bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive‐Behavioral Performance Pre‐ and Post‐Surgery in Parkinson’s Disease Patients Undergoing Deep Brain Stimulation
Authors: Fernandez Maria Cecilia , Giordano Ximena , Berrios Waleska , Barbieri Licina , Ciceri Agustina , Milicich Gaston Moreno , Cornejo Pablo Vera , Stefani Carla , Ciancaglini Lucia , Bestoso Jose , BAUSO Diego 
Published: January 2025

AbstractBackgroundParkinson’s Disease (PD) is known to cause cognitive and behavioral problems, especially in executive‐attentional areas. For some patients, medication is not effective, and surgery is considered a treatment option. However, changes in mood and cognition have been reported after surgical intervention in the subthalamic nucleus (STN) or the internal globus pallidus (GPi), but the literature is inconsistent. This study aims to examine PD patients' cognitive and behavioral performance before and after deep brain stimulation (DBS) surgery in a patient population from Argentina.MethodOur study involved a retrospective analysis of 24 patients who underwent DBS surgery, half of whom received surgery in the STN area and the other half in the GPi. We evaluated cognitive function using neuropsychological tests and neuropsychiatric symptoms using the Beck Depression Inventory and Neuropsychiatric Inventory before and 1 year after the surgery. Variables of age, sex and years of education were evaluated and average values of each domain were calculated in the pre‐surgical test, to be later compared with values obtained in the post‐surgical evaluation, according to the brain nucleus operated on.ResultThe study included patients between the ages of 43 and 69 with an average education level of 10.5 years. After surgery, those who underwent STN intervention (83.3% male) showed improved executive‐attentional domains but a slight decline in visuospatial construction and semantic fluency. Behavioral improvements were observed, with a decrease in symptoms from 12.5% pre‐surgery to 2.33% post‐surgery, while mood worsened (37.5% vs. 41.7%), but not significantly. On the other hand, patients undergoing GPi intervention (83.3% male, 16.7% female) showed slight declines in memory, executive‐attentional functions, and semantic fluency but positive changes in mood‐behavioral aspects (0% and 11.1%, respectively).ConclusionWe found that patients who underwent DBS experienced subtle changes in cognitive performance a year after surgery. While STN intervention showed improvement, those who underwent GPi intervention experienced a slight, nonsignificant decline. However, the study acknowledges that a larger sample size is needed for more substantial results.
Integrative Metabolomics and Whole Transcriptome Sequencing Reveal Role for TREM2 in Metabolism Homeostasis in Alzheimer’s Disease
Authors: Wang Meng , Qin Qi , Tang Yi 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder and the most common cause of dementia worldwide. Dysregulation of various metabolism pathways may mediate the development of AD pathology and cognitive dysfunction. Variants of triggering receptor expressed on myeloid cells‐2 (TREM2) are known to increase the risk of developing AD. TREM2 plays a role in AD development by maintaining cellular energy and biosynthesis, but the precise mechanism through which it accomplishes this is unknown.MethodIn the present study, we explored whether TREM2 plays a role in AD development by maintaining cellular energy and biosynthesis with the help of an AD mouse model (APP/PS1). First, we performed untargeted metabolomics analysis of hippocampal tissues from APP/PS1 transgenic AD mice (APP/PS1‐TREM2 KO mice) and APP/PS1 transgenic AD mice (APP/PS1 mice), which revealed the changes of different metabolites after TREM2 knockdown. Next, we performed transcriptomic analysis to identify differentially expressed genes (DEGs). Finally, we used metabolomics and transcriptomics analysis to screen for genes associated with lipid metabolism.ResultMetabolomic analysis of hippocampal tissue from APP/PS1 and APP/PS1‐TREM2 knockout (KO) mice found that TREM2 KO was associated with abnormalities in several metabolism pathways, and the effect was particularly pronounced in lipid metabolism and glucose metabolism pathways. Consistently, transcriptomic analysis of these mice determined that most differentially expressed genes were involved in energy metabolism pathways. We screened seven differentially expressed genes in APP/PS1‐TREM2 KO mice that may influence AD development by altering energy metabolism. Integrative analysis of the metabolomic and transcriptomic profiles showed that TREM2 may regulate lipid metabolism and sphingolipid metabolism by affecting lipoprotein lipase (LPL) expression, thereby influencing AD progression.ConclusionTREM2 knockout was found to be associated with abnormalities in multiple metabolic pathways in AD mice, particularly lipid metabolism and glucose metabolism. Also, LPL is a novel gene that may affect lipid metabolism and sphingolipid metabolism in AD mice.
Understanding the mechanisms of lateral parietal memory modulation in Alzheimer's Disease
Authors: Slayton Matthew A , McAllister Margaret L , Rothrock Jane , Belhadj Sarrah , Gillette Kirsten D , Hovhannisyan Mariam , Cabeza Roberto , Davis Simon W 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is characterized by progressive impairment of cognition and memory, including the loss of episodic memory. The use of non‐invasive brain stimulation therapies to modulate memory encoding processes is a promising avenue for potential treatment. Previous studies have shown that the use of Transcranial Magnetic Stimulation (TMS) applied to lateral parietal cortex can improve memory in older adults who have received a diagnosis of Mild Cognitive Impairment. This effect may be driven by the modulation of connectivity between parietal cortex and the hippocampus, structures which support the encoding of semantic information into memory. And yet, while modulation of cortical‐hippocampal connectivity helps to establish a systems‐level explanation for the parietal memory benefit for TMS, it does not explain the benefit on the level of memory representation—i.e., the most basic evidence we have of what visual and semantic information underlies memory formation. Previous work from our lab has found that TMS can change memory representations in the hippocampus.MethodHere we present new data from a study applying this approach to MCI, using rTMS to an individualized site in parietal cortex to boost memory function, while monitoring daily changes in behavior and brain physiology over the course of three days. Immediately after rTMS, patients perform a semantic encoding task where they view everyday objects while fMRI is collected, after which they complete recognition memory tasks. To ask whether memory performance improvements are driven by the modulation of visual or semantic information in the brain, we use Representational Similarity Analysis (RSA), a computational method that can reveal the changes in visual and semantic representations over the course of TMS.ResultConsistent with the role of lateral parietal cortex as a hub for the processing of abstract knowledge, we show that semantic representations show greater TMS‐related changes and are more directly associated with improvements in memory success, whereas visual representations are not.ConclusionIncreasing the representation of abstract knowledge is a potential underlying mechanisms by which neuromodulation boosts episodic memory in MCI, which may lead to reliable clinical applications of noninvasive brain stimulation in AD.
Alzheimer’s Disease (AD): Depression is associated with lower Mini‐Mental State Exam (MMSE) Scores
Authors: Komatsu Caroline 
Published: January 2025

AbstractBackgroundNeuropsychiatric symptoms (NPS) are core features of AD and depression is a common co‐morbidity in people with AD, affecting overall outcomes and decreasing quality of life.Method205 outpatients with the diagnosis of AD conforming criteria proposed by NINCDS‐ADRDA (2011), followed‐up at a public university hospital, had their Geriatrics Depression Scale – 15 (GDS ‐15) and MMSE scores evaluated.Results125 patients (60,97%) were diagnosed with depression and 80 patients (39,03%) were not diagnosed with depression. From the depression group, 20 patients (16%) presented severe cognitive impairment (MMSE < 10), 50 patients (40%) presented moderate cognitive impairment (MMSE = 10 – 20) and 55 patients (44%) presented mild cognitive impairment (MMSE > 20). From the non‐depression group, 10 patients (12,5%) presented severe cognitive impairment, 30 patients (37,5%) presented moderate cognitive impairment and 40 patients (50%) presented mild cognitive impairment. Both groups, depression and non‐depression, had on average the same educational level: 3,02 and 3,42 years, respectively.ConclusionIn this sample of patients with AD, depression is associated with lower MMSE scores when compared to non‐depression group.
Adenosine receptor 1 signal mediates the high salt diet induced tau pathology and behavioral abnormalities by suppression of Cers1
Authors: Zhu Ling‐Qiang 
Published: January 2025

AbstractBackgroundAdenosine receptor 1 (A1R) is the predominant subtype of adenosine receptors, primarily distributed in memory‐associated brain regions such as the cortex, hippocampus, and cerebellum. It actively participates in plasticity‐regulated synaptic transmission and is crucial for functions related to sleep, arousal, cognition, learning, and memory. In a recent study, we reported that an elevation in A1R signaling mediates aberrant neuron‐glial crosstalk in Alzheimer’s disease. However, the role of A1R signaling in mediating tau pathology and behavioral abnormalities induced by a high salt diet, an independent risk factor for dementia and cognitive impairment, remains unclear.MethodWe used western blot and qPCR to determine the expression of different protein and mRNAs. Morris water maze was used to examine learning and memory. Virus based shRNA delivery was used to silence the A1R and Cers1 expressionResultHere, we first reported that the Mef2c/miR‐133a/A1R signaling pathway is activated in the hippocampus of mice treated with a high salt diet (HSD). This activation is accompanied by tau pathology and disruption of neuron‐glial crosstalk. Application of KW3902, a specific A1R antagonist, or silencing of A1R, rescued tau pathology, neuron‐derived astrocytic activation, and synaptic dysfunction in HSD mice. Furthermore, we identified that the inhibition of Cers1, resulting from the deficiency of the cAMP‐guided pathway, led to both PP2a suppression and Lcn2 release, potentially underpinning the toxic effects of A1R activation in HSD mice. Artificial overexpression of Cers1 not only ameliorated tau pathology and astrocytic activation but also alleviated synaptic and memory impairments in HSD mice.ConclusionOur study unveils a novel signaling pathway mediating high salt diet‐induced brain dysfunction and provides a new therapeutic target for related diseases.
Nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts
Authors: Zhou Weichen , Karan Kalpita R , Gu Wenjin , Klein Hans‐Ulrich , Sturm Gabriel , De Jager Philip L. , Bennett David A. , Hirano Michio , Picard Martin , Mills Ryan E 
Published: January 2025

AbstractBackgroundThe transfer of mitochondrial DNA into the nuclear genomes of eukaryotes (Numts) has been linked to lifespan in non‐human species and recently demonstrated to occur in rare instances from one human generation to the next.MethodHere we investigated numtogenesis dynamics in humans in two ways. First, we quantified Numts in 1,187 post‐mortem brain and blood samples from different individuals. Second, we tested the dynamic transfer of Numts using a repeated‐measures whole genome sequencing design in a human fibroblast model that recapitulates several molecular hallmarks of aging.ResultIn the ROSMAP dataset, compared to circulating immune cells (n = 389), post‐mitotic brain tissue (n = 798) contained more Numts, consistent with their potential somatic accumulation. Within brain samples we observed a 5.5‐fold enrichment of somatic Numt insertions in the dorsolateral prefrontal cortex compared to cerebellum samples, suggesting that brain Numts arose spontaneously during development or across the lifespan. Moreover, more brain Numts was linked to earlier mortality. The brains of individuals with no cognitive impairment who died at younger ages carried approximately 2 more Numts per decade of life lost than those who lived longer. In the lifespan model, the longitudinal experiments revealed a gradual accumulation of one Numt every ∼13 days. Numtogenesis was independent of large‐scale genomic instability and unlikely driven cell clonality. Targeted pharmacological perturbations including chronic glucocorticoid signaling or impairing mitochondrial oxidative phosphorylation (OxPhos) only modestly increased the rate of numtogenesis, whereas patient‐derived SURF1‐mutant cells exhibiting mtDNA instability accumulated Numts 4.7‐fold faster than healthy donors.ConclusionCombined, our data document spontaneous numtogenesis in human cells and demonstrate an association between brain cortical somatic Numts and human lifespan. These findings open the possibility that mito‐nuclear horizontal gene transfer among human post‐mitotic tissues produces functionally‐relevant human Numts over timescales shorter than previously assumed.
Understanding the cellular responses to anti‐Abeta antibodies to gain insights into mechanisms of ARIA
Authors: Foley Kate E. , Weekman Erica M , Wilcock Donna M. 
Published: January 2025

AbstractAnti‐amyloid immunotherapy holds great promise for our patients and their families as the first disease‐modifying therapy for the treatment of Alzheimer’s disease (AD) to be approved. Positive clinical trials for lecanamab and donanemab showed significant and rapid lowering of brain amyloid burden and a significant slowing of cognitive decline. Amyloid‐related imaging abnormalities (ARIA) in the form of vasogenic edema (ARIA‐E) and micro ‐ and macro‐ hemorrhages (ARIA‐H) remain the major obstacle to broad use of these agents. Significant cerebrovascular pathology precludes treatment due to enhanced risk of ARIA. In addition, it is known that ApoE4 carriers are at a significantly increased risk of ARIA incidence, with 25‐40% of homozygotes developing ARIA. Understanding the mechanisms underlying ARIA is of critical importance to increase safety and broaden the use of anti‐amyloid immunotherapy.Using mouse models of amyloid deposition, we have performed systemic and intracranial anti‐beta‐amyloid antibody administration to study the potential mechanisms of both amyloid clearance and cerebrovascular disruptions that lead to ARIA. We have found that microglial activation is present along the vessels that are laden with cerebral amyloid angiopathy (CAA). Furthermore, coincident with microhemorrhage occurrence is increased expression and activity of matrix metalloproteinases (MMPs) MMP9 and MMP3. MMPs are known to degrade basement membranes and tight junction proteins that could lead to disruption of the blood‐brain barrier and, ultimately, edema and hemorrhage. in fact, it has long been understood that MMP9 plays a critical role in the hemorrhagic transformation of ischemic stroke. We have performed single‐cell transcriptomic analysis to examine the glial responses following a single anti‐amyloid immunotherapy and we find significant microglial population shifts and also enhanced signaling from microglia to perivascular macrophages, potentially implicating these cells as a key player in the development of ARIA.Ultimately, discovering the mechanisms of ARIA will result in the development of safer, next‐generation antibody therapy that has reduced ARIA risk, and also could lead to the identification of adjunct treatments that can be co‐administered with the anti‐amyloid immunotherapy to prevent the occurrence of ARIA in those at risk.
The relationship between right and left hemisphere regional tau and proper name recall from Logical Memory story recall
Authors: Olson Hayley A , Langhough Rebecca E. , Bruno Davide , Hermann Bruce P , Basche Kristin E , Miess Beryl , Kaminski Noelle , Mandel Olivia , Christian Bradley T. , Johnson Sterling C. , Betthauser Tobey J. , Mueller Kimberly D 
Published: January 2025

AbstractBackgroundSensitive screening for early Alzheimer’s disease (AD)‐related cognitive decline are needed. Prior research links high beta‐amyloid (Aβ) levels to reduced proper name (PN) retrieval in individuals without cognitive impairment. We examined whether language‐related regional tau from PET associated with Logical Memory (LM) proper name recall, accounting for LM covariates.MethodParticipants included n = 396 from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) with Logical Memory (LM) story recall, amyloid PET ([11C]Pittsburgh Compound‐B, PiB), and [18F]‐MK‐6240 tau PET; all were unimpaired at LM baseline. Outcomes included z‐scores for LM delayed total score (“total‐LM”) and PN delayed LM subscore (“PN‐score”) from the visit most adjacent to PET‐tau imaging. Amyloid PET burden (visit adjacent to tau PET) was summarized as a global PIB DVR (PiB index, cerebellum GM reference region, graphical analysis). Left and right volume‐weighted MK‐6240 SUVR (inferior cerebellar GM reference regions) averages were calculated for regions previously associated with PN retrieval, including temporal pole, anterior temporal gyrus, anterior middle gyrus, and anterior inferior gyrus (“PN‐regional‐tau‐network”). We compared results from two ANCOVA models (L vs. R regional network as predictors) for each outcome (PN‐score, total‐LM). Covariates in each model included age at LM, sex, WRAT‐3 reading, and PiB index (to replicate prior analyses). To account for unexplained variance from global tau in entorhinal cortex, residuals from a regression of global tau on PN‐regional‐tau‐network were also included.ResultTable 1 displays demographics overall and by tau status (T+/T‐). Overall mean age was 67 (SD = 7); n(%) = 80(20.2%) were T+. Left and right PN‐regional‐tau‐networks were significant predictors of PN‐score (β = ‐.06, R2 = .190, β = ‐.08, R2 = .192, respectively) and total‐LM (β = ‐.08, R2 = .201, β = ‐.09, R2 = .202, respectively; Table 2, Fig 1). In sensitivity analyses removing n = 23 participants with MCI or dementia, Right‐hemisphere PN‐regional‐tau (but not left) was still a significant predictor of PN‐score (β = ‐.06, R2 = .190), and L and R PN‐regional‐tau significantly predicted total‐LM (β = ‐.06, R2 = .134, β = ‐.07, R2 = .136, respectively).ConclusionLogical Memory story recall measures may be sensitive to tau burden in specific language regions; right hemisphere tau in the PN‐regional‐network may be particularly sensitive to early tau burden. Future directions include characterizing regional PET patterns and plasma‐biomarker‐related preclinical rates of change in these outcomes.
Deep Learning Model for Forecasting Propagation of Amyloidopathy in Alzheimer’s Disease
Authors: Jeong ByeongChang , Kim Daegyeom , Seo Surin , Lee Seung‐Hoon , Jeong Hyun‐Ghang , Han Cheol E ,   The Alzheimer’s Disease Neuroimaging Initiative
Published: January 2025

AbstractBackgroundAmyloid‐β accumulation is a pivotal factor in Alzheimer’s disease (AD) progression. As treatment for AD has not been successful yet, the most effective approach lies in early diagnosis and the subsequent delay of disease progression. Hence, this study introduces a deep learning model to predict amyloid‐β accumulation in the brain.MethodWe mathematically modeled the diffusion of amyloid‐β based on its biological traits, encompassing generation, clearance, and diffusion. We converted the model into a deep learning framework with multi‐layer perceptron (MLP) and graph convolutional neural network (GCN) (Kipf et al., 2016) to forecast the accumulation of the protein. We extracted the necessary information from various neuroimage data, including T1 structural magnetic resonance (MR) images, 18F‐Florbetapir positron emission tomography (PET) scans, and diffusion weighted MR images (DWI), to simulate the diffusion of the protein (Figure 1). We used longitudinal data of 146 subjects, incorporating 436 data points.ResultThe proposed model accurately predicted amyloid‐β after 2 years (Figure 2), showing a high correlation in the test dataset (median = 0.8273, IQR = [0.7708, 0.8692]), outperforming the previous model (average 0.58) (Kim et al., 2019). We examined generation and clearance terms, mapping top 30% ROIs onto the brain by averaging each term across subjects (Figure 3). The regions with early AD amyloid‐β accumulation are believed to be related to the default mode network and prefrontal network (Palmqvist et al., 2017) supported by Figure 3a. The effectiveness of amyloid‐β clearance may be influenced by brain activity (Mergenthaler et al., 2013; Ullah et al., 2023). Earlier studies reported diminished metabolism in specific regions during the early AD (Chételat et al., 2020; Kantarci et al., 2021). The proposed model identified high clearance regions (Figure 3b), aligning with regions showing normal metabolism.ConclusionWe introduced a deep learning model that simulates the diffusion of amyloid‐β with strong predictive performance and interpretation. While parameters were optimized for the entire group, accuracy varied for some subjects. Also, further investigation is needed to interpret each term comprehensively. Despite the need for individual optimization and additional interpretative analysis, the model may contribute to the diagnosis of AD.
Efficacy and safety of computerized cognitive training combined with SSRIs for treating cognitive impairment among patients with late‐life depression: A 12‐week, randomized controlled study
Authors: Wang Xiao , Zhang Qinge 
Published: January 2025

Abstract背景:BackgroundThis randomized, open‐label study examined the therapeutic effects of computerized cognitive training (CCT) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late‐life depression (LLD).方法: MethodStudy data were collected from May 5, 2021, to April 21, 2023. Outpatients who met diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) criteria (HAMD‐17) ≥ 18 and a total score on the MOCA) <26 were randomly assigned to receive up to 12 weeks of CCT and SSRIs treatment (n = 57) or SSRIs and Control treatment (n = 61). The primary outcome was the change in Alzheimer’s Disease Assessment Scale‐Cognitive Subscale (ADAS‐Cog) scores from baseline to week 12 between the two groups. Mixed model repeated measures (MMRM) analysis was performed on modified intention‐to‐treat (mITT) and completer populations.结果: ResultThe full analysis set (FAS) included 118 patients (CCT and SSRIs group, n = 57; SSRIs and Control group, n = 61). Over the 12‐week study period, the reduction in the ADAS‐cog total score was significant (P < 0.001) in both groups, while MMRM analysis revealed a significantly greater reduction in cognitive function (ADAS‐cog total scores) from baseline to posttreatment in the CCT and SSRIs group than in the SSRI and Control group [(F (1,115) = 13.65, least‐squares mean difference [95% CI]: −2.77 [−3.73, −1.81], p<0.001)]. There were significantly greater improvements in depression symptoms (measured by the HAMD‐17) in the CCT and SSRIs group than in the control group [MMRM, estimated mean difference (SE) between groups −3.59 [−5.02, −2.15], p < 0.001]. The least‐squares mean changes in the HAMA scores and NPI scores between baseline and week 8 were greater in the CCT and SSRIs group than in the control group (all P < 0.05). The most frequent adverse events (AEs) in both groups were dry mouth, somnolence, and constipation. There was no significant difference in the incidence of adverse events between the two groups.结论:ConclusionCCT combined with SSRIs was efficacious and well tolerated in LLD patients with cognitive impairment.