bluuebunny/crossref_metadata_2025_split huggingface dataset:
Network changes and compensation mechanisms of wake‐promoting neurons across AD continuum
Authors: Grinberg Lea T. 
Published: December 2023

AbstractBackgroundSleep is a complex process regulated by various neural mechanisms, including those promoting wakefulness, those promoting sleep, and those regulating the circadian clock. Recent research has revealed that wake‐promoting neurons, specifically those found in the noradrenergic locus ceruleus (LC), the orexinergic (ORX) neurons in the lateral hypothalamic area (LHA), and the histaminergic neurons in the hypothalamic tuberomammillary nucleus (TMN), are particularly vulnerable to the AD‐tau pathology found in the early stages of Alzheimer’s disease (AD). These studies have uncovered how these neurons accumulate AD‐tau, the extent to which they die in AD, and specific correlations with polysomnographic readings. Notably, a complex pattern of neuronal dysregulation within and among these wake‐promoting neurons has been observed, suggesting the existence of robust compensatory mechanisms in an attempt to overcome dysfunction. Thus, understanding the vulnerability of these nuclei to AD requires network‐based studies. These studies are crucial for informing disease‐specific treatment for sleep disturbance and identifying factors underlying the vulnerability of these neurons.MethodsResults from several ongoing experiments in the Grinberg Lab, including methods such as quantitative pathology, molecular profiling and clinicopathological correlationResultsFor example, the hypocretin (orexin) receptor 1 (HCRTR1) shows upregulation in orexin neurons from early AD stages, while no changes are observed in the LC or TMN. Additionally, while the LC shows an early pattern of upregulation of genes associated with neuroinflammation, early dysregulation in the ORX is related to synapse‐related genes. Furthermore, circadian genes such as CRY1 and CRY2 show upregulation in the ORX but downregulation in the TMN during AD progression.ConclusionThis talk will focus on current knowledge, including unpublished data, based on studies in humans, on the vulnerability of wake‐promoting neurons in AD, with a particular emphasis on similarities and contrasts in the patterns of dysregulation among these nuclei during AD progression, in conjunction with changes in the suprachiasmatic nucleus, the circadian clock, and regional expression of circadian genes.
Neural responses to peripheral infection in Alzheimer’s disease model mice
Authors: Fitz Nicholas F , Lu Yi , Saibro‐Girardi Carolina , Lefterov Iliya , Koldamova Radosveta 
Published: December 2023

AbstractBackgroundClinical and animal studies have suggested that peripheral inflammation affects the central nervous system (CNS) and may be a major factor in the pathophysiology of neurodegenerative diseases like AD. Furthermore, a variety of signaling factors originating in the periphery, such as inflammatory mediators, have been associated with the regulation of brain barrier functions. Here, we hypothesized that the presence of peripheral inflammation dysregulates brain barriers’ integrity and induces neuroinflammation with consequences on amyloid pathology.MethodIn this study, we employed an AD mouse model nasally infected with Staphylococcus aureus to assess the impact of chronic or acute peripheral inflammation on brain transcriptome and amyloid pathology. We utilized both single cell and Spatial Transcriptomics to better determine transcriptional response to peripheral inflammation.ResultThe chronic exposure increased the diffuse and compact amyloid plaques and blood cytokine levels. Following a short‐term exposure, single‐cell and spatial transcriptomics uncovered cell type‐ and spatial‐specific transcriptional changes indicating a dysregulation of the brain barriers, including the blood‐brain and the blood‐cerebrospinal fluid barriers. Brain macrophages exhibited increased Apoe expression and macrophage‐specific genes were upregulated at ventricular areas of infected mice. In addition, we report an increase of disease associated microglia genes around the Ab plaques, together with disbalances in neuronal expression in response to peripheral inflammation.ConclusionWe observed that low‐grade peripheral infection triggers transcriptional responses linked to brain barriers and brain infiltrated/resident macrophages indicate a fundamental importance of them in the mechanisms linking peripheral inflammation and AD pathogenesis. Finally, we showed that bacterial infection caused molecular changes restricted to specific cell types and/or brain spatial microenvironments, which highlights the relevance of studying brain molecular responses with high resolution in order to have new insights on AD etiology.
Integrated AD trial data from multiple sources and stakeholders
Authors: Maruyama Tetsuyuki 
Published: December 2023

AbstractThere is every reason to cheer recent advances is treatments and diagnostics for Alzheimer’s and other dementias, but enormous need remains, and progress is still too slow. An important way to accelerate new discoveries is through sharing of the vast amounts of relevant data, especially the data collect from human research participants. There is consensus among many researchers, clinicians, patients, and governments that data sharing accelerates science by increasing the utility of data. This allows for new analysis, meta‐analysis, and replication, inspiring new ideas and approaches.There are, however, challenges to data sharing. These include accessible and affordable infrastructure, tools, and resources to support data curation, sharing, and analysis. There also needs to be more incentives – to move away from siloed efforts and towards global collaboration.The Alzheimer’s Disease Data Initiative (ADDI) is dedicated to data sharing by advancing solutions to these challenges. The AD Workbench provides researchers with the infrastructure to share data and to discover data within a secure, cloud‐based environment.For data contributors, supports and resources are available to assist with harmonization and curation of data. There are also options available regarding permissioned access, whether the data is simply accessed on the AD Workbench or through federated sharing. For researchers, the AD Workbench offers compute resources, data analysis tools, and other resources to help advance their work.To both support work on the AD Workbench and to foster community and collaboration, AD Connect offers resource libraries, discussion forums, and other helpful information. We know that meaningful ADRD advances will not be made by any one person or organization. Bringing researchers together, to engage, interact, and inspire each other will help us move closer to fundamentally transforming ADRD research.
Abnormal functional activation during response inhibition in mild cognitive impairment: an fMRI study
Authors: Pommy Jessica , Umfleet Laura Glass , Cohen Alexander D , Ristow Kelly , Mason Lilly , Obarski Shawn , Franczak Malgorzata , Wang Yang 
Published: December 2023

AbstractBackgroundDeclines in response inhibition are observed both typical and atypical aging, i.e., mild cognitive impairment (MCI). Increased functional activation in frontoparietal regions during response inhibition has been interpreted to represent the emergence of a compensatory mechanism in older adulthood. While electrophysiology studies suggest the decline in response inhibition in MCI reflects a similar but amplified process as seen in normal aging this has not been examined thoroughly using functional MRI (fMRI).Methods31 cognitively normal older adults (M age = 73.6, 9 male) and 22 adult patients with MCI (M age = 67.2, 14 male) performed a Go/NoGo task during an fMRI scan. Group differences in accuracy and reaction time were examined for Go and NoGo trials. Individual BOLD signal change during task fMRI was examined, then voxel‐wise group comparison was conducted for MCI vs. HC groups, using age, gender, education, and gray matter density as covariates. Permutation‐estimated cluster size at alpha <.05 was defined to correct for errors of multiple comparisons.ResultsBehaviorally, the MCI group made significantly more errors during NoGo and Go trials (p<.001, p = .032, respectively), however, average reaction time did not differ significantly between groups. During NoGo trials, greater activation in the anterior default mode network (DMN), right dorsolateral prefrontal cortex (DLPFC), and motor areas was observed for MCI vs. HC, while during go trials, there was greater activation in DMN and right insula (corrected p<0.05). However, when Go vs. NoGo trials were examined, MCI showed more activation in right insula and DLPFC, but less activation in the motor area at trend level (p<0.05, uncorrected). While, there were no significant task performance differences between MCI subtypes (amnestic vs. non‐amnestic), amnestic MCI (aMCI) showed more activation in posterior DMN and dorsal attention area during NoGo trials (corrected p<0.05).ConclusionMCI demonstrated significantly greater activation during both Go and NoGo trials and made significantly more errors in performance during both trial types as well. While the MCI subtypes did not exhibit differences in performance on the task, the aMCI exhibited significantly greater activation in multiple regions. Our findings suggested inefficient DMN suppression during task performance in the MCI cohort, especially in the aMCI subgroup.
Financial hardship in families of older adults with physical disability, dementia or both: a population based study of the dementia research group 10/66
Authors: Márquez Inés Hernández , Acosta‐Castillo Gilberto Isaac , Ibarrola Mariana Longoria , Sosa‐Ortiz Ana Luisa 
Published: December 2023

AbstractBackgroundThe proportion of older people have consequences for labor and financial market. Older adults (OA) can consume economic resources that they cannot afford, total health care spending is three times greater in households with at least one OA with a disability, 70% of the costs of caring for someone with dementia are borne by families and reported emotional and financial hardships are twice as high for caregivers of this OA. This study focuses on the impact of physical and cognitive disabilities on the economic difficulties of the families.MethodThis was an observational, cross‐sectional study. It involved 2396 people aged 65 years and older, identified within the dementia research group protocols (DRG)10/66. Measures included the WHODAS 2.0 and the INDEP economic hardship study assessments. We performed descriptive statistics of the sociodemographic distribution and explored the association of physical disability, dementia, or both, with the presence of sociodemographic and economic variables with different types of supports for coping the “financial hardship” using bivariate tests and logistic regression models, odds ratios were estimated to assess the associations of interest.ResultThe distribution of disability with or without cognitive impairment was greater in women and cognitive impairment was greater in men (p = 0.010). When analyzing the distribution of the types of economic support, resorting to social assistance programs showed an association with the presence of cognitive impairment with disability odds ratio (OR) of 10.4 (95% confidence interval = 95%CI 1.3‐81.1) and without disability OR 8.0 (95%CI 1.1‐59.7) in the adjusted estimators (RR). Recourse to the work setting support was associated with the presence of disability in simple RR, OR 2.2(95%CI 1.2‐4.2) and adjusted OR 2.5(95%CI 1.3‐4.8). Support from friends or relatives was associated with the presence of disability and cognitive impairment also in simple RR OR 2.0 (95%CI 1.4‐3.0) and adjusted OR 2.1(95%CI 1.4‐3.3).ConclusionIn older Mexican adults, cognitive impairment increases the use of social assistance programs, physical disability increases the use of savings or property, and the presence of cognitive impairment with physical disability increases the use of social assistance programs, support in the work setting and from friends or family.
APOE4 Genotype Relates with Body Mass and Percent Fat Mass in Cognitively Normal Older Adults
Authors: Smith Aaron N. , Keller Jessica E , Taylor Matthew K , Burns Jeffrey M. , Sullivan Debra K 
Published: December 2023

AbstractBackgroundLower body mass is related to the progression of Alzheimer’s disease (AD). Carriers of the APOE e4 (APOE4) allele have an increased risk of developing AD, and APOE4 status has been shown to be associated with decreased body mass and fat mass in AD. However, this relationship in cognitively normal older adults is unclear. We investigated whether body mass index (BMI) and body composition are related with APOE4 status in cognitively normal older adults.MethodBaseline data from 211 cognitively normal older adults in an ongoing nutrition intervention RCT (Nutrition Intervention for Cognitive Enhancement; NICE study) were analyzed. Whole blood was attained, and genetic analyses were used to determine APOE genotype. Participants with ≥ 1 APOE4 allele were classified as APOE4 carriers. BMI was calculated from weight and height. Fat mass percentage was measured using dual energy x‐ray absorptiometry. We compared means between APOE4 carriers and non‐carriers for BMI and fat mass percentage using covariate‐adjusted ordinary least squares (OLS) regression models (i.e., ANCOVA), adjusting for age and sex. Statistical analyses were performed using R (v. 4.2.2; R Foundation, Vienna, Austria). Statistical significance was set at p < 0.05.ResultParticipants were 75% female with a mean age of 71.4 ± 4.9 years. 34% of participants were APOE4 carriers. Mean BMI and percent fat mass were 28.4 ± 4.6 kg/m2 and 40% ± 4.6, respectively. ApoE4 carriers had significantly lower BMI (27.5 kg/m2 ± 3.9 vs. 28.9 kg/m2 ± 4.8, p = 0.02) and lower body fat percentage (38% ± 8.0 vs. 42% ± 6.7, p < 0.01) compared to non‐carriers, respectively.ConclusionIn this study, cognitively normal older adult APOE4 carriers had lower BMI and lower body fat percentage compared to non‐carriers. These findings suggest that APOE4 status may influence body weight and body composition, which may represent a way APOE4 increases the risk of symptomatic AD. Future studies are needed to explore the mechanisms underpinning the relationship of APOE4 with decreased body mass and differential body compositions and to determine if these results are consistent in different life stages.
Exercise training mitigates the deleterious effects of experimental bed rest on intraindividual variability of executive functioning in older adults: A randomised controlled trial
Authors: Balbim Guilherme Moraes , Falck Ryan S , Barha Cindy K , Tai Daria , Best John R. , Hajj‐Boutros Guy , Madden Kenneth , Liu‐Ambrose Teresa 
Published: December 2023

AbstractBackgroundIn older adults, bed rest can occur because of chronic conditions, injury, surgery, or hospitalization. Extreme levels of physical inactivity due to bed rest initiate a downward spiral in several body systems. Exercise is a countermeasure to many of these changes; nonetheless, little is known about the effect of exercise on older adults’ cognition during bed rest. We thus examined the effects of exercise on the intraindividual variability (IIV) of cognitive performance in older adults exposed to 14 days of experimental 6° head‐down bed rest (HDBR) and whether sex moderates its effects. We chose IIV as our outcome measure because it is more sensitive than traditional summary scores of cognitive performance, albeit no studies have explored exercise effects on older adults’ IIV submitted to bed rest.MethodA non‐blinded, parallel‐group, randomised controlled trial. Twenty‐three healthy older adults aged 55‐65 were randomised to: 1) 14 days of HDBR (CON); or 2) 14 days of HDBR with daily aerobic and strength exercise (EX). Data were collected at baseline, HDBR completion, and end of seven‐day‐recovery. The National Institutes of Health Toolbox Cognitive Battery assessed executive function (Flanker Incongruent and Congruent and Dimensional Change Card Sort) and processing speed (Pattern Comparison). IIV was indexed by intraindividual coefficient of variation (ICV) and residual intraindividual standard deviation (R‐ISD), with R‐ISD as our primary measure of interest. Linear mixed models assessed group differences and the moderator role of sex.ResultAt HDBR completion, EX had significantly lower (better) Flanker incongruent ICV (Estimated mean difference = ‐0.10, 95%CI ‐0.19;‐0.003, p = 0.022) and R‐ISD (Estimated mean difference = ‐3.63, 95%CI ‐6.10;‐1.17, p = 0.005) vs. CON. Sex moderated the effect of exercise; females in EX had significantly lower Flanker incongruent ICV vs. CON (Estimated mean difference = ‐0.23; 95%CI ‐0.34;‐0.12, p<0.001). At the end of the seven‐day recovery, EX had significantly lower Flanker incongruent R‐ISD vs. CON (Estimated mean difference = ‐3.11, 95%CI ‐5.70;‐0.052, p = 0.019). Summary scores and processing speed IIV changes were not statistically significant (ps>0.05).ConclusionExercise during HDBR preserved executive functioning, especially in females. Our findings support the delivery of exercises to older adults during bed rest to preserve their cognitive function.
Emotional Enhancement of Memory in Alzheimer’s Disease: A Systematic Review
Authors: Kapoor Arunima , Levine Linda , Mather Mara , Nation Daniel A. 
Published: December 2023

AbstractBackgroundProgressive decline in episodic memory is a hallmark of Alzheimer’s disease (AD). Emotional arousal is known to enhance memory. The amygdala, locus coeruleus, hippocampus, and other regions, are key brain structures involved in the facilitation of memory through emotions. Amygdala‐mediated enhanced encoding of emotionally arousing stimuli or events may improve memory in AD patients, however whether this effect is present in patients with AD remains unclear.MethodA systematic search of the literature was conducted in accordance with PRISMA guidelines to identify relevant literature on emotional enhancement of memory (EEM) in AD. We utilized MEDLINE and PsycInfo. Search terms related to emotional memory and Alzheimer’s were searched as keywords and mapped to medical subject headings.Result1545 studies were screened; 40 were included. Participant age ranged from 64 to 84 years. Sample sizes ranged from 20 to 126. Only 11 of the 40 (27.5%) included brain MRI and evaluation of amygdala volume. 34 studies examined long‐term memory. Results showed that 12 out of 34 studies (35.3%) showed clear EEM for long‐term memory among participant with AD. A further 10 studies (29.4%) found that EEM was influenced by stimuli type, valence of emotion, level of encoding, or intensity of emotion. Yet 12 studies (35.3%) found no effect of EEM in AD. Of the 6 studies that specifically explored flashbulb memories in AD, 3 found no EEM and 3 observed that the effect was content‐dependent, such that personal details were remembered more often than factual details of events.ConclusionStudies which included brain imaging showed that amygdala volume is the strongest predictor of EEM in AD, regardless of level of cognitive impairment. The conflicting literature on EEM in AD reveals the importance of evaluating volumes or networks of brain regions known to be involved in emotional memory processing. AD patients included in these studies likely had varying degrees of atrophy in the amygdala, locus coeruleus, hippocampus and frontal regions involved in modulating emotional memories. However, without confirmation from brain imaging, the integrity of these brain structures cannot be established. Future studies are needed to confirm whether atrophy of important brain regions diminishes EEM in AD.
Stereotype threat in telephone‐administered neuropsychological assessment in older Veterans with and without cognitive impairment
Authors: DeCaro Renée , Kasha Sabrina , Marin Anna , Turk Katherine W , Budson Andrew E 
Published: December 2023

AbstractBackgroundNeuropsychological evaluation is ubiquitous in Alzheimer’s disease clinical care and research—from diagnosing cognitive deficits to evaluating treatment and outcomes. However, performance during evaluation can depend on factors other than one’s cognition, including stereotype threat. Stereotype threat occurs when people feel at risk of conforming to stereotypes about their social group, in this case, memory declines associated with aging. While stereotype threat in neuropsychological evaluation in healthy older adults has been established, we tested, for the first time, this construct in older adults with cognitive impairment.MethodTwenty older adults (range 63 – 89; mean age = 77.2, SD = 6.8) recruited from the Veteran’s Affairs Boston Healthcare system were administered a telephone Repeatable Battery of Neuropsychological Assessment (RBANS). Following baseline assessment, one‐week later participants received a stereotype threat condition prior to neuropsychological evaluation. Participants also received a reduced threat condition which de‐emphasized memory diagnosis (during a separate week, counterbalanced with the threat condition). In the fourth week and final session, supplemental measures were administered, including a telephone‐MoCA, demographics, and surveys measuring mood, dementia worry, beliefs about aging, and subjective memory complaints. Planned analyses include a mixed‐effects analysis of variance, with group (healthy; cognitively impaired) and condition (stereotype‐threat; threat‐reduced).ResultsOlder adults with cognitive impairment demonstrated lower performance across all domains of the RBANS, including list learning, story recall, fluency, digit span, delayed recall, and recognition, ηp
2 = .87‐.99. Older adults with impairment scored numerically lower but not statistically lower in list learning under stereotype threat (M = 17.4; SD = 6.6) compared to the reduced threat condition (M = 19.9; SD = 7.2). Confirmation of the analyses, including examination of covariates, will follow final subject recruitment (N = 28).ConclusionWe found that stereotype threat did not significantly impact performance of healthy older adults and older adults with cognitive impairment. We note that small, numerical differences emerged for list learning. Differences of just one point in neuropsychological evaluation can be impactful, especially with respect to norms and cutoff scores. As such, the results carry implications for neuropsychological evaluation in clinic practice and research broadly.