bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot study of Myocardial MIBG Scintigraphy with 123I‐FP‐CIT SPECT in Isolated REM Sleep Behavior Disorder
Authors: Miyagawa Toji , Vernon Cynthia , Przybelski Scott A. , Min Hoon‐Ki , Fields Julie A. , Forsberg Leah K. , St. Louis Erik K , Kantarci Kejal , Lowe Val J. , Boeve Brad F. 
Published: January 2025

AbstractBackgroundAutopsy studies in Lewy Body Disease (LBD) indicate that cardiac sympathetic denervation precedes Lewy body pathology and neuronal loss in the brain. Myocardial 123I‐metaiodobenzylguanidine (MIBG) scintigraphy noninvasively assesses postganglionic cardiac sympathetic denervation in LBD and is considered an important biomarker in the international diagnostic criteria of Dementia with Lewy Bodies and Parkinson’s Disease (PD). Despite the internationally recognized importance of MIBG scintigraphy in LBD, its use in neurodegenerative disorders is not FDA approved for this indication and is rarely used in the US for neurological research. We sought to add MIBG scintigraphy to our multimodal imaging research in prodromal LBD. We launched pilot MIBG scintigraphy study in isolated REM Sleep Behavior Disorder (iRBD) individuals, who are typically regarded as representing evolving LBD.MethodWe conducted MIBG scintigraphy and 123I‐FP‐CIT SPECT in seven individuals with iRBD including two RBD with mild cognitive impairment (MCI), one with PD, and one healthy control (mean age of 71.5±8.3). Heart‐to‐mediastinum (H/M) ratio of the MIBG uptake on delayed image (3‐4 hours after Adreview® injection) was calculated with MIM. Cutoff value of 1.68 was used for determining abnormal H/M ratio (Yoshita et al, 2006). Nigrostriatal dopamine transporter uptake was evaluated with DaTQUANT 2.0 software.ResultFour iRBD participants including two RBD with MCI had abnormal MIBG scintigraphy (mean age 73.5±8.6, delayed H/M ratio 1.25±0.29)) and three iRBD participants had a normal scan (mean age 67.8±4.5, delayed H/M ratio 2.57±0.25). Delayed H/M ratio was 1.00 for the PD participant and 2.60 for healthy control participant. Among the four iRBD participants with abnormal MIBG scintigraphy, one participant had 123I‐FP‐CIT SPECT with DaTQUANT putamen z‐score <‐2.0 and three participants had z‐score in the range of ‐1.5 and ‐1.0. All iRBD participants with normal MIBG scintigraphy had normal 123I‐FP‐CIT SPECT with DaTQUANT putamen z‐score >‐1.0.ConclusionMIBG scintigraphy was abnormal in half of this small cohort. Our preliminary data suggests its utility in detecting early signs of evolving LBD. Increasing the number of the MIBG scintigraphy in iRBD participants and controls are planned to determine if MIBG scintigraphy can facilitate early detection of progression for use in clinical trials targeting LBD.
Alzheimer's disease staging with [18F]MK6240 and [18F]Flortaucipir ‐ the HEAD study
Authors: Soares Carolina , Povala Guilherme , Bauer‐Negrini Guilherme , Lussier Firoza Z , Ferreira Pamela C.L. , Bellaver Bruna , Amaral Livia , Zalzale Hussein , Madeiros Marina Scop , Cehula Juli , Bloomquist Madeleine , Oliveira Markley , Felix Cynthia , Rodrigues Matheus Scarpatto , Ruppert Emma Patrice , Abbas Sarah , Zimmer Eduardo R. , Pascual Belen , Gordon Brian A. , Lowe Val J. , Oh Hwamee , soleimani‐meigooni David N. , Rosa‐Neto Pedro , Tudorascu Dana , Jagust William J. , Klunk William E , Baker Suzanne L. , Pascoal Tharick A. 
Published: January 2025

AbstractBackgroundUtilizing PET amyloid‐beta (Aβ) and tau for staging Alzheimer’s Disease (AD) has demonstrated potential in identifying individuals with varying degrees of disease severity, applicable to both clinical trials and practice. However, the diverse binding characteristics of tau tracers pose challenges to the application of this staging across different ligands. In this study, we evaluate a novel staging framework proposed by the AA working group, employing Aβ PET and either [18F]MK6240 or [18F]Flortaucipir in individuals participating in a head‐to‐head study of tau PET tracers. This will provide insights into the robustness of this framework when applied across different tau ligands.MethodWe evaluated 154 people (89 CU and 65 CI), with MK6240, Flortaucipir, Aβ‐PET, MRI. SUVRs used inferior cerebellar gray as reference. Participants were categorized in Aβ positivity(A), using visual read, and tau positivity (T) in medial temporal lobe(MTL) and neocortex(NEO). Tau MTL(TMTL) and NEO positivity were defined as average +3 SD of youngs. NEO moderate(TMOD) and high(THIGH) was defined as below and above median SUVR of NEO‐positive individuals. Individuals were grouped as: A‐T‐, A+T‐, A+TMTL+(early), A+TMOD+(intermediary), and A+THIGH+(advanced).ResultsWe found that the distribution of the number of individuals across the five AD stages was comparable when using both MK6240 and Flortaucipir tracers (Figure 1). However, upon examining the concordance within each group, we found a low concordance of 30% (3/10) between tracers in the early tau stage (A+TMTL+). Concordance increased in the intermediary stage A+TMOD+, with a rate of 65% (9/14), and further increased to 79% (11/14) in the advanced stage (A+THIGH+). The A+T‐ group exhibited the highest concordance between tracer results, at 95% (21/22).ConclusionOur findings indicate that the application of this framework across different populations using different tau tracers can lead to a compatible distribution among groups. However, in a direct comparison, we noted that this did not necessarily result in high concordance between groups, as group shifts were observed that depended on the cutoffs used (data not shown). These results emphasize the necessity for harmonization of tau PET tracers prior to their utilization for stage determination.
Investigating the association between cholinergic integrity and amyloid burden using cholinergic anatomy and [18F]‐FEOBV PET in individuals with Down Syndrome from the ABC‐DS and TRC‐DS cohorts
Authors: Russell Jason K , Conley Alexander C , Boyd Brian , Schlossberg Rachel , Stranick Allison , Rosenberg Adam J , Acosta Lealani Mae Y. , Rafii Michael , Shokouhi Sepideh , Newhouse Paul A 
Published: January 2025

AbstractBackgroundAdults with Down Syndrome (DS) have the highest risk of developing Alzheimer’s disease (AD) worldwide. Triplication of the amyloid precursor protein gene on chromosome 21 results in early amyloid accumulation and Alzheimer’s pathology. The cholinergic system is known to decline early in the development of AD and plays a fundamental role in observed cognitive deficits. In the present work, we assess the association between amyloid accumulation and cholinergic integrity.Method188 individuals from the ABC‐DS cohort (U01AG051406; U01AG051412; U19AG068054) were assessed cross‐sectionally. Basal forebrain volumes were calculated using the ScLimbic FreeSurfer pipeline for the basal forebrain (Ch1‐Ch4) and the DnSeg pipeline for Ch4 volumes. Linear regressions were performed between centiloid values, age, and basal forebrain volumes. Nine individuals recruited for a TRC‐DS sub‐study underwent a multimodal imaging assessment, including [11C]‐PiB PET and [18F]‐FEOBV PET imaging. Global centiloid values were calculated using PMOD, with regional SUVRs calculated using PetSurfer with GTM for partial volume corrections. Linear regressions were performed between global centiloid, regional [11C]‐PiB SUVR, and regional [18F]‐FEOBV SUVR.ResultIn ABC‐DS and the TRC‐DS sub‐study, global amyloid accumulation was positively associated with age (p<0.0001 and p=0.041). Age and global amyloid accumulation were negatively associated with Ch1‐Ch4 (p<0.005) and Ch4 (p<0.05) cholinergic basal forebrain volumes. In the TRC‐DS sub‐study, global amyloid accumulation negatively associated with [18F]‐FEOBV uptake in the amygdala (p<0.05), statistical trends were observed in the thalamus and left entorhinal cortex (p<0.08). Regional [11C]‐PiB uptake was negatively associated with [18F]‐FEOBV uptake in the left inferior temporal and right pericalcarine cortices (p<0.05), with statistical trends observed in the right amygdala, left pericalcarine, and left fusiform cortices (p<0.08).ConclusionMeasures of cholinergic integrity were found to decline with increasing amyloid in individuals with DS across two cohorts, utilizing different methodologies. In the ABC‐DS cohort, we observed a reduction in basal forebrain nuclei volume with increasing age and amyloid accumulation. The basal forebrain contains cholinergic and noncholinergic neurons. To understand whether this volume reduction was from cholinergic loss, we assessed the integrity of cholinergic terminals using [18F]‐FEOBV PET and found regional cholinergic integrity negatively associated with both global and regional amyloid accumulation.
Increased Myeloid Progenitor Inhibitory Factor 1 and Dysbiosis in Mild COVID‐19 Patients With No Change in Alzheimer's Disease Markers
Authors: Giridharan Vijayasree V , Catumbela Celso , Kluwe‐Schiavon Bruno , Arent Camila O. , Borba Laura A. , Bagatini Margarete D. , Ignácio Zuleide M , Pedro Lucas C , Ceretta Luciane B , Quevedo João , Morales Rodrigo , Reus Gislaine Z , Barichello Tatiana 
Published: January 2025

AbstractBackgroundThe persistent neurological symptoms seen in long COVID survivors are attributed to immune system dysfunctions and changes in the microbiome induced by SARS‐CoV‐2 infection. In addition to the initial respiratory manifestations, a significant portion of COVID‐19 patients present with neurodegenerative symptoms. Our hypothesis suggests that disruptions in inflammatory signals and alterations in the gut microbiome post‐COVID‐19 play pivotal roles in the development of neurodegenerative complications among individuals experiencing prolonged effects of the disease.MethodIn our cross‐sectional study, we enrolled individuals with post‐COVID‐19 (n = 26) and age‐ and sex‐matched healthy controls (n = 57). Our objective was to conduct a comprehensive examination of neuropsychiatric symptoms, lipid profiles, oxidative stress markers, inflammatory signals, and Alzheimer's disease (AD) markers in plasma samples and gut microbiome status using feces samples from post‐COVID patients. Depressive and anxiety symptoms were evaluated using the Hamilton Rating Scale, while cognitive performance was assessed with standardized measures. The intricate details of the gut microbiome status were revealed through 16S rRNA sequencing.ResultThe investigation uncovered no statistically significant differences in anxiety or cognitive status however the depression was elevated in post‐COVID‐19 as compared to healthy subjects. Further, AD markers (Aβ42, Aβ40, t‐tau, and p‐tau) and oxidative stress markers displayed no discernible distinctions between the two groups. A noteworthy discovery was the significant increase in CCL23, the macrophage inhibitory protein‐3, among COVID‐19 patients. CCL23, known for its role in inflammation and host defense, has recently been linked to neuroinflammation in the early stages of AD. Furthermore, apoptosis markers Caspase‐3 and ‐8 were significantly elevated in COVID‐19 patients. While α‐diversity in the gut microbiome showed no significant differences, β‐diversity indicated a notable distinction between the control and post‐COVID‐19 groups. Furthermore, post‐COVID‐19 individuals displayed a decreased abundance of the phylum Verrucomicrobia and genus Akkermansia, a short‐chain fatty acid producer, and microbial group significantly associated with intestinal barrier permeability and cognitive improvement.ConclusionWhile longitudinal studies are essential for a comprehensive understanding of the behavioral trajectory of COVID‐19 individuals, the current results indicate that CCL23 levels and changes in microbiome status may function as early indicators of post‐COVID neurological and neuropsychiatric outcomes.
Digital biomarkers of sleep and nocturnal behaviour derived from contactless longitudinal sleep monitoring predict cognitive decline and deterioration in daily function in people living with dementia
Authors: Kolanko Magdalena A. , Soreq Eyal , Golemme Mara , Walsh Chloe , Giovane Martina Del , Sharp David J 
Published: January 2025

AbstractBackgroundGrowing evidence suggests sleep disturbance may promote Alzheimer’s disease (AD) pathology. However, the relationship between sleep and AD progression remains poorly defined due to lack of longitudinal sleep monitoring methods. We previously presented a novel approach for contactless sleep monitoring in people living with dementia (PLWD)1. Here, we examine the association between the Dementia Research Institute Sleep Index (DRI‐SI) ‐ an interpretable measure of sleep disturbances derived from contactless sensor data ‐ and clinical disease progression.MethodWithing’s Sleep Analyser was used to monitor 120PLWD taking part in a home‐monitoring study between 2019‐2023 (46k total nights). Participants were assessed 6‐monthly with ADAS‐Cog and Pittsburgh Sleep Quality Index (PSQI), and 3‐monthly with Neuropsychiatric Inventory (NPI) and Bristol Activities of Daily Living Scale (BADL). We used mixed linear models to examine the association between each assessment and the DRI‐SI score and variability. Additionally, a predictive model using an explainable boosting regressor was constructed to assess the DRI‐SI’s ability to predict ADAS‐Cog, PSQI, NPI and BADL scores.ResultWe included 107 participants (69 AD, 38 non‐AD dementia) with sufficient contemporaneous questionnaire and sleep‐mat data. Minute‐to‐minute timeseries were extracted from the sleep‐mats to calculate nightly DRI‐SI scores (Figure 1). Longitudinally, there was a significant gradual decline in ADAS‐Cog and BADL scores over the 18‐month follow‐up, while the NPI and PSQI showed little change (Figure 2). The DRI‐SI score and variability were significantly associated with BADL (Coef.=2.0±0.6, Z=3.3, P=0.001; Coef.=3.9±1.7, Z=2.3, P=0.02). ADAS‐Cog and NPI were also significantly associated with the DRI‐SI score, but not the DRI‐SI variability (Coef.=3.4±1.1, Z=2.95, P=0.003; Coef.=3.1±0.9, Z=3.3, P=0.001). Interestingly, no association was seen between the DRI‐SI and PSQI. The predictive model demonstrated significant predictive power for ADAS‐Cog and BADL scores, indicating the potential of DRI‐SI as a digital biomarker for cognitive and daily function in dementia (Figure 3c,d).ConclusionOur results suggest that DRI‐SI, a novel digital biomarker of sleep disturbance and night‐time behaviour in dementia derived from contactless remote sleep‐monitoring, associates with measures of cognition and function in dementia. As such, DR‐SI shows great promise for better predicting dementia progression, personalizing treatments, and augmenting outcomes in clinical trials.
White matter abnormalities in association with amyloid and tau deposition in a diverse cohort with increased risk for Alzheimer’s disease
Authors: Blujus Jenna K , Rego Eliza , Bica Sarah , Demos Kathryn , Lee Athene KW , Riddle Meghan C. , Wing Rena R. , Salloway Stephen , Maillard Pauline , Fan Audrey P. , Decarli Charles , Vemuri Prashanthi , Lockhart Samuel N. , Baker Laura D , Landau Susan M. , Oh Hwamee ,   for the U.S. POINTER Study Group and the Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundNeuritic plaques with fibrillar beta‐amyloid (Aβ) peptides and tau‐protein neurofibrillary tangles, hallmark features of Alzheimer’s disease (AD) pathology, have been concomitantly associated with white matter (WM) integrity loss, while a unique effect of each pathology on WM integrity in a more demographically diverse population remains unknown.MethodTo examine the degree to which each pathology affects WM integrity in a more diverse non‐demented cohort, Aβ and tau PET, diffusion‐weighted imaging (DWI), and cognition (memory and executive function composites) were examined from the U.S. POINTER neuroimaging participants (N=608; age=68.34±5.2; 61.8% females; 29% Aβ+) and a subset of Alzheimer’s Disease Neuroimaging Initiative (ADNI) participants (N=291; age=72.85±7.3; 50% females; 39% Aβ+) (Table). Aβ‐positivity was determined using tracer‐specific standardized cut‐offs. Tau SUVR was estimated for each Braak stage. For WM integrity, voxel‐based GLMs were applied to FSL‐processed fractional anisotropy (FA) maps using Braak stage tau SUVR and Aβ‐positivity status, along with covariates of age, sex, and b‐value profiles.ResultIn U.S. POINTER, independent from Aβ‐positivity status, greater tau burden in Braak stages I and II was related to lower FA across the tracts including the superior longitudinal fasciculus, fornix (cres), corpus callosum, and anterior thalamic radiation (Figure). Average FA from supra‐threshold clusters for Braak I and II significantly predicted executive function but not episodic memory. No association between FA and tau burden in Braak stages III/IV or V/VI was found. In the ADNI sample, greater tau burden in Braak I was related to lower FA mostly in left inferior longitudinal fasciculus and left uncinate fasciculus, while negative associations with FA became more diffuse with tau load in Braak III/IV and V/VI. Average FA from supra‐threshold clusters significantly predicted both episodic memory and executive function scores. Across both samples, after accounting for tau burden in each Braak stage, there were no association between Aβ‐positivity status and WM integrity.ConclusionDistinct associations between tau burden, WM integrity, and cognition were found across the studies, indicating greater impact of early tau burden on WM integrity in U.S. POINTER, accounting for Aβ‐positivity status. Factors contributing to the distinct associations across studies need further investigation.
GEAR 2.0 ‐ Communication and Shared Decision Making
Authors: Carpenter Christopher R 
Published: January 2025

AbstractAging adults worldwide are presenting to the emergency department with acute and subacute illness and injury confounded by often unrecognized cognitive impairment, including dementia and delirium. Conveying medical information and weighing various diagnostic and therapeutic approaches during times of emergency is difficult for all aging adults. In adult ED populations without dementia, communication is imperfect with incomplete recollection of test results, presumptive diagnoses, prescriptions, and follow‐up recommendations. Communication strategies striving to improve ED nurse/physician‐to‐patient information exchange such as TeachBack are ineffective in non‐dementia populations and untested in subsets with dementia or their care partners. Increasingly, healthcare disparities associated with dementia detection and interventions are acknowledged. For example, limited health literacy is one source of disparity, interacts with the severity of dementia, is one communication barrier, and yet is not routinely evaluated in ED settings. Shared Decision Making is an evolving approach to engage patients and families in complex medical conversations, but emergency medicine shared decision making research often excludes individuals with dementia by design. This session will explore theoretical opportunities to improve medical decision‐making during times of emergency for persons living with dementia and their care partners.
Theta‐ and alpha‐band functional connectivity are associated with longitudinal tau accumulation in asymptomatic individuals expressing Aβ pathology
Authors: Rudolf Jonathan Gallego , Wiesman Alex I , Baillet Sylvain , Villeneuve Sylvia ,   PREVENT‐AD Research group
Published: January 2025

AbstractBackgroundRecent studies suggest that tau pathology spreads between functionally connected (FC) brain regions. The accumulation of amyloid‐beta (Aβ) promotes neural hyper‐activity in asymptomatic older adults, which might enhance tau spreading. We assessed the relationship between band‐specific neurophysiological FC and the rate of tau accumulation over time and tested whether this association is dependent on the presence of Aβ pathology.MethodWe measured cortical Aβ deposition using positron emission tomography (PET) and resting‐state neurophysiological activity using magnetoencephalography (MEG) at baseline, as well as longitudinal cortical tau PET deposition (mean time between scans = 4.3 years), in a group of cognitively unimpaired older adults with family history of Alzheimer’s Disease (PREVENT‐AD cohort; N = 84). Region‐specific measures (i.e. Aβ, tau, MEG timeseries) were extracted from 68 cortical parcels of the Desikan‐Killiany atlas. Neurophysiological FC between cortical regions was estimated across delta, theta, alpha and beta frequency bands using the corrected amplitude envelope correlation (AEC‐c). A global Aβ standardized uptake value ratio (SUVR) was calculated by taking the average across a set of early Aβ accumulating regions. Individual‐specific tau epicenters were defined as the six cortical regions with the highest levels of baseline tau‐PET binding. The annual rate of change in tau SUVR between the first and second scan was calculated for each cortical region (Figure 1). Linear mixed‐effects models were designed to test if the neurophysiological FC connectivity of each cortical parcel with tau epicenters was related to increased longitudinal tau accumulation in that region, and whether this association was dependent on baseline levels of Aβ pathology.ResultTau epicenters identified across individuals were mainly localized in temporal and medial posterior brain regions. Regional increases in theta‐ and alpha‐band FC with tau epicenters at baseline related to greater longitudinal tau accumulation in individuals expressing higher levels of global Aβ pathology (Figure 2).ConclusionOur results suggest that tau spreads across cortical regions that are functionally connected in the theta‐ and alpha‐bands, but only in individuals with high levels of cortical Aβ. This finding supports the notion that Aβ‐related neural hyper‐activity promotes tau spreading across the cortex following individual‐specific patterns of FC in asymptomatic older adults.
Simvastatin restores neurovascular coupling and cognition in APP mice
Authors: Huth Maria Paula Faccin , Bourourou Miled , Lesage Frédéric , Hamel Edith , Zimmer Aline R. 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) is the leading cause of dementia worldwide and vascular dysfunction represents one of the first abnormalities in AD spectrum. Brain imaging techniques that use changes in hemodynamic signals to measure alterations in neurovascular coupling (NVC) have proven useful for early detection of cognitive deterioration. Pharmacological interventions targeting vascular risk factors, including simvastatin (SV), show promise in preventing dementia. To better understand the changes in brain NVC through the AD progression, we measured whisker‐evoked changes in hemodynamics signals and cognition longitudinally in a transgenic mouse model of AD (APP‐J20 mice) and wild‐type (WT) mice treated or not with SV.MethodHemodynamic signals following whisker stimulation (8Hz, 10 sec) were recorded longitudinally (3‐8 months) in anesthetized (ketamine/xylazine) and awake WT and APP mice, implanted with full cranial window, using optical imaging of intrinsic signals (OIS) (525, 590, and 625 nm), together with cognitive testing. The effects of SV treatment were evaluated after 2.5 and 5 months.ResultAPP mice displayed significant NVC deficits compared to WT littermates in both awake and anesthetized conditions. The anesthesia worsened the whisker‐evoked hemodynamic responses in APP mice. These changes were detected at early stage of the disease (3 months‐old), before the appearance of cognitive impairment (5.5 months‐old). SV treatment totally restored NVC and cognitive function after 5 months of treatment in APP mice.ConclusionThe longitudinal analysis of NVC supports their relevance as translational measures for early diagnosis. Our data with SV indicate that preventive cardiovascular strategy for individuals at risk of developing AD may bear promise in protecting brain function.