Oncogenic IDH1 drives robust loss of histone acetylation and increases chromatin heterogeneity.

Malignant gliomas are heterogeneous tumors, mostly incurable, arising in the central nervous system (CNS) driven by genetic, epigenetic, and metabolic aberrations. Mutations in isocitrate dehydrogenase (IDH1/2) enzymes are predominantly found in low-grade gliomas and secondary high-grade gliomas, with IDH1 mutations being more prevalent. Mutant-IDH1/2 confers a gain-of-function activity that favors the conversion of a-ketoglutarate (α-KG) to the oncometabolite 2-hydroxyglutarate (2-HG), resulting in an aberrant hypermethylation phenotype.

Clinical outcomes and cost-utility analysis of GKRS plus TKIs versus TKIs in patients with EGFR-mutant lung adenocarcinoma and brain metastases: a Markov decision model.

Objective: This study focuses on epidermal growth factor receptor-mutated lung adenocarcinoma, known for frequent brain metastasis. It aimed to compare the clinical outcomes and cost-effectiveness of combining Gamma Knife radiosurgery (GKRS) with tyrosine kinase inhibitors (TKIs) (GKRS+TKI group) versus TKIs alone (TKI group) for the treatment of patients with newly diagnosed brain metastasis in this condition.

Methods: Study characteristics of the two groups were matched using inverse probability of treatment weighting (IPTW).

Patient-reported outcome trajectories the first 24 months after surgery for cervical spondylotic myelopathy: a Quality Outcomes Database study.

Objective: Cervical spondylotic myelopathy (CSM) shows varying levels of improvement after surgical treatment. While some patients improve soon after surgery, others may take months to years to show any signs of improvement. The goal of this study was to evaluate postoperative improvement, patient-reported outcomes, and patient satisfaction up to 2 years after surgical treatment for CSM, which will help optimize the current treatment strategies and effectively manage patient expectations.

The impact of lower thoracic versus upper lumbar upper instrumented vertebra in minimally invasive correction of adult spinal deformity.

Objective: The goal of this study was to compare the impact of using a lower thoracic (LT) versus upper lumbar (UL) level as the upper instrumented vertebra (UIV) on clinical and radiographic outcomes following minimally invasive surgery for adult spinal deformity.

Methods: A multicenter retrospective study design was used. Inclusion criteria were age ≥ 18 years, and one of the following: coronal Cobb angle > 20°, sagittal vertical axis > 50 mm, pelvic tilt > 20°, pelvic incidence-lumbar lordosis mismatch > 10°.

A Case of Asymmetric Seizure Termination During an Acute Course of Right Unilateral Electroconvulsive Therapy.

Electroencephalogram (EEG) monitoring during electroconvulsive therapy (ECT) is commonly done using a 2-channel EEG in order to capture activity from both brain hemispheres, though many institutions may instead opt to utilize a 1-channel EEG, often for reasons of convenience. We present a novel case of asymmetric termination of EEG seizure activity during an acute course of right unilateral ECT, prompting a full neurological workup to investigate potential underlying structural or physiological causative factors. This case assists in informing the necessity of bilateral hemispheric EEG monitoring as well as highlights the importance of searching for undiagnosed or latent neurological dysfunction in certain clinical situations arising during ECT.

Mapping patterns of thought onto brain activity during movie-watching.

Movie-watching is a central aspect of our lives and an important paradigm for understanding the brain mechanisms behind cognition as it occurs in daily life. Contemporary views of ongoing thought argue that the ability to make sense of events in the 'here and now' depend on the neural processing of incoming sensory information by auditory and visual cortex, which are kept in check by systems in association cortex. However, we currently lack an understanding of how patterns of ongoing thoughts map onto the different brain systems when we watch a film, partly because methods of sampling experience disrupt the dynamics of brain activity and the experience of movie-watching.

Predicting cognitive decline from neuropsychiatric symptoms and Alzheimer's disease biomarkers: A machine learning approach to a population-based data.

Background: The aim of this study was to examine the potential added value of including neuropsychiatric symptoms (NPS) in machine learning (ML) models, along with demographic features and Alzheimer's disease (AD) biomarkers, to predict decline or non-decline in global and domain-specific cognitive scores among community-dwelling older adults.

Objective: To evaluate the impact of adding NPS to AD biomarkers on ML model accuracy in predicting cognitive decline among older adults.

Methods: The study was conducted in the setting of the Mayo Clinic Study of Aging, including participants aged ≥ 50 years with information on demographics (i.

Pterional vs. mini-pterional craniotomy for intracranial aneurysms: a systematic review and meta-analysis.

The mini-pterional craniotomy (mPT) was designed to be a minimally invasive alternative to the standard pterional (PT) approach. However, it remains unclear which technique produces better results. Thus, we aimed to perform a meta-analysis comparing functional, surgical, and aesthetic outcomes between mPT and PT in intracranial aneurysms.

The added value of anosmic subtype on motor subtype in Parkinson's disease: a pilot study.

This study investigates whether incorporating olfactory dysfunction into motor subtypes of Parkinson's disease (PD) improves associations with clinical outcomes. PD is commonly divided into motor subtypes, such as postural instability and gait disturbance (PIGD) and tremor-dominant PD (TDPD), but non-motor symptoms like olfactory dysfunction remain underexplored. We assessed 157 participants with PD using the University of Pennsylvania Smell Identification Test (UPSIT), Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (M-UPDRS), Montreal Cognitive Assessment (MoCA), 39-item Parkinson's Disease Questionnaire Summary Index (PDQ-39 SI), and 99mTc-TRODAT-1 imaging.

Evaluation of objective methods for analyzing ipsilateral motor evoked potentials in stroke survivors with chronic upper extremity motor impairment.

Ipsilateral motor evoked potentials (iMEPs) are believed to represent cortically evoked excitability of uncrossed brainstem-mediated pathways. In the event of extensive injury to (crossed) corticospinal pathways, which can occur following a stroke, uncrossed ipsilateral pathways may serve as an alternate resource to support the recovery of the paretic limb. However, iMEPs, even in neurally intact people, can be small, infrequent, and noisy, so discerning them in stroke survivors is very challenging.

A Hitchhiker's Guide Toward CSF Biomarkers for Neuro-Oncology.

Cerebrospinal fluid (CSF) has emerged as a valuable liquid biopsy source for glioma biomarker discovery and validation. CSF produced within the ventricles circulates through the subarachnoid space, where the composition of glioma-derived analytes is influenced by the proximity and anatomical location of sampling relative to tumor, in addition to underlying tumor biology. The substantial gradients observed between lumbar and intracranial CSF compartments for tumor-derived analytes underscore the importance of sampling site selection.

Real‐world utilization of diagnostic tests for mild cognitive impairment, Alzheimer’s disease, and other dementias in Medicare fee‐for‐service beneficiaries.

Background: Use of neuroimaging [e.g. magnetic resonance imaging (MRI), positron emission tomography (PET), or computed tomography (CT) scan], cerebrospinal fluid (CSF), and blood biomarker tests can contribute to a more accurate and earlier diagnosis of Alzheimer’s disease (AD).

Role and Prognostic Implications of Venous Outflow Assessment in Acute Ischemic Stroke.

Introduction: The venous outflow profile (VOP) is a crucial yet often overlooked aspect affecting stroke outcomes. It plays a major role in the physiopathology of acute cerebral ischemia, as it accounts for both the upstream arterial collaterals and cerebral microperfusion. This enables it to circumvent the limitations of various arterial collateral evaluation systems, which often fail to consider impaired autoregulation and its impact on cerebral blood flow at the microcirculatory levels.

Distinguishing Early Mild Cognitive Impairment from Late Mild Cognitive Impairment through Free‐Water Diffusion Tensor Imaging: A Comparative Analysis.

Background: Mild Cognitive Impairment (MCI) represents an intermediate stage between normal age‐related cognitive decline and more severe degenerative conditions such as Alzheimer's disease. Understanding the differences between Early‐MCI (EMCI) and Late‐MCI (LMCI) is crucial to facilitate early diagnosis and future clinical interventions. This study employed free‐water diffusion tensor imaging (FW‐DTI) to explore the differences in white matter alterations between EMCI and LMCI.

Clinical performance of plasma P‐tau217 for the identification of primary Alzheimer’s disease pathology or co‐pathology in sporadic frontotemporal dementia.

Background: As new anti‐amyloid immunotherapies emerge for Alzheimer’s disease (AD), it is clear that early diagnosis of AD pathology is crucial for treatment success. This can be challenging in atypical presentations of AD and, together with our reliance on CSF or PET scans, can, at times, lead to delayed diagnosis. Here, we further explore the possible role of plasma tau phosphorylated at threonine 217 (P‐tau217) for the detection of primary AD or AD co‐pathology when frontotemporal dementia spectrum disorders are the main clinical presentation.

Brain Functional Flexibility and its Relationship to the Preclinical Stage of Alzheimer’s Disease.

Background: Characterizing pathological and functional features of the preclinical stage of Alzheimer’s Disease (AD) is essential as Amyloid beta (Aβ) and tau, the pathological hallmarks of AD, start to accumulate years prior to the onset of clinical symptoms. Whether Aβ and/or tau are related to the brain’s ability to functionally reconfigure in time (functional flexibility) remains unclear despite its important role in behavior and cognition.

Method: We included 233 cognitively unimpaired individuals with family history of AD from the PREVENT‐AD cohort who underwent both Positron Emission Tomography (PET) and functional Magnetic Resonance Imaging (fMRI).

A Clinical Decision‐Making Tool to Identify Red Flags for Remote Cognitive Assessment: An Expert Consensus Study from the Canadian Consortium on Neurodegeneration in Aging.

Background: Remote diagnostic assessment of cognitively impaired individuals offers numerous potential benefits including increased access to care. However, remote cognitive and behavioral assessment also has limitations, and may not be appropriate for certain patients. Currently, evidence‐based guidance on virtual assessment readiness is lacking.

Inflammation links in Alzheimer’s Disease: connecting fluid proteomics and TSPO PET.

Background: Emerging evidence underscores the importance of neuroinflammation in the progression of Alzheimer’s disease (AD) pathophysiology. Recent studies indicate the involvement of the inflammatory mechanisms both in amyloid‐ β (Aβ) and tau deposition in the brain. Nevertheless, due to the complexity of the immune responses and the intricate interplay between the peripheral and the central nervous systems, identifying biomarkers that reflect the brain´s inflammatory state in AD has been a challenge.

Longitudinal change of cerebral amyloid and tau and its association with plasma biomarkers in preclinical Alzheimer's disease.

Background: For medical purposes, amyloid‐beta (Aβ) and tau biomarkers are typically dichotomized into positive (+) and negative (‐) status to define individuals with Alzheimer’s disease (AD) pathology. Nevertheless, such AD proteinopathies start accumulating years before reaching clinically‐defined abnormality thresholds. We examined longitudinal change in PET Aβ and tau in cognitively unimpaired (CU) individuals; then we explored their baseline plasma levels and demographic characteristics.

Autoradiographic comparison of [11C]PiB and [18F]NAV4694 in post‐mortem human brain tissue.

Background: To evaluate the in vitro binding properties of [C]PiB and [F]NAV4694 head‐to‐head in post‐mortem human brain tissue.

Method: Autoradiography was used to assess uptake of [C]PiB and [F]NAV4694 in control (CN) and Alzheimer’s disease (AD) autopsy‐confirmed brain tissues. The study focuses on the analysis of the prefrontal cortex, inferior parietal cortex, posterior cingulate cortex and hippocampus sections in 11 CN and 11 AD cases.

Functional connectivity changes through Alzheimer’s disease continuum: disease onset, progression, and response to therapy.

Background: Hemodynamic signals are the basis of functional brain imaging techniques, such as fMRI and NIRS, and are often used to infer changes in resting‐state functional connectivity (RSFC) in Alzheimer’s disease (AD) and other dementias. Increasing evidence suggests that disruption of neuronal circuits has been associated with the AD continuum and may precede changes in Ab and tau biomarkers, neurodegeneration, and cognitive impairment. To better understand the changes in brain RSFC through the AD spectrum, we use hemodynamic signals to detect disease onset, progression, and response to therapy in a mouse model of AD.

Inflammation in the white matter relates to core Alzheimer's disease pathophysiological processes.

Background: In‐vivo PET imaging studies have demonstrated neuroinflammation (microglia reactivity) in the neocortex of Alzheimer’s disease (AD) patients. However, the extent and implication of microglia reactivity in white matter regions remains unclear. Here, we explored microglia reactivity in white matter using PET imaging of the translocator protein (TSPO) in relation to core AD biomarkers (amyloid, tau, and astrogliosis), microstructural damage, and cognitive decline.

Brain Age Gap Correlates with 18F‐NAV‐4694 and 18F‐MK‐6240 Standardized Uptake Value Ratio.

Background: It is feasible to train a model on a healthy cohort to estimate the chronological age from a T1‐weighted (T1w) MRI. This model can be used to estimate the apparent brain age of subjects with Alzheimer's Disease (AD). The difference between the true chronological age and the apparent brain age, called Brain Age Gap (BAG), is a potential feature to estimate the level of pathology and neurodegeneration of an individual patient with AD.