bluuebunny/crossref_metadata_2025_split huggingface dataset:
Capturing Morphometric Patterns of Alzheimer's Disease Progression with a TV‐L1 Ordinal Machine Learning Model
Authors: Zhao Yuji , Gutman Boris A 
Published: December 2022

AbstractBackgroundThe most common neurodegenerative disease, Alzheimer’s disease (AD) constitutes about two thirds of cases of dementia overall [1]. Mild cognitive impairment (MCI) is considered to be a transitional stage between aging and AD [2]. This general AD staging information and ample MCI data motivate a further investigation on the subcortical shape analysis incorporating MCI data in AD study. We therefore designed a novel logistic regression model to explore more morphometric patterns associated with the disease progression of AD.MethodIn this study, we used T1‐weighted MRI data of 225 controls, 398 MCI patients and 195 AD patients from the ADNI‐1 dataset. We designed an ordinal logistic regression model [3] regularized by total variation (TV) and L1 penalization term [4]. Unlike the binary or conventional multi‐class classifiers, our TV‐L1 ordinal classifier is capable of sparse‐spatially utilizing ordinal morphometric features to learn potential ordinal patterns and predict normal control, MCI and AD all at once in a single model. We extracted vertex‐wise thickness features in 7 subcortical regions [5] and trained our model with all 14 regions of interest (ROI) across the whole brain. To evaluate the performance and find the optimal hyper‐parameters in our classification task, we computed the precision, recall score and f‐score with a 4‐fold cross‐validation (CV) grid search. For comparison we also trained a TV‐L1 logistic regression model binary classifiers for controls and AD.ResultTable 1 shows the confusion matrix, precision, recall score and f‐score. Based on the 4‐fold CV, the average precision and recall score for control, MCI and AD are 0.457 and 0.443 respectively. The weights map of the trained TV‐L1 logistic regression model is shown in Figure 1, and that of the TV‐L1 ordinal classifier in Figure 2.ConclusionBy designing an TV‐L1 ordinal logistic regression machine learning model, we performed a shape feature‐based classification for controls, MCI and AD with f1 score substantially above chance across all three AD stages. The trained weights map reveals subtle morphometric patterns associated with the disease progression from a cognitively normal state to MCI and eventually AD stage. This could potentially provide more insights for clinical studies of AD.
Dopaminergic and noradrenergic integrity are differentially associated with late‐life memory performance
Authors: Dahl Martin J , Bachman Shelby L , Dutt Shubir , Düzel Sandra , Lindenberger Ulman , Kühn Simone , Werkle‐Bergner Markus , Mather Mara 
Published: December 2022

AbstractBackgroundAge‐related deficits in dopaminergic neuromodulation play a key role in determining memory decline. Facilitated by technical advancements, recent research has also implicated noradrenergic neuromodulation in shaping late‐life memory development. However, investigations disentangling the contribution of the two neuromodulators to the neurobiological basis of human cognitive aging are scarce.MethodWe collected high‐resolution magnetic resonance imaging (MRI) data of the dopaminergic substantia nigra–ventral tegmental area and the noradrenergic locus coeruleus of 320 younger and older adults at two time points (T1, T2; ∼1.9 years delay). The imaging protocol included three scans sensitive for the substantia nigra–ventral tegmental area and locus coeruleus—a Fast‐Spin‐Echo [FSE] sequence, and a Magnetization‐Transfer sequence, acquired once with a dedicated magnetic saturation pulse [MT+] and once without, resulting in a proton‐density like image [MT–]. We aggregated the information shared across imaging modalities by estimating multimodal latent factors expressing dopaminergic and noradrenergic integrity.Participants also completed a comprehensive cognitive battery at three time points (T1, T2, T3), including tests of fluid intelligence, episodic and working memory. We used structural equation modeling to evaluate cross‐sectional associations of substantia nigra–ventral tegmental area and locus coeruleus integrity with late‐life cognition. In a second set of models, we probed longitudinal changes in substantia nigra–ventral tegmental area and locus coeruleus integrity (T1–T2) and used them to predict participants’ future cognitive performance (at T3).ResultCross‐sectionally, we found differential associations of dopaminergic and noradrenergic nuclei with late‐life cognition. While locus coeruleus integrity was related to better episodic memory across several memory tasks, substantia nigra–ventral tegmental area integrity was related to working memory performance. Moreover, consistent with a largely shared biosynthesis of the neuromodulators, dopaminergic and noradrenergic nuclei were positively related. Longitudinally, we found that older age was associated with more‐negative change in substantia nigra–ventral tegmental area and locus coeruleus integrity (T1–T2). Importantly, changes in locus coeruleus integrity reliably predicted future episodic memory performance (at T3).ConclusionThese findings support the utility of in‐vivo indices for catecholaminergic integrity and highlight differential roles of dopaminergic and noradrenergic neuromodulation in late‐life cognitive decline.
Neuroinflammation is associated with the rising of early Alzheimer’s disease pathology in amyloid‐negative elderly
Authors: Wang Yi‐Ting , Bezgin Gleb , Tissot Cécile , Lussier Firoza Z , Therriault Joseph , Servaes Stijn , Stevenson Jenna , Arias Jaime Fernandez , Kang Min Su , Rahmouni Nesrine , Rosa‐Neto Pedro 
Published: December 2022

AbstractBackgroundAmyloid‐β (Aβ) and tau are the two well‐recognised pathological hallmarks of Alzheimer’s disease (AD). In the recent decades, increasing evidence supports neuroinflammation as one of the earliest pathomechanistic alterations throughout the AD continuum. However, little is known about the spatial and temporal patterns of neuroinflammatory processes based on AD pathological status. Furthermore, it also remains elusive how longitudinal change of neuroinflammation affects cerebral amyloid and tau load in the trajectory of AD.MethodWe examined a total number of 122 subjects (mean age= 65.6 years, 66.4% women, 33.1% APOEɛ4 carriers) from the TRIAD cohort at McGill University Research Centre for Studies in Aging. Neuroinflammation, cerebral Aβ load and tau deposition were assessed with positron emission tomography (PET) radiotracers [11C]PBR28, [18F]AZD4694 ([18F]NAV4694) and [18F]MK6240 respectively. Amyloid‐β positivity was determined by a cortical composite [18F]NAV4694 SUVR threshold of 1.55, based on previously published method. Voxelwise analyses were performed to evaluate the relationships between cerebral amyloid load and neuroinflammation. A subgroup of 42 subjects who had underwent two‐year follow‐up PET scans were used to study how the longitudinal change of neuroinflammation affects other AD hallmarks.ResultAt early stages of amyloid pathology, we found a positive linear relationship between neuroinflammation and amyloid load. Voxelwise analyses also revealed a stronger association between amyloid and neuroinflammation among the Aβ‐negative subjects. Longitudinally, the increase of neuroinflammation was linked to the accumulation of cerebral amyloid and tau in Aβ‐negative subjects.ConclusionNeuroinflammation was associated with amyloid at early stages of amyloid pathology. In addition, elevation of neuroinflammation was associated with the increase of amyloid and tau accumulation in Aβ‐negative subjects.
Plasma Markers of Neurodegeneration Associated with Postoperative Delirium in an Older Elective Arthroplasty Population
Authors: Sweeney Aoife , Passmore Anthony Peter , Beverland David , McGuinness Bernadette , McAuley Daniel F , Mawhinney Tim , O'Brien Seamus , Schott Jonathan M , Heslegrave Amanda , Zetterberg Henrik , Cunningham Emma L 
Published: December 2022

AbstractBackgroundPostoperative delirium (POD) is associated with subsequent cognitive decline. It is not yet clear to what extent that is because delirium indicates underlying neurodegeneration.MethodAn observational cohort study of postoperative delirium (POD) in an elective arthroplasty population recruited 315 individuals aged over 65, without a diagnosis of dementia. Blood was sampled pre‐operatively at the time of anaesthesia and on day 1 postoperatively. Following surgery, delirium was assessed daily on days 1‐3 postoperatively. Stored plasma was analysed for markers of inflammation and neurodegeneration. Statistical analysis was carried out to determine associations of these markers with POD.ResultThose who developed POD (n = 44) had statistically significantly lower preoperative plasma amyloid‐beta 1‐40 (Aβ40; p=0.01) and postoperative day one plasma Aβ42/40 ratio (p=0.02) compared to participants who did not develop POD. A change in postoperative plasma neurofilament light (NFL), a marker of axonal degeneration, relative to preoperative NFL was associated with POD (p=0.028). POD was also associated with a statistically significantly change in postoperative plasma phosphorylated tau181 (pTau181) relative to preoperative levels (p<0.001).ConclusionDevelopment of POD in an older population without a diagnosis of dementia is associated with both i) preoperative plasma markers in keeping with neurodegeneration and ii) a different pattern of postoperative change in plasma markers of neuronal damage compared to people who did not develop POD. This suggests that i) people, without a pre‐existing diagnosis of dementia, who develop POD after elective arthroplasty surgery are more likely to have underlying neurodegeneration and ii) participants developing POD have a different neuronal response to peri‐operative insults than participants who do not develop POD.
Cerebral Small Vessel Disease and Gait Speed in Older Adults without Dementia
Authors: Vazquez Juan P , Verghese Joe , Allali Gilles , Barzilai Nir , Milman Sofiya , Blumen Helena M 
Published: December 2022

AbstractBackgroundDisturbances in gait have been found to be predictors of dementia and mobility disability in older adults. The relationship between cerebral small vessel disease (CSVD) and gait speed during simple (normal pace walking; NPW) and complex walking (walking‐while talking; WWT) conditions are not well understood. The current study examined the relationship between CSVD (as assessed as white matter hyperintensities and lacunes), NPW and WWT in older adults without dementia.MethodsNPW and WWT speeds were measured in 113 older adults (46.9% female, 53.1%% male, mean age=78.6±6.3) without dementia enrolled in the LonGenity study. Using an established rating system, white matter hyperintensities (WMH) and lacunes of presumed vascular origin were quantified from Fluid Attenuated Inversion Recovery (FLAIR) images from the same participants. Linear regression models adjusted for age, gender, global health, cohort, and estimated total intracranial volume were used to examine the association between NPW and DTW velocity and markers of CSVD.ResultsNumber of WMH in both the basal ganglia and the temporal lobes were associated with slower NPW velocity in our adjusted models (β=‐3.274 cm/s p=.047, β=‐3.113 cm/s p=.048, respectively). Number of frontal lobe WMH was associated with slower NPW velocity in our unadjusted model (β=‐3.316 cm/s p=.017) but not in the adjusted model (β=‐1.521 cm/s p=.262). WMH were not found to be significantly associated with WWT velocity. Lacunes of presumed vascular origin were not found to be significantly associated with neither NPW or DTW velocity. Significant interactions between measures of CSVD and gender, age, or cohort were not found in our models.ConclusionGait is a complex task requiring the integration of both cognitive and motor function across different brain regions. We find here that higher CSVD burden as measured by the presence of WMH in the basal ganglia and temporal lobes are independently associated with slower normal gait velocity. Interestingly, no such association was seen with WWT, a task requiring a higher cognitive load. Further studies are needed to establish temporality of these lesions with declines in gait velocity. Doing so may show utility of CSVD imaging markers as predictors of gait disturbances and dementia.
Roadmap to implementation of a fully automated blood‐based biomarker test to facilitate diagnosis and treatment in early Alzheimer’s disease
Authors: Carboni Margherita , Suridjan Ivonne , van der Flier Wiesje M. , Monsch Andreas U. , Burnie Nerida , Baldor Robert , Sabbagh Marwan N. , Vilaseca Josep , Cai Dongming , Quevenco Frances‐Catherine , Golebiewska Ewelina , Lah James J. 
Published: December 2022

AbstractBackgroundRoutine implementation of a fully automated blood based biomarker (BBBM) will expand access to diagnosis and initiation of disease modifying therapies (DMTs) in Alzheimer’s disease (AD). This analysis explores current obstacles in the AD diagnostic pathway, the unmet need for a BBBM test to facilitate referral decisions, and barriers to BBBM testing.MethodData are from quantitative (n=1,694 physicians) and qualitative (n=186 healthcare professionals/payers) surveys in US/China/UK/Germany/Spain and two Advisory Boards (US/Europe). Primary care physicians (PCPs) and specialists (neurologists/geriatricians/psychiatrists) were represented.ResultFrom the quantitative survey, between 17.8% (China) and 83.5% (France) patients with cognitive impairment present first to primary care, with the rest presenting directly to secondary care. 73% PCPs use cognitive assessment alone for referral, with 35% using laboratory results. Confirmatory testing with positron‐emission tomography (PET) or cerebrospinal fluid (CSF) analysis is rare in the primary care setting. PCPs request PET and CSF for 8% and 12% patients, respectively, compared with 40% and 36% for specialist neurologists. Most centers use local guidelines to decide CSF/PET referral. 31% of patients diagnosed with AD underwent CSF/PET. Time to clinical diagnosis varies between countries and pathways, from 14 weeks in primary care to 29 weeks for patients referred to a specialist.The Advisory Board considered a minimally‐invasive, patient‐friendly BBBM with high negative predictive value (NPV > 90%) and moderate positive predictive value for Ab positivity could act as triage, excluding patients not needing confirmatory testing, while freeing capacity and allowing timely intervention for all others. The BBBM test would be useful in primary and secondary care, although payer coverage in primary care may limit its immediate use. In secondary care, the BBBM test could reduce unnecessary/invasive amyloid testing, and streamline the diagnostic pathway.ConclusionAn easy‐to‐use, minimally invasive BBBM test that detects amyloid pathology could be used with other tests/assessments to guide further diagnostic procedures or onward referral, reducing time to diagnosis and allowing timely access to potential DMTs. BBBMs have potential to be a first biomarker test, providing early‐stage information on underlying pathophysiology.
Novel Diagnostic 64Cu PET Imaging Agents for Alzheimer’s Disease
Authors: Mirica Liviu M 
Published: December 2022

AbstractBackgroundMetal radiotracers exhibit beneficial properties that can improve in vivo positron emission tomography (PET) imaging over traditional radionuclides, such as longer half‐lives, facile last‐stage radiolabeling steps, and the potential for dual imaging‐therapy applications. Among such radionuclides, 64Cu exhibits a longer half‐life (t1/2 = 12.7 h) that allows for later PET imaging times and the ability to distribute 64Cu imaging agents to facilities that do not have an on‐site cyclotron.MethodThe employed approach uses a bifunctional chelator with two Aβ‐interacting fragments that dramatically improves the Aβ‐binding affinity and lipophilicity for favorable blood‐brain barrier (BBB) penetration, while the use of optimized‐length spacers between the Cu‐chelating group and the Aβ‐interacting fragments further improves the in vivo Aβ‐binding specificity and brain uptake of the corresponding 64Cu PET imaging agent.ResultHerein, we report to a novel molecular architecture for 64Cu PET imaging agents that show appreciable in vivo brain uptake and exhibits high specific affinity for beta‐amyloid aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of WT mice.Conclusion
64Cu PET imaging agents can be used for in vivo imaging of beta‐amyloid aggregates.
The relationship between cerebrospinal fluid neurofilament light protein biomarker and cortical thinning across the spectrum of Alzheimer’s disease
Authors: Yadlapalli Vineetha , Sharp Elizabeth , Oh Hwamee 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) is an age‐related neurodegenerative disease pathologically characterized by beta‐amyloid plaque accumulation and tau‐protein neurofibrillary tangles in the brain. Recent research has sought to identify additional potential biomarkers for earlier detection and treatment of the disease, including one such protein named cerebrospinal fluid neurofilament light protein (CSF NfL). Despite CSF NfL’s essential contributions to forming the neuronal cytoskeleton and supporting neuroaxonal function, the roles of CSF NfL in longitudinal AD progression and AD‐related neurodegeneration remain to be elucidated. This study examined the relationships between baseline CSF NfL levels and cortical gray matter atrophy along the spectrum of AD on a longitudinal scale over the span of two years.MethodWe included 179 study subjects (mean age = 74.21; 90 Females) with 60 cognitively normal (CN) individuals, 63 patients with late mild cognitive impairment (LMCI), and 56 AD patients from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Baseline CSF NfL measures and demographic data were downloaded from the ADNI study. Structural magnetic resonance imaging (MRI) scans from three time points (baseline, year 1, year 2) were processed and analyzed using FreeSurfer longitudinal analysis pipelines to compute percent changes in gray matter thickness for Year 1 (Y1) and Year 2 (Y2) compared with baseline, respectively.ResultBaseline CSF NfL was positively associated with greater cortical thinning across all study subjects, which were more pronounced in Y2. This relationship between baseline CSF NfL and cortical thinning remained the same in the AD diagnosis group. For the LMCI diagnosis group, there was no clear trend between baseline CSF NfL measures and percent changes in cortical thickness. Interestingly, a positive association between baseline CSF NfL value and percent changes in cortical thickness was observed in the CN diagnosis group at Y1, especially in the left hemisphere.ConclusionCSF NfL may contribute to the disease progression potentially through cortical atrophy and has an ability to predict cortical thinning over the short period of time. Longitudinal follow‐up analyses are warranted to incorporate its trajectory into the A/T/N classification system.
Associations Between Age, Hippocampal Volume, and Spatial Working Memory in Periadolescent Children: Preliminary Findings from the PRANK Study
Authors: Sexton Jennifer N , Ramirez Meghan K , Phipps Connor J , Heller Abi , Behm Lillian , Zatkalik Abigail L , Nickolas Kristen , Maerlender Arthur C. , Phatak Vaishali S , Cramer Justin A. , Blair James , Murman Daniel L , Warren David E 
Published: December 2022

AbstractBackgroundDuring childhood development, particularly the periadolescent epoch, significant changes in cognition and brain structure are known to occur. The development of spatial working memory (SWM), for example, continues throughout the teenage years. The hippocampus is necessary for normal SWM, as seen by the substantial memory deficits seen in patients with Alzheimer's disease (AD) and their associated hippocampal pathology. It is hypothesized that vulnerability to AD could be modulated by early brain development, so understanding the developmental relationship between hippocampal volume (HV) and SWM would provide a key baseline for comparison of different trajectories. Our ongoing study, Polygenetic Risk of Alzheimer’s Disease in Nebraska Kids (PRANK; R01 AG064247), measures brain structure/function, cognitive abilities, and Alzheimer’s polygenetic risk score in periadolescent children (age 8‐13). Here, we report preliminary data from PRANK measuring the association between HV, age, and SWM.MethodUsing preliminary data from the PRANK project, we investigated the association between SWM, age, and HV. Our sample included children (N=80, age 8‐13 years), recruited from the community and tested at University of Nebraska Medical Center; demographics were consistent with the recruitment area. SWM was measured using the Spatial Working Memory task between errors term from the Cambridge Neuropsychological Battery. Structural MRI data were collected using a 3T Siemens Prisma instrument. HV was measured using automated segmentation in Freesurfer.ResultSWM was associated with age, r(80) = ‐.334, p = .002, such that older children showed fewer spatial working memory errors than younger children. HV was not significantly associated with SWM, controlling for age, r(77) = ‐.027, p = .813. However, the direction of the relationship between HV and SWM (larger HV associated with fewer SWM errors) was consistent with previous literature (Faridi et al., 2015).ConclusionThese preliminary results suggest that increasing age is associated with better SWM in typical childhood; findings for HV were non‐significant. We anticipate that our study’s full sample will provide appropriate statistical power to test the association of SWM with HV. In future efforts, we will investigate this association as it relates to polygenic risk for Alzheimer’s disease and whether these results generalize to children with Down syndrome.
Comprehensive H2O Molecules Regulation via Deep Eutectic Solvents for Ultra‐Stable Zinc Metal Anode
Authors: Li Ming , Wang Xuanpeng , Hu Jisong , Zhu Jiexin , Niu Chaojiang , Zhang Huazhang , Li Cong , Wu Buke , Han Chunhua , Mai Liqiang 
Published: December 2022

AbstractThe corrosion, parasitic reactions, and aggravated dendrite growth severely restrict development of aqueous Zn metal batteries. Here, we report a novel strategy to break the hydrogen bond network between water molecules and construct the Zn(TFSI)2‐sulfolane‐H2O deep eutectic solvents. This strategy cuts off the transfer of protons/hydroxides and inhibits the activity of H2O, as reflected in a much lower freezing point (<−80 °C), a significantly larger electrochemical stable window (>3 V), and suppressed evaporative water from electrolytes. Stable Zn plating/stripping for over 9600 h was obtained. Based on experimental characterizations and theoretical simulations, it has been proved that sulfolane can effectively regulate solvation shell and simultaneously build the multifunctional Zn‐electrolyte interface. Moreover, the multi‐layer homemade modular cell and 1.32 Ah pouch cell further confirm its prospect for practical application.