bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abnormal thickening and thinning of the cerebral cortex in idiopathic normal‐pressure hydrocephalus
Authors: Kang Kyunghun , Han Jaehwan , Yoon Uicheul , Lee Ho‐Won , Lee Sang‐Woo , Jeong Shin Young 
Published: December 2020

AbstractBackgroundWe investigated differences in cortical thickness utilizing automated surface‐based cortical thickness analysis in 2 groups: idiopathic normal‐pressure hydrocephalus (INPH) patients who had a positive response to the cerebrospinal fluid tap test and healthy controls. We also explored whether a relationship exists between cortical thinning and gait disturbance in INPH patients. We hypothesized that INPH patients might show a characteristic pattern of cortical thickness change and that there may be unique relationships between cortical thinning and gait disturbance in INPH patients.MethodForty‐nine INPH patients and 26 healthy controls were imaged with MRI, including 3‐dimensional volumetric images, for automated surface‐based cortical thickness analysis across the entire brain. Gait disturbance features related to INPH were determined using the Gait Status Scale (GSS).ResultCompared with age‐ and gender‐matched healthy controls, unexpectedly, INPH patients showed statistically significant cortical thickening mainly in areas located in the high convexity of the frontal, parietal, and occipital regions. Additionally, cortical thinning mainly in temporal and orbitofrontal regions was observed in the INPH group relative to the control group. The GSS scores were negatively correlated with cortical thickness in the medial orbital part of the superior frontal gyrus, gyrus rectus, superior temporal gyrus, temporal pole, and insula.ConclusionA distinctive pattern of cortical thickness changes was found in INPH patients. We cautiously suggest that cortical thickening in INPH can result from reactive gliosis. Further, our results support the hypothesis that cortical thinning in INPH can result from neuronal degeneration. In addition, cortical thinning can play an important role in gait disturbances in INPH patients.
Clinical and biomarker trajectories in sporadic Alzheimer's disease: A longitudinal study
Authors: Yu Jin‐Tai , Wang Hui‐Fu , Shen Xue‐Ning , Li Jie‐Qiong , Suckling John , Tan Chen‐Chen , Wang Yanjiang , Feng Lei , Zhang Can , Tan Lan , Dong Qiang , Touchon Jacques , Gauthier Serge ,   Alzheimer’s Disease Neuroimaging Initiative
Published: December 2020

AbstractBackgroundIt has been documented that β‐amyloid (Aβ) deposition, tau pathology and neuronal degeneration precedes clinical symptoms in autosomal dominant Alzheimer's disease (AD). Since the divergence on pathogenesis between sporadic and familial AD limits the extension of these findings to sporadic AD, where and magnitude of pathologic processes in sporadic AD are of significant importance to clinical management.MethodIn this longitudinal study, we analyzed data from 982 ADNI participants with abnormal amyloid accumulations who underwent cerebrospinal fluid (CSF) test, brain imaging and cognitive assessments. We compared the levels of clinical outcomes and biomarkers at baseline and the rates of change in follow‐up between different stages of AD. The slope of the regression model over years was applied to estimate rates of change for Aβ deposition, tau alteration, hypometabolism, brain atrophy, and cognitive decline.ResultIn total 167 healthy controls, 133 patients with preclinical AD, 451 patients with MCI due to AD, and 231 patients with dementia due to AD were studied. The levels of clinical and biomarkers at baseline and their change rates at follow‐up significantly differed among the four groups. In terms of average years, Aβ deposition was observed over a range of 45·6 years for CSF Aβ, and 31·1 years with amyloid imaging, although Aβ markers began to be abnormal at 27·8 years for CSF Aβ and 26·3 years for neuroimaging. When Aβ markers exceeded the threshold, CSF tau and other non‐ Aβ markers started to change, and patients were estimated to take 29·1 years (CSF tau),12·7 years (memory), 12·2 years (hippocampus atrophy), 10·1years (hypometabolism) to transition from clinically normal to dementia. Finally, CSF p‐tau significantly increased as dementia onset approached.ConclusionOur results reveal the trajectory of biomarkers in sporadic Alzheimer's disease is led by Aβ accumulation, followed by CSF tau change, memory deficits, brain atrophy, hypometabolism, cognitive decline, and lastly CSF p‐tau increase.
Cultural adaptation of the Tailored Activity Program (TAP) in Chile: Implementation challenges and pilot testing
Authors: Gajardo Jean , Aravena Jose , Navarrete Ignacia , Slachevsky Andrea , Gitlin Laura N 
Published: December 2020

AbstractBackgroundThe Tailored Activity Program (TAP) provides people with dementia with activities tailored to their capabilities and trains caregivers in their use. The TAP has been previously cross‐culturally adapted in different settings and countries. This study was aimed to develop a cultural adaptation of the TAP in Santiago, Chile.MethodComplementary mixed‐method study following the 4‐phase Dynamic Adaptation Process (DAP) model (Aarons et al, 2012). Qualitative data was collected by conducting 1) interviews and ethnographic observation with caregivers, 2) weekly follow‐up meetings to provide ongoing feedback, and 3) a focus group with provider occupational therapists after the Implementation phase based on the DAP. Grounded theory (Strauss & Corbin, 1998) was used to guide qualitative analysis, to access the experiences of caregivers and providers, and to identify and describe adaptations and implementation outcomes based on the Framework and Coding System for Modifications and Adaptations of Evidence‐based Interventions (Stirman et al, 2013). Quantitative data for pilot testing was obtained through assessments at baseline and after intervention. Wilcoxon‐test and T‐test at p<0.05 were used to estimate the effect of the intervention on outcomes. Ethical approval was granted by the Ethics Scientific Committee "Servicio de Salud Metropolitano Oriente" in June 2017.ResultTen dyads (family caregivers and people with dementia) were recruited in this study after being referred from a neurologist specialized in dementia and they completed a regular 8‐session home‐based intervention of the TAP during 2017‐2018. Content, context, target level, and training adaptations were identified. After intervention, there was a statistically significant reduction on the number and severity of neuropsychiatric symptoms among individuals with dementia. Caregivers reported reduced depressive symptoms, improved perceived well‐being, and improved self‐confidence.ConclusionSociocultural adaptations were identified in the adaptation of the TAP to the local context in Chile. The TAP was highly accepted by participants, especially caregivers, who acknowledged its personalized problem‐solving approach and positive effects. Positive outcomes were shown in both people with dementia and caregivers, in consistence with previous studies.
Evaluation of extracellular vesicles isolated from the cerebrospinal fluid and plasma from former National Football League players at risk for chronic traumatic encephalopathy
Authors: Muraoka Satoshi , Jedrychowski Mark P. , Yang Zijian , Tatebe Harutsugu , DeLeo Annina M. , Yukawa Kayo , Ko Jina , Wang Katherine , Ikezu Seiko , Gygi Steven , Issadore David , Tokuda Takahiko , Stern Robert A , Ikezu Tsuneya 
Published: December 2020

AbstractBackgroundChronic Traumatic Encephalopathy (CTE) is a tauopathy that affects individuals with a history of mild repetitive brain injury frequently seen in contact sports. Initial neuropathologic change of CTE consists of perivascular deposition of phosphorylated tau (p‐tau) in cortical neurons. Tau pathology progresses to form neurofibrillary tangles in neurons throughout the brain in later stages when patients show more clinical symptoms. Extracellular vesicles (EV) are known to carry neuropathogenic molecules in neurodegenerative disease and able to cross the blood brain barrier. We therefore examined the protein composition of EV separated from cerebrospinal fluid (CSF) and plasma in former NFL players with cognitive dysfunction, and an age‐matched controls.MethodEVs were separated from CSF and plasma from former NFL players (n=4, 14) and controls (n=5, 12) by affinity separation or size exclusion chromatography, respectively. The EV protein profiling was characterized by SIMOA for tau and p‐tau and mass spectrometry. The protein data was analyzed for EV enrichment, differentially expressed proteins, pathway analysis and correlation with cognitive function, head impact and tau/p‐tau levels by biostatistics and bioinformatics.ResultThe level of t‐tau and p‐tau in plasma EVs from former NFL players was significantly elevated although there was no significant change in CSF EV compared to the control. The 95 proteins were commonly identified between the paired plasma‐CSF from the same patients, but there was no significant correlation with the disease status. Collagen alpha‐3(VI) chain (COL6A3), ‐1(VI) chain (COL6A1) and Reelin (RELN) were differentially expressed in former NFL players’ plasma EVs. A combination of these 3 proteins in plasma EV was able to distinguish former NFL players from controls with 85% accuracy by machine learning.ConclusionThese data suggest that COL6A3, RELN and COL6A1 in plasma EV can be potential biomarker for monitoring the CTE development. We need further evaluation of CSF EV by increasing the sample number size in future studies.
Estimating the global mortality from Alzheimer’s disease and other dementias: A new method and results from the Global Burden of Disease study 2019
Authors: Nichols Emma , Vos Theo 
Published: December 2020

AbstractBackgroundAlzheimer’s disease and other dementias (dementia) is currently a leading cause of mortality and morbidity globally, and the total number of individuals effected by dementia will likely increase in the future with corresponding increases in population growth and aging. However, inconsistencies in coding practices in vital registration systems both over time and between countries complicate the estimation of dementia mortality. This study updated and improved on previous methods developed for the Global Burden of Disease (GBD) study for the estimation of global dementia mortality.MethodWe conducted a systematic review on the excess risk of death in those with dementia, and analyzed these data using a Bayesian meta‐regression model. We calculated total excess deaths as the product of absolute risk and country‐by‐country prevalence estimates from the GBD study. We then multiplied the estimates of total excess deaths by the proportion of dementia deaths that occur in those with severe, end‐stage disease to calculate the total number of deaths that could be legitimately assigned to dementia as the underlying cause of death.ResultAttributable risk of dementia increased with age, reaching 0.17 (95% uncertainty interval, 0.05 to 0.58) in the 95+ age group. We estimated there were 1.55 (0.35 to 4.54) million deaths globally due to dementia in 2019. Far more deaths occurred in women (1.02 million; 0.23 to 2.96) than men (0.54 million: 0.12 to 1.58), giving a female to male ratio of 1.90 (1.82 to 1.99). Due to population aging, the all‐age mortality rates increased by 38.0%; 33.1 to 43.7 between 1990 and 2019.ConclusionThe increase in the number of dementia deaths will continue due to population aging. Given the rising volume of dementia mortality, the development of valid methods of mortality estimation for dementia is critical. This updated estimation method eliminated all dependency on estimates from vital registration systems, which are known to be biased. However, future efforts should aim to further strengthen this analysis in order to provide more accurate information on dementia mortality for use by both researchers and policy‐makers.
Generation of nonhuman primate models of Alzheimer’s disease
Authors: Sasaguri Hiroki , Sato Kenya , Kumita Wakako , Nagata Kenichi , Sakuma Tetsushi , Yamamoto Takashi , Saido Takaomi C. , Sasaki Erika 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of dementia worldwide. Despite the considerable research efforts, exact pathomechanisms still remain unknown, and no effective treatment is available. AD research field have mainly utilized mouse models for decades, but species differences between rodents and primates may constrain us from understanding the precise disease mechanisms.MethodWe utilized Transcription Activator‐Like Effector Nuclease (TALEN) to delete the 3’ splicing site (SS) of exon 9 of the presenilin 1‐encoding gene (PSEN1) in the common marmoset (Callithrix jacchus), a small new world primate.ResultWe successfully deleted the 3’ SS of the PSEN1 gene (PSEN1‐ΔE9) in the marmoset embryos by microinjection of TALEN, and obtained mutant PSEN1 neonates. Sequence analysis of mRNA in these embryos and neonates confirmed skipping of exon 9 as expected, which has been reported as a pathogenic mutation causing familial AD. Quantitative analysis of amyloid‐β (Aβ) in the cultured medium of primary fibroblasts revealed elevation of Aβ42/Aβ40 ratio in PSEN1‐ΔE9 fibroblasts. WB analysis detected un‐cleaved full‐length PS1 protein as well as N‐ and C‐terminal fragments of PS1 protein in the PSEN1‐ΔE9 fibroblasts.ConclusionTo our knowledge, we have successfully generated the word’s first AD model of non‐human primates. These animals are expected to show early amyloid pathology in the brain and to contribute to cutting‐edge research to elucidate primate‐specific mechanism in AD. In addition, we will make the mutant animals available to researchers worldwide in the fight against AD in the future.
Big data analysis of Korea health insurance review and assessment service for prescription quantity and cost of drugs on types of dementia from 2017 to 2019
Authors: Eun Hun Jeong , Choi Mal Rye , Kim Hyun Gi 
Published: December 2020

AbstractBackgroundRecently, the Republic of Korea has entered the aging society, and the diagnosis rate for dementia is increasing, and the number of prescription drugs is increasing accordingly. Therefore, this study intends to study the number of prescriptions and the cost of prescription according to the detailed type of dementia by using big data of Korea Insurance Review & Assessment Service.MethodAuthors visited the Big Data Hub at Korea Health Insurance Review & Assessment Service homepage. After extracting data on the prescription quantity and cost of drugs for 3 years from 2017 to 2019 for dementia subtypes(F00, F01, F02, F03) in Big Data Homepage, the data were analyzed and statistically verified using Microsoft Excel and IBM SPSS version 23.0. Jonckheere‐Terpstra test for hypothesis evaluation applicated. The currency exchange rate was 1170.24 Korean won per 1 US dollar as of January 25, 2020 ICD‐100(WHO 2007 version) Diagnostic criteria including F00 Dementia in Alzheimer`s disease(G30), F01 Vascular dementia, F02 Dementia in other diseases classified elsewhere, F03 Unspecified dementia were applicated.ResultPrescription Quantity from 2017 to 2019: 2017 F00 3,498,000,000 F01 302,024,085 F02 16,392,196 F03 109,765,584 2018 F00 40,602,837 F01 4,206,130 F02 3,009,702 F03 1,795,276 2019 F00 51,654,756 F01 3,229,505 F02 281,612 F03 1750040. Cost of Drugs from 2017 to 2019: 2017 F00 19,810,000,000won F01 1,985,000,000won F02 102,331,031won F03 713,251,799won 2018 F00 23,000,000,000won F01 2,340,000,000won F02 116,000,000won F03 771,000,000won 2019 F00 27,868,782,161won F01 1,709,269,727won F02 113,159,188won. Average Prescription Quantity Number for 3 years(p=0.602): F00 : 1,196,752,531 F01 : 103,153,240 F02 : 6,561,170 F03 : 37,770,300. Average Cost of Drugs for 3 years(p=0.602) : F00 : 23,559,594,054 Korean won(20,132,275.48 US dollar), F01 : 2,011,423,242 Korean won(1,718,812.59 US dollar), F02 : 110,496,740 Korean won(94,422.29 US dollar), F03 : 740,454,665 Korean won(632,737.44 US dollar).ConclusionFrom 2017 to 2019, drug prescriptions and medication costs are on the rise. Prescription and cost of dementia by type of dementia were highest in F00 Dementia in Alzheimer's disease (G30), followed by F01 Vascular dementia, F03 Unspecified dementia, and F02 Dementia in other diseases classified elsewhere.
Environmental toxicity exposure and ability to perform instrumental activities of daily living in several U.S. geographic locations
Authors: Feger Danielle M , Corrigan Anne E , Crane Breanna M , Carlson Michelle C 
Published: December 2020

AbstractBackgroundInstrumental activities of daily living (IADLs) are complex tasks important for independent living, such as cooking, shopping, and managing finances. Older adults may report difficulty performing IADLs in preclinical dementia or mild cognitive impairment (MCI). Cognitive function has been shown to be lower in individuals with increased environmental toxicity exposure. However, little is known about an individual’s environmental toxicity exposure in relation to their ability to perform IADLs. We hypothesize that older adults with greater environmental toxicity exposure will be more likely to report difficulty performing IADLs.MethodParticipant data (N=3578) were from the baseline year (1990) of the Cardiovascular Health Study (CHS). Average environmental toxicity exposure was estimated for each participant using 1990 data from the US Environmental Protection Agency Risk‐Screening Environmental Indicators (RSEI) model. Six IADLs were measured; IADL performance was discretized as 1 = proficient (no self‐reported difficulty performing any IADLs), and 0 = not proficient (any self‐reported difficulty). Average toxicity exposure was base‐10 log transformed to aid in model fitting. Univariate and multivariate logistic regression models estimated the relationship between environmental exposure and IADL proficiency; multivariate models were adjusted for participant age, sex, race, education, income, baseline Modified Mini‐Mental State score, and cohort recruitment site.ResultIn the univariate model, higher toxicity concentration was associated with decreased odds of IADL proficiency (OR=0.79, p<0.001). After adjustment, no significant relationship between toxicity exposure and IADL difficulty was observed (OR=0.929, p=0.553); however, individuals in North Carolina were less likely to report being proficient in all IADLs relative to those in California (OR=0.657, p=0.013), and individuals in Maryland were marginally less likely to report full IADL proficiency relative to those in California (OR=0.736, p=0.098).ConclusionIndividuals in North Carolina and Maryland were less likely to successfully perform all IADLs, even after adjustment for possible confounders. Ability to perform IADLs is critical for maintaining older adults’ independence, yet geographic location is rarely considered as a potential risk factor for IADL difficulty. It is unclear what factors beyond socioeconomic status contributed to observed regional disparities.
Evaluating everyday preferences assessment over time between people with cognitive impairment and their care partners
Authors: Wilkins James M , Okereke Olivia I 
Published: December 2020

AbstractBackgroundAs cognitive impairment progresses, people with cognitive impairment and dementia increasingly rely on surrogate decision‐makers for everyday activities. Yet, little is known about concordance over time on assessment of everyday preferences between persons with cognitive impairment and their care partners, acting as proxies.MethodThe sample included 44 dyads of persons with cognitive impairment (Clinical Dementia Rating Scale ≥ 0.5) and their care partners. We used the Preferences for Everyday Living Inventory (PELI) to assess preferences for activities and lifestyle choices among persons with cognitive impairment. The PELI was concurrently but separately administered to care partners, who answered as proxies. Assessments were completed at baseline and again approximately one year later. Paired sample t‐tests were used to assess for changes in repeat measures as well as to estimate differences in preference assessment between self‐ratings of persons with cognitive impairment and proxy‐ratings of care partners at baseline and one‐year follow‐up.ResultOur previous factor analysis of the 55‐item PELI identified four factors: autonomous choice, social engagement, personal growth, and keeping a routine. Within each factor of the PELI, there appeared to be consistency in self‐ratings for persons with cognitive impairment and proxy‐ratings by care partners between baseline and annual follow‐up (paired t‐test, p‐value > 0.05; Pearson correlation, r > 0.7). Comparing self‐ratings from persons with cognitive impairment and proxy‐ratings by their care partners, however, there was significant discrepancy for preferences related to “social engagement” (e.g., regular contact with family, meeting new people, volunteering) at baseline and one‐year follow‐up (paired t‐test, p‐value < 0.05). There did not appear to be significant differences by paired t‐test (p‐value > 0.05) with respect to the raw change scores from baseline and one year‐follow within each PELI factor.ConclusionThis study yields new insights regarding the stability of everyday preferences for persons with cognitive impairment over time as well as apparent stability in areas of significant discrepancy between self‐ratings of persons with cognitive impairment and the proxy‐ratings of care partners.
Gut microbiota interacts with intrinsic brain activity of patients with amnestic mild cognitive impairment
Authors: Peng Guoping 
Published: December 2020

AbstractBackgroundTo explore the potential relationships among gut microbiota (GM), local brain spontaneous activity and neuropsychological characteristics in amnestic mild cognitive impairment (aMCI) patients.MethodTwenty aMCI and 22 healthy control (HC) subjects were recruited. The GM composition was determined by 16S ribosomal RNA gene sequencing. Resting‐state functional magnetic resonance imaging scans were performed, and fractional amplitude of low‐frequency fluctuations (fALFF) was calculated across different frequencies. Spearman or Pearson correlation analysis was used to analyze the relationship between spontaneous brain activity and cognitive function, GM composition.ResultaMCI patients had altered GM state and local spontaneous brain activity as compared with HC subjects. Correlation analysis showed that aMCI and HC groups had different “GM–intrinsic brain activity interaction” patterns. In aMCI group, the relative abundance (RA) of Bacteroides from phylum to genus level was positively correlated with fALFF value in the right middle temporal gyrus in slow 4 and negatively with that of cerebellar vermis in typical band. The Clostridiaceae RA was positively correlated with the fALFF value of the right lingual gyrus in the typical band (0.01‐0.08 Hz). The Clostridiaceae and Blautia RA was positively correlated with the fALFF value of the left cerebellum in slow 4 (0.027–0.073 Hz). At slow 5 (0.01–0.027 Hz), the Firmicutes RA was negatively correlated with the fALFF value in the right inferior frontal gyrus. Correlation analysis showed that Clostridium members (Lachnospiraceae and Blautia) were positively while Veillonellaceae was negatively linked with cognition test. While Bacteroides was positively correlated with attention and computation, and negatively correlated with the three‐step command score.ConclusionaMCI patients have a specific GM‐intrinsic brain activity‐cognitive function interaction pattern.