bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship Between Weight‐Adjusted Waist Index (WWI) and Cognitive Function in Older Adults: A Cross‐Sectional Analysis of the NHANES 2011‐2014 Data
Authors: Qiu Xichenhui , Wei Changning 
Published: January 2025

AbstractBackgroundThe impact of obesity on cognitive function has engendered considerable interest. Weight‐adjusted waist index (WWI) emerged as a novel and innovative marker of obesity that has responded to weight‐independent abdominal obesity. However, the association between WWI and cognitive function remains unclear. To address this gap, the present study aims to explore the relationship between weight‐adjusted waist index (WWI) and cognitive performance in older adults.MethodThe datasets from the National Health and Nutrition Examination Survey (NHANES) 2011‐2014 were used in a cross‐sectional investigation. Multivariate regression and smoothing curve fitting were used to investigate the linear and nonlinear relationship between WWI and cognitive function, which was tested by neuropsychological tests, including CERAD‐WL, AFT, and DSST, respectively. Subgroup analysis and interaction tests were used to test whether this relationship was stable across groups. Machine learning models based on random forest facilitated the analysis of associations between WWI and cognitive metrics.ResultA total of 3472 participants were involved in the analysis. Results showed that WWI was significantly negatively associated with low scores on the CERAD‐WL [‐0.96 (‐1.30, ‐0.62)], AFT [‐0.77 (‐1.05, ‐0.49)], and DSST [‐3.67 (‐4.55, ‐2.79)], and this relationship remained stable after converting the WWI to a categorical variable. In addition, this significant negative association was more pronounced in men than women and diminished with advancing age. Non‐linear threshold effects were noted, with the correlations intensifying between WWI and CERAD‐WL when WWI surpassed 12.25, AFT when WWI surpassed 11.54, and DSST when WWI surpassed 11.66.ConclusionA higher WWI, indicative of increased abdominal obesity, was correlated with deficits in learning, memory, verbal fluency, and processing speed among older adults. The results suggest that abdominal obesity may be an essential factor in cognitive decline in older adults. The results demonstrated the importance of interventions to reduce abdominal obesity in protecting cognitive performance in older adults.
Repurposing renin‐angiotensin system‐targeting medications for treatment of cerebral amyloid angiopathy and associated cognitive‐behavioral deficits in Tg‐SwDI mice
Authors: Hernandez Ariana , Noto Natalia , Vogel Chana , Uribe Iliana , Bonetti Julianna , Wind Eleanor , Pulido‐Correa Victoria , Jeneske Mikayla , Echeverria Bianca , Restrepo Yazmin , Moen Shay , Chiduruppa Vedika , Speth Robert , Robison Lisa S 
Published: January 2025

AbstractBackgroundCerebral amyloid angiopathy (CAA), the accumulation of amyloid proteins in the cerebral vasculature, increases the risk of stroke and vascular cognitive impairment and dementia (VCID). Not only is there no treatment for CAA, but the condition is also highly comorbid with Alzheimer’s disease (AD), and its presence may serve as a contraindication to treating patients with anti‐amyloid therapies due to an increased risk of hemorrhage and edema. Therefore, it is crucial to identify novel treatments for individuals with CAA. Epidemiological studies suggest that certain antihypertensive medications, including those that target the renin‐angiotensin system (RAS), are associated with a decreased risk of dementia. This study assesses whether two FDA‐approved RAS‐targeting drugs: telmisartan [a moderately brain‐penetrant angiotensin receptor blocker (ARB)], and lisinopril [a brain‐penetrant angiotensin‐converting enzyme (ACE) inhibitor]; can be repurposed for the treatment of CAA.MethodsAt either ∼3 months (early intervention) or ∼8 months (later intervention) of age, male and female Tg‐SwDI mice began treatment with either telmisartan (1 mg/kg/day) or lisinopril (15 mg/kg/day) dissolved in drinking water or received plain drinking water only. Age‐ and sex‐matched C57BL/6J mice receiving plain drinking water served as wild‐type controls. Following 4 months of treatment, mice underwent blood pressure measurement followed by behavioral testing prior to euthanasia.ResultsVoluntary oral consumption delivered doses similar to the target dose for both drugs. At the doses used, telmisartan and lisinopril treatment did not significantly reduce blood pressure in Tg‐SwDI mice. Our findings thus far suggest that these drug treatments, particularly lisinopril, may mitigate cognitive‐behavioral deficits observed in Tg‐SwDI mice.ConclusionsOngoing experiments are being completed to increase sample sizes and investigate the potential benefits of telmisartan and lisinopril to mitigate neuropathological and cognitive impairment in Tg‐SwDI mice. If findings support our hypothesis, this will demonstrate that these drugs could be repurposed to prevent and/or treat CAA, reducing the worldwide burden of stroke and dementia.
Associations Between Alzheimer’s Disease and Obesity: Clinical Trials of NA‐831 for AD and NA‐931 for Obesity
Authors: Tran Lloyd , Tran Zung Vu , Vu Fern 
Published: January 2025

AbstractBackgroundNA‐831 is a new drug candidate, exhibiting neuroprotection, neurogenesis and memory enhancing properties for the treatment of Alzheimer’s Disease (AD). NA‐931 is an analog of NA‐831, regulating the homeostasis of the triple: IGF‐1, GLP‐1 and GIP functions for obesity.MethodA randomized clinical trial of NA‐831 was performed in 112 participants with mild and moderate AD, half received the drugs and half received placebo. The patients with MCI received 10 mg of NA‐831 and patients with mild and moderate AD received 30 mg of NA‐831 or placebo orally per day. Subjects with MCI to meet the NIA‐AA core clinical criteria, CDR score of 0.5 and a Memory Box score of 0.5 or greater at Screening and Baseline. MMSE score ≥22. Subjects with mild & moderate AD to meet the NIA‐AA core clinical criteria. MMSE: 17‐21.Animal Studies of NA‐931: A 14‐day study in diet‐induced obesity DIO‐NASH mice was conducted to evaluate the treatment of NA‐931 on obesity.ResultNA‐831 showed a significant improvement for patients with mild and moderate AD with the ADAS‐Cog‐13 score change of an average of 4.1 as compared to the placebo after 24 weeks of treatment (p = 0.001; ITT). CIBIC‐Plus showed 78% patients improved (p = 0.01; ITT). mNA‐831 was well‐tolerated at 30 mg/day. It was observed that 66% (12 of 18) patients having diabetes amongst 56 patients on the NA‐831 drug treatment reported a loss of 17‐23% of body weight over 6 months. Only 4 of 7% of 56 patients on placebo reported a loss of 3‐5% over 6 months. There were no serious adverse events observed.The study in DIO‐NASH mice had demonstrated that treatment with NA‐931 resulted in significant reductions in body weight up to 26% (p<0.0001), as well as reductions in plasma glucose and plasma triglycerides up to 23% and 34%, respectively (p<0.003 for each). NA‐931can reduce the body mass index, without causing the muscle loss.ConclusionAn association of Alzheimer’s disease and diabetes obesity has been suggested with clinical results of NA‐831 and NA‐931. However, whether this association is causal requires further evaluation.
Brain health in the clinical practice of Spanish neurologists: a national cross‐sectional survey
Authors: Lage‐Martinez Carmen , Zuniga Raquel Gutierrez , Giménez Sandra , Nowak Rafal , Zegarra‐Valdivia Jonathan Adrian , Falgàs Neus , Balasa Mircea , Lawlor Brian A , Leroi Iracema 
Published: January 2025

AbstractBackgroundBrain Health (BH) perspectives and practices among health care professionals constitute a crucial piece of information for developing tailored initiatives to foster BH at the regional level. We aim to characterize knowledge and clinical practices associated with BH in Spanish neurologists by a cross‐sectional survey.MethodAn original online survey was distributed by email among all members of the Spanish Society of Neurology. The survey included four sections: BH knowledge; BH‐related clinical practices; perspectives about the importance of BH in neurology practice; and limiting factors for BH promotion in daily practice.Result400 neurologists participated in the survey, and 75.8% fully completed it. Participants were 61.7% females, mainly workers in tertiary (71.0%) and public hospitals (85.7%), and 74.2% had a sub‐specialization. Many participants considered to be familiar (41.7%) or somehow familiar (43.6%) with the concept and recommendations of BH, but 48.7% did not know any supporting scientific study. A substantial percentage of respondents considered that BH cannot be improved in aging (19.2%) or dementia (21.1%). Clinical interview was the main tool to evaluate BH (81.3%), but 22.1% of neurologists did not routinely explore BH. A higher percentage of females than males declared to regularly ask patients about their familiar situation (68.9% vs 53.0%, p 0.018) and social activities (62.9% vs 47.8%, p 0.019) and recommended more frequently healthy diet (75.7% vs 64.9%, p 0.0080). Also, more females considered that it is important to develop BH plans (98.9% vs 89.4% males), even adjusting by age (p <0.0001). The main limiting factor for BH evaluation and promotion during clinical visits were time constraints (in 76.8% of cases), followed by scarcity of support resources (61.3%), but a significant number of neurologists with <10 years of experience considered lack of education about official BH recommendations as a limitation (26.5% vs 14.0% in >20 years, p 0.047).ConclusionThis survey was conducted as a situational analysis to guide next steps of the BH roadmap in Spain. While time constraints and scarcity of resources should be approached from a health policy perspective, we identify poor BH knowledge as an opportunity to improve BH related practices, especially among young neurologists.
Evaluating the Impact of Cardiometabolic Risk Factors on Neuroimaging‐Based Brain Age: A Deep Learning Approach
Authors: Tavakoli Fatemeh , Ma Da , Ge Yaorong 
Published: January 2025

AbstractBackgroundMid‐life and late‐life cardiometabolic abnormality are known modifiable risk factors for late‐life dementia. Neuroimaging‐based “brain age” has shown as a surrogate marker for brain health. This study aims to investigate the relationship between effect of cardiometabolic risk factors (CMRF) and accelerated brain aging,MethodT1‐weighted 3D MRIs from a total of 965 participants (47‐81 years, 53% female) in the UKBiobank data were included in this study. (80%( = 772) training and 20%( = 193) validation). 9 CMRF was extracted, including diastolic blood pressure (dbp), pulse rate (pr), glycated haemoglobin (HbA1c), HDL, glucos, systolic blood pressure (sbp), cholesterol, triglycerides. A brain‐age model pre‐trained using the UKBiobankd data – the Simple Fully Convolutional Network (SFCN) – was fine‐tuned on the brain‐extracted data derived from FreeSurfer (v5.3.0). The brain age gap (BAG) was calculated as the difference between their chronological age and the predicted brain age. Correlation between the CMRF and BAG was derived using the generalized linear model controlling the demographic factors, including age and sex.ResultThe model exhibited high accuracy with a training MAE of 2.05 years and a validation MAE of 2.77 years. Significant associations with the BAG were observed for sbp across genders with a p‐value of 0.0415, with gender‐specific correlations found for cholesterol and sbp in females (p = 0.0242 and 0.0163) and no significant correlations between males’ BAG and any CMRF.ConclusionThis study discerned the significance of cholesterol and systolic blood pressure as predictors of brain age, emphasizing their potential as markers for brain health in this demographic. Additionally, the observed gender disparities in the association of CMRFs with BAG highlight the necessity for gender‐specific considerations in the assessment and intervention of brain aging.
Genome‐Wide Associations of Cognitive Domains and their Correlation with Polygenic Risk Scores for Antidepressant Response in Late‐Life Depression
Authors: Elsheikh Samar , Marshe Victoria , Maciukiewicz Malgorzata , Islam Farhana , Men Xiaoyu , Gonçalves Vanessa SM , Felsky Daniel , Kennedy James L. , Mulsant Benoit H. , Reynolds Charles F. , Lenze Eric J. , Mueller Daniel 
Published: January 2025

AbstractBackgroundLate‐life depression (LLD) often coincides with cognitive decline, impacting antidepressant treatment outcomes. Investigating the genetic profile of cognitive function and its association with antidepressant response in individuals with LLD is crucial.MethodIn the Incomplete Response in Late‐Life Depression: Getting to Remission (IRL‐GRey) study, 307 older adults with major depressive disorder underwent 12‐week venlafaxine treatment. A genome‐wide association study (GWAS) of five cognitive domains using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was conducted. Functional annotations were performed using FUMA. Polygenic risk scores (PRSs) for antidepressant non‐remission and symptom improvement were using PRSice v2. Associations between PRSs and cognitive domains were analyzed, adjusting for age, sex, and genomic principal components. Bonferroni correction and permutation tests were applied to address multiple testing issues.ResultOut of the five cognitive domains, significant SNPs were identified for the attention domain (lead SNP rs67854110, beta = ‐9.91, CI = [‐13.12, ‐6.70], P = 4.4e−09). Top suggestive genes associated with language showed differential expression in the hypothalamus, cortex, and nucleus accumbens (Pbon = 0.001). The language gene set analysis exhibited significant enrichment with the GWAS Catalog set response to cognitive‐behavioral therapy in depression (P = 9.24e−11). Additionally, the top SNP associated with delayed memory (rs13087568, beta = ‐8.24, CI = [‐11.36, ‐5.11], P = 4.5e−07) was previously linked to depressive symptoms by other studies. Polygenic risk scores (PRS) for non‐remission negatively correlated with attention (PThreshold = 0.0001, NSNPS = 39, OR = 0.105 [0.016, 0.686], P = 0.019), immediate memory (PThreshold = 0.001, NSNPS = 320, OR = 0.074 [0.011, 0.490], P = 0.0072), and delayed memory (PThreshold = 0.01, NSNPS = 2449, OR = 0.107 [0.021, 0.540], P = 0.0074). PRS for symptom improvement showed a positive correlation with delayed memory (PThreshold = 0.001, NSNPS = 385, OR = 5.329 [1.056, 26.885], P = 0.044). However, none of the PRS associations survived the Bonferroni threshold.ConclusionThese findings suggest a genetic link between cognitive domains and antidepressant response in LLD, reinforcing previous associations. Understanding genetic contributions to cognitive decline in older adults with depression could aid in early identification and interventions to prevent dementia.
Patterns of Tau deposition in Alzheimer’s Disease
Authors: Srinivasan Dhivya , Nasrallah Ilya M. , Yang Zhijian , Erus Guray , Davatzikos Christos 
Published: January 2025

AbstractBackgroundSpread of tau tangles, one of the hallmarks of Alzheimer’s Disease (AD) is complex and heterogenous. While many studies focus on stereotypical patterns of tau, there are many individuals who deviates from Braak staging (ex.atypical tau). Understanding heterogeneity of tau spread and association with other factors has important implications in clinical trials. In this analysis, we derived four distinct patterns of tau using a data driven, deep learning‐based clustering method, Surreal‐GAN.MethodWe used data from 1445 (Amyloid+:792, Amyloid‐:653) subjects with 18F‐flortaucipir PET from the Alzheimer’s Disease Neuroimaging Initiative (ADNI; N = 803), HABS; N = 195 and A4; N = 447. We used study‐defined cut‐offs for deriving amyloid status for each study separately. In this analysis, we utilized tau regional standardized uptake value ratios(SUVR) calculated for each of the aparc+aseg FreeSurfer labels. We then applied Surreal‐GAN on the regional tau SUVR for Amyloid + subjects with Amyloid ‐ as reference group to determine the Tau spatiotemporal subtypes. We tested the associations between r‐indices and cognitive scores.ResultParticipants had a mean age of 71.8 (±4.8); 73.5(±6.2); 73.8(±7.6) years for A4, HABS and ADNI respectively. Surreal‐GAN showed optimal agreement indices for four patterns. Pattern r1 (r.occipital) shows the involvement of cuneus, lingual gyrus; pattern r2 (r.frontotemporal) shows frontal and temporal; pattern r3 (r.parietal) shows precuneus and inferior parietal and pattern r4 (r.typical) shows typical AD regions. Pattern r.occiptal was associated with language area of cognitive function(MMSE language domain); We observed significant associations of r.typical with composite memory scores in ADNI.ConclusionEmploying a data‐driven deep learning‐based approach, we derived more than one dissociable pattern of tau deposition. These findings could inform identification of subgroups of individuals who may or may not be responsive to particular clinical intervention.
Assessing perivascular spaces as a biomarker of Alzheimer’s disease in cognitively normal older adults
Authors: Houchin Lauren Abigail , Adams Jenna N. , Kim Soyun , Taylor Lisa M. , Sathishkumar Mithra , McMillan Liv , Harris Alyssa L. , Janssen Niels , Yassa Michael A. 
Published: January 2025

AbstractBackgroundPerivascular spaces (PVS), the small spaces surrounding vasculature in the brain which are critical for glymphatic clearance, are an emerging marker of cerebrovascular dysfunction. Abnormal expansion of PVS has been associated with Alzheimer’s disease (AD), and, therefore, may provide a measure of disease risk. Here, we investigate the relationship between PVS burden, memory performance, neurodegeneration, and biomarkers of AD pathology in community‐dwelling older adults without cognitive impairment.MethodWe included 120 participants from the Biomarker Exploration in Aging, Cognition, and Neurodegeneration (BEACoN) study. PVS segmentation was conducted utilizing T1‐weighted MRI and an open‐source deep learning algorithm (the “SHIVA‐perivascular spaces (PVS)” software package), producing two global outcome measures: PVS volume and number of PVS clusters. PVS volumes were converted to a volume fraction using white matter and basal ganglia volumes for each participant. We then investigated the relationship between perivascular spaces and 1) delayed recall scores on the Rey Auditory Verbal Learning Test (RAVLT), 2) hippocampal volume, derived from Freesurfer segmentation of T1‐weighted images and corrected for intracranial volume, and 3) amyloid‐beta (Aβ) pathology, assessed using 18F‐florbetapir‐PET, and quantified continuously with global SUVR values and thresholded for amyloid‐positivity at >1.11. Associations with PVS were tested using correlations and t‐tests with age, sex, and education as covariates.ResultGlobal PVS count and volume were not associated with RAVLT delayed recall scores. Additionally, while Aβ+ status was not significantly associated with PVS count or volume, a t‐test of mean SUVR using a median split of PVS count was trending toward significance (p = 0.07). Global PVS count was negatively correlated (r = ‐.228, p = 0.015) with hippocampal volume. When age, sex, and education were controlled for, the result was less robust but trending toward significance (p = 0.09).ConclusionOur results suggest that PVS may reflect early neurodegenerative changes and may be indicative of early AD pathological changes. Future efforts will examine longitudinal relationships and regional PVS values in regions associated with learning and memory, such as the medial temporal lobe.
Remote APOE counseling and genotyping via telehealth: Early findings from a new care delivery model in the United States
Authors: Rao Anitha , Anderson Leyla , Wilkes Travis , Verdooner Steven R 
Published: January 2025

AbstractIntroductionAPOE (apolipoprotein E) genotyping determines an individual’s risk of developing Alzheimer’s disease and unique pathological characteristics vital to treatment consideration. The presence of the ε4 allele is considered a dose‐dependent risk factor for late‐onset Alzheimer’s disease, with each additional copy of the allele adding to the risk. Genetic counseling and education are essential as disclosure can lead to psychosocial issues, employment issues, and family stress. Traditionally, genetic counseling for Alzheimer’s disease has occurred during face‐to‐face encounters, thereby marginalizing patients who live in rural and underserved areas with high social determinants of health. In this study, we evaluated the application of telehealth services for APOE‐specific genetic counseling with an emphasis on solutions‐based education promoting health literacy and equity.MethodsParticipants were enrolled into the program from an electronic referral process from a primary care or neurology outpatient practice. A HIPAA‐secure and encrypted electronic health system was used to conduct the telehealth visits. Consent was collected from all patients. A BrainHealth Educator (BHE), typically an RN, was trained on best practices and protocols on APOE testing from resources such as AGREEDementia.org. BHEs conducted pre‐ and post‐test education and counseling. In addition, BHEs coordinated logistics of at‐home buccal swab self‐collection and sample transportation to lab.ResultsA total of 29 patients enrolled in the genotyping program with 22 females and 7 males. Each patient had a 30‐minute pre‐test education that reviewed Mendelian inhertiance, APOE polymorphism combinations, and evidence based risk stratification for developing Alzheimer’s disease. All possible genotypes were represented amongst the study subjects (n = 29): E2/E2 (1), E2/E3 (3), E2/E4 (2), E3/E3 (12), E3/E4 (7), E4/E4 (1), pending (3).ConclusionsAdvancements in cognitive care are rapidly growing and there is a need for genetic risk assessment and stratification. Ordering genetic testing requires adequate pre‐test counseling to ensure appropriate timing and utilization. The interpretation and dissemination of genetic information requires structured support from a trained healthcare professional skilled with providing solutions‐based guidance. Under these circumstances, individuals can receive APOE‐specific genetic health information in a manner that enhances cognitive care planning, prevention, and treatment with targeted monoclonal antibody treatments.