bluuebunny/crossref_metadata_2025_split huggingface dataset:
Poor Colonoscopy Bowel Prep in Cognitively Impaired 85‐Year‐Old with Low Education: Another Case Example
Authors: Burt Juliana S , Joffe Yonah , Eversole Kara , Kimmet Faith , Estores David , Arias Franchesca , Chapin Benjamin A , Price Catherine C. 
Published: January 2025

AbstractIntroductionColonoscopies are routine procedures performed primarily on adults over the age of 50; however, there is little known about the influence of social determinants of health on successful completion of colonoscopies. Inadequate at‐home bowel preparation can result in increased procedure duration, decreased cancer detection, and may necessitate a repeated colonoscopy, putting undue stress on the patient. Research suggests neurocognitive disorder is a risk factor for poor bowel preparation in older adults; however, lower education may confound neurocognitive findings, independently contributing to risk of incomplete colonoscopies. Research reports patients with a high school diploma were significantly more likely to have inadequate bowel prep compared to patients with college education. The present case study underscores the importance of considering social determinants of health when scheduling patients for colonoscopies.Case Presentation DemographicsJR is an 85‐year‐old non‐Hispanic Black male referred for preoperative neuropsychological testing prior to a scheduled colonoscopy. He was raised in the rural South and became truant after the 4th grade. He currently lives alone, receiving limited assistance from family.BackgroundFive months prior to the scheduled colonoscopy, JR was admitted to hospital due to fecal impaction and rectal pain; he was referred for a colonoscopy to follow up his symptoms. Neuropsychological Testing: revealed 3rd grade reading level and deficits in list learning, delayed recall, and semantic fluency. Problem: The patient arrived disorientated to the purpose of the visit, believing he would undergo the colonoscopy on the day of the neuropsychological evaluation. Consequently, JR completed his bowel preparation the night before and had slept on his bathroom floor. Notably, the procedure was scheduled 13 days later. Outcome: Due to unnecessarily early completion of bowel prep and resultant need for more preparatory medication, the procedure was rescheduled for four weeks later. At the time of this report, JR’s procedure date has not arrived.DiscussionThis case supports research suggesting neurocognitive impairment and lower education are predictive of patients’ poor preoperative planning and bowel preparation. Moreover, this case highlights the need for increased family involvement and attention from providers for patients of advanced age, lower education, and neurocognitive impairment referred for colonoscopies.
Trends in Alzheimer’s Disease clinical outcome assessments in phase 2 and 3 clinical trials from 1993 to present
Authors: Gary Sarah T , Davis‐Aoki Reina , Verma Prateek , McDowell Bryan 
Published: January 2025

AbstractBackgroundClinical outcome assessments (COAs) are an important part of clinical trials to measure what is meaningful to patients and caregivers. This study aimed to examine trends in Alzheimer’s Disease (AD) COAs used in clinical trials, given the FDA’s recent emphasis on patient‐focused drug development and early AD.MethodClinicalTrials.Gov was programmatically accessed through its API on January 19, 2024. Phase 2 and 3 Interventional AD trials were further analyzed for inclusion of 6000+ COAs in the primary or secondary outcome measures field.Result997 studies were identified with start dates from 1993‐2025. COAs as primary or secondary outcomes have increased over time (50.0% of studies from 1993‐1999, 57.4% from 2000‐2009, 64.0% from 2010‐2019, 69.1% from 2020‐2023). The increase is mainly driven by an increase in COAs in the primary outcome (40.0% of studies from 1993‐1999 vs. 53.1% from 2020‐2023). ADAS‐Cog was the most common primary COA (19.1% of all studies) followed by CDR (7.0%), CIBIC+(3.3%) and ADCS‐ADL (2.9%). The percentage of studies using ADAS‐Cog as the primary outcome is trending downward, with only 13.0% of studies using ADAS‐Cog as primary in the past 5 years. The MMSE was the most common secondary COA (19.6% of all studies), followed by ADAS‐Cog (16.0%), NPI‐C (15.8%), and ADCS‐ADL (14.5%). Reference to mild cognitive impairment (MCI) in the primary/secondary outcome is trending upward, with no studies in the 90s, 2.2% in the 2000s, 4.6% in the 2010s, and 11.1% from 2020‐2023. In addition, there has been an increase in COAs for preclinical AD and MCI (e.g. PACC, MoCA, iADRS).ConclusionEven with the rise in biomarkers and focus on preclinical AD, COAs remain an important part of AD clinical trials, as shown by the continued and increasing usage as primary and secondary outcomes. Historically, ADAS‐Cog has been the gold standard in AD studies, and many approved AD studies have utilized it as primary endpoints with small delta between study drug and placebo. In recent times AD trials are shifting towards MCI‐AD and this has led to new endpoints like PACC and MoCA which are sensitive in identifying early cognitive deficits in patients.
A highly accurate blood test for Alzheimer’s disease pathology has performance equivalent or superior to clinically used CSF tests
Authors: Salvadó Gemma , Barthélemy Nicolas R. , Schindler Suzanne E. , He Yingxin , Janelidze Shorena , Collij Lyduine E. , Saef Benjamin A. , Henson Rachel L. , Chen Charles D. , Gordon Brian A. , Li Yan , Joie Renaud La , Benzinger Tammie L.S. , Morris John C. , Mattsson‐Carlgren Niklas , Palmqvist Sebastian , Ossenkoppele Rik , Rabinovici Gil D. , Stomrud Erik , Bateman Randall J. , Hansson Oskar 
Published: January 2025

AbstractBackgroundWith the emergence of Alzheimer's disease (AD) disease‐modifying therapies, identifying patients who could benefit from these treatments becomes critical. We evaluated whether a precise blood test could perform as well as established cerebrospinal fluid (CSF) tests in detecting amyloid‐β (Aβ) plaques and tau tangles.MethodPlasma %p‐tau217 (ratio of phosporylated‐tau217 to non‐phosphorylated mid‐region tau) was analyzed by mass spectrometry in the Swedish BioFINDER‐2 cohort (n=1,422) and the US Knight ADRC cohort (n=337, Table 1). Matched CSF samples were analyzed with clinically used and FDA‐approved automated immunoassays for Aβ42/40 and p‐tau181/Aβ42. The primary and secondary outcomes were detection of brain Aβ or tau pathology (Braak I‐IV), respectively, using PET imaging as the reference standard. Main analyses were focused on individuals with cognitive impairment (mild cognitive impairment and mild dementia), which is the target population for available disease‐modifying treatments. We assessed accuracy, positive and negative predictive values, and sensitivity of each biomarker, using cut‐offs derived at 90% specificity for a one cut‐off approach. We also tested a two cut‐off approach using cut‐offs derived at 95% specificity and 95% sensitivity, classifying participants as positive (above higher cut‐off), negative (below lower cut‐off) or intermediate (between these two cut‐offs).ResultPlasma %p‐tau217 was clinically equivalent to FDA‐approved CSF tests in classifying Aβ PET status, with an area‐under‐the‐curve (AUC) for both cohorts between 0.95‐0.97 (Figure 1A‐B). Plasma %p‐tau217 was generally superior to CSF tests in classification of tau‐PET with AUCs of 0.95‐0.98 (Figure 1C‐D). In cognitively impaired sub‐cohorts (BioFINDER‐2: n=720; Knight ADRC: n=50), plasma %p‐tau217 had an accuracy, positive predictive value and negative predictive value of 89‐90% for Aβ PET (Figure 2A) and 87‐88% for tau‐PET status (Figure 2C), which was clinically equivalent to CSF tests. These statistics further improved up to 95% using a two cut‐off approach (Figure 2B‐2D, respectively).ConclusionBlood plasma %p‐tau217 demonstrated performance clinically equivalent or superior to clinically used FDA‐approved CSF tests in the detection of AD pathology. Use of high performance blood tests in clinical practice can improve access to accurate AD diagnosis and AD‐specific treatments.
Application value of structural MRI combined with ASS1 in early diagnosis of Mild Cognitive Impairment
Authors: Chen Lele , Fan Xiang , Shan Hui , Yu Keyan , Lu Gaigai , Wei Zhuonan , Cheng Guanxun 
Published: January 2025

AbstractBackgroundMild cognitive impairment (MCI) refers to a transitional stage between the cognitively unimpaired (CU) and dementia, which is probable in the Alzheimer's disease (AD) continuum. Neuropsychological assessments and structural MRI are primary clinical examinations applied for diagnosing MCI. Hippocampal volume (HV) and medial temporal lobe atrophy (MTA) as recognized AD biomarkers are the most frequently used imaging markers in clinical application. However, HV or MTA is not sensitive enough in the early stage of AD. Recently, blood‐based biomarker analysis has demonstrated great potential for early AD diagnosis because it is simple and less invasive. It has been shown that argininosuccinate synthetase (ASS1) expression is increased in Alzheimer's disease neurons and glial cells, which also correlates with inducible nitric oxide synthase (iNOS) expression, and that there is a link between the increased NO production observed in Alzheimer's disease brains and iNOS expression. We aim to study whether ASS1 can provide additional value compared with HV in diagnosing MCI and validate the diagnostic utility of the combined model.MethodTwenty MCI patients and 20 CU were recruited and underwent neuropsychological assessment, MRI examinations, and the collection of blood. Protein quantification was analyzed by high‐resolution tandem mass spectrometry (MS/MS), and the ROC curve was plotted for selected biomarkers. The automated structure tool and SPSS 26.0 were used to analyze the HV and ASS1. We investigated the area under curve (AUC) of HV, and the combined model using both ASS1 and HV based on the logistic regression. The Delong test is used to compare the combined model with the single HV.ResultThe AUC of diagnosing MCI by HV was 0.788 (95%CI: 0.629 ‐0.901). When combining HV with ASS1, the AUC increased to 0.938 (95%CI: 0.813‐0.989). The Delong test results indicated a significant difference between the single HV and the combined model. (P=0.0188).ConclusionCombining plasma ASS1 could provide significantly additional value in detection of MCI, which also means plasma ASS1 and HV may be a potential early biomarker combination in diagnosing early AD.
Proteomic study of cerebrospinal fluid in patients with vascular cognitive impairment‐no dementia
Authors: Peng Sisi , Zhang Junjian 
Published: January 2025

AbstractBackgroundVascular cognitive impairment (VCI), including vascular cognitive impairment‐no dementia (VCIND) and vascular dementia, is a cognitive impairment syndrome caused by cerebrovascular disease and its risk factors. Among people over 60 years old, the prevalence of VCIND is about 15‐20%. VCIND, as the early stage of VCI, has become a focus of current research due to the fact that its patients are at greater risk of developing dementia and can benefit greatly from early intervention. The etiology and pathology of VCI are highly heterogeneous. Analyzing the key molecules in the development of VCI through omics approaches is conducive to a multidimensional understanding of the disease nature of VCI, and is important for identifying its targets for intervention.MethodWe screened for differential proteins in the cerebrospinal fluid (CSF) of VCIND patients and healthy control subjects by proteomic assays based on ultra‐performance liquid chromatography‐mass spectrometry (UPLC‐MS). Differential proteins and scores of cognitive assessments were subjected to pearson correlation analysis to screen out the differential proteins with correlation coefficients greater than 0.75. We constructed a mouse model of bilateral carotid artery stenosis (BCAS) and a cellular model of oxygen glucose deprivation (OGD), and targeted the differential proteins screened in CSF in the classic animal and cellular models of VCI mentioned above.ResultWe found significant between‐group differences in MoCA (p<0.001) and DSST (p<0.001) scores in non‐demented VCI patients compared to healthy controls. 75 differential proteins were screened in the cerebrospinal fluid of non‐demented VCI patients (fold change = 1.5, p<0.05), of which 38 were up‐regulated and 37 were down‐regulated. In cerebrospinal fluid, Cerebellin‐2 (Cbln2) was the only protein with a correlation over 0.75 for both MoCA and DSST assessment, and was significantly negatively correlated with cognitive assessments. Cbln2 expression was significantly higher in hippocampal tissues of BCAS mice as well as in OGD‐treated neuronal cells, which follows the same trend as the clinical findings.ConclusionCbln2 is a potentially important molecule in early stage of VCI.
Neuroanatomical Correlates of Functional Capacity in Activities of Daily Living in the Alzheimer´s Disease Continuum
Authors: Henriquez Fernando , Contreras Patricio Riquelme , Campo Cecilia Gonzalez , Lillo Patricia , Thumala Daniela , Martínez‐Pernía David , Okuma Cecilia , Demanet Michele , Saguez Rodrigo , Herrero Joaquin , Henriquez Rodrigo , Aboitiz Francisco , Chonchol Andrea Slachevsky 
Published: January 2025

AbstractBackgroundThe Alzheimer's Disease (AD) continuum is composed of Subjective Cognitive Decline (SCD), Mild Cognitive Impairment (MCI), and Alzheimer's Disease Dementia (ADD). Changes in grey matter volume (GMV), characteristic of the AD continuum, are related to cognitive and activities of daily living (ADL) impairments. ADLs are divided into three domains: i) Basic (BADL), ii) Instrumental (IADL), and iii) Advanced (AADL), and their study is critical for understanding the evolution and adequate follow‐up of patients. To date, the neuroanatomical basis of impairment in ADL has not been addressed. This work aimed to study the relationship between GMV and the ADL domains in the AD continuum.MethodA cross‐sectional study of 77 SCD, 30 MCI, and 23 ADD, matched for age, sex, and education, was conducted. ADLs were assessed with the Technology‐Activities of Daily Living Questionnaire (T‐ADLQ). A voxel‐wise regression analysis (with the SPM module) was performed to explore the association between GMV and the domains of ADLs. Total Intracranial Volume (TIV) was entered as a covariate. The analysis was performed for each patient group (MCI and ADD) in tandem with the SCD group to increase sample size, data variance, and statistical power.ResultRegression analysis for ADD‐SCD (Figure 1a) shows that in ADD patients (Table 1), AADLs were associated with decreased GMV in temporal, frontal, parietal, and insular regions. IADLs were also associated with temporal, frontal, parietal, and insular areas but were more widely distributed. BADLs were associated with temporal, frontal, and insular structures. The MCI‐SCD analysis (Figure 1b) shows that in patients with MCI (Table 2), AADLs were associated with temporal areas and IADLs with temporal, frontal, and parietal regions. BADLs had no significant associations.ConclusionAssociations between ADL domains with decreased GMV were more widely distributed in ADD compared to the MCI group, with a pattern similar to the neurodegenerative progression in the AD continuum. This finding highlights the potential of diverse neuroanatomical markers of functional capacity at different stages of the AD continuum. Such markers could hold significant relevance for the classification and follow‐up of patients from an ADL perspective, thereby improving the understanding of the consequences in daily life.
The Digital Clock and Recall can predict functional impairment in individuals with and without cognitive impairment and triage those in need of further assessment
Authors: Ciesla Marissa C , Toro‐Serey Claudio , Jannati Ali , Gomes‐Osman Joyce Rios , Banks Russel , Showalter John , Tobyne Sean , Pascual‐Leone Alvaro 
Published: January 2025

AbstractIntroductionEvaluation of functional dependence in activities of daily living (ADLs) and instrumental activities of daily living (iADLs) is necessary for dementia diagnosis. ADL and iADL questionnaires are typically employed, but with progressive cognitive impairment, a care partner must step in to assist with these tests, causing logistical burdens. Pre‐screening tools that triage patients in need of formal functional assessment would optimize clinical workflows. Here we evaluated whether the Linus Health Digital Clock and Recall (DCRTM), a brief automatically‐scored test of multiple cognitive domains, could concurrently predict functional impairment among individuals with and without cognitive impairment.MethodsWe collected data from 922 participants in the Bio‐Hermes‐001 multi‐site study (age mean±SD = 72±6.6; 57% female; years of education mean±SD = 15±2.71; primary language English), classified as cognitively unimpaired (n = 402), mild cognitively impaired (n = 298), or probable Alzheimer’s dementia (n = 242) based on clinical consensus and neuropsychological evaluation. We split participants, each including 2000 speech and drawing DCR metrics and age, into training (80%) and test (20%) sets, ensuring equal rates of functional impairment across sets (Functional Activities Questionnaire ≥ 6; 25% rate). We performed recursive feature elimination on 10‐fold cross‐validated random forests (5 repetitions) on the training set to identify the best model and feature set. Model performance was evaluated on the test set.ResultsThe optimal model (500 features) classified functional impairment with 0.77 sensitivity, 0.82 specificity, 0.90 negative predictive value (NPV), 0.61 positive predictive value (PPV), 0.86 area under the receiver operating characteristic curve (AUC), and 0.80 accuracy. The most predictive features were the duration of speech during recall and the placement of clock components.ConclusionThe DCR, a brief digital cognitive assessment with automatic scoring that can be completed in primary‐care settings, can also be used to identify individuals in need of further evaluation and engagement of care partners as informants. The high NPV can reassure healthcare professionals when no further assessment of ADLs and iADLs is indicated. These results also enable identifying care partners who are likely to benefit from receiving personalized recommendations or training to assist them in caregiving tasks and alleviate caregiver burden.
Tau deposition is associated with neurite abnormalities in white matter tracts and cortical grey matter regions in dementia with Lewy bodies
Authors: Mak Elijah , Reid Robert I. , Przybelski Scott A. , Lesnick Timothy G. , Schwarz Christopher G. , Senjem Matthew L. , Raghavan Sheelakumari , Vemuri Prashanthi , Jack Clifford R. , Min Hoon‐Ki , Jain Manoj K. , Miyagawa Toji , Forsberg Leah K. , Fields Julie A. , Savica Rodolfo , Graff‐Radford Jonathan , Jones David T. , Botha Hugo , St. Louis Erik K , Knopman David S. , Ramanan Vijay K. , Dickson Dennis W. , Graff‐Radford Neill R , Ferman Tanis J , Petersen Ronald C. , Lowe Val J. , Boeve Brad , O'Brien John T , Kantarci Kejal 
Published: January 2025

AbstractBackgroundDementia with Lewy bodies (DLB) frequently co‐occurs with Alzheimer’s disease (AD) pathologies, exacerbating disease progression. Biophysical models of diffusion imaging data, such as Neurite Orientation Dispersion and Density Imaging (NODDI), may reveal novel insights into the neurobiological substrates of AD on cortical and white matter microstructural injury.MethodA cohort of 57 DLB patients on the DLB spectrum (33 clinically probable DLB and 14 prodromal DLB) and 57 cognitively unimpaired (CU) controls underwent NODDI and PET imaging with [18F]‐Flortaucipir and [11C]‐PiB (Table 1). NODDI parameters were derived from white matter tracts and grey matter regions using the JHU “Eve” and Mayo Clinic Adult Lifespan Template atlases, respectively. Conditional logistic models were used to compare these parameters between the two groups, accounting for the 1:1 matching on age and sex. The associations of tau and amyloid‐β with NODDI parameters across the white matter tracts were examined with linear regressions. A region‐by‐region approach was adopted to evaluate the relationships of tau and amyloid‐β with grey matter NODDI, adjusting for age, APOE, and local grey matter volumes.ResultDLB spectrum patients exhibited extensive white matter abnormalities relative to CU, including lower fractional anisotropy, higher mean diffusivity (MD), and lower tissue‐weighted neurite density (tNDI). In grey matter, these deficits were paralleled with higher MD and lower tNDI and ODI, primarily in the temporoparietal and posterior cortices. Regression models revealed significant associations of elevated [18F]‐Flortaucipir uptake with deficits in temporal and limbic white matter tracts and a temporal‐lobe pattern of higher MD and lower tNDI in the cortex (Figure 1). No associations were observed with [11C]‐PiB in the DLB spectrum.ConclusionThese findings demonstrated an in vivo relationship between tau deposition and neurite deficits that spatially aligned with the canonical AD “cortical signature” of neurodegeneration in both white matter tracts and grey matter regions in DLB. Our study underscores the detrimental impact of AD pathology in DLB and provides a rationale for further investigations into the underlying mechanisms of AD in DLB. Future longitudinal studies tracking the progression of these changes could inform therapeutic strategies for DLB in the presence of AD pathologies
The effect of comorbidities on Alzheimer’s disease/cognition by race/ethnicity and the mediating role of AD pathologies measured by blood biomarkers
Authors: Wang Shanshan , Nguyen Uyen‐sa , Hall James , Petersen Melissa , O'Bryant Sid E. , Nandy Rajesh 
Published: January 2025

AbstractBackgroundThe study aims to assess the associations of comorbidities (hypertension, dyslipidemia, diabetes, chronic kidney disease [CKD], and depression) with mild cognitive impairment (MCI), Alzheimer’s dementia (AD dementia), and cognition by race/ethnicity; and to examine whether blood AD biomarkers mediate the associations.MethodWe used data from the baseline and visit 2 of the Health & Aging Brain Study‐Health Disparities (HABS‐HD) study. 2057 participants were included in the cross‐sectional analyses, and 792 participants, who were cognitively normal at baseline and had follow‐up data, were included in the longitudinal analyses. Race/ethnicity was categorized into Latinos, non‐Hispanic Black, and non‐Hispanic Whites. Blood AD biomarkers included amyloid β40 (Aβ40), amyloid β42 (Aβ42), total tau, phosphorylated tau 181(p‐tau 181), and neurofilament light chain (NfL). Blood AD biomarker changes between the two visits were calculated. Global cognition was assessed by the Mini Mental State Examination (MMSE). Causal mediation analyses were used.ResultIn the cross‐sectional analyses, the odds of AD dementia and MCI increased with higher levels of Geriatric Depression Scale (GDS) scores across all races/ethnicities. In the longitudinal analyses, those with CKD (β=‐0.431, 95% CI: ‐0.812, ‐0.049) and higher levels of GDS score (β=‐0.027, 95% CI: ‐0.050, ‐0.004) were negatively associated with global cognition at visit 2. While triglyceride (β=0.002, 95% CI: 0.0003, 0.003) and hemoglobin A1c (β=0.086, 95% CI: 0.002, 0.170) values were positively associated with global cognition at visit 2. Changes in Aβ40 and Aβ42 were found to be significantly associated with global cognition in both the overall sample and the Latino sample. The natural indirect effect of triglyceride on global cognition through changes in Aβ40 (β=0.0002, 95% CI: 0.00002, 0.0006) was found to be significant among the overall sample, with 15.80% of the association being mediated via changes in Aβ40.ConclusionOur study is the first to examine the mediating role of blood AD biomarkers in associations of various comorbidities with AD and cognition by race/ethnicity. We found that changes in Aβ40 mediated the associations between triglyceride and global cognition, providing evidence that amyloid pathology might be the underlying mechanism.