. Meta‐regression was performed to identify factors contributing to the variance of prevalence rate. A systematic review was also performed to study the impact of MBI in cognitive outcomes and its correlation to pathology and genetics of Alzheimer’s Disease (AD).ResultEleven studies conducting among all 15689 subjects were subjected into meta‐analysis revealing a pooled prevalence of MBI at 33.5% (95% CI 22.6‐46.6%). Seven studies conducting among 1358 MCI subjects were subjected into meta‐analysis revealing a pooled prevalence at 45.5% (95% CI 36.1‐55.3%). Four studies conducting among 13153 CN subjects were subjected into meta‐analysis revealing a pooled prevalence at 17% (95% CI 7.2‐34.9%). Five studies conducting on 1158 SCI or CN‐AR subjects were subjected into meta‐analysis revealing a pooled prevalence at 35.8% (95% CI 21.4‐53.2%). Systematic review of 13 studies showed MBI has a significant impact on cognitive deterioration, and it is associated with pathology and genetics of AD.ConclusionMBI is common in MCI, CN, and SCI and CN‐AR subjects. Our finding is potentially useful in planning future clinical trials.
Alternatives to medication for the prevention of aggression by psychogeriatric patients: The challenge to adopt a new protocol
Authors: Gokkel Paul , Anderegg Arthur 
Published: December 2021

AbstractBackgroundAn increasing number of patients with dementia and a lack of personnel in nursing homes is deteriorating the quality of life and causes more aggression incidents by nursing home residents. These patients experience behavioral and psychological symptoms of dementia, such as psychosis, aggression, agitation. Antipsychotics are commonly prescribed off‐label to manage these symptoms, despite warnings from the regulatory agencies regarding the increased risk of mortality associated with their use in elderly patients. Another fact is that this medication does not provide a hundred percent guarantee for the safety of the staff members. In many countries there is a policy to reduce fixation and isolation of aggressive patients. Therefore the nursing staff has less tools to prevent physical aggression by patients. Staff members informed us about this situation and we have designed an user friendly aggression prevention device, which limits the arm movements of the patient. In contrast to fixation the user can still perform all daily activities. This device is comfortable to wear, contrary to fixation. This device only prevents hitting movements with fully extended arms by a maximal 90 degree bending angle of the elbow. Also effective throwing with objects is inhibited. Product samples of this patented invention were made and tested for safety and effectiveness by martial art experts. After a positive result we offered this new medical device on request of a staff member, a renowned psychiatrist, to a health care organization for a medical trial. The product is registered in the European Union as a medical device Class I: NL‐CA002‐2017‐42023. This invention was considered by several medical experts as a significant improvement to the safety in health care. However the hesitance of some managers to break with old protocols and try out something new was the reason to cancel the trial. We are looking for organizations (nursing homes, psychogeriatric hospitals etc) that can test this medical device.
Association of life‐course depression with the risk of dementia in late life: A nationwide twin study
Authors: Yang Wenzhe , Li Xuerui , Pan Kuan‐Yu , Yang Rongrong , Song Ruixue , Qi Xiuying , Pedersen Nancy L , Xu Weili 
Published: December 2021

AbstractBackgroundDepression in later life has been linked to dementia, yet whether depression is a prodromal phase or risk factor for dementia is still under debate. Thus, looking into the time window of depression occurrence may help unveil the nature of this link. We aimed to examine the association of depression with dementia from a life‐course perspective, and to explore the roles of genetic and early‐life environmental factors shared by twins, and education in this association.MethodWithin the Swedish Twin Registry, 41,727 dementia‐free twin individuals (mean age 60 years) were observed for 18 years to detect incident dementia. Life‐course depression was ascertained from the Patient Registry and divided as early‐, mid‐, late‐, early‐ to mid‐life, mid‐ to late‐life, and lifelong depression according to the age of occurrence. Dementia was ascertained based on the same registry. Generalized estimating equation (GEE) model was used for unmatched case‐control analysis and conditional logistic regression was used for co‐twin matched case‐control analysis.ResultOf all participants, 2,832 (6.8%) had depression and 3,258 (7.8%) developed dementia. In the multi‐adjusted GEE model of unmatched analysis, the odds ratio (OR) of dementia was 1.93 [95% confidence interval (CI): 1.69–2.21] for depression at any age. In stratified analyses, the ORs (95% CIs) of dementia were 0.98 (0.51–1.90) for early‐life, 1.46 (1.09–1.95) for mid‐life, 2.16 (1.82–2.56) for late‐life, 1.62 (0.60–4.35) for early‐ to mid‐life, 2.24 (1.49–3.36) for mid‐ to late‐life, and 2.65 (1.17–5.98) for lifelong depression respectively. No statistically significant difference in ORs from the unmatched and co‐twin matched analyses was observed (P = 0.60). In joint exposure analysis, the dementia risk associated with mid‐life depression was attenuated by education ≥8 years.ConclusionNot only late‐life depression, but also depression beginning from midlife is associated with dementia. Genetic and early‐life environmental factors seem not to account for the association. Higher education might buffer the impact of mid‐life depression on dementia.
Masupirdine (SUVN‐502): A promising clinical candidate for the management of agitation in Alzheimer’s dementia
Authors: Nirogi Ramakrishna , Jayarajan Pradeep , Tadiparthi Jayaprakash , Shinde Anil K , Rasheed Mohammed Abdul , Goyal Vinod Kumar , Bhyrapuneni Gopinadh , Benade Vijay , Palacharla Veera Raghava Chowdary , Ravula Jyothsna , Jetta Satish 
Published: December 2021

AbstractBackgroundMasupirdine is a potent and selective 5‐HT6 receptor antagonist and has completed Phase‐2 clinical proof of concept studies in patients with Alzheimer’s type dementia. 5‐HT6 receptors are G‐protein coupled receptors mainly localized in the brain regions primarily involved in cognition and behavior i.e., cortex, dorsal hippocampus and striatum. Evidence from the studies in animal models suggests that 5‐HT6 receptor antagonists may have a potential role in controlling neuropsychiatric behavior such as agitation.MethodMasupirdine has been evaluated in a phase‐2a proof‐of‐concept, 26‐week, randomized, double‐blind, placebo‐controlled, multicenter, parallel groups in United States under active US IND. Sub group analyses has been carried out to evaluate the effects of masupirdine on domains related to agitation/ aggression using Neuropsychiatric Inventory (NPI‐12) scale.Masupirdine was also tested in resident intruder task to evaluate its effects on animal model relevant to aggression. Additionally, masupirdine has been evaluated using microdialysis technique to assess its effect on the modulation of monoaminergic neurotransmitters.ResultIn Phase‐2 clinical study subgroup analyses, masupirdine showed robust efficacy in agitation/aggression scores in subjects who had baseline symptoms of agitation/aggression. The effect observed was greater than the minimum difference observed to be clinically important. Similar beneficial effects were observed on extended composite NPI‐12 score related to agitation/ aggression (agitation/ aggression + aberrant motor behavior + sleep and nighttime behavior disorder). Masupirdine was found to be safe and well tolerated in this study. In preclinical animal models, masupirdine reduced the aggressive behaviour in resident intruder task and increased neurotransmitters with role in modulation of agitation and aggression.ConclusionMasupirdine showed clinically meaningful improvement in the neuropsychiatric symptoms associated with agitation/aggression in patients with AD and reduced aggression in animal models. Masupirdine could be a differentiated novel therapeutic option for the management of agitation/ aggression in Alzheimer’s patients.
Idiopathic normal pressure hydrocephalus with synucleinopathy: Diagnosis and treatment
Authors: Han Sang‐Won , Park Young Ho , Ryoo Nayoung , Kim Kitae , Pyun Jung Min , Kim Sangyun 
Published: December 2021

AbstractBackgroundIdiopathic normal pressure hydrocephalus (iNPH) is characterized by the classic triad of gait disturbance, urinary incontinence, and cognitive impairment in the presence of ventriculomegaly, which is ameliorated by the removal of CSF, and is diagnosed by excluding known risk factors for communicating hydrocephalus including meningitis, traumatic brain injury, subarachnoid hemorrhage, and brain irradiation. Shunt surgery is indicated for iNPH patients who respond to the removal of CSF.MethodA 70‐year‐old man presented with a 2‐year history of progressive disturbances of gait, balance, control of urination, and cognition. His family reported that he exhibited dream enactment behavior. Brain MRI showed enlarged lateral ventricles and disproportionately enlarged subarachnoid space hydrocephalus. Although our iNPH patient whose gait disturbance was improved by lumbar puncture with CSF removal, FP‐CIT PET showed reduced DAT binding bilaterally throughout the striatum, including the caudate nucleus and the putamen.ResultIt is known that patients with iNPH present with normal presynaptic DAT binding in the striatum. However, although our iNPH patient’s gait disturbance was improved by LP with CSF removal, FP‐CIT PET showed reduced DAT binding throughout the striatum. Given that 25% of iNPH patients who underwent shunt surgery were revealed to have a diagnosis other than iNPH, we supposed our patient might have a concomitant neurodegenerative disorder affecting presynaptic nigrostriatal neurons. His dream enactment behavior suggests underlying synucleinopathy. Recently, Broggi et al. reported that the striatal dopaminergic deficit on DAT scan was common (46.7%) in patients with iNPH. And the long‐term outcome of shunt surgery of patients with abnormal DAT scan was not favorable.Furthermore, it is also known that the improvement of gait after the removal of CSF rarely persists for more than a few days in patients with iNPH. However, the response after CSF removal sometimes could be sustained, as in our patient, for a few months, which might be attributed to the elasticity of the ventricular wall.ConclusionFor iNPH patients with clinical features suggesting synucleinopathy such as REM sleep behavior disorder, DAT scan could be considered to identify concurrent synucleinopathy before shunt surgery, even in cases with initial response to high‐volume lumbar puncture.
Development of educational system for paramedics specializing to dementia elderlies analyzed by artificial intelligence and its learning effects
Authors: Honda Miwako , Une Saki , Gineste Yves , Nakazawa Atsushi 
Published: December 2021

AbstractBackgroundWhile the number of emergency transfer of dementia elderlies to acute care hospitals has being increasing, paramedics are facing challenges to perform their duties promptly due to difficult communication with patients.ObjectivesTo develop the standardized educational system for paramedics specializing to dementia elderlies with the use of artificial intelligence.DesignSingle arm, pre‐post study. Participants are paramedics in a metropolitan area of Japan.ExposureThe two sessions of standardized multimodal communication training program which contains lecture and workshop were provided twice, 1 month apart. The training consists three parts. 1: Mechanism and clinical manifestations of dementia, 2: Communication skills: face‐to‐face interaction; mutual gaze, geometric characteristics and duration of eye contact, verbal communication with phonetic elements, and touch interactions. 3: Interaction strategies with dementia elderlies in emergency situation. All participants performed the rescue simulation training before the training and 1 month after the completion of the training, which were video‐recorded and analyzed by artificial intelligence (AI). The video was taken by wearable camera with eye‐trackers (1st person camera) and fixed camera (3rd person camera). The satisfaction survey of effectiveness on their work and the Jefferson Scale of Empathy for healthcare professionals were also taken.Main OutcomesThe primary outcome is the change of communication skills in physical position, distance, eye contact with patients, phonetic elements and touch. The system to analyze face‐to‐face communication; mutual gaze, geometric characteristics and duration of eye contact by AI was developed by our team. Other elements of communications were evaluated manually. Secondary outcome were satisfaction and the empathy to patients.Result31 paramedics enrolled the study. Prior to the training, 88% had experienced any difficult condition taking care of dementia patients. The video analysis showed significant change of the interactive communication in the direction of approach, eye contacts and duration of mutual gaze. 96.7% considered the training was effective for their daily work and 97.5% of participants recommended this training to a colleague. The score of empathy scale showed no significant change.ConclusionThe educational system for paramedics specializing to dementia with the use of artificial intelligence is effective for their work.