bluuebunny/crossref_metadata_2025_split huggingface dataset:
Centiloid harmonisation across PET cameras without using paired scan
Authors: Li Shenpeng , Bourgeat Pierrick , Lebrat Leo , O'Keefe Graeme , Fripp Jurgen , Villemagne Victor L , Rowe Christopher C. , Dore Vincent 
Published: June 2023

AbstractBackgroundThe Centiloid (CL) scale allows quantification of amyloid‐b accumulation across multiple PET tracers for the diagnosis of Alzheimer’s disease. The CL quantification on different PET cameras may result in significant quantification bias when merging cohorts acquired from multiple cameras or in the longitudinal studies when change of camera occurs. In this study, we propose a harmonisation method, based on the non‐negative matrix factorisation (NMF), to reduce the quantification bias between different cameras without using paired scans.MethodThree hundred and forty‐eight 18F‐NAV4694 scans from Australian Imaging Biomarkers and Lifestyle study acquired on three PET cameras (N = 116 each), Siemens Biograph mCT, Philips Allegro and Philips Gemini TF64 were used to train the model. Participants who switched camera between two consecutive timepoints were selected as the validation data. Seventeen participants imaged on the Biograph mCT and Gemini (2.63±0.51 years scan interval), and fifty‐two participants imaged on the Gemini and Allegro (2.73±0.73 years). One hundred participants who have two scans (2.26±0.82 years) on Gemini were used to define a reference rate of change (CL/year). Figure 1 illustrates the harmonisation workflow.ResultFigure 2 compares the curves of CL change rate against baseline CL for mCT to Gemini compared to the reference. The harmonised fitting is closer to the reference than the one without harmonisation in the low to middle CL range. The fitting in high CL range (CL>80) deviates from the reference probably because of the lack of subjects in this range. Figure 3 compares the results between Phillips Allegro and Gemini TF 64. The harmonised fitting in Figure 3 is nearly parallel to the reference for the entire CL range. In contrast, the fitting on the unharmonized data shows negative rate of change for the very negative subjects and much higher CL change rate for the very positive subjects, which are strongly different compared to the reference.ConclusionWe propose a practical and economical CL harmonisation for different PET cameras without using paired data. The NMF based method shows promising results for scanner harmonisation, though more validation are needed in future for different PET models.
Relationship between blood pressure and cognitive decline in normal cognitive population: A four‐year follow‐up study in rural Xi'an
Authors: Wang Jin 
Published: June 2023

AbstractBackgroundHypertension is a modifiable risk factor for cognitive impairment, although the relationship between hypertension and cognitive impairment is not fully understood. The objective of to clarify the relationship between blood pressure and cognitive decline in cognitive normal population through a longitudinal follow‐up study.MethodCognitively normal population was selected from people who lived in the suburbs of Xi’an, China.The mini‐mental state examination (MMSE) and neuropsychological battery were used to assess cognition. Four years later, MMSE was tested again and cognitive decline was defined as a decrease in MMSE scores ≥2 points.The relationship between blood pressure parameters [systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP),] and cognitive impairment was analyzed by logistic regression models using interaction and stratified analysis. Blood pressure and age were regarded as both continuous and categorical data。ResultA total of 1024 participants completed the study, among whom 168 subjects (16.41%) presented cognitive decline.Interaction analysis for the total population showed that SBP (when regarded as continuous data) was positively correlated with cognitive impairment (OR = 1.173 [95% CI,1.030‐1.335] per 10mmHg, P = 0.016); however, the age by SBP interaction term was inclined to be negatively correlated with cognitive impairment (OR = 0.850 [95% CI, 0.711–1.016] per10mmHg×year, P = 0.074), indicating that the relationship between SBP and cognitive impairment was age‐dependent. When the blood pressure and age were considered as binary data, the results were similar to those obtained when they were considered as continuous variables.Stratified multivariate analysis revealed that the relationship between SBP (when regarded as continuous data) and cognitive impairment was positive for patients aged 50‐59 years (OR = 1.209 [95% CI:1.025–1.427] per 10mmHg, P = 0.024).However, positive results were not obtained for DBP and MABP.ConclusionElevated blood pressure is positively correlated with cognitive impairment in the middle age(50‐59), but this positive association declines with increasing age.
Beta‐amyloid regions related to amyloid positivity using a feature selection method
Authors: Ko Hyunwoong 
Published: June 2023

AbstractBackgroundCerebral beta‐amyloid (Aβ) is a hallmark of AD. Few studies have revealed which of the regional Aβ markers are associated with abnormal levels of Aβ status. The aim of the current study was to identify multivariate regional Aβ markers predicting Aβ positivity (Aβ+).MethodSeven hundred and sixty‐five participants from the ADNI‐2 cohort at baseline visit were included in the study. We used regional Aβ uptake as predictors in a predictive model. Flobetapir PET images were classified as Aβ‐positive if the standard uptake value ratio was over 1.1. The least absolute shrinkage and selection operator (LASSO) model with 1,000 bootstrap was implemented to identify regional Aβ traits to predict cortical amyloid burden from participants.ResultOut of 116 predictors, 27 markers in cortical thickness significantly predicted Aβ+ among participants at baseline. After bootstrapping, 2 phenotypes had 95% confidence intervals that did not overlap zero: left precuneus (β = 0.684) and right rostral middle frontal region (β = 0.605).ConclusionThese results demonstrated that several brain regions are related to abnormal levels of cerebral Aβ. These markers suggest robust sign that may capture AD pathology. To this end, this research was supported by the MSIT (Ministry of Science and ICT), Korea, under the ITRC (Information Technology Research Center) support program (IITP‐2022‐2017‐0‐01630) supervised by the IITP (Institute for Information & communications Technology Promotion).
Brain responses to energy intake and its association with cognition in Alzheimer’s Disease
Authors: Li Runzhi , Xu Jun , Yao Zeshan , Wang Yanli , Jiang Jiwei , Li Wenyi , Zhang Yuan , Jia Ziyan 
Published: June 2023

AbstractBackgroundTo evaluate the brain response to energy intake using cerebral blood flow(CBF) in Alzheimer’s disease (AD), mild cognitive impairment (MCI) and healthy controls (HC) and its relationship with cognition.MethodA self‐comparison design was used to test the effects of energy intake on brain activity in participants with AD (n = 30), MCI participants (n = 32), and HC (n = 30) and its relationship with cognitive function. Brain perfusion was measured using arterial spin labeling (ASL) functional brain imaging. Participants arrived at the site in the morning and underwent the ASL‐MRI with at least 10 hours fasting overnight. Then the second ASL‐MRI at 30 minutes after eating a standard breakfast was performed. Energy response ΔCBF was computed by subtracting the fasting CBF from the postprandial CBF obtained from ASL‐MRI. Whole brain grey matter voxel‐wise paired T test and linear regression analyses were used for statistical analysis.ResultAD and MCI group had different energy response ΔCBF pattern with HC group. In AD group, energy intake induced a significantly decreased CBF in temporal lobe including lateral inferior and superior temporal gyrus, right superior temporal gyrus, parietal lobe including bilateral superior and inferior parietal lobe, postcentral gyrus and precuneus, most of occipital lobe and frontal lobe including right rolandic operculum, right precentral gyrus and left middle frontal gyrus. (q < 0.05, false discovery rate corrected). MCI had similar energy intake response pattern with AD. HC group had no significantly changed CBF response to energy intake. Energy response ΔCBF in the vicinity of the superior temporal gyrus showed significant negative correlation with Minimum Mental State Examination (MMSE) in all AD, MCI and HC groups.ConclusionThe different energy response ΔCBF pattern may help to characterize the energy disorder in AD and may indicate the different brain energy rescue effect in the three groups. Energy response ΔCBF in the superior temporal gyrus is an indicator of cognitive function in AD.
Examining disease‐modifying roles of neurons in Alzheimer’s disease using a novel stem‐cell‐based human‐mouse chimeric transplantation model
Authors: Qu Wenhui , Lam Matti , Menon Vilas , Hargus Gunnar 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) and AD‐related dementias (ADRD) are fatal neurodegenerative diseases that impair the cognitive function of more than 40 million people worldwide without effective treatments. Despite the high prevalence of AD and ADRD, molecular mechanisms of neurodegeneration are only partially understood. Emerging evidence supports the physiological relevance of using induced pluripotent stem cell (iPSC) to model AD and related dementias. This study is set to determine neuron‐autonomous changes in AD iPSC‐derived neurons in vitro and in vivo.MethodIn vivo and in vitro characterization of iPSCs. We have differentiated human iPSC‐derived neural cells carrying the familial AD V717I (London) mutation in the amyloid precursor protein (APPV717I) into mature neurons in vitro and employed Seahorse assay, whole transcriptomic profiling, mass spectrometry for 150 key metabolites of the intermediary metabolism, immunostainings, and biochemical assays. We have also transplanted human AD iPSC‐derived neural cells into the brains of adult immunocompromised mice. We then microdissected human grafts and employed single nucleus RNA sequencing (snRNA‐seq) to better understand the transcriptomic changes in transplanted cells at single‐cell resolution. We will then compare the transcriptomic data of the graft with preliminary or published snRNA‐seq data on post‐mortem brain tissue from AD patients.Resultwe have also observed reduced baseline respiration in APPV717I neurons compared with their isogenic controls. Alterations of metabolic pathways were also observed in AD neurons, both in the pathway analysis of whole transcriptome profiles and in metabolomics studies. To further explore the molecular changes of iPSC‐derived AD neurons and to confirm key findings, AD or control neural cells were transplanted into the brains of immunocompromised mice and they showed robust survival and differentiation into neurons. snRNA‐seq on microdissected grafts is underway to better understand the transcriptomic changes in transplanted cells at single‐cell resolution.ConclusionPreliminary results show cell‐autonomous changes of AD iPSC‐derived neurons in vitro and successful transplantation of human iPSC‐derived AD neural cells in vivo suggest the feasibility of modeling AD using this innovative in vivo human stem cell model.
Safety profile of lycopene, ellagic acid and hesperetin combination regimen in the brain of balb c mice
Authors: Adeyemo Oluwatobi Adewumi , Ajiboye Oyedele Ebenezer , Osinowo Princess Boluwatife , Awogbindin Ifeoluwa Oluleke , Olayinka Ebenezer Tunde 
Published: June 2023

AbstractBackgroundThe pathophysiology of neurodegenerative diseases, particularly Alzheimer’s disease is multifactorial. However, with scientific evidences suggesting that various antioxidants possess different protective mechanisms, thus hypothetically/theoretically no single natural compound can adequately abrogate these plethora of neurodegenerative cascades. Hence, there is a need for a paradigm shift from the usual monotherapy directed management of neurodegeneration. Therefore, this study investigated the effects of combined administration of three antioxidants namely; hesperetin, lycopene and ellagic acid in the brain of balb c mice.MethodThirty (30) male balb/c mice were grouped and administered orally with respect to each of their weights for Twenty eight (28) days as follows: Group I (Control)‐ Dimethyl sulfoxide (DMSO) in olive oil, Group II‐ Lycopene (5mg/kg body wt), Ellagic acid (15mg/kg body wt), Hesperetin (20mg/kg body wt) dissolved in DMSO and olive oil, Group III‐lycopene(10mg/kg body wt), Ellagic acid (30mg/kg body wt), Hesperetin(40mg/kg body wt) dissolved in DMSO and olive oil.ResultThe combination regimen at both doses show no significant difference in the concentration of nitric oxide (NO), protein carbonyl (PC), reduced glutathione (GSH), hydrogen peroxide (H2O2), malondialdehyde (MDA) level, activity of catalase (CAT) in the brain. Furthermore, the numbers of spared pyramidal and purkinje neurons of the cortex (sensorimotor cortex, hippocampus) and cerebellum at both doses were increased respectively but not significant when compared with their age‐matched control. Also, neuronal nuclei (NeuN) immunohistochemical staining revealed a slightly elevated matured neuronal population, as well as decreased ionized calcium binding adaptor molecule 1 (Iba1) expressions.ConclusionIn conclusion, this study suggests that the combined regimen is not only safe, but also enhanced cell viability in normal condition and could be promising in the management of neurodegenerative diseases.
High concordance between plasma amyloid β biomarkers by IP‐MALDI‐MS and visual assessment of amyloid PET
Authors: Kaneko Naoki , Nakamura Akinori , Yoda Ritsuko , Kato Takashi , Sekiya Sadanori , Ito Kengo , Iwamoto Shinichi , Tanaka Koichi 
Published: June 2023

AbstractBackgroundAbnormal amyloid‐β (Aβ) deposition in the brain has been defined as the earliest pathological change of Alzheimer disease (AD). We combined immunoprecipitation (IP) with MALDI‐TOF MS to develop IP‐MALDI‐MS, which is an analytical technique for plasma Aβ. This technique has previously revealed that APP669‐711/Aβ1‐42 ratio, Aβ1‐40/Aβ1‐42 ratio, and a combination of these two biomarkers (a composite biomarker) in human plasma correlates highly with SUVR obtained from amyloid PET (Nakamura et al., Nature, 2018). In this work, we validated a concordance between plasma Aβ biomarkers by IP‐MALDI‐MS and visual amyloid PET status with an independent dataset from the previous report.MethodPlasma samples were obtained from 41 Aβ+ and 55 Aβ‐ subjects classified using PET with PIB tracer in National Center for Geriatrics and Gerontology. Aβ‐related peptides were immunoprecipitated from the sample spiked by stable isotope‐labeled (SIL) Aβ1‐38 using beads coupled with anti‐Aβ antibody. After the IP was performed two times consecutively, Aβ‐related peptides eluted from the antibody beads were applied to MALDI‐TOF MS. SIL‐Aβ1‐38 was used as an internal standard for normalizing an intensity of each Aβ‐related peptide. APP669‐711/Aβ1‐42 ratio and Aβ1‐40/Aβ1‐42 ratio were calculated from those intensities and then the composite biomarker was generated as previous reported.ResultAPP669‐711/Aβ1‐42 ratio, Aβ1‐40/Aβ1‐42 ratio and the composite biomarker were significantly higher in the Aβ+ group than the Aβ‐ group (p < 0.001). IP‐MALDI‐MS discriminated Aβ‐PET positivity with high AUC in APP669‐711/Aβ1‐42 ratio (92.8%), Aβ1‐40/Aβ1‐42 ratio (95.7%) and the composite biomarker (95.8%). Furthermore, an accuracy of the three biomarkers was 89.6‐92.7% in the Aβ+/‐ classification.ConclusionOur results demonstrated high concordance of plasma Aβ biomarkers with visual amyloid PET status. The measurement by IP‐MALDI‐MS can provide the biomarker values highly associated with Aβ‐PET positivity.
Association of short tandem repeats with neuropathological features in late‐onset of Alzheimer’s disease brains
Authors: Lee Annie J , Klein Hans‐Ulrich , Schneider Julie A , Bennett David A , De Jager Philip L , Narzisi Giuseppe , Zody Michael , Vardarajan Badri N 
Published: June 2023

AbstractBackgroundLate‐Onset Alzheimer’s Disease (LOAD) is characterized by genetic heterogeneity and there is no single model explaining the genetic mode of inheritance. Short tandem repeats (STRs), which are hyper‐mutable sequences in the human genome could explain some of the missing heritability in LOAD. STRs are involved in several neuro‐degenerative disorders. We systematically evaluated the impact of 31 disease‐associated STRs on neuropathological LOAD features.MethodFrom whole‐genome sequencing (WGS) data in for 1,134 unrelated individuals of European ancestry from Religious Orders Study (ROS) and Rush Memory and Aging project (MAP) cohorts, we identified known pathogenic STRs in 31 loci using ExpansionHunter. WGS was generated from DNA extracted from blood and brain tissues. We tested the association of STRs with a) neuropathological LOAD status, b) beta‐amyloid levels, c) neurofibrillary tangle (NFT) burden, d) global measure of pathology based on the scaled scores of 5 brain regions and e) estimated slope of global cognition using longitudinal measurements. Regression models adjusting for age, sex and first three principal components. Subsequently, we examined if STRs influenced gene expression in dorsolateral prefrontal cortex (DLPFC), posterior cingulate cortex (PCC) and the anterior cingulate (AC) and tested if the association of STRs with neuropathological traits were mediated by altered gene expression.ResultTGC repeat in ATXN1 was associated with cognitive decline (b = ‐0.007, p = 0.014) and risk of clinical AD (b = 0.126, p = 0.03). Variation in CAG repeats in ATN1 was associated with cognition (b = 0.004, p = 0.022) and risk of pathological AD (b = ‐0.069, p = 0.035). Longer Repeats at ATXN1 increased gene expression in DLPFC (b = 0.012, p = 0.049) and PCC (b = 0.019, p = 0.006) and repeats in ATN1 altered DLPFC (b = 0.01, p = 0.016) and PCC (b = 0.01, p = 0.026) expression. Mediation analysis determined that the effect of the CAG repeats in ATN1 on tau was mediated by gene expression in PCC (p = 0.004).ConclusionWe demonstrate that disease causing STRs influence the underlying gene expression in brain and are associated with neuropathological and cognitive endophenotypes of AD. This suggests that STRs could explain some of the missing heritability in LOAD.
Financial Behaviors and Experiences of Financial Loss in those with Alzheimer’s disease and Frontotemporal Dementia: Preliminary findings from a survey
Authors: Narayan Claudine K. , Stein Colin M. , Ake Jeannie M. , Benavides Andrea , Huey Edward D. , Goldman Jill , Mejia Arlene , Chapman Silvia , Joyce Jillian L. , Stern Yaakov , Cosentino Stephanie , Sunderaraman Preeti 
Published: June 2023

AbstractBackgroundOlder adults are increasingly experiencing financial loss, with annual costs estimated to be about $2.9 billion. The risk of experiencing financial loss is magnified in those with neurodegenerative conditions, including Alzheimer’s disease (AD) and Frontotemporal Dementia (FTD). However, limited information exists on the frequency and amount of money lost, and the behaviors that contribute to such loss in these conditions. The current study sought to characterize the nature of financial losses in AD and FTD, and to identify risk factors in an effort to prevent or mitigate financial loss.MethodSurvey data were collected from ten caregivers of individuals clinically diagnosed with AD or FTD recruited via the Neurodegeneration‐Associated Psychiatric Syndromes study and caregiver support groups at Columbia University Medical Center. Survey items queried demographic information, details of financial loss, level of concerns experienced by care partners and patients, and financial behaviors resulting in financial losses (Table 1).ResultCaregivers had known the patients on average for 46 years. Out of 10 patients, 6 experienced financial loss. See Table 2 for detailed results. While the same number of patients with AD and FTD lost money, those with FTD lost money more frequently and to a larger amount than those with AD. Caregivers of FTD patients expressed a higher degree of concern relative to those with AD. Moreover, most AD patients were described as being concerned about their financial ability, as compared to none of the FTD patients having concern for their financial ability. Additionally, 3 of 5 FTD patients were reported to have engaged in repetitive spending as compared to none of the AD patients.ConclusionPreliminary data indicate a high prevalence of financial loss (60%) in AD and FTD. The intensity of financial loss and related caregiver burden appears higher in FTD, with caregivers describing repetitive spending and less concern about difficulties, likely tied to the lack of insight which is a core feature of this disease. These findings can guide caregiver supervision and interventions to preserve family funds.
Subjective memory complaints, white matter hyperintensities, and cognitive decline in a population‐based cohort study
Authors: Dhana Anisa , Decarli Charles , Dhana Klodian , Krueger Kristin R , Desai Pankaja , Evans Denis A , Rajan Kumar B 
Published: June 2023

AbstractBackgroundSubjective memory complaints (SMCs) are associated with a faster cognitive decline and dementia; whether this relationship results from irreversible structural brain alterations, such as white matter hyperintensities (WMH), requires investigation. We aimed to determine the association of SMCs with WMH and cognitive decline and investigate the role of WMH on the relationship between SMCs and cognitive decline.MethodWe studied 917 participants (63% African Americans and 60% women) from the population‐based Chicago Health and Aging Project (CHAP), who responded to questions about SMCs, underwent magnetic resonance imaging of the brain, and had valid cognitive data on two or more visits during the follow‐up period. SMCs were obtained by self‐report questionnaire, and based on frequency and severity of concerns, we categorized participants into three groups: not concerned, moderately concerned, and very concerned.ResultOf 917 participants eligible for the study, 158 (17.2%) had no SMCs concerns, 671 (73.2%) had moderate concerns, and 88 (9.6%) were very concerned. SMCs were associated with larger WMH volumes and faster cognitive decline. Compared to participants with no concerns, those very concerned had 0.833 (95%CI 0.203, 1.463) units higher WMH volumes and 174% faster cognitive decline (‐0.049; 95%CI ‐0.076, ‐0.022). The association between SMCs and cognitive decline was statistically significant only among individuals with large WMH volumes; that is, very concerned individuals with large WMH volumes had 428% faster cognitive decline annually (‐0.077; 95%CI ‐0.144, ‐0.011) than participants with no concerns. In participants with low volumes of WMH, SMCs were not associated with a faster cognitive decline (P‐value = 0.595).ConclusionOur study suggests that SMCs, frequently reported by the elderly, are an important sign of cognitive impairment, especially in people with brain atrophies, such as large WMH volumes.