bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of Global Cognition Trajectories with Medial Temporal Brain Stiffness in Aging and Alzheimer’s Disease
Authors: Pavuluri KowsalyaDevi , Huston John , Ehman Richard L. , Manduca Armando , Vemuri Prashanthi , Jack Clifford R. , Senjem Matthew L. , Murphy Matthew C. 
Published: December 2023

AbstractBackgroundCognitive decline with aging and neurodegeneration is caused by various neurobiological processes at molecular, cellular, and organ levels. Advanced imaging techniques that detect tissue microstructural alterations may predict cognitive decline earlier than atrophy measures. Tissue‐level mechanical properties are thought to primarily reflect the rigidity and tension of extracellular matrix‐cytoskeleton matrix (https://doi.org/10.1038/s41586‐019‐1516‐5) and can be measured noninvasively by Magnetic Resonance Elastography (MRE) (https://doi.org/10.1126/science.7569924). These properties are sensitive to pathophysiological processes that characterize neurological disease including dementias. This study examines the role of medial temporal lobe stiffness in predicting global cognitive decline in participants along the Alzheimer’s disease spectrum.MethodSeventy‐five participants underwent MRE, MRI, amyloid PET imaging, and cognitive assessments with informed consent, and the study was approved by the Mayo Clinic IRB. MRE stiffness maps were calculated by neural network inversion, and medial temporal (MT) stiffness extracted (https://doi.org/10.1002/mrm.29226https://doi.org/10.1016/j.nicl.2023.103328). White matter hyperintensity (WMH) load, average cortical thickness of AD signature regions, PiB‐PET standardized uptake ratio (PiB‐SUVr), and global cognition z‐scores were each computed (https://doi.org/10.1016/j.neurobiolaging.2020.09.005). Linear mixed effect models were used to assess the effects of MT‐stiffness and its interaction with follow‐up time on global cognition. The additional effects of cortical thickness, WMH, and PiB‐SUVr, and their interactions with cognition follow‐up time were evaluated.ResultTable 1 summarizes results from three mixed effect models. MT‐stiffness and its interaction with time were significant predictors in models 1 (MT‐stiffness only) and 2 (MT‐stiffness+cortical thickness). In model 3 (MT‐stiffness+cortical thickness+PiB‐ratio+WMH), MT‐stiffness alone did not reach significance (P= 0.058), but its interaction with time was a significant predictor. Fig.1 shows global cognition z‐scores with age. Figs. 2A,2B, and 2C show global cognition prediction trajectories. These results suggest that softer MT‐stiffness predicts faster cognitive decline. MT‐stiffness was a significant predictor of cognitive score even when controlling for other biomarkers such as cortical thickness, PiB‐SUVr, and WMH. These results indicate that stiffness measurements can add predictive value regarding cognitive decline in addition to atrophy and amyloidosis.ConclusionBrain mechanical alterations capture microstructural changes that may aid in understanding disease progression and provide information about future cognitive decline in elderly participants along the Alzheimer’s disease continuum.
Computerized serious game‐based cognitive training in subjective cognitive decline
Authors: Brill Esther , Krebs Christine R. , Brem Anna‐Katharine , Klöppel Stefan 
Published: December 2023

AbstractBackgroundThe neurodegenerative process in Alzheimer’s Disease (AD) commences long before the onset of clinically relevant symptoms. Subjective cognitive decline (SCD) has predictive value towards AD and lends itself as target for non‐pharmacological preventive interventions such as serious game‐based computerized cognitive training (CCT). CCT is effective in attenuating cognitive decline in older adults with mild cognitive impairment or dementia (Hill et al., 2017), however, results in SCD are heterogeneous and long‐term adherence to trainings at home remain a challenge. Additionally, this study aims at addressing shortcomings of previous CCT studies such as comparisons to passive but also active control conditions, matched e.g. for the social elements, crucial for adherence.MethodIn this ongoing bi‐centric, randomized controlled trial (RCT) with parallel groups, participants aged 60 ‐ 85 years with SCD are randomized to one of three study arms (Brill et al., 2022). We compare serious game‐based CCT against a passive wait list control condition and an active control condition (watching documentaries). CCT here focuses on episodic memory, semantic and spatial ability, each leading to one composite score. The protocol in both training conditions entails five weekly at‐home sessions for ten weeks (50 sessions) and weekly on‐site group meetings.ResultAdherence among the current 135 participants was very high. The scores of cognitive function increased in both training groups over the ten weeks’ period, irrespective of the training condition. Baseline imaging data demonstrate strong activations of networks related to spatial ration and episodic memory. Analysis of longitudinal data is ongoing.ConclusionOur preliminary results indicate no specific advantage of CCT over an active control condition in improving cognitive performance. Modulating biological (AD biomarkers) but also psychological factors (e.g. motivation) require further analysis in our dataset. Social elements such as interactive groups meetings seem to be effective in ensuring adherence across training conditions.
Keywords:Computerized cognitive training, serious games, subjective cognitive decline
Gamma‐band transcranial alternating current stimulation in amnestic mild cognitive impairment: A pilot study
Authors: Zanto Theodore P. 
Published: December 2023

AbstractBackgroundAmnestic mild cognitive impairment (aMCI) is a pre‐dementia stage of Alzheimer’s disease (AD) associated with dysfunctional episodic memory and limited treatment options. Recent findings from animal models of AD show that 40 Hz (gamma) stimulation (e.g., through light, sound, magnetic, or electrical stimulation sources) can improve episodic memory and learning, can facilitate neurogenesis, and can also reduce biomarkers associated with AD pathology including beta‐amyloid (Aβ) and tau. Although preliminary studies regarding the efficacy of gamma stimulation in humans has been promising, evidence is limited, neuroplastic changes are unclear, and the feasibility of electrical‐based gamma stimulation is still under investigation. Here, we aimed to characterize feasibility and neuroplastic changes associated with possible improvements in episodic memory following electrical non‐invasive neurostimulation.Method13 individuals with aMCI received eight 60‐minute sessions of 40‐Hz (gamma) transcranial alternating current stimulation (tACS), in a single‐arm design. Primary outcomes assessed side‐effects and drop‐out as indicators of feasibility. Secondary outcomes included episodic memory, plasma‐based Aβ and tau. Exploratory measures included neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP) and white matter fractional anisotropy. Additionally, neuroplastic changes were characterized by resting state functional connectivity (RSFC) within an episodic memory network and neuronal excitatory/inhibitory (Glx/GABA) balance via magnetic resonance spectroscopy.ResultResults revealed that gamma tACS was feasible (minimal side effects and no drop‐outs due to tACS). Moreover, aMCI participants demonstrated improvement in multiple metrics of episodic memory, but no changes in Aβ, tau, NfL, or GFAP. Improvements in episodic memory were most pronounced in participants who had the highest modeled tACS‐induced electric fields and exhibited the greatest changes in RSFC – all within an episodic memory network. Increased RSFC was also associated with greater hippocampal excitability and higher baseline white matter integrity across numerous tracts.ConclusionThis study highlights the potential of gamma tACS to improve episodic memory in an aMCI population by modulating functional connectivity and excitability within an episodic memory network.
Adaptive video games for the assessment and rehabilitation of dementia
Authors: Sander Florian , Manera Valeria , Krebs Christine R. , Touya Maylis , Fischer Elia Luca , Popa Traian , Guevara Andrea Brioschi Brioschi , Anguera Joaquin A , Gazzaley Adam , Klöppel Stefan , Allali Gilles , Demonet Jean‐François , Robert Philippe , Sokolov Arseny A 
Published: December 2023

AbstractBackgroundNeurorehabilitation in dementia becomes an increasingly relevant topic and requires early detection of signs of domain‐specific cognitive decline. To this end, neuropsychological testing is usually performed in specialized centers, which can be difficult to reach for people living in rural regions for example. These centers also usually have long waiting‐lists, which can defer proper diagnosis for long periods of time. Today, increasing attention is devoted to developing rapid cognitive screening batteries that are easy to administer remotely, and have a game‐like interface to reduce test anxiety, capture attention and increase motivation. In terms of treatment, “serious videogames” share the same stimulating, motivating and adaptive qualities, and are surfacing and showing real promise as a viable treatment option (Sokolov et al., 2020).MethodRegarding assessment: We conducted an observational multi‐centric study, evaluating the reliability of the mobile and adaptive serious videogame ACE‐X in detecting cognitive deficits in patients with subjective cognitive decline and mild neurocognitive disorders consulting specialized memory clinics in Bern and Lausanne in Switzerland, and Nice in France.Regarding neurorehabilitation and serious games: We have tested a closed‐loop adaptive cognitive exergame in healthy older adults (Anguera et al., 2022), patients with stroke (NCT05169632) and multiple sclerosis (NCT03737825).ResultsRegarding assessment: The results indicate that ACE‐X can reveal deficits in working memory and multi‐tasking relevant for everyday life.Regarding neurorehabilitation and serious games: The outcomes show sustained benefits in attention, working memory and everyday life. These findings pave the way for integrated, cognitive‐physical, closed‐loop adaptive training for the cognitive neurorehabilitation of people with dementia.ConclusionDetecting subclinical signs of cognitive decline in the aging population is crucial, as it allows to put in place early ‐ and thus more effective ‐ interventions. Closed‐loop adaptive assessment serious video games may be used to perform large‐scale screenings of elderly people at home, to identify those that may benefit from a referral to a medical practitioner. Subsequently, interventional serious video games may represent a promising tool for cognitive neurorehabilitation of cognitive decline due to neurodegeneration.
Fully Automated Lumipulse Plasma Amyloid and phosphorylated Tau assays for Progression to Alzheimer’s disease in Mild Cognitive Impairment patients
Authors: Silva‐Spínola Anuschka , Leitão Maria João , Santana Isabel , Nadal Alicia , Bastard Nathalie Le , Baldeiras Inês 
Published: December 2023

AbstractBackgroundLumipulse G automated immunoassays represent the most widely used method for the quantification of Alzheimer’s disease (AD) biomarkers in cerebrospinal fluid (CSF)1. Less invasive blood‐based markers confer a promising tool for AD diagnosis at prodromal stages (Mild Cognitive Impairment‐MCI)2. Highly sensitive assays for the quantification of amyloid‐beta (Aβ) and phosphorylated Tau‐181 (p‐Tau181) in blood are showing promising results3. In this study we evaluated the clinical performance of the available Lumipulse plasma markers for progression to AD.MethodA group of 138 patients (22 neurological controls‐NC, 72 MCI and 44 AD) recruited at the Dementia Clinic of Centro Hospitalar Universitário de Coimbra (CHUC) was included. Data regarding baseline CSF levels of Ab42, Ab40, t‐Tau and p‐Tau181 was available, allowing for characterization into ATN categories4. Baseline Ab42, Ab40 and p‐Tau181 levels were determined in stored plasma samples using high‐throughput fully automated Lumipulse assays. Progression from MCI to AD dementia was assessed at follow‐up (mean 5.9±3.0 years; 36 converted ‐MCI‐AD/36 stable ‐MCI‐St).ResultIn the total cohort, correlations between CSF and plasma were moderate for p‐Tau 181 (r = 0.61, p<0.001), weak for Aβ42 (r = 0.28, p = 0.001) and non‐significant for Aβ40 (r = ‐0.05, p = 0.54). Plasma p‐Tau181 levels were significantly increased while Aβ42, Aβ42/Aβ40 and Aβ42/p‐Tau181 were significantly decreased (p<0.001) in patients classified as MCI‐AD and AD in relation both to NC and MCI‐St. Plasma p‐Tau181 showed a robust performance in differentiating NC+MCI‐St vs. MCI‐AD+AD (AUC = 0.89, 95%CI:0.83‐0.94), MCI‐St vs. MCI‐AD (AUC = 0.89, 95%CI:0.81‐0.96) and CSF A+ vs. A‐ (AUC = 0.84, 95%CI:0.77‐0.91). Plasma Aβ42/p‐Tau181 gave similar AUC results (AUCs = 0.88, 0.84 and 0.83) and showed no significant differences compared to p‐Tau181 alone (p = 0.34, 0.33 and 0.92). For MCI‐St vs. MCI‐AD, when maximizing for sensitivity (0.92, specificity 0.67), baseline plasma p‐Tau181 levels higher than 1.69 pg/mL predicted future AD dementia (HR = 11.5; 95%CI = 10.9‐12.1).ConclusionOur results show that the measurement of p‐Tau181 in peripheral blood has great potential as a non‐invasive prognostic screening tool for AD dementia in MCI patients.1. Delaby C, et al. Alzheimer’s Dement. 2021; 2.Teunissen CE, et al. Lancet Neurol. 2022; 3.Palmqvist S, et al. Nat Med. 2021; 4.Jack CR, et al. Alzheimer’s Dement. 2018
Ten‐Year Trajectories of Cognitive Function and Their Lifestyle Predictors Among Older Koreans
Authors: Lim Seungju , Kim Ahram , Lim Young Myoung , Han Yebin , Park Ji‐Hyuk 
Published: December 2023

AbstractBackgroundAs the number of dementia patients increases, there is a growing concern regarding the cognitive decline of older Koreans. Lifestyle factors such as physical activity (PA), social engagement (SE), and adverse health behavior (AH) were considered as part of an engaged lifestyle that may effects of advanced age on cognitive function.ObjectivesTo examined the ten‐year trajectories of cognitive function and associated lifestyle factors among young‐old (55‐64), middle‐old (65‐74), and old‐old (75+) Koreans.MethodsData came from the Korean Longitudinal Study of Ageing (KLoSA) between 2008‐2018 waves. Participants were classified as young‐old group (N = 2,346), middle‐old group (N = 2,407), and old‐old group (N = 1,436). Ten‐year cognitive function was assessed using a Korean version of the Mini‐Mental State Examination (K‐MMSE) score. Lifestyle factors, included as observed exogenous time‐invariant variables, were assessed through three domains : PA (regular exercise status, regular exercise duration); SE domain (the variety of social activities, the frequency of participating in); AH (alcohol consumption, smoking status). Latent growth curve modelling and multi‐group analysis were performed.ResultsThis study found that older Koreans reported an average K‐MMSE score of 24.317 at baseline and experienced cognitive decline every years by −0.195. There were differences between the young‐old, middle‐old, old‐old age groups in cognitive trajectories and associated lifestyle factors. The cognitive trajectory of the old‐old groups, whose cognitive function decreased the fastest, was associated to a short exercise period (β = 0.437, p< 0.05) and inactive participation in social activities (β = 0.180, p< 0.01).ConclusionAs the influence of lifestyle factors were differed by age groups, it suggests that age‐specific approaches to cognitive health promotion should be considered.
Keywords:Cognitive trajectory, Latent growth model, Lifestyle, Older Koreans
Detection of behavioral, depressive, and anxious symptoms in patients with Subjective Cognitive Complaints
Authors: Berrios Waleska , Caporale Sofia , Deschle Florencia , Moreno Maria Cecilia , Bustos Claudia , Cervino Cecilia , Saglio Laura , Santajuliana Franco , Povedano Guillermo 
Published: December 2023

AbstractBackgroundSubjective Cognitive Complaints (SCC) are frequent in Neurology. They may be defined as the self‐perception of cognitive decline without objective deficits in Neuropsychological tests. SCC have been associated with poorer cognitive performance, a higher risk of developing Cognitive Impairment or Dementia as well as neuropsychiatric symptoms such as depression and anxiety.Depression and anxiety are frequent mental health issues, with a remarkable impact on cognitive function. An increase in prevalence in both of them is estimated during the COVID‐19 pandemic. Also, behavioral symptoms have a negative impact on quality of life. Nevertheless, they may remain unnoticed if not investigated or without a family report.The objective is to report the frequency of depression, anxiety, and behavioral symptoms in a population with SCC.MethodWe selected patients with cognitive complaints and normal neuropsychological test performance. Demographic data, and behavioral, depressive, and anxious symptoms were collected. Anxious symptoms were assessed with the Beck Anxiety Inventory‐(BAI) and depressive symptoms with the Beck Depression Inventory‐(BDI‐II) and the Geriatric Depression Scale‐(GDS‐15). Neuropsychiatric Symptoms Inventory‐(NPI) was also investigated when an accompanist was available.Result166 patients were included. The mean age was 63.13 (SD 12.2) years, Mean Education was 11.25 (SD 3.62) years. In this sample the frequency of anxiety symptoms was 44.57% (n = 74) according to BAI; 48,64% (n = 36) were mild, 32.43% (n = 24) moderate and 18.93% (n = 14) severe. BDI‐II and GDS‐15 detected depression symptoms in 33.13% (n = 55) of the patients; 58.18% (n = 32) were mild, 32.72% (n = 18) moderate and 9.09% (n = 5) severe. In 59 cases we administer the NPI; 76.27% (n = 45) reported a symptom.ConclusionOur study showed a significant frequency of anxiety and depression symptoms as well as behavioral symptoms in patients with SCC. This reminds us how valuable it is to assess behavioral, depressive, and anxious symptoms in standard Neuropsychological Testing to take a comprehensive approach to the patients. Future studies will help to determine dementia‐developing predictors.
Hyperintensity on Diffusion‐Weighted MRI and Clinical Correlations in Probable Creutzfeldt‐Jakob Disease
Authors: Rhee Hak Young , Park Key Chung 
Published: December 2023

AbstractBackgroundAlthough definite diagnosis for Creutzfeldt‐Jakob disease(CJD) requires tissue confirmation, diffusion‐weighted imaging (DWI) of the brain has an important role in the diagnosis of CJD. Also elevated CSF total tau (t‐tau) is considered as an useful CJD biomarker revealing neuro‐axonal damage although it is not specific for CJD. In this study, we attempted to find out the association between DWI abnormality and CSF t‐tau in CJD patients.MethodWe retrospectively analyzed the medical records reported as human prion disease.The patients who had been diagnosed and reported as human prion disease to Korea Disease Control and Prevention Agency (KDCA) by medical institutions in South Korea during the period of January 1, 2019 to December 31, 2019 were included in this study. The clinical information of the reported patients had been reviewed by a clinical review committee of KDCA for CJD and the patients who had fulfilled the criteria for probable CJD were evaluated for clinical, radiological, and laboratory findings.ResultA total of 186 patients had been reported as suspected human prion disease during the one‐year period and 53 patients who satisfied the criteria for human prion disease were included in the analysis. The most common clinical presentation was cognitive change, followed by cerebellar dysfunction and extrapyramidal symptoms. Hyperintense lesions on DWI were observed in 52 patients (98%). The involvement of neocortex was observed in almost all patients (98%) and asymmetrical and bilateral hyperintensities on DWI were common. Among neocortex, the most commonly involved region was parietal lobe, followed by frontal lobe, temporal lobe, and occipital lobe. DWI abnormality in striatum and/or thalamus was observed in 65.3% of patients. CSF t‐tau was elevated in sporadic CJD patients (8998.3±11903.7 pg/ml) There was no significant association between the extent of the lesions on DWI and CSF t‐tau.ConclusionIn this study,most of the patients with probable CJD showed DWI abnormality mainly on neocortex (parietal > frontal > temporal > occipital) but the association between the pattern of DWI abnormality and the level of CSF t‐tau was not observed.
Associations between glymphatic function and BBB water exchange rate and perfusion in a Latinx cohort
Authors: Shao Xingfeng , Liu Xiaodan , Barisano Giuseppe , Ringman John M , Wang Danny J.J. 
Published: December 2023

AbstractBackgroundThe glymphatic system is thought to clear waste products from the brain by facilitating the exchange of interstitial fluid (ISF) with cerebrospinal fluid (CSF) through aquaporin‐4 (AQP4) water channels present in astrocyte endfeet. A recent non‐invasive MRI method, diffusion tensor image analysis along the perivascular space (DTI‐ALPS), has been proposed for evaluating brain clearance function and has shown reduced glymphatic function in various neurological disorders such as Alzheimer’s disease. However, the role of microvascular perfusion and blood‐brain barrier (BBB) permeability in the glymphatic system remains unclear. In this study, we used a novel diffusion‐prepared arterial spin labeling (DP‐ASL) MRI technique to measure BBB water exchange rate (kw) and cerebral blood flow (CBF) and studied their relationships with the DTI‐ALPS score.Method44 Latinx subjects (20 male; age = 65.6±5.6 years) were recruited from the USC MarkVCID study. Imaging parameters for DP‐ASL were: resolution = 3.5×3.5×8mm3, 10 slices, scan time 10 mins. kw was calculated from the ratio of intra‐ and extra‐vascular perfusion signals with total‐general‐variation (TGV) regularized single‐pass approximation (SPA) modeling and CBF was calculated from PLD = 1800ms data using one‐compartment Kety model. kw and CBF maps were normalized into the MNI space and regional analysis was performed in the frontal/temporal/parietal lobe, and subcortical regions. Association between ALPS score and CBF/kw values were studied by linear regressions. P<0.05 was considered as significant.ResultFig.1 shows kw and CBF maps from three representative subjects with increasing ALPS scores (top to bottom). ALPS was significantly correlated with kw in MTL (β = 1.7e‐3,P = 0.04) and a positive trend was observed between ALPS and whole brain average kw (P = 0.11). While significant correlations were found between ALPS and CBF in multiple brain regions including frontal lobe (β = 7e‐3,P = 0.009), temporal lobe (β = 7e‐3,P = 0.002), parietal lobe (β = 4e‐3,P = 0.03), MTL (β = 8e‐3,P = 0.03), ACC (β = 6e‐3,P = 0.005), PCC (β = 4e‐3,P = 0.02), precuneus (β = 4e‐3,P = 0.04) and whole brain (β = 8e‐3,P = 0.01). Fig.2 shows scatter plots of ALPS versus kw (A) and CBF in MTL and whole brain, respectively.ConclusionThis is the first study in Latinx population demonstrating positive correlations between ALPS score and both CBF and kw, suggesting a possible involvement of blood flow and BBB water exchange rate in the glymphatic system.