bluuebunny/crossref_metadata_2025 huggingface dataset:
Line source representation for laser-generated ultrasound in aluminum
Authors: Bernstein Johanna R. , Spicer James B.
Published: July 2002

Modeling the ultrasound generated by a laser source is critical for using noncontact laser-generated ultrasonic systems for the characterization of material properties. In this work, a laser line source was modeled and verified experimentally by measuring the ultrasonic shear wave signal generated in aluminum with a broadband laser generation/electromagnetic acoustic transducer (EMAT)-detection system. Results of calculations and experiments show that the amplitude directivity of a laser line source is identical to that of a point source in the plane perpendicular to the line axis while the temporal dependence differs.
Effects of ipsilateral and contralateral precursors on the temporal effect in simultaneous masking with pure tones
Authors: Bacon Sid P. , Healy Eric W.
Published: July 2002

In tone-on-tone masking, thresholds often decrease as the onset of the signal is delayed relative to the onset of the masker, especially when the frequency of the masker is higher than the frequency of the signal. This temporal effect was studied here by using a tonal “precursor,” whose offset preceded the onset of the tonal masker (and signal). Under the right conditions, the precursor can reduce or eliminate the temporal effect by decreasing the threshold for a signal at masker onset, presumably for the same reason that the threshold decreases as a signal is delayed relative to the onset of a masker. In the present study, the frequency of the signal was 4000 Hz, and the frequency of the masker and precursor was typically 5000 Hz. In experiment 1, the precursor was presented to the ear receiving the masker and signal (ipsilateral precursor); in experiment 2, it was presented to the opposite ear (contralateral precursor). The results from experiment 1 can be summarized as follows: the ipsilateral precursor (a) reaches its maximum effectiveness (in reducing the temporal effect) for precursor durations of 200–400 ms; (b) is ineffective once the delay between its offset and the onset of the masker reaches about 50–100 ms; (c) is generally ineffective when its level is 10 or more dB lower than the level of the masker, but is effective when its level is equal to or greater than the level of the masker; and (d) becomes progressively less effective as its frequency is either increased or decreased relative to the frequency of the masker. The results from experiment 2 can be summarized simply by stating that the contralateral precursor is ineffective in reducing the temporal effect. These results suggest that the effect of the precursor may be mediated peripherally.
Associative polymers bearing n-alkyl hydrophobes: Rheological evidence for microgel-like behavior
Authors: English Robert J. , Raghavan Srinivasa R. , Jenkins Richard D. , Khan Saad A.
Published: July 2002

Rheological techniques are used to probe the behavior of hydrophobic alkali-swellable emulsion (HASE) polymers, bearing n-alkyl hydrophobes, in aqueous alkaline media. The polymers possess a comb-like architecture with a polyelectrolyte backbone (ethyl acrylate-co-methacrylic acid) and hydrophobes (∼16 per polymer chain) tethered to the backbone via polyether side chains. The size of the hydrophobes is varied from n-C8 to n-C20 in this study. It is shown that, at such a level of hydrophobic modification, and at relatively high polymer concentrations, the microstructure in these polymer systems is akin to that existing in concentrated microgels. Thus, the original polymer latex particles swell extensively in alkaline media and disintegrate to form a system of close-packed, compressible (“soft”) aggregates. This is reflected in the rheological response of the system where we observe a high steady shear viscosity with no zero-shear plateau at low shear rates followed by considerable shear thinning and, a characteristic power-law behavior (G′, G″∼ω0.4) under oscillatory shear persisting over a broad range of time scales. Concentration-independent master curves are obtained for the storage modulus, G′, with the level of G′ increasing with hydrophobe size. The similarity in the dynamic response suggests that there exists a qualitative equivalence in microstructure over the range of systems, the only difference being the “softness” or compressibility of the particles. Data from this study are also contrasted with those for a similar HASE polymer bearing a smaller number of alkylaryl hydrophobes [J. Rheol. 41, 427–444 (1997)]. In the latter case, the rheology can be interpreted in terms of hydrophobic associations and chain entanglements occurring in solution. Thus, subtle variations in molecular architecture are shown to cause significant differences in morphology and microstructure for these polymer systems.
Oxygen Vacancy‐Mediated Growth of Amorphous Discharge Products toward an Ultrawide Band Light‐Assisted Li–O2 Batteries
Authors: Li Fei , Li Ma‐Lin , Wang Huan‐Feng , Wang Xiao‐Xue , Zheng Li‐Jun , Guan De‐Hui , Chang Li‐Min , Xu Ji‐Jing , Wang Yu
Published: February 2022

Photoassisted electrochemical reaction is regarded as an effective approach to reduce the overpotential of lithium–oxygen (Li–O2) batteries. However, the achievement of both broadband absorption and long term battery cycling stability are still a formidable challenge. Herein, an oxygen vacancy‐mediated fast kinetics for a photoassisted Li–O2 system is developed with a silver/bismuth molybdate (Ag/Bi2MoO6) hybrid cathode. The cathode can offer both double advantages for light absorption covering UV to visible region and excellent electrochemical activity for O2. Upon discharging, the photoexcited electrons from Ag nanoplate based on the localized surface plasmon resonance (LSPR) are injected into the oxygen vacancy in Bi2MoO6. The fast oxygen reaction kinetics generate the amorphous Li2O2, and the discharge plateau is improved to 3.05 V. Upon charging, the photoexcited holes are capable to decompose amorphous Li2O2 promptly, yielding a very low charge plateau of 3.25 V. A first cycle round‐trip efficiency is 93.8% and retention of 70% over 500 h, which is the longest cycle life ever reported in photoassisted Li–O2 batteries. This work offers a general and reliable strategy for boosting the electrochemical kinetics by tailoring the crystalline of Li2O2 with wide‐band light.
Electrically Programmable Interfacial Adhesion for Ultrastrong Hydrogel Bonding
Authors: Liu Yaqian , Wang Pudi , Su Xing , Xu Liang , Tian Zhuoling , Wang Hao , Ji Guojun , Huang Jianyong
Published: February 2022

Adjustable interfacial adhesion is of great significance in smart‐hydrogel‐related engineering fields. This study presents an electroadhesion strategy for universal and ultrastrong hydrogel bonding with electrically programmable strength. An ionic hydrogel containing lithium ions is designed to achieve hydrated‐ion‐diffusion‐mediated interfacial adhesion, where external electric fields are employed to precisely control spatiotemporal dynamics of the ion diffusion across ionic adhesion region (IAR). The hydrogel can realize a universal, ultrastrong, efficient, tough, reversible, and environmentally tolerant electroadhesion to diverse hydrogels, whose peak adhesion strength and interfacial adhesion toughness are as high as 1.2 MPa and 3750 J m−2, respectively. With a mechanoelectric coupling model, the dominant role of the hydrated ions in IAR played in the interfacial electroadhesion is further quantitatively revealed. The proposed strategy opens a door for developing high‐performance adhesion hydrogels with electrically programmable functions, which are indispensable for various emerging fields like flexible electronics and soft robotics.
2D FeOCl: A Highly In‐Plane Anisotropic Antiferromagnetic Semiconductor Synthesized via Temperature‐Oscillation Chemical Vapor Transport
Authors: Zeng Yi , Gu Pingfan , Zhao Zijing , Zhang Biao , Lin Zhongchong , Peng Yuxuan , Li Wei , Zhao Wanting , Leng Yuchen , Tan Pingheng , Yang Teng , Zhang Zhidong , Song Youting , Yang Jinbo , Ye Yu , Tian Kesong , Hou Yanglong
Published: February 2022

2D van der Waals (vdW) transition‐metal oxyhalides with low symmetry, novel magnetism, and good stability provide a versatile platform for conducting fundamental research and developing spintronics. Antiferromagnetic FeOCl has attracted significant interest owing to its unique semiconductor properties and relatively high Néel temperature. Herein, good‐quality centimeter‐scale FeOCl single crystals are controllably synthesized using the universal temperature‐oscillation chemical vapor transport (TO‐CVT) method. The crystal structure, bandgap, and anisotropic behavior of the 2D FeOCl are explored in detail. The absorption spectrum and electrical measurements reveal that 2D FeOCl is a semiconductor with an optical bandgap of ≈2.1 eV and a resistivity of ≈10−1 Ω m at 295 K, and the bandgap increases with decreasing thickness. Strong in‐plane optical and electrical anisotropies are observed in 2D FeOCl flakes, and the maximum resistance anisotropic ratio reaches 2.66 at 295 K. Additionally, the lattice vibration modes are studied through temperature‐dependent Raman spectra and first‐principles density functional calculations. A significant decrease in the Raman frequencies below the Néel temperature is observed, which results from the strong spin−phonon coupling effect in 2D FeOCl. This study provides a high‐quality low‐symmetry vdW magnetic candidate for miniaturized spintronics.
The problem with open geospatial data for on‐farm research
Authors: Prince Czarnecki Joby M. , Jones Mary Ann
Published: February 2022

Scientists are under increased pressure to provide research data freely and openly to all interested parties as a means of furthering science. More than sharing data, there is an additional expectation that data comply to Findable, Accessible, Interoperable, Reusable (FAIR) principles. The requirement to share data presents challenges for farm geospatial data. The primary contention of this commentary is that data sharing requirements will make on‐farm research increasingly difficult while also not achieving the stated purposes of opening data. De‐identification of farm geospatial data is not sufficient to protect privacy, reducing likelihood of participation in research. Moreover, de‐identified farm geospatial data will have greatly reduced reusability. Limited guidance is available on appropriate mechanisms for sharing of farm geospatial data. This commentary briefly summarizes benefits and realities of data sharing, expands discussion to support the primary contention, and concludes with high‐level suggestions for moving forward.
Suppression of cannibalism in the intertidal copepod Tigriopus japonicus (Mori, 1932) and improvements in population density using artificial substrates
Authors: Koga Shinichi , Takayama Yoshiki , Toda Tatsuki
Published: February 2022

The present study investigated population growth, egg production and cannibalism in the intertidal harpacticoid copepod Tigriopus japonicus (Mori, 1932). Copepods were cultured on artificial substrates with different surface areas, from 13.5 × 103 to 10.6 × 104 mm2, to clarify the effect of surface area in a culture vessel on population density. The cannibalism rate at a surface area of 10.6 × 104 mm2 was significantly lower (by a sixth) than that at 13.5 × 103 mm2. These results suggest that artificial substrates play a role in preventing cannibalism by providing shelter and can increase the stocking population density of T. japonicus in a vessel.
Higher global efficiency in functional brain network could delay cognitive decline in amyloid‐positive individuals: The cognitive reserve theory
Authors: Seo Eun Hyun , Yoon Hyung‐Jun , Heo Mina ,   for the Alzheimer’s Disease Neuroimaing Initiative
Published: February 2022

Background

It is known that cognitive reserve (CR) support resilience against the effects of brain pathology. However, it still remains to be elucidated what can be served as a proxy for the CR. In the current study we investigated whether particular functional brain features have protective effect for future cognitive decline. We also examined if the relationship is different according to amyloid‐beta (aß) positivity.

Method

Functional MRI data, clinical and neuropsychological data, and follow‐up information were downloaded from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. In the final analysis, 48 cognitively normal (CN) elderly and 46 elderly with mild cognitive impairment (MCI) were included. Cognitive decline was measured by mini mental status examination (MMSE) change score from baseline and the last follow‐up. Resting state function image data processing was carried out using FMRIB’s Software Library and Brain Connectivity Toolbox. Cox proportional hazards models were conducted to investigate the associations between several cognitive reserve proxies and future cognitive decline. In addition, the relationship was explored separately for aß positivity

Result

Mean follow‐up month were 45.84 (50.33 for CN, 41.15 for MCI). Based on MMSE change score, 41 were identified as cognitively decliners. Among baseline functional brain network parameters (density, clustering coefficients, path length, and global efficiency) education, and American National Adult Reading Test (AMNART) error score, and 4 ADNI neuropsychological summary scores, global efficiency (HR=2.04, 95% CI 1.07‐3.91) and ADNI‐EF score (HR=0.41, 95% CI 0.26‐0.64) were significant in the Cox proportional hazard model (Figure1A). This association was observed only in aß positive group, whereas no significant association was found in aß negative group (Figure 1BC).

Conclusion

Our findings indicate that higher global efficiency in functional brain network and better executive function could delay cognitive decline, especially in aß positive group. Cognitive reserve is to preserve cognitive function better in the presence of brain pathology. Our study preliminary suggest that higher brain efficiency could play a key role in cognitive reserve in elders.
Serum oxylipins indicate subcortical ischemic vascular disease in patients with clinical stroke
Authors: Yu Di , Taha Ameer , Pedersen Theresa , Joel Ramirez , Goubran Maged , Ozzoude Miracle , Gao Fuqiang , Casaubon Leanne , Bartha Robert , Symons Sean , Kwan Donna , Dowlatshahi Dar , Hassan Ayman , Mandzia Jennifer , Sahlas Demetrios J. , Saposnik Gustavo , Arnott Stephen R. , Tan Brian , Lanctôt Krista L. , Masellis Mario , Black Sandra E. , Swartz Richard H. , Swardfager Walter ,   The ONDRI Study Group
Published: February 2022

Background

Subcortical ischemic vascular disease (SIVD) is the most common vascular pathology found in patients with late onset dementia. The soluble epoxide hydrolase (sEH) enzyme inactivates anti‐inflammatory and vasoactive cytochrome p450 derived polyunsaturated fatty acid epoxides by converting them into cytotoxic dihydroxy (diol) oxylipin species. Previously, we found that the ratios of linoleic acid (LA) diols to epoxides were associated with more white matter hyperintensity (WMH) in patients with transient ischemic attack; however, it remains univestigated if these oxylipins can identify SIVD in patients with ischemic stroke of heterogenous cerebrovascular pathologies such as large vessel occlusion and lacunar infarcts.

Method

The study cohort comprises patients from the Ontario Neurodegenerative Disease Research Initiative, who has clinical stroke of either large or small vessel etiology (according to TOAST criteria). 4 LA oxylipins (12,13‐dihydroxyoctadecamonoenoic acid (12,13‐DiHOME), 12,13‐epoxyoctadecenoic acid (12,13‐EpOME), 9,10‐DiHOME, 9,10‐EpOME) were extracted from blood and quantified with a targeted ultrahigh pressure liquid chromatography mass spectrometry (UPLC‐MS/MS) WMH and perivascular spaces (PVS) were quantified from structural MRI scans using a personalized semi‐automatic processing pipeline (Lesion Explorer). The associations between oxylipins and small vessel disease markers were examined using linear regression models.

Result

In 80 stroke patients (n=50 large vessel disease and n=30 lacunar infarcts), the ratio of 12,13‐DiHOME to its epoxide sEH substrate 12,13‐EpOME was higher among patients with small vessel etiology (F1,79 = 4.55, p = 0.036). In linear regression models controlling for age, sex, APOE, waist hip ratio, diabetes, and hyperlipidemia, the same ratio, and the ratio of 9,10‐DiHOME/9,10‐EpOME were positively associated with volume of deep (β = 0.338, p = 0.004; β = 0.288, p = 0.012, respectively) and periventricular (β = 0.316, p = 0.003; β = 0.400, p < 0.001, respectively) WMH. The same ratios were associated with higher volumes of perivascular spaces in the white matter (β = 0.293, p = 0.013; β = 0.276, p = 0.016, respectively) but not in the basal ganglia (β = 0.145, p = 0.212; β = 0.086, p = 0.450, respectively).

Conclusion

Oxylipins derived from sEH activity may contribute to cerebral small vessel disease and to stroke of small vessel etiology.
Dynamic states of resting‐state connectivity in patients with mild cognitive impairment
Authors: Palmer William C. , Park Sung Min , Rane Swati ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: February 2022

Background

Resting‐state functional connectivity (rsFC) has demonstrated promise as a biomarker for Alzheimer’s disease. Traditional rsFC assumes that brain connectivity is unvarying during the entire acquisition window. However, recent studies show that brain connection patterns or states are dynamic and change within a few seconds. We modified existing analyses of dynamic functional connectivity to identify differences between patients with Mild Cognitive Impairment (MCI) and controls.

Method

50 MCI patients (22 males, 74±8 years old) and 55 controls (35 males, age=75±8 y.o.) from ADNI3 with T1 and fast BOLD fMRI (TR=600ms) images were analyzed. Preprocessing consisted of motion correction, despiking, physiological noise correction, and registration to MNI space. Sliding windows had a stride length of 1 TR and contained 50 TRs. Correlation matrices were generated between brain regions of the default mode (DMN), salience (Sal), dorsal attention (DAN), and frontoparietal (FPN) networks. The data was then harmonized using ComBat to remove scanner‐related differences. Distinct brain connectivity patterns or states were extracted with Davies‐Bouldin optimized k‐means clustering. Dwell time (i.e., the number of TRs for which a state is sustained) and transition probability (i.e., the probability of changing state) were calculated. Significant differences were assessed using a t‐test without correcting for multiple comparisons.

Result

We identified eight states (Figure 1). No significant differences were discovered in dwell time (Figure 2). Six transition probabilities had p<0.05 (Figure 3). These included the transition from 2 to 5 (p=0.03), 2 to 6 (p=0.04), 2 to 7 (p=0.04), 4 to 3 (p=0.005), 6 to 3 (p=0.01), 8 to 4 (p=0.05), and 8 to 7 (p=0.05).

Conclusion

Our study showed MCI patients were less likely to transition from state 4 to 3 compared to controls. State 4 is characterized by positive rsFC within the DMN and FPN as well as between the networks. Compared to state 4, state 3 had decreased rsFC within the DMN and FPN and between the networks. State 3 also shows increased positive rsFC within and between Sal and DAN. Interaction between the 4 networks has been implicated in AD. The inability to perform this transition could explain cognitive deficits observed in MCI.
Urokinase plasminogen activator (uPA) as a novel biomarker for cerebral amyloid angiopathy
Authors: Vervuurt Marc , Zhu Xiaoyue , Schrader Joseph , de Kort Anna M. , Marques Tainá M. , Kersten Iris , Schreuder Floris H.B.M. , Klijn Catharina J.M. , Kuiperij H. Bea , Van Nostrand William E , Verbeek Marcel M.
Published: February 2022

Background

Diagnosis of the highly prevalent disease cerebral amyloid angiopathy (CAA) is mainly based on radiological identification of cerebral micro‐ or macrobleeds (according to the diagnostically acclaimed Boston Criteria) in the end‐stage of disease. Body fluid biomarkers (e.g. in cerebrospinal fluid) could potentially act as alternatives and allow for earlier identification of disease in a minimally invasive manner. We have explored the involvement of potential CAA‐biomarker urokinase plasminogen activator (uPA) in CAA development and progression in human patients and rodent disease models (rTg‐DI). Additionally, we analyzed uPA cerebrospinal fluid (CSF) levels in rTg‐DI models and human CAA patients versus controls to assess diagnostic accuracy of uPA as a biomarker for CAA.

Method

PLAU gene expression and uPA localization were studied in cerebrovascular tissue of a rTg‐DI models and wild‐type rats, alongside a human sporadic CAA patient and a control subject, using rt‐qPCR and immunohistochemistry respectively. Additionally, CSF Aβ40 and uPA levels were determined in rTg‐DI rats and in human patients with possible or probable CAA (according to the Boston Criteria; n=28), and control subjects (n=40), using ELISA.

Result

Immunohistochemistry showed strong overexpression of uPA in brain tissue of rTg‐DI models and human CAA patients. Additionally, uPA showed a strong colocalization with Aβ peptides, restricted to the vasculature of rTg‐DI rats and human CAA patients. Expression and localization of both uPA and Aβ peptides were negligible in controls. Additionally, CAA rats displayed significant overexpression of the PLAU gene in brain vasculature as well as significant elevation of uPA in their CSF. In humans, CSF Aβ40 levels were reduced in CAA patients (7.66 ± 3.36 ng/mL) compared to controls (9.58 ± 3.88 ng/mL, p=0.04). CSF uPA levels were higher in CAA patients (median (IQR): 92.0 (76.1 ‐ 109.0) pg/mL compared to human controls (68.5 (56.6 ‐ 78.4) pg/mL; p<0.001). CSF Aβ40 and uPA combined yielded the highest AUC (0.87) to distinguish CAA from controls.

Conclusion

uPA was overexpressed in rTg‐DI rats and its levels were significantly elevated in both rodent and human CAA. CSF Aβ40 and uPA serve as excellent biomarkers to discriminate CAA from controls, especially when combined.
Spatial mapping of subcellular disease pathways and cytoarchitecture to anatomical brain regions for multi‐scale brain simulation with The Virtual Brain
Authors: Stefanovski Leon , Bülau Konstantin , Martin Leon , Courtiol Julie , Diaz‐Cortes Margarita‐Arimatea , Langford Chloê , Palmer Jessica , Ritter Petra ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

Background

Comprehensive knowledge bases as NeuroMMSig, a knowledge base of multimodal mechanistic signatures, catalog knowledge about Alzheimer's Disease (AD) and its underlying candidate mechanisms. Besides, digital atlases provide information about cytoarchitectonics and receptor densities, e.g. JuBrain at the EBRAINS platform of the Human Brain Project. However, a gap exists presently with respect to the integration of the various knowledge sources. The Virtual Brain (TVB) is a full brain simulation platform that integrates multimodal imaging data with mathematical brain networks. We present a methodology to map semantic information about AD to 3D brain atlases and to use it for simulations with TVB – increasing the biological plausibility of whole‐brain simulations and disease specificity.

Method

Our framework allows topological assignment of brain‐related data from different sources to the Multimodal surface‐based cortical parcellation (MMP) of the Human Connectome Project. Our tool allows mapping of stochastic information from the literature database SCAIView to brain regions. The relevance score for a specific query is calculated for anatomy‐related words from the anatomic ontology Uberon, which we transfer by a unique matrix to MMP parcels. Re‐sampling by the fsaverage brain space of freesurfer allows interoperability with other atlases. In addition, atlas‐annotated data from EBRAINS and neuroimaging data are co‐registered with MMP, enabling knowledge integration into a standardized 3D brain space.

Result

Our methodologic pipeline can be used as a software to map semantic information to the brain, which we demonstrate with NeuroMMSig pathways. We further demonstrate how the resulting maps constrain TVB simulations. Face validity is provided through reproducing group‐level (AD versus controls) results of simulations integrating subject‐specific positron emission tomography when semantic information about AD stages is integrated into TVB. We elucidate how brain maps derived from different semantic queries can change simulated brain dynamics fundamentally. Literature‐derived NMDA receptor densities show significant differences between AD and healthy controls. When used to constrain TVB models, this leads to an in silico disruption of functional subnetworks in AD.

Conclusion

We developed a tool for mapping semantic knowledge to anatomical brain regions. This enables multi‐scale brain simulations with increases biological plausibility and disease‐specificity for translational research.
Understanding the knowledge and attitudes to dementia in Sub‐Saharan Africa: A systematic review
Authors: Larweh Maxwell
Published: February 2022

Background

A direct result of an ageing population is an increase in the prevalence of chronic non‐communicable diseases such as dementia. Creating dementia awareness and promoting positive attitude is key in early symptom recognition, diagnosis, help seeking and clarifying misconceptions about dementia. This review sought to explore the knowledge and attitudes about dementia in SSA, where there has been a rapid increase in the number of people with dementia within the last decade, and a region where spirituality and superstitions affect health behaviours.

Method

Six electronic databases were searched from inception to present using a predetermined search strategy and a defined eligibility criteria. Our search initially produced 1853 articles. Three independent reviewers screened the results in two phases and 14 articles were finally selected for this review. All included papers were assessed for quality with the Mixed Methods Appraisal Tool. Relevant information about the studies were extracted by three independent investigators and recorded on a standardised form. Data synthesis followed a thematic analysis and overall themes were discussed narratively.

Result

Three themes were apparent; Dementia Conceptualization, Care Arrangements and Social Responses and Dementia Gaps. A consistent finding across majority of the studies was the poor to fair knowledge of dementia among the study populations. Majority of people believed dementia was part of normal ageing and a biomedical definition of dementia was vastly lacking. Treatment seeking was pluralistic with people often combining modern medicine, traditional medicine and their religious faith. Caregiving in dementia was considered a filial responsibility with positive and negative attributes described. Negative attitudes surrounding dementia originated from the superstitions and beliefs related to dementia causation such as the belief in witchcraft. The psychological sequalae from caregiving coupled with societal representations of dementia contribute to stigmatization and abuse of persons with dementia in SSA. Dementia training for health professionals, social support for caregivers and public education were identified as urgent needs.

Conclusion

Dementia literacy is relatively poor in SSA. There is evidence of numerous challenges faced by persons with dementia, their caregivers and health professionals involved in dementia care. Culturally appropriate education campaigns are essential in advancing a dementia friendly SSA.
Magnetoencephalography insights to dementia and drug intervention
Authors: Hughes Laura E. , Adams Natalie E. , Phillips Holly , Murley Alexander G. , Shaw Alexander , Nesbitt David , Cope Thomas E. , Bevan‐Jones W. Richard , Passamonti Luca , Rowe James B.
Published: February 2022

Background

Magnetoencephalography (MEG) is a promising tool for experimental medicine in dementia, and a core technology for the Dementias Platform UK. It quantifies in vivo human network and synaptic physiology, with high‐dimensional data at a millisecond time‐scale. Its proven sensitivity to neurodegenerative disease has applications in diagnostics and early detection, mechanistic studies of pathogenesis, and biomarkers to accelerate clinical trials and evidence target engagement. Here, we build on recent work with Serotonin and GABA‐ergic modulation, to illustrate MEG insights into the neurophysiological effects of the NMDA receptor antagonist Memantine. We use Frontotemporal dementia and Progressive supranuclear palsy (bvFTD, PSP) as demonstrator conditions in view of their focal glutamatergic deficits.

Method

24 Patients with bvFTD and PSP, and 20 healthy controls underwent magnetoencephalography, 7T MRI spectroscopy and a battery of cognitive tests in a double‐blind placebo‐controlled crossover design, using Memantine 10mg/Placebo. We test the relationship between cortical oscillations, baseline glutamate concentration and response to pharmacological intervention.

Result

Neurophysiological activity was impaired in patients, with diminished low frequency oscillations and disrupted cortical connectivity. These abnormalities correlated with reduced baseline glutamate concentration. Memantine enhanced the neuronal response, particularly in prefrontal regions.

Conclusion

MEG provides insights into targetable pathophysiological effects of neurodegeneration and markers for treatment studies. It is sensitive to disease and individual differences in pathophysiology, reliable, safe, well‐tolerated and sufficiently scalable for early phase trials. MEG evidence of selective neuronal dysfunction and network reorganisation can couple with microcircuit models for synaptic assays, or be used directly as a readout for interventional studies. MEG is ideally suited to support both academic and pharma initiatives, with quantitative tools for early phase clinical trials, illustrated here with Memantine, but applicable to other compounds.
Factors influencing atrophy progression in primary progressive aphasia
Authors: Lombardi Jolina , Mayer Benjamin , Huppertz Hans‐Jürgen , Straub Sarah , Semler Elisa , Uttner Ingo , Kassubek Jan , Diehl‐Schmid Janine , Danek Adrian , Levin Johannes , Fassbender Klaus , Fliessbach Klaus , Schneider Anja , Jahn Holger , Kornhuber Johannes , Landwehrmeyer Bernhard , Lauer Martin , Prudlo Johannes , Wiltfang Jens , Schroeter Matthias L. , Ludolph Albert , Otto Markus ,   German FTLD Consortium
Published: February 2022

Background

Primary progressive aphasia (PPA) is a rare primarily language‐related neurodegenerative disorder that subdivides into the non‐fluent (nfvPPA) and the semantic variant (svPPA). Atrophy progression shows variant‐specific patterns, however, its extent seems highly individual and thus difficult to predict.

Method

We investigated volumetric changes in patients with nfvPPA (n=18) and svPPA (n=15) with an MRI scan (3D T1 MPRAGE sequence, 3T) at baseline and 2‐years follow‐up that were recruited from the prospective German FTLD‐consortium study. According to the LONI Probabilistic Brain Atlas (Shattuck et al., 2009), 56 brain regions were assessed with automated atlas‐based volumetry (Huppertz et al., 2010). Longitudinal volumetric changes were analyzed by means of the R software (www.r‐project.org). A possible impact of group, adjusted for age and sex, had been investigated using a linear mixed effect model. Atrophy progression for each region over two years was correlated (Pearson or Kendall rank correlation; 95% BCa bootstrap CI with 1000 replicates) with age at symptom onset, years of education, and disease duration to review a possible relation.

Result

Volume change within 2‐years revealed parts of the left frontal lobe (up to ‐10%) and subcortical regions in nfvPPA and parts of the left temporal lobe (up to ‐15%) and the hippocampus/amygdala complex in svPPA as most progressive.

A correlation analysis with age at symptom onset rendered no relevant results. Higher educated patients showed more atrophy in the right parahippocampal gyrus in nfvPPA and less atrophy in white matter portions of the left superior frontal, the bilateral middle and inferior frontal, the right middle and bilateral lateral orbitofrontal and the bilateral cingulate gyrus in svPPA. Shorter disease duration correlated with higher atrophy in the caudate and putamen in nfvPPA, and in the left middle and inferior temporal gyrus, the right superior and bilateral middle occipital gyrus, the left cuneus, and left angular gyrus in svPPA.

Conclusion

Age at symptom onset showed no interrelation with atrophy progression in PPA. Higher education levels seem to slow white matter decrease of frontal areas in svPPA. Shorter disease duration is related to increased volume loss in some primarily affected regions in both nfvPPA and svPPA.
A residual marker of cognitive reserve modifies the cross‐sectional and longitudinal association between memory and glucose hypometabolism in Alzheimer’s disease
Authors: Ersoezlue Ersin , Rauchmann Boris‐Stephan , Perneczky Robert ,   For the Alzhemer's Disease Neuroimaging Initiative
Published: February 2022

Background

The cognitive reserve (CR) hypothesis was proposed to explain inter‐individual differences in the association between observed cognitive function and estimated neurodegenerative burden, e.g. in Alzheimer’s disease (AD). Latent CR marker approaches were suggested as a promising method to predict reserve.

Method

Amyloid‐β (Aβ)‐negative, cognitively normal and Aβ‐positive, cognitive impaired (Clinical Dementia Rating global score >= 0.5) individuals participating in the AD Neuroimaging Initiative (ADNI) were classified as healthy controls (HC, N=138) and AD spectrum (ADS, Baseline N=462, Follow‐Up N=211), respectively. A latent CR marker (CRM) was obtained by multilinear regression analysis in the entire study cohort, defined as the residual global cognitive performance remaining after accounting for neuropathological burden (CSF Aß42 and total Tau levels and APOE ε4 carrier status) and demographic variables. Mean standardized uptake value ratio (SUVR) values for regions of interests (ROIs) of left and right angular gyrus (L/R‐ANG), bilateral posterior cingulate (PCC), left and right inferior temporal gyrus (L/R‐TEMP) were derived from FDG‐PET data. In separate analyses for HC and ADS, the interactive effects of the memory cognitive composite (MEM) and latent CR marker on FDG‐PET SUVR values were tested for the five cortical ROIs at baseline and 24‐months follow‐up data.

Result

In ADS, higher CRM attenuated the relationship between MEM and FDG‐PET SUVR in L‐TEMP, R‐TEMP and L‐ANG at baseline, and in L‐TEMP, R‐TEMP, L‐ANG and R‐ANG in the longitudinal analyses. In HC, however, no interaction was observed.

Conclusion

Patients with higher CR maintained their memory performance better in the face of AD‐related glucose hypometabolism . Therefore, the present study supports the use of a residual CRM to improve our understand of inter‐individual differences in the resilience against neurodegeneration, both cross‐sectionally and longitudinally.
Cognitive remediation therapy for participants with late‐life schizophrenia
Authors: Golas Angela C , Elgallab Bishoy , Abdool Petal S , Bowie Christopher R , Rajji Tarek K
Published: February 2022

Background

Older patients with schizophrenia have an elevated risk of dementia; enhancing their cognitive function holds promise for delaying dementia in this population. Cognitive deficits strongly predict function in schizophrenia. Anticholinergic medication burden (ACB) compounds age‐related cognitive declines in late‐life schizophrenia (LLS). Cognitive remediation (CR) improves cognition in schizophrenia, however literature in LLS is sparse. This study examined the effect of CR on cognitive performance in participants with LLS. We also assessed CR tolerability, the interaction between ACB and the effect of CR on cognition.

Method

We adapted CR from our pilot study to a larger group. CR was provided over 12, twice‐weekly, therapist‐guided group sessions. Computerized drill‐and‐practice exercise difficulty levels were adjusted automatically based on performance. Participants were assessed at baseline and at study completion using clinical and cognitive measures.

Result

Thirty‐four participants were enrolled, 20 (mean (SD) age: 66.0 [5.8]) completed 92.3% (22.14 [1.98]) CR sessions; the ITT group (N=34) attended 72.9% (17.50 [7.23]) sessions. Global cognition did not improve (completers: p=0.80, ITT: p=0.86) with negligible effect size (completers: d=0.08; ITT d=0.04). There was no significant improvement in executive function (completers: p=0.16; ITT: p=0.33). Medication ACB was inversely associated with total MoCA score, accounting for 8.9% of the variance in final MoCA score (p=0.02).

Conclusion

Overall, CR was well tolerated but did not improve global cognition or executive functioning in this outpatient sample with LLS. A higher ACB was associated with greater cognitive impairment and a poorer response to CR. Future studies need to better characterize potential variables serving to limit the response to CR, including the number and frequency of CR sessions and the role of ACB.
Sex differences in genetic susceptibility of hippocampal subfields: A polygenic association study
Authors: Genius Patricia , Arenaza‐Urquijo Eider M. , Operto Greg , Evans Tavia E. , Brugulat‐Serrat Anna , Falcon Carles , Minguillón Carolina , Fauria Karine , Adams Hieab H.H. , de Moura Manuel Castro , Piñeyro David , Esteller Manel , Guigó Roderic , Navarro Arcadi , Molinuevo Jose , Gispert Juan Domingo , Vilor‐Tejedor Natalia ,   for the ALFA study
Published: February 2022

Background

The hippocampus is involved in several complex diseases which display sex differences in their prevalence. Therefore, it can be hypothesized that sex‐specific genetic vulnerability in hippocampal formation might partially explain these differences. The aim of this study was to investigate whether the genetic predisposition to several complex diseases showed sex‐specific associations with the volumes of hippocampal subfields.

Method

A total of 1,071 cognitively unimpaired participants (45‐74 years) at increased risk for Alzheimer's disease (AD) (ALFA study), with available genotyping and neuroimaging data were included (62.6% women). Genetic predisposition was calculated through polygenic risk scores (PRSs) computed using the PRSice tool (v.1.25). A total of 33 PRSs were estimated from the most recent genome‐wide association meta‐analyses for several neurodegenerative, vascular and metabolic diseases, as well as for biomarkers of AD. Association analyses included the volumes of the hippocampal subfields quantified through high‐resolution 3D‐T1‐weighted magnetic resonance imaging scans and determined using Freesurfer (v.6.0). Sex‐stratified association analyses were estimated using linear regression models adjusted for age, education, and total intracranial volume. The threshold of significance was established by approximating the total number of effective tests. The resulting adjusted significance threshold was set at p <0.005.

Result

PRSs were equally distributed among women and men, sharing a common pattern of variability [Figure 1]. Both groups showed increased genetic susceptibility for abnormal levels of AD biomarkers and for vascular, brain, as well as sleep disorders. Association analyses showed significant sex differences associated to several hippocampal subfields [Figure 2]. Specifically, in women, increased genetic risk of multiple sclerosis and neurodegenerative diseases was associated with larger cornu ammonis 1 (CA1), hippocampal tail and molecular layer, as well as with increased volume of the whole hippocampus. In men, a raised genetic risk of cerebral infarction, epilepsy and both short and long duration of habitual sleep was associated with reduced volumes of CA1, molecular layer, subiculum, and dentate gyrus.

Conclusion

We provide evidence that genetic susceptibility differentially influences on hippocampal subfield volumes according to sex. This may explain sex‐specific patterns of neurodegeneration and biological vulnerabilities.
The speed limits of tau spreading: The contribution of regional amyloid and education
Authors: Hönig Merle C. , Bischof Gerard N. , Dzialas Verena , van Eimeren Thilo , Drzezga Alexander ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: February 2022

Background

Here, we investigated the contribution of education and regional amyloid as potential de‐ and accelerators in the spread of tau pathology.

Method

85 amyloid‐positive subjects (age=76.80±1.08, education=16.70 ±.50 years, M/F=42/43) were included, for whom [18F]AV‐1451 PET at two timepoints, baseline [18F]AV‐45 PET, ApoE‐status and clinical information were available at ADNI. [18F]AV‐1451 PETs were intensity‐standardized (reference: inferior cerebellum) and z‐transformed (control sample: 35 amyloid‐negative subjects). Baseline and follow‐up tau‐PET z‐maps were converted to volume‐maps (z‐score threshold > 1.96). Based on these volume‐maps, tau‐changes over time were assessed: 1) tau speed (i.e. newly affected volume at follow‐up), 2) tau level rise (i.e. tau increase in previously affected volume). These two dependent variables were used in regression analyses including education, global amyloid, baseline tau, ApoE, cognitive function, sex, and age as predictors. Additionally, baseline amyloid‐burden was regionally correlated in 32 Freesurfer‐ROIs with newly tau‐affected volume and with mean z‐score change in five Meta‐ROIs (entorhinal cortex, inferior‐temporal, precuneus, middle‐occipital, oribito‐frontal), correcting for multiple comparisons.

Result

Education contributed as decelerator (β=‐.322, p=.037), whereas global amyloid (β=.262, p=.029) and baseline tau (β=.283, p=.028) facilitated tau speed. Tau level rise was positively associated with age (β=‐.211, p=.017) and baseline tau (β=.710, p<.001). Tau spread to the precuneus was related with greater cingulate amyloid‐burden, whereas tau level rise in temporal, parietal and occipital regions was associated with orbito‐frontal and cingulate amyloid‐burden.

Conclusion

A combination of de‐ and accelerating factors and regional dissociations likely contribute to the temporo‐spatial evolution of tau pathology.
Prediction of amyloid pathology in cognitively unimpaired individuals using structural MRI
Authors: Cumplido‐Mayoral Irene , Ingala Silvia , Lorenzini Luigi , Wink Alle Meije , Haller Sven , Molinuevo Jose , Wolz Robin , Palombit Alessandro , Schwarz Adam J. , Chetelat Gaël , Payoux Pierre , Martinez‐Lage Pablo , Frisoni Giovanni , Fox Nick C , Ritchie Craig W. , Wardlaw Joanna M , Waldman Adam , Barkhof Frederik , Vilaplana Verónica , Gispert Juan Domingo ,   EPAD Consortium,   ADNI study
Published: February 2022

Background

Structural MRI measurements can contribute to the prediction of amyloid pathology in cognitively unimpaired (CU) individuals. In this work, we aimed at studying the predictive capacity, robustness, and generalizability of ML techniques to predict amyloid‐β pathology in CU individuals, as well as identifying key brain regions contributing to this prediction.

Method

We included 653 and 250 CU individuals from the EPAD and ADNI studies, respectively, with available T1w MRI and CSF Aβ42 measurements. Subjects were categorized as amyloid‐β positive (Aβ+) or negative (Aβ‐) according to established cut‐offs (CSF Aβ42<1000pg/mL for EPAD and <880pg/mL for ADNI). Volumes and cortical thickness in regions of the Desikan‐Kiliany atlas were obtained with Freesurfer 6.0, as well as the Total Intracranial Volume (TIV). We trained XGBoost classifiers to predict amyloid‐β positivity using age, sex, education, MMSE, APOE‐ɛ4 status, volumes/TIV, and cortical thickness measurements. To study the generalizability of the classifier, we performed within‐cohorts classification (train and test within the same cohort); and between‐cohorts classification (train with one cohort and test with another). We performed the latter classification, both with the original samples, and following a bootstrapping approach to force balanced data in the training. With the classification results, we conducted a ROC analysis and, additionally, calculated SHAP values to determine the most important brain regions used to predict Aβ+.

Result

Similar classification performance was achieved when training/testing within ADNI (ROC‐AUC=0.72 (0.59‐0.84)) and within EPAD (ROC AUC=0. 68 (0.60‐0.76)) (Figure 1A). In the between cohort’s analysis, ROC‐AUC decreased slightly in both cases (Figure 1B) but was consistent over subsampling of individuals. Train with ADNI and test with EPAD gave ROC‐AUC=0.61 (0.58‐0.64) and train with EPAD and test with ADNI gave ROC‐AUC=0.59 (0.54‐0.66). The most important features used for prediction were similar for both ADNI and EPAD (Figure 2). The increased volume and/or thickness of some brain regions, such as superior frontal areas, predicted Aβ+. The decrease in cingulate cortex was also seen. APOE‐ɛ4 status also had a high impact on classification performance.

Conclusion

The use of structural MRI measurements in combination with Machine Learning can provide additional capacity to predict amyloid‐β status in CU individuals.
Study protocol: SOcial LImitations Turn Up DEmentia (SOLITUDE)—Impact of COVID‐19 social isolation on patients’ cognition and mental health and on carers’ wellbeing
Authors: Manca Riccardo , De Marco Matteo , Blackburn Daniel J , Russell Gregor , Evans Kimberly , Kirkland Sarah , Amin Jay , Davies Lynn , Firth Claire , Raymont Vanessa , Colston Amanda , Collett Zoe , Kumar Pramod , Balckman Sarra , McCoy Shani , Davies Rhys , Robertson Selina , van Diepen Erik , Venneri Annalena
Published: February 2022

Background

Social isolation and loneliness are both known to exert detrimental effects on mental health and cognitive functioning, as well as on medial temporal lobe volume in older adults. Reduced social interactions have also been found to increase the risk of cognitive decline and dementia in older people. Since restrictions to social contacts have been imposed to tackle the current Coronavirus Disease 2019 (COVID‐19) pandemic, this study aims to investigate the long‐term impact of the resulting social isolation on people with mild dementia and their carers.

Method

This study has been implemented using a multi‐centre longitudinal observational design to monitor mental health (9‐item Patient Health Questionnaire and Neuropsychiatric Inventory Questionnaire), cognitive performance (telephone Mini‐Mental State Examination and Telephone Assessment of Cognitive Function) and quality of life (Quality of Life in Alzheimer's Disease) of patients with mild dementia due to neurodegenerative aetiologies, as well as carers’ burden (12‐item Zarit Burden Interview). Additionally, a structured interview is included to assess the potential impact of social isolation on everyday functioning of patients and carers. Participants are assessed telephonically at three time‐points: baseline and two follow‐ups after 3 and 6 months.

Result

Six centres across the UK have confirmed capacity and capability to recruit up to eighty participants. Between September and December 2020, twenty‐nine participants have been recruited across different sites and completed the baseline assessment. Moreover, nine participants have already completed the 3‐month follow‐up.

Conclusion

This study (predicted completion date: July 2021) is expected to provide valuable insights into the potential long‐term consequences of lockdown measures on people with dementia and their carers. Moreover, it will enable the identification of potential risk/protective factors for decline in mental health and cognition due to extensive changes in patients’ social environment. Findings from the SOLITUDE study may inform preventative and management strategies for decline in mental function targeting people with dementia, who may be the most affected by social isolation and loneliness.