bluuebunny/crossref_metadata_2025_split huggingface dataset:
Longitudinal risk estimation of progression from normal cognition to amnestic mild cognitive impairment: The independent contribution of ATN biomarkers
Authors: Zhao Lei , Shi Lin , Luo Yishan , Mok Vincent C.T. ,   for the Alzheimer Disease Neuroimaging Initiative
Published: June 2023

AbstractBackgroundIt is still not clear about the independent contribution of ATN biomarkers (amyloid beta [A], pathologic tau [T], and neurodegeneration [N]) on top of neuropsychological tests for risk estimation of amnestic mild cognitive impairment (aMCI) in subjects with normal cognition (NC).MethodWe included 306 NC subjects who underwent neuropsychological tests and were available for ATN biomarkers with cerebrospinal fluid (CSF) examinations, MRI and FDG‐PET at baseline. The involved ATN biomarkers included CSF‐Aβ, CSF‐Ptau, CSF‐Tau, FDG‐PET and an MRI‐based Alzheimer’s disease resemblance atrophy index (AD‐RAI) calculated by AccuBrain. The study cohort was divided into training cohort (n = 204, 19.6% developed aMCI within 4.73±2.83 years) and validation cohort (n = 102, 20.6% developed aMCI within 4.67±2.72 years). All the demographic features and neuropsychological tests (Table 1) were entered into the cox regression model with backward elimination to predict time to incident aMCI (the subscores of FAQ and ADAS‐cog were also entered as candidate predictors), and the resulting model based on the training cohort was treated as the basic model. Individual ATN biomarkers were added on top of the basic model for cox regressions, and the enriched models would be tested in the validation cohort using time‐dependent AUC (t‐AUC) if they presented higher Chi‐squares than the basic model in training cohort.ResultThe features that survived backward elimination for the basic model were shown in Table 2. Only the enriched model with Ptau or AD‐RAI presented higher Chi‐square than the basic model in the training cohort (p<0.05, Table 3). In the validation cohort, the model Basic+(AD‐RAI) presented significantly higher t‐AUC (0.770∼0.859) than the basic model through year 2∼7 and Basic+Ptau through year 1∼4 (p<0.05, Figure 1). The model with Ptau only presented significantly higher t‐AUC than the basic model for year 7 (p = 0.02). Also, adding Ptau on top of Basic+(AD‐RAI) presented no significant increase of t‐AUC for any time point (Figure 1). These findings indicated that Basic+(AD‐RAI) may be used as the optimal model for predicting risk of aMCI (nomogram shown in Figure 2).ConclusionAD‐RAI consistently presented independent contribution to predicting aMCI among NC subjects on top of demographic characteristics and neuropsychological tests.
Immunity gene IFITM3 variant: relation to cognition and Alzheimer pathology
Authors: Pyun Jung‐Min , Park Young Ho , Han Moon‐ku , Hodges Angela , Jang Jae‐Won , Bice Paula , Kim SangYun , Saykin Andrew J. , Nho Kwangsik 
Published: June 2023

AbstractBackgroundIFITM3, an innate immune response protein and inhibitor of viral infection, was reported to modulate amyloid‐β production in Alzheimer’s disease (AD). We aimed to identify single‐nucleotide polymorphisms (SNPs) in IFITM3 associated with cognition and AD biomarkers.MethodWe used genetic, longitudinal cognition and AD biomarker data from Alzheimer’s Disease Neuroimaging Initiative (ADNI; N = 1,565) and AddNeuroMed (N = 633) as discovery and replication samples, respectively. First, we performed gene‐based association analysis of SNPs in IFITM3 with cognitive performance. Second, we performed SNP‐based association analysis in IFITM3 with cognitive decline and AD biomarkers from amyloid positron emission tomography (PET), cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI).ResultGene‐based association analysis showed that IFITM3 was significantly associated with cognitive performance (permutation‐corrected p = 1.25×10−3). Particularly, among two SNPs (rs10751647, rs2091850) in IFITM3 significantly associated with cognitive performance, rs10751647 was associated with cognitive decline in ADNI, which was replicated in AddNeuroMed. In addition, rs10751647 was significantly associated with amyloid‐β deposition measured by amyloid PET scan, CSF phosphorylated tau levels, and entorhinal cortical thickness measured by MRI scan in ADNI. The association of rs10751647 with entorhinal cortical thickness was replicated in AddNeuroMed. Participants with minor alleles (C) of rs10751647 have less cognitive decline, less amyloid and tau burden, and less brain atrophy. eQTL analysis showed that rs10751647 is associated with IFITM3 expression levels in blood and brain.ConclusionThis suggests that rs10751647 in IFITM3 is associated with less vulnerability for cognitive decline and AD biomarkers, providing mechanistic insight regarding involvement of immune activity and infection in AD.
The intrinsic locus coeruleus functional connectivity change in older adults with subjective memory complaint
Authors: Gong Liang , Zhang Bei ,   Alzheimer’s Disease Neuroimaging Initiative
Published: June 2023

AbstractBackgroundThe locus coeruleus (LC) is critical for late‐lift cognitive processing by modulating the norepinephrine system, which is often the first place Alzheimer’s pathology appears. Previous researches have identified that the LC was associated with late‐life cognitive ability. This study aims to investigate whether the intrinsic LC functional connectivity (LC‐FC) is altered in older adults with subjective memory complaints (SMC).MethodA total of 199 participants were selected from the Alzheimer’s Disease Neuroimaging Initiative database, including 95 SMC older adults and 104 cognitively normal individuals (CN). Bilateral LCs were selected to construct the LC functional connectivity based on resting‐state fMRI data. The cognitive function was evaluated by using the ADNI composite executive function (ADNI‐EF) and memory (ADNI‐Mem) scores at baseline and 24 months later. Data were analyzed using the voxel‐wise two‐sample t‐test and partial correlation analysis, we utilized permutation testing with threshold‐free cluster enhancement (TFCE) to multiple comparison correction.ResultThere were no significant differences in demographic information and cognitive function between the two groups. In the left LC‐FC network, compared to CN group, the SMC group showed increased LC‐FC in the left salient network (anterior insula, and frontal operculum cortex), hippocampus, and right default mode network(DMN, inferior temporal gyrus), while they had decreased LC‐FC in left inferior temporal gyrus. No significant difference in the right LC‐FC network between the two groups. The altered FC between left LC and right inferior temporal gyrus (DMN) was significantly associated with ADNI‐EF performance in the SMC group, controlled the effect of age, gender, and APOE genotype (r = ‐0.404, p = 0.002), and the FC between LC and right ITG was also associated with executive function performance after 24 months in SMC group.ConclusionThe present study manifested the abnormal intrinsic LC functional connectivity in elder adults with SMC. In addition, the FC between LC and default mode network was associated with the executive function performance in SMC. These findings might suggest an LC norepinephrine system compensatory mechanism in cognitive processing in older individuals with SMC.
Imaging correlates of premorbid personality in the Frontotemporal Dementia ‐ Amyotrophic Lateral Sclerosis (FTD‐ALS) spectrum
Authors: Gallingani Chiara , Vinceti Giulia , Carbone Chiara , Fiondella Luigi , Zucchi Elisabetta , Martinelli Ilaria , Tondelli Manuela , Salemme Simone , Mandrioli Jessica , Chiari Annalisa , Zamboni Giovanna 
Published: June 2023

AbstractBackgroundFrontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) belong to the same neurodegenerative spectrum. Factors determining phenotypic expression are unknown; however, it is common observation that personality differs between phenotypes: ALS patients tend to display a pleasant and nice attitude, while FTD patients frequently exhibit antisocial behaviours and lack of empathy. We therefore aimed at testing if FTD and ALS patients have different premorbid personalities, and, consequently, different organizations in the brain networks involved in social behaviour and motor function.MethodWe recruited FTD and ALS patients presenting to Modena University Hospital Neurology Clinics. Patients’ premorbid personality was assessed through the NEO Personality Inventory 3, which evaluates five main personality factors (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness). Brain MRI scan including T1‐weighted and resting state fMRI sequences was performed. Data were analysed with voxel‐based morphometry and probabilistic independent component analysis.Result50 patients (30 FTD, 17 ALS, and 3 FTD‐ALS) were recruited. A significant difference in premorbid personality emerged in the Openness and Extraversion domains, meaning that ALS patients – in their premorbid life – showed higher sociability, loquacity and optimism and were more prone to new experience, ideas, and emotions than FTD patients, respectively. Structural imaging analysis showed a positive correlation between premorbid Neuroticism and grey matter density of the hippocampus bilaterally (left>right) across all patients. Group comparisons of fMRI data showed greater functional connectivity (FC) in ALS compared to FTD patients within the Salience Network (SN) in the right insula, putamen, nucleus accumbens, and the left thalamus. FC within the SN positively correlated with premorbid Openness across all patients.ConclusionPremorbid personality differs between patients with ALS and FTD, and relates to different degrees of FC within the Salience Network. This suggests that premorbid personality may represent a vulnerability marker to the development of specific phenotypes along the FTD‐ALS spectrum.
Does awareness of condition change over time in people with mild‐to‐moderate dementia? Longitudinal findings from the IDEAL cohort
Authors: Alexander Catherine Maria , Martyr Anthony , Clare Linda ,   in collaboration with the IDEAL programme research team
Published: June 2023

AbstractBackgroundAlthough awareness is known to vary in people with dementia, little is known about longitudinal trajectories of awareness of condition in people with mild‐to‐moderate dementia. Exploring this could help understand the concepts around awareness, and reasons for apparent impaired awareness, relevant to person‐centered care.MethodWe used longitudinal data from the IDEAL programme for 917 community‐dwelling people diagnosed with mild‐to‐moderate dementia. Using a validated checklist, we assessed awareness of personal difficulties associated with dementia at three timepoints over two years. Changes in awareness from baseline were examined. Focusing on people with low awareness at baseline, we used case‐matching to compare characteristics between people who gained awareness over time, and those who continued with low awareness.ResultAt baseline, 83 people showed low awareness of personal dementia‐related difficulties. Following up this group, after attrition we examined data for 49 people at T2 and 25 people at T3. Most people remaining in the study had gained awareness at T2 and T3. Gains were seen up to four or more years after diagnosis. Five people continued to deny any of the common difficulties associated with dementia at all timepoints. These five reported slightly more comorbid conditions than matched cases. Few other distinguishing features were evident but in comparison, the people who came to acknowledge difficulties showed greater deterioration in cognitive and functional ability by T3.ConclusionOver time, self‐reported awareness of dementia‐related difficulties can change in people with mild‐to‐moderate dementia. Awareness gains, seen in most people remaining in the study at T2 and T3, may have been prompted by deteriorating abilities. Reasons for ongoing low awareness were difficult to establish and may relate to individual circumstances including comorbidity. This highlights the individual complexity and dynamic nature of awareness in dementia and challenges the concept of impaired awareness as a fixed disease‐related condition.
Mid‐ to late‐life physical and recreational activities: Associations with late‐life cognition
Authors: Gavett Brandon E , Widaman Keith F. , McKenzie Cathryn , Chooi Cheyenne K , De Leon Fransia S. , Fletcher Evan M , Farias Sarah Tomaszewski , Mungas Dan M. 
Published: June 2023

AbstractBackgroundPhysical and cognitively stimulating recreational activities are lifestyle factors that may modify risk of late‐life cognitive decline. We sought to examine the role of retrospective ratings of mid‐life (age 40) physical and recreational activity engagement – and change in these activities from age 40 to study entry – in predicting late‐life cognition. We hypothesized that higher self‐reported levels of physical and recreational activities at age 40, and less decline in these activities over time, would be associated with higher levels of late‐life cognition and less rapid cognitive decline.MethodData were obtained from 898 participants in the University of California Davis Aging and Diversity Cohort, a longitudinal study of cognitive aging in demographically and cognitively diverse older adults. Participants ranged in age from 49‐93 years (M = 75, SD = 7.19). Self‐reported physical and recreational activity participation at age 40 and at study entry were quantified using the Life Experiences Assessment Form. Confirmatory factor analysis established the unidimensionality and longitudinal measurement invariance of physical and recreational activity levels at age 40 and at study entry. Change in activities was modeled using latent change scores. Cognitive outcomes were obtained annually (range = 0‐17 years) using the Spanish and English Neuropsychological Assessment Scales, which measures episodic memory, semantic memory, visuospatial processing, and executive functioning. Multilevel structural equation modeling was used to regress four cognitive intercepts and one global cognitive slope onto age 40 and change factors for physical and recreational activities, in separate models.ResultPhysical activity engagement at age 40 was strongly associated with cognitive performance in all four domains at study entry and with global cognitive slope. However, change in physical activities was not associated with cognitive outcomes. In contrast, recreational activity engagement – both at age 40 and change after age 40 – was predictive of cognitive intercepts and slope.ConclusionMid‐life physical and recreational activity engagement were strongly associated with late‐life cognition – both level of performance and rate of future decline. However, the data suggest that maintenance of recreational activity engagement (e.g., writing, taking classes, reading, arts & crafts) after age 40 is more strongly associated with late‐life cognition than continued maintenance of physical activity levels.
The significance of the Calbindin‐D in Alzheimer’s disease
Authors: Mroczko Barbara , Kulczynska‐Przybik Agnieszka , Borawska Renata , Dulewicz Maciej , Doroszkiewicz Julia , Karpiuk Magdalena , Slowik Agnieszka 
Published: June 2023

AbstractBackgroundAlzheimer’s disease is a heterogeneous, progressive, and devastating neurodegenerative disease. In addition to the accumulation of Aβ and tau, neuropathological processes in the early stage of AD are accompanied by calcium dysregulation, which might cause the loss of synapses and then dysfunctions of the neural network. Calbindin‐D is abundant throughout the central nervous system (CNS) and one of the neuronal protective factors, also involved in calcium homeostasis. It has been reported that the depletion of Calbindin‐D in AD transgenic mice brain elicited significant alterations in apoptosis, synaptic transmission, and cytoskeleton organization. Despite of the reduced Calbindin expression in the brains of mice and patients with AD, still the role of this protein in AD‐related dysfunction is tested. To obtain better insights into the pathological significance of the protein we assesed the concentarion of Calbindin‐D in cerebrospinal fluid of patients with AD and non‐demented controls.MethodThe study group included 34 subjects: patients with AD and controls without cognitive impairments. The cerebrospinal fluid (CSF) concentrations of tested proteins were measured with the use of multiplexing technique.ResultThe CSF concentrations of Calbindin‐D were elevated in AD patients in comparison to non‐demented controls. Additionally, the CSF levels of Calbindin‐D positively correlated with tau as well as phTau181, and negatively with MMSE in the whole study group.ConclusionOur preliminary study indicates a potential role of Calbindin‐D in the development of AD, although the question, whether this protein can be useful in clinical practice of dementia requires further examination.
A new BACE‐1 inhibitor peptide from Macrorhynchia philippina
Authors: Renzo Karine Cristie Quaglio Banagouro , Kitahara Marcelo V , Sciani Juliana Mozer 
Published: June 2023

AbstractBackgroundAlzheimer’s Disease (AD), the most common cause of dementia, is characterized by the amyloid plaques accumulation, generated after the APP cleavage by enzymes, being the most important the beta‐secretase‐1 (BACE1) (Hardy and Selkoe, 2002). Small‐molecule BACE1 inhibitors reduced the production of amyloid‐β peptide, but clinical trials have demonstrated some adverse effects, although non‐progressive and reversible, which indicates that BACE1 inhibition should be better investigated (McDade et al., 2021). Peptides are molecules few explored in the drug development field, but have several advantages, such as specificity, bioavailability and ability to cross the brain‐blood barrier (BBB) (Craik et al., 2013). Marine animals are a rich source of peptides, some of them already used in the clinics (Malve, 2016). Thus, the objective of this work was to find new BACE1 inhibitor peptides from Macrorhynchia philippina venom, a Brazilian marine animal.MethodM. philippina venom was obtained by methanol/acetic acid extraction and tested in SH‐SY5Y neurons for toxicity evaluation. The extract was analyzed by mass spectrometry for peptides identification and sequencing, and had their secondary structure determined and prepared for molecular docking with BACE1 (PDB code 2VKM), conducted by MDockPep serve (Xu and Zou, 2020). Results were analyzed by UCSFChimera, and molecules were selected according to their positioning in the enzyme active site, with distance lower than 3 Å between atoms. Selected molecules were also analyzed by ProtParam tool (Gasteiger et al., 2005) for determining physico‐chemical properties, BBB permeability and stability.ResultNineteen peptides were obtained, and none of them have already been described, according to similarity analysis by BLAST algorithm. None of them caused significant cytotoxicity for neurons. From that, 10 were positioned in the BACE1 active site after a global docking analysis, in the same place than a known inhibitor (Ki 1.8 nM). One of them was stable, according to algorithms created from known peptides and high aliphatic index. Moreover, the peptide had high hydrophobicity, according to GRAVY index, indicating high BBB permeation.ConclusionOne new peptide was obtained with potential activity on BACE1 inhibition, with suitable characteristics for a drug. The bioactive peptide represents a good alternative for AD treatment.
The Markers in Neuropsychiatric Disorders Study (The MiND Study): moving neurofilament light and other markers into the clinic to improve care for people with symptoms and illnesses of the mind and brain
Authors: Eratne Dhamidhu , Lewis Courtney , Kang Matthew , Keem Michael H , Dobson Hannah , Santillo Alexander , Li Qiao‐Xin , Stehmann Christiane , Loi Samantha M , Walterfang Mark , Watson Rosie , Yassi Nawaf , Blennow Kaj , Zetterberg Henrik , Janelidze Shorena , Brodtmann Amy , Darby David G , Walker Adam J , Dean Olivia , Kaylor‐Hughes Cath , Gunn Jane , Goranitis Ilias , Pan Tianxin , Fowler Christopher J , Masters Colin L. , Collins Steven J , Berkovic Samuel F , Velakoulis Dennis ,   The MiND Study Group
Published: June 2023

AbstractBackgroundAccurate, timely diagnosis of neuropsychiatric symptoms, in particular distinguishing primary psychiatric from neurological disorders and in younger people, can be challenging. Neurofilament light (NfL) and other blood biomarkers have shown promise to reduce the diagnostic odyssey and improve outcomes. The MiND Study in investigating the diagnostic utility of NfL and other markers, to distinguish neurological/neurodegenerative from psychiatric disorders, to lead to a widely available, routine screening blood test.MethodsWe assessed NfL, p‐tau181 and GFAP in broad cohorts, including: patients assessed for neurocognitive/psychiatric symptoms at Neuropsychiatry and other services, in a wide range of disorders including Alzheimer disease, frontotemporal dementia, schizophrenia, bipolar disorder, depression, functional neurological disorders, Niemann‐Pick Type C, epilepsy.ResultsUpdates on the The MiND Study progress and findings that NfL differentiated diverse neurodegenerative from psychiatric disorders, with 90+% accuracy, from over 500 patients/participants, will be presented, with real patient and family stories to demonstrate the challenges and potential clinical impact of The MiND Study. Plasma P‐tau181 levels distinguished Alzheimer disease (mainly younger sporadic), from non‐Alzheimer. As recruitment, sample analysis, data collection is ongoing, the most up to date results including GFAP, cognitive and neuroimaging markers, will be presented.ConclusionsNfL shows great promise as a diagnostic screening blood test, akin to a “CRP for the brain”. Plasma p‐tau181 shows strong diagnostic utility in younger‐onset Alzheimer disease. NfL could dramatically alter clinical care of patients with neuropsychiatric and neurological symptoms, improving outcomes for patients, their families, the healthcare system, and clinical trials, facilitating precision medicine algorithmic diagnostics incorporating other biomarkers and clinical/cognitive markers, for real‐world clinical settings.