bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating proteins associated with rate of cognitive decline based on APOE genotype
Authors: Fohner Alison E , Brody Jennifer A. , Sitlani Colleen , Xue Diane , Longstreth W.T. , Odden Michelle , Austin Thomas R. , Gerszten Robert Edgardo , Trittschuh Emily H. , Psaty Bruce M. , Seshadri Sudha 
Published: January 2025

AbstractBackgroundAPOE genotype is the most important genetic risk factor for Alzheimer’s disease (AD), but whether it affects the proteins associated with AD risk is unclear. Circulating proteins may reveal biology underlying pathologic processes.MethodsWe evaluated log2 standardized levels of 4979 proteins quantified using modified aptamer technology [SomaScan] in plasma from 2725 participants in the Cardiovascular Health Study who were free of dementia and stroke. Participants were recruited from 4 sites in the United States and plasma samples were obtained in 1992/1993. Cognitive decline was measured with annual modified mini mental state exams (3MSE) and digit symbol substitution tests (DSST) over 7 years. APOE genotype was classified as e4 carrier, e2 carrier, or non‐carrier. Adjusting for sex, age, race, education, and study site, we used linear mixed effects modeling to evaluate whether the association of each protein with rate of cognitive decline differed based on APOE genotype. We ran two models: one comparing APOE e4 to the other genotypes and another comparing APOE e2 to the other genotypes. A p‐value of 2.1x10‐5 was considered significant.ResultsMean age of participants was 74 years, 61% were female, 15% were Black, 25% were APOE e4 carriers, 17% were APOE e2 carriers, and mean cognitive follow‐up was 5.2 years. For 3MSE, 38 proteins had significant interactions with time and APOE e4 carrier status (Table 1) and 15 proteins with APOE e2 carrier status (Table 2). For DSST, only 3 proteins had significant interaction with time and APOE e4 carrier status and none with APOE e2. Proteins included those involved in lipid transport, neuronal differentiation, immune response, and cell signaling.ConclusionsLarge‐scale proteomic profiling identified circulating proteins differentially associated with cognitive decline based on APOE genotype. Many of the proteins are involved in pathways previously implicated in AD risk. Replication and other characterization are needed to clarify how APOE genotype may affect mechanisms involved in cognitive decline and AD risk.
Prostatic malignancy with paraneoplastic subacute encephalitis with unique imaging characteristics
Authors: Singh Mridula , Sahu Suman Kumar , Kushwaha Suman , Maheshwari Siddharth , Panda Ashwin Kumar , Mustafa Alisha 
Published: January 2025

AbstractBackgroundProstatic malignancy with paraneoplastic subacute encephalitis –A rare syndromeMethodWe present a case of 76 year old male without any previous comorbidity and addiction who manifested a rapid neuropsychiatric decline with a frontotemporal syndrome over a period of 6 months. He was anemic and cerebrospinal fluid study showed 10 cells with lymphocytic predominance. The extensive workup of csf for infection, malignancy revealed nothing. His workup for metabolic, neuroinfection and stroke came out negative. His PSA came 4 times the upper limit and MRI brain showed T2 hyperintensity in left temporal lobe with punctate contrast enhancement and atrophy of right temporal lobe with enlarged temporal horn. His MRI pelvis showed PIRADS 4 lesion highly suggestive of malignancy. His paraneoplastic markers came negative. As our institute being neuropsychiatric one, we had to refer the patient to multispecialty hospital. The patient succumbed to illness within two months after referral from our institute while undergoing treatment for the malignancy.ResultProstatic malignancy causing paraneoplastic rapidly progressive dementia with unusual MRI features.ConclusionLimbic encephalitis presents with short term memory loss, complex partial seizures and neuropsychiatric complaints. Our case presented subacutely as frontotemporal syndrome. The signal abnormalities in the mesial temporal lobes without contrast enhancement are the typical MRI findings. In our case patient had extensive involvement of temporal lobe with contrast enhancement, so likey an overlap between limbic encephalitis and encephalomyelitis. To the best of my knowledge none of the case in past had this MRI feature.
ATN system and disease‐modifying treatment eligibility in a hospital‐based cohort
Authors: Cecchetti Giordano , Canu Elisa , Rugarli Giulia , Coraglia Federico , Basaia Silvia , Calloni Sonia Francesca , Vezzulli Paolo Q. , Spinelli Edoardo G. , Santangelo Roberto , Caso Francesca , Falini Andrea , Magnani Giuseppe , Filippi Massimo , Agosta Federica 
Published: January 2025

AbstractBackgroundThis study aims at applying the AT(N) classification to a cohort of patients with Alzheimer’s disease (AD) and related disorders, and to investigate how many cases would be eligible for the emerging disease‐modifying treatments.MethodWe conducted a retrospective evaluation of 429 patients referred to the Memory Center of IRCCS San Raffaele Hospital in Milan. Patients underwent clinical/neuropsychological assessments, lumbar puncture, structural brain imaging, and positron emission tomography (FDG‐PET). Patients were stratified according to AT(N) classification, group comparisons were performed and the number of eligible cases for anti‐β amyloid monoclonal antibodies was calculated.ResultSociodemographic and clinical features were similar across groups. Although the clinical presentation was similar, the A+T+N+ group showed more severe cognitive impairment in memory, language, attention, executive, and visuospatial functions compared to other AT(N) groups. Notably, T+ patients demonstrated greater memory complaints compared to T‐ cases. FDG‐PET outperformed MRI and CT in distinguishing A+ from A‐ patients. Although the 60.8% of the observed cases were A+, only the 17.2% were eligible for amyloid‐targeting treatments.ConclusionThe AT(N) classification is applicable in a real‐world clinical setting. The classification system provided insights into clinical management and treatment strategies. Low cognitive performance and specific regional FDG‐PET hypometabolism at diagnosis are highly suggestive for A+T+ or A‐T+ profiles. This work provides also a realistic picture of the proportion of AD patients eligible for disease modifying treatments emphasizing the need for early detection.Funding: Foundation Research on Alzheimer Disease. Next Generation EU/National Recovery and Resilience Plan, Investment PE8‐Project Age‐It.
Microstructural assessment of the locus coeruleus‐entorhinal cortex pathway and association with ATN markers in patients with cognitive impairment
Authors: Aiello Marco , Borrelli Pasquale , Cavaliere Carlo , Marizzoni Moira , Ribaldi Federica , Garibotto Valentina , Scheffler Max , Jelescu Ileana O , Jovicich Jorge , Salvatore Marco , Frisoni Giovanni B. , Pievani Michela 
Published: January 2025

AbstractBackgroundThis study investigated microstructural features of the locus coeruleus to entorhinal cortex pathway (LC‐EC) in relation to amyloid (A), tau (T), neurodegeneration (N) markers and cognitive impairment in memory clinic patients.Method124 participants were recruited from the Geneva Memory Clinic (n=30 cognitively unimpaired – CU; n=80 MCI and n=14 dementia ‐ CI) and underwent clinical assessment, 3T MRI scan including diffusion weighted imaging, amyloid PET, and tau PET. Diffusivity indices (fractional anisotropy ‐ FA, mean, axial and radial diffusivities ‐ MD, AxD, RD) were assessed in the LC‐EC pathway using a probabilistic atlas. A, T, N markers were assessed both as continuous and dichotomous measures. Differences in LC‐EC microstructure according to ATN markers and diagnosis were assessed with ANOVA models (FDR correction). Linear regression models were used to test whether LC‐EC pathway microstructure predicted cognitive impairment independently of ATN markers.ResultLower FA (p=0.020) and higher MD, RD and AxD (p<0.005) was observed in participants with tau positivity in the EC (TEC+, Braak stage ≥1) compared to tau negative subjects (TEC‐). Higher MD, RD and AxD was observed in neurodegeneration positive (N+, medial temporal atrophy) versus negative (N‐) participants (p<0.001), and CI versus CU (p<0.016). There was no difference in LC‐TE microstructure between amyloid positive (A+) and negative (A‐) subjects (p>0.05) nor between tau positive (T+; Braak stage ≥4) and negative (T‐) subjects (p>0.05). The regression model showed that RD of the LC‐EC tract was associated with clinical diagnosis and mini mental state examination score independently of ATN markers (p<0.05).ConclusionOur results indicate that LC‐EC microstructural measures, specifically RD, are sensitive in detecting CI and provide complementary information over ATN biomarkers. Associations with T suggest that LC‐TE microstructural alterations show regional specificity in the EC.
Mapping culturally sensitive assessment and care for Moroccan migrants with dementia in Spain
Authors: Taiebine Mohamed 
Published: January 2025

AbstractBackgroundGiven the context of globalization, epidemiological and health disparities create socio‐cultural barriers to specialized and appropriate care for people living with dementia in non‐Western countries, particularly in Spain, where Moroccan migrants maintain their position as the largest registered foreign community. We aimed to map cultural, clinical, and linguistic challenges and facilitators of dementia assessment and care for this population.MethodsWe investigated articles published in English, Spanish, and Arabic in different medical, allied health, social, and human sciences databases that addressed assessment and care for Moroccan migrants with dementia (MMWD) and their caregivers in Spain. Demographic, epidemiological, clinical, linguistic, socio‐cultural, and socio‐economic features as well as facilitators and barriers to assessment and care were summarized.ResultsThe main findings emphasized the importance of embracing the socio‐cultural values of the host country, as well as maintaining bi‐cultural and bilingual status. The principal challenges included lack of translating and interpreting services, paucity of neurocognitive tools in Moroccan Arabic, and dearth of bi‐cultural and bilingual practitioners, while the facilitators were mainly the training of healthcare staff about dementia and capitalizing on cross‐cultural translation and adaptation of best evidence‐based interventions and assessment tools in dementia in Moroccan Arabic and Spanish.ConclusionsEnabling cultural appreciation, inclusion and cross‐cultural competency should encourage stakeholders, practitioners, caregivers, and clients to respond culturally and linguistically to the unique features of elderly Moroccan Arabic migrants or those who are well‐established as Moroccan‐Spanish citizens. Implementing person‐centered care and culturally salutogenic approaches might erase frontiers in language, care, culture, and place of origin.
MRI‐driven Analysis of EEG Connectivity in Alzheimer’s Disease and Behavioral Frontotemporal Dementia
Authors: Cecchetti Giordano , Basaia Silvia , Canu Elisa , Curti Davide G. , Cursi Marco , Spinelli Edoardo G. , Caso Francesca , Fanelli Giovanna F. , Bellini Anna , Magnani Giuseppe , Agosta Federica , Filippi Massimo 
Published: January 2025

AbstractBackgroundPrevious EEG studies highlighted the potential of analyzing neural oscillatory activity for differentially diagnosing Alzheimer’s disease (AD) and frontotemporal dementia (FTD). We recently studied primary progressive aphasia (PPA) variants associated with AD and FTD, revealing distinctive patterns of alterations in linear lagged connectivity (LLC) values within the default mode network (DMN) and the salience network (SN). This study utilizes the same functional MRI‐driven model for source reconstruction to investigate LLC values across typical amnestic AD and the behavioral variant of FTD (bvFTD).MethodIn this cross‐sectional, single‐center study, we consecutively recruited AD, bvFTD, and healthy subjects from the Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. Resting‐state 19‐channel EEG data were acquired, and LLC values estimated across 6239 voxels at the whole‐brain level using standardized low‐resolution brain electromagnetic tomography (sLORETA). Subsequently, LLC values were averaged within SN and DMN maps derived from functional MRI data of healthy controls using seed‐based analysis. Network‐based statistics (5000 permutations‐based adjustment) were employed to compare LLC values among study groups.Result39 bvFTD patients, 39 AD subjects, and 21 healthy controls were enrolled. AD patients exhibited elevated connectivity at delta frequency band in both DMN and SN (p<0.01), and decreased values at alpha2 band in both DMN (p = 0.04) and SN (p = 0.03) compared to controls. Furthermore, AD patients displayed higher LLC values at theta band than both bvFTD and healthy subjects within both DMN and SN (p = 0.01). BvFTD patients exhibited a significant increase in EEG connectivity at delta band compared to healthy individuals, specifically within SN (p = 0.05). No other significant differences were observed.ConclusionLLC findings in AD patients align with our previous studies, indicating a comprehensive disruption of neural oscillatory activity, with theta frequency band emerging as a potential biomarker of AD. Consistent with our study in PPA patients, FTD patients exhibited a connectivity alterations at delta band limited to anterior cerebral regions. EEG holds promise in the differential diagnosis between AD and bvFTD, suggesting a link with underlying pathology.Funding: Foundation Research on Alzheimer Disease. Next Generation EU/National Recovery and Resilience Plan, Investment PE8‐Project Age‐It.
Efficacy of vocal biomarkers in detecting cognitive impairment: interim findings from US and Indian populations
Authors: Larsen Erik , Murton Olivia , Song Xinyu , Weiss Erica , Emmeline Ayers , Zwerling Jessica , Sharath Veena , Jacob Soumya , Sigamani Alben , Pradeep V.G. , Verghese Joe 
Published: January 2025

AbstractBackgroundVocal biomarkers are emerging as potentially meaningful health indicators in multiple domains, including cognition. Because voice‐enabled devices are widespread, automated vocal analysis could become a useful modality for early detection and monitoring of cognitive impairment. To assess the efficacy of vocal biomarkers in identifying cognitive impairment we evaluated prosodic speech features on vocal tasks in a research cohort from Kerala, India, and a referral cohort from the Montefiore‐Einstein Center for the Aging Brain in the Bronx, NY.Methods157 participants (38% female, mean age 67 (4.9)) in India, and 57 participants (65% female, mean age 76 (6.3)) in NY completed voice protocols and cognitive screening (Addenbrooke's Cognitive Examination‐III in India, mean 81 (13); Blessed Information Memory Concentration Test in NY, mean 6.0 (3.7)). Prosodic speech features on vocal tasks with low and high mental effort were compared to performance on cognitive screening. Speech feature values were characterized using means and standard deviations, and subgroup distributions were compared using ratio of means, Cohen’s d for effect size, and significance testing using independent sample t‐tests.ResultsMean speech rate across conditions in syllables/minute was 100 (37) for the India and 107 (34) for the US cohort; pause duration in seconds was 0.68 (0.40) and 0.56 (0.33), respectively. Participants with worse performance on cognitive screening exhibited reduced speech rates and increased pause durations—23% variation in the Indian and 4% in the US cohort. Tasks with higher mental effort mirrored these effects, with about 25% variation in both cohorts. Mental effort had medium to large effect size (0.6‐0.9) and was statistically significant (p<0.01), while cognitive impairment achieved similar effect size and statistical significance for the India cohort only.ConclusionThese preliminary findings reinforce the potential of vocal biomarkers, especially speech rate and pause duration, as potential indicators of cognitive impairment in older adults. The results align with our goals to develop accessible vocal biomarker technology and support continued investigation into their utility in clinical and everyday settings, development of predictive analytics, and incorporating these into existing vocal biomarker platforms.
Association between gene expression and neurodegeneration in dementia with Lewy bodies
Authors: Habich Annegret , Baumann Janna M. , Schwarz Christopher G. , Przybelski Scott A. , Pardini Matteo , Calizzano Francesco , Inguanzo Anna , Oppedal Ketil , Blanc Frédéric , Lemstra Afina Willemina , Hort Jakub , Brendel Matthias , Ochoa‐Figueroa Miguel A , Garibotto Valentina , Kramberger Milica G. , pilotto andrea , Boeve Brad F. , Aarsland Dag , Westman Eric , Dierks Thomas , Kantarci Kejal , Morbelli Silvia , Jonkman Laura E. , Ferreira Daniel 
Published: January 2025

AbstractBackgroundPatterns of regional atrophy and hypometabolism have been observed in dementia with Lewy bodies (DLB). However, determinants of regional vulnerability to structural and functional neurodegeneration remain largely unexplored. First, we investigated the association between regional gene expression and grey matter volumes in probable DLB patients. Since hypometabolism presumably precedes overt brain atrophy, we additionally investigate the association between regional gene expression and hypometabolism in DLB.MethodTo investigate the association between gene expression and regional volumes, 165 DLB patients along with 165 age‐ and sex‐matched healthy controls from three European centres and the Mayo Clinic (USA) were included. Regional volumes were quantified from MRI using SPM12 in 112 cortical, subcortical, and cerebellar brain regions, and compared between groups, using w‐scores. Regional expression data of seven genes involved in the formation and degradation of pathological protein aggregates (APOE, APP, BIN1, GBA, MAPT, SNCA, TMEM175) was extracted from six healthy donors from the Allen Human Brain Atlas and correlated with regional volumetric w‐scores. To assess the predictive value of regional gene expression on regional volumes we used Gaussian stepwise backwards linear regression including all seven genes as predictors. To investigate the association between gene expression and hypometabolism, we are currently applying the same analysis pipeline to FDG‐PET data of 139 DLB patients from 8 European centres.ResultMost brain regions showed lower volumes in DLB patients compared to healthy controls, with differences being most pronounced in occipital and parietal lobes. Regional expression of APOE correlated positively with regional volumes in DLB. Conversely, regional expression of MAPT correlated negatively with regional volumes. Both APOE and MAPT gene expression were significant predictors of regional volumes in the regression analysis. None of the other gene expression values was significantly associated with regional volumes in DLB.ConclusionOur findings show that regional expression of genes associated with the abnormal accumulation of amyloid and tau, common co‐pathologies in DLB, partially account for the brain atrophy pattern observed in DLB patients. Analyses are ongoing for the hypometabolism pattern. Our finding emphasises the relevance of co‐pathologies in predicting atrophy progression and identifying potential targets for future disease‐modifying treatments.
Relationship Between Social Support and Global Cognition by Level of Neighborhood Disadvantage in the HABS‐HD Cohort
Authors: Rhoads Tasha , Cobos Kimberly , O'Bryant Sid E. , Miller Justin B ,   the HABS‐HD Study Team
Published: January 2025

AbstractBackgroundPrior research has demonstrated the positive association between social support and cognition. Specifically, greater social support has been linked with improved cognitive performance and reduced risk of dementia. In particular, emotional support has been identified as a key dimension in the relationship between social support and cognition. This study examined how the relationship between social support and cognitive functioning varies by neighborhood disadvantage, as measured by the Area Deprivation Index (ADI), in a diverse sample of older adults.MethodData from 2811 participants (629 Non‐Hispanic Black, 1107 Hispanic, 1075 non‐Hispanic White individuals) from the community‐based Health & Aging Brain Study–Health Disparities (HABS‐HD) cohort were examined. Three composite social support subscales were computed based on self‐report questionnaire responses to describe the following dimensions: Companion support (e.g., accompanying an individual during activities), Emotional support (e.g., having others to confide in or turn to for advice), and Assistance support (e.g., providing help with household tasks). Separate regressions were stratified by ADI quintile. Each regression included all subscales as predictors along with age, sex, and education as covariates. The Mini‐Mental State Exam (MMSE) Total Score was used to reflect global cognition (outcome).ResultRegressions indicated overall significant models for each level of neighborhood disadvantage. Within ADI 1 (least disadvantage), ADI 2, and ADI 5 (greatest disadvantage), Assistance support emerged as a significant predictor of global cognition. Within ADI 2, Companion support also significantly predicted global cognition. Finally, within ADI 3, Emotional support significantly predicted global cognition. There were no significant social support subscale predictors evident within ADI 4.ConclusionOverall, these findings highlight the generally robust, protective effect of social support on cognitive abilities in this large, diverse cohort of older adults. However, variations across subtypes of social support between neighborhood contexts were evident. This highlights the importance of social support for brain health among individuals across levels of socioeconomic status, although these effects may be somewhat weaker at higher levels of neighborhood disadvantage. This finding underscores the fact that greater resources to promote brain health should be directed towards individuals living in areas of greater neighborhood disadvantage.