bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of a short version of the Everyday Cognition scale (ECog‐12) to detect cognitive impairment
Authors: Manjavong Manchumad , Diaz Adam , Eichenbaum Joseph , Ashford Miriam T. , Aaronson Anna , Miller Melanie J. , Kang Jae Myeong , Mackin Scott R , Tank Rachana , Landavazo Bernard , Truran‐Sacrey Diana , Farias Sarah Tomaszewski , Weiner Michael S. W. , Nosheny Rachel L. 
Published: January 2025

AbstractBackgroundThe Everyday Cognition questionnaire is a sensitive tool for measuring decline in activities of daily living and can differentiate dementia from normal cognition. There is limited data on comparing the ECog‐12 performance by raters (self vs. informant/study‐partner) and scoring systems (continuous average score vs. a categorical grouping) to differentiate cognitive statuses.MethodECog‐12 data were extracted from the 39‐item version collected in the Alzheimer’s Disease Neuroimaging Initiative. Participants (n = 1593) were divided into subgroups based on diagnosis. The average and categorized ECog‐12 scores were calculated. Logistic regression was used to evaluate the ECog‐12 performance in five different diagnostic groups, including discriminating between cognitively unimpaired (CU; n = 666) vs. cognitive impairment (CI; MCI and AD), CU vs. MCI (n = 707), CU vs. AD (n = 220), AD vs. MCI, and CI with amyloid pathology (n = 532) vs others. Simple logistic regression models with the ECog‐12 score as the sole independent variable were used to evaluate the association with CI, and multiple logistic regression models with participant characteristics included as covariates. This procedure was repeated for self/participants (PT) and study‐partners (SP; n = 1571) reports.ResultECog‐12 cut‐off scores of 1.36 (PT) and 1.45 (SP) distinguish CU from CI with AUC 0.7 (0.68‐0.73) and 0.78 (0.76‐0.8). Adding a memory‐concern question to the ECog‐12 of PT increased the AUC to 0.78. Any consistent SCD (categorized scores) of PT and SP provided AUC 0.69 (0.67‐0.71) and 0.78 (0.76‐0.8). Average ECog‐12 of PT and SP can differentiate between MCI and CU (AUC: 0.69, 0.75), AD and CU (AUC: 0.74, 0.93), AD and MCI (AUC: 0.57, 0.77), and amyloid‐positive CI and others (AUC: 0.65, 0.75). Average ECog‐12 of SP had a higher association with CI than PT (OR 35.45 vs. 8.79, 95%CI 22.41‐58.03 and 6.32‐12.43, respectively).ConclusionThe ECog‐12 of SP showed higher performance in differentiating between the different cognitive statuses and higher prognostic value than that of PT. A memory concern question enhanced the performance of ECog‐12 of PT. The ECog‐12 (PT and/or SP) could be a valuable tool for quickly (and potentially remotely) assessing a person’s cognitive status for research studies and in clinical practice.
Cognitive screening in the emergency department: Agreement between the patient‐ and caregiver‐completed AD8
Authors: Galske James , Sather Anna , Chera Tonya , Hwang Ula , Carpenter Christopher R , Gettel Cameron 
Published: January 2025

AbstractBackgroundImpaired cognition is prevalent in older adults in the emergency department (ED), but many cases go unrecognized. The Ascertain Dementia 8 (AD8) is a validated, self‐administered screening tool that can be used by patients and caregivers to assess for early cognitive changes associated with dementia. However, little is known regarding the degree of alignment between respondents in the ED setting. Our objective was to assess the agreement between the patient‐(pAD8) versus caregiver‐completed AD8 (cAD8).MethodsWe conducted a prospective observational study of community‐dwelling older adults aged 65+ years seeking emergency care and their caregivers between October 2021 and November 2023. Patients with a diagnosis of dementia indicated in the electronic health record were excluded. Collected by trained research assistants, AD8 scores ranged from 0‐8, with scores 2+ indicating cognitive impairment. Patients and caregivers were blinded to the others’ AD8 rating. The intraclass correlation coefficient (ICC) was used to assess the agreement of the presence or absence of cognitive impairment based on pAD8 and cAD8 scores.ResultsOur analytic sample included 538 dyads, of which 34.7% of patients were male with a mean age of 73.5. A total of 132 (24.5%) patients scored themselves as cognitively impaired versus 201 (37.4%) patients were scored as cognitively impaired by their caregivers. Between groups, an ICC of 0.519 (95% CI 0.454‐0.578) demonstrated moderate agreement in identifying cognitive impairment based on pAD8 and cAD8 scores.ConclusionApproximately 1 in 4 older adults without a dementia diagnosis in the emergency department identified themselves as having cognitive impairment, with caregivers even more likely to identify cognitive impairment in accompanied older adult patients. With current guidance suggesting that the pAD8 be used in the absence of the cAD8, these findings highlight important differences to account for based on the respondent when screening for cognitive impairment.
APP Gene Duplication Unraveled: A Unique Case of Atypical Dementia with Prominent Psychiatric Concerns in a Hispanic Male
Authors: Castro Julia , Velazquez Sandra Azareli Garcia , Kautz Tiffany F. , Mendoza Crystal , Salardini Arash , Seshadri Sudha , Parker Alicia S. , Sullivan A. Campbell 
Published: January 2025

AbstractBackgroundAPP duplications are a rare form of familial Alzheimer’s disease (AD). Research has shown variability in clinical presentation with full duplications. There is limited information on those with partial duplications, especially in underrepresented minorities.MethodsA 64 y/o Hispanic male presented with a 2.5 year history of anxiety, restlessness, coarsening behavior, cognitive and functional decline, and motor changes. We present findings from neuropsychological evaluation, neurological exam, neuroimaging, and genetic testing. Plasma‐based biomarkers are pending.ResultsThe clinical course is notable for rapid onset of anxiety at age 62 with intrusive thoughts, delusional beliefs, and repeated psychiatric hospitalizations. Motor changes include myoclonic jerks, increased restless with pacing and rocking, and bradykinesia. The family described a 30lb weight loss without dieting, dietary changes with a preference for sweets, withdrawal from social interactions, and poor judgment. DaT scan was positive; synuclein biopsy was negative. Brain MRI revealed remote left basal ganglia lacune and superficial parietal atrophy. Neuropsychological assessment revealed prominent executive dysfunction, and amnestic verbal learning and recall, with preserved visual learning. Family history included late‐onset forgetfulness in his mother and abnormal behaviors in maternal half‐cousins.Genetic sequencing uncovered a partial APP gene duplication (exons 1‐11, including the initiator codon). Illumina SNP chromosomal microarray confirmed a 21q duplication also including the CYYR‐1 and CYYR1‐AS1 genes, with the partial APP duplication defined as “uncertain” per ACMG guidelines.ConclusionThis case study describes an atypical dementia syndrome in a 64 y/o Hispanic male with a partial APP gene duplication. The clinical syndrome is notable for neuropsychiatric symptoms and parkinsonism. This report is consistent with recent work highlighting atypical dementia among a small proportion of those with APP duplications. However, our findings show the ramifications of a partial duplication within an underrepresented population, emphasizing the need for further exploration.
Brain Barrier Aging is Associated with Changes in Brain Plasticity and Decline in Processing Speed: A Proteomic Study of Human Cerebrospinal Fluid
Authors: Elahi Fanny 
Published: January 2025

AbstractBackgroundProtective brain barriers, such as blood‐brain barrier, become dysfunctional with age. The BBB is a dynamic and selective barrier, gating the passage of molecules and cells to and from the brain. The function of this barrier is critical for the maintenance of brain homeostasis. BBB dysfunction has been reported in aging and disease states, with downstream consequences on long‐range neuro‐glial networks subserving emotions, cognition, movement, and sensations. The molecular mediators of the effect of BBB leakage on neuro‐glial networks is not well understood.MethodsUsing large‐scale proteomics and targeted ELISA assays to interrogate over 7000 proteins in cerebrospinal fluid (CSF) of highly phenotyped aging older adults, we interrogated signatures of BBB dysfunction in aging and AD. Our analytical workflow consisted of principal component analysis, linear modeling, and ontology analyses.ResultsWe identified distinct CSF‐proteomic signatures for leaky BBB and demonstrate associations with markers of synaptic dysfunction and slowed processing speed. We found several associations between BBB leakage and upregulation in pathways classically thought to be neurodevelopmental including Ephrin and neuropilin signaling. We validated our findings in an independent Alzheimer’s disease dataset.ConclusionThis study presents a multivariate approach for investigating large‐scale omics data and provides insights into the potential mechanisms for vascular cognitive aging, with a focus on aging of the brain’s barriers.
Psychosis in Neurocognitive Disorder for Ethnoculturally Diverse Older Persons
Authors: Isaac Estevana Juanita , Federman Alex , Sano Mary , Siu Albert , Mindt Monica Rivera , Zhu Carolyn W. 
Published: January 2025

AbstractBackgroundThere is longstanding evidence that the presence of psychosis in neurocognitive disorders is associated with faster deterioration of cognitive function. These reports also describe greater care partner burden, higher rates of institutionalization and functional decline, especially among ethnoculturally diverse persons. The goal of this study is to examine the association of race/ethnicity with rates of psychosis in neurocognitive disorders among ethnoculturally diverse older persons.MethodData are from the National Alzheimer’s Coordinating Center Uniform Dataset, a longitudinal dataset with annual patient assessments from ∼40 National Institute of Aging funded Alzheimer’s Disease Research Centers. Participants aged 40‐95 years as of June 2023 with mild cognitive impairment (MCI) or dementia were included. Psychosis was defined as clinician diagnosed visual or auditory hallucinations or delusions. Race and ethnicity were self‐reports categorized as non‐Hispanic White (NHW), NH‐Black/African American (AA), Hispanic/Latino, Asian, and American Indian/Native Alaskan (AI/NA). Associations between race/ethnicity and psychosis were estimated using multivariable generalized estimating equation (GEE) models with repeated measures of outcomes and covariates (severity of cognitive impairment, age, sex, history of anti‐psychotic medication use and history of mood disorder). Analyses stratified by age of cognitive impairment onset (40‐65 years and 65‐95 years) were also performed.Result25,731 participants had a mean age 72.5±9.7, 51% female, 76% NHW, 12% NH‐Black/AA, 8% Hispanic/Latino, 3% Asian and 1% AI/NA (Table 1). At baseline, 15,646 (60.8%) had MCI and 10,085 (39.2%) had dementia. The rate of psychosis was highest among Hispanic/Latino (15.7%), AI/NA (14.7%) and Black/AA (12.5%) (Graph1). In adjusted analysis, NH‐Black/AA had significantly greater odds of psychosis (OR 1.73, 95% CI 1.17‐2.19), including visual hallucinations (OR 1.33, 95% CI 1.18‐1.51), auditory hallucinations (OR 1.69, 95% CI 1.41‐2.03) and delusions (OR 1.73, 95% CI 1.56‐1.92) (p<0.05) (Table 2). Hispanic/Latino and AI/NA participants had even greater odds of psychosis than NHWs (Table 2). Only Black/AA and Hispanic/Latino participants with early‐onset neurocognitive disorder (40‐65 years) had greater odds of psychosis than NHWs (Table 2).ConclusionBlack/AA, Hispanic/Latino and AI/NA individuals were more likely to be diagnosed with psychosis in neurocognitive disorders when compared to NHWs. More research is needed to explore psychosocial, neuropathology and genetic factors involved.
Global and local process on the Rey Complex Figure Test in older adults
Authors: Seo Eun Hyun , Yoon Hyung‐Jun , Kim Seung Gon , Choi Kyu Yeong , Ha Jung‐Min , Kim Hoowon , Lee Kun Ho 
Published: January 2025

AbstractBackgroundRecent studies have shown that the Rey Complex Figure Test (RCFT) is useful for early detection of Alzheimer’s disease (AD). While RCFT is known as a test for visuoconstruction and memory, it demands executive components during copying and recalling of the complex figure. This study aims to explore which features of executive function are involved in RCFT performance and which of them are clinically significant indicators in older adults.MethodWe included 4540 participants (2384 cognitively normal, 272 subjective cognitive decline, 1662 mild cognitive impairment, 222 dementia) from the GARD Cohort in Korea. Based on the qualitative analysis by Cherrier et al (1999), we further divided the RCFT score into six groups (gestalt/ detail/ left/ right/ upper/ lower) to explore specific executive component. The RCFT subscores were compared between groups using ANCOVAs. Partial eta squared (η2p
) was calculated for effect size. Linear regression analysis with stepwise selection was performed to examine associations between the RCFT subscores and other neuropychological scores.ResultThe six subscores from copy, immediate recall, and delayed recall trials were all significantly different among CN, SCD, MCI, and dementia groups. Based on η2p, ‘detail’ score on copy trial (η2p, = 0.228) ‘gestalt’ scores on memory trials (η2p, = 0.185 for delayed; η2p, = 0.213 for delayed) showed largest effects. In terms of relations to cognitive domain, for copy trial, both ‘gestalt’ and ‘detail’ scores were associated with tests of psychomotor (ß = 0.074∼0.193, all p <0.0001), delayed verbal memory (ß = 0.067∼0.077, all p <0.0001), and executive functions (ß = ‐0.176∼‐0.185, all p <0.0001). For memory trials, ‘gestalt’ scores were mainly associated with tests of executive functions (ß = ‐0.069∼‐0.100, all p <0.0001), whereas, ‘detail’ scores were mainly associated with tests of psychomotor and attention (ß = ‐0.073∼‐0.144, all p <0.0001).ConclusionOur results suggest that the RCFT performance involves cognitive process regarding strategic planning and organization of a fractional figure into whole object. In particular, local process on copy trial, measured by ‘detail’ score and global process on memory trials, measured by ‘gestalt’ score may be a useful indicator of early cognitive impairment. It may be necessary to collect procedural features during RCFT performance to capture perceptual organisation strategies.
Does Apolipoprotein E polymorphism play a role in familial Alzheimer’s Dementia
Authors: Vinod Pratibha , Sen Somdatta , Jayasankar Pavithra , Janardhanan Meghana , Paul Pradip , Viswanath Biju , Jain Sanjeev , Harbishettar Vijaykumar , Sivakumar Palanimuthu Thangaraju , Purushottam Meera 
Published: January 2025

AbstractBackgroundApo E4 is the best studied genetic risk factor for sporadic Alzheimer’s disease. Apo E2 homozygosity is associated with a lower risk of Alzheimer’s disease. While rare and common variants in genes encoding APP metabolism are strongly linked to familial dementia, however family history and ApoE 4 genetic risks have been found to co‐occur.Aim to evaluate the frequency of Apo E polymorphisms and their relationship with the of family history and clinical characteristics in a cohort of 483 patients with Alzheimer’s dementia.MethodPersons with Alzheimer’s dementia were identified from a tertiary care center in India. Their family history status, and detailed clinical characteristics were collected. Genotyping was done at the apolipoprotein E (Apo E) locus using real time PCR.ResultOf the 483 patients analyzed; 142 patients had a family history of Alzheimer’s dementia in at least one first degree relative. Absence of Apo E2 homozygosity was noted in the sample. Patients with family history had a higher likelihood of an Apo E4 carrier status (OR = 1.6071; Confidence Interval 1.0840 to 2.3829 p = 0.00182).The Apo E4 frequency in the overall sample was 25.05%.ConclusionThere is a correlation between Apo E4 carrier status and the likelihood of a positive family history. It remains to be known whether family history effects are separable from Apo E4 related effects.
Poor sleep quality as a potential trigger for cognitive deficits
Authors: Carnes Anna , Piñol‐Ripoll Gerard , Ariza M , Cano N , Segura Barbara , Junqué Carme , Garoellda M 
Published: January 2025

AbstractBackgroundIn the present study we aimed to assess the cognition of post‐COVID condition (PCC) participants regarding their sleep quality, and to analyse different possible moderators of this effect, such as quality of life (European Quality of Life‐5 Dimensions, EQ‐5D), fatigue (Chadler Fatigue Questionnaire, CFQ), cognitive reserve (Cognitive Reserve Questionnaire, CRC), and subjective cognitive complaints (Memory Failures of Everyday Questionnaire, MFE‐30).MethodWe included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) that were assessed with a comprehensive neuropsychological battery and different questionnaires.ResultWe included 373 individuals with PCC and 126 healthy controls (HCs) from the NAUTILUS Project (NCT05307549 and NCT05307575) that were assessed with a comprehensive neuropsychological battery and different questionnaires. We found that PCC participants with poor sleep quality have a 4.3% greater risk of having immediate verbal memory deficits the greater the MFE‐30 score (Odd Ratio (OR) 1,043; Confidence Interval (CI) 1,023‐1,063). Also, they multiply their risk of having immediate verbal memory disorders by 2.4 when the EQ‐5D is low (OR 0,33; CI 0,145‐0,748), and they have less risk of having delayed visual memory deficits the greater the CRC (OR 0,963; CI 0,929‐0,999). With processing speed performance, PCC participants and poor sleep quality have a 6.7% greater risk of having deficits the greater the MFE (OR 1,059; CI 1,024‐1,096) and the risk of slowing processing speed triples the lower the EQ‐5D (OR 0,021; CI 0,003‐0,141).ConclusionThese results indicate that poor subjective sleep quality plays a role as a potential trigger for cognitive deficits. Therapeutic strategies to maximize sleep quality would be reducing not only sleep disturbances, but perhaps also cognitive impairment in PCC participants.
Functional connectivity associations with markers of disease progression in GRN mutation carriers
Authors: Flagan Taru M. , Chu Stephanie A. , Häkkinen Suvi , Zhang Liwen , McFall David , Heller Carolin , Rohrer Jonathan D. , Brown Jesse A. , Lee Alex Jihun , Fernhoff Kristen , Pasquini Lorenzo , Mandelli Maria Luisa , Tempini Maria Luisa Gorno , Yokoyama Jennifer S. , Sturm Virginia , Appleby Brian , Dickerson Brad C , Domoto‐Reilly Kimiko , Foroud Tatiana M. , Geschwind Daniel H. , Ghoshal Nupur , Graff‐Radford Neill R , Grossman Murray , Hsiung Ging‐Yuek Robin , Huang Eric J. , Huey Edward D. , Kantarci Kejal , Karydas Anna M. , Kaufer Daniel , Knopman David S. , Litvan Irene , MacKenzie Ian R , Mendez Mario F. , Onyike Chiadi U. , Petrucelli Leonard , Ramos Eliana Marisa , Roberson Erik D , Rojas Julio C. , Tartaglia Maria Carmela , Toga Arthur W. , Weintraub Sandra , Forsberg Leah K. , Heuer Hilary W. , Boeve Brad F. , Boxer Adam L. , Rosen Howard J. , Miller Bruce L. , Moreno Fermin , Seeley William W. , Lee Suzee E. ,   the ARTFL/LEFFTDS Consortia
Published: January 2025

AbstractBackgroundAutosomal dominant progranulin (GRN) mutations are a common genetic cause of frontotemporal lobar degeneration. Though clinical trials for GRN‐related therapies are underway, there is an unmet need for biomarkers that can predict symptom onset and track disease progression. We previously showed that presymptomatic GRN carriers exhibit thalamocortical hyperconnectivity that increases with age when they are presumably closer to symptom onset. However, whether hyperconnectivity arises concomitantly with markers of neurodegeneration remains unclear.MethodUtilizing T1 and task‐free functional magnetic resonance imaging (tf‐fMRI) from 49 presymptomatic and 26 symptomatic GRN mutation carriers, we determined the relationships between functional connectivity as measured by voxel‐wise whole brain degree and GRN‐relevant markers of disease progression, which included plasma neurofilament light chain (NfL) concentrations, CSF complement C1q and C3b protein levels, grey matter atrophy, and OCD symptom severity.ResultNfL concentrations were associated with frontotemporoparietal and thalamic hyperconnectivity in presymptomatic GRN carriers and extensive regions of atrophy in symptomatic carriers. Complement levels were associated with regions of hyperconnectivity, but not gray matter, in symptomatic carriers. Presymptomatic carriers with thalamic hyperconnectivity tended to have lower grey matter volume in bilateral insula and left lateral parietal cortex, which are among regions that deteriorate in GRN‐FTD. OCD symptom severity was associated with hypoconnectivity across all GRN carriers.ConclusionIn presymptomatic carriers, the co‐occurrence of hyperconnectivity, high NfL, and low gray matter suggests that tf‐fMRI hyperconnectivity may portend the onset of the neurodegenerative phase. These findings point toward hyperconnectivity as an indicator of approaching symptomatic onset.
Moving along the ALS‐bvFTD spectrum: changes in MEG‐based brain network topology
Authors: Govaarts Rosanne 
Published: January 2025

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) with only motor impairment (ALS‐pure motor) and the behavioral variant of frontotemporal dementia (bvFTD) are hypothesized to be the extreme ends of the ALS‐bvFTD spectrum. This spectrum also encompasses ALS patients with mild to severe cognitive impairment (ALSci) and/or behavioral impairment (ALSbi), including ALS with concomitant bvFTD.In a previous study, using magnetoencephalography (MEG), in early symptomatic ALS patients we showed resting‐state functional connectivity changes in frontal, limbic and subcortical regions that overlap considerably with bvFTD. These findings showed the potential of MEG to detect brain changes in early symptomatic phases of ALS and contribute to our understanding of the disease spectrum, with ALS and bvFTD at the two extreme ends.In our current study we used MEG in a longitudinal design, to investigate the changes in brain network topology of ALSci/bi over time as compared to ALS‐pure motor and bvFTD patients.MethodResting‐state MEG was recorded in ALS‐pure motor (n = 9), ALSci/bi (n = 16) and bvFTD (n = 16) at baseline and mean (SD) 5.4‐month (0.8) follow‐up, and projected to source‐space. The corrected version of the amplitude envelope correlation (AECc) was applied to compute frequency‐band specific functional connectivity between brain regions, from which the backbone of the functional networks was constructed using the Minimum Spanning Tree (MST) approach. Reference MSTs were computed based on the average functional connectivity matrix for either ALS‐pure motor or bvFTD, against which the networks of ALSci/bi were compared. Post‐hoc, measures of global and local network topology were compared (i.e. tree hierarchy, leaf fraction, diameter and betweenness centrality).ResultAt baseline, ALSci/bi patients’ theta‐band brain networks resembled those of ALS‐pure motor more than those of bvFTD. At follow‐up, ALSci/bi patients appear to shift towards the bvFTD group in the beta band. This was reflected by the fact that ALSci/bi patients moved away from ALS‐pure motor patients overtime and their beta‐band networks resembled those of bvFTD at follow up. No significant differences in global or local network topology were found.ConclusionOur findings suggest that brain networks of ALSci/bi patients move along the ALS‐bvFTD spectrum over time and become closer to bvFTD‐like topology.