bluuebunny/crossref_metadata_2025_split huggingface dataset:
A gatekeeper for amyloid status based on FDG‐PET and genetic risk in patients with mild cognitive impairment
Authors: Doering Elena , Hönig Merle C , Bischof Gerard N , van Eimeren Thilo , Drzezga Alexander 
Published: February 2022

AbstractBackgroundAmyloid‐β (Aβ) accumulation is a characteristic hallmark for Alzheimer’s disease (AD), which is known to be modified by the APOE genotype. Current diagnostic recommendations for AD include the assessment of amyloid status (A‐status: Aβ+ or Aβ‐) through positron‐emission‐tomography (PET) or invasive lumbar puncture. Amyloid‐PET imaging is costly and currently not generally covered by insurance companies. FDG‐PET, in contrast, is comparably inexpensive, commonly available and often employed to assess extent and localization of neurodegeneration (N‐status) in patients with (mild) cognitive impairment (MCI). We aimed to explore, whether advanced machine learning allows for an approximation of the A‐status from FDG‐PET data and APOE genotype, which could make these biomarkers a gatekeeper in deciding on the need for additional amyloid testing.MethodModels for the approximation of the A‐status were trained for APOE4 carriers (APOE‐c) and non‐carriers (APOE‐nc) in parallel. We included 574 FDG‐PET scans of patients with MCI from the ADNI cohort (185 Aβ‐APOE4‐nc; 107 Aβ+APOE4‐nc; 46 Aβ‐APOE4‐c; 236 Aβ+APOE4‐c). A‐status was determined from established cut‐off values for cerebrospinal fluid and/or amyloid‐PET. Using SPM12, regional FDG‐PET standardized uptake value ratios were extracted from spatially normalized scans for 90 brain regions. Different machine learning classifiers were trained on 70% of the data, while the remaining 30% (n=85 (APOE4‐c); n=88 (APOE4‐nc)) were reserved for testing. APOE‐c and ApoE‐nc models were trained to maximize precision of Aβ‐ and Aβ+, respectively (“relevant instances”), as well as the percentage of relevant instances identified by a classifier (“recall”) by means of the F1/10‐score. Finally, we estimated the contribution of individual brain regions towards classification performance with permutation importance.ResultIn the test set, amyloid status was predicted with a precision of 85% (APOE4‐c) and 87% (APOE4‐nc) and a recall of 93% (APOE4‐c) and 58% (APOE4‐nc). Patterns of neurodegeneration in temporal and frontal (APOE‐nc) and temporo‐parietal regions (APOE‐c) most heavily influenced the classification process (see Figure 1).ConclusionWe propose a highly precise and biologically plausible gatekeeper for amyloid status in MCI patients with varying genetic risk using FDG‐PET. Further validated, our models could serve to reduce the number of patients requiring amyloid testing to determine AD‐related etiology of ongoing neurodegeneration.
Reductions in biomarkers of Alzheimer’s disease pathophysiology following treatment with aducanumab were associated with slowing in clinical decline
Authors: Rajagovindan Raj , Chen Tianle , Nisenbaum Laura , Tian Ying , Muralidharan Kumar Kandadi , Dent Gersham , He Ping , Castrillo‐Viguera Carmen , Haeberlein Samantha Budd 
Published: February 2022

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) and tau in the brain. Aducanumab is a human monoclonal antibody that selectively targets aggregated forms of Aβ. In clinical studies, aducanumab treatment resulted in dose‐ and time‐dependent reduction in Aβ levels accompanied by slowed clinical decline.MethodParticipants in the Phase 1b PRIME study (NCT01677572) were randomized to receive aducanumab (1, 3, 6, or 10 mg/kg [fixed‐dose or titrated]) or placebo every 4 weeks (q4w). The effects of aducanumab on clinical endpoints and amyloid positron emission tomography (PET) composite standard uptake value ratio (SUVR) were evaluated at the end of randomization (Week 54).In the Phase 3 EMERGE (NCT02484547) and ENGAGE (NCT02477800) studies, participants were randomized (1:1:1) to received high‐dose aducanumab (10 mg/kg), low‐dose aducanumab (3 mg/kg), or placebo q4w. At Week 78, the effects of aducanumab on clinical endpoints were assessed; the effects on AD biomarkers were assessed in PET and CSF substudies. In the EMERGE and ENGAGE substudies, participant‐level correlations between change from baseline in clinical measures (measured by CDR‐SB, MMSE, ADAS‐Cog 13, and ADCS‐ADL‐MCI) and change from baseline in amyloid PET SUVR or CSF biomarkers (p‐tau and t‐tau) at Week 78 were examined. The same analysis between clinical decline (measured by CDR‐SB and MMSE) and change in amyloid PET SUVR was investigated in PRIME at Week 54. Group‐level correlation between treatment effect on Aβ levels as measured by PET and clinical decline was conducted across all 3 studies.ResultFindings from EMERGE suggest that reduction in AD biomarker levels (amyloid PET, CSF p‐tau, and CSF t‐tau) following treatment with aducanumab are associated with slowing in cognitive decline. Analyses from PRIME are supportive of these findings. In ENGAGE, in which a clinical treatment effect of aducanumab was not observed, correlations were less apparent. However, group‐level analyses based on data from PRIME, EMERGE, and ENGAGE demonstrated a correlation between aducanumab treatment effect on amyloid pathology and clinical measures.ConclusionThe correlation analyses between biomarkers and clinical measures provide evidence that aducanumab‐induced reduction in biomarkers of AD disease pathophysiology is associated with reduced clinical decline.
Methodologies used to study the effectiveness of social robots in long‐term and community care settings
Authors: Asl Aysan Mahmoudi , van der Roest Henriëtte G , Ulate Mauricio Molinari , Martin Manuel Angel Franco 
Published: February 2022

AbstractBackgroundIn a search for innovative dementia care strategies, a new research field has been dedicated to design social robots for older adults with cognitive impairments and dementia in order to promote their quality of life through communication and social interactions. Although the results are promising, the quality of studies on effectiveness of social robots in elderly adults is still low due to several methodological limitations (1). Therefore, we aimed to review the methodologies used so far for conducting studies with social robots in long‐term and community care settings with people with dementia and elderly adults.MethodSearches in PubMed, Web of Science, PsycInfo, and Cinahl yielded 33 studies included in the final review after applying inclusion and exclusion criteria. Reviews were conducted by two authors independently.ResultAcross 33 papers, 23 different social robots were examined on elderly adults and PwD, investigating acceptability, usability and effectiveness. A variety of study designs such as RCTs, mixed methods, cross‐sectional, cohort and quasi‐experimental designs were employed. Individual and group‐based interventions took place in private households, long‐term care facilities and laboratories during single or multiple sessions. Data were collected through observation, questionnaires, interviews and physiological tests. Most revealed improvements were found in mood, engagement and participation. However, improvements in quality of life, depression and cognition were not significant.ConclusionDespite the promising results, due to the insufficient methodology, failures and ambitious findings remain within the many aspects of the enquiry. Appropriate experimental designs such as RCTs with large sample sizes and individual intervention sessions might be established for effectiveness studies. For acceptability/usability studies, a cohort design with long‐term intervention would serve best. We also recommend a mixed‐method of data collection for any of three effectiveness, acceptability and usability related outcomes. Multiple interaction sessions running for more than one month might help researches to draw significant results and reveal the long‐term impact of the robots. Reference: Abdi J, Al‐Hindawi A, Ng T, Vizcaychipi MPJBo. Scoping review on the use of socially assistive robot technology in elderly care. 2018;8(2):e018815.
White matter hyperintensities in the splenium of the corpus callosum predict cognitive decline in memory clinic outpatients
Authors: Garnier‐Crussard Antoine , Dauphinot Virginie , Cotton François , Teillac Achille , Cavedo Enrica , Tran Philippe , Chetelat Gaël , Salmon Pierre Krolak ,   MEMORA Group
Published: February 2022

AbstractBackgroundWhite matter hyperintensities (WMH) are very frequent in ageing and related to worse cognition. Recent studies suggest that WMH in the corpus callosum (CC) are particularly relevant in neurocognitive disorders, as they are strongly associated with lower cognitive performance, as well as amyloid and neurodegeneration biomarkers. This study examined whether WMH in subregions of the CC (genu, body, splenium) affect cross‐sectional and long‐term longitudinal (up to 5 years) cognitive performance in patients recruited from a memory clinic.MethodThis study included memory clinic outpatients from the MEMORA cohort who had a brain MRI (T1 and FLAIR scans) within 6 months of the baseline visit. QyScore® software was used for the automatic segmentation of WMH in the CC and hippocampal volumes (HP). The cross‐sectional and longitudinal relationships between regional WMH in the CC and cognitive performance, as measured with the mini‐mental state examination (MMSE), were assessed using multivariable linear regressions and mixed models.ResultAmong 236 patients included (mean age 76.2±8.8 years old; mean MMSE 23.6±4.9), 111 were diagnosed with probable Alzheimer’s disease (AD), 20 with vascular cognitive impairment (VCI), 22 with mixed AD‐VCI, 18 with another neurological disease and 65 with a subjective cognitive complaint. Cross‐sectional analyses disclosed that higher WMH in the splenium of the CC were associated with reduced MMSE (p=0.03, n=199) after adjustment for diagnosis and education. The relationship did not remain significant after adjustment for HP and total WMH. Longitudinal analyses with a follow‐up up to 5 years showed that the MMSE declined faster in patients with higher WMH in the splenium of the CC (p<0.001, n=143) after adjustment for education, diagnosis, HP and total WMH (Figure). WMH in the genu and in the body of the CC were not associated with MMSE decline (respectively p=0.92 and p=0.23, n=124, Figure).ConclusionWMH in the splenium of the CC were associated with cognitive decline, whereas WMH in the genu and the body were not. This study highlights the clinical relevance of posterior CC WMH in a memory clinic population.
COVID‐19 and preclinical Alzheimer disease: Driving, mobility, activity and experiences of older adults in the United States
Authors: Bayat Sayeh , Babulal Ganesh M , Widener Michael , Schindler Suzanne E , Morris John C , Mihailidis Alex , Roe Catherine M 
Published: February 2022

AbstractBackgroundAs the world grapples with the COVID‐19 pandemic, there have been widespread disruptions to everyday life due to social distancing. Older adults with Alzheimer disease (AD) are at increased risk of morbidity and mortality from COVID‐19. It is unknown how COVID‐19 affects the mobility patterns of older adults with preclinical AD. Since before the pandemic, we have been monitoring the driving behaviors of older adults, enabling us to evaluate the impact of the pandemic on individuals with and without preclinical AD.MethodWe used in‐vehicle Global Positioning System (GPS) devices to study driving behaviors of 115 older adults enrolled in the DRIVES study (aged 65+) from 1/1/2019 to 31/12/2020. The cohort included 62 individuals with preclinical AD (PreAD) and 53 without preclinical AD (CTL), as determined by cerebrospinal fluid biomarkers. All participants completed an online survey about their overall experiences during the pandemic. Using the GPS data, we determined the average monthly distance travelled, and the number of visitations to destinations categorized as food shopping, place of worship, restaurant, leisure, or health. All measures were computed monthly.Resultoth groups experienced an approximate 40% decline in average monthly distance travelled overall after the start of the pandemic (PreAD: 1287.92 to 783.38 km vs. CTL: 1751.26 to 1053.29 km). Visits to places of worship, restaurants, leisure and health places declined by 70%, 46%, 23%, and 23% for the PreAD group, and by 48%, 31%, 48%, and 22% for the CTL group, respectively. However, the pandemic did not result in a significant decline in Food Shopping among either of the groups. Overall, compared to the CTL group, the PreAD group experienced a higher level of stress in response to the recommendations for socially distancing (p<0.01), more uncertainty about their risk of COVID‐19 (p<0.05), more decline in trips for worship (p<0.05) and less decline in trips for leisure (p<0.01).ConclusionOur findings indicate decreased mobility in all older adults during the pandemic, with the preclinical AD group exhibiting more decline in trips to places of worship, less decline in leisure activities, and increased stress and uncertainty in response to COVID‐19.
Tau accumulation using [18F]MK6240 PET is associated with increase in executive dysfunction in prodromal AD
Authors: Pallen Vanessa , Lussier Firoza Z. , Poltronetti Nina Margherita , Therriault Joseph , Bezgin Gleb , Arias Jaime Fernandez , Rahmouni Nesrine , Stevenson Jenna , Stevenson Alyssa , Kang Min Su , Mathotaarachchi Sulantha , Tissot Cécile , Benedet Andréa Lessa , Wang Yi‐Ting , Pascoal Tharick A. , Gauthier Serge , Rosa‐Neto Pedro 
Published: February 2022

AbstractBackgroundDecline in executive function has been noted to precede other forms of cognitive decline in the prodromal stage of Alzheimer’s disease (Clark et al., 2011). The D‐KEFS Color‐Word Interference test (CWIT) is a cognitive test that measures executive function across several conditions. Few studies have explored the relationship between tau deposition and executive dysfunction. However, to date, no study has explored this relationship in prodromal AD. This study aimed at exploring such associations.MethodWe looked at cognitively unimpaired and impaired elderly individuals from the TRIAD cohort in Montreal, QC who underwent neuropsychological evaluations across 2 time points. In vivo tau accumulation was assessed at baseline with [18F]‐MK6240 PET. Standardized uptake value ratio was calculated 90‐110 minutes post‐injection using cerebellar grey matter as the reference region. Voxel‐wise linear regression models were applied with the rate of change of CWIT condition 3 and 4 completion times as predictor variables with tau tracer binding being the response variable. Age, sex, education, Geriatric Depression Scale score, APOEε4, diagnostic group, and amyloid‐β status were included as covariates in regression models. Results were corrected for multiple comparisons using random field theory with a cluster threshold of p < .001.ResultA total of 105 (CN=65;MCI=36;AD=4) individuals were included in this analysis, with mean follow‐up time of neuropsychological evaluation being 15.9 months. We found that brain [18F]‐MK6240 uptake was correlated with change in D‐KEFS CWIT condition 3 and 4 completion times, with a greater pattern of association in condition 3 (inhibition). For condition 3, associations were strongest in the precuneus, posterior cingulate, and primarily right dorsal frontal and parietal regions. For condition 4 (flexibility), we found a strong association in the left temporal pole and left dorsal frontal regions.ConclusionThese results support previous claims that tau follows a distinct regional distribution similar to that of the dorsal attention network which is related to higher order cognitive function such an inhibition and switching (Hansson et al., 2017). Additionally, given that most individuals in this study were CN or MCI, our findings suggest that tau pathology is associated with a decrease in executive function even in prodromal stages of AD.
The relationship among Aβ‐42 and p‐Tau biomarkers, functionality and cognition in patients without cognitive impairment and patients with Alzheimer’s dementia
Authors: Valu dos Santos Lorena Aline , Burgos Ivonne Carolina Bolaños , Costa Mônica Vieira , de Oliveira Hansen Erika , Dias Natália Silva , da Fonseca Aristeu Mascarenhas , Miranda Mariana Figueiredo , Miranda Millena Figueiredo , Gomes Giulia Costa , de Mattos Viana Bernardo , Bicalho Maria Aparecida Camargos 
Published: February 2022

AbstractBackgroundComparison between functionality and cognition in elderly patients with Alzheimer’s dementia (AD) and without cognitive impairment with positive and negative Aβ‐42 and p‐Tau biomarkers evaluated using the Luminex technique.MethodPatients with Alzheimer’s dementia and normal cognition (control) were recruited. They were divided in two groups according to their clinical diagnosis: AD group (n=30) and control group (CTRL) (n=10). The AD group was then divided in patients with positive (n=21) and negative (n=9) Aβ‐42 and p‐Tau biomarkers. The participants were submitted to sociodemographic. The general cognition was evaluated through the following instruments: the Mini‐Mental State Examination (MMSE), semantic verbal fluency (SVF), animal fluency, short term memory, and recognition of CERAD battery, and functionality was evaluated by the Pfeffer scale. Samples from the cerebrospinal fluid (CSF) of patients were collected, processed, and stored at ‐80°C until use. The Luminex technique was then used for the Aβ‐42, t‐Tau, p‐Tau, t‐Tau/Aβ‐42 ratio, and p‐Tau/Aβ‐42 ratio biomarker analysis. Obtained data was processed and analyzed through the software SPSS 22.0.ResultComparison between control patients and patients with AD, as defined by clinical diagnosis, did not show significant differences regarding to Aβ‐42 expression in CSF (U=91,000; p=0,067), (AD=1119,0360, SD=708,98952 vs CTRL=775,2623 SD=341,67835). However, there was a significant difference between groups concerning t‐Tau protein, (U=198,500; p=0,028), p‐Tau (U=250,00, p=0,001) and p‐Tau/Aβ‐42 ratio (U=238,00; p=0,005). In terms of cognitive variables, all showed significant differences between groups: MMSE (U=46,500, p=0,001), SVF (U=39,000; p<0,001), short term memory (U=27,000, p<0,001), recognition (U=72,500,p=0,014), as well as functionality (U=258,500, p<0,001). There was no difference regarding the age (U= 201,500; p=0,109) and formal education (U=201,500, p=0,109). As for the AD groups with positive and negative biomarkers, there was no significant difference in cognitive variables, age, formal education, and functionality.ConclusionAD group with negative biomarkers non differ in terms of cognition. Comparing the control and AD groups, there were differences in functionality, cognition, and biomarkers. However, comparing AD groups in terms of biomarkers, there was no difference in functionality performance, short‐term memory, fluency and general cognition. Therefore, the biomarkers do not indicate significant cognitive differences in the group of patients with dementia.
Low‐dielectric constant and viscosity tetrafunctional bio‐based epoxy resin containing cyclic siloxane blocks
Authors: Zhang Pengbo , Yao Tongjie , Xue Kangle , Meng Xianbin , Zhang Junying , Liu Li 
Published: February 2022

AbstractBio‐based epoxy resins with low‐dielectric constant, low viscosity and excellent mechanical properties have great significance for the future of advanced electronic and microelectronic industries. Cyclosiloxane segment possesses low polarity, high‐dissociation energy, and elevated molecular volume, thereby making it useful for the synthesis of materials with low dielectric constant and viscosity. Herein, a tetrafunctional eugenol‐based epoxy resin (DEP) based on a cyclosiloxane structure was designed and prepared through a hydrosilylation reaction. Allyl glycidyl ether (AGE) was selected as a reference compound and generated a silylation epoxy resin (AGDEP). The viscosity of these silicone‐containing tetrafunctional epoxy monomers (< 0.315 Pa·s) was significantly lower than that of the conventional oil‐based epoxy resin (14.320 Pa·s). After curing with methyl hexahydrophthalic anhydride (MHHPA), the dielectric constant of DEP‐MHHPA was as low as 2.8 (10 MHz), which was superior to that of EP‐MHHPA. Notably, the glass transition temperature (Tg) of DEP‐MHHPA was as high as 100.3°C. The tensile strength and elongation at break of DEP‐MHHPA were estimated to be 66.1 MPa and 6.0%, respectively. Multifunctional eugenol‐based epoxy monomers with low‐dielectric constant and viscosity provide an efficient guideline for building epoxy‐based materials to better design future‐oriented engineering materials.
Persistent phosphors for luminous paints: A review
Authors: Thejo Kalyani N. , Jain Abhilasha , Dhoble S. J. 
Published: February 2022

AbstractThe article briefly reports the fundamental scientific principles and landmarks in the field of luminescence and further enlightens the importance of persistent phosphor that is now widely used in luminous paints. Its main focus is on phosphorescence that makes use of lanthanides that have gained paramount importance in various cross‐sections of luminescent applications. Both inorganic and organic afterglow materials, synthesis and characterization along with skilled researchers' essential updates on emerging trends and efforts are elucidated at length. It exclusively reviews the red/green/blue organic/inorganic/hybrid phosphorescent materials and the latest advances in the development of novel long afterglow materials that can accelerate the green technology in the world of luminescence.
Longitudinal assessment of magnetization transfer ratio, brain volume, and cognitive functions in diffuse axonal injury
Authors: Macruz Fabiola Bezerra de Carvalho , Feltrin Fabrício Stewan , Zaninotto Ana , Guirado Vinícius Monteiro de Paula , Otaduy Maria Concepcion Garcia , Tsunemi Miriam Harumi , Nucci Mariana Penteado , Rimkus Carolina , Andrade Celi Santos , Leite Claudia da Costa 
Published: February 2022

AbstractBackgroundDiffuse axonal injury (DAI) is a frequent mechanism of traumatic brain injury (TBI) that triggers a sequence of parenchymal changes that progresses from focal axonal shear injuries up to inflammatory response and delayed axonal disconnection.ObjectiveThe main purpose of this study is to evaluate changes in the axonal/myelinic content and the brain volume up to 12 months after TBI and to correlate these changes with neuropsychological results.MethodsPatients with DAI (n = 25) were scanned at three time points after trauma (2, 6, and 12 months), and the total brain volume (TBV), gray matter volume, and white matter volume (WMV) were calculated in each time point. The magnetization transfer ratio (MTR) for the total brain (TB MTR), gray matter (GM MTR), and white matter (WM MTR) was also quantified. In addition, Hopkins verbal learning test (HVLT), Trail Making Test (TMT), and Rey–Osterrieth Complex Figure test were performed at 6 and 12 months after the trauma.ResultsThere was a significant reduction in the mean TBV, WMV, TB MTR, GM MTR, and WM MTR between time points 1 and 3 (p < .05). There was also a significant difference in HVLT‐immediate, TMT‐A, and TMT‐B scores between time points 2 and 3. The MTR decline correlated more with the cognitive dysfunction than the volume reduction.ConclusionA progressive axonal/myelinic rarefaction and volume loss were characterized, especially in the white matter (WM) up to 1 year after the trauma. Despite that, specific neuropsychological tests revealed that patients’ episodic verbal memory, attention, and executive function improved during the study. The current findings may be valuable in developing long‐term TBI rehabilitation management programs.