bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between the number of subjective cognitive decline domains involved and the neuroimaging biomarkers of Alzheimer’s disease: The SILCODE Study
Authors: Wang Xiaoqi , Sun Yu , Bi Qiuhui , Shu Ni , Han Ying 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD), one of the earliest manifestations in preclinical Alzheimer’s disease (AD), may involve one or more cognitive domains including memory, language, executive and others. Converging evidence has revealed the association between SCD and AD biomarkers such as amyloid deposition and neurodegeneration alterations. However, most of the studies about SCD limited to memory domain and whether the increasing number of SCD domains involved is related to the neuroimaging biomarkers of AD remains largely unknown.MethodMultimodal imaging techniques, including 18F‐florbetapir PET (AV45‐PET), 18F‐fluorodeoxyglucose PET (FDG‐PET), structural and resting‐state functional MRI, were performed in 63 SCD subjects and the regional imaging measures of 12 selected regions of interests (ROIs) were calculated, namely standard uptake value ratio (SUVr) of AV45‐PET and FDG‐PET, cortical thickness and fractional amplitude of low‐frequency fluctuation (fALFF) values. The total number of cognitive domains with reported complaints and the severity of memory complaints were assessed for each SCD subject. Partial correlation analyses were conducted to test the relationship between these SCD features and the neuroimaging markers of AD.ResultSCD who reported multidomain complaints (multidomain SCD, md‐SCD, n=34) had greater amyloid burden, elevated fALFF values and thickened cortical thickness in the posterior cingulate gyrus and middle temporal gyrus than SCD who reported merely memory complaints (single domain SCD, sd‐SCD, n=29) (Figure 1). Even when regarded as continuous variable, the number of SCD domains involved was positively correlated with the degree of amyloid load in posterior cingulate, fALFF values in middle temporal, posterior and anterior cingulate and cortical thickness in precuneus (Figure 2). Additionally, the severity of memory complaints measured by the SCD questionnaire (SCD‐Q9) was only related to cortical thickness, but no significant association with other imaging markers was found (Figure 3).ConclusionAn increased number of SCD domains involved was correlated with amyloid accumulation and may also be indicative of an underlying compensatory mechanism medicated by brain structures and functions alterations. Therefore, the reported number of SCD domains may be a potential valuable feature of SCD‐plus for AD risk and is promising for predicting AD pathologies.
Connecting with minority group Indonesians in the Netherlands
Authors: Utomo Amalia Fonk 
Published: December 2020

AbstractBackgroundThere are 16.151 registered Indonesian living in The Netherlands (source: Indonesian Embassy in The Netherlands). Around 800.000 Dutch people in 4 generations have Indo‐European roots. Besides Indo‐Europeans, around 40.000 people from Moluccan descent live in the Netherlands.(source: latitudes.nu) and 1.500 Indonesian are studying in The Netherlands, Alzheimer Indonesia Nederland & Alzheimer Nederland have a collaboration under the Twinning Program of Alzheimer's Disease International. This is a three‐year program for 2017‐2019 and a renewal of the previous program and funded by the Dutch government. Part of the funding is directed to activities for Indonesians in The Netherlands.MethodIn 2017 a foundation, Stichting Alzheimer Indonesia Nederland was created in the Netherlands to support and raise awareness within the Indonesian community living in the Netherlands about dementia and efforts in Indonesia. Accessing Indonesian Communities: religious, art and culture, professionals and government sharing information about the foundation and developments in Indonesia by connecting to more than 20 Alzheimer Indonesia’s chapters. By mid 2019 more than 2000 Dementia Friends and 50 volunteers are arranged in 8 cities: Groningen, Den Haag, Eindhoven, Amsterdam, Arnhem, Rijswijk, Zoetermeer, Rotterdam – The Netherlands and 2 cities in Indonesia: Jakarta and Malang. The foundation also connected to home care and nursing homes, an Alzheimer centre at the University and Alzheimer Café and two migrant organisations. We found that it is useful to explain Indonesian culture and behavior with the aim to help them to make their care accessible to Indonesian people. This is useful for both home care and nursing home care.Result4000 Dementia Friends, 60 volunteers, 83 Activities, 16 Cities in The Netherlands and 4 Cities in Indonesia.ConclusionInstead of generalisation, customized social, culture and religion approach and treatment are needed and helpful for minority migrant.
Memory and music: The role of musical training in verbal and visual working memory in musician and non‐musician adult subjects: Preliminary results
Authors: Garcia Lydia Moya , Feldberg Carolina , Tartaglini María Florencia , Hermida Paula Daniela , Irrazabal Natalia , Somale Verónica , Stefani Dorina 
Published: December 2020

AbstractBackgroundMemory has been studied broadly in recent decades. Within the different systems that constitute this multidimensional construct, working memory is one of the components that generated the most unknowns, given the various processes put into play for its operation. The Cognitive Reserve Theory’s framework postulated that musical training is an activity that can help to protect and enhance such mnemic processes and those related to it. The main objective of this study is to explore the possible differences in working memory between musicians and non‐musicians normal adults.MethodThe steps for a cross‐sectional study were used. A total of 77 subjects between 18 and 55 years (32 musicians and 45 non‐musicians) were interviewed. The main materials used were Musical Training Questionnaire‐Argentine (Gooding, Abner, Jicha, Kryscio and Schmitt, 2014; Feldberg et al., 2019) to quantify the musical training in each subject (musicians also should have at least 5 years of musical training), and BIMeT‐Verbal and Visuospatial versions (Injoque‐Ricle, Barreyro, Formoso and Burin, 2018; Barreyro, Injoque‐Ricle, Formoso and Burin, 2019) to asses various aspects of verbal and visuospatial working memory. Measures of central tendency and dispersion were obtained to describe the socio‐demographic and musical training variables. Consequently, a normality test was performed and the Mann‐Whitney U test was used to contrast performance between groups. An error probability minor or equal to 0.05 was established, and data were analyzed by SPSS statistical software version 22.0.ResultThe results indicated a better performance by the group of musicians in a great extent of tests that set up the BIMeT‐V (direct letters score, p=0.049; direct letters span, p= 0.013; digit‐letter score, p=0.007; digit‐letter span, p=0.016) and BIMeT‐Ve (simple star score, p=0.001; simple star span, p=0.001; interferic star score, p=0.000; interferic star span, p=0.001; interferic blocs score, p=0.000; interferic blocs span, p=0.000).ConclusionThe results of this work are consistent with those that have been previously researched, providing evidence regarding the role of music training in enhancing mnesic processes, especially in verbal and visuospatial aspects of working memory.
A comparison of neurocognitive decline in older adults in same‐sex and opposite‐sex relationships
Authors: Manca Riccardo , Venneri Annalena 
Published: December 2020

AbstractBackgroundIndividuals from sexual minorities experience health inequalities that have a detrimental impact on both physical and mental health. This disadvantage may particularly affect ageing people by exacerbating symptoms of chronic conditions, such as Alzheimer’s disease (AD) and generating more complex care needs. However, neurocognitive functioning and impairments due to neurodegenerative diseases in the lesbian, gay and bisexual (LGB) ageing population remain under‐investigated. Race and mood problems may confer higher risk for subjective cognitive complaints, while being in a relationship may mitigate the risk of cognitive impairment in LGB older adults.MethodClinical data for this study were selected from the National Alzheimer’s Coordinating Center’s Uniform Data Set and structural MRI data included were collected in 14 Alzheimer’s Disease Research Centres. Twenty patients with AD and 20 healthy controls (HC) in same‐sex relationships were identified and matched to groups of participants (20 AD and 20 HC) in opposite‐sex relationship by sex, age, education, cognitive status, diagnosis and APOE status. Interactions between diagnosis and relationship on all measures were investigated. Additional post hoc analyses were carried out in the same‐sex and opposite‐sex groups separately.ResultNo diagnosis‐by‐relationship interactions were found on any variable, although patients in the same‐sex group were more likely to present with at least one neuropsychiatric symptom. The opposite‐sex group had grey matter atrophy mainly in medio‐temporal and insular areas, while in the same‐sex group it extended also in medial frontal and posterior cingulate areas.ConclusionOur preliminary findings suggest that neurocognitive decline due to AD may express similarly across individuals, independently of relationship type, thus further suggesting a possible role of relational status as a protective factor. However, the same‐sex group of patients, compared to HC, appeared to be more likely to experience at least one neuropsychiatric symptom and to have atrophy in fronto‐limbic and insular areas, in line with previous studies. Future investigations should clarify whether AD‐related symptoms may manifest differently in people from sexual minorities, along risk and protective factors, in order to inform prevention programs and treatment planning.
Reasons for study exclusion by sex in lanabecestat studies AMARANTH and DAYBREAK‐ALZ
Authors: Zimmer Jennifer A. , Andersen Scott W. , Wessels Alette M. , Shering Craig , Sims John R. 
Published: December 2020

AbstractBackgroundSex‐based differences in pathophysiology and clinical presentation of Alzheimer’s Disease (AD) have been reported. These differences could impact trial eligibility. This analysis of screening data assesses the most common reasons for exclusion within sex.MethodPhase 2/3 AMARANTH (NCT02245737) enrolled early AD (MCI due to AD, mild AD dementia) with MMSE 20‐30 and RBANS DMI ≤85. Phase 3 DAYBREAK‐ALZ (NCT02783573) enrolled mild AD with MMSE 20‐26. For MCI, NIA‐AA criteria were met, with CDR of 0.5 and memory box score ≥0.5. For mild AD, NIA‐AA criteria were met, with CDR of 0.5 or 1 and memory box score ≥0.5. Both studies enrolled participants 55‐85 years‐of‐age with proof of amyloid (PET scan or cerebrospinal fluid). Excluded participants meeting prespecified criteria were permitted ≤2 rescreens. Reasons for exclusion and patients randomized are presented by sex. The top three reasons for exclusion are compared by female and male subsets. In AMARANTH, participants could fail >1 criterion. For DAYBREAK‐ALZ, MMSE exclusion is further divided into MMSE score subsets (<20 or >26, when available). Statistical comparisons are made using Pearson’s Chi‐Square and not adjusted for multiplicity.ResultFor both studies, proportions of females represented in reasons for exclusion and randomization are similar (AMARANTH: 52% vs. 53%; DAYBREAK‐ALZ: 57% vs. 59%). In AMARANTH, MMSE score not within range was more commonly reported and lack of presence of amyloid was less commonly reported in the female subset than the male subset (17.8% vs 13.5% (p<0.001) and 22.4% vs 24.5% (p<0.05) of reasons, respectively). In DAYBREAK‐ALZ, proportions of reasons for exclusion in sex subsets were similar. However, MMSE score <20 was more common and MMSE score >26 less common as a reason for exclusion in the female subset compared to the male subset (females vs. males: score <20: 24.6% vs 18.3%, score >26: 12.8% vs 19.7%; p<0.001 for each).ConclusionThese results suggest females presenting for screening may have more advanced disease. Possible reasons include late referral of females due to advanced verbal memory skills delaying recognition of disease, social circumstances, faster disease progression of females identified from clinical trial site databases, or differences in educational attainment.
Amyloid imaging for cognitive studies in cohorts with racial and ethnic diversity
Authors: Sano Mary , Zhu Carolyn W , Aloysi Amy , Grossman Hillel , Loizos Maria , Hedden Trey , Kinsella Michael T , Neugroschl Judith 
Published: December 2020

AbstractBackgroundTo compare rates of amyloid positivity in non‐Hispanic whites with diverse cohorts including Hispanic, Black, Asian, and other research participants.MethodsParticipants were enrolled in the ADRC, completed the Unified Data Set (UDS) and underwent amyloid imaging (2011‐2019). Racial and ethnic origin was self‐reported. Referral source and study enrollment were recorded. Amyloid images received a clinical read by a neuro‐radiologist who was blinded to patient characteristics used to determine amyloid status, regardless of study‐specific amyloid determination.Results191 cases who had received amyloid imaging were identified. 113 were non‐Hispanic white and 78 were minorities (36 non‐Hispanic Black, 28 Hispanic, 6 Asian, 8 other). Aside from the most common referral source from physicians (42%) for participants in both white and minority groups (42%), referral sources differed between white and minority participants. Amyloid imaging was performed using Amyvid (florbetapir F18 injection, n=94) and Neuraceq (florbetaben F18, n=97, 50.8%) tracers but usage differed between white and minority groups. Participant characteristics were: mean age 68.1 (SD=10.8) at time of scan, 52.9% male, mean CDR Sum of Boxes 0.8 (SD=1.3), 57.9% had no Apolipoprotein e4 alleles. Differences in these measures were not statistically significant between white and minority groups. Education (16.7±2.5 vs. 15.0±3.3) and cognitive composite scores (5.0±1.8 vs. 4.5±1.4) were higher in white compared to minority group (both p<0.01). Amyloid positivity was 27.4% (31/113) in whites, significantly higher than 9.0% (7/78) among minorities (p=0.002). Both groups demonstrated increasing amyloid positivity with age with whites ranging from 11.8% in those younger than 70, 34.0% in those age 70‐79, to 66.7 % in those 80 or older, and ranging from 4.7%, 14.3%, 14.3% in minorities in the same age groups, respectively. Results from analysis restricted to those with a UDS determined diagnosis of normal cognition, aMCI or AD remained the same.ConclusionsIn this relatively small convenience sample from diverse sources of recruitment and differential use of tracers for imaging studies we confirm previous impressions of lower rates of amyloid positivity in aging minority cohorts despite poorer cognitive performance. Both white and minority cohorts demonstrated age related increase in the presence of brain amyloid positivity.
Novel insights into risk of dementia after traumatic brain injury: A systematic review, meta‐analysis, and heterogeneity analysis
Authors: Gardner Raquel C. , Bahorik Amber L , Mangal Paul , Allen Isabel Elaine , Yaffe Kristine 
Published: December 2020

AbstractBackgroundTraumatic brain injury (TBI) is an established risk factor for dementia. Risk estimates have varied substantially across studies with recent studies reporting higher risk in veterans, men, or at the extremes of age. We performed the largest and most comprehensive systematic review of risk of post‐TBI dementia with the aim of specifically investigating contributors to heterogeneity including age, sex, and veteran status.MethodWe performed a systematic review and meta‐analysis of all‐cause dementia after all‐severity TBI (search window 1/1990‐1/2019). We identified observational studies reporting age‐adjusted risk for all‐cause dementia after TBI among individuals with average age ≥40 years. Data were pooled using random‐effects models. Between study variability was assessed using the I2 index. We further evaluated sources of heterogeneity according to covariates including mean age, sex distribution (majority male vs. majority female), veteran status, design (case‐control vs. cohort), outcome/exposure ascertainment (ICD‐9 vs. other) and publication year using sub‐groups and meta‐regression analysis. Funnel plot inspection and Egger and Begg statistics were used to evaluate publication bias.ResultData from 41 studies representing N=7,736,173 individuals were included in the analysis. Overall pooled risk ratio (RR) for dementia after TBI was 1.71 (95% confidence interval [CI] 1.47,1.98) with no evidence of publication bias. There was substantial heterogeneity (I2= 98.6%; Q test p<0.001). Removal of each study in turn did not reduce heterogeneity. No significant differences were observed in risk estimates for dementia after TBI according to veteran status, study design, outcome/exposure ascertainment, or publication year (all p’s >0.09). However, risk estimates were significantly higher in studies with lower mean age (mean age <50y RR 2.52 [1.80,3.53]; 50‐70y RR 1.73 [1.34,2.24]; >70y RR 1.41 [1.17,1.71]; p=0.01; see Figure) and in studies that were majority male (majority male RR 2.16 [1.74‐2.69]; majority female RR 1.44 [1.22,1.70]; p=0.01). Mean age and sex distribution accounted for 27.5% and 27.9%, respectively, of the observed heterogeneity.ConclusionTBI is associated with a 71% increased risk for dementia. While risk was not modified by veteran status, risk was significantly higher in studies with younger mean age and majority male populations. These findings may inform targeted TBI prevention efforts.
Differential transcript usage unravels transcriptional alterations in Alzheimer's disease human brains
Authors: Marques‐Coelho Diego , Iohan Lukas , Lambert Jean‐Charles , Costa Marcos Romualdo 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of dementia in aging individuals. Several studies have shown that 60‐80% of late‐onset AD attributable risk has an important genetic component. However, a comprehensive overview of gene expression alterations in the diseased brain remains elusive.MethodIn this work, we compared the differential expression of genes in different regions (temporal and frontal lobes) of the brain of healthy and AD adult subjects from three large datasets: MAYO Clinic; Mount Sinai Brain Bank (MSBB) and ROSMAP. We also used isoform switch analysis to identify genes with altered transcript usage. Finally, we assigned altered genes to specific cell types of the adult brain and evaluate the expression of AD risk genes previously identified in pan‐genomic association studies.ResultWe show that gene expression is dramatically altered in the temporal lobe (TL), but not in the frontal lobe (FL), suggesting regional specificities in transcriptional alterations. Moreover, we show that a large set of genes without alteration in the classical differential expression (DEG) analysis do have alterations in the transcript usage ratio in AD. Ontology analysis for genes with differential transcript usage (gDTUs) show enrichment for key biological processes associated with AD pathology, which are not observed for DEGs only. Using single‐cell RNAseq data, we are able to assign DEGs and gDTUs to individual cell types of the adult brain and show that genes associated with synaptic transmission are mostly affected in GABAergic neurons. Lastly, we show that 52 out of 116 putative AD risk factors expressed in neural cells, microglia or endothelial cells of the adult human brain are differentially expressed in the TL, whereas only 13 are altered in the FL of AD patients. Among those altered genes, we detect an increased expression of APP isoforms containing the Kunitz protease inhibitor (KPI) domain, which is associated with plaque deposition.ConclusionAltogether, our work proposes a novel integrative strategy to analyse transcriptional data in AD based on both gene/transcript expression and cell‐type specificities and reveal an alteration of APP expression that could contribute to explain the increased production of Abeta 1‐42 in the AD brain.
Assessment of beta‐amyloid deposition using gray matter delineation by early‐phase F‐18 florbetaben PET in patients with brain atrophy
Authors: Jeong Shin Young , Yoon Uicheul , Kang Kyunghun , Lee Sang‐Woo 
Published: December 2020

AbstractBackgroundIn patients with brain atrophy, it can be difficult to distinguish between pathologic amyloid accumulation of gray matter and nonspecific uptake of white matter in F‐18 florbetaben (FBB) PET. We evaluated gray matter edges delineation method derived from the perfusion phase of FBB PET (GM_eFBB) and investigated whether standard visual diagnosis (STD) can be improved the confidence level and concordance rate when we used STD combined GM_eFBB in patients with idiopathic normal pressure hydrocephalus (iNPH).MethodTwo‐phase FBB PET and brain MRI were performed in 42 iNPH patients with subjective cognitive impairment. Gray matter delineation using each individual’s brain MRI (GM_MR) was performed and a cut‐off value of SUVR was evaluated to find the GM_eFBB closest to GM_MR. Two nuclear medicine physicians blindly and independently evaluated all late‐phase FBB images, initially employing the STD method and later the STD combined GM_eFBB method. Binary classification (positive/negative) and subjective confidence (three‐point scale) of diagnosis were evaluated. A Pearson correlation coefficient (PCC) between GM_eFBB and GM_MR was determined, and the Wilcoxon signed‐rank test was used to evaluate differences in subjective confidence between two methods. Intraclass correlation coefficient (ICC) and concordance correlation coefficient (CCC) were determined for two methods.ResultThe GM_eFBB obtained by cut‐off value that determined as 50% of the peak SUVR was closest to the GM_MR. PCC was greater than 0.97 for all lobes (p<0.0001). The STD combined GM_eFBB method resulted in significantly greater subjective confidence in the readings (p = 0.027). The CCC for the STD method was 0.65, and for the STD combined GM_eFBB method was 0.73. The ICC was higher for the STD combined GM_eFBB method (0.73, 95%CI 0.56–0.85) than for the STD method (0.65, 95% CI 0.44–0.79). The binary classification was concordant in 83.3% of the scans using the STD method and in 88.1% of the scans using the STD combined GM_eFBB method.ConclusionThe STD combined GM_eFBB method can facilitate assessment of beta‐amyloid deposition in gray matter in patients with iNPH. The method may be applicable to patient with brain atrophy who may be difficult to judge of beta‐amyloid presence in gray matter.