bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of increasing levels of blood C‐reactive protein on the loci for inflammatory, SPI1 and CD33, for Alzheimer’s disease
Authors: Huang Jinghan , Tao Qiushan , Ang Ting Fang Alvin , Farrell John , Zhu Congcong , Wang Yixuan , Stein Thor D. , Lunetta Kathryn L. , Massaro Joseph , Mez Jesse B. , Au Rhoda , Farrer Lindsay A. , Qiu Wei Qiao , Zhang Xiaoling 
Published: June 2023

AbstractBackgroundPreviously, we found that elevated blood C‐reactive protein (CRP) increased the impact of the apolipoprotein ε4 allele (APOE ε4) on the risk of Alzheimer’s disease (AD).1 In this study, we hypothesized that interactions between CRP and other AD‐associated genes also increase AD risk.MethodSNPs in 10 AD risk loci, which also encode proteins related to inflammation, were used to test interaction with CRP on AD risk using additive model or dominant model with Cox proportional hazards regression and survival analysis.ResultThere were 279,176 UKBB white participants with average age (mean±SD) 60.1 ± 5.5 years including 53.9% females and 803 (0.3%) incident AD cases among 8.3 ± 0.9 years follow‐up on average. We found that for higher concentrations of serum CRP, the AD risk increased for SNP genotypes in 3 AD associated genes (SPI1, CD33 and CLU). Using Cox proportional hazards model in stratified genotype analysis, the hazard ratios (HR) for the association between higher CRP level (≥ 10 vs < 10 mg/L) and the risk of incident AD were 1.94 (95% CI: 1.33‐2.84, p<0.001) among SPI1 rs1057233‐AA genotype, 1.75 (95% CI: 1.20‐2.55, p = 0.004) for CD33 rs3865444‐CC genotype, and 1.76 (95% CI: 1.25‐2.48, p = 0.001) for CLU rs9331896‐CC+CT genotype, respectively. All models adjusted for age at baseline, sex, years of education, APOE ε4 and population principal components. In contrast, these associations were not observed in the other genotypes of these genes. Similar results for SPI1 and CD33 genotypes impacted by elevated CRP levels were observed for MCI to AD conversion and CSF AD biomarkers including t‐Tau and p‐Tau in the ADNI cohort (p<0.01).ConclusionElevated blood CRP released in peripheral inflammation may be an important mediator in the association of genetic variants in SPI1, CD33 and CLU in addition to APOE ε4 for AD risk. Monitoring of CRP levels may be useful for more precise intervention and prevention of AD for these genotype carriers.1. Tao Q, Ang TFA, DeCarli C, et al. Association of Chronic Low‐grade Inflammation With Risk of Alzheimer Disease in ApoE4 Carriers. JAMA Netw Open. Oct 5 2018;1(6):e183597. https://doi.org/10.1001/jamanetworkopen.2018.3597
Haploinsufficiency of progranulin causes cell type specific impairments in PINK1/Parkin mitophagy
Authors: Casey Jackie M. , Melandri Daniela , Arber Charles , Soutar Marc , Holler Christopher J. , Kukar Thomas , Isaacs Adrian M , Rohrer Jonathan D. , Pocock Jennifer M , Plun‐Favreau Helene , Wray Selina 
Published: June 2023

AbstractBackgroundGRN mutations that result in progranulin haploinsufficiency cause frontotemporal dementia (FTD). Mitophagy, the selective autophagy of damaged mitochondria, is impaired in several neurodegenerative diseases. A number of genes linked to FTD (e.g. OPTN, SQSTM, VCP and TBK1) are also known to play a role in mitophagy. Xenophagy, the selective autophagy of non‐host pathogens, relies on some of the same proteins as mitophagy (Parkin and TBK1) and is reduced in GRN knockout mice. Progranulin has also been found to play a role in mitophagy in mouse kidney cells. We therefore hypothesised that loss of progranulin could lead to defective mitophagy in neurons, astrocytes and microglia.MethodsWe investigated PINK1/Parkin mitophagy in astrocytic‐like H4 cells and neuron‐like Parkin overexpressing SHSY5Y cells (PoE‐5Ys) +/‐ siRNA against GRN. We also examined induced pluripotent stem cells (iPSCs) from four controls, three patients with FTD‐associated GRN mutations (R493X and C31fs) and a CRISPR series from the human iPSC Neurodegenerative Disease Initiative1,2,3 (iNDI) with an isogenic control, heterozygous and homozygous R493X mutation lines. The iPSCs were differentiated to cortical neurons, astrocytes and microglia. PINK1/Parkin mitophagy was induced using Antimycin A (respiratory complex III inhibitor) and oligomycin (ATP synthase inhibitor). PINK1 accumulation, levels of S65 phosphorylated ubiquitin (pUb), other mitophagy markers as well as proteins hypothesised to play a role in the mechanism were examined using western blotting and immunofluorescence (ICC).ResultsLower levels of pUb were detected in PoE‐5Ys treated with oligomycin/antimycin following GRN knockdown. There was a significant reduction in mitophagy in GRN siRNA treated H4 cells, detected by ICC and western blotting of mitophagy markers. Initial results from iPSC neurons found no significant difference in mitophagy between control and patient lines. Work is ongoing in a larger set of iPSC neurons, astrocytes and microglia. Preliminary results suggest that reducing progranulin affects mitophagy in astrocytes but has a limited effect on mitophagy in neurons.ConclusionsThe results suggest that progranulin has a cell specific role in mitophagy with progranulin regulating stability and/or activity of PINK1. Current work aims to understand the mechanisms of this process and to dissect cell‐type specific contributions of progranulin to mitophagy.
Heart rate variability is associated with global cognition and cognitive impairment: Results from the einstein aging study
Authors: Derby Carol A. , Qin Jiyue , Liu Grace , Koorathota Sharath , Wang Cuiling , Sloan Richard P. 
Published: June 2023

AbstractBackgroundThe role of autonomic function in cognitive impairment is unclear. Heart rate variability (HRV) provides a feasible, non‐invasive measure of cardiac autonomic control. We examined whether HRV is associated with global cognition and cognitive impairment using 7‐day ambulatory ECG assessments in the Einstein Aging Study.MethodAnalyses included 84 participants free of dementia (mean age 78.1 (± 5.2) years; 82% female; 39% non‐Hispanic White, 44% non‐Hispanic Black, mean education 14.7 (± 3.3 years)). Participants wore a small, single lead ECG device continuously over 7 days. Power spectral analyses were applied to determine HRV over 5‐minute epochs in the high (0.15‐0.40 Hz, hfHRV) and low (0.04‐0.15 Hz, lfHRV) frequency bands, and values were log transformed. Demographics, comorbidities, and cognition were assessed during clinic visits. Two tests per domain evaluated memory, executive function, language, visuo‐spatial and attention with impairment defined as performance ≥ 1.5 SD below the age, sex, education standardized norm on at least one test. Global cognition was assessed using the MoCA, and Mild Cognitive Impairment (MCI) was defined using Jak‐Bondi criteria. Associations of HRV with cognition were examined using logistic (MCI, domain specific impairment) and linear (MoCA) regression adjusting for age, sex, race/ethnicity and education, diabetes, and hypertension.ResultMean MoCA score was 24 (SD 3.5), 21 (25%) had MCI and impairment was identified in 25% (memory), 28.6% (executive function), 21.4% (attention), 17.9% (language) and 27.4% (visuospatial). Both hfHRV and lfHRV were inversely associated with MCI (OR per 1 SD increase in log HRV: 0.47, p = 0.02 for hfHRV and 0.42, p = 0.01 for lfHRV) and with memory impairment (OR per 1 SD increase in log HRV: 0.52, p = 0.03 for hfHRV and 0.43, p = 0.01 for lfHRV). Higher hfHRV and lfHRV were each associated with better MoCA score (β for 1 SD increase in log HRV: 0.65, p = 0.046 for hfHRV; 0.80, p = 0.02).ConclusionWhether HRV is associated with cognitive impairment remains unclear, particularly the role of hfHRV, indicative of parasympathetic control. Findings suggest that hfHRV is related to cognitive performance and impairment. Results for lfHRV also suggest joint effects of the sympathetic and parasympathetic systems.
Dyadic associations between cognitive functioning and depressive symptoms among older adult spouses over time in the Mexican Health and Aging Study
Authors: Monin Joan , McAvay Gail , Samper‐Ternent Rafael 
Published: June 2023

AbstractBackgroundMarriage has important influences on cognitive and mental health. Although studies are increasingly showing interpersonal effects of cognition and depression in couples in the United States, there is a need to replicate these findings in other countries. The present study examined the bidirectional associations between older adult spouses’ cognitive functioning and depressive symptoms over time in the Mexican Health and Aging Study (MHAS) using an actor partner interdependence model.MethodData was from the MHAS, a national study of adults aged 50 and older residing in Mexico. The current study focuses on three interviews conducted in 2012, 2015 and 2018. We identified, 1,800 individuals (age 65 and over), consisting of 905 couples who had direct interviews in 2012 and at least one follow‐up direct interview in 2015 or 2018. Of these, 1,774 (98.6%:) had a direct interview in 2015, and 1389 (77.2%) completed the 2018 assessment. Cognitive functioning was measured with the MHAS Cognitive Battery. Depressive symptoms were measured with a 9‐item, modified Center for Epidemiologic Studies Depression Scale for the Mexican population. Covariates included socio‐demographics, physical functioning, comorbidities, and smoking status.ResultStructural equation models testing longitudinal actor partner interdependence effects revealed a person’s own cognitive functioning and depressive symptoms predicted their own follow‐up cognitive functioning and depressive symptoms, respectively (see Table 1). Second, one’s own depressive symptoms was associated with more depressive symptoms in the spouse. Third, a person’s own cognitive functioning predicted their own depressive symptoms, and one’s own depressive symptoms predicted their own cognitive functioning across time. There were no significant interpersonal effects for cognitive functioning.ConclusionThese findings partially replicate previous research in older adult couples in the United States and highlight dyadic influences on mental health. However, in contrast to our prior research the current study found no association between spouses’ cognitive functioning. This difference highlights the importance of replicating studies of predictors of cognitive functioning across cultures. Future research is also needed to elucidate cultural mechanisms for interpersonal associations.
MRI free water as a biomarker for cognitive performance: Validation in the markvcid consortium
Authors: Maillard Pauline , Hillmer Laura J. , Lu Hanzhang , Arfanakis Konstantinos , Gold Brian T. , Bauer Christopher E. , Kramer Joel H. , Staffaroni Adam M. , Stables Lara , Wang Danny J.J. , Seshadri Sudha , Satizabal Claudia L. , Beiser Alexa S. , Habes Mohamad , Fornage Myriam , Mosley Thomas H. , Rosenberg Gary A. , Singh Baljeet , Singh Herpreet , Schwab Kristin , Corriveau Roderick A , Helmer Karl G. , Greenberg Steven M. , Decarli Charles , Arvind Caprihan 
Published: June 2023

AbstractBackgroundFree Water (FW), a Diffusion Tensor Imaging‐based biomarker kit has been demonstrated by the MarkVCID consortium to have excellent instrumental validity1. We sought to determine its clinical relevance by investigating association of FW with clinically meaningful aspects of vascular contributions to cognitive impairment and dementia (VCID) in the MarkVCID consortium cohort as well as 5 independent settings.MethodThis study included individuals from the MarkVCID UH3 phase cohort2 (N = 523) and 5 independent legacy cohorts: University of California Davis Alzheimer Disease Research Center3 (ADRC UCD, N = 173), MarkVCID UH2‐ phase data from University of California San Francisco4 (UH2 UCSF, N = 182) and RUSH Alzheimer Disease Center5 (N = 302), Framingham Heart Study6,7 (FHS, N = 2902) and Atherosclerosis Risk in Communities8 (ARIC, N = 1837). Table 1 summarizes participants’ characteristics. Our goal was to evaluate whether mean FW (mFW) computed within the white matter tissue as provided by the kit1 is cross‐sectionally associated with a composite measure of executive functions (EFC) derived from item‐response theory (IRT) generated score9,10, which incorporates scores from NACC Uniform Data Set Version 3 neuropsychological tests11. To test this hypothesis, a linear regression was used with EFC score as the dependent variable and mFW as the independent variable, adjusting for age, sex and education. In a second model, this model was additionally adjusted for presence of diabetes, smoking and hypertension to estimate the added contribution of mFW above vascular risk factors.ResultHigher mFW was associated with lower EFC scores (see Figure 1) in all the subject groups studied. In the MarkVCID cohort (ß = ‐3.54, p<0.0001), as well as in the five legacy cohorts (UH2 UCSF: ß = ‐3.54, p<0.0001, RUSH: ß = ‐1.905, p = 0.00597, ADRC: ß = ‐6.18, p<0.0001, FHS: ß = ‐4.06, p<0.0001, ARIC: ß = ‐1.24, p<0.0001). Adjusting for vascular risk factors did not significantly change these associations (p values< 0.01).ConclusionFindings from this study indicated that mean FW is a sensitive biomarker of cognitive performances, providing strong evidence of the clinical rational of FW as a sensitive biomarker of WM injury in association with cognition for future observational studies and clinical trials in the context of VCID.
Using telepresence robots as a tool for virtual research during the COVID‐19 pandemic
Authors: Lake Charlie , Hung Lillian , Wong Joey , Hussein Ali , Mann Jim , Gregorio Mario 
Published: June 2023

AbstractBackgroundLong‐term care (LTC) settings have been disproportionately affected by the COVID‐19 pandemic. It is necessary to investigate unmet needs and explore practical strategies for supporting LTC residents and staff. However, visitation restrictions and staff shortages have created barriers to conducting research in healthcare settings. Innovative methods and tools are needed for conducting research to support the research process. Telepresence robots enable virtual connections via videoconferencing and give a feeling of the person’s presence from a remote location. This study focuses on exploring the researchers’ experiences of using a telepresence robot as an interview tool.MethodWe interviewed a team of 10 researchers who used a telepresence robot to virtually conduct research during the COVID‐19 pandemic in British Columbia, Canada. The team includes academic researchers, graduate students and people living with dementia. Semi‐structured one‐to‐one interviews were conducted by Zoom virtual meetings. Thematic analysis was performed to identify themes.ResultAnalysis of the data produced five themes on benefits and challenges with respect to using a telepresence robot to conduct interviews with residents in LTC. Themes of benefits: (1) Use as a Research Enabler, (2) More accessible and engaged research process, and (3) Increased Environmental Inclusion and Engagement. Themes of challenges: (4) Lack of Infrastructure and Resources, and (5) Training and Technical Obstacles. Based on the results, we offer “ROBOT” – an acronym created for actionable recommendations that inspire and support others to use telepresence robots for research. These recommendations include Realign to adapt, Organize with champions, Blend strategies, Offer timely technical assistance, and Tailor training to individual needs.ConclusionThis study offers unique and practical insights into using telepresence robots as a safe and innovative tool for conducting research remotely. Our results demonstrate that people living with dementia can be engaged meaningfully in research during the pandemic. Future research should apply more creativity and flexibility in adopting technology to expand possibilities for involving people with dementia in research.
Segmental bioimpedance variables in association with mild cognitive impairment due to Alzheimer disease
Authors: Doan Dieu Ni Thi , Ku Boncho Uk , Jun Min‐Ho , Lee Kun Ho , Kim Gahey Uk , Kim Jaeuk U 
Published: June 2023

AbstractBackgroundRecognizing and monitoring changes in body composition can reveal early signs of body vital status, thereby applying appropriate therapies or lifestyle changes which may help to reverse the risk of MCI. This study aims to examine the association between body composition and bioimpedance variables with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD).MethodWe obtained four water‐related and six impedance‐related variables for upper and lower extremities as well as several whole body composition variables such as fat (%), body cell mass (%), water volume (TBW_FFM), and metabolic rate (BMR) from segmental multi‐frequency bioelectrical impedance analysis (MF‐BIA) for 938 elderly participants, including 672 cognitively normal individuals (CN) and 266 MCI subjects. Participants’ characteristics, anthropometric information, and the selected BIA variables were described and statistically compared between CN and MCI subjects. The correlations between the selected BIA and neuropsychological tests such as the Korean version of Mini‐Mental State Examination (K‐MMSE) and Seoul Neuropsychological Screening Battery – second edition (SNSB‐II) before and after controlling for age and sex were also examined. Univariate and multivariate logistic regression analyses with the estimated odds ratios were conducted to investigate the associations between these BIA variables and MCI prevalence and for different gender groups.ResultOur MCI samples were shown to be slightly older, more depressive, and have significantly poorer cognitive abilities compared to CN subjects. The partial correlations upon controlling for age and sex between the selected BIA variables and neuropsychological tests were not magnificent. However, after accounting for age, sex, GDS score, and the significant comorbidities, resistance and reactance in lower extremities survived to be associated with MCI with ORs (95%CI) of 0.81 (0.68‐0.96) and 0.79 (0.67‐0.94), respectively. After stratify by gender, these variables remained significant in only female group.ConclusionThe reductions in segmental body resistance and reactance increase the incidence of MCI, these patterns are more pronounced in the lower extremities and especially in female subjects. These two variables can be considered as early bioimpedance changes in MCI due to AD.
Functionality according to frailty and cognitive status: Differences between scoring procedures for the Lawton‐Brody IADL scale
Authors: Facal David , Soage Sandra , Nieto‐Vieites Ana , Campos‐Magdaleno Maria , Pérez‐Blanco Lucía , Felpete Alba , Navarro‐Pardo Esparanza , Pereiro Arturo X 
Published: June 2023

AbstractBackgroundFrailty is the state of physiological vulnerability that hindered age‐related decline that precedes disability. However, some functional decline in IADLs is expected, particularly when co‐occurring with Mild Cognitive Impairment (MCI). Our aim was to analyze differences in IADLs between prefrailty and frailty participants with or without MCI. Three scoring procedures for the Lawton & Brody Scale administered to informants were used to analyze IADL differences: 1) Raw scoring: percentage calculation of the raw scores considering all the items; 2) Gender‐corrected scoring: percentage calculation of the IADLs that continue to be carried out but excluding in men the 3 elements traditionally associated with the female gender role (i.e., housekeeping, food preparation, and laundry); 3) Past‐performance corrected scoring: percentage calculation of the IADL activities that the person could perform in the past but now performs with greater difficulty or no longer performs.MethodThe sample comprised 285 Spanish community‐dwelling older adults, without diagnosis of dementia nor disability. MoCA test was used to objectively measure cognitive functioning. Participants were classified using the frailty phenotype: No‐frailty (i.e., met no criteria), pre‐frailty (i.e., met one‐two criteria), and frailty (i.e., met three or more criteria). Presence of MCI were considered to further classify the participants considering cognitive status.ResultsDifferences between No‐frailty (N = 80), (Pre)frailty without MCI (N = 123), and (Pre)frailty with MCI (N = 62) groups were tested using non‐parametric tests (see Figure 1). Group differences (Kruskal‐Wallis tests) were found using Raw (H = 11.30, p<0.01) and Past‐performance corrected scores (H = 10.57, p<0.01). For both, lower IADL scores were found in the (Pre)frailty with MCI compared with the No‐frailty group (Raw scoring: Z = ‐3,37, p<0.01; Past‐performance corrected scoring: Z = ‐1,97, p<0.05) and compared with (Pre)frailty without MCI group (Raw scoring: Z = ‐2,86, p<0.01; Past‐performance corrected scoring: Z = ‐2,65, p<0.01).ConclusionDifferences in IADLs were found between groups with and without MCI using raw and proportional scores considering past performance skills. Between‐group differences in participants without cognitive impairment did not reach significance regardless of their frailty status. Results using the gender‐corrected score suggest a lower sensitivity for detecting functional impairment in men when this procedure is used.
The Korean brain aging study for the early diagnosis and prediction of Alzheimer’s disease (KBASE): Cognitive data harmonization
Authors: Yi Dahyun , Byun Min Soo , Risacher Shannon L. , Craft Hannah , Crane Paul K , Trittschuh Emily H. , Mez Jesse B. , Choi Seo‐Eun , Hohman Timothy J. , Cuccaro Michael L. , Lee Michael L. , Scollard Phoebe , Gibbons Laura E , Mukherjee Shubhabrata , Nho Kwangsik , Saykin Andrew J. , Lee Dong Young 
Published: June 2023

AbstractBackgroundKBASE is a prospective cohort study launched at Seoul National University (SNU), South Korea, in 2014 using similar design and methods as the North American Alzheimer’s Disease Neuroimaging Initiative (ADNI). The KBASE cohort consists of well‐characterized participants (420 cognitively normal, 140 mild cognitive impairment, and 90 AD dementia) (Figure 1). It includes systematic longitudinal collection of comprehensive clinical, cognitive and lifestyle data, multimodal neuroimaging, and bio‐specimens for the first six years (“KBASE1”) at a single center. “KBASE2: Korean Brain Aging Study, Longitudinal Endophenotypes and Systems Biology” (NIH Grant U01AG072177) is the second phase of KBASE, launched in collaboration with Indiana University and other institutions. KBASE2 began in 2021, and has similar assessment protocols to the KBASE1. The NIA AD Sequencing Project (ADSP) will perform GWAS and whole genome sequencing (WGS).MethodNeuropsychological data will be harmonized by the study team and members of the ADSP Phenotype Harmonization Consortium. Comprehensive cognitive data were collected using a battery of standardized tests (Table 1). Harmonization and co‐calibration will enable comparative analyses with cognitive data from similar studies with largely non‐Hispanic white (NHW) cohorts, including the ADNI and AIBL, and ultimately the range of other aging and dementia cohorts including those with underrepresented multi‐ethnic populations. WGS and GWAS data will be harmonized and shared by the ADSP.ResultCognitive data harmonization processes are underway and have begun to address the challenges of language and cultural differences. Initial steps include mapping tests and items into an English template. Harmonization and co‐calibration efforts will include identifying appropriate anchor items and accounting for differences in test items that were made to be more culturally and linguistically appropriate. Additional challenges include the wide range of educational attainment as well as gender effects on educational opportunities. A bilingual neuropsychologist who is trained and licensed in the U.S. and a bilingual psychometrics expert are deeply involved in harmonization processes.ConclusionHarmonized KBASE cognitive data will be shared with the ADSP and other investigators for use in quantitative phenotype analyses, as well as other pooled, integrative, and comparative studies of other multiethnic, multilingual, U.S., and international cohorts.