bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Moderating Effect of Apolipoprotein E Genotype on the Relationship Between Total Cholesterol and Memory
Authors: Emrani Sheina , Kunicki Zachary J. , Villa Priscilla , George Kristen M 
Published: December 2023

AbstractBackgroundHyperlipidemia is associated with increased risk of Alzheimer’s disease and related dementias (ADRD). Apolipoprotein E (APOE) plays a key role in lipid transport and is regulated by APOE. APOEe4 carriage may increase ADRD risk by altering lipid metabolism in the brain. We sought to understand the relationship between total cholesterol and memory when moderated by APOEe4 carriage hypothesizing that the negative effects of elevated total cholesterol on memory would be strongest among APOEe4 carriers.MethodParticipant data were extracted from the Alzheimer’s Disease Neuroimaging Initiative (ADNI‐1) database. Total cholesterol and APOEe4 carriage were measured from blood samples collected at baseline. Rey Auditory Verbal Learning Test (RAVLT) measured delayed recall and recognition normed using the Mayo’s Older Americans Normative Studies (MOANS). We used multiple regression to examine the relationship between total cholesterol, APOEe4, and cognition, controlling for age, gender, and education. Total cholesterol by APOEe4 carriage interactions were tested using a p<0.1.ResultAmong 1776 participants, 55% (n = 978) were male and average age was 74 (SD = 7). APOEe4 non‐carriers had a mean total cholesterol of 192 (SD = 40) mg/dL compared to 197 (SD = 40) among APOEe4 heterozygotes and 200 (SD = 42) among APOEe4 homozygotes (Table 1). Higher total cholesterol was associated with better delayed recall performance (β = 0.01, p = .01). There was a significant interaction (β = ‐0.01, p = .07) such that higher total cholesterol among APOEe4 non‐carriers was associated with better delayed recall (β = 0.01) whereas higher total cholesterol among APOEe4 homozygotes was associated with worse delayed recall (β = ‐0.004) (Figure 1). When modeling recognition, there was no main effect of total cholesterol; however, there was a significant interaction between total cholesterol and APOEe4 (β = ‐0.01, p = .09). This interaction showed a positive relationship between total cholesterol and recognition in APOEe4 non‐carriers (β = 0.003) but a negative relationship in APOEe4 homozygotes (β = ‐0.01) (Figure 1).ConclusionCompared to non‐carriers, APOEe4 carriers, particularly homozygotes, may be especially sensitive to the deleterious effects of elevated total cholesterol on memory performance. This study adds to the extant literature demonstrating an effect of APOEe4 allele on the relationship between cholesterol and cognition.
Depression prevalence and sex differences in mild cognitive impairment and mild dementia due to autopsy‐confirmed Alzheimer’s disease or vascular neuropathology
Authors: Tall Sakina Ouedraogo , Yeruva Rajashekar , Chen Maria , Masurkar Arjun V. 
Published: December 2023

AbstractBackgroundDepression is increasingly recognized as a modulator of dementia risk and course, and is associated with multiple etiologies of cognitive decline. While it has been studied in clinically diagnosed cohorts, which may suffer from diagnostic error, there is less information in neuropathologically‐defined subjects. We sought to define the depression prevalence and sex difference at mild cognitive impairment (MCI) and mild dementia in an autopsy‐confirmed cohort of Alzheimer’s disease (AD) and vascular neuropathology.MethodRetrospective data was gathered from the National Alzheimer’s Coordinating Center database on autopsy‐confirmed cases of primary Alzheimer’s disease (AD) and vascular neuropathology. Prevalence of depression was measured by the Geriatric Depression Scale score > = 5 during any visits at MCI (n = 364 AD cases, n = 51 vascular cases) and mild dementia (n = 557 AD cases, n = 24 vascular cases). We excluded those without pathology report, sex data or GDS results. Groups were compared via the chi‐squared test.ResultDepression prevalence was equal in MCI from AD and vascular neuropathology (27% in each, p = 0.9974). At mild dementia, depression was significantly more prevalent in vascular neuropathology compared to AD (37% versus 20%, p = 0.0363). In AD, at MCI there was no sex difference in depression prevalence (male 28% versus female 27%, p = 0.7560) but at mild dementia there was a female predominance (male 16% versus female 25%, p = 0.0075). In contrast, with vascular neuropathology, at MCI there was a trend for female predominance (male 21% versus female 33%, p = 0.3181) and no sex difference at mild dementia (male 38% versus female 36%, p = 0.9158).ConclusionThese results demonstrate that the prevalence of depression in cognitive disorders is driven by etiology, stage, and sex, which promotes further mechanistic studies on the interaction of these factors. Moreover, this illustrates the importance of depression screening in dementia, especially in females and those with suspected vascular etiology.
A glioma mimic which almost went under the knife
Authors: Dubey Shubham , P Naveen , Dubey Ayush 
Published: December 2023

AbstractBackgroundThere are many causes of acute dementia. While on one hand, it is essential to suspect a diagnosis based on clinical symptomatology and examination, radiological findings sometimes pose challenge leading to confusion regarding therapy being offered. An interesting case is discussed here.MethodA female patient of age 39 years showed up in Neurology OPD with symptoms of forgetfulness, confusion, socially inappropriate behaviour and somnolence for around 15 days. There was no history of seizures, hallucinations or sensory symptoms. With a clinical diagnosis of acute dementia, she was subjected to brain imaging.ResultContrast enhanced brain MRI showed ill‐defined non enhancing T2 and FLAIR hyperintense lesion involving bilateral hypothalamus, adjoining antero‐inferior aspect of both thalami, bilateral medial basal ganglia & cavum septum in bilateral symmetrical fashion. There was no evidence of venous thrombosis and on the basis of above findings, a diagnosis of low grade glioma was considered and biopsy was planned. But, before going for invasive procedure, other possibilities were explored. With a suspicion of Wernicke’s encephalopathy, iv thiamine was tried with no benefit. Autoimmune workup showed positive NMDA receptor antibodies and hence, immunotherapy was tried to which, patient responded completely.ConclusionNMDA encephalitis can present with variable MRI findings. Thus, a possibility of this entity should always be considered in differentials for young female patients presenting with acute dementia like picture.
Mechanistic Insights of Meglitinides Drug Repurposing and Delivery to Brain for Metabolic Syndrome Linked Neurodegenerative Disease
Authors: Wadhwa Geetika , Taliyan Rajeev 
Published: December 2023

AbstractBackgroundMetabolic syndrome (MS) includes clusters of metabolic disorders and type 2 DM (T2DM) is most common MS which cause insulin resistance (IR). The IR mediated dysregulation of signaling cascades in brain increase the production and secretion of Aβ, p‐tau which prompt to Alzheimer’s (AD). Therefore, repaglinide (REP) a meglitinides drug is used, which act by targeting ATP binding cassette and evidence indicated that REP increase neuronal survival via upregulating ATF‐6 gene and blocking the DREAM. Thus, there is huge possibility that REP regulate and modulate the expression of pro‐apoptotic protein, anti‐apoptotic protein, calcium homeostasis and may eventually reduce the neuronal cell death.MethodsIn, in vitro studies, primarily cytotoxicity assay was performed on SHSY‐5Y cells and to mimic the neurodegenerative condition, the cells were treated with streptozotocin (STZ, 2.5mM). Further, to check the efficacy of REP in AD, in vivo studies were performed using HFD fed STZ induced murine model. The HFD was fed for 16 weeks followed by administration of STZ (30mg/kg; i.p) in wistar rats for induction of DM linked AD.ResultsIn vitro and in vivo studies were conducted to understand the neuroprotective potential of the REP. It was observed that the REP shows cellular viability of ∼80‐85% and no morphological changes in the cells were identified. Additionally, the results have shown that REP increase the cell viability of STZ treated SHSY‐5Y cells by ∼1.2‐fold and significantly (p<0.01) decreased the oxidative stress in H2O2 treated cells. After treatment of REP (4 mg/kg,p.o) for 4 weeks in DM linked AD wistar rats, a significant (p<0.01) decrement in Aβ, tau proteins, TNF‐α, IL‐6, MDA, NO and increment in BDNF, SOD, GSH level was observed compared to disease control rats. Further, in behavioral studies a significant improvement (p<0.01) in the retention memory and spatial memory was observed after the REP treatment. Additionally, a significant (p<0.05) increase in Bcl‐2, ATF‐6 expression, and decrement in Bax, Caspase‐3 expression indicates reduction in neuronal cell death then the disease rats.ConclusionIn summary, it concluded that REP act as a neuroprotective agent which might be used to treat MS linked AD.
An examination of the impact of age and sleep quality on neurocognition within a multi‐ethnic sample
Authors: Slaughter Alexander W. , Arentoft Alyssa , Cham Heining , Oleas Denise S. , Schuck Lauren A , Camuy Alicia M , Breen Elizabeth Anne , Zhu Danqi , Talavera Sandra , Mindt Monica Rivera ,   Study of African‐Americans and Latinas/os for Understanding Dementia (SALUD)
Published: December 2023

AbstractBackgroundOlder adults and ethnoracially diverse groups (e.g., non‐Latinx Black (NLB), Latinx) are at higher risk of poor sleep quality. Poor sleep is linked to neurocognitive (NC) decline in middle/older adults, but much of the sleep literature has relied on global NC screening measures. This study examined the effects of age and sleep quality on NC functioning within a multi‐ethnic sample of middle/older adults utilizing a multi‐domain NC battery.MethodThis cross‐sectional study included 119 middle/older adults (M
age = 65.3, SD
age = 6.9; 46% NLB, 31% Latinx, and 23% non‐Latinx White (NLW); 63% female) who completed demographic questionnaires, the Pittsburgh Sleep Quality Index (PSQI), and a comprehensive NC battery. PSQI global and component scores (e.g., Daytime Dysfunction; PSQI‐DD) measured subjective reporting of sleep quality. Demographically‐adjusted NC T‐scores were used to compute 8 NC‐domain and global average T‐scores. Pearson’s correlations, ANOVA, and multiple regressions were used to test hypotheses.ResultGlobal NC was not related to any PSQI components, and the PSQI components did not differ across ethnoracial groups (all p’s<.05). However, within‐group correlations revealed that the relationship between PSQI components and NC domains significantly differed across ethnoracial groups. For example, frequency of sleep medication usage was significantly negatively correlated with executive functioning in the NLB group (r = ‐.39, p = .02), but not NLW or Latinx groups. Multiple regressions, including age and the interactions between race/ethnicity and PSQI component scores, significantly predicted 21‐39% of the variance in all NC domains (p’s<.05), except attention/working memory (p = .60). The interaction between PSQI‐DD and ethnoracial status significantly predicted memory (p’s<.05); this relationship was positive in the NLW group (B = 20.20), yet negative in the NLB (B = ‐1.16) and Latinx (B = ‐0.56) groups (ps<.05).ConclusionDisordered sleep may have a greater impact on NC functioning, namely memory, among middle/older adults from diverse ethnoracial groups, who are already at heightened risk for NC decline. Importantly, global cognitive screening may be insufficient in examining the effects of sleep quality on NC in middle/older adults. Given the ethnoracial differences in sleep quality, future research should consider culturally‐tailored sleep interventions. Using objective sleep quality measures (e.g., actigraphy) may better quantify sleep components.
GWAS identifies genetic factors associated with severity of cerebral amyloid angiopathy pathology
Authors: Godrich Dana , Pasteris Jeremy , Martin Eden R. , Schellenberg Gerald D. , Pericak‐Vance Margaret A. , Cuccaro Michael L. , Scott William K. , Kukull Walter A. , Montine Thomas J. , Beecham Gary W. ,   the Alzheimer Disease Genetics Consortium
Published: December 2023

AbstractBackgroundCerebral amyloid angiopathy (CAA) commonly co‐occurs with Alzheimer’s disease (AD) pathologies, leading to an increased risk and severity of cognitive decline. While CAA is known to impact cognitive impairment, the genetics of CAA are not well understood, and most previous sample sizes have been small. To address this gap, we conducted a genome‐wide association study (GWAS) of CAA pathology to identify genetic factors that are associated with this understudied AD‐related amyloidosis.MethodWe utilized data from 6,038 autopsied and genotyped individuals from the National Alzheimer’s Coordinating Centers (NACC) who were evaluated for CAA pathology upon autopsy. Participants were age 50+ at death and non‐Hispanic white. Genetic data were available from SNP arrays imputed to TOPMed and analyses were conducted only on common variants (MAF >0.01). GWAS performed ordinal logistic regression to determine the effects of genetic variants on CAA pathology (coded as 0, none; 1, mild; 2, moderate; 3, severe). Models adjusted for sex, age at death, and the first three genetic principal components (PC‐AiR; GENESIS; R v4.2). We then meta‐analyzed across the cohorts (METAL).ResultWe observed genome‐wide significant associations with CAA severity at established AD loci, including APOE (top SNP: rs429358, MAF = 0.155, P = 1.6E−86) and BIN1 (top SNP: rs6733839, MAF = 0.397, P = 3.9E−08). We observed a novel association with CAA pathology on chromosome 9 (top SNP: rs10908023, MAF = 0.258, P = 4.3E−11).ConclusionThis is the largest study to date aimed at identifying genetics factors associated with CAA pathology. Our findings offer new insights into the genetics of CAA, a common player in the AD landscape. We acknowledge the need for a larger dataset and are now expanding the study by sample size and by including additional ADRD phenotypes to gain a better understanding of the full spectrum AD/ADRD. Continuing to uncover the genetic underpinnings of CAA could potentially help us think about AD treatment in new ways and mitigate the negative side‐effects of brain swelling and bleeding that have been observed in recent clinical trials.
Brain catecholaminergic neurons control monocytes deployment to sites of injury and their loss exacerbate cognitive deterioration in an animal model of Alzheimer’s Disease
Authors: Croese Tommaso , Abellanas Miguel Angel , Ramos Javier Maria Peralta , Arad Michal , Medina Sedi , Castellani Giulia , Schwartz Michal 
Published: December 2023

AbstractBackgroundThe CNS constantly monitors the organism’s internal state and orchestrates adaptive responses to perturbation of the body’s homeostasis. Emerging evidence revealed that the brain can also instruct immune responses, which in turn can affect the condition of other organs, including the brain itself.MethodWe used neuronal retrograde‐labelling, flow‐cytometry, mass cytometry, scRNAseq and cognitive tests in animal model of Alzheimer’s disease (5xFAD) to study the relevance of the brain Brain‐Immune axis in the context of Alzheimer’s Disease.ResultsWe found that catecholaminergic neurons are in direct communication with the spleen, the major secondary lymphoid organ of our body. This connection is impaired in an animal model of neurodegeneration (Alzheimer’s Disease ‐ AD), and undermining this communication at early stage of the disease accelerated disease manifestation. We found that monocytes are the most sensitive cell type to noradrenaline released by the splenic nerve and halting neuronal inputs to the spleen impairs monocytes’ migratory capacity. Monocytes are needed to cope with neurodegenerative diseases and acute CNS damage. Upon splenic denervation, we observed reduced number of monocytes in the brain of AD mice and impaired microglia maturation. Upon denervation of the spleen, reduced number of infiltrating monocytes was also observed in a model of retina excitotoxic damage.ConclusionsThese results highlight a novel pathway through which the CNS can control immune function and therefore trigger tissue repairing processes.
A random population survey of adults aged 65 and over who deny recent cognitive changes asking the question “Do you want to know your risk of developing Alzheimer’s Disease via a simple blood test” after being told that researchers now believe that it is possible detect Alzheimer’s Disease prior to symptoms with a simple blood test
Authors: Curtis Craig T , Meador Jenna 
Published: December 2023

AbstractBackgroundRecent advances in blood biomarkers may soon enable clinicians to detect AD many years prior to cognitive decline with great accuracy. This survey address whether older adults would want a blood test to know whether they are at risk of developing AD.MethodRandom subjects who denied recent memory problems were approached on the sidewalk in a 55+ retirement community setting. The following scenario was presented: Scientists have learned that Alzheimer’s Disease starts 10‐20 years before symptoms, such as memory loss, begin. Your doctor can now order a simple blood test that will detect Alzheimer’s Disease before you get symptoms. Knowing that this blood test can show if you will get Alzheimer’s Disease, would you want the blood test?ResultData collected from 31 respondents reveal that 29 out of 31 (94%) were “familiar” with AD and 22 (71%) reported they knew someone who had been diagnosed with AD. When given the hypothetical scenario above, 23 (74%) wanted the blood test, 4 (13%) did not want the blood test and 4 (13%) were unsure if they wanted the blood test. Only 12 (39%) stated they received any type of memory testing at their annual doctor’s visit.ConclusionA surprisingly large number of respondents in our survey want to know their risk of developing AD. These results indicate a significant portion of the general population do want a simple blood test to know their risk of developing AD and do not seem afraid of knowing their risk of AD.The survey results also indicated that 94% were familiar with AD, indicating a high level of AD awareness in society. Only 39% reported receiving any type of memory testing at their annual doctor’s visit. Based on these results, clinicians should receive additional AD education so they are better prepared to discuss AD risk factors.Our survey indicates a large number of older adults are interested in a blood test that determines their risk of AD.Further work will include increasing the number of participants to 500 to further strengthen the data set.
Slow‐breathing induced hypocapnia mitigates deficit of vasoreactivity measured in patients with cognitive impairment
Authors: Marmarelis Vasilis , Chui Helena C , Billinger Sandra A , Joe Elizabeth B , Shin Dae , Hashem Suhaib , Rizko Jasmin , Aaron Stacey E , Cardim Danilo , Zhang Rong 
Published: December 2023

AbstractBackgroundA multi‐center study in Los Angeles (USC), Kansas City (KUMC) and Dallas (UT‐SWMC) has been quantifying the dynamics of CO2 vasoreactivity in MCI/AD patients and cognitively normal controls under spontaneous resting conditions. The goal is to develop effective vasoreactivity physio‐markers for early diagnosis of MCI and pre‐clinical AD, based on previous findings of significantly reduced vasoreactivity in MCI patients [Marmarelis et al., J. Alzh. Dis. 56:89‐105, 2017]. Here, we report on the effects of slow‐paced breathing upon these physio‐markers.MethodSpontaneous changes in arterial blood pressure (ABP), end‐tidal CO2 (etCO2), and cerebral blood flow velocity (CBFV) in middle cerebral arteries were recorded under resting conditions over two 6‐8 min sessions, separated by session of slow‐paced breathing (6 breaths/minute), in 47 MCI and 25 AD patients and 58 age‐matched cognitively normal controls. Using our novel methodology, we obtained predictive models of the dynamic effects of ABP and etCO2 upon CBFV using the universal convolutional form of linear dynamic models, which are defined by the respective “kernels” estimated from time‐series data. The etCO2‐to‐CBFV kernel is used to compute indices (physio‐markers) that quantify the vasoreactivity in each participant.ResultThe vasoreactivity index for each participant is computed from the integrated etCO2‐to‐CBFV kernel as the time‐average over the first 30 sec. The average kernels for patients and controls are shown in Figures 1‐2 for the two sessions respectively. Note the smaller kernel values for patients – while the difference is reduced after slow‐paced breathing. The obtained vasoreactivity indices are significantly smaller for 72 patients (MCI and AD taken together) vs 58 controls for the first session [p = 0.018; mean (SD): 0.057 (0.539) vs 0.424 (1.076)] but NOT for the session after slow‐paced breathing [p = 0.237; mean (SD): 0.193 (0.731) vs 0.361 (0.863)]. Average etCO2 was lower after paced‐breathing [p = 10−6; mean (SD): 36.23 (6.18) vs 33.44 (6.36)].ConclusionQuantitative analysis of cerebral CO2 vasoreactivity under resting spontaneous conditions in 72 MCI/AD patients vs 58 age‐matched controls, before and after slow‐paced breathing, revealed that the significant vasoreactivity deficit in MCI/AD patients is mitigated (at least temporarily) after slow‐paced breathing. This effect may be due to observed hypocapnia induced by slow‐paced breathing.
Recruitment and Engagement of LGBTQIA+ Older Adults for The Stonewall Generations Study
Authors: Flatt Jason D. , Tate Jacq , Klenczar Brittany 
Published: December 2023

AbstractBackgroundAccording to the Alzheimer’s Association, approximately 350,000 LGBTQIA+ older adults in the U.S. currently have Alzheimer’s disease and related disorders (ADRD), increasing to over a million by 2030. Our recent research suggests that 1 in 7 LGBTQIA+ older adults report problems with their memory and thinking (subjective cognitive decline), which was much higher than their cisgender (not transgender), heterosexual counterparts. However, very few studies have assessed the cognitive function of LGBTQIA+ older adults.MethodsWe are utilizing tailored recruitment and engagement strategies to recruit a racial/ethnically diverse sample of at least 250 LGBTQIA+ and 250 non‐LGBTQIA+ older adults aged 50+ from the U.S. with a range of cognitive function from healthy to mildly impaired. Our recruitment and engagement approaches are guided by community‐based participatory research approaches that focus on building trust, collaboration, cultural humility, and giving back to the community.ResultsWe have been utilizing novel methods to recruit and engage LGBTQIA+ older adults and community organizations across the U.S. into The Stonewall Generations Study. Our current efforts involve a diverse recruitment plan that relies on recruitment via social media (e.g., Facebook, Twitter), referrals from community organizations, local outreach (tabling at community resource fairs, attending Pride and other LGBTQIA+ focused events), presenting to LGBTQIA+ aging service organizations, and developing unique social and educational engagement events.ConclusionsOur current efforts to recruit and engage LGBTQIA+ older adults are important because they can help to identify ways to improve representation of diverse communities in Alzheimer’s disease and aging research. There is a need for tailoring research and recruiting and engaging diverse older adults, especially LGBTQIA+, into research and finding ways to address the health and Alzheimer’s disease risk of underserved populations. The Stonewall Generations Study aims to increase knowledge of culturally‐relevant recruitment and engagement strategies and identify targets for preventative interventions to decrease ADRD risk among LGBTQIA+ older adults.