bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting cognitive decline in a low‐dimensional representation of brain morphology
Authors: Lamontagne‐Caron Rémi , Desrosiers Patrick , Potvin Olivier , Duchesne Simon , Doyon Nicolas ,   the Alzheimer’s disease neuroimaging initiative, and the CIMA‐Q
Published: December 2023

AbstractBackgroundIdentifying early signs of neurodegeneration due to Alzheimer’s disease (AD) is a necessary first step towards preventing cognitive decline. Individual cortical thickness measures, available after processing anatomical magnetic resonance imaging (MRI), are sensitive markers of neurodegeneration. However, cortical decline in aging and high inter‐individual variability complicates the determination of AD‐related neurodegeneration on trajectories. Further, the high‐dimensional nature of these trajectories necessitate the use of a transformation into lower‐dimensional spaces in order to perform comparative statistical analyses, model decline, and identify criteria differentiating pathological from normal trajectories.MethodIn this project, we computed trajectories in a 2D representation of a 62‐dimensional manifold of individual cortical thickness measures. To compute this representation, we used a nonlinear dimension reduction algorithm called Uniform Manifold Approximation and Projection (UMAP). We first created a UMAP embedding on measurements from 6,237 cognitively healthy participants (3,556 women) aged 18 to 100 years old from the NOMIS database. We then projected longitudinal data from 537 mild cognitively impaired (MCI) subjects and 340 AD subjects from ADNI into this embedding. Each participant had multiple visits (n ≥ 2), one year apart. Finally, differences in trajectories were analysed by clustering the reduced data and comparing the positional variations through time between MCI and AD subjects. The validity of the approach was verified through cross‐validation.ResultFirst, the embedding was shown to be positively associated (r = 0.65) with participants' age (see figure 1) in the NOMIS data. When projected in this space, differences between ADNI’s MCI and AD distributions were found (see figure 2). Average trajectories between clusters were shown to be significantly different between MCI and AD subjects (see figure 3). Moreover, we showed that some clusters and trajectories between clusters were more prone to host AD subjects. Finally, cross‐validation showed an accuracy of up to 72% at predicting cognitive decline in MCI participants over 2,000 bootstrap iterations.ConclusionA 2D low‐dimensional cortical thickness representation embeds sufficient discriminatory information as to predict decline to AD in MCI participants with strong accuracy.
Blood biomarkers of Alzheimer’s disease as predictors of eligibility for disease‐modifying treatment
Authors: Rosenberg Anna , Solomon Alina , Matton Anna , Wistbacka Ulf Öhlund , Hall Anette , Bonnard Alexandre , Daniilidou Makrina , Hagman Göran , Rydén Marie , Ashton Nicholas J. , Zetterberg Henrik , Kivipelto Miia 
Published: December 2023

AbstractBackgroundBlood biomarkers show promise in screening for Alzheimer’s disease (AD) brain pathology, but best predictors of eligibility for disease‐modifying treatment remain unclear. We have previously reported estimates for potential eligibility for anti‐amyloid treatment in a real‐life memory clinic setting (Rosenberg et al., Neurology 2022); the current study explored associations between AD blood biomarkers and treatment eligibility.MethodStudy population consisted of 224 patients from the Karolinska University Hospital Theme Aging Memory Clinic, with complete data (clinical, CSF, MRI, and plasma biomarkers Aβ40, Aβ42, NFL, GFAP, ptau181, ptau231). In total, 57% had subjective cognitive impairment, 21% mild cognitive impairment, and 22% dementia. Blood biomarkers were analysed using ultrasensitive Single molecule array (Simoa). Logistic regression models were used with zero‐skewness log‐transformed blood markers as predictors of treatment eligibility (defined based on the published use recommendations for anti‐amyloid treatment aducanumab). Areas under the curve (AUCs) were calculated for a pragmatic model including age, sex, and global cognition (MoCA) (base model), and for each model including blood biomarkers (alone and in combinations, with or without base model).ResultThirty‐two out of 224 patients (14%) were classified as potentially eligible for anti‐amyloid treatment. AUC for the base model was 0.65 (95% confidence interval 0.56–0.74). AUCs for models including only blood markers were 0.76 (0.69–0.83; Aβ42/40), 0.77 (0.70–0.84; NFL), 0.80 (0.73–0.88; GFAP), 0.81 (0.74–0.89; ptau181), 0.83 (0.76–0.90; ptau231), and 0.87 (0.82–0.93; all markers). AUC was 0.89 (0.83–0.94) for the full model (all data). In a scenario where the base model was combined with a single blood marker, highest AUCs were observed for models including ptau231 or GFAP (both 0.83, 0.75–0.90).ConclusionAll blood biomarkers, individually and combined, outperformed the commonly available clinical variables in predicting potential eligibility for disease‐modifying treatment. Ptau markers, especially ptau231, and GFAP seem most promising in this context.
CSF Alzheimer’s Disease Biomarker Changes in Veterans with Mild Traumatic Brain Injury
Authors: Li Ge , Iliff Jeffrey J , Shofer Jane , Mayer Cynthia L , Meabon James , Zetterberg Henrik , Blennow Kaj , Peskind Elaine R 
Published: December 2023

AbstractBackgroundTraumatic brain injury (TBI) has been reported to increase risk of Alzheimer’s dementia (AD). It remains unknown whether mild TBI (mTBI) caused by blast in Veterans confers a similar increase of risk. This study investigated early AD changes defined by cerebrospinal fluid (CSF) AD biomarkers in Veterans with blast mTBI.MethodFifty‐one Veterans with mTBI, 34 non‐mTBI Veterans, and 51 non‐mTBI civilians were recruited from Seattle, Washington. Age‐matched Veteran and civilian non‐mTBI participants had no lifetime history of TBI. All blast‐mTBI Veterans had experienced at least one war zone blast or combined blast/impact exposure, with acute symptoms meeting VA/Department of Defense criteria for mTBI. All participants underwent standardized clinical and neuropsychological assessments and lumbar puncture for collection of CSF. CSF biomarkers were measured at the Clinical Neurochemistry Lab in Mölndal, Sweden, using Meso Scale Discovery (MSD) assays for Aβ40 and Aβ42, and Innotest ELISAs for phosphorylated Tau181 (pTau181) and total Tau (tTau).ResultDifferences in all 4 CSF AD biomarkers between participants with and without mTBI were highly age‐dependent and most pronounced in older ages (Figure 1). Both CSF Aβ40 and Aβ42 became lower as age increasing in the mTBI group starting around age 40‐45 years, while they increased with age in the non‐mTBI participants. In contrast, CSF tTau and pTau181 mean levels remained relatively constant with age in participants with mTBI, but increased after age 45 in the non‐mTBI participants. Consequently, for participants aged 50+ years, Veterans with mTBI had lower mean AD biomarkers than the non‐mTBI participants. Similarly, the differences in cognitive performance were age‐dependent, i.e., poorer performance in older Veterans with mTBI than in the non‐mTBI participants. Furthermore, the relationships between CSF Aβ42 and cognitive performance were also age‐dependent; specifically, in participants aged 45+ years, lower CSF Aβ42 level was associated with poorer performance on tests of verbal fluency and memory.ConclusionThe earliest AD biomarker, CSF Aβ42, started to decrease in middle‐aged Veterans with mTBI, more than a decade earlier than those without mTBI in our earlier study, suggesting mTBI may accelerate brain deposition of Aβ and increase risk for AD.
Viability of an EEG‐based Automatic System for Early Dementia Screening
Authors: Agatic Filip , Dreo Jurij , Jug Jan , Pavlovcic Tisa , Ogrin Ajda , Aljaz Barbara , Sakic David 
Published: December 2023

AbstractBackgroundBased on recent demographic projections the worldwide number of people with dementia will triple by the year 2050, a socio‐economic burden that will disproportionally affect low‐ and middle‐income countries (Nandi et al., 2022). Therefore, a reliable, objective and cost‐effective screening methods are needed to be able to apply early interventions and slow down a decrease in quality of life for millions of patients. To address this issue, we explore viability of an EEG based system as an affordable solution for early dementia screening.MethodThe tested system includes a mobile amplifier (mBrainTrain) with 24 channel sponge EEG cap (Greentek) and a custom software (BDI) for EEG data acquisition and analysis (BrainTrip). The BDI software automatically detects and removes common EEG artifacts, calculates spectral EEG features known to be associated with cognitive decline (Sanchez‐Reyes et al., 2021), and uses density clustering and a multi‐layer perceptron classifier to predict the cognitive ability using a score between 0 and 100. We tested 448 senior participants who undertook five cognitive screening tests (MoCA, ADAS‐cog, ACE‐III, Eurotest, Phototest) and eight minutes resting state EEG recording on three separate sessions.ResultOur previous analysis was performed on about 50% of the total included subjects, which we now expended to the full dataset. Additionally, more provisions were made to prevent potential overfitting in building the final predictive model. Setting the cut‐off value of the BDI at 50 points, the specificity was at 97% and sensitivity at 65% compared to a consensus of all other cognitive tests. Assuming a dementia prevalence of 10%, the BDI test achieved an accuracy of 94%.ConclusionBased on the high accuracy of the EEG‐based assessment in detecting cognitive decline and dementia, it could be a promising option for dementia screening. It is an efficient, low‐cost and non‐invasive option for early intervention, especially in a primary healthcare setting.
An Alzheimer’s disease blood test study in a diverse community‐based population: Preliminary results from SEABIRD
Authors: Li Melody , Li Yan , Schindler Suzanne E. , Yen Daniel , Sutcliffe Siobhan , Babulal Ganesh M. , Benzinger Tammie L.S. , Lenze Eric J. , Bateman Randall J. 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) blood tests are needed to aid in the evaluation of dementia, but the performance of these tests should be evaluated in diverse groups and real‐world settings. The goals of the Study to Evaluate Amyloid in Blood and Imaging Related to Dementia (SEABIRD) were to enroll 1120 participants to determine the participant acceptability and validity (relative to amyloid PET) of a plasma amyloid‐β 42/40 test in a diverse, community‐based sample of older adults, and explore the impact of important factors (age, race, education, cognition, APOE genotype, and medical conditions) on the blood test’s performance.MethodSEABIRD measured plasma amyloid‐β 42/40 in a diverse population of older adults in the Saint Louis, Missouri, USA area. Participants completed a blood collection, cognitive screening (AD8® dementia screening interview and Montreal Cognitive Assessment [MoCA]), and a survey about their study experience and perceptions of the blood test. A subset of participants completed additional blood collection for reproducibility, amyloid PET and MRI for validation of the blood test, and the Clinical Dementia Rating® (CDR) for validation of the cognitive screening measures.ResultOf the 859 participants enrolled in this ongoing study, 20.6% self‐identified as Black or African American and the percentage of APOE ε4 carriers was 30.2% (Table 1). Compared to the general population, SEABIRD participants were more likely to be female, aged 70‐79 years, and highly educated. They were less likely to report high cholesterol, diabetes, kidney disease, and stroke, and more likely to report depression. The receiver operating characteristic area under the curve for distinguishing cognitively unimpaired (CDR = 0) from cognitively impaired (CDR>0) individuals was 0.72 for the informant‐rated AD8, 0.46 for the self‐rated AD8, 0.70 for the MoCA, and 0.79 for the AD8/MoCA composite (Table 2). Survey results indicated that the blood test was well accepted (Figure 1), but it was perceived more positively by white and highly educated individuals.ConclusionA study of an AD blood test achieved rapid enrollment, broader diversity than typical AD cohorts, and high rates of participation. These results suggest that an AD blood test could be used for screening in a diverse clinical population.
Physical Inactivity and Social Determinants of Health Among Older Adults with Mild Cognitive Impairment and Dementia
Authors: Bartley Mairead M. , Baer‐Benson Henry , Schroeder Darrell R. , St Sauver Jennifer , Khera Nandita , Griffin Joan M. 
Published: December 2023

AbstractBackgroundPhysical activity can improve the physical health of people living with mild cognitive impairment (MCI) and dementia and may have cognitive benefits. Identifying modifiable social factors inhibiting physical activity among this group is important. We examined the relationship between reported physical activity levels and social determinants of health (SDOH) in a population of older adults living with MCI or dementia.MethodWe included people with a diagnosis of MCI or dementia, age 55 years and older, who were empaneled to Community Internal Medicine at Mayo Clinic (Rochester, Minnesota), had a clinic visit between June 1, 2019 and June 30, 2021 and had completed a SDOH questionnaire. We focused on 8 SDOH domains: education, depression, alcohol use, stress, financial resource strain, social connections, food insecurity and transportation needs. Self‐reported activity levels were categorized as inactive (0 minutes of exercise per week), insufficiently active (10‐140 minutes per week) or sufficiently active (≥150 minutes per week). SDOH domains were compared according to physical activity level using χ2 tests and multinomial logistic regression.ResultA total of 3224 persons with MCI (n = 1371) or dementia (n = 1853) who had completed questions on physical activity were included. Of these, 1936 (60%) were characterized as physically inactive and 837 (26%) insufficiently active. Characteristics associated with an increased likelihood of physical inactivity were older age, female sex, obesity, lower education, dementia diagnosis, depression risk and increased social isolation (all p<0.001).ConclusionPhysical inactivity is common among people living with MCI and dementia. Physical activity levels may be influenced by many modifiable factors, highlighting potential areas for intervention in this population.
Cross vendor test‐retest validation of diffusion tensor analysis along the perivascular space (DTI‐ALPS) method for evaluating glymphatic system function in vascular cognitive impairment and dementia (VCID)
Authors: Liu Xiaodan , Barisano Giuseppe , Shao Xingfeng , Jann Kay , Ringman John M , Lu Hanzhang , Arfanakis Konstantinos , Arvind Caprihan , Decarli Charles , Gold Brian T. , Maillard Pauline , Satizabal Clandia L. , Fadaee Elyas , Habes Mohamad , Stables Lara , Singh Herpreet , Fischl Bruce , van der Kouwe Andre J. , Schwab Kristin , Helmer Karl G. , Greenberg Steven M. , Wang Danny J.J. 
Published: December 2023

AbstractBackgroundGlymphatic system (GS) is a recently discovered brain‐wide perivascular fluid transport system in the cerebral nervous system (CNS)(Benveniste H et al., 2019) The impairment of glymphatic transport has been demonstrated to be associated with several neurological diseases, in particular the vascular cognitive impairment and dementia (VCID)(Tang J et al., 2022). The diffusion tensor analysis along the perivascular space (DTI‐ALPS) was proposed to non‐invasively evaluate the GS clearance dysfunction which has been used to investigate the GS in various pathologies(Taoka T et al., 2017, Hsu JL et al., 2022). However, studies on the cross‐vendor and test‐retest reliability of DTI‐ALPS method are lacking. The current study aimed to perform cross‐vendor, inter‐rater and test‐retest validations of DTI‐ALPS method by using a cohort from the MarkVCID consortium.MethodFifty participants’ DTI data from the MarkVCID consortium (consists of 7 sites) were included in this study: 15 participants were scanned on four MRI scanners; 35 participants underwent two MR scans within 14 days. The DTI data were acquired used a single shell, b = 1000s/mm2, 40‐direction with a voxel size of 2.02.02.0mm3 and six b = 0 s/mm2 on 3T MR scanners from seven sites, including two Siemens systems, one Philips system and one GE system. Two pipelines by using DSI studio and FSL software were developed for data processing and ALPS index calculation (Figure 1). The mean ALPS (mALPS) index was obtained by the average of bilateral ALPS index and was used for testing the inter‐rater, cross‐vendor and test‐retest reliability. The association between mALPS index and Montreal Cognitive assessment (MoCA) scores were evaluated using a general linear model with age and gender as covariate.ResultThe Bland‐Altman plot and scatterplot illustrated the validation results of the mALPS index analyzed using DSI studio and FSL pipelines (Figure 2). The mALPS index demonstrated favorable inter‐scanner reproducibility (ICC = 0.77 to 0.95, P< 0.001), inter‐rater reliability (ICC = 0.96 to 1, P< 0.001) and test‐retest repeatability (ICC = 0.89 to 0.95, P< 0.001). A significantly positive correlation was observed between mALPS index and MoCA scores (r = 0.502, P< 0.01) (Figure 3).ConclusionThe mALPS index offers a robust potential biomarker for evaluating GS clearance function in VCID.
The use of Event Related Potentials to predict amyloid PET status among patients from a memory disorders clinic
Authors: Chadalavada Myna , Marin Anna , Schiloski Kylie A , Suh Cheongmin , Uppal Prayerna , Palumbo Rocco , Budson Andrew E , Turk Katherine W 
Published: December 2023

AbstractBackgroundAmyloid PET scans provide in vivo evidence of Alzheimer’s Disease (AD) however, due to high cost and limited insurance coverage, they are not available as part of standard clinical care. Event Related Potentials (ERPs) are inexpensive, and non‐invasive method to directly measure brain physiology that may allow an alternative method for detection of AD pathology.MethodWe investigated whether ERPs together with neuropsychological data are predictors of amyloid PET status in patients with memory complaints. Older veterans aged 50‐100 were recruited from a memory disorders clinic at VA Boston Healthcare System. Participants underwent a standard neuropsychological battery and an ERP auditory oddball protocol. Twenty‐eight patients had a positive amyloid PET scan, and thirty‐nine patients had a negative amyloid PET scan.ResultsTwo neuropsychological measures (CERAD Delayed Recall and MMSE) were predictors of amyloid PET status. Increased P200 target amplitude (Figure 1B), and decreased P200 standard latency (Figure 1A) in patients with amyloid PET positive scan were found. ERP‐P200 amplitude in response to target tones and ERP‐P200 latency in response to standard tones were also predictors of amyloid PET status. The highest classification accuracy was obtained when combining CERAD Delayed Recall, MMSE and ERP‐P200 standard latency.ConclusionERP‐P200, especially when combined with cognitive measures of delayed memory and overall cognitive function, was predictive of amyloid beta (Aβ) load in the brain of patients from a memory disorder clinic. Increased P200 amplitude, and decreased P200 latency in patients with amyloid PET positive scan might suggest hyperactivation of perceptual bottom‐up processes to compensate for AD‐related synaptic loss in the fronto‐parietal networks.
Recalibrating narratives of gender differences in ADRD research: Lessons and opportunities from the Global South
Authors: Esiaka Darlingtina 
Published: December 2023

AbstractSex and gender differences in brain health and cognitive decline are increasingly visible as we grapple with the profound impact of Alzheimer’s disease and related dementia (ADRD). However, the conventional narratives of sex and gender differences in ADRD research are often grounded in mainstream Global North cultural values. Despite its manifestation, the indigenous and non‐western concepts of sex and gender and the intersecting narratives of social vulnerability remain largely unexplored. Accurate characterization of sex and gender differences in ADRD must include narratives evident in high‐incidence populations or regions beyond the Global North. A full account of sex and gender differences in ADRD requires changing the narrative to interweave critical approaches. Specifically, it requires that we systematically examine how to reframe, repair, or otherwise change narratives about sex and gender differences in AD/ADRD research that do not reflect the experiences of people in the Global South. The talk will serve as a resource and a call to action regarding how one can produce and critically consume knowledge that affirms and represents all experiences ‐ including indigenous people and people in the Global South. Further, it will foster innovative approaches to empirical research on sex and gender differences in AD/ADRD and help us understand current research findings in the field and their limited capacity to inform research and clinical practice outside of the Global North.
Can Plasma Optical Density or Transmission be used for helping AD Diagnosis?
Authors: Li Wei , Arnold Elizabeth , Jenkins Bradley , Hemby Leslie , Patel Hailey , Vobbilisetty Nandini , Li Daniel , Mamaeva Olga , Maqbool Muhammad 
Published: December 2023

AbstractBackgroundCurrently, diagnosis of Alzheimer’s disease (AD) mainly relies on clinical and neuropsychological tests, which are not only costly but also time‐consuming and burdensome to the patients. The only way to confirm an AD diagnosis is the post‐mortem detection of amyloid plaques and neurofibrillary tangles. The research on biomarkers has some significant progresses in recent years but none is available to be used clinically that can meet the sensitivity and specificity requirements.MethodBlood samples were collected from participants with different diagnoses: early‐onset AD, late‐onset AD, and those without an AD diagnosis (controls). 22 participants had early‐onset AD, 72 participants had late‐onset AD, and 48 participants were in the control group. The optical density (OD), as well as transmission, were measured from blood plasma samples using a densitometer. An analysis of variance (ANOVA) was performed using the diagnosis group as the independent variable with post hoc Bonferroni correction.ResultThe optical density for the late‐onset AD group was 0.356 ± 0.009, which is significantly higher than the counterpart measure for the control group of 0.313 ± 0.012 (p = 0.015). By contrast, the optical density for the early‐onset AD group was 0.361 ± 0.017, which is not significantly different from the late‐onset group (p = 1) or the control group (p = 0.065). As expected, the late‐onset AD group had an average transmission of 0.947 ± 0.002, which is at the level compared with the early‐onset AD group of 0.947 ± 0.004 (p = 1) but significantly lower than the same measure from the control group of 0.958 ± 0.003 (p = 0.006).ConclusionThe physical properties of blood plasma: OD or transmission can help with an AD diagnosis, which is particularly useful for diagnosing late‐onset AD.