bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in oculo‐motor activity during a cognitive challenge can distinguish clinical stages of early Alzheimer’s disease
Authors: Sorinas Jennifer , Fernandez Gerardo , Shulz Matias , Vallejo Vanessa , Snædal Jón , Hannesdottir Kristin , Curcic Jelena 
Published: June 2023

AbstractBackgroundThe eye adapts to the demands of our behavior [1], its motor activity has proven to be a feasible method for measuring cognition in both health and disease [2]. This study assessed the sensitivity of oculo‐motor features in a benign cognitive challenge model with the purpose of identifying objective efficacy readouts for clinical drug trials in early Alzheimer’s disease (AD).MethodFifty participants, aged 60 to 80 years, performed a reading task in two sessions conducted the same day, morning and evening (i.e. the “cognitive challenge”), with an average inter‐session period of 9.28h, during which participants were not allowed to take naps or consume stimulating beverages. Participants were distributed across four cohorts corresponding to progressive stages of early AD [3]: 1) amyloid negative, cognitively healthy (control group), 2) amyloid positive pre‐symptomatic AD, 3) Mild Cognitive Impairment (MCI) due to AD (pre‐dementia group) and 4) mild AD (mild‐dementia group). ViewMind technology was used to track the oculo‐motor activity [4].ResultNone of the four cohorts reported increased levels of sleepiness during the challenge. However, cohorts showed significantly different oculo‐motor responses during the cognitive challenge (Table 1). The control group showed evidence of learning effects on the reading during the challenge reflected in no change in pupil size, longer saccades, less fixations and shorter gaze. Within the pre‐symptomatic group, however, a negative impact of the challenge was observed in a decrease in pupil size and increase in fixations. However, some learning effects were nevertheless seen in this cohort, in shorter gaze and longer saccades. In pre‐dementia group the learning effects were lost and participants demonstrated difficulty performing the task reflected in decreased pupil size and longer gaze. Finally, the mild‐AD participants showed an increase in fixations, longer gaze and no change in pupil size indicating a pattern of poor reading performance during the challenge.ConclusionOur preliminary results demonstrate that oculo‐motor activity may reflect changes in cognitive resources induced by a benign challenge in progressive clinical stages of early AD. These promising results support continued investigation into the potential of eye‐tracking during reading as a sensitive and objective measure .
Human Alzheimer’s postmortem raphe brain heterogeneity: Single cell RNAseq 10X genomics approach
Authors: Reddy Arubala P. , Peng Joyce , Mechref Yahia , Reddy Hemachandra P 
Published: June 2023

AbstractBackgroundThe complexity of subcortical brain remains unexplored due to complex neuronal structure and heterogeneity of neuronal populations in the brain. Raphe brain regulates multiple physiological events like stress, memory, feeding, sleep, movement, balance, and many others. ere we present the single cell RNAsec (scRNAseq) analysis of raphe tissue from the postmortem brains of Alzheimer’s disease Braak Stages VI and control subjects.MethodPostmortem raphe brains acquired from NIH‐NeuroBioBank. Intact cells were collected using Cell Raft AIR System. Single cell suspension of neurons and synthesized cDNA and normalized cDNA using library preparation. The samples were processed in NextGen v3‐1 using 10X Genomics Chromium system. The library was sequenced ± 200 million PE150 reads /sample on Illumina Novaseq. The sequences were mapped against GRCh38 using Cell ranger v6.1.ResultThe data will be analyzed using 10X genomics cell ranger and Loup Browser tools. Further functional genomics tool DAVID
) v6.8 and (
IPA
) will be used to analyze heterogeneity of raphe brain and various presynaptic neuronal modulation in 1. AD and control, 2. AD and control males and 3. AD and control females. The most astringent analysis of data showed 5% mitochondrial genes, . We will also analyze the therapeutic targets and biological pathways. Heterogeneity of raphe and genes triggered in AD pathology will also be investigated.ConclusionThe raphe connectivity to Alzheimer’s disease and other dementias was a hot‐topic in 1980s research and somehow lost interest in the last 2 decades. The concept of serotonin neuromodulation evolves in recent years due to new concept of serotonin connecting intracellular and intracellular neuromodulation, use of serotonin drug targets in behavior alterations in dementia and early depression and aggression might be a causal factor to neurodegenerative onset much before classic pathologies of the disease appear. Our study will reveal the heterogenous neuronal population in complex raphe region of the brain and how the microenvironment changes neurotransmission in the forebrain. We will present extensive analysis on neuronal population of raphe and its role in AD and healthy subjects. The results will be a AD and ADRD models to pinpoint the changes in 5HTsynthesis and neuromodulation to forebrain and cerebellum.
Evaluation of cognition with the eyelink: Saccadic eye movements in healthy subjects
Authors: Tüfekci Işıl Yağmur , Koçoğlu Koray , Boz Hatice Eraslan , Akkoyun Müge , Ekin Merve , Akdal Gülden 
Published: June 2023

AbstractBackgroundThe aim of this study is to determine the normative data of eye movements models for healthy individuals between the ages of 18‐77.Method76 healthy subjects were included in 3 age groups as 18‐44, 45‐59, 60+. Neuropsychological assessment with five cognitive domains, was applied. EyeLink 1000 Plus was used to record and pro‐saccade and anti‐saccade eye movement paradigms. Amplitude, latency, anticipatory saccades, express saccades, correct saccade response, corrected saccade and uncorrected saccade responses were analyzed.ResultIn antisaccade results, correct saccade response, latency, amplitude, anticipatory saccade, express saccade, corrected saccade response, uncorrected saccade were significantly different between the groups (p<0.05). Significant difference was also found in prosaccade latency (p<0.001). In the 18‐44 age group, executive functions were highly negatively correlated with antisaccade latency (r = ‐0.744, p = 0.000), and language was meanly negatively correlated with latency (r = ‐0.514, p = ‐0.010). In the 45‐59 age group, a medium level of negative correlation was observed between executive functions and latency (r = ‐0.501, p = 0.025). Language and express saccade (r = ‐0.515, p = 0.020) were meanly negatively correlated in the 45‐59 year age group. In the 60+ age group, a medium level of negative correlation was found between attention and latency (r = ‐0.414, p = 0.021). In this age group, executive functions and uncorrected saccade (r = ‐0.396, p = 0.027) were weakly negatively correlated.ConclusionDecline in cognitive functions that occur with aging might affect eye movements. The relationship between antisaccades and cognitive functions in our preliminary study may attract attention to antisaccades in evaluation of cognition.
Peer Mentorship with Lewy Body Disease: A protocol for co‐developing and piloting a program for post‐diagnostic support
Authors: Booi Laura , Swaffer Kate , Medsger Helen Bundy , Murphy Damian , Leroi Iracema 
Published: June 2023

AbstractBackgroundSocial isolation, loneliness and stigma are some of the most detrimental psychosocial effects of living with dementia, including Lewy Body Disease (LBD). Peer‐to‐peer support between newly diagnosed people living with LBD and more experienced people living with LBD has the potential to reap extremely positive effects for both parties, and their care partners (CP). This presentation will discuss a protocol and the developments of a project to co‐develop a peer mentorship program (PMP) with people living with LBD and their CP.MethodsCo‐design workshops with people living with LBD and their CPs will take place to co‐develop the curriculum for the PMP. The PMP will be delivered via video conference technology. Alongside this, collaborations with volunteer, community and social enterprises will be incorporated into the project design, to maximize shared learnings from other community led peer mentorship programs. Thus far these programs include peer mentorship programs for incarcerated individuals and those living with HIV.ResultsThe PMP is in the design stage and further components of this project are underway to incorporate the lived expertise of those with LBD and their CPs, as well as clinicians to the design. Recruitment of piloting participants for the PMP is expected in the second half of 2022.ConclusionThe PMP will offer guidance for shared experiential learning so that the person living with LBD and their CP will be better educated and equipped to support themselves and each other through the care pathway. The solution offered via the PMP contributes to improving access to information in an affordable way and to becoming integrated into the post‐diagnoses care pathway as an option for social prescribing.
The relationship between inflammatory biomarker trajectory and cognitive change following elective non‐cardiac surgery in older adults
Authors: Scott David A , Silbert Brendan S , Evered Lisbeth A , O'Bryant Sid E. , Hall James 
Published: June 2023

AbstractBackgroundSurgery in the older patient is associated with short‐ and long‐term cognitive changes, including delirium, post‐operative cognitive dysfunction (POCD) and neurocognitive decline (NCD). The inflammatory response to surgery may be a contributing factor. We investigated the association between inflammatory biomarkers and cognitive change up to 3 months following surgery.MethodWe recruited 70 older adults undergoing elective non‐cardiac surgery. Baseline and 3 month neurocognitive and functional assessments were performed, and delirium was assessed for 5 days following surgery. A control group of age‐similar subjects underwent assessment at similar time points. Blood was collected in 55 patients at baseline and post‐surgery at 30 min, 6h, 24h and 48h for inflammatory biomarker analysis (Tumor Necrosis Factor (TNF)‐α, Interleukin (IL)‐6, IL‐10, IL‐18). POCD was attributed if there was ≥ 1.96 SD decline in two or more neuropsychological tests compared with time‐matched controls. NCD major and mild was attributed according to DSM‐V criteria.ResultPatients underwent a range of non‐cardiac surgical procedures and were aged 69.5 (SD 6.7)y and 48.6% were female. Mean baseline MMSE was 27.1 (7.5). Delirium was identified post‐operatively in 4% of subjects. At 3 months, 18 (32.7%) subjects had some form of cognitive decline: POCD 7%, Mild NCD 16% or Major NCD 15%. IL‐6 was significantly elevated following surgery and remained so to 48h. IL‐10 was elevated at 6h but declined to baseline by 48h. Both IL‐18 and TNF‐α were transiently lower than baseline at 30 minutes, but then returned to close to baseline levels. There was no association between inflammatory biomarker levels and delirium or cognitive change at 3 months.ConclusionWe have confirmed the presence of new cognitive decline in a significant number of older patients up to 3 months following non‐cardiac surgery. We identified changes in inflammatory biomarkers, especially IL‐6 which was elevated for at least 48h, but no association with cognitive change. Ongoing research will address more specific biomarkers of neuronal injury.
Plasma Neurofilament Light (NfL) associated with retest learning effects on ambulatory cognitive assessments of processing speed: Results from the Einstein Aging Study (EAS)
Authors: Qin Jiyue , Wang Cuiling , Katz Mindy J. , Zetterberg Henrik , Blennow Kaj , Engeland Christopher G. , Hakun Jonathan G. , Pavlovic Jelena , Derby Carol A. , Sliwinski Martin J. , Lipton Richard B. 
Published: June 2023

AbstractBackgroundMeasurement burst designs, using ambulatory cognitive assessments facilitate the dissociation of retest effects from optimal (“asymptotic”) performance. Dissociating these features via cognitive process modeling may reveal indices of subtle cognitive impairment that signal risk for neurocognitive decline. We investigated cross‐sectional associations between plasma NfL (a biomarker of neurodegeneration), retest improvements, and optimal performance on the Symbol Match task, which assesses processing speed by response time (RT), in a racially/ethnically diverse community‐based EAS Study cohort.MethodAnalyses included 283 EAS participants free of dementia (Mean age = 77.4 years, SD = 4.8, Range = 70‐91; 67% Female; 46% Non‐Hispanic White, 40% Non‐Hispanic Black). Among them, 82 met the Jak/Bondi criteria of mild cognitive impairment (MCI). Participants completed a smartphone cognitive battery, resulting in up to 96 assessment sessions (six times per day for 16 days). Plasma NfL concentration was measured using a Single molecule array assay. A mixed‐effect negative exponential model was used to examine the associations between plasma NfL and indices of subtle cognitive impairment adjusting for covariates including age, gender, education, and race/ethnicity. Retest improvement was measured by the exponential decrease in RT across sessions and optimal performance was measured by asymptotic RT (fastest performance).ResultOn average, the RT of the Symbol Match task was 3.4 seconds (SD = 0.9). Mean plasma NfL level was 23.9 pg/mL (SD = 17.5). Higher plasma NfL levels were associated with a reduced retest improvement rate per session (estimate = ‐0.011, 95% confidence interval (‐0.013, ‐0.008) corresponding to one SD increase in plasma NfL, p<0.001). No significant association between plasma NfL and optimal cognitive performance was found. Stratified analyses showed NfL’s association with retest improvement was larger in non‐Hispanic Whites than in non‐Hispanic Blacks (‐0.009 vs ‐0.002), although formal testing of the interaction between NfL and race was not significant. Results remained very similar excluding participants with MCI.ConclusionHigher plasma NfL was associated with a reduced retest improvement rate on a smartphone processing speed task, highlighting its potential value for identifying subtle cognitive impairment. Longitudinal data from larger samples, a broader array of biomarkers and of ambulatory cognitive tests, are required to fully explore these issues.
Using amyloid PET as a biomarker to detect progression of early Alzheimer disease
Authors: Ali Muhammad , Mafimoghaddam Samira , Sung Yun Ju , Wang Fengxian , Fernandez Maria Victoria , Archer Derek B , Hohman Timothy J. , Satizabal Claudia L. , Yang Qiong , Beiser Alexa S. , Wang Ruiqi , Gordon Brian A. , Benzinger Tammie L.S. , Xiong Chengjie , Morris John C , Bateman Randall J. , Karch Celeste M. , McDade Eric , Goate Alison , Seshadri Sudha , Mayeux Richard , Sperling Reisa A. , Buckley Rachel F. , Properzi Michael J , Johnson Keith A. ,   Dominantly Inherited Alzheimer Network (DIAN),   Alzheimer’s Disease Neuroimaging Initiative (ADNI), Cruchaga Carlos 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD), the most common form of dementia, is a complex polygenic disease with genetic, cellular, pathologic, and clinical heterogeneity. Recently, significant attempts have been made for identifying AD biomarkers for reliably tracking disease progression in its early asymptomatic stages. To this end, amyloid PET imaging has provided useful information tracking accumulation of parenchymal amyloid beta (Aβ) deposits in the brain. Previous investigations have conducted genetic association studies of CSF Aβ42, both continuously as well as using a threshold for amyloid positivity, and identified novel genes and loci potentially contributing to the preclinical stage in AD. In a recent case‐control based study using amyloid PET as a quantitative trait, Raghavan et al., identified a novel locus for amyloidosis within RBFOX1 gene in 4,314 participants, however, further investigations are needed to replicate and expand on these findings.MethodIn order to investigate the underlying genetic basis for brain amyloidosis in AD, we systematically analyzed the largest collection of amyloid imaging data (N = 6,320), across multiple ethnicities from multicenter cohorts (ADRC, A4, DIAN, ADNI, ADNIDOD, UPitt, and HABS) as a quantitative trait to identify the functional variants and genes driving the association of AD. Furthermore, we have conducted diagnosis‐, gender‐, and APOE‐stratified analyses to investigate the effect of these variables on the brain amyloidosis.ResultPreliminary results found a strong APOE signal in chr19 (min P = 1e‐185) and a genome‐wide significant hit (P = 2e‐08) in the chromosome 7 (potentially, associated to TMEM106B gene) warranting further investigation (Fig. 1). Moreover, some suggestive signals were detected in chr10 (P = 1e‐07) and chr12 (P = 5e‐07). Consistent with previous finding, we found RBFOX1 to be associated with increased amyloid burden (β = 0.07), however, the signal was only nominally significant (P = 0.03). Additional analyses including multi‐ancestry meta‐analysis using FHS, AIBL, and EISAI cohorts and post‐GWAS analyses are ongoing.ConclusionThe identification of pre‐clinical AD‐specific molecular signatures and pathways will enable the characterization of appropriate therapeutic targets for the prevention and/or treatment of AD. Results generated from our investigation will further serve to generate prediction models for amyloid positivity and Mendelian Randomization (MR) analyses.
Divergent patterns of cognitive deficits and structural brain alterations between older adults in mixed‐sex and same‐sex relationships
Authors: Manca Riccardo , Correro Anthony N , Gauthreaux Kathryn , Flatt Jason D. 
Published: June 2023

AbstractBackgroundSexual minority (SM) or lesbian, gay, bisexual, and queer older adults experience health disparities that may cause cognitive decline. Several studies have reported higher rates of subjective cognitive complaints in SM older adults, but evidence of increased cognitive decline has been inconsistent. One study found that older adults with Alzheimer’s disease (AD) in same‐sex relationships (SSR), compared to mixed‐sex relationships (MSR), had more severe neuropsychiatric symptoms associated with atrophy in fronto‐temporal regions. We sought to compare behavioral and structural brain parameters of SSR and MSR older adults and evaluate their impact on cognitive performance.MethodNational Alzheimer’s Coordinating Center data were selected according to the following inclusion criteria: 55+ years of age, presence of a co‐participant, and availability of brain volume and mean thickness data. Clinical Dementia Rating® (CDR®) scores were used to assign participants to cognitively impaired (CI; CDR®≥0.5) or cognitively unimpaired (CU; CDR®<0.5) groups. We identified 1076 MSR (583 CU) and 38 SSR (25 CU) participants with Mini‐Mental State Exam (MMSE) and Neuropsychiatric Inventory Questionnaire (NPI‐Q) data within six months of a study visit. Comprehensive neuropsychological test results were available for a sub‐sample of participants (940 MSR and 33 SSR). General linear models were used to investigate the effects of diagnosis, relationship, and NPI‐Q scores on structural and cognitive outcomes.ResultThe MSR group presented with more impairments. Diagnosis‐by‐relationship interaction effects were observed for brain parameters: 1) CI‐MSR had more atrophy in occipital, medio‐temporal, and frontal areas; 2) CU‐MSR had reduced volume/thickness in orbito‐frontal, insular, and anterior cingulate cortices. The MSR groups had greater executive, memory, and language deficits. Neuropsychiatric symptom severity was negatively associated with volume and thickness of bilateral temporo‐cingulate areas and total MMSE scores in the MSR groups only.ConclusionMSR older adults had greater cognitive and behavioral impairments compared to SSR older adults. CI‐MSR had greater grey matter atrophy in areas particularly affected by AD (i.e., medio‐temporal regions). Our results suggest that SM older adults may present with less neurocognitive impairment on comprehensive assessment, despite previous evidence of subjective complaints. Further investigations are needed to clarify factors influencing cognitive decline in older SM.
In the context of a deprived neighborhood, does self‐identified race cause dementia?
Authors: Zhang Xiao , Chang Chung‐Chou H , Ganguli Mary 
Published: June 2023

AbstractBackgroundAlthough accumulating evidence has shown that individual socioeconomic status affects dementia incidence, it remains unknown whether a higher degree of neighborhood disadvantage which is independent of individual socioeconomic status contributes to the excess risk of dementia among African Americans (AA).MethodIn the Monongahela‐Youghiogheny Healthy Aging Team and 15104 Senior Project, two population‐based prospective cohort studies in an economically disadvantaged Rust Belt community, 2733 participants aged 65+ years were assessed for their health history, lifestyle, and cognitive functioning. Mild cognitive impairment (MCI) or dementia was defined as Clinical Dementia Rating score ≥0.5. Each participant was assigned an Area Deprivation Index (ADI) value according to the census block group where one resided, indicating the level of neighborhood disadvantage. In cross‐sectional data, racial differences in the odds of MCI or dementia were assessed using weighted logistic regressions. Inverse probability weighting was used to balance AA and European Americans (EA) with respect to 1) ADI, 2) other confounders (age, sex, APOE*4 genotype, cardiometabolic diseases, individual socioeconomic status, health‐related behaviors, use of regular health services, functional health literacy, and air pollution [PM2.5]), and 3) ADI and other confounders.ResultThe frequency of MCI and dementia were 648 (24%) and 25 (0.9%), respectively. AA had significantly higher proportion of MCI or dementia (35% vs. 24%, p = 0.001) and higher mean ADI (96 vs. 79, p<0.0001) than EA. Being AA was associated with higher odds of MCI or dementia compared to being EA (odds ratio [OR] = 1.71, 95% confidence interval [CI] = 1.26 ‐ 2.33, unadjusted model). After balancing racial groups with respect to ADI only, the difference between AA and EA no longer reached the level of significance. When balancing all other confounders only, the OR was 1.66 (95% CI = 1.04 ‐ 2.67) and the confounders explained 5.2% of the observed disparity. After balancing both ADI and other confounders, the difference again became non‐significant (OR = 1.61, 95% CI = 0.93 ‐ 2.80) and resulted in 11.1% of the MCI or dementia disparity being explained.ConclusionA higher degree of neighborhood disadvantage may contribute to the excess risk of MCI or dementia found among AA.