bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathways towards Cognitive resilience in the context of amyloid pathology: a longitudinal matched study design
Authors: Aguillar Pablo , Akinci Muge , Palpatzis Eleni , Bejanin Alexandre , Arenaza‐Urquijo Eider M 
Published: January 2025

AbstractBackgroundCognitive resilience can be defined as better‐than‐expected cognitive performance in the context of Alzheimer’s disease (AD) pathologies or increased AD risk. We investigated pathways associated with cognitive resilience trajectories in amyloid positive (A+) and/or APOE4 cognitively unimpaired (CU) older adults including brain resilience, resistance to AD pathologies and vascular pathology.MethodWe included 534 CU ADNI participants with available cognitive data, longitudinal amyloid‐PET ( [18F]florbetaben and [18F]florbetapir) and structural MRI (gray matter volumes) and, as ubset with tau‐PET ( [18F]AV1451) (n = 287) and white matter hyperintensities (n = 467) volume data (n = 534). We performed a one‐to‐one matched design, aligning participants by their baseline amyloid levels, MMSE scores, and age within an average follow‐up time of 6 years (68.18 ±32 months). We identified 44 CU participants ‐ defined as cognitive resilient ‐ who were A+ and/or APOE4 carriers and remained CU and 44 CU A+ matched participants who converted to MCI or AD (non‐resilient). To assess brain resilience, resistance to pathologies and vascular pathways, at baseline, t‐test were performed with gray matter volumes, amyloid (n = 44), tau (n = 12) and WM measurements (n = 27) as outcomes of interest. Longitudinally, linear mixed effect models were used to examine the interaction between cognitive resilient status (resilient vs non) and time on regional amyloid and tau deposition, and gray matter volume.ResultAt baseline, cognitive resilient participants were characterized by lower tau burden in temporal regions (Figure 1). Longitudinally, cognitive resilient participants showed lower tau accumulation in medial temporal and limbic areas, including the insular and anterior cingulate cortices, and lower volume loss in fusiform, inferior temporal and entorhinal cortex (Figure 2). Unexpectedly, cognitive resilience participants showed greater amyloid increases notably in the anterior cingulate, although both groups showed increased amyloid accumulation. Sensitivity analysis adjusting by conversion time, to rule out the impact of varying accumulation rates due to disease progression, rendered similar results.ConclusionOur results suggest that processes downstream amyloid deposition including resistance to tau and brain maintenance might be key to maintain cognitive function in the presence of amyloid pathology.
The impact of polygenic cardiovascular risk on Alzheimer’s‐like brain changes
Authors: Lenhoff Sarah‐Alexis , Page Frederick A , Nowell Joseph , Edison Paul 
Published: January 2025

AbstractBackgroundA growing body of evidence demonstrates the relationship between cardiovascular risk and the risk of dementia development. Researchers have identified several genetic links between cardiovascular diseases and Alzheimer’s disease, including the apolipoprotein E and methylenetetrahydrofolate reductase (MTHFR) genes. Here we evaluated the impact of cardiovascular polygenic risk on pathological brain changes associated with Alzheimer’s disease, to elucidate the potential mechanism by which cardiovascular risk induces brain damage.Methodsn ≈ 30,000 participants were evaluated from the UK Biobank database. The standard cardiovascular polygenic risk score was acquired for all participants. Where data was available the following data was downloaded; hippocampal volume and total grey matter volumes, white matter hyperintensity volume, whole brain grey matter and temporal cerebral blood flow, and diffusion‐weighted imaging outcomes. Linear regressions were performed to evaluate the influence of cardiovascular polygenic risk on brain changes in various regions implicated in Alzheimer’s disease.ResultsA higher cardiovascular polygenic risk demonstrated the strongest association with an increased deep white matter hyperintensity volume. Increased polygenic risk was additionally associated with a reduced total grey matter volume. In the parahippocampal part of the cingulum, higher polygenic risk was associated with increased mean diffusivity and reduced orientation dispersion. No association was shown with cerebral blood flow.ConclusionGenetic cardiovascular risk was demonstrated to be associated with several Alzheimer’s‐like neurodegenerative changes. A strong association was shown with white matter hyperintensities and decreased total brain volume, indicating the vulnerability to cognitive impairment in those with higher cardiovascular risk. Screening cardiovascular genetic risk at mid‐life could provide a useful tool to implement therapeutic intervention, not only to reduce the risk of cardiovascular disease but to prevent the development of Alzheimer’s disease.
The Relationship between Subjective Visual Impairment and Domain‐Specific Cognitive Performance in Cognitively Normal Older Adults and MCI Patients
Authors: Sergio Jordan P , Dubois Abigail , Thompson Louisa I. , Strenger Jennifer , Price Ashley N. , Stradtman Megan , Sinoff Stuart , Snyder Peter J. , Alber Jessica 
Published: January 2025

AbstractBackgroundAge is the greatest risk factor for self‐reported visual impairment (VI) and Alzheimer’s Disease (AD). While prior studies demonstrate associations between VI and cognitive screening measures in older adults, the relationship between VI and specific cognitive domains remains unexplored. We examined the relationship between subjective VI and executive function, attention, visuospatial construction, episodic memory, and processing speed.MethodParticipants were older adults aged 55‐80: 58 cognitively unimpaired (CU) (MoCA>=26, CDR=0) and 19 MCI patients (MoCA>19, <24, CDR=.5). Subjective VI was measured with the National Eye Institute Visual Function Questionnaire (NEI‐VFQ). A neuropsychological battery including the MoCA, CDR, Digit Symbol Substitution Test (DSST), Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and Free and Cued Selective Reminding Test (FCSRT) was administered to assess cognition. Partial correlations controlling for age and years of education compared subjective VI scores to cognitive scores. A multivariate, repeated measures ANCOVA was run on a subset (N=23) of participants with 1 year follow‐up data to determine whether group performance differed over time on NEI‐VFQ and DSST.ResultThere were significant correlations between scores on the composite NEI‐VFQ and both the DSST and visuospatial sub‐scale of the RBANS in the CU and patient groups (p<.05). CU adults showed a greater practice effect over time on the DSST than the patient group, who declined in performance. Specifically, CU APOE E4 carriers had a larger increase in DSST score over 12 months than non‐carriers, along with a larger increase in subjective VI on the NEI‐VFQ.ConclusionAttention, processing speed, visuospatial construction, and executive function performance was related to a standardized measure of subjective VI in CU older adults and MCI patients. After 12 months, CU APOE E4 carriers showed a stronger practice effect than CU non‐ carriers on the DSST, concomitant with increase in subjective VI. Subjective measures of VI may serve as a tool in early detection of cognitive impairment, although increases in VI over time co‐occurred with increased practice effects in CU APOE E4 carriers. Longitudinal studies are ongoing to examine the predictive value of subjective VI on cognitive impairment.
AssociatIion of metabotropic glutamate receptor 5 with amyloid deposition in Alzheimer's disease's patient and mouse models
Authors: Savoldelli Serena , Kong Yanyan , Maschio Cinzia , Konetiko Uwe , Mu Linjing , Klohs Jan , Nitsch Roger M. , Ni Ruiqing 
Published: January 2025

AbstractBackgroundMetabotropic glutamate receptor 5 (mGluR5) modulates excitatory glutamatergic synaptic transmission and plays an important role in learning and memory, and in the pathphysiology of Alzheimer’s disease (AD). Here, we aimed to assess the alterations of mGluR5 in the hippocampus of AD patients and mouse model, and the association with amyloid pathology.MethodImmunofluorescence staining was performed on postmortem brain tissue from 35 AD patients and 36 control patients, as well as on the brain tissue slices from 15 months‐old 3×Tg and arcAβ mouse models of AD amyloidosis. Autoradiography was performed on brain tissue slices from arcAβ mice using mGluR5 tracer [18F]PSS232. Proteomic profiling and pathway analysis were performed on hippocampal tissue from six 15 months‐old 3xTg mice and six age‐matched wildtype mice.ResultReduced levels of mGluR5 were observed in the hippocampus of AD patients compared to non‐demented control. Ex vivo autoradiography revealed a reduced level of [18F]PSS232 in the hippocampus and striatum of arcAβ mice compared to nontransgenic littermate mice. Reduced mGluR5 immunoreactivity was observed near 6E10‐positive Aβ plaques in the hippocampus. In contrast, upregulated levels of Shank3, Grin2a, Grin2b, and Grm5; and upregulation of glutamatergic pathway (GO and KEGG pathway enrichment analyses) were detected in hippocampal tissue from 3xTg mice compared to wildtype mice.ConclusionThis study revealed a reduction in the level of mGluR5 in the hippocampus of AD patients, and a strain‐dependent alteration of mGluR5 in mouse models of AD.
Research Lumbar Puncture Recruitment, Safety and SOPs in Black/African American and white middle‐age participants
Authors: Likos Kelly D. S. , Hu William T. , Verble Danielle D , Trotti Lynn Marie , Benameur Karima , Scorr Laura M , Butts Brittany , Wharton Whitney 
Published: January 2025

AbstractBackgroundThe Wharton Lab has collected CSF for over 10 years as a primary endpoint in NIH/NIA funded longitudinal observational studies and clinical trials in cognitively normal individuals with a parental history of Alzheimer’s disease (AD). LPs provide vital data on AD risk and progression and time specific information on efficacy for clinical interventions, yet few investigators include research LPs, for fear of clinical implications, lack of specialized clinicians, and perceived unwillingness of participants to consent to LPs, particularly in minoritized participantsMethodComprehensive data is collected on willingness to take part in LP, safety, and procedure specifics, including side effects. Twenty milliliters of CSF are obtained using fluid drip or aspiration methods. Twenty‐four hours post LP, the study team contacts the participant for LP follow up using a standardized questionnaire (potential side effects, severity, and home care initiated). Daily follow‐up with the participant occurs until side effects subsideResultOur data in 122 participants enrolled (1R01AG066203‐02) indicate that 1) show that research LPs are safe and well tolerated and 2) cognitively normal, middle‐aged participants are willing to undergo multiple LPs, regardless of race, ethnicity, and gender.Participants were 51.1% Black or African American and 45.2% Non‐Hispanic White, 76.3% female and have an average BMI of 27.8. 9.6% of individuals self‐excluded because of LP requirement. Of 139 LPs preformed, 93.9% of LPs were successful. 13.1% of participants reported a headache 24‐hours post LP. 78.8% of participants reported no side effects. Headache(n=10) and lower back pain(n=4) were the most common side effects. When side effects occurred post LP, 16.3% initiated home care suggested by the research team, with hydration being the most common(n=6).LPs were most successful with a 22 Whitacre needle, followed by a 22 Quincke needleConclusionData show that research LPs are safe and well tolerated in diverse cohorts, and that individuals are willing to take part in research LPs. Regular LP discussion and education for potential subjects is encouraged. Increased education and discussion of research LPs with the research team provides opportunities to discuss the procedure with the potential participant during the recruitment, consent, and screening processes
Implementation of Blood‐based Biomarkers in a Large Dementia Care Clinic: Case‐based Report from the UCSF Memory and Aging Center
Authors: Breithaupt Andrew , Bui Nhat Minh , Gonzalez Yasmeen , Joie Renaud La , Ljubenkov Peter A. , Possin Katherine L , Rojas Julio C. , soleimani‐meigooni David N. , Staffaroni Adam M. , Stephens Melanie , Tsoy Elena , Windon Charles , Boxer Adam L. , Rabinovici Gil D. , Miller Bruce L. , VandeVrede Lawren , Ellingson Tara 
Published: January 2025

AbstractSeveral new blood‐based biomarkers (BBMs) of Alzheimer’s disease and related neuropathologies have completed late‐stage validation and are beginning to be used in the clinical setting. However, the role of BBMs in various clinical settings, especially their specific context‐of‐use, remains an open question for the field. Several studies are beginning to systematically collect information on BBM real‐word diagnostic performance, but as BBMs transition from research settings to clinical implementation, experience from clinical providers in specialty centers can inform and guide use. In this session, BBM implementation at a large specialty care center, the University of California San Francisco (UCSF) Memory and Aging Center (MAC), will be discussed. The UCSF MAC is a division of the Department of Neurology dedicated to the diagnosis and care of patients with cognitive problems and their families, and the MAC has 32 clinicians who collectively evaluate over one thousand new patients a year with cognitive concerns. Additionally, the MAC recently launched an Alzheimer’s Infusion Core, dedicated to evaluating patients for the newly approved disease‐modifying treatments (DMT). Within the context of the UCSF MAC, integration of BBMs into clinical care will be reviewed using a case‐based format, including a description of overall provider usage, impact on differential diagnosis and subsequent management, and perceived role in the work‐up for patients interested in DMTs. Additional discussion will touch upon logistics and challenges to implementation, with a road map for future clinical integration.
Real world implementation of blood biomarkers in primary care
Authors: Willis Deanna R , Brosch Jared R. , Fowler Nicole R , Hammers Dustin B. , Summanwar Diana 
Published: January 2025

AbstractPrimary Care (PC) clinicians are faced with numerous competing demands and priorities for maximizing patient care. These challenges make the implementation of strategies for early detection of Alzheimer’s Disease (AD) complex. Few real‐world implementation projects about early detection of AD in PC exist. From 2022‐2023 the Davos Alzheimer’s Collaborative (DAC) Health System Preparedness Flagship project included seven United States academic affiliated PC clinics. We implemented digital cognitive assessments using the Linus Health Core Cognitive Evaluation at routine PC encounters. Patients who failed the cognitive assessment were offered, as part of a research pilot, C2N Diagnostics’ blood biomarker (BBM) test, PrecivityAD, with results disclosure. PCPs were approached to receive education about BBM for AD and to consent to deliver results themselves or defer delivery to the research team. Of the patients approached for BBM, more than half declined. Providers were split on their willingness to deliver results. For patients whose provider did not elect to deliver results or who was unable to deliver results in the timeframe needed, a trained Registered Nurse was trained and observed to disclose results. This session will share perspectives on these real‐life facilitators and barriers to implementing cognitive screening and BBM in PC and how more fully engaging the whole primary care team may help mitigate some of these barriers.
Performance of plasma NTK biomarkers to detect amyloid‐β pathology in cognitively unimpaired individuals at risk of Alzheimer’s disease
Authors: Escalante Armand González , Milà‐Alomà Marta , Brum Wagner Scheeren , Ashton Nicholas J. , Ortiz‐Romero Paula , Minguillon Carolina , Shekari Mahnaz , Anastasi Federica , del Campo Marta , Quijano‐Rubio Clara , Kollmorgen Gwendlyn , Gispert Juan Domingo , Zetterberg Henrik , Vilor‐Tejedor Natalia , Blennow Kaj , Suárez‐Calvet Marc 
Published: January 2025

AbstractBackgroundAlzheimer disease (AD) plasma biomarkers change in the preclinical stage of AD. However, the robustness of the discrimination performance of these biomarkers, as well as their association with longitudinal primary pathology (amyloid and tau) changes, is less understood. We aimed to determine the ability of baseline and longitudinal plasma amyloid‐β (Aβ)42/40, p‐tau181, GFAP and NfL to detect primary pathology in CU individuals at risk of AD.MethodPlasma biomarkers were measured using the NeuroToolKit (NTK), a panel of robust prototype biomarker assays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland), in CU participants of ALFA+. We assessed their performance for detecting early signs of amyloid‐positivity (as defined by CSF Aβ42/40 <0.071 or amyloid PET ≥12 Centiloids) using ROC analyses. We simulated the impact of random variability on each biomarker’s detection performance. Finally, we tested the baseline and longitudinal association of plasma biomarkers with longitudinal changes of primary pathology over three years.ResultsWe included 403 CU participants (49.3‐73.6 years old), 135 (33.5%) were CSF amyloid‐positive (Table 1), and 345 had amyloid PET available (15.7% PET amyloid‐positive). Plasma Aβ42/40 had the highest performance for Aβ‐positivity discrimination [AUC(CSF):0.87, AUC(PET):0.90], followed by p‐tau181 [AUC(CSF):0.72, AUC(PET):0.81]. Adding plasma NTK ApoE4 significantly improved the performance of plasma p‐tau181 and GFAP [AUC: 0.79 and 0.81]. Plasma Aβ42/40 was the most sensitive biomarker to the addition of random variability, while the others remained moderately stable (Figure 1). In PET amyloid‐negative individuals, lower baseline plasma Aβ42/40 was associated with longitudinal increases in amyloid PET Centiloids and CSF p‐tau181. In the low‐Aβ‐burden group (CSF amyloid‐positive, PET amyloid‐negative), higher baseline plasma p‐tau181 was associated with longitudinal increases in CSF p‐tau181. Plasma GFAP changed concurrently with amyloid, both CSF and PET, before amyloid PET becomes positive (Table 2).ConclusionsPlasma Aβ42/40 had the best performance in detecting Aβ pathology, but its discrimination performance was more sensitive to measurement variability. Plasma Aβ42/40 and p‐tau181 predict longitudinal changes in amyloid and tau pathology. Plasma GFAP changed concurrently with amyloid pathology. Overall, our study showed that different blood‐based biomarkers offer distinct information in preclinical AD, making each of them valuable for diagnostic, prognostic or monitoring purposes.
The US‐Based DIAMOND Lewy Toolkit: Overview and management of motor symptoms
Authors: Leverenz James B , O'Brien John T , Taylor John‐Paul 
Published: January 2025

AbstractLewy body dementia (LBD) clinically is characerized by a complex myriad of cognitive, behavioral, motor, sleep and autonomic symptoms that can be challenging to manage, particularly in the context of the fluctuations that are so characteristic for these patients. The DIAMOND Lewy Toolkits offer a resource to support clinicians in recognizing and managing this range of symptoms observed in LBD. This session will provide a guided introduction to the DIAMOND Lewy Toolkits, offering a framework to leverage the toolkits in support of patient centered care. In addition to an overview of the DIAMOND Lewy program (Dr. Leverenz), he will focus on motor symptom management. Subsequent speakers will address neuropsychiatric and sleep symptoms (Dr. Chiadi), cognition and autonomic dysfunction (Dr. Scharre) and the adaptation of the DIAMOND Lewy Tool kits in the U.S. (Dr. Amodeo).
Misperception of night‐to‐night sleep quality in Alzheimer’s and Lewy body disease
Authors: Washburn Alex , Winer Joseph R. , Romero America , Yutsis Maya , Henderson Victor W. , Poston Kathleen L. , Zeitzer Jamie M , Mormino Elizabeth 
Published: January 2025

AbstractBackgroundObjective sleep measures obtained from actigraphy (wrist‐worn accelerometry) reveal sleep disruption patterns and may serve as indicators of neurodegenerative disease. However, whether individuals’ subjective account of their sleep quality corresponds to objective sleep measurements from the previous night is an area little studied. In particular, whether neurodegenerative disease modifies these associations is unknown.MethodN=111 participants including healthy controls (HC) and individuals with Alzheimer’s disease (AD) and Lewy body (LB) disease were recruited from the Stanford Alzheimer’s Disease Center and the Stanford Aging and Memory Study, with a mean of 6.3 ± 1.4 days of paired actigraphy/questionnaire data. Each morning, participants rated their overall sleep quality, sleep depth, well‐restedness, and mental alertness on a 0‐4 Likert scale, which were combined into a latent subjective sleep score using confirmatory factor analysis (Figure 1). Nightly sleep duration and wake after sleep onset (WASO, time awake after falling asleep) were objective actigraphy‐derived variables of interest. Linear mixed models were used to assess differences in the relationship between objective sleep variables and the subjective sleep score between disease etiologies.ResultAcross all participants, subjective sleep scores were associated with the previous night’s objective recording. However, this association showed an interaction with etiology such that increasing WASO predicted reduced subjective sleep quality in HC participants, whereas for participants with AD and LB, subjective sleep quality did not relate to WASO (Figure 2a). In contrast, subjective sleep quality was predicted similarly by sleep duration in AD, LB, and HC participants: as sleep duration increased, subjective sleep quality increased (Figure 2b). These relationships also held when binning by cognitive impairment status (normal, mild cognitive impairment, dementia) or MoCA score rather than etiology.ConclusionA significant difference in how objective sleep disruption predicts subjective sleep quality for AD and LB participants relative to HC participants suggests that individuals' perception of their night‐to‐night sleep quality may be impaired in the context of neurodegenerative disease.