bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma pTau217 Predicts AD and Disease Progression in a Diverse Cohort
Authors: Lah James J. , Roberts Blaine Russell , Watson Caroline M , Johnson Erik C.B. , Hales Chadwick M , Qiu Deqiang , Wingo Thomas S. , Seyfried Nicholas T , Jeromin Andreas , Levey Allan I. 
Published: January 2025

AbstractBackgroundPlasma pTau217 detects AD pathology and show longitudinal changes dependent on baseline pathology. However, previous studies have been restricted to cohorts with limited diversity. We evaluated performance of plasma pTau217 in detecting AD and predicting disease progression in a diverse cohort from the Emory Goizueta ADRC.MethodWe analyzed plasma pTau217 levels using AlzPath antibody and the Simoa HD platform. The cohort includes 410 Controls, 100 MCI, and 249 AD cases with research consensus diagnoses, 38.4% self‐identified African American (AA) individuals, with a subset of 478 cases with CSF AD biomarkers. Baseline plasma samples were analyzed for accuracy in classifying diagnosis and predicting progression (i.e., Control to MCI or MCI to AD). Paired samples for 244 participants were used to determine longitudinal changes.ResultIn baseline samples, median pTau217 levels were 0.318 pg/ml in Controls, 0.678 pg/ml in MCI, and 1.151 pg/ml in AD. Differences between Control, MCI, and AD were significant (p<0.0001 for all pairwise comparisons) for the entire cohort and within self‐identified AA and White subgroups. Group comparison by race revealed lower pTau217 in AA vs. White individuals among Controls (0.297 vs. 0.351; p<0.0001) and AD (1.046 vs. 1.266; p<0.05) groups. In longitudinal samples, progressors had higher pTau217 at baseline compared to non‐progressors (Controls: 0.939 vs. 0.336, p<0.0001; MCI: 1.056 vs. 0.678, p=0.040). Plasma pTau217 increased across all longitudinal samples at 0.020 pg/ml/yr. Rate of increase in pTau217 was higher among those with AD at baseline compared to Control non‐progressors (0.077 vs. 0.017; p=0.035). No other group differences reached statistical significance but analysis was limited by small sample sizes.ConclusionBaseline plasma pTau217 levels are different among Control, MCI, and AD cases for AA and White individuals, and higher baseline levels are associated with higher rate of longitudinal increase and predict disease progression. However, AA individuals collectively have lower pTau217 levels than White individuals regardless of disease status. Self‐identifies racial differences in plasma pTau levels must be addressed when using cut‐points for both research and clinical applications.
Age‐related differences in the relationship between sleep quality and cortical thickness
Authors: Kim Hyun , Zhang Yisha , Huber Benjamin , Rueppel Elizabeth , Goldberg Terry E. , Lee Seonjoo ,   human connectome project
Published: January 2025

AbstractBackgroundWhile the association between sleep quality and brain health is well established, the role of aging in this relationship is largely unknown. This study aimed to examine the interaction between sleep and age on cortical thickness using samples from large‐scale cohort studies. Age was examined in both linear and non‐linear (quadratic) terms, in order to determine the presence of critical age ranges that may exhibit more significant sleep‐related brain structural changes.MethodSample included 700 adults (mean age 59.63 [age range 36‐90], 55.9% female) from the Human Connectome Project‐Aging (HCP‐A). Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). Magnetic resonance imaging (MRI) data was obtained from T1‐weighted structural images using a 3T scanner, and cortical thickness indices were derived using the FreeSurfer pipeline. The interaction between sleep and age on cortical thickness was tested using the moderation analysis using linear regression models, with sex, race, and use of sleep medication as covariates. The same analyses are planned on a separate dataset from the Nathan Klein Institute (NKI) cohort in order to replicate these findings.ResultThere was a significant interaction term between the PSQI and non‐linear age term (age2) on the insula (b=0.67, CI=0.03‐1.30, p=.04) and the middle temporal cortical thickness (b=0.58, CI=0.03‐1.13, p=.04), indicating that sleep quality may be associated with cortical thickness distinctly in different age groups. A visual examination of this relationship indicated that cortical thickness for individuals between the ages 53 and 78.ConclusionAge may have a significant role in the relationship between sleep and cortical thickness. Middle‐aged and older adults may be most vulnerable to sleep‐related changes in the brain structures. These findings will be tested using a separate dataset.
Prevalence of Oropharyngeal Dysphagia in Patients With Advanced Cognitive Impairment
Authors: de Miranda Souza Ana Carolina Borges , Morillo Lilian Schafirovits 
Published: January 2025

AbstractIntroductionPatients with severe cognitive impairment, with the progression of the disease, show behavioral impairments, loss of functionality and, in many cases, swallowing changes (dysphagia). Dysphagia comes with serious complications that can cause health damage, such as malnutrition, dehydration and serious lung damage secondary to aspirations. Eating process goes beyond nutritional intake, as it has a social, cultural, behavioral, physical and cognitive component. OBJECTIVE: To correlate swallowing changes with the severity of symptoms that are present in patients with advanced cognitive impairment, monitored by the multidisciplinary team at an University hospital in the state of São Paulo.MethodThis is a longitudinal observational retrospective study, carried out through analysis of medical records of patients followed at the Advanced Cognitive Impairment Outpatient Clinic (ACCA) over a period of one year. A comparison was made between the swallowing functionality scale (ASHA NOMS) and clinical dementia rating sum of boxes score (CDR‐SB).ResultsThe prevalence of patients with Alzheimer’s disease was 33.3% of the sample of this population, followed by mixed dementia (Alzheimer’s and vascular). In August 2022, 27.5% of patients had ASHA 6 or 7, 23.5% had ASHA 5, 47.1% had ASHA 4 or less and 25.5% of the patients had CDR 3 (sum of boxes 17). After a year, only 11.7% had ASHA 6 or 7 (normal and/or adapted swallowing), 33.3% of patients had ASHA 5 and 49% had ASHA 4 or less (needs restrictions and adaptations of consistencies, use of strategies, food supplementation and/or use of alternative feeding routes), despite dementias progression CDR 3 (sum of boxes 18) in 31.4% of the total amount. Comparing 2022 datas of ASHA and CDR scale, an inverse proportionality relationship was found with statistical relevance (p = 0.05), but this finding did not remain in 2023 (p = 0.73).ConclusionOropharyngeal dysphagia is present in many cases of cognitive impairment and speech therapy assessment is essential to identify changes in swallowing, manage and make dietary adaptations aiming to maintain, for nutrition or comfort, a safe oral route, avoiding respiratory infections and, consequently, mortality.
Dynamics of Handwriting for Cognitive Assessment
Authors: Chavez Gabrielle , Thebaud Thomas , Butala Ankur , Dehak Najim , Moro‐Velazquez Laureano , Oh Esther S 
Published: January 2025

AbstractBackgroundPrevious studies have shown that motor dysfunction can be an indicator of AD. We measured the observable and dynamic characteristics of spirals drawn by people with AD.MethodWe instructed 23 AD and 40 healthy control (CTRL) participants to perform a range of handwriting tasks on a digital tablet using a pen. We instructed the participants to draw spirals in three different ways with: i) left hand; ii) right hand; iii) dominant hand while repeating the occlusive word “Pa‐ta‐ka.” From the drawing samples of 63 participants collected over multiple sessions, we computed 14 time‐independent, explainable features from the shape of the spirals and the dynamics of the drawings (duration, fundamental frequencies using Fourier transform etc.). Those features were compared between the two studied groups using Welch's t‐test with a false discovery rate (FDR) correction.ResultRight SpiralsWe found there is a significant difference (p‐value<0.01) for the Duration and Fundamental Frequency (FF) with respect to Origin vs Total Number of Points, and FF with respect to Center vs Total Number of Points. Furthermore, the Average Loop Speed is significant (p‐value<0.05).Left SpiralsWe found there is a significant difference (p‐value<0.05) for all features.Pataka SpiralsAdditionally, there is a significant difference (p‐value<0.05) for AD and CTRL participants concerning the Duration, Average Loop Speed, and FF Origin and FF Center.All SpiralsWe compared all spiral samples based on only their group type, either AD or CTRL. We found that all features resulted in a significant difference (p‐value<0.01).ConclusionThough there was no notable visual variation between AD and CTRL spirals, we did find there were significant differences among dynamical characteristics like duration, loop speed, and frequencies. We can conclude that AD participants tend to take longer drawing spirals which result in lower Average Speed per Loop than their CTRL counterparts. Additionally, the FF extracted from both groups indicate that higher frequencies are found in AD participants.
Patterns of Tau Deposition by Cognitive Subtype in the Alzheimer's Disease Neuroimaging Initiative
Authors: Scollard Phoebe , Gibbons Laura E. , Choi Seo‐Eun , Lee Michael L. , Klinedinst Brandon S , Trittschuh Emily H. , Mez Jesse , Saykin Andrew J. , Nakano Connie , Sanders Elizabeth , Lila Eardi , Risacher Shannon L. , Mormino Elizabeth , Smith Viktorija , Carlson Mackenzie L. , Young Christina B. , Crane Paul K. , Mukherjee Shubhabrata 
Published: January 2025

AbstractBackgroundCognitive subtypes of Alzheimer’s Dementia (AD), defined by a relative impairment in a particular domain of cognition, have previously been shown to be associated with patterns of gray matter atrophy. Here we assessed the association of these subtypes with patterns of tau deposition measured in vivo using tau PET imaging in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).MethodWe included amyloid positive individuals with AD and Mild Cognitive Impairment (MCI). We selected the first diagnosis visit for AD and the most recent visit for MCI. Previously, AD individuals were categorized into AD‐Memory, AD‐Language, AD‐Executive, AD‐Visuospatial, AD‐Multiple domains, or AD‐No domain subtypes based on a relative cognitive impairment. These methods were extended to categorize MCI individuals. The AD/MCI‐Memory, AD/MCI‐Visuospatial, and AD/MCI‐No domain groups were large enough for our analyses. The tau PET scan closest to the subtyping visit was selected (median 49 days between scan and visit). Tau deposition for 35 brain regions (left and right sides averaged) were included as predictors. Separate five‐fold cross validated LASSO regressions were run for each of the three pairwise comparisons. Each model was repeated 100 times with different random fold selections to assess the stability of results.ResultWe included 240 individuals (118 AD; 122 MCI) in our analyses (Table 1). There was some variation in the chosen models across repetitions with the AD/MCI‐Visuospatial versus AD/MCI‐No domain comparison varying the most (Table 2). We limit interpretation to those regions that appeared in ≥70% of repetitions. The amygdala was consistently selected in all pair‐wise comparisons. Higher tau deposition in this region was associated with a higher likelihood of being in AD/MCI‐Memory. Higher tau deposition in the postcentral region was associated with a lower likelihood of being in AD/MCI‐Memory compared to AD/MCI‐Visuospatial. Coefficients on consistently selected regions in the AD/MCI‐visuospatial versus AD/MCI‐No domain comparison were small. Figure 1 summarizes the top results from our analyses.ConclusionWe found heterogeneity in regional tau deposition among three cognitive subtypes. Future work will make use of additional cohorts with harmonized cognitive and imaging data. We plan to incorporate all cognitive subtypes and evaluate lateral asymmetry.
Impact of TDP‐43 co‐pathology on limbic cortical microstructure in Alzheimer’s disease: evidence from an autopsy‐confirmed cohort with in vivo diffusion MRI
Authors: Torso Mario , Ridgway Gerard R , Hardwidge Jamie , Hardingham Ian , Chance Steven A ,   National Alzheimer’s Coordinating Center,   Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: January 2025

AbstractBackgroundTDP‐43 (TAR DNA‐binding protein 43) is one of the most frequently observed co‐pathologies in Alzheimer's disease (AD). Recognizing the diversity of pathological features in individuals with AD, including the presence of TDP‐43, may lead to more personalized and effective treatment approaches.We investigate ante‐mortem cortical microstructural changes in MRI with subsequent autopsy confirmation of Alzheimer’s disease neuropathological changes (ADNC) with and without TDP‐43 comorbidity.MethodParticipants with ADNC and ante‐mortem MRI were obtained from the National Alzheimer's Coordinating Center (NACC; n=46) and the Alzheimer's Disease Neuroimaging Initiative (ADNI; n=8). Participants were grouped based on TDP‐43 presence (36 AD “pure” and 18 AD with TDP‐43). Thal phase, CERAD neuritic plaque assessment, Braak NFT, and combined ABC score, were used as AD neuropathological hallmarks. Cases with TDP‐43 ≥ Stage 2 were considered AD with TDP‐43.Structural and diffusion MRI were used to calculate cortical diffusivity measures in five functional macroregions: Primary Sensory, Unimodal, Limbic/Proisocortex, Heteromodal and Primary Motor (Ffytche & Wible 2014, PMID:24936089; Mesulam 1998, PMID:9648540).Cortical mean diffusivity and three minicolumn‐inspired cortical diffusivity measures were calculated: the angle between the radial minicolumnar direction and the principal diffusion direction (AngleR); the principal diffusion component parallel with the minicolumns (ParlPD), and the diffusion components perpendicular to the minicolumns (PerpPD+) (Torso et al. 2022, PMID:36281682).Groups were characterized using clinical, demographic, and neuropathological data (see table). Differences in diffusion metrics were tested adjusting for interval between MRI scan date and autopsy date, scanner manufacturer, diffusion b‐value, age and sex, with FDR correction (pFDR<0.05).ResultThe Limbic/Proisocortex macroregion exhibited significantly higher AngleR (F1,36= 7.978; pFDR=0.04) in AD with TDP‐43 (AngleR mean 1.135) compared to the AD pure group (1.055).ConclusionDiffusion MRI can detect differences in cortical microstructure of AD with TDP‐43 co‐pathology, suggesting more extensive cortical damage in AD with TDP‐43 comorbidity that involves Limbic cortical areas (cingulate, entorhinal, parahippocampal, and temporal pole).Consistent with previous findings regarding early cortical changes associated with amyloid deposition and neuroinflammation (Torso et al. 2022, PMID:36281682 Torso et al. 2323 PMID:37794477), the diffusion‐derived metric AngleR appears particularly sensitive to subtle effects, such as the impact of TDP‐43 in addition to ADNC.
White Matter Integrity of Age‐Related Hearing Loss and Cognitive Impairment
Authors: Nemati Samaneh , Arjmandi Meisam , Newman‐Norlund Roger , Newman‐Norlund Sarah , Fridriksson Julius 
Published: January 2025

AbstractBackgroundEmerging research, underscored by the UK National Institute of Health and Care Excellence and the US National Institutes of Health, suggests that age‐related hearing loss (ARHL) is linked to the development of dementias such as Alzheimer's disease (AD). In this study, we aim to investigate the neural correlates of ARHL and cognitive impairments based on the changes in white matter (WM) microstructures in a population of non‐demented adults.Method129 participants (94 female) aged between 20‐79 years old (Mean = 51.35 ± 20.65) were recruited as part of the Aging Brain Cohort at the University of South Carolina (ABC@UofSC). Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA). Hearing ability was evaluated by measuring pure‐tone thresholds (PTT) and words‐in‐noise (WIN) thresholds. Structural T1 weighted and diffusion tensor imaging (DTI) scans were administered, and data preprocessing was performed with our nii_preprocess automated pipeline, available for public use. Changes in the WM integrity were measured using fractional anisotropy (FA) and mean diffusivity (MD). Finally, we examined the relationship between DTI metrics (FA and MD) and hearing and cognitive performance using region‐of‐interest‐based regression analysis.ResultOur investigation identified a constellation of brain regions where lower FA and higher MD were significantly associated with both poorer auditory and cognitive processing. Specifically, poorer cognitive performance, as reflected by lower MoCA total scores, was associated with lower FA and higher MD values across major interconnecting pathways, including superior longitudinal fasciculus, fornix, corona radiata, and splenium of corpus callosum. Individuals with poorer hearing sensitivity and difficulty in words‐in‐noise recognition showed reduced FA and increased MD in fornix, superior longitudinal fasciculus, optic tract, and corona radiata (anterior and posterior sections).ConclusionOur findings reveal that the integrity of the white matter tracts across multiple brain regions is correlated with both auditory and cognitive performance, suggesting that these tracts may underlie a shared neural substrate for hearing and cognitive processes. The identified brain regions offer promising neural targets for the early detection of ARHL and cognitive impairments, as well as potential neural substrates for applying effective intervention strategies aimed at reducing the risk of dementia.
ATN plasma biomarkers and digital cognitive performance in adults with type 1 diabetes: data from the GluCog study
Authors: Fonseca Luciana Mascarenhas , Beeri Michal S , Hawks Zoë W , Jung Laneé , Cleveland Michael , Delgado Nikki , Bulger Jane , Grinspoon Elizabeth , Janess Kamille , Sliwinski Martin J. , Weinstock Ruth S , Chhatwal Jasmeer P. , Kivisäkk Pia , Germine Laura Thi , Chaytor Naomi Sage 
Published: January 2025

AbstractBackgroundHighly specific ATN plasma biomarker assays for neurodegenerative diseases have been developed, but their associations with cognition vary in different populations. Kidney disease, common in diabetes, may decrease the predictive precision of those biomarkers. The aim of this study was to characterize for the first time the relationships between plasma ATN biomarkers and cognitive function in adults with T1D.MethodAdults with T1D mean age 49 years (range 19‐84), 53% female, mean HbA1c 7.6% who participated in the Glycemic Variability and Fluctuations in Cognitive Status in Adults with T1D study and had plasma β‐amyloid42/40, p‐tau181, neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels measured using Quanterix, and p‐tau217 using AlzPath assays, were included (N=114). Self‐administered online cognitive tests (TestMyBrain.org) were used: Digit Symbol Matching (processing speed), Gradual Onset Continuous Performance (cognitive control, attention), Multiple Object Tracking (visual working memory); Vocabulary (verbal reasoning), Matrix (non‐verbal reasoning), Simple Reaction Time (psychomotor speed), Letter‐Number Switching (cognitive flexibility), Visual Paired Associates (visual memory), Flicker (working memory), and Paced Serial Addition Test (PSAT, working memory, attention). Bivariate correlation analyses between cognitive function and biomarkers were performed. Significant correlations after false discovery rate were re‐analyzed using linear multiple regression with biomarker assigned as outcome and cognitive function as predictors in separate models, adjusting for age, sex and education.ResultAll biomarkers were correlated with cognitive function in bivariate analysis. Multivariate analyses revealed that higher concentrations of ptau181 and GFAP were associated with longer reaction time for correct responses, PSAT (β=0.002, p=0.011 and β=0.057, p=0.012, respectively), and higher β‐amyloid42/40 concentration was associated with better vocabulary performance (β=0.028, p=0.009). Associations remained significant after including kidney‐related disease or other diabetes features as adjustments.ConclusionPTau181, GFAP and β‐amyloid42/40 were associated with cognitive performance in adults with T1D. Working memory speed was related to ptau181 and GFAP, suggesting it may be an early indicator of neurodegeneration in this population. The positive association between β‐amyloid42/40 and Vocabulary, a measure of crystalized cognitive ability, suggests protective mechanisms related to cognitive reserve. Investigation on ATN biomarkers and longitudinal cognitive decline is crucial for disentangling their role in T1D.
Serum Soluble CD14 is Associated with Insulin Resistance and Cortical Inflammation in Nonhuman Primates Consuming Western versus Mediterranean Diets
Authors: Frye Brett M. , Negrey Jacob D. , Sutphen Courtney L. , Craft Suzanne , Shively Carol A. , Register Thomas C. 
Published: January 2025

AbstractBackgroundDiet composition is associated with neurodegenerative disease risk including Alzheimer’s Disease (AD). The adverse effects of Western‐style diets may be moderated, in part, by systemic as well as central inflammation, whereas the neuroprotective effects of Mediterranean diets may work through mechanisms that promote anti‐inflammatory phenotypes. Systemic inflammation also may induce insulin resistance, another risk factor for AD. However, controlled trials of human dietary patterns are not available nor has the impact of such diet patterns on systemic and central inflammation been examined in nonhuman primates.MethodHere we determine the effects of long term (31 months) consumption of a Mediterranean (n=16) or Western (n=21) diet in cynomolgus monkeys (Macaca fascicularis). We examined relationships between the circulating marker of monocyte activation soluble CD14 (sCD14) and lateral temporal cortical transcriptional profiles associated with proinflammatory (Cyclin dependent kinase 14 [CDK14]), and anti‐inflammatory/neuroprotective (lunatic fringe [LFNG], mannose receptor C type 2 [MRC2], solute carrier family 3 member 2 [SLCA32], butyrophilin subfamily 2 member A1 [BTN2A1], katanin regulatory subunit B1 [KATNB1], transmembrane protein 268 [TMEM268]) transcripts. We also analyzed associations between sCD14 and insulin and glucose responses in an intravenous glucose tolerance test (ivGTT).ResultOn average, individuals in the Mediterranean diet group showed decreased signatures of monocyte activation, reflected by lower levels of circulating sCD14 compared to the Western group (mean difference±SE: 137.2±70.01, t=1.960, p=0.058). Serum sCD14 was negatively associated with anti‐inflammatory/neuroprotective brain transcripts: SL3CA2 (R=‐0.359, p=0.029), MRC2 (R=‐0.437, p=0.007), TMEM268 (R=‐0.304, p=0.067), BTN2A1 (R=‐0.300, p=0.071). sCD14 also was positively related to fasting insulin levels (R=0.401, p=0.021) and insulin area under the curve (R=0.350, p=0.046) in the ivGTT.ConclusionThese results demonstrate relationships between sCD14, a circulating marker of monocyte activation, insulin resistance, and a neuroinflammatory transcriptional profile in the temporal cortex. Mediterranean diet consumption was previously shown in these subjects to significantly alter circulating monocyte profiles toward an anti‐inflammatory phenotype and to preserve insulin sensitivity relative to Western diet consumption. The findings support multisystem anti‐inflammatory effects of Mediterranean diet consumption which may be mediated via integrated pathways. This work captures the complex interplay of diet composition, insulin resistance, inflammation, and brain health.