bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular and inflammatory plasma biomarkers correlate with human post‐mortem cerebral vascular pathology
Authors: Winder Zachary , Lee Tiffany , Abner Erin L. , Nelson Peter T. , Neltner Janna , Jicha Gregory A. , Wilcock Donna M. 
Published: February 2022

AbstractBackgroundVascular Cognitive Impairment and Dementia (VCID) is a common cause of dementia in Western populations. Small‐vessel disease (SVD), a VCID subtype, can present as arteriolosclerosis and microinfarcts. Currently, identifying this pathology clinically is limited to MRI, which is expensive, limited in terms of small vessel resolution and not widely available. Therefore, a more accessible screening tool is needed to clinically evaluate SVD. Here, we evaluate the relationships between vascular and inflammatory plasma biomarkers with global levels of SVD pathology in human brain.MethodPlasma and brain tissue samples were obtained from the University of Kentucky Alzheimer’s Disease Research Center (UK‐ADRC) Brain Bank. Cases were selected from participants who had an available plasma sample from within two years of death. These plasma samples were analyzed using a digital immunoassay (Quanterix Simoa) to determine biomarker levels of placental growth factor (PlGF), matrix metalloproteinase 9 (MMP9), and tumor necrosis factor α (TNFα). Biomarker levels were categorized by quartiles. Pathological evaluation was performed by UK‐ADRC neuropathologists, blind to clinical data. The association of plasma markers with neuropathology was estimated via multinomial and binary logistic regressions adjusted for age and sex. Global arteriosclerosis was examined using a scale of none/mild/moderate/severe, with none being the reference. Presence or absence of microinfarcts was also examined.ResultIncluded cases (n=93) were age 82.0±9.2 years at death; 46.7% were female. Higher plasma placental growth factor (PlGF) levels were associated with less severe arteriolosclerosis: odds ratio (OR)=0.8 (95% CI 0.5‐1.3), 0.8 (0.5‐1.5), and 0.6 (0.2‐1.7); higher plasma MMP9 levels were associated with more severe arteriolosclerosis (OR=1.0 (0.5‐2.1), 0.7 (0.3‐1.5), 0.7 (0.2‐2.4), comparing odds of mild, moderate, and severe to none, respectively), though these results were not statistically significant. Lower plasma PlGF and MMP9, and higher TNFa, were associated with higher odds of microinfarction: OR=0.59 (0.33‐1.02), 0.74 (0.38‐1.42), and 2.28 (0.84‐6.20), respectively.ConclusionOur results, while based on a small sample, suggest plasma PlGF and MMP9 levels have an inverse relationship with global SVD pathology, while plasma TNFa is positively correlated with increased global SVD pathology. These results provide support for potential use of plasma biomarkers as a clinical screening tool for SVD pathology.
Mealtime nonverbal communications among nursing home staff and residents with dementia: A secondary analysis of videotaped observations
Authors: Liu Wen , Williams Kristine N , Batchelor Melissa , Perkhounkova Yelena , Hein Maria 
Published: February 2022

AbstractBackgroundMealtime difficulties are common among nursing home (NH) residents with dementia. Quality communications between staff and residents are critical to engage residents in eating. This study characterized dyadic nonverbal communications between nursing home staff and residents and evaluated relationships of nonverbal communications with individual characteristics.MethodsThis secondary analysis of 110 videotaped mealtime observations involved 25 residents and 29 staff (42 unique dyads) in 9 NHs. Nonverbal communication behaviors were coded using the refined Cue Utilization and Engagement in Dementia mealtime video‐coding scheme. Codes for staff nonverbal behaviors include 8 negative and 26 positive behaviors (modification for resident ability n=12, care approaches n=7, and dining environment n=7). Codes for resident nonverbal behaviors include 5 positive/neutral behaviors and 22 negative behaviors (chewing/swallowing difficulties n=4, functional impairment n=6, and resistive behaviors n=12).ResultsStaff modifications for resident ability (41.9%) were more prevalent than modifications of care approaches (35.1%) and dining environment (13.6%). Staff negative behaviors (9.3%) (33.5%) were more frequent compared to functional impairment (9.9%). Residents demonstrated positive/neutral behaviors (20.9%). Resident chewing/swallowing difficulties were correlated with resident eating function (p=.002). Resident functional impairment was correlated with staff education (p=.026) and resident age (p=.013), gender (p=.013), and dementia stage (p=.003). Resistive behaviors were correlated with resident comorbidity (p=.003), dementia stage (p=.049), and eating function (p=.001). Resident positive behaviors were correlated with staff race (p=.005) and resident age (p=.002), dementia stage (p=.049), and eating function (p=.002). Modifications for resident functional/cognitive ability were correlated with resident eating function (p<.001), while modifications of care approaches were correlated with staff race (p<.001) and years in current NH (p<.001), as well as with resident gender (p=.003) and eating function (p<.049). Modifications of dining environment were correlated with staff gender (p=.017) and years in current NH (p=.046), as well as with resident dementia stage (p=.008) and eating function (p<.001). Staff negative behaviors were correlated with resident comorbidity (p=.008).ConclusionsDyadic mealtime nonverbal communications were dynamic, interactive, and complex. Multiple individual characteristics were related to dyadic nonverbal communications. Findings may inform development of individualized, person‐centered mealtime care interventions.
Plasma TDP‐43 in neurodegenerative diseases assayed with immunomagnetic reduction
Authors: Yang Shieh‐Yueh , Liu H.C. , Chiu Ming‐Jang , Lin Chin‐Hsien , Chen Hsin‐Hsien 
Published: February 2022

AbstractBackgroundTDP‐43 is a promising biomarker for frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). However, studies on TDP‐43 in human biofluid are rare. In this work, the authors utilized an ultrasensitive technology, called immunomagnetic reduction (IMR), to develop the reagent for assaying TDP‐43.MethodThe preclinical performance characteristics of the TDP‐43 reagent, such as the standard curve, detection limits, assay linearity, dilution recovery range, assay reproducibility, spike recovery, reagent stability, and interference tests, were explored according to the CLSI guidelines. Plasma samples from normal controls (NC, n = 27) and from patients with frontotemporal dementia (FTD, n = 9), Alzheimer’s disease (AD, n = 34) and Parkinson’s disease (PD, n = 10) were collected for TDP‐43 assays using the IMR TDP‐43 reagent.ResultThe low‐detection limit of assaying TDP‐43 was 0.68 fg/ml, and the upper‐detection limit was 100 pg/ml. There was no significant interference effect when assaying TDP‐43 mixed with hemoglobin, bilirubin, intralipid, albumin, etc. The FTD patients had significantly higher levels of plasma TDP‐43 (0.419±0.193 fg/ml) compared to the NC subjects (0.163±0.097 fg/ml), AD patients (0.165±0.082 fg/ml) and PD patients (0.069±0.068 fg/ml). Through analysis of the ROC curve, the cut‐off value of plasma TDP‐43 for discriminating FTD from the other patient groups was 0.237 fg/ml, which resulted a clinical sensitivity of 0.889 and a specificity of 0.831.ConclusionThese results demonstrate the feasibility of assaying plasma TDP‐43 to specifically identify FTD.
A role for astrocytes and microglia in synapse loss in Alzheimer’s disease
Authors: Tzioras Makis , Daniels Michael , Davies Caitlin , Hooley Monique , He Xin , Dando Owen R. , Hardingham Giles , McColl Barry , Spires‐Jones Tara L. 
Published: February 2022

AbstractBackgroundNeuropathologically, synapse loss correlates most strongly with the progressive cognitive decline observed in Alzheimer’s disease (AD). Despite strong evidence from genetic studies implicating changes in glia as important for disease risk, we are only beginning to understand the role that microglia and astrocytes play in synapse degeneration in AD.MethodIn this study, we have used high resolution imaging of post‐mortem brain tissue to examine whether glia contain synaptic proteins in AD. Cultures of primary mouse and human microglia were exposed to pHrodo‐tagged synapses from human AD or control post‐mortem brain for phagocytosis assays. Mouse models expressing AD associated genes were used for RNA sequencing and translating ribosomal affinity purification (TRAP) followed by RNA sequencing.ResultWe observe both astrocytes and microglia contain synaptic proteins in human AD more than in control brain. Cultured microglia phagocytose synapses from AD brain more and faster than those from control brain. RNA sequencing in AD model mice revealed strong increases neuroinflammatory signals including transcripts expressed in microglia and astrocytes and decreases in transcripts related to synaptic function. When examining the astrocyte specific changes with TRAP, we observed increases in phagosome and lysosome related pathways.ConclusionTogether, our results indicate that microglia and astrocytes play a role in synapse degeneration or clearance of dead synapses in Alzheimer’s disease.
Effects of 6 months of multicomponent exercise on DTI parameters of MCI in the AD continuum
Authors: Ribeiro Isadora Cristina , Teixeira Camila Vieira de Ligo , Rezende Thiago Junqueira Ribeiro , Magalhaes Thamires Naela Cardoso , Cendes Fernando , Balthazar Marcio 
Published: February 2022

AbstractBackgroundThe cognitive changes in Mild Cognitive Impairment (MCI) can be associated to the neurodegeneration of Alzheimer´s pathology, such as white matter atrophy. Increasing evidence demonstrates that physical activity is an important modifiable factor not only for cardiovascular fitness, but also for brain health. Therefore, the aim of this study was to analyze possible effects of 6 months of multicomponent exercise (MEP) on structural connectivity of MCI in the AD continuum.Method19 MCI subjects were diagnosed using the core criteria of the NIA/AA for MCI and altered CSF amyloid. All of them underwent MRI on a 3.0T Philips Achieva scanner. They were divided into MEP group (3x/week for 6 months) and control group (CG, were stimulated to continue with their normal routine). Aerobic fitness was assessed by graded maximal exercise testing on a motor‐driven treadmill. For WM analysis, we used the Tract‐based‐spatial‐statistics (TBSS) method (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/TBSS) to compare the diffusion parameters maps (fractional anisotropy FA, medial diffusivity MD, radial diffusivity RD, axial diffusivity AxD) between times (p‐value<0.05).ResultRepeated measures Anova indicated significant differences between groups and within groups (p=0.008 and p=0,011, respectively), while MEP showed higher values of VO2max (from 24.0 (4.3) to 27.3 (4.4) ml/kg/min‐1), CG reduced (21.0 (3.8) to 19.7 (2.3) ml/kg/min‐1) after 6 months. TBSS demonstrated an increase in FA and AxD values for MEP while FA and AxD values decreased in CG, in the following areas: corpus callosum, forceps major, corticospinal tract, inferior fronto‐occipital fasciculus, inferior and superior longitudinal fasciculus and cingulum. In the same areas mentioned above, MD and RD values decreased for MEP group and increased for CG after the intervention period.ConclusionWe found a positive influence of multicomponent exercise under supervision on aerobic fitness and in the DTI parameters of the participants. Six months of MEP seems to increase the white matter integrity of MCI due to AD.
Social contact, social participation, and their changes among elderly people in the United States during the COVID‐19 pandemic
Authors: Zhang Yun , Luo Amber , Hou Luke , Clouston Sean AP 
Published: February 2022

AbstractBackgroundThe study aims to assess changes of social contact and social participation during the COVID‐19 pandemic among the US elderly, and what roles the prior physical and cognitive performances of the elderly played.MethodData were from the National Health and Aging Trends Study (NHATS) COVID‐19 questionnaire in 2020 (n=3,188, response rate=80.5%).1 Data was linked to the 2019 round to include the demographics, physical and cognitive performances of the participants. Participants that reported COVID‐19 diagnosis and symptoms (n=288) and represented by proxies (n=414) were excluded. Frequencies of social contact with family and friends (phone calls/emails/texts/person visits) and with health care providers, and social participation (working, volunteering, attending religious services, and attending organized activities) prior to and during the COVID‐19 were compared using paired t test for summed scores, Wilcoxon signed rank for paired categorical variables, and McNamara test for paired binary variables. Weighted linear and logistic regressions adjusted for multiple covariates were used to investigate the effects of prior physical and cognitive performances on social contact and social participation, prior to, during, and changes in the COVID‐19.ResultA total of 2,486 participants were included (mean age: 78.24 years; female: 56.20%; non‐Hispanic White: 88.43%). The COVID‐19 resulted in significant increased social contact with family and friends but decreased social participation, among the elderly. Furthermore, elder people with better prior physical performance reported significant increased social contact with family and friends and social participation, both prior to and during the COVID‐19, while they reported significant decreased social participation during the COVID‐19. Specially, better prior physical performance was associated with significant increased video calls and volunteering work during the COVID‐19. However, prior cognitive ability was not found a significant risk factor.ConclusionThe COVID‐19 pandemic affected the pattern of social contact and social participation of the US elderly. Prior physical performance, rather than prior cognitive ability, significantly affected the social way old people respond to a pandemic crisis.
Cognitive decline and healthy aging: An online activities and psychoeducational program for older adults in the context of COVID‐19 pandemic: Preliminary results
Authors: Feldberg Carolina , Tartaglini María Florencia , Hermida Paula Daniela , Somale Maria Veronica , Orellano Anabell , Ortiz Juan , Teran Claudio , Kasten Sergio , De Cara Josefina , Degtiar Marina , Langer Camilo , Benetti Laureana , Redoni Emiliano , Garcia Claudia 
Published: February 2022

AbstractBackgroundThe preventive and compulsory social isolation regulations due to COVID‐19 affected the entire population, but this became more emphasized in the group of older adults. Many older adults who attended workshops, retirement centers and clubs had to interrupt their activities. This has impacted negatively on their activity level, socialization, and emotional state. The aim of the present study is to analyze preliminary results of the implementation of an online activities and psychoeducational program to prevent cognitive decline and promote healthy aging habits in older adults who live in Argentina in the context of Covid‐19 Pandemic.MethodDesign: Descriptive study. Subjects: 396 self‐validated older adults, male and female. Instruments: socio‐demographic and social participation questionnaire. Procedure: The intervention consists of a series of workshops (yoga, meditation, gym, singing lessons, memory, preparation for retirement and reflection about grief) and monthly specialist ´s talks on different topics about healthy aging. All the activities where done through zoom platform. All participants where offer one to one capacitation and written material about how to use this platform. Older adults could choose in how many activities they would take part in.ResultData of 396 older adults who have taken part in the on‐line version of the program on 2020 indicate that median age was 70.66 years old (ds= 8,7) of which 86 % were women. 73 % took part in specialists talks and 68 % on workshops and talks.ConclusionThese results provide empirical evidence regarding the need to implement online intervention programs for older adults. Participating in an online educational program could increase participant’s cognitive healthy habits literacy, empowerment and engagement in brain health promotion activities, which in turn could reduce their dementia risk and feeling of loneliness in pandemic context.
Disentangling brain heterogeneity via semi‐supervised deep‐learning and MRI: Application to dimensional representations of Alzheimer’s disease
Authors: Yang Zhijian , Nasrallah Ilya M. , Shou Haochang , Wen Junhao , Doshi Jimit , Habes Mohamad , Erus Guray , Abdulkadir Ahmed , Resnick Susan M. , Wolk David A. , Davatzikos Christos 
Published: February 2022

AbstractBackgroundHeterogeneity of neurodegenerative diseases, including Alzheimer’s disease (AD), has hampered precision diagnosis and prognosis. Machine learning methods are able to dissect neuroanatomical heterogeneity and enable identification of disease subtypes via their imaging signatures.MethodWe apply a novel semi‐supervised deep‐learning clustering method to derive dimensions of neurodegeneration, and investigate longitudinal paths in this dimensional system. Analyses used structural MRIs (from the Alzheimer’s Disease Neuroimaging Initiative and the Baltimore Longitudinal Study of Aging; total 2,832 participants; 8,146 scans) including controls and patients with Mild Cognitive Impairment (MCI) and AD.ResultSmile‐GAN identified 4 neurodegenerative patterns/axes (Figure 1): P1, normal anatomy; P2, mild/diffuse atrophy; P3, focal medial temporal atrophy; P4, advanced neurodegeneration. Further application to longitudinal data revealed two distinct progression pathways: P1→P2→P4 and P1→P3→P4. Clinically, P2 participants showed worse performance in executive function than P3 participants (median ADNI‐EF= ‐0.29 vs. ‐0.1, with p=0.038) but had better memory (ADNI‐MEM= ‐0.13 vs. ‐0.39, with p=0.003) (Figure 2). Progression to P4 occurred more rapidly from P3 than P2, with median survival time to progression of 4.5 years and 3.2 years for P2 and P3 MCI/Dementia participants, respectively. Baseline expression of these patterns predicted the pathway and rate of future neurodegeneration, with high accuracy for determining whether P1 participants would progress and whether they would progress to P2 or P3 (Cox‐proportional‐hazard model average concordance index (CI) on the validation set of 0.8±0.02). Pattern expression offered better performance (CI=0.72±0.02) in predicting clinical conversion from MCI to Dementia compared to amyloid/tau (CI=0.69±0.02), with all three together showing modest improvement over pattern performance (CI=0.76±0.02). A composite risk score comprised of pattern probabilities, Abeta, pTau, presence of APOE E4, and ADAS‐cog score was able to predict survival time with an average concordance index, 0.78±0.02 on randomly split validation sets. (Figure 3).ConclusionFour reproducible volumetric patterns, and 2 major longitudinal pathways were revealed using deep learning, which can be determined on an individual patient basis and has implications for rate of future decline. These pattern‐based biomarkers can enrich the N‐dimension of the A/T/N framework which may inform on clinical trial enrollment and monitoring outcomes in a more personalized manner.
Relationship between brain tissue loss and levels of blood biomarkers in patients with Alzheimer’s disease
Authors: Jahng Geon‐Ho , Lee Jiyoon , Rhee Hak Young , Ryu Chang‐Woo , Choe Wonchae 
Published: February 2022

AbstractBackgroundThe heme oxygenase‐1 (HO‐1) is known as up‐regulator in AD. The peptidylprolyl isomerase A (PPIA) (also known as cyclophilin A, CyPA) provides protection of neurons against copper‐mediated oxidative stress. The inositol‐requiring enzyme 1 (IRE1) is a major stress transducer in endoplasmic reticulum (ER) stress and abnormal protein aggregation. There is no study to evaluate the relationship between gray matter volume (GMV) loss and the three blood‐based biomarkers. Therefore, in this study, we evaluated the relationship between imaging biomarker by GMV changes and blood biomarkers by plasma levels of HO‐1, PPIA, and IRE1 in the groups of cognitively normal (CN), amnestic mild cognitive impairment (MCI), and AD participants.MethodWe obtained MRI and plasma levels of the three blood biomarkers from 45 CN, 34 amnestic MCI, and 39 AD. To assess the relationship between GMV or WMV loss and the three blood biomarkers, the voxel‐based multiple regression analysis was performed for using all participant data. In addition, region‐of‐interest (ROI)‐based analysis was performed to determine correlations between ROI‐based brain tissue volumes and plasma biomarkers. To investigate the relationship between GMV or WMV at each ROI and the plasma levels of HO‐1, PPIA, and IRE1, we performed the Pearson correlation analyses.ResultThe CypA value was significantly positively correlated with MMSE scores. The HO‐1 value was significantly negatively correlated with age, but was positively correlated with the K‐MMSE score. The IRE1 value was significantly positively correlated with age, but was negatively correlated with K‐MMSE scores. GMV was positively correlated with CypA and HO‐1, but negatively correlated with IRE1.ConclusionOur study demonstrates that subjects with AD have lower circulating levels of HO‐1 than subjects with MCI and the plasma HO‐1 levels were positively associated with the global GMV. This also shows that subjects with AD have lower circulating levels of CyPA than cognitively normal control and the plasma CyPA levels were positively associated with the GMV whereas subjects with AD have higher circulating levels of IRE1 than subjects with MCI and normal control.
Diagnostic accuracy of the telephone interview for cognitive status (TICS) for the detection of dementia in primary care in the Netherlands
Authors: Abdulrahman Hanna 
Published: February 2022

AbstractBackgroundDementia is underdiagnosed in primary care, partly due to limited time and lack of simple diagnostic tools. In the Netherlands, the Mini‐Mental State Examination (MMSE) is the most frequently used diagnostic tool for cognitive screening in clinical practice. The MMSE has several limitations in primary care. The telephone interview for cognitive status (TICS), might be a simple and accurate alternative for cognitive screening, particularly when in‐person testing is not feasible.Methods810 community‐dwelling older people, aged 86.4 years (±2.4SD), with no dementia at baseline, recruited from the prevention of Dementia by Intensive Vascular care (preDIVA) observational extended (POE) trial, and were administered the TICS. Electronic health records of all participants with a TICS ≤30, and a random sample of participants with a TICS‐score >30, were screened for the presence of a dementia diagnosis. Multiple imputation was performed to manage missing data and to correct for verification bias.Results19.1% (155/810) of participants had a TICS‐score ≤30, vs 82.1% (655/810) of participants with a TICS‐score >30. Electronic health records reported 8.4% (13/154) of participants with TICS ≤30 had been diagnosed with dementia, versus none of the participants with a TICS‐score >30. The optimal TICS cut‐off score of the imputed data was at ≤30, with a sensitivity of 86.9%, specificity of 94.9%, positive predictive value of 77.4%, negative predictive value 97.2%, and an area under the curve of 90.9% (95%CI=81.2‐90.9).ConclusionThe TICS seems to be a valid and reliable screening instrument for excluding dementia in primary care, particularly when face‐to‐face screening is not feasible. The ability of TICS to reach large numbers of people at low cost, could contribute to more efficient medical management in primary care.