bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Brain Amyloid Status Using the NIH Toolbox for Assessment of Neurological and Behavioral Function (NIHTB)
Authors: Cheng You , Ho Emily , Weintraub Sandra , Rentz Dorene M. , Gershon Richard C. , Das Sudeshna , Dodge Hiroko H 
Published: December 2023

AbstractBackgroundAmyloid‐beta (Ab) plaque is a pathophysiological hallmark of Alzheimer’s disease (AD). As anti‐amyloid monoclonal antibodies enter the market, predicting brain amyloid status is critical to determine treatment eligibility. Here, we predicted brain amyloid status in the Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging (ARMADA) study using machine learning.MethodsARMADA, a multisite study, aimed to validate the National Institute of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in older adults with different cognitive abilities (normal, MCI, early AD dementia). We used cognition, emotion, motor, sensation scores from NIHTB, and demographics to predict amyloid status measured by PET or CSF. Each site used its own criteria to define the amyloid PET positivity (Positive for AD biomarkers, Negative, Visual reading unavailable) or CSF result (Consistent with AD, Not consistent with AD, Borderline, Indeterminate). Amyloid positivity was defined as PET being “Positive for AD biomarkers” or CSF being “Consistent with AD.” We applied LASSO and random forest models and used the area under the receiver operating curve (AUROC) to evaluate the ability to identify amyloid positivity.ResultsOf 462 ARMADA participants, 199 had either PET or CSF information (mean age 76.3 ± 7.7, 51.3% women, 42.3% some or complete college education, 50.3% graduate education, 88.9% White, 33.2% with positive AD biomarkers). The random forest model reached AUROC of 0.74 with higher specificity than sensitivity (AUROC 95% CI:0.73 – 0.76, Sensitivity 0.50, Specificity 0.88) on the held‐out test set; higher than the LASSO model (0.68 (95% CI:0.68 – 0.69)). The 10 features with the highest importance from the random forest model are: picture sequence memory, cognition total composite, cognition fluid composite, list sorting working memory, words‐in‐noise test (hearing), pattern comparison processing speed, odor identification, 2‐minutes‐walk endurance, 4‐meter walk gait speed, and picture vocabulary. Overall, our model revealed the validity of measurements in cognition, motor, and sensation domains, in associating with AD biomarkers.ConclusionOur results support the utilization of the NIH toolbox as an efficient and standardizable AD biomarker measurement that is better at identifying amyloid negative (i.e., high specificity) than positive (i.e., low sensitivity) cases.
Significance of a positive tau pet scan with a negative amyloid pet scan
Authors: Robinson Carling G. , Lee Jeyeon , Min Paul H , Przybelski Scott A. , Josephs Keith A , Jones David T. , Radford Jonathan Graff , Boeve Brad , Knopman David S. , Jack Clifford R. , Petersen Ronald C. , Machulda Mary M. , Fields Julie A. , Lowe Val J. 
Published: December 2023

AbstractBackgroundThe implications of a positive tau (T) Positron Emission Tomography (PET) with a negative beta amyloid (A) PET are not well understood. We investigated cognitive performance in participants who were positive on tau PET but negative on beta amyloid PET.MethodWe evaluated 98 participants from the Mayo Clinic Study of Aging (MCSA) and the Mayo Clinic Alzheimer’s Disease Research Center (ADRC) who were positive for Flortaucipir (FTP) and negative for PiB PET. Participants were classified as A‐ and T+ based on Standardized Uptake Value Ratios (SUVr) of FTP and PiB PET scans, and were matched 2:1 to amyloid negative and tau negative cognitively unimpaired controls from the MCSA. Cognitive test scores were compared between the combined ADRC/MCSA group and MCSA only group. We also examined clinical diagnoses in our cohort. The most common were Alzheimer’s Disease, mild cognitive impairment (MCI), Dementia with Lewy Bodies (DLB) and Frontotemporal dementia (FTD) amongst others.ResultThere were no significant differences in demographic features or PiB SUVr between groups. There were significant differences in APOE genotype between groups. In the combined ADRC/MCSA group, 25% of A‐T‐ and 13% of A‐T+ were APOE e4 carriers (p = 0.016), and in the MCSA only group, 27% of A‐T‐and 10% of A‐T+ were APOE e4 carriers (p = 0.010). In the combined ADRC/MCSA group, the A‐T+ group demonstrated lower performance than the A‐T‐ group on the Mini Mental Status Exam (MMSE) (p<0.001), Wechsler Memory Scale‐Revised Logical Memory I (p<0.001) and Logical Memory II (p<0.001), Auditory verbal Learning Test Delayed Recall (AVLT) (p = 0.004), Category fluency animals (p = 0.005), Category fluency vegetables (p = 0.021), Trailmaking test A (p<0.001), Trail making test B (p<0.001), Wechsler Adult Intelligence Scale‐IV (WAIS‐IV) (p = 0.002), and Unified Parkinson’s Disease Rating Scale part III (UPDRS III) (p = 0.003). In the MCSA only group, the A‐T+ group had lower scores on Logical Memory II (p = 0.022), AVLT delated recall (p = 0.04), and WAIS‐R block design (p = 0.035) compared to the A‐T‐group.ConclusionPositive tau PET in the absence of beta‐amyloid positivity is associated with lower cognitive performance.
Memory retrieval activation moderates the effect of Alzheimer’s disease pathology on memory performance
Authors: Vockert Niklas , Molloy Eóin N. , Pilar Andrea Pacha , Binette Alexa Pichet , Remz Jordana , Rajah Natasha , Villeneuve Sylvia , Maass Anne 
Published: December 2023

AbstractBackgroundCognitive reserve (CR) is a concept explaining better than expected cognitive performance given the degree of brain disease. More specifically, as a compensation mechanism, individual differences in patterns of brain activity during fMRI tasks may explain differential susceptibility to pathological burden. CR might already manifest in early preclinical Alzheimer’s disease (AD) stages.MethodParticipants of the longitudinal PREVENT‐AD study have well‐characterized AD biomarkers via [18F]AV1451 and [18F]NAV469 PET for Aβ and tau as well as repeated MRI measurements including a memory retrieval task. Participants also completed cognitive testing with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We selected a subsample of 82 cognitively unimpaired older adults (age: 67.9 ± 4.8 years; 24 male) with (f)MRI data within 2 years of PET. PET‐ and MRI‐based ATN biomarkers were reduced to a single composite measure for AD pathological load (PL; Fig.1). We extracted mean retrieval‐related fMRI activation (hits versus correct rejections) from specific regions, comprising all task‐positive regions (pFWE < 0.05), all task‐negative regions, entorhinal cortex, precuneus, and inferior parietal cortex. Subsequently, we tested fMRI activation as a moderator variable between PL and delayed memory performance in line with the CR framework.ResultActivation in task‐positive regions showed an interaction (moderation) effect with PL on memory performance (p = 0.033). In individuals with low retrieval activation in the task‐positive network, AD pathological load was related to poorer memory performance, whereas this association was diminished in individuals with high retrieval activation. This moderation was not significant for task‐negative regions (p = 0.104). We observed a similar interaction for tau and activity in the entorhinal cortex (p = 0.0003) as well as for Aβ and activity in the precuneus (p = 0.056) and inferior parietal cortex (p = 0.010).ConclusionOur results indicate that the association between early AD pathology and memory performance differs dependent on the level of fMRI activation during memory retrieval, with an attenuated effect of pathology on memory at high levels of activation. It remains open if higher activity in the retrieval network serves as a functional reserve, or whether it reflects adaptive functional changes due to early pathology.
EEG‐based Analysis Reveals Different Effective Connectivity Patterns between Healthy Controls and MCI Patients in Motion Detection Tasks
Authors: Renli Alina Brighty , Sun Boxin , Gu Ming , Li Tongtong , Kavcic Voyko , Giordani Bruno 
Published: December 2023

AbstractBackgroundBrain connectivity has been proposed to identify people at risk for mild cognitive impairment (MCI). Existing work has mainly focused on functional connectivity which reflects the mutual dependence between brain regions. Effective connectivity, which represents the directed connectivity from one brain region to the other, is expected to provide more details on directed information flow in the brain network. The present study investigates how cognitive engagement changes the effective connectivity in the brain.MethodOur research focuses on task‐based EEG (64‐channel), where participants were asked to perform a motion direction discrimination task. The current dataset includes 56 consensus‐diagnosed, community‐dwelling African Americans (ages 60‐90 years, 28 healthy controls (HC) and 28 MCI patients) recruited through the Wayne State Institute of Gerontology and Michigan Alzheimer’s Disease Research Center with subjective cognitive complaints.We evaluated the effective connectivity at different time periods of the motion‐detection task across all the possible EEG region pairs using causalized convergent cross‐mapping (cCCM) of the current source density. For each task trial, the successive time periods being examined included: (I) stimulus onset to Go indication, (II) Go indication to motion‐stop, and (III) the button‐press period. For each subject, we calculated the mean, maximum and minimum of the cCCM vector for each EEG region pair and each time‐period, then selected the region pairs where the cCCM‐based effective connectivity of HC and MCI show a significant difference (p‐value<0.05).ResultOur analysis indicated that typically, MCI participants show more active effective connectivity or need more effort from stimulus onset to Go indication and then to motion stop, but HC participants show higher maximum and minimum effective connectivity values during the button‐press period, where coherent coordination is required among many region pairs.ConclusionHC and MCI do show significant differences in effective connectivity during each of the three periods of a motion detection task (marked by stimulus onset, Go indication, and button‐press) over many region pairs. Our analysis provides a massive pool of possible features for future biomarker development for effective discrimination of HC and MCI.
Funding: NSF‐2032709/Li; NIH‐1R21AG046637‐01A1/Kavcic and NIH‐1R01AG054484‐01A1/Kavcic; NIH‐P30AG053760/Paulson and NIH‐P30AG072931/Paulson.
Anabolic Androgenic Steroid predisposes to the neuropathology of Alzheimer’s disease: insights from Animal model
Authors: Memudu Adejoke Elizabeth , Moses Abel O 
Published: December 2023

AbstractBackgroundAnabolic androgenic steroids (AASs) are synthetic derivatives of testosterone use for body enhancement by athletes and its use has been abused over the years. Various studies have reported the harmful potential of AAS use, however, there is need to document its possibility as a risk factor in neuropathology of dementia. This study is to demonstrate potential of AAS as a risk factor in Alzheimer’s disease (AD) pathology by demonstrating changes in the neuro‐morphology, astrocytic proliferation and neurofibrillary tangle formation in animal model.MethodTwenty (20) adult male Wistar rats used were divided into four groups (A‐D), treated as follows, Control (A), Olive oil as vehicle (B), oral 120mg/kg of AAS for 21days (C), and 7 days withdrawal group following 120mg/kg/ 21days of AAS intake (D). Serum was assayed for lipid peroxidation marker Malondialdehyde (MDA) and antioxidant enzyme ‐superoxide Dismutase (SOD). The prefrontal cortices were processed and stained for Nissl (chromatophilic) bodies, astrocytes immunohistochemistry and Bielschowsky stain for neurofibrillary tangles.ResultAAS treated group has characteristic pathology of AD demonstrated by the presence of necrosis, chromatolysis, marked astrocytic proliferation and presence of neurofibrillary tangles using Bielschowsky stain along with an increase in MDA and decline in endogenous SOD activities as compared with the control and olive oil treated groups. The withdrawal group (D) had a notable or mild restoration of the neurons demonstrated by presence of few necrotic neurons, reduced reactive astrocytes (astrogliosis) proliferation, decline in MDA with an increase in SOD when compared to the AAS treated group.ConclusionAAS has the potential to predispose individual to the neuropathology of AD characterized by neurodegeneration, astrogliosis, neurofibrillary tangles even in the presence of endogenous antioxidant enzyme, however, upon discontinuation endogenous antioxidant enzyme level increases enabling neuro repair via mobbing off free radicals generated by AAS.
Cognitive reserve in figural and verbal memory in healthy older adults – preliminary results
Authors: Fischer Larissa , Molloy Eóin N. , Schwarck Svenja , Vockert Niklas , Hochkeppler Anne , Schumann‐Werner Beate , Büchel Anna‐Therese , Sick Florian , Kreißl Michael C. , Düzel Emrah , Maass Anne 
Published: December 2023

AbstractBackgroundCognitive reserve plays an important role in individual trajectories of age‐related memory decline, with education and semantic fluency representing cognitive reserve proxies (CRPs). Higher CR may attenuate well‐known effects of ageing on the brain, such as decreases in grey matter volume (GMV). We hypothesised that the known associations between age‐related GMV and cognition would be (differentially) attenuated by CRPs.MethodWe analysed 3‐Tesla T1‐weighted Multi‐Echo MPRAGE and cognitive data (Verbal Learning and Memory Test (VLMT), Rey Complex Figure Test (RCFT), and Regensburg Verbal Fluency Test (RWT)) from 51 cognitively normal adults (73.2±7.62 years, 31 male) in our new cohort established within the CRC1436 (https://sfb1436.de/). MRI data were pre‐processed and analysed using CAT12. We performed a whole‐brain linear regression to first assess age‐related reductions in GMV (covariates: sex, total intracranial volume (TIV), education), extracting mean betas for significant regions of interest (ROIs). We investigated the relationship between GMV in age‐vulnerable regions and memory using linear regressions in R (covariates: age, sex, TIV), and assessed CRPs as moderators on this relationship. Finally, we tested whether CRPs explained variance in memory performance over and above that of GMV and age. We accounted for multiple testing via Benjamini‐Hochberg‐correction.ResultWhole brain analyses identified bilateral hippocampal GMV as negatively associated with age (Fig.1). Linear regression analyses yielded a significant positive association between bilateral hippocampal GMV and figural memory (Fig.2). However, we observed no significant moderation by CRPs on this relationship. Finally, we observed weak evidence for cognitive reserve when adjusting for GMV and age, with higher variance explained by CRPs (Table 1). Semantic fluency positively predicted a figural memory composite when adjusting for right (p = 0.006) as well as left hippocampal GMV (p = 0.014). Education positively predicted verbal memory when adjusting for right (p<0.001) as well as left hippocampal GMV (p<0.001).ConclusionConsistent with operational definitions, our results provide weak evidence for semantic fluency and for education as CRPs in figural and verbal memory, respectively. However, our findings are preliminary, given the future addition of more participants. Nevertheless, these results provide important first insights into cognitive reserve in this developing cohort.
Investigating the Role of the Accumulation of Depressive Symptoms for the Risk of Dementia
Authors: Klee Matthias , Bodelet Julien , Muniz‐Terrera Graciela 
Published: December 2023

AbstractBackgroundDepressive symptoms vary over the life course and may result from a multitude of causes. With consolidating evidence about depressive symptoms as risk factor of dementia, and previous findings suggesting shared biological pathways of depression and dementia, involving e.g., inflammation, it remains unclear if depressive symptoms reflect a causal risk factor, or an early sign of dementia. We sought to explore the role of depressive symptoms accumulation over time regarding dementia incidence in old age.MethodWe applied the functional relevant life course exposure model (fRLM) to the Survey of Health Aging and Retirement in Europe (SHARE). More precisely, we modelled the accumulation of depressive symptoms, measured with the EURO‐D scale, over time utilizing functional regressions. Data from waves 2 (2006) to 8 (2020) of SHARE was used to examine the association of depressive symptoms with incident self‐report physician‐diagnosis of dementia.ResultIn total, 3,717 participants aged 65 to 70 without dementia at baseline (M [SD] age at baseline = 67.42 [1.70] years) with complete data, participation in at least 2 waves prior to dementia diagnosis or 3 waves prior to loss to follow‐up (M [SD] participation = 3.67 [0.88] waves, MD [SD] follow‐up = 8.0 [2.9] years) were included (58.7% female). Higher exposure to depressive symptoms over time was associated to higher dementia incidence (OR [95% CI] = 3.66 [1.84‐5.87]). Moreover, relevance of depressive symptoms for dementia incidence varied across time windows, suggesting differential associations of depressive symptoms to dementia risk as a function of age. Highest relevance of exposure to depressive symptoms was observed for age 72‐75, i.e., close to diagnosis (Median [SD] age at diagnosis = 76 [3.26] years).ConclusionWhile we observed an association of depressive symptoms with dementia risk, our novel approach extends on previous findings suggesting highest relevance, i.e., predictive ability of depressive symptoms close to diagnosis. Given a build‐up of pathological changes relating to dementia starting as early as two decades prior to cognitive impairment and diagnosis, this suggests depressive symptoms not to be a causal risk factor but rather an early sign or accompanying symptom of dementia.
Impact of Infection Control Measures on Effectiveness of Cognitive Stimulation Therapy
Authors: Choy Jacky Chak Pui , Wong Gloria HY 
Published: December 2023

AbstractBackgroundPeople living with dementia are at higher risk of contracting and dying from SARS‐CoV‐2. Protection measures such as wearing a mask remained necessary in dementia service facilities, despite their limiting effects on communication and interactions. Their impacts on existing evidence‐based psychosocial interventions offered in these facilities, such as Cognitive Stimulation Therapy (CST), are yet unknown.MethodMixed‐methods study using data from a larger randomised controlled trial partially disrupted by the COVID‐19 pandemic. People with mild or moderate dementia randomised into receiving CST (n = 72) were compared with those receiving usual care (n = 72) for cognitive (ADAS‐Cog) and quality of life (QoL‐AD) changes. To investigate the impact of infection control measures on CST effectiveness, interaction effect between timing of enrolment (before vs after COVID‐19 outbreak) and intervention group was tested. Focus groups were conducted with persons with dementia who have received CST and their families (n = 22).ResultParticipants who received CST reported better quality of life (B = 4.195, F = 28.159, p <0.001) compared with those who received usual care, controlling for demographics and antidementia medications. For cognition, an interaction effect was observed (F = 4.557, p = 0.036) between timing of enrolment and group. CST maintained cognition only in groups before COVID‐19 outbreak (marginal means of ADAS‐Cog improvement: +0.453 in CST vs ‐1.465 in usual care) but not in groups after the outbreak (‐2.104 vs +0.716). Persons living with dementia and their families reported difficulties hearing, being heard, recognising and interacting with other CST group members, and reduced efforts in participation due to discomfort wearing a mask,ConclusionInfection control measures may reduce the cognitive benefits of CST, which may be due to their effects on speech intelligibility and other interactions in a psychosocial intervention group. In the post‐COVID era, alternative measures such as virtual CST delivered via an online meeting platform should be investigated.
Influence of Epigallocatechin gallate stabilized Gold nanoparticles in amyloid beta fibril inhibition
Authors: Subramaniyam Rajalakshmi , Balashanmugham Umamahesh 
Published: December 2023

AbstractBackgroundA pathological Hallmark of Alzheimer’s Disease (AD) is the significant deposition of amyloid beta (Aβ) plaques in the brain. Several studies were reported to inhibit the Aβ fibrillation using nanoparticles, nanoclusters and bioconjugate nanomaterials for Alzheimer’s treatment. In recent years, natural compound (phytochemicals) have been largely used to study and identified as promising agents for the prevention and treatment of neurodegenerative diseases including AD.MethodGold nanoparticle with appropriate surface conjugates with higher affinity has been studied and acknowledge the interaction between Bio‐Nano interfaces. The surface covering or anchoring conjugates will play a major role in vitro and in vivo. Herein, we reported Epigallocatechin gallate (EGCG) stabilized gold nanoparticle (AuNps) were synthesised as a Aβ inhibitor.ResultThe synthesised EGCG‐AuNps Characterized using UV‐Vis Spectroscopy, DLS, XRD, SEM (EDAX) and TEM (SAED) and the biocompatibility were studied by using MTT and scratch assay. The synthesised EGCG‐AuNPs inhibiting Aβ aggregation, dissociation Aβ fibrils which lead to prevent plaque formation, which confirmed using Thioflavin T‐assay and TEM studies.ConclusionThis work provides new insights into the synthesised AuNps as functional therapeutic agent for AD.