bluuebunny/crossref_metadata_2025_split huggingface dataset:
The utility of neuropsychological process scores in verbal recall and verbal fluency in persons with or at risk for dementia: Data from COMPASS‐ND
Authors: Phillips Natalie , Sollazzo Katrina 
Published: December 2023

AbstractBackgroundSubjective cognitive decline (SCD) is considered a risk state for decline to mild cognitive impairment (MCI) or dementia due to Alzheimer’s disease (AD). By definition, individuals with SCD report concerns about changes in cognitive function but perform within normal limits on formal testing. This study examined whether neuropsychology process scores on tests of auditory learning and memory (the Rey Auditory Verbal Learning Test, RAVLT) and semantic and phonemic oral fluency were able to distinguish subtle difficulties in cognition, over and above total scores.MethodWe used data from the Comprehensive Assessment of Neurodegeneration and Dementia (COMPASS‐ND) study to examine performance in 60 cognitively normal (CN) older adults with no cognitive complaints (mean age = 69 years; mean education = 16 years), 55 participants with SCD (age = 70; education = 17), 102 with MCI (age = 72; education = 16), and 47 with AD (age = 75; education = 15). Participants were matched on age and education, except for AD participants who were older. Age and education were co‐variates in all analyses. For the RAVLT, we examined delayed recall total scores, and process measures of primacy and recency recall on the second learning trial. For fluency, we examined total scores, and process measures of clustering, switching, word frequency, and age of acquisition.ResultRAVLT: An item position by group interaction revealed that primacy scores better distinguished all participant groups (CU>SCD>MCI>AD) than delayed recall (CU = SCD = MCI>AD). The left subiculum hippocampal subfield volume was positively associated with primacy scores in the MCI group, controlling for intracranial volume and age. Oral fluency: Both phonemic and semantic total scores discriminated CN, MCI, and AD participants in a stepwise manner; there was a non‐significant trend for SCD participants to perform more poorly than CN. Process scores did not provide additional discrimination.ConclusionThese findings indicate that primacy scores for episodic recall are sensitive to subtle memory deficits in SCD and may reflect hippocampal atrophy, supporting the clinical use of using serial position effects in the assessment of MCI and SCD.Learning Objective(s): Participants will learn about more detailed scoring methods for common neuropsychological tests, their sensitivity to subtle cognitive deficits in SCD, and their relationship with neuroanatomical structures.
Primacy and recency effects in verbal memory are differentially associated with post‐mortem frontal cortex p‐tau217 level in a mixed sample of community‐dwelling older adults
Authors: Gicas Kristina M , Honer William G , Petyuk Vladislav A , Wilson Robert S. , Boyle Patricia A , Leurgans Sue E. , Bennett David A. A 
Published: December 2023

AbstractBackgroundEmerging research indicates plasma phosphorylated (p)‐tau217 levels may demonstrate sensitivity to preclinical and symptomatic Alzheimer’s disease (AD). Serial position effects (primacy and recency) in verbal memory are sensitive cognitive markers of early AD; however associations between these measures and p‐tau217 in postmortem brain samples are unclear. In a mixed sample of older adults, this study examined how primacy and recency scores measured years before death are associated with post‐mortem levels of p‐tau217, with p‐tau202 as a complementary post‐mortem measure of early tau phosphorylation.MethodData were used from the Rush University Religious Orders Study and the Memory and Aging Project. Participants were 1098 community‐dwelling older adults (68.9% female, M
age = 80.1) who were non‐demented at baseline and followed until death (M
follow‐up years = 9.2; status at death: 34.7% unimpaired, 26.0% mild cognitive impairment, 39.3% dementia). Baseline serial position scores were calculated as the proportion of words recalled from the beginning (primacy) and end (recency) of the CERAD Word Memory List. A neuropathological exam classified Braak stage. A middle frontal gyrus tissue sample was used to quantify p‐tau217 and p‐tau202 with selected reaction monitoring proteomics. Linear regression analyses examined associations of cognitive scores with p‐tau, adjusting for age, sex, education, APOE e4 status, Braak stage, and time to death.ResultAs expected, higher Braak scores were associated with higher levels of brain p‐tau217. In the fully adjusted model, higher baseline primacy scores (b = ‐.27, p = .026), but not recency scores (b = ‐.02, p = .901), were associated with lower levels of p‐tau217 but not p‐tau202 in middle frontal cortex. Higher delayed recall (b = ‐.08, p = .007), but not immediate recall (b = ‐.01, p = .071), was also associated with lower p‐tau217.ConclusionPrimacy scores measured years before death were associated with the outcome of post‐mortem brain levels of p‐tau217, but not p‐tau202. The differential associations of serial position scores with p‐tau suggest they may add complementary information about early neuropathological changes when used in conjunction with routine delayed recall scores. These findings further contribute to evidence for p‐tau217 as a sensitive biomarker of AD.
Long‐term neuropathological effects of amyloid‐β immunization revealed by spatial transcriptomics
Authors: van Olst Lynn , Simonton Brooke , Ramakrishnan Abhirami , Piehl Natalie , Teregulova Victoria , Norman Jeanette , Nicoll James AR , Boche Delphine , Gate David 
Published: December 2023

AbstractBackgroundModern Alzheimer’s disease (AD) therapeutics include immunization against amyloid‐β (Aβ). Intriguingly, neuropathological examination of the first active Aβ vaccination trial (Elan Pharmaceuticals’ AN1792) showed some patients with evidence of Aβ clearance 15 years post‐vaccination. Yet, these patients progressed to severe dementia before death, possibly due to ongoing tau propagation. The AN1792 trial was halted when some participants developed aseptic meningoencephalitis driven by auto‐aggressive T cells. Imaging features of meningoencephalitis experienced by AN1792 subjects are pathologically reminiscent of amyloid‐related imaging abnormalities (ARIA) that currently hamper clinical trials and the therapeutic use of passive Aβ immunotherapy for AD.MethodHere, we utilized spatial transcriptomics to sequence RNA from formalin‐fixed paraffin‐embedded (FFPE) cortical brain sections from a unique neuropathological cohort of 14 immunized AD cases and a placebo‐control from AN1792. Additional controls included 6 naïve (unimmunized) AD cases and 3 non‐neurological disease controls.ResultWe reveal a cytotoxic and migratory phenotype of infiltrating T cells in the meninges of AD patients immunized against Aβ. Specifically, brain infiltrating T cells express cytotoxic genes (e.g. GZMA), activation genes (e.g. CD74 and B2M), and migratory genes (e.g. ITGAL and VCAM1). Additionally, we discovered genetic signatures that distinguish cortical areas cleared of Aβ in immunized AN1792 subjects.ConclusionWe show that active Aβ immunotherapy induces long‐term adaptive immune effects in the AD cortex.
TRAILBLAZER‐ALZ 3 – A Deeper Dive into Time‐to‐Event Trials
Authors: Pugh Melissa A M 
Published: December 2023

AbstractBackgroundThe pathophysiologic process of Alzheimer’s Disease (AD) is underway before cognitive decline becomes evident (i.e.; preclinical AD). Beginning treatment during this phase is believed to lead to beneficial outcomes in terms of disease progression. TRAILBLAZER‐ALZ 3 (TB3; NCT05026866) is an ongoing Phase 3 decentralized clinical trial assessing the effect of donanemab, a monoclonal antibody that removes amyloid plaques via microglial‐mediated clearance, versus placebo on clinical progression in preclinical AD. Clinical outcomes are assessed virtually by using central raters, psychometric examinations, and self‐administered tests. The primary endpoint of interest is the time to clinical progression as measured by the Clinical Dementia Rating scale global score (CDR‐GS).MethodTwo of the most frequently used methods to analyze time‐to‐event data are Kaplan‐Meier curves and Cox proportional hazards models. In TB3, the primary endpoint will be assessed via a Cox proportional hazard regression model. The key assumptions that will be made with this modeling approach are proportionality and censoring. Proportionality refers to the relative hazard being constant over time and how to treat censored observations, which refers to patients who do not reach the event during the observation period. While this approach has been used in fields such as oncology, we have adapted it for the assessment of time to clinical progression of AD cognitive decline. From this approach the hazard ratio, an estimate on the instantaneous risk, can be calculated. This measure can give insight, at a given time point, of the risk of progression of AD that a participant has.We will also look at additional considerations of collecting data in a decentralized remote manner, such as missing data due to technology issues, and highlight the approaches that will be used to analyze additional cognitive and biomarker data.ResultThis investigation will show that we have adapted analytic techniques to determine the time to clinical progression of AD as measured by an increase in CDR‐GS from baseline at 2 consecutive visits.ConclusionWe present an analytical method of assessing potential treatments to slow disease progression during the preclinical AD phase without requiring centralized assessment sites.
BrainChart cortical thickness centile scores: a generalizable tool to detect age‐inappropriate cortical neurodegeneration in Alzheimer’s disease
Authors: Parker Thomas D , Bethlehem Richard A.I. , Seidlitz Jakob , White Simon R , Bernstock Joshua D , Bourke Niall , David Michael CB , de Taurines Anastasia Francoise L Gailly , Giovane Martina Del , Graham Neil SN , Kolanko Magdalena A , Zimmerman Karl A , Malhotra Paresh A , Patel Maneesh , Scott Gregory PT , Alexander‐Bloch Aaron , Bullmore Edward T , Sharp David J 
Published: December 2023

AbstractBackgroundIdentifying age‐inappropriate cortical neurodegeneration on structural MRI is a key component of Alzheimer’s disease (AD) assessment. However, widely available reference standards that enable objective interpretation are lacking. BrainChart (www.BrainChart.io; https://github.com/BrainChart/Lifespan) calculates age and sex adjusted centile scores for structural MRI metrics using normative data from 101,457 participants across the lifecourse and can be applied across different datasets. We applied this approach to regional cortical thickness estimates and explored its utility in identifying patients with AD associated neurodegeneration.MethodsCross‐sectional BrainChart cortical thickness centile scores were calculated for 241 individuals with pathologically confirmed AD (median scan time prior to death 5.8 years), as well as 1432 cognitively normal participants (CN) from the NACC dataset. Area under the receiver operating characteristic curve (AUC) analyses were performed to identify the cortical regions that best identified patients with pathologically confirmed AD. This approach was then applied to 305 participants from the ADNI‐3 cohort, all of whom underwent clinical amyloid (florbetapir) PET and tau (flortaucipir) PET within 6 months of structural MRI (CN = 185; Mild Cognitive Impairment (MCI) = 95); AD = 26).ResultsThe top ten performing regions for differentiating pathologically confirmed AD from CN in the NACC dataset were entorhinal, middle temporal, inferior parietal, isthmus cingulate, fusiform, supramarginal, inferior temporal, superior temporal, precuneus and temporal pole. AUCs ranged from 0.72 – 0.77 (figure 1 and table 1). Combining these ten regions into a single model significantly improved diagnostic separability (AUC = 0.81, figure 1). Optimal cut‐points for individual regions ranged from the 25th centile to the 35th centile, with sensitivities ranging from 57.7% to 68.9%, and specificities ranging from 72.6% to 80.9%. Using progressively lower centile scores increased specificity but decreased sensitivity (table 1).In ADNI‐3 participants, a combined model of the same ten regions derived from the NACC dataset was able to discriminate amyloid and tau pet positive AD patients from amyloid and tau negative CN (AUC = 0.98), as well as amyloid and tau positive MCI patients from amyloid and tau negative CN (AUC = 0.85) (figure 2).ConclusionBrainChart age and sex adjusted cortical thickness centile scores, derived from an extensive normative dataset, represent a generalizable method for objectively identifying cortical neurodegeneration in AD.
Dysphasia after stroke and legal capacity
Authors: Voskou Panagiota 
Published: December 2023

AbstractBackgroundAlthough after stroke dysphasia or aphasia is not equal to incapacity, the legal capacity of patients can be doubted. The patients’ ability to fully comprehend the given information and make decisions may be impaired. Stroke is sudden, life threatening and likely to affect capacity even in the absence of dysphasia. There are currently no published guidelines in the management of legal issues for patients and professionals.MethodA literature review in the Pubmed database has been made, using the key‐words: stroke, legal capacity, decision‐makingResultBrain injury after stroke may impair appreciation of decisions’ consequences and/or communicating decisions effectively, while the capacity to reason remains. Stroke may affect various brain areas, i.e. prefrontal cortex involved in decision‐making (ventromedial prefrontal cortex damage may lead to impulsive decision‐making). A right‐brain stroke may cause poor executive function, lack of initiation or neglect. Left‐hemisphere strokes may lead to aphasia and reduced capacity evaluation. The dysphasic may understand more than he can express, or vice versa.Difficulties further compounding communication problems include: reading and writing; numeracy; inattention/concentration; fatigue; emotional control (lability); perseveration; intellectual functioning. Receptive aphasia can impair understanding medical options, while expressive aphasia may prevent communicating relative decisions.Patients may also be susceptible to undue influence regarding testamentary and financial capacity due to communication deficits and varying levels of dependence. Depression following stroke can further impair capacity.ConclusionThe patient may have a communication rather than a capacity deficit. Judging a patient’s ability to weigh information is often the most difficult aspect of legal capacity assessment. There is little literature or high court jurisdiction regarding whether dysphasia after stroke impairs patients’ capacity. Evaluation of the prerequisites for legal capacity requires a multi‐professional cooperation.
A machine learning examination of the utility of CSF, neuroimaging, and plasma biomarkers in late onset Alzheimer Disease
Authors: Meeker Karin L. , Luckett Patrick H. , Barthélemy Nicolas R. , Hassenstab Jason J. , Xiong Chengjie , Cruchaga Carlos , Benzinger Tammie L.S. , Schindler Suzanne E. , Bateman Randall J. , Holtzman David M. , Morris John C , Gordon Brian A. , Ances Beau 
Published: December 2023

AbstractBackgroundAlzheimer disease (AD) biomarkers are crucial to understanding disease pathophysiology, aiding accurate diagnosis, and identifying target treatments. Although the number of biomarkers continues to grow, the utility and uniqueness of each is poorly understood.MethodData were obtained from 527 community dwelling volunteers enrolled in memory and aging studies at the Charles F. and Joanne Knight Alzheimer Disease Research Center at Washington University in St. Louis, MO. Hierarchical clustering was used to group 27 cross‐sectional imaging, cerebrospinal fluid (CSF), and plasma measures of Aβ, tau, neuronal injury, and inflammation drawn from magnetic resonance imaging, positron emission tomography (PET), mass‐spectrometry assays, and immunoassays. Neuropsychological and genetic measures were also included. Feature selection identified the strongest predictors of amyloid PET positivity across the entire cohort. Models also predicted cognitive impairment across the entire cohort and in amyloid PET positive individuals.ResultFour main clusters emerged reflecting core AD pathology (amyloid and tau), neurodegeneration, AT8 antibody‐associated phosphorylated (p‐tau), and neuronal dysfunction and inflammation. Relative to other measures, markers from the core AD pathology cluster were the best predictors of amyloid PET status with CSF pT217/T217 (%) being the most prominent followed by CSF pT111/T111 (%) and CSF ptau181/Aβ40. In the entire cohort, Aβ and tau markers (CSF pT217/T217 (%), total‐tau/Aβ40, ptau181/Aβ40) were also the best predictors of dementia. When examining only those with positive amyloid PET, CSF total‐tau/Aβ40 was the strongest predictor of cognitive impairment followed by tau PET, CSF ptau181/Aβ40, and pT217/T217 (%). Plasma Aβ42/40 alone did not perform as well as other PET and CSF measures. CSF measures of neuronal dysfunction and inflammation were relatively poor predictors of amyloid and cognitive status.ConclusionAlthough many AD biomarkers are interrelated, relatively few have the ability to strongly predict clinical status. Relative to other markers, CSF pT217/T217 (%) is the best predictor of amyloid and impairment status across all individuals, while CSF total‐tau/Aβ40 is the best predictor of impairment in individuals already on the AD trajectory. Most non‐specific markers perform poorly in the context of AD. The current research provides insight into which biomarkers may be most useful in AD clinical practice and trials.
Explorations of Caregiver Health and Well‐Being
Authors: Anderson Maria E 
Published: December 2023

AbstractBackgroundRecent projections have found that the global prevalence of dementia is expected to grow rapidly through 2050, rising from an estimated 57.4 million cases in 2019 to an estimated 152.8 million cases by 2050. This has alarming public health consequences, as dementia takes a toll socially, emotionally, and financially, with a global societal cost of $1.3 trillion dollars in 2019. Caregivers are at the forefront of this crisis, with more than 11 million individuals in the US providing unpaid care for individuals with dementia, estimated at 16 billion dollars worth of care/year. Studies investigating the factors that impact caregiver burden are lacking. This study aims to 1) qualitatively examine caregiver burden and quality of life (QoL) 2) identify/highlight factors that might provide support and/or improve caregiver QoL.MethodThis is a qualitative, cross‐sectional study that will use a series of interviews and questionnaires to collect data. The studies will be created on, and deployed using, Qualtrics software, a commonly used platform for survey studies.ResultPrevious research suggests that factors impacting caregiver burden and QoL will be highly individualized across demographics such as socioeconomic status and race, and that QoL will be, on average, lower among caregivers as a group compared to the general population. We hypothesize that engagement in various lifestyle factors, particularly those that are self‐focused, regardless of amount of time spent on them, will correlate with higher QoL and lower caregiver burden scores.ConclusionThe factors that predict caregiver burden and quality of life are an important and often under‐examined part of dementia care. This study, expected to be completed in Spring 2023, will contribute to the current understanding of caregiver’s experiences, and provide practical ideas to help increase QoL and reduce burden.
Neuropsychological Characteristics of Wandering in Patients with Drug‐naïve Alzheimer’s Disease
Authors: Yang Youngsoon 
Published: December 2023

AbstractBackgroundWandering represents one of a major problem occurring in patients with Alzheimer’s disease (AD). To find the disproportionate neuropsychological deficit and behavioral psychological symptoms in dementia (BPSD) of AD patients with wandering compared to AD patients without wandering, this study examined the set of neuropsychological tests and caregiver‐administered neuropsychiatric inventory (CGA‐NPI).MethodsPsychotropic‐naïve (drug‐naïve) probable AD patients with wandering (64) and without wondering (278) were assessed with the Seoul Neuropsychological Screening Battery, which included measures of memory, intelligence, and executive functioning.ResultsPatients with wandering had lower scores in the Rey‐Osterrieth Complex Figure copy, Fist‐edge‐palm, Alternating hand movement tests compared to patients without wandering. The degree of wandering in AD patients was significantly related with CGA‐NPI subdomains of aggression, disinhibition, depression, and delusions.ConclusionsThis study showed that 1) AD patients with wandering have disproportionately cognitive deficit suggesting frontal and right parietal dysfunctions, 2) wanderings are related with specific BPSD. Considering these results, AD patients with wandering may have specific neuronal anatomic substrates related with pathology of Alzheimer.
A multi‐omic approach to elucidate novel disease mechanisms and biomarkers for psychosis in Alzheimer’s disease
Authors: Pishva Ehsan , Kouhsar Morteza P , Weymouth Luke Stephen , Smith Adam R. , Wedatilake Yehani , Torkamani Ali , Sweet Robert , Ballard Clive G , Mill Jonathan , Kofler Julia , Bergh Sverre , Selbæk Geir , Lunnon Katie , Creese Byron 
Published: December 2023

AbstractBackgroundPsychosis is a debilitating syndrome occurring in 40‐60% of people with Alzheimer’s disease (AD) and corresponds with a more severe disease course. Evidence suggests that psychosis in AD is associated with a distinct profile of microbiological changes, but little is known about the molecular processes driving etiology.MethodGenome‐wide DNA methylation, small non‐coding (nc) RNAs (microRNA, transfer RNA, piwiRNA) and long coding and ncRNAs (mRNA, lincRNA, cicular RNAs) were quantified from 248 whole blood samples obtained from the Norwegian registry of persons assessed for cognitive symptoms (NorCog) cohort. Multi‐omics profiles of AD patients with psychosis (AD+P) were compared to the patients without psychosis (AD‐P).ResultThere were significant differences in DNA methylation, small ncRNAs, and long coding and ncRNAs between AD+P and AD‐P patients. Further analysis revealed specific genomic regions and molecular pathways that were differentially methylated or expressed in AD+P patients compared to AD‐P patients.ConclusionOur findings suggest that there may be distinct molecular signatures associated with AD psychosis, and that these differences may potentially be used as biomarkers for the early detection and diagnosis of AD psychosis.