bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thalamic‐insomnia phenotype in genetic E200K Creutzfeldt‐Jakob disease: A PET/MRI study
Authors: Chu Min , Chen Zhongyun , Xie Kexin , Ye Hong , Wu Liyong 
Published: June 2023

AbstractBackgroundInsomnia and thalamic involvement are hallmarks of fatal familial insomnia; however, it was occasionally reported that genetic E200K Creutzfeldt‐Jakob disease (CJD) patients had also manifested thalamic‐insomnia phenotype. The study aimed to explore the clinical and neuroimage characteristics of genetic E200K CJD by comprehensive neuroimage analysis.MethodsSix genetic CJD patients carried Glu to Lys change at codon 200 (E200K) mutations on prion protein gene (PRNP), thirteen sporadic CJD (sCJD), and twenty‐two age‐ and sex‐matched normal controls were enrolled in the study. All participants completed hybrid positron emission tomography/ magnetic resonance imaging (PET/MRI) examinations. The high signal was visually inspected on diffusion weighted imaging (DWI) sequence. 18F‐fluorodeoxyglucose positron emission tomography (18F‐FDG‐PET) and structural images were quantitively analyzed by statistically parameter mapping (SPM). Clinical and image characteristics are compared between genetic E200K CJD patients and sporadic CJD patients.ResultsThere was no group difference in age (49.0±7.1 versus 55.0±4.9 versus 52.7±7.3, p = 0.193) and gender (3/3 versus 4/9 versus 11/11, p = 0.513) between genetic E200K CJD, sCJD, and normal controls. Insomnia was the main complaint in the genetic E200K CJD patients’ group (4/2 versus 1/12, p = 0.007). Hyperintensity, hypometabolism but not predominant atrophy of the thalamus was found by visual inspection in genetic E200K CJD patients. A decreased trend was found on gray matter volume (uncorrected p<0.0001) and metabolism (FWE corrected) of the thalamus in genetic E200K patients.ConclusionThe clinical and image characteristics of genetic E200K CJD mimic fatal familial insomnia, manifested as a thalamic‐insomnia phenotype, indicating some specific underlying pathological changes might exist in E200K mutations. PET measurement is a sensitive approach to help identify the functional changes of the thalamus in prion disease.
Erythrocyte indices in creutzfeldt–jakob disease predict survival time
Authors: Kong Yu , Chen Zhongyun , Zhang Jing , Wu Liyong 
Published: June 2023

AbstractBackgroundCreutzfeldt–Jakob disease (CJD) is a devastating neurodegenerative disease caused by propagation of abnormally folded prion proteins (PrPSc). Some fluid biomarkers have been reported to be associated with disease duration in CJD. Based on studies which have found that prion protein (PrPC) played a role in erythrocytic hematopoiesis, we evaluated the association between peripheral red blood cell indices and survival time in CJD.MethodWe retrospectively collected data on peripheral red blood cell indices, including red blood cell (RBC) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW), from 125 CJD patients. Cox proportional hazard models were generated to determine whether red cell indices correlated with survival time of patients with CJD.ResultOf the 125 included participants, 70 (56%) were male, and the mean age at diagnosis (SD) was 60.3 (9.5) years. Hemoglobin levels (hazard ratio 1.710, 95% CI 1.124‐2.600, p = 0.012) and HCT (hazard ratio 1.689, 95% CI 1.112‐2.565, p = 0.014) were significantly associated with survival time after controlling for sex, age, and Barthel Index. Red blood cell count, MCV, MCH, MCHC, and RDW were not associated with survival time before or after adjusting for covariates.ConclusionOur study found that Hb and HCT were significantly associated with survival time in patients with CJD. These results may inform evaluation of the mechanisms of interaction between prion disease and hematopoiesis, and indicate that Hb and HCT may be potential prognostic biomarkers.
Predicting cognitive decline using neuropsychiatric symptoms in prodromal Lewy body disease
Authors: Wright Laura M , Donaghy Paul , Burn David , Taylor John‐Paul , O'Brien John T , Yarnall Alison J , Matthews Fiona E , Firbank Michael J , Thomas Alan J , Lawson Rachael A 
Published: June 2023

AbstractBackgroundNeuropsychiatric symptoms (NPS) in Lewy body diseases, including dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) dementia, occur frequently and at an early stage in disease progression. Such symptoms are significantly associated with quality of life, caregiver burden and functional limitations. Limited evidence exists, however, outlining the relationship between NPS and cognitive decline.MethodsData from 217 participants were derived from three cohort studies. Patients diagnosed with either MCI with Lewy bodies (MCI‐LB, n = 67), PD‐MCI (n = 56) or Alzheimer’s disease (MCI‐AD, n = 39) and a group of healthy older adults (n = 55) completed comprehensive neuropsychological and neuropsychiatric assessment and were followed up longitudinally for a median of three years. NPS identified at baseline by the Neuropsychiatric Inventory (NPI) were included as predictors in linear regressions and linear mixed effects models to assess the relationship between NPS and performance on a range of cognitive tests both at baseline and longitudinally.ResultsAt baseline, NPS were most prevalent and severe among the MCI‐LB group (49% with NPI score >4 in at least one symptom) and least prevalent in controls (7% with NPI score >4). Total NPI score was not related to baseline cognitive function in any domain in any group. Greater baseline total NPI score was associated with steeper rates of decline among PD‐MCI patients on a measure of processing speed (p = .01). Among healthy adults, only sleep disturbance was associated with steeper rates of decline on global cognition (p = .005). None of the patient groups showed any association between individual NPS and decline on a measure of global cognitive function.ConclusionsThe lack of a significant relationship found between NPS and either global cognitive function or decline in global cognition seen among MCI patients suggests that at this prodromal stage of disease, NPS appear to be of limited clinical impact and indicates that the mechanisms of cognitive and neuropsychiatric symptoms may differ in early Lewy body disease. Future work will investigate these mechanisms using multimodal imaging data from this cohort.
Mortality across the Alzheimer’s disease clinical stages: An analysis using the U.S. National Alzheimer’s Coordinating Center Uniform Data Set
Authors: Crowell Valerie , Reyes Adriana , Gustavsson Anders , Gsteiger Sandro , Zhou Summera , Vassilaki Maria 
Published: June 2023

AbstractBackgroundUnderstanding mortality risk across the Alzheimer’s disease (AD) clinical stages is essential for resource planning and estimating the value of disease modifying therapies (DMTs), which may slow progression. Such studies are lacking.MethodThe study used the Uniform Data Set of the National Alzheimer’s Coordinating Center (NACC) from September 1, 2005 to March 1, 2021 to assess mortality risk across the AD clinical stages. It included 12,414 participants aged ≥ 50 years, who contributed to the following stages: cognitively unimpaired (CU n = 11,458), incident prodromal AD (n = 937), and AD dementia (n = 745). AD etiology and stage were established based on clinical evaluation and cognitive, behavioral, and functional scores. Study centers report mortality for actively followed participants. Participants contributed observation time until all‐cause death, disease progression, discontinuation, loss to follow‐up, data cutoff or the last visit before a longer than 36‐month gap in visits or recorded scores.Hazard ratios for each AD stage versus CU were estimated using Cox proportional hazards models. Least absolute shrinkage and selection operator facilitated final predictor selection.ResultParticipants’ mean age (SD) at study entry was 71.0 years (SD 9.2) (34.9% males). Participants with incident mild, moderate, and severe AD had increased mortality risk relative to CU after controlling for age, sex, education, apolipoprotein E ε4 genotype status, BMI, and residence type. Relative all‐cause mortality risk by AD stage decreased with increasing age; the HRs (95% CI) for mortality at 65 years of age were 6.7 (2.7‐16.9), 14.8 (8.8‐24.8), and 30.1 (16.7‐56.8) for mild, moderate and severe AD respectively; at 80 years of age, the corresponding HR (95% CI) were 2.4 (1.7‐3.3), 3.1 (2.4‐3.9), and 6.6 (4.8‐9.1). Male sex (HR = 1.75, 95% CI 1.52‐2.04) and residing in an institution (vs. private residence; HR = 3.11, 95% CI 2.28‐4.25) significantly increased relative all‐cause mortality risk.ConclusionRelative all‐cause mortality risk increases with AD severity, and more so at younger ages. Despite data limitations, findings are significant as efforts to delay disease, for instance with DMTs, could not only improve patient and caregiver quality of life and reduce costs, but also extend the lives of patients with AD.NIA/NIH Grant U24 AG072122 funds the NACC database.
The associations of SNAP use and memory function among us older adults: Findings from the health and retirement study
Authors: Lu Peiyi , Kezios Katrina L , Lee Jongseong , Wimer Christopher T , Hazzouri Adina Zeki Al 
Published: June 2023

AbstractBackgroundStudies on the health effect of Supplemental Nutrition Assistance Program (SNAP) on the cognitive health of older adults are scarce. In this study, we examined the associations of SNAP use and memory function trajectories among US older adults.MethodOur sample included 3,555 SNAP‐eligible participants (aged 50+) from the 1996 Health and Retirement Study survey, among whom 559 were SNAP users and 2,996 were non‐users. SNAP eligibility was constructed based on household income and assets compared to the federal criterion. Memory function was assessed biennially from 1996 through 2016. To account for pre‐existing differences in characteristics and variations in survey attrition between SNAP users and non‐users, we modeled the probability of SNAP use and of attrition using pre‐SNAP exposure (i.e., 1994) demographic and health covariates. We then modeled trajectories of memory function across SNAP use using linear mixed effect models weighted by the inverse probability of treatment (i.e. SNAP use) and of attrition. We also cross‐examined the results in a propensity score (PS) matched sample (N = 1,050).ResultSNAP users in 1996 had lower socioeconomic status and worse health at baseline than SNAP non‐users, and were more likely to be lost to follow‐up. Results using IP‐weights suggested SNAP users had worse memory scores at baseline but slower memory decline compared with non‐users (annual decline rate is ‐0.038 standard units [95%CI = ‐0.044, ‐0.033] for non‐users and ‐0.043 [95%CI = ‐0.046, ‐0.040] for users). Results from the PS‐matched sample also showed SNAP users had slower memory declines compared with non‐users (annual decline rate was ‐0.052 units [95%CI = ‐0.055, ‐0.050] for non‐users and ‐0.048 units [95%CI = ‐0.051, ‐0.046] for users).ConclusionAfter accounting for pre‐existing differences between eligible SNAP users and non‐users as well as differential loss to follow‐up, our findings suggested that SNAP participation is associated with slower memory decline among eligible older adults.
Consensus harmonization of brain‐secreted extracellular vesicles isolation and validation protocols for blood biomarker work in Alzheimer’s disease: An international overview
Authors: Badhwar AmanPreet , Hirschberg Yael , Sukreet Sonal , Udeh‐Momoh Chi T. , Iulita M. Florencia , Sandebring‐Matton Anna , Winston Charisse N. , Haqqani Arsalan S. ,   Exosome Working Group (EWG) of the Biofluid‐Based‐Biomarkers Professional Interest Area (BBB‐PIA) of the Alzheimer’s Association
Published: June 2023

AbstractBackgroundIsolation of brain‐secreted extracellular vesicles (BEVs) from blood, provides a novel, minimally invasive way to sample brain tissue in individuals along the Alzheimer’s disease (AD) continuum. BEVs in blood demonstrate enormous potential to serve as a novel AD biomarker discovery platform and treatment tool. However, at present, BEV isolation and validation protocols vary from center to center. Given the growing popularity of immunoprecipitation (IP)‐based BEV isolation methods, we assessed the brain‐specificity of reported cell‐surface and cargo proteins associated with this category of methods.MethodWe performed a systematic evaluation of BEV isolation and validation protocols from 34 published articles investigating biomarker potential of blood‐isolated BEVs in AD. Proteins used for polyethylene glycol‐based precipitation followed by IP‐capture BEV isolation, or as BEV biomarker candidates, were compiled. The proteins were categorized by brain specificity, abundance, extracellular accessibility and extracellular vesicles presence by examining their expression from publicly available datasets in over 60 human tissue types, including 13 central nervous system (CNS) regions and 48 peripheral tissues.ResultWe compiled 68 unique IP or biomarker protein candidates. Analyses demonstrated that of these, 22 had extracellular domains (that could be used for BEV isolation), 7 were membrane proteins lacking extracellular domains, and the remaining were intracellular proteins. Moreover, >50% of the compiled proteins were present in extracellular vesicle datasets, >20% were considered highly CNS specific, and ∼60% demonstrated moderate‐to‐high CNS abundance (Fig.1). Furthermore, in addition to confirming that some proteins widely used for IP‐based BEV isolation are CNS‐enriched (e.g., L1CAM, Fig. 1B), we also identified, at least, 5 additional proteins with higher CNS abundance and specificity, extracellular domains, and known to be present in extracellular vesicles.ConclusionConsensus harmonization of BEV isolation and validation protocols are essential steps in blood‐isolated BEV biomarker work in AD, and is advocated by the Alzheimer’s Association BBB‐PIA. This harmonization of BEV protocols is crucial, given the growing interest in developing minimally‐invasive AD biomarker discovery tools, and the increasing number of researchers worldwide conducting BEV biomarker work. Moreover, the additional proteins identified by the EWG‐BBB‐PIA will lead to better IP‐based BEV isolation from blood.
Using the clock drawing test to differentiate impairments in executive functioning between Alzheimer’s Dementia and Parkinson’s disease
Authors: Bakir Danah , Trivedi Mehul Alkesh , Ala Tom , Zec Ronald F , Kouzi Ahmed El , Agamah Alikem Miriam , Porter Nicholas , Unnam Pavani , Hascup Erin R. , Hollinshead Madison G. , Kohlrus Stephanie R. 
Published: June 2023

AbstractBackgroundPrevious studies suggest the usefulness of CDT in distinguishing between neurodegenerative diseases. The purpose of this study was to examine differences in CDT performance in individuals with AD and PD compared to normal controls.MethodsTotal of 194 participants. Four groups included in analysis: patients that met diagnostic criteria for late MCI/mild AD, moderate AD, PD with no cognitive impairment, and normal controls. All participants completed MMSE and CDT. MMSE score ≤ 23 considered moderate AD, MMSE score >24 considered mixed late MCI/mild AD, all PD patients had MMSE score >24.ResultsAn ANOVA was used to examine group differences in CDT and MMSE scores. There was a significant main effect of group for both CDT and MMSE scores (p < 0.001). Moderate AD group had significantly lower MMSE scores compared to other groups (average MMSE score of 19.4 for moderate AD compared to 26.6 for mild AD, 26.9 for Parkinson’s, and 28.2 for controls). Post‐hoc t‐tests (Bonferroni corrected for multiple comparisons) showed moderate AD group had significantly higher error scores on CDT compared to controls (p<0.001). Moderate AD group also had significantly higher error score compared to both MCI/mild AD and PD patient groups (p<0.001). No statistical significance existed in error scores between MCI/mild AD group compared to controls (p = 0.134) or to Parkinson’s disease (p = 1.000). No statistical significance in CDT error scores between the Parkinson’s group compared to controls (p = 0.904). Findings suggest executive functioning may only begin to significantly decline in advanced stages of AD.ConclusionOur findings suggest that deficits in executive functions measured by CDT is impaired in moderate AD but relatively preserved in MCI/mild AD and PD with no cognitive impairment, which is consistent with previous studies. One limitation of the study is that we did not include a copy trial for the CDT, which may support that our findings are due to executive dysfunction rather than visuospatial deficits. Future directions include increasing sample sizes, including individuals with PD with cognitive impairment, and using novel digital versions of the CDT to different variables of the CDT such as time to start and complete, visuospatial coordination, and graphic size.
Proposal of new clinical diagnostic criteria for fatal familial insomnia
Authors: Chu Min , Xie Kexin , Chen Zhongyun , Zhang Jing , Ghorayeb Imad , Rupprecht Sven , Reder Anthony T , Garay Arturo , Honda Hiroyuki , Nagayama Masao , Shi Qi , Zhan Shuqin , Nan Haitian , Zhang Jiatang , Guan Hongzhi , Cui Li , Guo Yanjun , Wang Jiawei , Dong Xiaoping , Rosa‐Neto Pedro , Gauthier Serge , Wu Liyong 
Published: June 2023

AbstractBackgroundEarly and accurate diagnosis of fatal familial insomnia (FFI) is critical for effective screening; however, this rare disease remains difficult to recognize. This work aimed to propose a new diagnostic criterion for fatal familial insomnia (FFI) with optimal sensitivity, specificity, and likelihood ratio.MethodsAn international group of experts was established and 128 genetically confirmed FFI cases and 281 non‐FFI prion disease controls are enrolled in the validation process. The new criteria were proposed based on the following steps with 2‐round expert consultation: 1) Validation of the 2018 FFI criteria. 2) Diagnostic item selection according to statistical analysis and expert consensus. 3) Validation of the new criteria.ResultsThe 2018 criteria for possible FFI had a sensitivity of 90.6%, specificity of 83.3%, the positive likelihood ratio (PLR) of 5.43, and negative likelihood ratio (NLR) of 0.11; the probable FFI criteria had a sensitivity of 83.6%, specificity of 92.9%, the PLR of 11.77, and NLR of 0.18. The new criteria included more specific and/or common clinical features, 2 exclusion items, and summarized a precise and flexible diagnostic hierarchy. The new criteria for possible FFI had a sensitivity of 92.2%, specificity of 96.1%, a PLR of 23.64, and NLR of 0.08, while the probable FFI criteria had a sensitivity of 90.6%, specificity of 98.2%, the PLR of 50.33, and NLR of 0.095.ConclusionA new clinical diagnostic criteria was proposed for FFI, which will be practical at the clinic for early recognition of FFI and differentiation from other prion diseases then help further referral and genetic test.
Optical coherence tomography in the diagnosis of primery neurodegenerative diseases
Authors: Makhnovich Ekaterina Vladimirovna , Bogolepova Anna Nicolaevna , Andreevna Kovalenko Ekaterina , Alekseevna Osinovskaya Nina 
Published: June 2023

AbstractBackgroundThe priority task of the world community of neurologists is the early diagnosis of dementia, which is associated with an increase in life expectancy of the population. Among all dementias, Alzheimer’s disease occupies a leading position. Existing criteria for Alzheimer’s disease do not allow a diagnosis at the stage of predementia. New predictors of cognitive deficits, as such a method, scientists hope for optical coherence tomography.Method90 patients were examined, divided into 3 groups: the first group ‐ patients with Alzheimer’s disease (AD), meeting the NINCDS ADRDA criteria, the second ‐ patients with vascular dementia (VD), meeting the NINDS‐AIREN criteria. According to the criteria, each group of BA and DM consisted of 21 (70%) women and 9 (30%) men, mean age 65 years [61; 67] ∖ 66 [60; 69] years respectively. The third group included patients with open‐angle glaucoma (POAG) ‐ 20 (66.7%) women and 10 (33.3%) men, mean age 70 years [62; 76] years.ResultAccording to the results of OCT in the area of the optic disc, there were no statistically significant differences in the width of the neuroretinal rim between the groups. In the VAD group, the thickness of the peripapillary layer of nerve fibers in the upper and lower temporal quadrants was greater than in the DA and POAG groups. OCT in the macular region revealed a decrease in the thickness of the retina and the inner plexiform layer in the upper and lower quadrant of the peripheral region, as well as a decrease in the thickness of the nerve fibers, the ganglionic layer in the lower quadrant of the peripheral region in the OP and POAG groups compared with the VAD group.ConclusionBased on the data obtained, it can be concluded that in AD, degenerative changes in the retina are observed in the peripheral region, while in VD, the process is more pronounced in the foveal (central) region of the retina. In conclusion, it should be noted that a comprehensive ophthalmological examination can become one of the key and affordable methods for the early diagnosis of BA.
The cerebrospinal fluid Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB) concentration in Alzheimer’s Disease (AD)
Authors: Doroszkiewicz Julia , Kulczynska‐Przybik Agnieszka , Dulewicz Maciej , Borawska Renata , Slowik Agnieszka , Mroczko Barbara 
Published: June 2023

AbstractBackgroundAlzheimer Disease (AD) is a common neurodegenerative disorder which is the most widespread form of dementia in the world. The disease is characterized by amyloid‐β peptides, phosphorylated tau proteins and neuroinflammation. Because of late manifestation of the disease, it is pivotal to find new biomarkers that can help detect AD in the earliest phases. Glycoprotein nonmetastatic melanoma protein B (GPNMB) is a transmembrane endogenous glycoprotein involved in neuroinflammation. Recent studies have confirmed GPNMB presence in the microglia in AD patients brains, especially near amyloid‐β plaques, although the exact role of this protein in AD is still not fully known. Furthermore, it has been observed that GPNMB may negatively influence secretion of proinflammatory cytokines form macrophages making this glycoprotein possibly protective to neuroinflammation. Thus, the purpose of our research was to measure the concentration of GPNMB in cerebrospinal fluid of AD patients and non‐demented controls and compare with classical AD biomarkers.MethodThe concentrations of GPNMB was measured in cerebrospinal fluid (CSF) of 17 AD patients and 17 non‐demented controls using multiplexing method.ResultGPNMB concentrations were significantly higher in AD patients in comparison to non‐demented controls. Moreover, increased CSF levels of GPNMB correlated positively with Tau, pTau181, age and negatively with Aβ‐42, Aβ‐42/Aβ‐40 ratio and MMSE in the whole study group.ConclusionFindings of our research suggest a potential role of GPNMB in pathology of AD. However, follow‐up studies on larger study group are needed.