bluuebunny/crossref_metadata_2025_split huggingface dataset:
Point of care measurement of blood tau in Alzheimer’s dementia
Authors: Bayoumy Sherif , Salminen Teppo , Hok‐A‐Hin Yanaika S. , van der Flier Wiesje M. , Vanbrabant Jeroen , Stoops Erik , Vanmechelen Eugeen , Verberk Inge M.W. , Teunissen Charlotte E. 
Published: June 2023

AbstractBackgroundSeveral assays reliably measure cerebrospinal fluid (CSF) total tau (t‐tau) protein for Alzheimer’s diseases (AD) diagnosis. However, CSF sampling is invasive and hampers availability of biomarker testing in AD. Therefore, less invasive blood t‐tau assays are needed, preferably on different platforms to enable implementation in different clinical settings. Point‐of‐care (POC) platforms enable the development of practical and easily implemented assays. Here, we aim to develop and compare two blood t‐tau POC‐assays, (1)on the Ella microfluidics platform and (2)using upconversion‐nanoparticle based lateral flow (UCNP‐LF), for use in AD diagnosis.MethodThe prototype assays were developed with the same pair of antibodies (capture‐mAb: ADx205 and detector‐mAb: ADx204 having epitopes in respectively the regions aa 194‐204 and 1‐20) and were calibrated using a recombinant protein (2N4R tau). For the Ella‐assay, we validated the analytical sensitivity, precision (4 different runs) and parallelism. The acceptance range was set to <15% coefficient of variation (CV) for precision and 85‐115% of slope‐accuracy for parallelism. Detectability of t‐tau was assessed using 20 plasma samples, including 10 AD‐dementia patients (age: 64±9y, 60%F) and 10 controls (age: 67±8y, 50%F). For the UCNP‐LF assay, spiked buffer and serum were used for preliminary performance testing.ResultFor the Ella assay, we determined a limit of detection (LoD) of 3 pg/mL based on mean signal of 16 blanks plus 10x SD (figure1). The assay quantified t‐tau in the clinical samples above assay blank with an average intra‐assay CV of 5.3%. Average intra‐ and inter‐assay CV for QC plasma samples were 8% and 11.4%. The assay showed robust mean parallelism response of (95%) (figure 2). Median t‐tau concentration in AD samples was 36.9 pg/mL vs 8 pg/mL in controls. The prototype UCNP‐LF assay showed a LoD of 92 pg/mL, based upon spiked buffer with the recombinant protein, and 102 pg/mL for spiked serum (figure3). The UCNP‐LF assay has a read‐out time of 30 minutes.ConclusionThe prototype assays showed promising preliminary performance. Next, a technology comparison using Bland‐Altman graphs on samples of at least two different clinical groups, would be measured using a reference immunoassay platform, such as Simoa.
Correlation between quantitative and qualitative assessments of white matter hyperintensities in patients from a multicentric memory clinic population
Authors: Longo Clarisse , Cavedo Enrica , Gordon Elizabeth , Samper‐Gonzales Jorge , Schwarz Adam J. ,   MEMENTO study group
Published: June 2023

AbstractBackgroundWhite matter hyperintensities (WMH) can be visualized as abnormal T2 signal in the periventricular, deep and subcortical white matter on Magnetic Resonance Imaging (MRI). WMH increase with age and are associated with stroke, cognitive decline and dementia. The most common visual rating scale used to assess WMH in the clinical setting is the Fazekas scale (Fazekas et al., 1987). The current study investigated the relationship between WMH volume (expressed as a % of intra‐cranial volume (ICV)) calculated using an automated method included in the QyScore® medical device, and Fazekas scores in a multicentric memory clinic population at baseline.Method1959 participants from the MEMENTO cohort (Age 71.02 +/‐ 8.61, 1218 Female, MMSE 27.95 +/‐ 1.91) had 3DT1 and T2 FLAIR MRI scans analyzed with QyScore®, an FDA‐approved and CE‐marked image analysis software. 814 had amyloid status from CSF or PET, of which 216 were Amyloid+. WMH volumes are reported in mL, corrected for %ICV. Correlation between Fazekas deep white matter (DWM) scores and quantitative WMH measurements was ascertained by Spearman’s rank correlation.ResultThere was a significant positive correlation between Fazekas DWM scores and WMH %ICV (0.76 p<0.001) for the total sample, amyloid positive (0.81 p<0.001) and negative (0.72 p<0.001) patients. The correlation was also strong when separated by clinical diagnosis: patients with Subjective Cognitive Complaint (SCC, N = 305, AGE: 69.87 +/‐ 8.03, 197 female, MMSE: 28.86 +/‐ 1.17) and MCI (N = 1638, Age: 71.2 +/‐ 8.69, 1014 Female, MMSE: 27.8 +/‐ 1.95) presented Fazekas DWM scores correlated with WMH %ICV (0.66 p<0.001 for SCC; 0.77 p<0.001 for MCI).ConclusionThe automated quantification of ICV‐corrected WMH were well‐correlated to Fazekas DWM scores. Considering that visual rating of WMH is time consuming and suffers from intra and inter‐operator variability, the quantitative assessment of WMH load provided by QyScore® may improve the assessment of patients with cognitive impairment.
Associations between an individual’s need for cognitively stimulating activities, brain damage and cognitive functioning: Results from The Maastricht Study
Authors: Truin Lotte S. , Köhler Sebastian , Schram Miranda T. , van Boxtel Martin P.J. , Backes Walter H. , Jansen Jacobus F.A. , van Dongen Martien , de Vries Nanne , de Vries Hein , Eussen Simone J.P.M. , Stehouwer Coen D.A. , de Vugt Marjolein , Deckers Kay 
Published: June 2023

AbstractBackgroundDementia is a global health challenge. Currently, there is no curative treatment for dementia and therefore risk reduction through lifestyle modifications has become more prominent with high cognitive activity as a promising target. This study explored the association between an individual’s need to engage in cognitively stimulating activities, brain damage and cognitive functioning in the Dutch general population.MethodThis study used cross‐sectional data from the population‐based cohort The Maastricht Study (N = 4,209; mean age 59.06 ± 8.58 years, 50.11% women). Need For Cogntion (NFC) was measured with the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed and executive functioning and attention. Standardized volumes of white matter hyperintensities (WMH) and cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3 Tesla MRI. Multiple linear regression analysis was used to explore the association between NFC and cognitive functioning, NFC and WMH and NFC and CSF. Binary logistic regression analysis was used to assess the association between NFC and CSVD. Interaction between brain damage or cognitive impairment (a score of <1.5 standard deviation below the mean on any of the three cognitive domains) and NFC on cognitive functioning was tested by including interaction terms in the regression analyses.ResultHigh NFC was positively associated with cognitive functioning (β: 0.21, p = <0.001) and negatively associated with CSVD (OR: 0.74, p = 0.005). These associations were independent of demographic and somatic factors. A dose‐response relationship between NFC and cognitive functioning was observed. There was no statistically significant association between NFC and WMH or CSF. No interaction between CSVD, WMH or CSF and NFC on cognitive functioning was found. Cognitive impairment did not moderate the association between NFC and cognitive functioning.ConclusionA high need for engaging in cognitively stimulating activities is associated with better cognitive functioning and less brain damage. This is in line with previous research. These results indicate that, in middle‐aged populations, stimulating cognitive activity may be an opportunity for risk reduction of cognitive decline and dementia.
Characterizing oldest‐old SuperAgers based on cognitive domains and demographic factors: The Life After 90 study
Authors: Biswas Roshni , Kawas Claudia H. , Gilsanz Paola , Whitmer Rachel A. , Mungas Dan M. , Decarli Charles , Glymour M. Maria , Corrada María M. M. 
Published: June 2023

AbstractBackgroundSuperAgers are individuals who maintain superior cognitive performance despite advanced age. Most studies define SuperAgers as superior performers only in episodic memory. Our aim was to assess in a diverse oldest‐old cohort if superior performance in one domain indicates superior performance in other domains and explore demographic characteristics.MethodsThe LifeAfter90 study is a multi‐ethnic cohort of members of Kaiser Permanente Northern California aged 90 or older. Baseline verbal episodic memory (VEM), semantic memory (SM), and executive function (EF) were evaluated using the Spanish and English Neuropsychological Assessment Scale (SENAS). SuperAgers were individuals who scored above the mean of domain and race‐specific SENAS scores from a reference cohort aged 65‐70 years. The reference group were similar participants from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study. To assess the association between age, sex, education, and being a SuperAger, odds ratios (OR) and 95% confidence interval (CI) were calculated using multiple logistic regression.ResultsThe 617 study participants (236 men and 381 women) had a mean age of 92.9 years (Table1). 53.6% of individuals were SuperAgers in one domain, 22.8% in any two domains, and 7.7% in all three domains. 7.0% of individuals were SuperAgers in SM and EF, 4.5% in VEM and EF, and 3.5% in VEM and SM (Figure1). SuperAgers were younger than non‐SuperAgers. Women were more likely to be SuperAgers in VEM (OR = 2.13; 95%CI: 1.43,3.18) and EF (OR = 2.18; 95%CI: 1.44,3.30) and less likely in SM (OR = 0.49; 95%CI: 0.34,0.71) compared to men. Higher education was related to being a SuperAger in SM (OR = 1.85; 95%CI: 1.28,2.67) and EF (OR = 2.56; 95%CI: 1.74,3.78) but not VEM (Table2).ConclusionIn this diverse cohort of oldest‐old SuperAgers we found that exceptional episodic memory performance does not indicate exceptional performance in other cognitive domains. Education was not a predictor of exceptional performance in all domains. Future work should investigate predictors of exceptional cognitive aging after age 90.
Regional cerebral atrophy correlates with amyloid accumulation in preclinical Alzheimer’s disease
Authors: Imabayashi Etsuko , Ishii Kenji , Toyohara Jun , Kojima Narumi , Tago Tetsuro , Sakata Muneyuki , Wagatsuma Kei , Ishibashi Kenji , Tokumaru Aya M. , Kim Hunkyung 
Published: June 2023

AbstractBackgroundThis study was aimed to evaluate the regional hierarchical brain atrophy among the preclinical to mild cognitive impairment (MCI) stages of Alzheimer’s disease associated with amyloid deposition using [18F]flutemetamol positron emission tomography and volumetric magnetic resonance imaging.MethodThis was a prospective, single‐cohort study of volunteers who were living independently in Itabashi‐ku (Tokyo, Japan). One hundred thirty‐six participants (female/male = 96/40, mean age/standard deviation = 79.2/4.0 years) were recruited. Two subjects, one with meningeal thickening and another with sequelae in the brain, and 17 visually amyloid‐negative MCI subjects who possibly had neurodegenerative disease other than Alzheimer’s disease were excluded from the further analysis. We applied voxel‐based regression slope analysis between composite voxel of interest values calculated with Cortex ID Suite (GE Healthcare) on [18F]flutemetamol positron emission tomography and volumetric magnetic resonance images in three groups: 70 amyloid‐negative cognitively normal (CN) participants, 29 amyloid‐positive cognitively normal (PreC) participants, and 18 amyloid‐positive MCI (MCI+) participants. Statistical Parametric Mapping 12 software was used for analysis.ResultEven in the cognitively normal stage, the PreC group showed a larger slope of atrophy in the basal forebrain and middle frontal gyri than the CN group. In the MCI+ group, the slopes were larger in the lateral and medial parietal lobes, uncus, and right lateral temporal areas.ConclusionThe speed of amyloid‐related atrophy in the basal forebrain and middle frontal gyri was quick even in the preclinical stage of Alzheimer’s disease. As no significant slope changes were observed among the three groups in the medial temporal area, except for the uncus, the well‐known medial temporal atrophy in early Alzheimer’s disease might not be related to the accumulation of amyloid.
Mediterranean diet and longitudinal change of white matter hyperintensity in cognitively intact young and older adults
Authors: Song Suhang , Gaynor Alexandra M. , Cruz Emily , Lee Seonjoo , Gazes Yunglin , Habeck Christian , Stern Yaakov , Gu Yian 
Published: June 2023

AbstractBackgroundA healthy dietary pattern, Mediterranean diet (MeDi), has been reported to be associated with better brain and cognition. White matter hyperintensities (WMHs), seen in brain magnetic resonance imaging, are considered to be due to cerebral small vessel diseases and have been shown to predict faster cognitive decline in older adults. However, current evidence on the association between MeDi and WMH is inconsistent and longitudinal data are scarce. This study aims to examine whether better adherence to MeDi is associated with less accumulation of WMH over time.MethodThis longitudinal study was conducted among 183 cognitively intact adults aged 20‐80 years. MeDi was calculated from dietary data assessed by a self‐reported food frequency questionnaire, ranging from 0‐55, with a higher score indicating better adherence. WMH was assessed by 3T MRI, and log‐transformed prior to analyses. A one‐sample T‐test was used to examine if WMH burden increased from baseline to follow‐up over an average of five years. Multivariable linear regression was used to estimate the effect of MeDi on the change in WMH. Covariates included age, gender, race/ethnicity, education, IQ, follow‐up interval, caloric intake, baseline WMH, baseline total gray matter volume, and baseline mean cortical thickness. Moderation effects by age (young: <43, middle‐aged: 43‐65, and older: ≥65 years), sex, and race/ethnicity (non‐Hispanic White and other, non‐Hispanic Black, and Hispanic) were examined, followed by stratification analyses.ResultAmong all participants, WMH increased from baseline to follow‐up (mean difference [follow‐up‐baseline][standard error(SE)] = 0.31[0.04], p<0.001). A higher MeDi was associated with less increase of WMH (β[SE] = ‐0.014[0.006], p = 0.034), adjusting by all covariates. The association between MeDi and WMH change was moderated by age group (young group as the reference, p‐interaction[middle‐aged*MeDi] = 0.024, p‐interaction[older*MeDi] = 0.017), adjusting by follow‐up interval: the association was observed among the young group (β[SE] = ‐0.038[0.010], p<0.001), but not among the middle‐aged ((β[SE] = ‐0.002[0.013, p = 0.872]) or the older group ((β[SE] = ‐0.002[0.009], p = 0.836). No significant moderation effects by sex or race/ethnicity were found, adjusting by age and follow‐up interval.ConclusionBetter adherence to MeDi was associated with reduced increase of WMH over time. Following a healthy diet, especially at an early age, may help maintain a healthy brain.
Validation of a new cognitive screening tool, the Brain Health Test‐7, for identification of mild cognitive impairment and early dementia
Authors: Hwang Tzung‐Jeng , Wang Pei‐Ning , Chen Cheng‐Sheng , Chen Jiahn‐Jyh , Hsu Chih‐Cheng 
Published: June 2023

AbstractBackgroundThe Brain Health Test‐7 (BHT‐7) was developed to identify patients with mild cognitive impairment (MCI) and early dementia. Here we report the validity of the BHT‐7 versus the Mini‐Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in subjects of different psychiatry or neurology clinics.MethodPatients with the chief complaint of memory decline were recruited in this study from the outpatient clinic of psychiatry or neurology in 3 different kinds of hospitals between November 2017 to December 2020. All patients underwent the evaluation of the BHT‐7, MMSE, MoCA, and CDR by trained research assistants or board‐certified psychologists. The final clinical diagnosis (normal, MCI, dementia) was made by consensus meeting, taking into account all available data, including clinical history and symptoms, brain image, cognitive tests, and CDR. Demographic data (age, gender, and education level) and the scores of the MMSE, MoCA, and BHT‐7 between groups were compared. Logistic regression was adopted for analysis of optimal cutoff values, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the ROC curve.ResultWe enrolled a total of 1090 subjects (normal 402, MCI 317, dementia 371); of them, 705 (64.7%) were female. There was a statistically significant difference in age, years of education, and 3 cognitive test scores among the 3 groups of subjects. Compared with the MMSE and MoCA, the BHT‐7 performed slightly better in differentiating MCI and dementia. In sub‐group analysis (divided based on 6 years of education), the BHT‐7 still performed slightly better than MMSE and MoCA. The testing time for the BHT‐7 was about 5‐7 minutes, shorter than that of the MMSE and MoCA. For BHT‐7, the cutoff point was 17 between normal and MCI, and 14 between normal and dementia. These cutoff points of BHT‐7 were consistent through 3 different settings (medical center’s psychiatry and neurology clinics, and outpatient clinic of a psychiatry center). In contrast, the cutoff points were inconsistent for MMSE and MoCA in different settings.ConclusionThe results support that BHT‐7 may be a useful cognitive screening tool for MCI or early dementia in various clinic settings.
Sleep quality and memory performance in a lifespan sample of racially/ethnically diverse adults
Authors: Hokett Emily , Lao Patrick J. , Turney Indira C , Martinez‐Amezcua Pablo , Starks Tiara M. , Brickman Adam M. , Palta Priya , Manly Jennifer J. 
Published: June 2023

AbstractBackgroundWhile studies have shown that Non‐Latinx Black and Latinx adults sleep less and more poorly than Non‐Latinx White adults, the cognitive consequences of poor sleep in Non‐Latinx Black and Latinx adults are understudied. Moreover, it is unclear if negative factors that disproportionately affect racial/ethnic minorities, including discrimination, may result in racial/ethnic differences in the relationship between sleep and cognition. We hypothesized that poorer quality sleep and inadequate sleep duration (e.g., short or long sleep) is associated with poorer memory performance, and the strength of these associations would differ by racial/ethnic group.MethodOur analysis included non‐Latinx Black, non‐Latinx White, and Latinx participants across the adult lifespan recruited from the community of Northern Manhattan as a part of the Offspring study. Participants self‐reported their sleep duration and quality over the past month using the Pittsburgh Sleep Quality Index, which we used to calculate global sleep quality. We evaluated memory with the Buschke Selective Reminding Task. We used general linear models to estimate mean differences in sleep duration and quality for racial/ethnic groups. We used multivariable regression to estimate relationships of sleep duration and quality with delayed recall in the total sample and stratified by racial/ethnic group. Models were adjusted for age, sex, and years of education.ResultBlack and Latinx adults reported lower sleep duration and poorer quality sleep than Non‐Latinx White adults. In the overall sample, higher quality sleep was associated with better delayed recall performance. We also found linear and quadratic relationships between sleep duration and delayed recall. Taken together, high quality sleep and adequate sleep duration was linked with better delayed recall. Stratified analyses revealed that these effects were strongest in the Latinx group and were not present among non‐Latinx Black and non‐Latinx White participants.ConclusionNon‐Latinx Black and Latinx adults report lower sleep duration and poorer sleep quality compared to Non‐Latinx White adults. We observed stronger associations between poor sleep quality and sleep duration and memory performance in Latinx adults. Future work will determine which psychosocial factors (e.g., social support, discrimination) underlie racial/ethnic sleep disparities and mediate racial/ethnic differences in the cognitive consequences of poor sleep.
Prediction of cognitive impairment in morphologically‐ and immunohistochemically‐stained whole slide images reveals white matter alterations
Authors: McKenzie Andrew T , Marx Gabriel A. , Koenigsberg Daniel , Sawyer Mary , Iida Megan A , Walker Jamie M. , Richardson Timothy E. , Campanella Gabriele , Attems Johannes , McKee Ann C. , Stein Thor D. , Fuchs Thomas J , III Charles White , Farrell Kurt W. , Crary John F. 
Published: June 2023

AbstractBackgroundAge‐related cognitive impairment is complex and multifactorial, with numerous underlying and frequently co‐morbid pathological correlates. Given that conventional measures are imperfect predictors of cognitive impairment, improved approaches are urgently needed to identify correlated histopathological changes in an unbiased way.MethodsWe used a weakly supervised deep learning algorithm, clustering‐constrained‐attention multiple‐instance learning (CLAM), on digitized whole slide images of human brain tissue sections from a group of elderly individuals without significant amyloid‐beta deposition to predict the presence or absence of cognitive impairment. The brain tissue sections were from the hippocampus and frontal cortex and were either morphologically stained with LH&E or immunohistochemically stained for hyper‐phosphorylated tau. We used attention analysis to pinpoint the underlying architectural and cellular features that the top‐performing models used for the predictions.ResultsDespite noisy labels of cognition, our trained models were able to predict the presence of cognitive impairment with an accuracy that significantly beat chance, in both the morphologically stained and immunohistochemically stained whole slide images. Attention‐based analysis of the features most associated with cognitive impairment in both types of whole slide images analyzed suggests that the models identified white matter alterations in donors with cognitive impairment.ConclusionsThe deep learning method for the prediction of cognitive impairment that we present, which appears to be minimally influenced by the human‐identified visually salient aspects of whole slide images, may help to discover unexpected aspects of the pathophysiology associated with cognitive impairment in the elderly.