bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of FDG PET in the assessment of dementia syndromes: numbers from a reference center in Recife, Brazil
Authors: Pinheiro Mariana Gonçalves Maciel , da Silva Alberto Henrique Torres Trindade , Nunes Luiz Eduardo Duarte Borges , Arca Vitor Maia , Silva Milena Beatriz de Araújo , Barbosa Breno José Alencar Pires 
Published: January 2025

AbstractBackgroundPositrons Emission Tomography associated with Computed Tomography – PET/CT using the 18F‐fluorodeoxyglucose is a well‐established exam for the context of dementia evaluation. However, FDG PET is a method still unavailable in most centers and diagnostic accuracy depends on the development of a flowchart that involves proper indication by clinicians and specialized evaluation by nuclear medicine specialists. Our study aims to investigate the indications of FDG PET in the differential diagnosis of dementia in a single center; secondarily, to evaluate how this method aided the diagnostic process.Methodsingle‐center, descriptive analysis of patients with an initial diagnosis of neuropsychiatric syndromes that underwent FDG PET between 2018‐2023. We used an Excel chart to register clinical data and diagnostic hypothesis, followed by the FDG PET results. The final classification of each patient’s clinical diagnosis and image diagnosis findings was: concordant, discordant and undetermined concordation.Result56 patients were included. The mean age was 71 years‐old and 55.36% were female. The diagnostic impression of the PET‐CT report of these cases showed 13 non‐specific changes in the metabolic view, 16 changes compatible with Alzheimer’s Disease (AD), 7 Lewy Bodies Dementia (LBD), 11 Frontotemporal dementia (FTD), 1 was associated with Mild Cognitive Decline (CLD). Furthermore, 7 of the reports were described as “Negative for dementia” and 1 as progressive supranuclear palsy (PSP). The main indications for PET‐CT scans were suspicion between the diagnosis of AD versus FTD and AD versus LBD. Suspicions for pseudodementia and other diseases progressing to cognitive impairment were also evaluated. Of the 56 patients in the sample, 14 (25.00%) of the clinical impressions were discordant with the results of the imaging exam, 24 (42.86%) were concordant and in 18 (32.14%) comparisons the exam pointed to indeterminate result.ConclusionIn this study, we observed that PET‐CT had the contributive potential to diagnostics of dementia in the majority of analyzed cases, in which it added value to initial clinical suspicions. In this sense, expanding data and carrying out new studies is still necessary.
Carotid stiffening with impaired damping is associated with cognitive impairment and reduced cerebral perfusion in elderly adults
Authors: Tang Jianing , Zhao Tianrui , Joe Elizabeth B , Pahlavian Soroush Heidari , Chui Helena C , Yan Lirong 
Published: January 2025

AbstractBackgroundEmerging evidence indicates that arterial stiffening is associated with aging and cognitive impairment. Arterial stiffness is typically assessed by measuring pulse wave velocity (PWV) between carotid and femoral arteries. A recent study has introduced a fast oblique‐sagittal PC‐MRI (OS PC‐MRI) technique that allows for simultaneously quantifying carotid PWV (cPWV) and CCA‐ICA damping factor (cDF) within 2 minutes. This study aims to investigate the relationship between the pulsatile measures by OS PC‐MRI and cognitive impairment and cerebral perfusion in elderly adults.MethodForty elderly participants (22 female,73.3 ± 7.7 years) were enrolled in the study and underwent MRI scans at 3T including a vessel scout, retrospectively gated OS PC‐MRI (n=40), and pCASL (n=25). Neuropsychological tests were also conducted, including Clinical Dementia Rating (CDR, n=29), Mini‐Mental State Exam (MMSE, n=29), and Montreal Cognitive Assessment (MoCA, n=40). As shown in Figure 1, in OS PC‐MRI, Pearson correlation was performed to test the associations of the metrics pulsatile measures with cognitive functions and cerebral perfusion.ResultElevated cPWV was strongly associated with cognitive decline after controlling for age, gender, and years of education (cPWV vs. MoCA: r = ‐0.36, p = 0.03; cPWV vs. MMSE: r = ‐0.53, p = 0.005;) (Figure 2a). The participants with CDR>0 (n=19) showed higher cPWV values compared to those with CDR=0 (p=0.0045) (Figure 2b). cDF showed a significant correlation with MoCA (p = 0.036) (Figure 2c). Increased cPWV was also associated with downstream CBF in gray matter (p=0.034) and AD‐related regions (Figure 3).ConclusionOur results showed that both elevated CCA‐ICA PWV and DF were strongly associated with cognitive impairment and downstream cerebral perfusion deficits in elderly adults. These findings suggest that arterial stiffening with reduced damping leads to excessive transmission of pulse energy to downstream vasculature resulting in microvascular dysfunction and thus cognitive impairment.
The DICE Approach to Intervene the Behavioral and Psychological Symptoms of Dementia: a Study Protocol
Authors: Zheng Yaonan , Zhang Xingyu , Xia Mengmeng , Wang Huali 
Published: January 2025

AbstractBackgroundThe “Describe‐Investigate‐Create‐Evaluate” (DICE) approach has been considered as a guide for managing behavioral and psychological symptoms of dementia (BPSD). However, the implementation of DICE approach may be limited by few available resources. With the development of AI technology, the effectiveness of AI‐aided DICE algorithm for BPSD management has yet to be determined. Therefore, this study aims to examine the effectiveness of the AI‐aided DICE algorithm for managing BPSD in low‐resource setting.MethodsThe cluster randomized controlled trial will be conducted in 12 medical facilities where geriatric psychiatrists are not fully installed. One hundred and eighty‐four persons with mild and moderate BPSD will be enrolled and randomized to the AI‐aided DICE group (n = 92) and usual care group (n = 92). In the AI‐aided DICE group, all participants will receive comprehensive assessment on a digital triage platform to identify individualized needs and target symptoms, be prescribed with personalized management plan based on the AI‐aided decision process, be monitored about the implementation of management plan, and receive follow‐up assessment to evaluate the effectiveness. The neuropsychiatric inventory questionnaire and caregiver burden inventory will be used to measure primary and secondary outcomes. assess caregiver burden, records of care and adverse event. The study duration for each participant will be 12 weeks.DiscussionWe expect that the study will examine the effectiveness of the AI‐aided DICE algorithm for managing BPSD in low‐resource setting. The findings will support the implementation of AI‐aided algorithm and leverage the practice for quality care for dementia.
Temporal dynamics of brain connectivity across the dementia spectrum
Authors: King Jace B , Prigge Molly B.D. , Duff Kevin , Hoffman John M. 
Published: January 2025

AbstractBackgroundTraditional functional connectivity is calculated as the correlation between resting‐state fMRI time series from pairs of brain regions or networks. Our innovative method extracts time series information from cross‐correlations curves between brain regions, thus deriving the relative duration of functional connections. These temporal analysis methods provide a means for examining how the timing of brain connections is affected across the dementia spectrum. This study extends previous research efforts into understanding the neural correlates of dementia by applying innovative resting‐state functional connectivity analysis methods to a sample of cognitively intact older adults (HC), individuals with mild cognitive impairment (MCI), and Alzheimer’s disease (AD).Method109 participants were included in this analysis (HC: n=47, 29 female, age=72.13±4.68; MCI: n=32, 18 female, age=73.84±5.14; AD: n=30, 19 female, age=77.37±6.45). All study participants were administered the Mini Mental Status Examination (MMSE), and completed MP2RAGE structural imaging and two 15‐minute resting fMRI scans. Cross‐correlation curves were constructed utilizing the Pearson correlation coefficient between pairs of times series for each of the 17 brain networks in the Yeo et al. parcellation. Correlation values were recorded at each of ±20 lags by shifting one of the time points by one volume. Sustained connectivity is derived from the full width at half maximum of the curve (Figure 1A) whereas lag‐based connectivity utilizes the correlation value at each lag. T statistics and p‐values are reported for across‐group connectivity values. Partial correlations were computed between connectivity measures and MMSE scores. All results include controlling for the effects of mean head motion, age, and sex.ResultSustained connectivity demonstrated distributed increases across groups (Figure 1B; HC<MCI<AD; pFDR<.05). At zero‐lag, we see decreased connectivity in MCI and AD compared to HC; however, as lag‐based connectivity is increased, we see increases in connectivity corresponding to diagnostic groups (Figure 2; HC<MCI<AD). Across study participants, both sustained and lag‐based connectivity were negatively correlated with MMSE scores (Figure 3; pFDR <.05).ConclusionTaken together, these findings suggest that functional connections between brain networks persist longer across disease states and that this longer duration of connectivity may reflect increased cognitive demand related to underlying cognitive processes.
The effect of traumatic brain injury and post‐traumatic stress disorders on AD pathologies, small vessel changes and ultimately cognitive function
Authors: Sibilia Francesca , Cen Steven , Choupan Jeiran , Hazany Saman , Ayala Rene , Cheng Jocelyn , Nejatpoor Tiana , Sheikh‐Bahaei Nasim 
Published: January 2025

AbstractBackgroundAlthough many studies have shown that traumatic brain injury (TBI) and post‐traumatic stress disorder (PTSD) regardless of their severity, are associated with a significantly increased risk of all‐cause dementia, the specific pathophysiological mechanisms that underlie these associations remain poorly understood, resulting in discordance findings among different studies and contradictory claims in the current literature.In this study we investigated the effect of TBI and PTSD on the level of amyloid, tau, as well as markers of small vessel health including white matter hyperintensity and perivascular spaces and consequently assessed their effect on the cognitive function in order to understand the pathways through which TBI and PTSD may result in dementia.MethodThe participants in this study were MCI cases drawn from the ADNI‐DOD (n=58). Cognitive performance was assessed using the Mini‐Mental State Exam (MMSE) and Clinical Dementia Rating (CDR). Inclusion criteria for TBI involved the history of moderate to severe nonpenetrating head trauma as well as combat history or presence in the battlefield. Inclusion in the PTSD group required a minimum Clinician Administered PTSD Scale (CAPS) score of 40 points. PET images with tracers AV1451 and AV45 were obtained. Perivascular spaces (PVS) volume fraction in the total white matter and basal ganglia was obtained using automated segmentation pipeline developed at our institute, as well as the grade of white matter hyperintensities.ResultThe volume of PVS in the white matter was found to be significantly higher in veterans with PTSD (p=0.01) or with TBI (p=0.02) after age adjustment. Elevated amyloid was also found in veterans with PTSD 1.3 (1.23‐1.39) vs. 1.23 (1.1‐1.53), p=0.05 and trend of increased amyloid with TBI 1.3 (1.18‐1.44) vs. 1.28 (1.23‐1.31), p=0.09. Our day also indicates a strong correlation between amyloid and CDR (adjusted ranking score correlation of 0.45 (p<0.01) among veteran sample.ConclusionPreliminary evidence showed the association from PTSD to amyloid as well as TBI to amyloid. Since amyloid strongly associated with cognitive function, it may suggest a biological pathway from PTSD and/or TBI through amyloid deposition to cognitive decline in veteran. Larger sample will be needed to confirm the causal pathway.
Association of plasma neurofilament light and white matter hyperintensity on memory: Differential findings across Apolipoprotein E risk groups in normal aging
Authors: So Mae Yue , Maillard Pauline , Jin Lee‐Way , Farias Sarah Tomaszewski , Decarli Charles , Sapkota Shraddha 
Published: January 2025

AbstractBackgroundNeurocognitive trajectories in normal aging are a result of complex and synergistic associations of multiple risk domains. Blood‐based, neuroimaging, and genetic biomarkers all play fundamental roles that span decades leading to cognitive decline. We study all three risk domains on memory using an ethnoracially diverse cohort. Specifically, we examine (1) independent associations of plasma Neurofilament Light (pNfL) levels and white matter hyperintensity volume (WMHV) on episodic memory (EM), (2) pNfL levels on WMHV, and (3) synergistic model with pNfL and WMHV to predict EM, independently and as stratified by Apolipoprotein E (APOE) risk groups.MethodWe used an ethnically diverse cohort of cognitively normal (CN) older adults from the University of California, Davis‐Alzheimer’s Research Center (n=299, Table 1). EM was measured using the Spanish and English Neuropsychological Assessment Scales across eleven waves. WMHV and pNfL levels were obtained at baseline. Statistical analyses included a latent growth modeling to establish latent EM growth model, and regression analyses to test independent associations and stratification with APOE. APOE genotype risk was examined as ε4‐/ε4+. Age was centered at 75 years, and sex and education were included as covariates.ResultFirst, higher pNfL level was associated with steeper EM decline (Table 2). Second, higher WMHV was associated with lower EM performance and steeper EM decline. Third, higher pNfL level was associated with higher baseline WMHV. Fourth, in the combined model, higher pNfL level was associated with steeper EM decline, higher WMHV was associated with lower EM performance, and higher pNfL level was associated with higher baseline WMHV. When stratified by APOE genotype risk, higher pNfL level and higher WMHV were associated with steeper EM decline only in the APOE ε4‐ group. However, higher pNfL level was associated with higher baseline WMHV across APOE ε4‐ and ε4+ groups (Figure 1).ConclusionWe observed that the association between pNfL and EM, and WMHV and EM are both modified by APOE genotype (Figure 1). However, the relationship between pNfL and WMHV is present regardless of genetic risk. Examining biomarkers across multiple domains may lead to novel and effective clinical interventions in diverse CN populations.
Elevated IRS‐1 pS616 Pathology in Human Hippocampal Area CA1 as a Biomarker of Preclinical and Alzheimer's Disease Dementia
Authors: Gu Xuelin , Distel Tim , Talbot Konrad 
Published: January 2025

AbstractBackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disease whose risk can be assessed in the AT(N) framework based on brain levels of Aβ and pathological tau with or without neuronal injury. This helps determine if a cognitively normal or mildly cognitively impaired (MCI) person has clear signs of AD pathogenesis. The AT(N) framework might be enhanced by also considering brain insulin resistance (BIR), which is a common feature in AD dementia (ADd). However, a clear biomarker for brain insulin resistance has yet to be identified. Some studies have identified elevated insulin receptor substrate‐1 phosphorylated at S616 (IRS‐1pS616) in ADd, with conflicting results in other studies. Here, we observed IRS‐1pS616 is mostly limited to cell nuclei in hippocampal field CA1 of normal cases but becomes prominent in neuronal cytoplasm in ADd cases, quantifying this pathological feature using artificial intelligence‐based analysis.MethodsWe performed quantitative immunohistochemical studies on fixed hippocampal sections from 217 age‐ and sex‐matched cases: 68 non‐cognitively impaired (NCI), 13 preclinical (PrCl; i.e., NCI but A+T+), 24 non‐amnestic MCI (naMCI), 32 amnestic MCI (aMCI), and 80 ADd from 3 brain banks (University of Pennsylvania [UPenn], Rush University, and the Banner Research Institute) for β‐amyloid (NAB228), phospho‐tau (AT8), and IRS‐1pS616 (44‐550G). Immunoreactive cells and plaques were quantified using supervised deep‐learning U‐Net neural networks with additional morphology‐based criterions.ResultsDemographical characteristics of study participants are presented in Table 1. The density of CA1 neurons with IRS‐1pS616 pathology was significantly elevated in ADd cases across all cohorts, in PrCl cases from some cohorts, but not in MCI cases (Figure 1). Significant associations were found between IRS‐1pS616, β‐amyloid, and phospho‐tau pathologies in regression analyses, which were weak between IRS‐1pS616 cells and β‐amyloid plaques (Figure 2). No significant differences in IRS‐1pS616 pathology were found between APOE genotypes.ConclusionThese results suggest that elevated IRS‐1pS616 pathology in hippocampal field CA1 is a potential biomarker for BIR in preclinical and ADd, which may be treatable with antidiabetics in the class of incretin receptor agonists shown to reduce BIR in ex vivo preparations of the hippocampus from MCI and ADd cases (see Abstract 89821).
Distinct associations between the neurite microstructure of white matter bundles, tau pathology and cognitive decline in preclinical Alzheimer's disease
Authors: Gozdas Elveda , Hosseini Hadi 
Published: January 2025

AbstractBackgroundRecent advancements in molecular positron emission tomography (PET) enable precise tracking of tau pathology in Alzheimer's disease (AD). Tau pathology typically begins focally in the medial temporal lobe, rapidly expanding due to amyloid‐β (Aβ) influence. This expansion may lead to neurodegeneration along connected pathways to the tau epicenters, resulting in cognitive decline. Our study utilized PET scans, diffusion Orientation Dispersion and Density Imaging (NODDI), and longitudinal memory data to investigate the intricate connections between tau accumulation and neurite microstructures in white matter bundles connected to the tau epicenter and resulting cognitive decline.MethodThe study had 155 participants, including 90 cognitively normal (CN) and 65 mild cognitive impairment (MCI) from the Alzheimer's Disease Neuroimaging Initiative dataset (Table 1). The study included cortical tau accumulations in the entorhinal cortex (EC) to the hippocampus (H) and neurite microstructures of the cingulum hippocampal bundle (CHB). The study also included longitudinal episodic memory scores measured using the Rey Auditory Verbal Learning Test Immediate (RAVLT‐I).ResultThe association between tau accumulation in EC and H in the right and left hemispheres was found to be significantly related to the increased isotropic water (FISO) of HCB (p<0.01). In contrast, the fiber complexity (ODI) along the CHBshowed a correlation with tau accumulation in the right EC (p=0.03, t=2.31) and H (p=0.02, t=‐2.33) for the entire sample. It's worth noting that significant correlations between FISO and ODI and tau accumulations in the epicenters remained significant for the amyloid‐positive group (Aβ+ CN and MCI). Also, the tau aggregation in the retrosplenial cortex (RSC) was significantly correlated with the neurite layout of CHB (p<0.05). Finally, we explored the correlation between the microstructural changes in neurites along the CHB and cognitive decline. The linear mixed effect model showed a significant interaction effect of tau_EC (left)xCHB_ODI (left)xtime (p=0.03, f=4.58) and tau_RSC (left)xCHB_ODI (left)xtime (p=0.04, f=4.4) for predicting cognitive decline over three years.ConclusionOur research has revealed significant connections between the tau accumulation in tau epicenters and posterior regions and the microstructures of neurites along CHB, suggesting that CHB plays a crucial role in tau spreading and cognitive decline.
Brainstem Volume and White Matter Characteristics Associated with Cognitive Performance in Healthy Middle‐aged Adults
Authors: Li Yanrong , Caillaud Marie , Gallagher Isabelle , Youn Cherry , Park Jessica , Haley Andreana 
Published: January 2025

AbstractBackgroundTraditionally linked to essential physiological functions, the brainstem is now acknowledged for its role in cognition and dementia. Abnormal tau protein accumulation starts in the brainstem. Late life brainstem volume at baseline also predicts later Alzheimer's Disease conversion. Yet, brainstem's association with cognitive function in healthy middle‐aged adults has been insufficiently studied. This research investigates the brainstem’s structure, focusing on volume and white matter integrity, and their correlation with cognitive performance in this healthy middle‐aged adults.MethodA total of 202 middle‐aged adults aged 40 to 60, free of clinical conditions were enrolled. They underwent a comprehensive neuropsychological assessment evaluating their executive function, attention, and memory performance. T1 and diffusion tensor images (DTI) were collected on a 3T scanner. Brainstem and total intracranial volumes (TIV) were extracted from the T1 images. Fractional anisotropy (FA) values of superior and middle cerebellar puncle were extracted from the DTI images.ResultAfter controlling for age, sex, education, and total intracranial volume, larger brainstem volume is significantly associated with better memory performance (F(5, 196) = 6.185, R2 = 0.1363, P < .001; βbrainstem vol = .069, P = .025) but not attention or executive function. Additionally, APOE4 carrier status significantly moderates the correlation between brainstem volume and attention (F(7, 85) = 2.902, R2 = 0.193, P < .01; βbrainstem vol:APOE4 status = .131, P = .034). After controlling for age, sex, and education, higher superior cerebellum peduncle FA value is significantly associated with better memory (F(4, 128) = 6.58, R2 = 0.1706, P < .001; βSCP FA= 5.098, P = .0018), attention (F(4, 128) = 4.706, R2 = 0.13, P = .001; βSCP FA= 3.983, P = .009), and executive function (F(4, 128) = 2.963, R2 = 0.085, P = .022; βSCP FA= 3.945, P = .018).ConclusionThe study highlights the brainstem's significant association with memory performance and attention in middle‐aged adults, particularly among APOE4 carriers. This emphasizes the brainstem's potential as an early indicator of cognitive decline. The significant correlation between brainstem FA values and cognitions suggests that further exploration of other brainstem's measures should be included in future studies.