bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary diagnostic criteria for prodromal behavioral variant frontotemporal dementia: Mild behavioral and/or cognitive impairment
Authors: Barker Megan S , Gottesman Reena T , Manoochehri Masood , Forsberg Leah K. , Heuer Hilary W. , Boeve Bradley F. , Boxer Adam L. , Rosen Howard J. , Cosentino Stephanie , Rascovsky Katya , Huey Edward D. ,   ALLFTD Consortium
Published: December 2021

AbstractBackgroundAt present, no research criteria exist for the diagnosis of prodromal behavioral variant frontotemporal dementia (bvFTD). Leveraging data from carriers of pathogenic genetic mutations as a proxy for frontotemporal lobar degeneration pathology, we sought to develop and test a proposed set of research criteria for prodromal bvFTD, termed “Mild Behavioral and/or Cognitive Impairment in bvFTD” (MBCI‐FTD).MethodParticipants included 68 carriers of a pathogenic mutation in microtubule‐associated protein tau (MAPT), or progranulin (GRN), or a repeat expansion in chromosome 9 open reading frame 72 (C9orf72), with mild behavioral and/or cognitive changes. Based on extensive clinical workup, the prodromal mutation carrier group was divided into a Development Group (N=22) and a Test Group (N=46). The Development Group was selected to be the subset of the prodromal mutation carriers for whom we had longitudinal evidence of conversion to a bvFTD phenotype, and were used to develop the criteria. The Test Group was the remainder of the prodromal mutation carriers (e.g., single visits only) and was used to validate the criteria. Familial non‐carriers were included as controls (N=165).ResultFrequencies of behavioral and neuropsychiatric features, neuropsychological deficits, and social cognitive dysfunction in prodromal mutation carriers and non‐carrier controls were assessed. Based on sensitivity and specificity analyses, seven core features were identified: apathy without moderate‐severe dysphoria, behavioral disinhibition, irritability/agitation, reduced empathy/sympathy, repetitive behaviors (simple and/or complex), joviality/gregariousness, and appetite changes/hyperorality. Supportive features include a neuropsychological profile of impaired executive function or naming with intact orientation and visuospatial skills, reduced insight for cognitive or behavioral changes, and poor social cognition. Three core features or two core features plus one supportive feature are required for the diagnosis of Possible MBCI‐FTD; Probable MBCI‐FTD requires imaging or biomarker evidence, or a pathogenic genetic mutation. The proposed MBCI‐FTD criteria correctly classified 95% of the Development Group of prodromal mutation carriers, and 41% of the Test Group, with a false positive rate of <10%.ConclusionWe present the first diagnostic criteria for prodromal bvFTD. Future research should prioritize establishing generalizability to non‐genetic cases, and testing the specificity of these criteria against psychiatric, neurologic and other neurodegenerative diseases.
Altered central and peripheral glutathione in Alzheimer disease and mild cognitive impairment: A meta‐analysis
Authors: Chen Jinghan Jenny , Thiyagarajah Mathura , Song Jianmeng , Chen Qi Zhen , Herrmann Nathan , Lanctôt Krista L. 
Published: December 2021

AbstractBackgroundIncreasing evidence implicates oxidative stress (OS) in Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS‐mediated neurodegeneration, though post‐mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of brain and peripheral GSH may shed light on GSH changes, with implications for its role as a biomarker and therapeutic target. Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta‐analysis.MethodStudies published before June 2020 containing measurements of in vivo brain or peripheral GSH in MCI or AD with a HC group were identified using Medline, PsychInfo, and Embase. Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher‐Garwood Point Resolved Spectroscopy (MEGA‐PRESS versus non) in AD and MCI, and peripheral GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias respectively.ResultsFor brain GSH, 4 AD (AD=175, HC=272) and 4 MCI (MCI=254, HC=260) studies were included. For peripheral GSH, 26 AD (ADD=981, HCl=993) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH did not differ in AD or MC compared to HC; however, the subgroup of studies using MEGA‐PRESS reported lower brain GSH in AD (SMD [95%CI] = ‐1.47 [‐1.91, ‐1.02], p=0.02) and MCI (‐1.08 [‐1.53,‐0.64], p=0.01). Peripheral GSH was lower in AD (‐0.94 [‐1.37, ‐0.51], p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (‐0.66 [‐1.11, ‐0.21], p=0.02). Significant heterogeneity was observed in all analyses and supported the use of random effect models. Egger’s test indicated risk of publication bias in MCI brain GSH literature.Conclusion
In vivo measures of GSH in AD and MCI had significant heterogeneity. Peripheral analyses suggested intracellular GSH decreases may be prominent in early disease stages with both intra‐ and extracellular decreases in later stages. Brain GSH may be decreased in AD and MCI but heterogeneity and potential bias indicate the need for measurement standardization and replication.
Oxidative stress biomarkers in individuals with Down syndrome: Implications to the pathogeny of Alzheimer's disease
Authors: de Mendonça Gabriella Ayub , Forlenza Orestes Vicente 
Published: December 2021

AbstractBackgroundThe concentration and activity of a set of oxidative stress markers in peripheral blood of individuals with Down syndrome (DS), individuals with mild cognitive impairment (MCI) and with Alzheimer’s disease (AD) were determined to study the possibility of AD biomarkers based on oxidative stress.MethodPlasma was obtained from control individuals (n=30) and individuals with DS (n=30), MCI (n=30) and AD (n=30) and six markers of oxidative stress were analyzed: the plasma concentrations of three markers of lipid peroxidation (malondialdehyde, 4‐hydroxynonenal and protein carbonyls), quantified by enzyme‐linked immunosorbent assays, as well as the activity of three enzymes involved in the regulation of oxidative stress (SOD1, catalase and glutathione peroxidase), assessed by colorimetric assays.ResultLevels of catalase and malondialdehyde were significantly higher in Down syndrome group than for controls. The SOD activity was also higher in Down syndrome group than for controls. None of the markers presented different levels relating the control group and the MCI and AD groups.ConclusionDespite being expressed differently in Down syndrome, stress oxidative biomarkers do not seem to be strong and differential markers for dementia in individuals with DS, MCI and AD.
The women’s Alzheimer’s prevention center at Cleveland Clinic: Centering women in Alzheimer’s prevention care and research
Authors: Caldwell Jessica ZK , Crocker‐Sabbagh Ida , Kaplan Nikki , Sabbagh Marwan N 
Published: December 2021

AbstractBackgroundWomen represent two‐thirds of individuals currently diagnosed with Alzheimer’s disease (AD), and up to 40% of current AD cases may be attributed to modifiable lifestyle‐based risks. Our Women’s Alzheimer’s Prevention Center (WAPC) is designed to offer women personalized assessment and recommendations regarding known lifestyle risks for AD and support best practices for lifetime brain health.MethodThe WAPC is a clinic first and foremost, for women of any age who self‐report risk for AD. Target age is 40‐60, with opportunity for approximately 400 women to participate over three years. Research participation is optional. Women undergo comprehensive online and in‐person assessment including measures of mood, sleep, diet, exercise, stress, cognition, current medical health, and medical and family history. Women have an in‐person, two‐hour results and recommendations visit with a neuropsychologist and family medicine physician, in which they received specific and personalized recommendations for reducing their modifiable AD risks. A lab panel including AD‐specific risk factors is ordered at this visit and reviewed at a 2‐month follow‐up visit with the family medicine physician. Women receive quarterly assessment of memory, treatment satisfaction, and adherence, as well as one‐year follow‐up reassessment. Scientific goals of the WAPC include assessing patient satisfaction and treatment adherence for practice improvement, and assessing women’s collective one‐year success in reducing lifestyle risks for AD based on self‐report and objective measures of physical health.ResultTo date, 61 women patients have been seen for initial assessment and recommendation visits.ConclusionThe WAPC is the only women‐specific Alzheimer’s prevention center in the country, and offers unique opportunities to study women’s use of and satisfaction with comprehensive prevention services and recommendations, as well as a long‐term opportunity to assess impact of prevention lifestyle on women’s specific indicators of AD risk.
Increased functional connectivity of the precuneus in individuals with a family history of Alzheimer’s disease
Authors: Green Zachary D. , Vidoni Eric D , Swerdlow Russell H , Burns Jeffrey M. , Morris Jill K , Honea Robyn A 
Published: December 2021

AbstractBackgroundFirst‐degree relatives of individuals with late‐onset Alzheimer’s Disease (AD) have increased risk for AD, with children of affected parents at an especially high risk. We sought to test how structural or functional abnormalities in the default mode network (DMN) during the brain’s “resting state” characterized individuals at risk for AD.MethodWe used MRI and fMRI to study cognitively healthy individuals (n=28) with and without AD family history (FH+ and FH‐, respecitvely), those with amnestic mild cognitive impairment (aMCI; n=31) and early‐stage AD (n=25). We tested connectivity within the DMN, as well as measures of volume and thickness within both the medial temporal cortex and in selected seed regions. Our primary hypothesis was that there would be a linear decline within the risk groups on all measures of AD risk (FH‐>FH+>aMCI>AD).ResultAs expected, we identified significantly decreased medial temporal cortex volumes in the aMCI and AD groups compared to both nondemented groups. We also observed patterns of connectivity across risk groups that suggest a nonlinear relationship of change, such that the FH+ group showed increased connectivity compared to the FH‐ and AD groups. This pattern emerged primarily in connectivity between the precuneus and frontal regions.ConclusionWe present distinct structural and functional brain imaging profiles for two AD‐risk groups; cognitively healthy, FH+ individuals, and individuals with aMCI. These results add to a growing literature that suggests compensatory brain function in otherwise cognitively healthy individuals with a family history of AD.
Transfer learning with related tau PET radioligands improves 3D neural network performance
Authors: Zou James , Park David , Johnson Aubrey S , Tomljanovic Zeljko , Devanand Davangere P. , Luchsinger Jose , Brickman Adam M. , Kreisl William Charles , Provenzano Frank 
Published: December 2021

AbstractBackgroundNeural networks are increasingly being applied towards neuroimaging problems in AD, but performance is often limited by lack of adequate numbers of samples. This is commonly alleviated by pre‐training the model on a related task beforehand (i.e. ‘transfer learning’). To our knowledge, there exists no set/standard of widely available pretrained model weights for 3D medical images. Tau PET radiotracers such as AV‐1451 and MK‐6240 have highly similar binding patterns, and so may be well suited to transfer learning tasks.MethodSubjects with AV‐1451 scans (n=446) were downloaded from ADNI, while subjects with MK‐6240 scans (n= 320) were pooled from multiple studies recruiting at CUIMC. We trained multiple 3D neural networks (all with the same modified InceptionV3 architecture) to differentiate patients (i.e. MCI/AD) from controls based on their tau PET scan, both with and without pretraining information from prior training iterations of our models. We compare performance on holdout sets for each validation fold (n= 64 for MK‐6240 and n=89 for AV‐1451) using DeLong’s test for ROC curves and analyze features learned by models with t‐SNE plots.ResultThe AV‐1451 Model pretrained on MK‐6240 scans had superior performance to the AV‐1451 model not using pretraining (AUC = 0.74 vs. 0.91, Z = ‐5.5, p < 0.0001), whereas there was no significant difference with pretraining for MK‐6240 models (AUC = 0.84 vs. 0.83, Z = 0.47 ,p = 0.6). Visually, there appears to be greater separation in model learned features following pretraining in the AV‐1451 model.Conclusion3D pretraining for neural networks involving PET imaging could be accomplished with related but structurally different radioligands, though more work is needed into determining why certain pretraining experiments are successful. This procedure can enable better training of complex models with fewer constraints due to sample size.
Error relationship to an everyday monitoring in mild cognitive impairment: Cognitive correlates and task
Authors: Pagán Carolyn R. , Arrota Kayela , Cunningham Reanne , Schmitter‐Edgecombe Maureen 
Published: December 2021

AbstractBackgroundAccurate error monitoring is important for successful completion of everyday tasks and use of compensatory strategies. This work examined error monitoring in individuals with amnestic MCI (aMCI) as compared to healthy older adults (HOA) using a computerized task. We also examined cognitive domains associated with error monitoring and the contribution of error monitoring to objective and self‐reported measurement of everyday functioning.MethodsTwenty‐four individuals with aMCI and 24 HOAs were administered a battery of neuropsychological tests (domains assessed: attention, working memory, executive functioning, memory, language, visuospatial abilities); a sustained attention task that included an error‐monitoring score (Sustained Attention to Response Task; SART); a naturalistic, performance‐based measure of everyday functioning (Day Out Task; DOT); and self‐ and informant‐report measures that captured everyday dysexecutive difficulties (DEX).Results
T‐test comparisons revealed the aMCI group (M = 0.48; SD = 0.22) exhibited poorer error monitoring (measured by the number of accurately self‐corrected errors on the SART divided by total errors) compared to the HOA group (M = 0.71; SD = 0.23), d = 1.02. Partial correlation analyses with age as a covariate revealed significant correlations between the error monitoring score and the cognitive domains of working memory and executive functioning for both the aMCI group and the HOA group. Hierarchical regression analyses revealed that after accounting for age and global cognitive status, the SART error monitoring score significantly predicted DOT total time, but not accuracy, as well as both self‐ and informant DEX scores.ConclusionThis study revealed that the ability to recognize errors was significantly poorer in individuals with aMCI compared to HOAs and most associated with the cognitive domains of executive functioning and working memory. After controlling for age and general cognitive status, error monitoring predicted performance in everyday functioning as assessed by a naturalistic, performance‐based test and questionnaires assessing everyday dysexecutive difficulties. This suggests that if individuals with aMCI do not recognize performance inaccuracies, they will not be able to correct errors, leading to mistakes in everyday task completion and reduction in implementation of appropriate compensatory strategies. These results implicate error monitoring as a potential target for early interventions with individuals with aMCI.
Factors associated with subjective cognitive decline in older adults in pre‐clinical dementia phases
Authors: Rivera‐Fernandez Claudia , Soto Marcio 
Published: December 2021

AbstractBackgroundThe phase of subjective cognitive decline (SCD) has shown inconsistency as a preclinical phase of dementia. Recent data show a greater association with emotional disturbances than cognitive aspects. Our objective was to analyze the factors associated with SCD in preclinical phases of dementia. Recent data show a greater association with emotional disturbances than cognitive aspects. Our objective was to analyze the factors associated with SCD in preclinical phases of dementia.MethodWe evaluated 94 older adults (Mean Age = , SD = ) with the MMSE, the Pfeiffer functional scale and the Yesavage geriatric depression scale. We also used a neuropsychological protocol that included memory, executive function, visuospatial, fluency and processing speed tasks. We applied a principal component analysis (PCA) to reduce dimensionality. Finally, we use logistic regression considering SCD as a dichotomous variable and sociodemographic and components extracted as a predictor.ResultWe observed that 48.35% of the older adults manifest subjective cognitive decline. Regression analysis shows that emotion (OR=1.839, IC95%: 1.268‐2.667) and older age (OR=1.282, IC95%: 1.068‐1.538) are associated with higher risk for SCD. Surprisingly, higher scores in memory factor are associated with an increased risk for SCD (OR=3.243, IC95%: 1.163‐9.038). On the other hand, lexical access factor Is associated with reduced risk of SCD (OR=0.389; IC95%: 0.159‐0.953).ConclusionThe SCD phase seems to be more associated with emotional states than cognitive performance, even older adults with better memory scores shows more complains about their cognitive performance. We suggest to follow‐up the sample and use validated instruments of SCD, neuroimaging data or fluid markers, to deep in the construct and validate its relevance as clinical marker.
Falls predict cognitive status
Authors: Gray Michelle , Paulson S. , Gills J.L. , Glenn J.M. , Madero E.N. , Myers J. , Campitelli A. , Jones M. , Vincenzo J. , Walter C. 
Published: December 2021

AbstractBackgroundCognitive impairment is associated with increased falls and fall risk among older adults. In fact, studies have significantly predicted falls between high and low cognitive functioning community‐dwelling older adults. However, many negative cognitive changes occur years before significant cognitive changes arise. Thus, the purpose of the present investigation was to determine the ability of falls to predict cognitive status using a digital Digit Symbol task (Neurotrack Technologies, Inc., Redwood City, CA).MethodSixty‐nine community‐dwelling older adults (80.7 ± 5.4 years) volunteered to complete a falls history questionnaire and a digital Digit Symbol task. Cognitive groups (High [HDS] and Low Digit Symbol [LDS] function) were determined based on age‐sex normative values. Logistic regression analysis was conducted predicting cognitive group placement using age, sex, education, and previous falls within previous 12 months.ResultBy knowing the four predictor variables (falls, age, sex, education), cognitive group (HDS vs. LDS) was predicted correctly 80% of the time. Sensitivity and specificity were 90% (37 of 41) and 64% (18 of 28), respectively. The addition of fall risk was not statistically significant; however, it increased sensitivity by 4% and specificity by 13%.ConclusionThe results suggest that knowing falling status may help identify older adults with cognitive impairment, specifically deleterious changes in processing speed. While the mechanisms cannot be elucidated from the present investigation, others have suggested slower processing speed is associated with impaired balance; thus, leading to falls. Future research is needed to further examine the relationship between falls and cognitive performance in hopes that identifying fallers could lead to more extensive cognitive testing.
In silico differential gene expression analysis in tissue databases from patients with Alzheimer’s disease, to identify potential new biomarkers
Authors: del Carmen Silva‐Lucero Maria , Rivera‐Osorio Jared , Yogesh Muley Vijaykumar , Lopez‐Toledo Gustavo , Sanchez Cintia P. , del Carmen Cardenas‐Aguayo Maria 
Published: December 2021

AbstractBackgroundAlzheimer's disease (AD) is a neurodegeneration that accounts for 60‐70% of dementia cases. Symptoms begin with mild memory difficulties and evolve towards cognitive impairment. The underlying risk factors remain largely unclear for this heterogeneous disorder. Discovery of AD biomarkers will allow early detection and the discovery of new treatments. Bioinformatics has become a relevant research tool which have led to the identification of several pathways related to AD.MethodOpen access databases of RNA microarrays of tissue from the medial temporal lobe (MTL) and peripheral blood of AD patient, were analyzed after background correction and data normalization, Limma package was used for DEA throw statistical R programming language. Data were corrected with the Benjamini and Hochberg approach and the genes with p values equal to or less than 0.05 were considered significant. The direction of the change in gene expression was determined by its variation in the "log2‐fold change" between controls and patients. We performed a functional enrichment analysis of GO using goana and topGO‐Limma (Smyth et al., 2016).ResultWith MTL brain tissue database (EMEXP 2280) we obtained 359 down regulated genes (DR) and 324 up regulated genes (UR), the UR pathways were: transcription, mitochondrial function and hydrolase activity, while DR were: gene expression and regulation of cell proliferation, nuclear alterations, transmembrane receptor signaling. Analysis with KEGGp showed that metabolic pathways were UR and cytokine pathways and their receptors were DR. The blood samples analysis (PBMC, E‐GEOD‐18309) showed 383 genes DR and 257 genes UR. Finally, the intersection of the differentially expressed genes in the two databases showed 34 genes shared between the brain and blood arrangements and TRIM58 matched in both databases.ConclusionOur in‐silico analysis of AD brain tissue identifies several UR genes related to mitochondria, function, transcription, and hydrolase activity, while gene expression, regulation of proliferation and nuclear alterations were DR. On the other hand, blood databases showed DEG such as TRIM58 (E3 ubiquitin ligase), that is involve in ubiquitination. Protein identified here could be valuable as possible new AD biomarkers.