bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood and life‐course socioeconomic position and cognitive function in adult population of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: Filigrana Paola , Moon Jee‐Young , Gallo Linda C , Fernandez‐Rhodes Lindsay E , Perreira Krista M , Daviglus Martha L , Thyagarajan Bharat , Garcia‐Bedoya Olga L , Cai Jianwen , Lipton Richard B. , Kaplan Robert C. , González Hector M , Isasi Carmen R 
Published: December 2023

AbstractBackgroundThe Hispanic/Latino population experiences extensive socioeconomic adversity across the lifespan and is at greater risk of cognitive decline. Yet little is known about the role of life‐course socioeconomic position (SEP) and cognitive function in this population. We assessed the association between childhood SEP and cognitive function in Hispanic/Latino adults, whether this association is mediated by midlife SEP, and whether socioeconomic mobility is associated with cognitive function.MethodWe used baseline data (2008‐2011) from 9556 adults aged 45‐74 years of the Hispanic Community Health Study/Study of Latino (HCHS/SOL), a multi‐center cohort study conducted in four major U.S cities. We determined childhood SEP using parental educational attainment. Midlife SEP was determined through an index combining participants’ education and household income. We classified participants into socioeconomic mobility categories from childhood to adulthood (e.g., persisting low, upward mobility). Cognitive function was ascertained using neurocognitive tests, including the Six‐Item Screener; Brief‐Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association (or Word Frequency), and the Digit Symbol Substitution Test. Using confirmatory factor analysis and these tests we created a global cognition score. We also standardized z‐score of these neurocognitive measures. Survey linear regression models were performed adjusting for age, sex, Hispanic background, U.S born, smoking, depression, and cardiovascular factors. We also conducted mediation analysis to decompose the direct effect of childhood SEP on cognition and the indirect effect through midlife SEP.ResultChildhood SEP showed a graded association with cognitive function in adulthood with a dose‐response relationship across levels of parental education (β and [95% Confidence Interval (CI)]): Elementary/middle school vs. No schooling 0.34 [0.25‐0.43]; High school (HS) vs. No schooling: 0.53 [0.42‐0.64]; and >HS vs. No schooling: 0.68 [0.57‐0.79]). High midlife SEP was also associated with greater cognitive function relative to low midlife SEP. 37% (95% CI 32%‐44%) of the association between childhood SEP and cognition was mediated through midlife SEP. Holding a high SEP over the life‐course was associated with greater cognitive performance (β: 0.90, 95% CI: 0.79‐1.00) as compared with a persisting low SEP.ConclusionThis study provides evidence that childhood and life‐course SEP influence cognitive performance in adulthood
Association between dietary diversity and cognitive impairment in community‐dwelling older adults
Authors: Kiuchi Yuto , Tsutsumimoto Kota , Doi Takehiko , Kurita Satoshi , Nishimoto Kazuhei , Makizako Hyuma , Shimada Hiroyuki 
Published: December 2023

AbstractBackgroundMild cognitive impairment (MCI) is an intermediate state between normal cognitive aging and dementia, and it is a target population for interventions in dementia prevention. Dietary diversity is associated with the risk of dementia. However, the association between dietary diversity and MCI, remains unclear. The present study aimed to examine whether dietary diversity is associated with cognitive impairment, including MCI, in community‐dwelling older Japanese adults.MethodThis cross‐sectional study was conducted using data from the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes. MCI and global cognitive impairment (GCI) were assessed using the Mini‐Mental State Examination and National Center for Geriatrics and Gerontology‐Functional Assessment Tool (NCGG‐FAT), which are multicomponent neurocognitive tests that include memory, attention, executive function, and processing speed. Participants with one or more cognitive decline were defined as having MCI. Dietary diversity was assessed using the diet variety score (DVS). DVS assessed the one‐week consumption frequency of ten food groups and either 0 or 1 point was allocated to each category based on the following responses: (1) “eat almost every day” (1 point), (2) “not eaten almost daily” (0 points). Older adults with a DVS of 3 or more points were defined as having high dietary diversity.ResultData included 8,987 older adults (mean age: 73.9 ± 5.5 years; men: 44.3%). The overall prevalence of MCI and GCI followed; 17.1% (n = 1,538) and 8.4% (n = 753), respectively. The proportion of patients with a high dietary diversity was 69.9% (n = 6,286). Multinomial logistic regression analysis revealed high dietary diversity was associated with MCI (OR 0.83, 95% CI 0.73‐0.94) and GCI (OR 0.77, 95% CI 0.65‐0.92) after adjusting for covariates.ConclusionThis study showed that high dietary diversity was associated with a lower proportion of MCI and GCI among older adults. Ingesting a wide variety of foods contributes to the enhancement of cognitive function among older adults.
Association between physical, cognitive and social activity and incident sarcopenia among older adults with cognitive decline: A 4‐year longitudinal study
Authors: Nishimoto Kazuhei , Tsutsumimoto Kota , Doi Takehiko , Kurita Satoshi , Kiuchi Yuto , Shimada Hiroyuki 
Published: December 2023

AbstractBackgroundCognitive decline and sarcopenia are associated with each other among older adults. However, it is unclear that the prospective association of older adults with cognitive decline with incident sarcopenia. Therefore, the purpose of this study was to examine longitudinal association between physical, cognitive and social activities and incident sarcopenia among older adults with cognitive decline.MethodAmong older adults with cognitive decline (MMSE score range: 18 to 27) aged 65 years or older who participated in the National Center for Geriatrics and Gerontology, 1440 participants (mean age: 71.6 ± 4.9, man: 53.3%) were included after excluding those who meet the exclusion criteria. The participants were asked about the status of implementation concerning physical (PA), cognitive (CA) and social activity (SA), respectively. The participants were categorized to high/low‐PA, high/low‐CA and high/low‐SA group. Sarcopenia was defined by the European Working Group on Sarcopenia in Older People2, and participants were classified as robust or sarcopenia.ResultDuring 4 years, 361 (25.1%) participants developed sarcopenia. After adjusting for covariates (age, sex, education level, medication, current smoking and alcohol), the logistic regression analysis model showed that low‐PA group (OR 1.77, 95%CI 1.23‐2.56) and low‐SA group (OR 1.40, 95%CI 1.05‐1.85) had a significantly higher risk of incident sarcopenia compared with each high group. Low‐CA group had no significant association with incident sarcopenia.ConclusionIn older adults with cognitive decline, low physical and social activity in daily life influences the future incidence of sarcopenia. On the other hand, cognitive activity might not be effective in preventing incident sarcopenia, especially among older adults with cognitive decline.
Evaluation of BTXBrain‐Tau, an AI‐powered automated quantification software for Flortaucipir PET images
Authors: Kang Seung Kwan , Kim Daewoon , Shin Seong A , Kim Yu Kyeong , Choi Hongyoon , Lee Jae Sung 
Published: December 2023

AbstractBackgroundPositron emission tomography (PET) has been used to visualize the distribution of brain biomarkers associated with AD. Flortaucipir (18F‐AV‐1451) is a tau‐specific PET tracer that has been used to detect tau pathology in AD. However, the accurate quantification of Flortaucipir PET images requires an accurate spatial normalization of the image data. We evaluated BTXBrain‐Tau, an AI‐based automated quantification software that does not require an MRI, on the Flortaucipir data. In comparison, performance on automatic quantification was demonstrated against conventional MRI‐based spatial normalization results.MethodIn the previous study, BTXBrain‐Tau was pretrained with approximately 1000 amyloid PET images. To fine‐tune the network, 180 Flortaucipir images were obtained from Seoul National University Hospital. Trained network was evaluated using 146 Flortaucipir images from the ADNI. Each image had been quantified using FreeSurfer at UC Berkeley, and these quantifications served as the “ground truth.” Spatial normalization was also performed using SPM12 with 3D T1 MRI to demonstrate the proposed method’s superiority. The results were compared using four Braak stage‐based composite regions of interest. Statistical analysis of the results was conducted using linear regression and intraclass correlation coefficients.ResultThe linear regression slopes for BTXBrain‐Tau were 0.95, 0.97, 1.03, and 0.95 for four regions of interest (ROIs), outperforming the results of SPM12 (0.81, 0.80, 0.81, 0.79). The R‐squared values also showed superior performance for BTXBrain‐Tau (0.94, 0.98, 0.95 and 0.98) compared to SPM12 (0.88, 0.97, 0.91 and 0.96). ICCs between the ground truth and SPM12 normalization results were 0.93, 0.96, 0.94 and 0.96 for SPM12, however, these values were improved in BTXBrain‐Tau processing (0.97, 0.99, 0.97 and 0.99).ConclusionThe results demonstrated that BTXBrain‐Tau was able to generate spatially normalized images without the use of 3D MRI input. Statistical analysis revealed a high degree of correspondence between the FreeSurfer‐based quantification and the proposed method. Additionally, the study demonstrated the generalizability of the network by assessing its performance on different types of test data, (training on Asia, testing on Caucasian). These results suggest that BTXBrain‐Tau is a promising tool for the accurate quantification of Flortaucipir PET images, which could lead to early detection and precise staging of Alzheimer’s disease.
AlzPED: Raising the Standards for Preclinical Efficacy Testing of Candidate Therapeutics in Alzheimer’s Disease
Authors: Chakroborty Shreaya , Viswanathan Jaya , Gallofre Maria Fe Lanfranco , Martin Zane , Petanceska Suzana S , Refolo Lorenzo M 
Published: December 2023

AbstractBackgroundPositive findings of therapeutics and interventions from studies conducted in Alzheimer’s disease (AD) animal models are often not translated to effective treatments. Assessments of these studies highlight the lack of methodological rigor and inadequate reporting practices as contributive to the preclinical to clinical translation gap in AD therapy development. AlzPED/Alzheimer’s Disease Preclinical Efficacy Database, developed by the NIA, is a searchable and publicly available knowledgebase that prioritizes and promotes the use of rigorous methodology in the planning of animal studies through its Rigor Report Card. The Rigor Report Card, through its checklist of experimental design elements, creates awareness of reporting recommendations and standards early in the research process and provides a practical and easy approach to planning a therapeutic study in animals.MethodUsing key word‐driven literature searches published studies are acquired and curated by two experts for bibliographic details, funding source, study goals and principal findings, data on relevant translational criteria like therapy type, therapeutic agent, therapeutic target, animal models, and AD‐related outcome measures, prior to publication in the database. Rigor in study design and methodology is evaluated with the Rigor Report Card.ResultAlzPED hosts curated summaries from nearly 1300 published preclinical therapeutic studies in AD animal models, and data related to 251 therapeutic targets, 1123 therapeutic agents, 210 animal models, more than 2000 AD‐related outcome measures, and thousands of principal findings. Evaluation of Rigor Report Cards from each study demonstrates significant under‐reporting of critical elements of methodology such as power/sample size calculation, blinding, randomization, balancing for sex, animal genetic background, and inclusion/exclusion criteria, these being reported by fewer than 35% of the nearly 1300 curated studies. These serious deficiencies in reporting critical elements of methodology diminish the scientific rigor, reproducibility, and translational value of the preclinical studies.ConclusionRigorous experimental design and transparent reporting are clearly essential if animal studies are to inform future research, science policies, and successful clinical trials. Adopting a standardized set of best practices like those proposed by AlzPED can improve the predictive power of preclinical studies in AD animal models and promote the effective translation of preclinical drug testing data to the clinic.
Herpes Simplex Virus Infection and in vivo Alzheimer’s Disease Pathologies
Authors: Chang Yoon Young , Byun Min Soo , Yi Dahyun , Ahn Hyejin , Kim Min Jung , Jung Joon Hyung , Kong Nayeong , Sohn Bo Kyung , Lee Jun‐Young , Kim Yu Kyeong , Lee Yun‐Sang , Kang Koung Mi , Sohn Chul‐Ho , Lee Dong Young 
Published: December 2023

AbstractBackgroundInterest in the role of Herpes Simplex Virus (HSV) infection in the pathogenesis of Alzheimer’s disease (AD) has increased in recent years. However, previous studies yielded inconsistent findings and no studies have yet investigated the relationship between HSV infection and in vivo AD pathologies such as beta‐amyloid (Aβ) and tau deposition in brain. We examined whether the level of serum anti‐HSV immunoglobulin G (IgG) antibodies (HSV‐IgG), an index of past infection of HSV, is associated with in vivo Aβ and tau deposition in nondemented individuals. We also investigated the modulating effect of HSV‐IgG titer on the relationship between Aβ and tau deposition.MethodA total of 426 nondemented older individuals (55‐90 years old) were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) cohort. All participants underwent comprehensive clinical assessment, [11C]‐Pittsburgh Compound B positron emission tomography (PET), and blood sampling for measurement of serum HSV antibodies. A subset of participants (N = 129) underwent [18F] AV‐1451 PET. Individuals whose HSV‐IgG titer was lower than 25 percentile of the whole group was classified as the HSVlow group, while those with HSV‐IgG titer higher than 25 percentile were classified as the HSVhigh group.ResultThere was no significant difference in age, sex, clinical diagnosis (cognitive normal vs. mild cognitive impairment), and apolipoprotein E e4 positivity (APOE4) between the HSVlow (N = 106) and HSVhigh (N = 320) groups. In terms of AD biomarkers, neither global Aβ nor tau deposition was different between the HSVhigh and HSVlow groups, even after controlling the effect of age, sex, and APOE4. However, there was a significant HSV group x Aβ deposition interaction effect on tau deposition (p = 0.037), suggesting the level of HSV‐IgG modulates the relationship between Aβ and tau deposition. Subsequent subgroup analyses showed a significant positive association between Aβ and tau deposition only in the HSVhigh group (p < 0.001), but not in the HSVlow group.ConclusionOur finding suggests that past HSV infection may aggravate the influence of Aβ on tau deposition. In regard of AD prevention, the result also supports that more attention needed to be paid to controlling HSV infection.
Non‐physical Leisure Activity patterns and Cognitive Function in 4,121 Hong Kong older adults with no major neurocognitive disorders
Authors: Lam Linda Chiu Wa C.W. , Lee Allen TC , Chan Wai Chi , Wong Samuel YS , Ma Suk Ling , Lin Cuichan CW , Fung Ada WT , Yip Benjamin HK , Cheng Calvin Pak Wing , Lai Frank HY , Cheng Sheung Tak 
Published: December 2023

AbstractBackgroundEmerging evidence supports the role of lifestyle in maintenance of cognitive function. Physical exercise, diet and sleep are found to play important roles in cognitive health at later life. In this recently completed epidemiological study in Hong Kong, we explored if non‐physical leisure activity participation also contributes to cognitive function in older adults.MethodThe Hong Kong Mental Morbidity Survey for Older People (HKMMSOP) is a commissioned study supported by the Health and Medical Research Fund of the Hong Kong SAR. From 2019 till 2022, we have successfully assessed 4,369 community dwelling older adults (60 years or over). 4,121 participants satisfied clinical Dementia Rating (CDR) of either 0 or 0.5. Assessments included Montreal cognitive assessment (MoCA), cumulative illness rating for physical disease burden, Clinical Interview Schedule – Revised (CIS‐R) for depressive and anxiety symptoms, types of physical exercise (aerobic, mind body, resistance muscle training, stretch), types of non‐physical activities (cognitive, social, spiritual, volunteering, passive solitary) activities were counted as positive if regular practice frequency were once weekly or more.ResultOf the 4,121 participants, 3118 were cognitively healthy (CDR = 0), 1003 had mild neurocognitive disorder with CDR 0.5. The mean age and education (years) was 68.9(SD 6.9)(range 60‐98) and 9(SD 4.5) respectively. 44% were men. The mean MoCA score was 24.4 (SD 4.0). Regression analysis with MoCA score as the dependent variable showed that cognitive, volunteer and spiritual activities were significant factors (after controlling for gender, age, education, physical health burden, psychological symptoms (CIS‐R), and total number of physical exercise)(R2 = 295). In the CDR 0 group, cognitive and spiritual activities are significant factors (R2 = 0.184). In the CDR 0.5 group, cognitive and volunteer activities are significant (R2 = 0.196).ConclusionThe HKMMSOP provides empirical evidence on the association between cognitive function and apparently pro‐mental wellbeing leisure activities. The observation that the introspective spiritual activities being significant factor in healthy, and external volunteering activities being significant in mild cognitively impaired group should invite further replication and exploration on the associated mechanisms.
Memory interference in APPswe/PS1dE9 mice: Role of astrocytic β‐adrenoreceptors
Authors: Choudhury Rupsa Roy , Kushwaha Srishti , Karunakaran Smitha 
Published: December 2023

AbstractBackgroundPrevious studies have reported that long‐term β‐adrenoceptor (β‐AR) agonist, isoproterenol hydrochloride (IPE), treatment brings about beneficial effects in an induced model of Alzheimer’s disease (AD) by neutralizing microglial inflammatory morphology against soluble amyloid β oligomers (PMID: 30093491). However, we do not have a clear understanding of how such treatment impacts astrocyte morphology, and whether that afford beneficial effects. Introducing a proactive memory interference step to the classical novel object recognition (NOR) paradigm impairs long‐term memory formation in 2‐month‐old familial model of AD ‐ APPswe/PS1dE9 (APP/PS1) mice. Long‐term IPE treatment rescued long‐term memory. In this study we attempt to understand the impact of long‐term IPE treatment on astrocyte morphology, and how they bring about the reversal in cognitive deficits.Method(1) Mice were taken through a proactive interference step in which they were exposed to objects of varied shape, size and colour before taking them through NOR paradigm. (2) Mice were treated with β‐AR agonist IPE at P26 (0.05g/litre) in drinking water for 21 days till P47. (3) They were sacrificed at 2‐months of age by transcardial perfusion and 100µm coronal sections of hippocampus were stained with astrocytic markers GFAP and S100β by immunohistochemistry. The number and morphology of astrocytes were analysed using ImageJ, SMorph (PMID: 34137444) and Imaris software.ResultOur observations suggest that NOR memory is intact in 2‐month‐old APP/PS1. However, introducing an object‐based short‐term interference before NOR leads to recognition memory deficits in APP/PS1 but not in wild‐type mice. Treatment with IPE restored long‐term memory of APP/PS1 mice to normal levels, thereby protecting them from the effects of interference during the NOR task. Our preliminary findings indicate that IPE impacts the morphology of astrocytes and thus contribute to the reversal of recognition deficits in APP/PS1 at 2 months of age.Conclusionβ‐AR activation can bring about morphological changes in astrocytes that in turn can modulate memory representations.
Association of estimated white matter hyperintensity age with cognition in hypertensive elderly
Authors: Kim Jun Sung , Bae Jong Bin , Han Ji Won , Oh Dae Jong , Suh Seung Wan , Kim Jae Hyoung , Kim Ki Woong 
Published: December 2023

AbstractBackgroundHypertension is associated with white matter hyperintensity (WMH) and cognitive impairment. Further, WMH is associated with cognitive impairment including executive, attention and visuospatial functions. The aim of this study was to investigate the effects of controlled hypertension (cHT) and previously developed concept, ‘WMH age’ on cognitive function and the mediating role of WMH in the effect of cHT on cognitive impairment.MethodWe enrolled 855 Koreans without dementia aged 60 years or older, 326 of whom completed 2‐year follow‐up assessment. We measured their blood pressure thrice in a sitting position using an automated blood pressure monitoring device. We estimated ‘WMH age’ of every participant using previously developed WMH probability map of healthy older Koreans. We analyzed the mediating effect of WMH age in the association of cHT and cognitive function using the PROCESS Macro model.ResultOld WMH age was associated with a faster decline in the Mini‐Mental Status Examination (MMSE; p = .003), Consortium to Establish a Registry for Alzheimer’s Disease total score (CERAD‐TS; p = .003), and Frontal Assessment Battery (FAB; p = .007). Old WMH age showed an approximately‐six times higher risk of incident mild cognitive impairment (OR = 6.47, 95% CI = 1.37 – 9.50, p = .024) compared to young or normal WMH age over the 2‐year follow‐up period in the cHT group. WMH age mediated the effects of cHT on the MMSE, CERAD‐TS, and FAB scores at baseline and two‐year follow‐up period.ConclusionWMH mediates the adverse effect of hypertension on cognitive function. Elders with cHT who have older WMH age may be at a higher risk of cognitive decline.