bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage and Haplotype Association of Cognitive SuperAging to Chromosome 14 in the Midwestern Amish
Authors: Dorfsman Daniel A. , Prough Michael B. , Gulyayev Alex V. , Caywood Laura J. , Clouse Jason E. , Herington Sharlene D. , Slifer Susan H. , Adams Larry D. , Laux Renee A. , Song Yeunjoo E. , Lynn Audrey , Fuzzell Sarada L. , Hochstetler Sherri D. , Miskimen Kristy L. , Main Leighanne R. , Wang Ping , Liu Yining , Moore Noel C. , Ogrocki Paula K. , Lerner Alan J. , Vance Jeffery M. , Cuccaro Michael L. , Pericak‐Vance Margaret A , Scott William K. 
Published: January 2025

AbstractBackgroundWhile Alzheimer’s disease and dementia prevalence increase with age, some older adults retain cognitive performance equal to those in mid‐life. One group, referred to as SuperAgers (SA), are ≥ 80 years old and demonstrate episodic memory function at or above the level expected for a middle‐aged adult. Genetic studies of SA may reveal heritable factors that promote superior cognition in older adults. This study utilizes an Amish sample to identify genetic factors underlying SA using both pedigree‐based and pedigree‐free analytical methods.MethodAdult Amish participants underwent a comprehensive neuropsychological examination. Those aged ≥ 80 with episodic memory ≥ the mean for ages 35‐44 and performance in non‐episodic memory tasks (e.g., language, executive function tests) within one standard deviation or better for their own age were considered SA (N = 83). Using family records, SA subjects were grouped into 16 pedigrees for parametric and non‐parametric linkage analysis in MERLIN. To assess the evidence of a shared haplotype across pedigrees, pairwise identical‐by‐descent segments were generated in the overall sample using iLASH and then assembled into multi‐sample IBD haplotype clusters using DASH. IBD haplotype frequencies were compared between SA and a comparison group comprised of age‐matched cognitively unimpaired non‐SA, as well as individuals exhibiting cognitive impairment (N = 304). Genetic variants within haplotypes of interest were tested for association with SA in GENESIS.ResultIn the parametric analysis, HLOD scores > 3 were detected on chromosomes 1 (peak at 44 Mb), 2 (203 Mb), 7 (30 Mb), 14 (100 Mb), and 20 (17 Mb). IBD haplotypes within a 5Mb region centered around the peak linkage signals were further assessed. The strongest haplotype‐based association was observed on a ∼660 Kb segment on chromosome 14 (αBonferroni‐adjusted = 1.4e‐4, p = 3.16e‐5). Single‐variant association testing within the boundaries of the chromosome 14 haplotype identified 6 strongly correlated intronic/intergenic variants enriched in SA (MAF = 0.01, αBonferroni‐adjusted = 1.8e‐5, p = 5.22e‐8).ConclusionThis investigation found evidence of linkage and association of SA to a region on chromosome 14. Multiple genes in the region including DLK1, implicated in hippocampal neurogenesis, represent candidate targets for further study.
A Pilot Study to evaluate feasibility of a teleneuropsychological protocol in older adults in Panama and Florida
Authors: Santos Luis Guillermo , Perez‐Lao Ambar R , Oviedo Diana C , Britton Gabrielle B , Smith Glenn E. 
Published: January 2025

AbstractBackgroundThe use of videoconference platforms for neuropsychological assessment was not as common among mental health practitioners before the COVID‐19 pandemic. However, due to lockdowns and quarantines worldwide, mental health professionals had to find a feasible alternative and shift to virtual evaluations. This increased the use of teleneuropsychology in both at a clinical and research level. Studies conducted during the pandemic provided evidence of the feasibility of virtual assessments, but data from low‐and middle‐income countries is scarce and conclusions from studies in other regions cannot be generalized. The objective of this study is to develop and apply a teleneuropsychological assessment battery on a group of elderly adults in Panama and Hispanics living in the United States.MethodThis is a multicenter study that will gather data from a Panamanian Cohort parallel to the current Florida‐based study Development and Validation of TeleNeuropsychology Normative Data for Older Adults (FLOAT). So far 80 participants over 50 years old have been assessed in Panama and Florida. Inclusion criteria includes passing a screening with TICS‐M for low risk of developing dementia and having basic knowledge and accessibility of electronic devices. Researchers contact potential participants through calls and WhatsApp chats to explain the study and obtain informed consent. Participants are then screened to see if they are eligible to be assessed through the video conference platform. Participants must complete the teleneuropsychological assessment battery from the National Alzheimer’s Coordinating Center (NACC), and different questionnaires to provide socio‐demographic and functional data. All information is gathered with the REDCap platform.ResultOne hundred participants will be assessed with a teleneuropsychology protocol in each cohort. Once all data is collected, it will be analyzed with multivariate statistics methods. We expect to describe the protocol’s feasibility assessing older adults in both locations.ConclusionTo our knowledge this is the first study of its kind in Panama and one of the only ones in the region. The study seeks to generate data that could be shared and applied for future research or clinical practice regarding teleneuropsychological assessments with older adults with similar cohorts.
Acute communication between microglia and other immune cells in the anti‐Aβ antibody injected cortex
Authors: Foley Kate E. , Krick Katelynn E. , Weekman Erica M. , Wilcock Donna M. 
Published: January 2025

AbstractBackgroundAnti‐Aβ immunotherapy use to treat Alzheimer’s disease is on the rise. While anti‐Aβ antibodies provide hope in targeting Aβ plaques in the brain, a major side effect of amyloid‐related imaging abnormalities (ARIA) persists with no known cause. As severe ARIA is typically seen within the first few infusions in human clinical trials, we sought to identify acute effects of anti‐Aβ antibody on brain.MethodTo determine cellular changes due to anti‐Aβ antibody exposure, we intracranially injected 14mo APP male and female mice with anti‐Aβ IgG1 (6E10) or control IgG1 into the cortex. After 24hrs or 3days, we harvested the cortex and performed a glial cell enriched preparation for single cell sequencing. Cell types, proportions, and cell‐to‐cell signaling was evaluated between the two injection conditions and two acute timepoints.ResultWe identified 23 unique cell clusters including microglia, astrocytes, endothelial cells, neurons, oligos/OPCs, immune cells, and unknown. The anti‐Aβ antibody injected cortices revealed more ligand‐receptor communications between cell types, as well as stronger communications at 24hrs. At 3days, while there were more L‐R communications for the anti‐Aβ antibody condition, the strength of these connections was stronger in the control IgG condition. Specific pathways such as CD48 and PD‐L1 were enriched in the anti‐Aβ antibody condition, but not the control IgG condition in microglia‐to‐microglia communication. We also found evidence of an initial and strong communication emphasis in microglia‐to‐peripheral immune cells at 24hrs, specifically in the TGFβ signaling pathway. Additionally, we found that peripheral immune cells that were exposed to anti‐Aβ antibody failed to signal via the TNF pathway, which was strongly enriched in the control IgG condition at both timepoints.ConclusionWe identify several pathways that differ between anti‐Aβ antibody and control IgG injections at acute timepoints. These data lay the groundwork for understanding the brain’s unique response to anti‐Aβ antibody and its predisposition to ARIA.
Characterizing Tau Neuropathology Across Brain Regions in Patients Carrying PSEN1 Jalisco Mutation
Authors: Breningstall Bayla M , Abdollahi Evan , Hiniker Anne , Hawes Debra , Ringman John M , Bienkowski Michael S 
Published: January 2025

AbstractBackgroundMutations in the presenilin 1 (PSEN1) gene cause early onset autosomal dominant Alzheimer’s Disease (AD), and the Jalisco mutation (A431E) is a subset found in people of Mexican descent (Yescas P, 2006). The Jalisco A431E mutation has been shown to produce distinct AD neuropathology such as cotton‐wool amyloid plaques as well as motor dysfunction like spastic paraparesis (Orozco‐Barajas, 2022). High levels of tau neuropathology have been observed with other PSEN1 mutations, but tau neuropathology in Jalisco patients has not been examined. Therefore, we sought to quantify the distribution of tau across a variety of brain regions in patients with A431E mutation and compare to patients with other PSEN1 mutations (A260V and T245P) or high stage sporadic AD.MethodTen coronal brain sections from 9 PSEN1 (n = 5 A431E; n = 2 A260V, n = 2 T245P) and 9 high stage AD subjects immunohistochemically labelled with AT8 were obtained from the USC Alzheimer’s Disease Research Center (ADRC). Regions analyzed included cerebral cortex (prefrontal, parietal, temporal, and occipital areas), hippocampus, striatum, midbrain, cerebellum, pons, and medulla. Ilastik, a machine‐learning based software, was trained on positive AT8 staining versus background pixels and applied this training to the whole slide image. This binary output was then overlaid with a manually drawn ROI atlas in the Quantitative Imaging Toolkit (QIT), and positive pixels per pixels of the region was used to calculate density of AT8 pathology.ResultAT8 density was significantly higher across the brain in patients with PSEN1 mutations compared to sporadic AD. Although small sample size is limited for these patient groups, we found that A431E patients had lower AT8 density in the hippocampus compared to other PSEN1 patients, most notably in dentate gyrus, as well as Brodmann Areas 35 and 36.ConclusionThese data show a high burden of tau fibrils as measured by AT8 across brain regions in people with PSEN1 mutations as compared to other high AD patients. Notably, A431E patients had different distributions than other PSEN1 patients. These findings help further characterize early onset autosomal dominant AD within patients of Mexican heritage and how tau neuropathology might contribute to its unique symptoms.
Comparing the Brief Assessment of Cognitive Health and Montreal Cognitive Assessment: Test‐retest reliability and sensitivity to cognitive change in older adults
Authors: Floden Darlene P , Curran Kelsey , Hogue Olivia , Krishnan Kamini , Saxena Saket A , Sonneborn Claire , Rothberg Michael B , Misra‐Hebert Anita D , Milinovich Alex P , Pfoh Elizabeth R , Fox Robert J , Kattan Michael W , Busch Robyn M 
Published: January 2025

AbstractBackgroundTest‐retest reliability for existing cognitive screening tests is typically poor and most have ceiling effects and restricted score ranges that mask the presence of subtle decline. The Brief Assessment of Cognitive Health (BACH) is a computerized cognitive screening tool that patients complete independently. It includes a complex memory test without ceiling effects and brief mood and history questions. The BACH generates a probability score for cognitive impairment that is highly accurate at predicting impairment on neuropsychological testing. The goal of this study was to determine if the psychometric characteristics of BACH (i.e., test‐retest reliability and sensitivity to cognitive change) are superior compared to a commonly used screening test, the Montreal Cognitive Assessment (MoCA).MethodNinety‐seven participants completed the BACH and MoCA at two timepoints. A mixed effects model was fit to derive between‐ and within‐subjects variability to calculate the intraclass correlation coefficient (ICC) to assess test‐retest reliability of the screening tools. A subset of 52 participants completed the same neuropsychological battery at both timepoints and individual composite cognitive change scores were calculated. Pearson correlations were used to determine the strength of relationships between the composite cognitive change score and change scores on the MoCA and BACH.ResultOn average, the ICC sample was 68 years‐old with 15 years education, and 56% were female. The median time between test sessions was 384 days (range 246‐1211). ICC for the BACH probability of impairment score was 0.59 (moderate reliability) whereas the ICC for the MoCA was 0.48 (poor reliability). For the cognitive testing sample (average age = 72 years, 16 years ed, 54% female), median time between test sessions was 336 days (range 263‐426). Composite cognitive change score was moderately related to BACH probability change (r = ‐0.49; CI = [‐0.68, ‐0.26]) and strongly related to BACH memory score change (r = 0.55; CI = [0.32, 0.71]). Composite cognitive change score was weakly associated with MoCA change score (r = 0.12; CI = [‐0.17, 0.38]).ConclusionThe BACH demonstrated moderate to strong test‐retest reliability and sensitivity to cognitive change, while observed MoCA psychometrics were below the cutoffs recommended for clinical practice. The BACH is a more accurate tool for cognitive surveillance in older adults.
Association between pulmonary function and cognition in urban Indian adults – A cross sectional analysis
Authors: Mallikarjun Divya N , S Monisha , Lingegodwa Abhishek Mensegere , Stezin Albert , Partha Ajith , M Amitha C , Narayanasamy Rajitha , R Meghana , Menon Meenakshi , Velavarajan Goutham , Vishwanath Vindhya , Malo Palash K , HS Sunitha , HS Deva Kumar , Agrawal Deepashri , Hameed Shafeeq K Shahul , Arvind Prathima , Sundarakumar Jonas S. , Issac Thomas Gregor 
Published: January 2025

AbstractBackgroundPulmonary Function Tests (PFTs) are the non‐invasive tests to measure the lung function. Relationship between pulmonary function and cognition is an emerging area of research, understanding this is crucial for prevention and management of dementia. Hence this study aims to investigate the association between pulmonary function and cognition.MethodThis cross sectional analysis includes the participants aged 45 years and above (N = 924) from an ongoing longitudinal study, the Tata Longitudinal Study of Aging (TLSA), conducted in urban Bangalore, India. The pulmonary function was assessed through spirometry, Z scores were calculated for Forced Vital Capacity (FVC), Forced Expiratory Volume in 1 second (FEV1), and Peak Expiratory Flow (PEF), then categorized into equal quartiles. Cognition was assessed using Addenbrooke’s Cognitive Examination III (ACE III). The association between pulmonary function and cognition was examined using multiple linear regression with three models: Model 1 – unadjusted, model 2‐adjusted for age and gender, model 3 – adjusted for age, gender, education, smoking status, depression, anxiety, hypertension, diabetes, cardiac illness and respiratory disease.ResultRegression analysis revealed an association between pulmonary function and cognition across all the models. In the fully adjusted model, compared to the lowest quartile (quartile 4), participants in highest quartiles of FVC performed better in ACE [quartile 1 (β = 2.36, 95% CI, 0.56‐4.15, p = 0.01), quartile 2 (β = 2.62, 95% CI, 1.08‐4.15, p = 0.001), quartile 3 (β = 1.87, 95% CI, 0.53‐3.22, p = 0.006)], similarly for PEF, participants in highest quartiles exhibited better ACE score [quartile 1 (β = 3.42, 95% CI, 2.02‐4.82, p <0.001), quartile 2 (β = 3.49, 95% CI, 2.16‐4.81, p <0.001), quartile 3 (β = 3.72, 95% CI, 2.41‐5.03, p ≤0.001)], there was no significant association found between FEV1 and ACE score.ConclusionThese findings indicate the link between pulmonary function and cognitive performance, highlighting the importance of respiratory well‐being in preserving the cognitive function.
A Study on Refractive Errors and Cognitive functions in the Aging Population
Authors: Velavarajan Goutham , M Amitha C , Partha Ajith , M Divya N , R Meghana , Menon Meenakshi , Lingegodwa Abhishek Mensegere , Stezin Albert , S Monisha , HS Dev Kumar , Narayanasamy Rajitha , Vishwanath Vindhya , Malo Palash K , Arvind Prathima , Hameed Shafeeq K Shahul , HS Sunitha , Singh Sadhana , Mondal Banashree , Agrawal Deepashri , Sundarakumar Jonas S. , Issac Thomas Gregor 
Published: January 2025

AbstractBackgroundRefractive errors are common visual comorbidities among the elderly. Cognitive dysfunction also occurs in this population. A study by Ong et al (2013) demonstrated an association of refractive errors with poor cognitive performance. In this study, we explored the potential association between refractive errors (RE) and cognitive functions (CF) in an elderly population from South India.MethodThis cross‐sectional analysis, based on the Tata Longitudinal Study on Aging (CBR‐TLSA) cohort (Sundarakumar et al., 2020), included participants with a minimum visual acuity of ≤ 0.52 LogMar using the LogMAR chart (Aurolab, India). Those meeting the criteria underwent objective refraction with a retinoscope (Welch Allyn, Dublin, USA) to classify RE (Emmetropia, Myopia, Hypermetropia). CF was assessed using Addenbrooke’s Cognitive Examination III (ACE III) and various cognitive tests, including Digit Forward/Backward, Trail Making Test A/B, Modified Taylor Complex Figure Immediate/Delayed Recall, Digit Simple Substitution Test (DSST), and COGNITO (Computerized assessment of adult information processing) battery domain‐specific tests. Cognitive tasks were performed post‐acuity correction with prescription glasses.ResultThe demographic characteristics of the study sample are mentioned in Table 1. Among 856 participants, 149 (17%) were Emmetropes, 224 (26%) were Myopes, and 483 (56%) were Hypermetropes. The Myopes performed poorly in TMT‐B (β = 14.9 (CI: 1.16, 28.68), p = 0.03), MTCF IR (β = ‐2.15 (CI: ‐3.8, ‐0.49), p = 0.01), MTCF DR (β = ‐2.2 (CI: ‐3.9, ‐0.48), p = 0.011), and reading and sentence comprehension (β = ‐0.37 (CI: ‐0.63, ‐0.11), p = 0.004) compared to emmetropes. Hypermetropic showed poor performance in Ace visuo‐spatial (β = ‐0.43 (CI: ‐0.79, ‐0.06), p = 0.02), MTCF DR (β = ‐1.5 (CI: ‐3.08, ‐0.03), p = 0.045), and showed better performance in Digit Forward Total Correct (β = 0.96 (CI:0.03,1.89), p = 0.04) & span (β = 0.53 (CI:0.07,1.004), p = 0.02).ConclusionOur study found that individuals with myopia and hypermetropia performed worse on certain cognitive tests compared to those with normal vision. Myopic individuals struggled with tasks involving complex figure recall and comprehension, while hypermetropic individuals had difficulties with visuospatial tasks and they did better in attention tasks. These findings suggest that corrected RE in older adults could contribute to cognitive challenges and needs to be further researched.
Influence of menopause on cognitive performance in aging Indian women: A cross‐sectional study
Authors: Pradhan Hitesh , Sundarakumar Jonas S. 
Published: January 2025

AbstractBackgroundStudies have reported the neuroprotective role of estrogen, and that the post‐menopausal state could be a risk factor for cognitive decline. However, the relationship between menopausal age and cognitive functions has not been adequately studied in the Indian population.MethodSrinivaspura Neuro Senescence and Cognition (SANSCOG) is an ongoing rural community‐based longitudinal study on aging in India. We analyzed baseline data (January 2018 – April 2023) of 1,473 post‐menopausal women with clinical and neurocognitive assessments. Age at menopause was categorized into premature (<41 years), early (41‐44 years), and normal (45‐54 years). Participants were excluded if they had undergone hormone replacement therapy and attained late menopause (≥55 years). Cognitive performance was assessed using Hindi‐Mental State Examination (HMSE). A linear regression model was used to examine the association between age at menopause and cognitive functions while adjusting for education, marital status, reproductive history, hypertension, diabetes, smoking, physical inactivity, and BMI. We also checked for the interaction between age and menopause.ResultPremature (β = ‐0.76, 95% CI = ‐1.47, ‐0.07) menopause was significantly associated with poorer cognitive performance. Additionally, older age (≥65 years), education, BMI, physical inactivity, and number of children were also significantly associated with cognitive performance. Women aged 65 years and above who attained premature menopause had significantly poorer cognitive performance compared to women aged less than 65 years who attained normal menopause (β = ‐4.64, 95% CI = ‐6.50, ‐2.79).ConclusionOur study shows that menopausal age is associated with cognitive performance. Among older women (≥65 years), premature menopause is adversely associated with cognitive performance, suggesting that the effects of reduced estrogen are likely to be evident in later life. Future work should explore the association of menopausal age with performance across individual cognitive domains and brain MRI.
Extensive antagonistic genetic underpinnings of sex disparities in Alzheimer’s disease and hypertension
Authors: Kulminski Alexander M. , Feng Fan , Kulminskaya Irina , Nazarian Alireza , Loiko Elena , Loika Yury 
Published: January 2025

AbstractBackgroundThe Alzheimer’s Association reports that more than two‐thirds of the approximately 5 million Alzheimer’s disease (AD) cases in the USA are women. With studies suggesting a high genetic heritability for AD, gaining a better understanding of the genetic architecture underlying sex disparities in AD and its risk factors could enhance the understanding of their mechanisms.MethodWe conducted genome‐wide association studies (GWAS) and pleiotropic meta‐analysis of AD and its risk factor—hypertension—in men and women of European ancestry. The AD GWAS focused on 168,962 men (including 6,229 cases) and 199,668 women (including 7,628 cases) from 10 cohorts. The hypertension GWAS included 177,597 men (96,835 cases) and 205,482 women (88,861 cases) from eight of the 10 AD cohorts. Sex‐specific associations were characterized by the Wald chi‐square test and Fisher’s method, and their significance was assessed at a false discovery rate q‐value of 5% or less.ResultGWAS of AD and hypertension identified 176 and 195 loci, respectively, on all chromosomes with the differences in the effects between sexes attaining q<0.05. Associations with AD were of the same directions in men and women only in one—the APOE gene—locus, with significantly larger adverse effect for the ε4‐encoding rs429358 polymorphism in women (β = 1.35, CI = 1.30‐1.41) than men (β = 1.16, CI = 1.10‐1.22). Associations with hypertension were of the same directions in each sex in 74 of 195 loci on all chromosomes, except chromosome 14. The ε4 allele showed no association with hypertension in either sex. No significant differences between sexes in the significant protective associations with AD and hypertension were identified for the ε2 allele. Our analyses revealed seven pleiotropic loci mapped to COL24A1, MGC4859‐PHF14, MFHAS1‐ERI1, SBF2, KICS2, BCL11B, and RPAP1 gene clusters characterized by the differences in the associations with AD and hypertension between sexes at q<0.05. In three underlined clusters, the associations with hypertension were of the same direction in men and women.ConclusionAlthough the APOE ε4 allele partly underlies AD‐related sex disparities, the most substantial contribution comes from antagonistic relationships between genes and AD in men and women. Sex‐specific pleiotropic loci suggest contribution of hypertension to these AD‐related sex disparities.