bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of caregiver tele‐health support and education intervention on the relationship between caregiver grief and quality‐of‐life
Authors: Gothard Sarah , Mooney Aimee , Tupper Emily , Lindauer Allison 
Published: January 2025

AbstractBackgroundCurrent research around caregiving for person’s with dementia (PWD) has historically emphasized caregiver burden. This leaves a gap of knowledge around other contributors to caregiving’s long‐term effects, including grief. The current analysis explores the relationship between caregiver grief and quality‐of‐life.MethodThe Tele‐STELLA study is a multi‐component, telehealth‐based intervention that teaches caregivers strategies to manage upsetting behaviors related to dementia in 8 weekly, 1‐hour sessions with professionals. The caregivers in this analysis (n = 138) cared for a family member with moderate to late‐stage dementia. A multilinear analysis was used to explore the relationship between grief and quality‐of‐life for 138 caregivers of PWD. Caregivers were women (73.2%) and white (87.0%), with 82.6% reporting financial security. On average, caregivers were engaged in their roles for 4.64 years (SD 3.69); 87.0% of the PWDs were in the moderate stage of dementia. Pre and post questionnaires queried caregivers about frequency of problematic behaviors and their reactions to the behaviors, grief, and household quality‐of‐life.ResultOf the 138 caregivers who started the 8‐week intervention, 98 (71%) completed both pre/post self‐reported data. Scatterplot visualization demonstrated a linear negative relationship between grief/quality‐of‐life at both pre and post intervention timepoints. Controlling for sex and care recipient dementia severity, a multilinear regression was performed and showed, at alpha 0.05, a significant negative relationship between quality‐of‐life and grief (p‐value: 0.00, B1: ‐0.17) at the pre‐intervention timepoint. Post‐intervention analysis of the same model showed the magnitude of the B1 coefficient of grief changed to ‐0.22 and an increased significance (p‐value: 0.00).ConclusionThis analysis found that grief in dementia caregiving had a strong negative relationship with quality‐of‐life and that this relationship became stronger after intervention. This may be due to caregivers’ increased awareness of grief, or to the progressive nature of dementia over the 8‐week intervention period, but still highlights grief’s impact on caregiver quality‐of‐life. Future longitudinal studies will be necessary to evaluate if grief can serve as a predictor of quality‐of‐life and long‐term health outcomes for caregivers, and how best to leverage that knowledge for interventions in this population.
Management of Cognitive and Autonomic Symptoms in LBD
Authors: Scharre Douglas W. 
Published: January 2025

AbstractSupport for the management of cognitive and autonomic features of Lewy body dementia (LBD) is offered in detail in this presentation. The US Based Diamond Lewy Cognitive Symptoms management document presents the unique cognitive profile of LBD with general principles for addressing these features along with detailed guidance in the use of cholinesterase inhibitors and Memantine. The US Based Diamond Lewy Autonomic Symptoms management document addresses the management of common autonomic symptoms including urinary dysfunction, male sexual dysfunction, excessive sweating, constipation, sialorrhea, gastroparesis and orthostatic hypotension in LBD.
Plasma p217+tau accurately discriminates Intermediate or Advanced Alzheimer's Disease biological PET stages
Authors: Feizpour Azadeh , Dore Vincent , Krishnadas Natasha , Bourgeat Pierrick , Doecke James D. , Saad Ziad S. , Triana‐Baltzer Gallen , Laws Simon M. , Shishegar Rosita , Huang Kun , Fowler Christopher J , Ward Larry , Masters Colin L , Fripp Jurgen , Kolb Hartmuth C. , Villemagne Victor L , Rowe Christopher C. 
Published: January 2025

AbstractBackgroundPlasma phospho‐tau biomarkers, such as p217+tau, excel at identifying Alzheimer’s Disease (AD) neuropathology. However, questions remain regarding their capacity to inform AD biological PET stages at group level and maintain the same precision at individual patient level.MethodParticipants included 248 cognitively unimpaired (CU) and 227 cognitively impaired (CI) individuals, with Janssen plasma p217+tau Simoa® assay, 18F‐NAV4694 Aβ PET (A) and 18F‐MK6240 tau PET (T) data. Biological PET stages were defined based on the draft NIA‐AA Revised Criteria (July 2023): Initial (A+T‐), Early (A+TMTL+), Intermediate (A+TMOD+), and Advanced (A+THIGH+). We used thresholds for A+ of 25 Centiloid and for THIGH of 80 Centaur (2.68 SUVRtemporo‐parietal). Adding an A‐T‐ stage for comparison, we assessed the performance of p217+tau in discriminating between these stages at the group level using Receiver Operating Characteristic (ROC) analysis and at the individual level using logistic regression.ResultPlasma p217+tau concentrations increased across the stages, with significant differences between them, except for the Initial and Early stages. Screening for Advanced (vs. lower stages), combined Intermediate/Advanced (vs. lower stages), or all stages (vs. A‐T‐), p217+tau showed good group‐level discriminations (AUC 0.91, 0.92 and 0.92; CI only: AUC 0.83, 0.89, 0.93, respectively). At the individual level, the likelihood of PET stage vs. p217+tau level showed good discrimination of A‐T‐ vs any A+ stage and of combined Intermediate/Advanced disease stage vs lower stages in the CI.ConclusionIn addition to accurately screening for A+ individuals, plasma p217+tau shows promise for separating persons with either Intermediate or Advanced stage AD from those at a lower stage, providing prognostic information and informing better selection for trials and disease modifying therapies.
Blood astrocyte biomarkers in AD: a systematic review and meta‐analysis
Authors: Holper Sarah , Loveland Paula M , Churilov Leonid , Italiano Dominic , Watson Rosie , Yassi Nawaf 
Published: January 2025

AbstractBackgroundWe performed a systematic review and meta‐analysis of blood astrocyte biomarkers in Alzheimer's disease (AD).MethodMEDLINE and Web of Science were searched without any restrictions on language, time, or study design, for studies reporting blood levels of the astrocyte biomarkers GFAP, YKL‐40, and S100B in AD patients. Pooled effect sizes were determined using Hedge's g method with a random effects model. The review was prospectively registered on PROSPERO (registration number CRD42023458305).ResultThe search identified 1186 studies; 36 met inclusion criteria (n=3366 AD patients, n=4115 cognitively unimpaired [CU]). Compared to CU individuals, AD patients had significantly higher GFAP and YKL‐40 levels (GFAP effect size 1.15, 95% CI 0.94‐1.36, P<.0001; YKL‐40 effect size 0.38, 95% CI 0.28‐0.49, P<.0001). Both biomarkers showed a trend towards a greater effect size in more advanced disease. No significant difference in blood S100B levels were identified.ConclusionOur findings reveal significant elevations in blood GFAP and YKL‐40 levels in AD patients across the clinical spectrum, suggesting that both biomarkers accurately reflect AD‐related pathology.
Comparison of [18F]MK6240 and [18F]Flortaucipir standardized uptake values (SUVs): the HEAD study
Authors: Tissot Cécile , Tsai Hsin‐Yeh , Tudorascu Dana , Lussier Firoza Z , Rahmouni Nesrine , Servaes Stijn , Therriault Joseph , Stevenson Jenna , Gordon Brian A. , Pascual Belen , Lowe Val J. , soleimani‐meigooni David N. , Oh Hwamee , Klunk William E , Rosa‐Neto Pedro , Jagust William J. , Pascoal Tharick Ali , Baker Suzanne L. 
Published: January 2025

AbstractBackgroundDifferences between on‐ and off‐target retention characteristics between [18F]MK6240 and [18F]Flortaucipir (FTP) complicate the harmonization across tracers. Our objective here was to separate the impact of the reference region by evaluating correlations between [18F]MK6240 (MK) and [18F]FTP standard uptake values (SUVs).MethodParticipants (Figure 1, n=90) received an amyloid‐β (Aβ) PET scan ([11C]PIB or [18F]NAV4694) and two tau‐PET scans: [18F]MK (90‐110 minutes post‐injection) and [18F]FTP (80‐100 minutes post‐injection). For all PET scans, the individual frames were realigned, averaged, and co‐registered to a Freesurfer 7.1‐segmented T1‐MPRAGE. SUVs were calculated in the reference region (inferior cerebellar gray), on‐target regions (entorhinal cortex, hippocampus, Braak III, Braak IV, Braak V, Braak VI) and off‐target regions (caudate, pallidum, putamen, thalamus, cerebellar white matter, choroid plexus, meninges, eroded white matter). We examined correlations between [18F]MK and [18F]FTP SUV values as a function of Aβ status, as well as their associations with age.ResultAll correlations (Figure 2) were significant at p<0.001. The interaction with Aβ status was significant for hippocampus, BraakIII‐V and the metatemporal region. In Aβ+ participants, [18F]FTP and [18F]MK6240 have similar SUVs in on‐target regions with a slope close to 1 except for in hippocampus and Braak VI. However, [18F]FTP SUVs, on average, were greater than [18F]MK SUVs in Aβ+ and Aβ‐ subjects in the reference region and all off‐target regions except for meninges, and in Aβ‐ subjects in the on‐target regions. Age correlated with [18F]FTP SUVs in Aβ‐ subjects in all regions (except the reference region, Braak VI and meninges) and [18F]MK SUVs in putamen and pallidum, but this correlation was only significant (p<0.01) when young and old subjects were included.ConclusionDespite [18F]MK’s higher affinity for tau and SUVR dynamic range being twice that of [18F]FTP, the SUVs in on‐target regions are similar. The higher [18F]FTP signal in the reference region appears to be the contributing factor to the lower dynamic range. The higher [18F]FTP signal in on‐target regions for Aβ‐ subjects may reflect the presence of off‐target signals in these subjects. Taking off‐target signals into account should improve correlations between the two tracers, especially when measuring the earliest deposition of tau.
Plasma phosphorylated tau 217 in relation to Alzheimer’s prevalence and cognition in Thailand
Authors: Hemachudha Pasin , Thanapornsangsuth Poosanu , Luechaipanit Watayuth , Hemachudha Thiravat 
Published: January 2025

AbstractBackgroundBiomarkers for Alzheimer's disease (AD) in blood samples has the potential to facilitate early diagnosis and improve the accuracy of AD diagnosis. Plasma phosphorylated tau (p‐tau) is a key biomarker for AD; however, its utility for estimating the prevalence of AD and screening for cognitive impairment is still limited.MethodThe study recruited 71 participants over the age of 40. Plasma p‐tau 217 levels and neuropsychological data were measured. AD prevalence was estimated using a pre‐defined cut‐off derived from an independent cohort with biomarker‐defined AD status according to the current framework (Jack et. al., 2018). The correlation between plasma p‐tau 217 levels and neuropsychological data were also evaluated.ResultThe median age of participants was 62 years and overall clinical dementia rating of 0. The median Montreal cognitive assessment (MoCA) and Mini‐Mental State Examination (MMSE) score was 26 and 29 consecutively. Plasma p‐tau 217 levels showed a negative correlation with both neurocognitive tests (MoCA, Rho = ‐0.082, P = 0.5; MMSE, Rho = ‐0.26, P = 0.027). The estimated prevalence of AD was 16.9% (95% CI 9.9‐27.3) when using plasma p‐tau 217 as a biomarker, which was lower than the prevalence estimated using amyloid abnormalities of 30.1% (Jansen et. al., 2022).ConclusionThe results of this study suggest the possibility of plasma p‐tau 217 for estimating AD prevalence and cognition. It may represent those at risk of clinical onset. However, further studies are needed to investigate its utility in risk stratification, and cognitive performance assessment.
Plasma N‐terminal tau fragment is associated with cognitive status and AD biomarkers of tau and neurodegeneration in older adults
Authors: Rao Yiwen , Ostaszewski Beth L. , Anderson Amirah K. , Shirzadi Zahra , Liu Lei , Yang Hyun‐Sik , Chhatwal Jasmeer P. , Selkoe Dennis J. , Schultz Stephanie A. ,   ADNI
Published: January 2025

AbstractBackgroundThe emergence of blood‐based biomarkers offers a cost‐effective and less invasive alternative to established neuroimaging and cerebrospinal fluid biomarkers. Newly developed fluid biomarkers, including N‐terminal tau fragment (NT1), have shown promise for identifying individuals at risk for Alzheimer’s disease (AD). Evidence has shown NT1 may be more abundant than full‐length tau across the AD continuum and has high sensitivity and specificity to separate cognitively normal (CN) individuals from those with mild cognitive impaired (MCI) and AD in discovery and replication cohorts. Here we quantify plasma NT1 in a large, well‐characterized cohort and examine the association between plasma NT1 and cross‐sectional clinical and biomarkers measures.MethodsSeven hundred and seventeen individuals enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who have plasma NT1, Aβ‐PET, MRI, and clinical (Clinical Dementia Rating; CDR) measures were included in this study (Table 1). NT1 was assessed using Quanterix Simoa HD‐X platform. PET, MRI, clinical, and other plasma measures were derived using previously described procedures in ADNI. Linear regressions were performed to assess the cross‐sectional association of NT1 with clinical and biomarkers measures, after adjusting relevant covariates.ResultsNT1 levels were elevated in cognitively impaired (MCI/AD; CDR>0) relative to CN (CDR=0) individuals (p=0.008, Figure 1A). Specifically, NT1 is elevated in the MCI group (CDR=0.5, MCI vs Aβ‐ CN group: p=0.005), but not the AD group (CDR>0.5, AD vs all other groups: p’s >0.206, Figure 1B). NT1 was associated with plasma phosphorylated (p)Tau‐181 (p=1.27x10‐9, Figure 2A) and plasma neurofilament light chain (NfL; p=5.68x10‐6, Figure 2B) but not hippocampal volume (p=0.239).ConclusionPlasma NT1 differentiated CN from MCI/AD individuals and was elevated particularly in the early symptomatic phase of disease. Plasma NT1 was associated with plasma markers of tau and neurodegeneration. Together these results suggest that plasma NT1 may be a useful biomarker of AD‐related tau pathology and neurodegeneration.
People with dementia as exercise video game testers: Gathering end‐user perspectives
Authors: Dove Erica , Wang Rosalie H. , Patterson Kara K. , Astell Arlene J. 
Published: January 2025

AbstractBackgroundCommercially available exercise video games (‘exergames’) can be used by people with dementia with the right (human) prompting and support. However, more information is needed about what makes these systems and games technologically accessible for this population, considering their cognitive difficulties. This study explores what works and doesn’t work for people with dementia when introducing new exergame systems and games to broaden opportunities for physical activity.MethodsThirty‐two people living with dementia (mean Montreal Cognitive Assessment score: 12.75/30) were recruited from four community‐based adult day programs in Canada. Participants were recruited as ‘game testers’ once weekly for six weeks at each day program. Participants with dementia tried different exergame systems (e.g., Xbox Kinect, Nintendo Switch) and games (e.g., darts, boxing, dancing, etc.). Concurrently, gameplay video recordings and feedback via the talk‐aloud protocol and audio‐recorded post‐game group debriefs were collected. Data were analyzed descriptively and are currently undergoing analysis using behavioural coding software to examine in‐game prompts and player movements.ResultsIn total, 292 gameplay turns occurred across the sessions. Some participants declined to play certain games after watching their peers experience accessibility challenges. Common reasons for ending a turn (beyond completing the game objective) included boredom, frustration, confusion, fatigue, and soreness. Systems with handheld controllers (e.g., Nintendo Wii) were less accessible for participants than gesture‐based controls due to the need to push buttons and attend to the controller while simultaneously performing physical motions. Additionally, games requiring multiple coordinated movements and those not accommodating additional age‐related impairments (e.g., range of motion impairments, mobility devices) were not widely accessible to this diverse group of participants.ConclusionsThis study highlights the importance of involving people living with dementia in game development. The findings reveal which elements of current exergames make them accessible or inaccessible for people living with dementia. These findings can help design new exergames to increase access to physical activity for people with dementia. The findings will also interest dementia service providers who want to use exergames to increase physical activity for people with dementia.
Understanding the variability in plasma biomarker levels in the context of established biomarkers of Alzheimer’s disease
Authors: Bluma Marina , Chiotis Konstantinos , Bucci Marco , Savitcheva Irina , Matton Anna , Kivipelto Miia , Jeromin Andreas , Santis Giovanni De , Molfetta Guglielmo Di , Ashton Nicholas J. , Blennow Kaj , Zetterberg Henrik , Nordberg Agneta K 
Published: January 2025

AbstractBackgroundPlasma biomarkers are on the verge of being introduced as screening tools for detecting Alzheimer's disease (AD). Yet, previous studies yielded contradictory results regarding the extent to which distinct plasma biomarkers reflect the key pathological changes associated with AD. This study aims to investigate the specific relationship between core AD biomarkers, such as amyloid PET and CSF pTau, and the novel plasma biomarkers.MethodWe analyzed plasma pTau181, pTau217, pTau231, GFAP, NfL, CSF pTau181, Aβ‐PET scans, and MRI/CT visual reads of atrophy (MTA and GCA) in a cohort of memory clinic patients (N=138) who underwent comprehensive clinical assessments at the Memory Clinic, Karolinska University Hospital, Stockholm, Sweden. Patients were classified according to the ATN system, for the presence of Aβ‐deposition (A), tau aggregation (T), and neurodegeneration (N) based on Aβ‐PET, CSF pTau and MRI/CT measurements, respectively. We utilized methods based on multiple linear regression to evaluate the distinct contributions of Aβ‐PET, CSF pTau, and neurodegeneration, on plasma biomarker levels, while also considering demographic variables.ResultWe found significant (p<0.05) positive associations between Aβ‐PET and plasma pTau181, pTau217, pTau231, GFAP, but not NfL. Similarly, significant positive associations were observed between CSF pTau and plasma pTau isoforms and GFAP. After accounting for the effect of Aβ‐PET, only plasma pTau217 and pTau231 remained significantly associated with CSF pTau. Among all, plasma pTau217 and GFAP exhibited the greatest effect sizes to distinguish between A+/A‐, whereas plasma pTau231 and pTau217 for distinguishing T+/T‐. Plasma NfL showed the highest effect size for distinguishing N+/N‐ among all plasma biomarkers. Dominance analysis indicated that Aβ‐PET had the highest relative importance in predicting pTau isoforms and GFAP values, followed by CSF pTau. Notably, pathology‐related AD biomarkers (Aβ‐PET and CSF pTau) explained the largest portion of variance in plasma pTau217(56%), GFAP (24%), pTau181(16.2%), pTau231(17%), but not NfL(0.6%).ConclusionAmyloid burden primarily drove changes in levels of the tested plasma biomarkers, except for NfL where atrophy played a role. Unlike plasma GFAP and pTau181, where the effect of CSF pTau was attenuated by the effect of Aβ‐PET, both pTau231 and pTau217 reflected changes in CSF pTau levels. Variance in plasma pTau217 levels appeared to be well explained by AD‐related pathological changes.
In‐vivo plasma biomarker concentrations correlate with postmortem AD‐neuropathology in the oldest old
Authors: Lorenz Linda M.C. , Rohde Susan K. , Luimes Maruelle C. , Fierro‐Hernández Patricia , Rozemuller Annemieke J.M. , Bank Netherlands Brain , Hoozemans Jeroen J.M. , Teunissen Charlotte , Holstege Henne 
Published: January 2025

AbstractBackgroundThere has been ongoing uncertainty to what extent plasma biomarkers are representative of neuropathological markers of AD pathology in the oldest old. A complicating factor is that with increasing age, Aβ‐ and Tau pathologies accumulate in the brains of cognitively healthy individuals to highly variable levels (Zhang & Ganz et al., 2022). The unique availability of both antemortem plasma biomarker concentrations and postmortem neuropathology in self‐reported cognitively healthy oldest old, offers a chance to explore whether levels of plasma biomarkers can serve as in‐vivo proxy of AD neuropathology.MethodsWe evaluated postmortem neuropathology of 48 centenarian brains, with a median MMSE score of 26 (range:16–30) at blood draw. We quantified plasma biomarkers Aβ40, Aβ42, Aβ42/40, pTau181, NfL and GFAP on the Simoa platform. The median interval between blood‐sample collection and brain donation was 1.3 (range:0–5.1) years. In addition to conventional spatio‐temporal staging systems such as Thal‐Aβ phase (median 2, range:0‐5) and Braak‐NFT stage (median 3, range:2‐5), we also quantified pathological load by measuring the percentage area of immunopositivity for total Aβ (range:0–9.0%), Aβ40 (range:0–3.3%), Aβ42 (range:0–11.5%), pTau‐217 (range:0–1.8%) and AT8 (pTau‐202/205; range:0–49.2%) in the cortex of the temporal pole. Partial Spearman correlations were conducted adjusted for age, sex, and time interval.ResultsPlasma pTau‐181 correlated with Aβ pathology loads, namely Aβ40 (r=0.48, p<0.001), Aβ42 (r=0.41, p=0.005) and total Aβ (r=0.48, p<0.001), as well as with spatio‐temporal Thal‐Aβ phase (r=0.45, p=0.003). Plasma pTau‐181 correlated with quantitative pTau pathology loads, specifically pTau‐217 (r=0.48, p=0.001) and AT8 (r=0.41, p=0.005), but not with spatio‐temporal Braak‐NFT stage (r=0.17, p=0.290). Furthermore, both plasma NfL and plasma GFAP also correlated with pTau‐217 load in the brain (r=0.30, p=0.0496; r=0.30, p=0.044, respectively). Plasma Aβ40, Aβ42, Aβ42/40 did not correlate with any neuropathology measure.ConclusionsResults reveals plasma pTau‐181, but not plasma Aβ, as a reliable indicator for both Aβ and pTau pathology loads in the temporal pole of the oldest old. The 100‐plus study cohort provides a promising opportunity to study the correlation between different pTau epitopes and the presence of pTau levels, as well as the presence of Tau pathology, including NFTs, neuropil threads, pre‐tangles and ARTAG.