Pure LATE-NC: Frequency, clinical impact, and the importance of considering APOE genotype when assessing this and other subtypes of non-Alzheimer's pathologies.

Pure limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (pure LATE-NC) is a term used to describe brains with LATE-NC but lacking intermediate or severe levels of Alzheimer's disease neuropathologic changes (ADNC). Focusing on pure LATE-NC, we analyzed data from the National Alzheimer's Coordinating Center (NACC) Neuropathology Data Set, comprising clinical and pathological information aggregated from 32 NIH-funded Alzheimer's Disease Research Centers (ADRCs). After excluding subjects dying with unusual conditions, n = 1,926 autopsied subjects were included in the analyses.

Cerebral perfusion and amyloidosis in the oldest-old.

Introduction: In a nested case-control study, we examined how cerebral perfusion relates to cognitive status and amyloid in the oldest-old (i.e., 90 years of age and older).

The Temporal Relation of Physical Function with Cognition and the Influence of Brain Health in the Oldest-Old.

Introduction: Physical function and cognition seem to be interrelated, especially in the oldest-old. However, the temporal order in which they are related and the role of brain health remain uncertain.

Methods: We included 338 participants (mean age 93.

Evaluating the updated LATE-NC staging criteria using data from NACC.

Introduction: Limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathologic change (LATE-NC) staging criteria were updated in 2023. We evaluated this updated staging using National Alzheimer's Coordinating Center data.

Methods: We examined associations of LATE-NC stages with cognition and other neuropathologic changes (NCs), and with cognition while accounting for other NCs, using multilevel regression models.

Associations of Amyloid Burden, White Matter Hyperintensities, and Hippocampal Volume With Cognitive Trajectories in the 90+ Study.

Background And Objectives: Amyloid pathology, vascular disease pathology, and pathologies affecting the medial temporal lobe are associated with cognitive trajectories in older adults. However, only limited evidence exists on how these pathologies influence cognition in the oldest old. We evaluated whether amyloid burden, white matter hyperintensity (WMH) volume, and hippocampal volume (HV) are associated with cognitive level and decline in the oldest old.

Comprehensive assessment of TDP-43 neuropathology data in the National Alzheimer's Coordinating Center database.

TDP-43 proteinopathy is a salient neuropathologic feature in a subset of frontotemporal lobar degeneration (FTLD-TDP), in amyotrophic lateral sclerosis (ALS-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and is associated with hippocampal sclerosis of aging (HS-A). We examined TDP-43-related pathology data in the National Alzheimer's Coordinating Center (NACC) in two parts: (I) availability of assessments, and (II) associations with clinical diagnoses and other neuropathologies in those with all TDP-43 measures available. Part I: Of 4326 participants with neuropathology data collected using forms that included TDP-43 assessments, data availability was highest for HS-A (97%) and ALS (94%), followed by FTLD-TDP (83%).

Longitudinal hippocampal atrophy in hippocampal sclerosis of aging.

Hippocampal sclerosis of aging (HS-A) is a common degenerative neuropathology in older individuals and is associated with dementia. HS-A is characterized by disproportionate hippocampal atrophy at autopsy but cannot be diagnosed during life. Therefore, little is known about the onset and progression of hippocampal atrophy in individuals with HS-A.

Characterization of hippocampal sclerosis of aging and its association with other neuropathologic changes and cognitive deficits in the oldest-old.

Hippocampal sclerosis of aging (HS-A) is a common age-related neuropathological lesion characterized by neuronal loss and astrogliosis in subiculum and CA1 subfield of hippocampus. HS-A is associated with cognitive decline that mimics Alzheimer's disease. Pathological diagnosis of HS-A is traditionally binary based on presence/absence of the lesion.

Dementia is associated with medial temporal atrophy even after accounting for neuropathologies.

Brain atrophy is associated with degenerative neuropathologies and the clinical status of dementia. Whether dementia is associated with atrophy independent of neuropathologies is not known. In this study, we examined the pattern of atrophy associated with dementia while accounting for the most common dementia-related neuropathologies.

Neuroimaging in the Oldest-Old: A Review of the Literature.

The oldest-old, those 85 years and older, are the fastest growing segment of the population and present with the highest prevalence of dementia. Given the importance of neuroimaging measures to understand aging and dementia, the objective of this study was to review neuroimaging studies performed in oldest-old participants. We used PubMed, Google Scholar, and Web of Science search engines to identify in vivo CT, MRI, and PET neuroimaging studies either performed in the oldest-old or that addressed the oldest-old as a distinct group in analyses.

Utility of MRI in the identification of hippocampal sclerosis of aging.

Introduction: Hippocampal sclerosis of aging (HS) is a common pathology often misdiagnosed as Alzheimer's disease. We tested the hypothesis that participants with HS would have a magnetic resonance imaging (MRI)-detectable hippocampal pattern of atrophy distinct from participants without HS, both with and without Alzheimer's disease neuropathology (ADNP).

Methods: Query of the National Alzheimer's Coordinating Center database identified 198 participants with MRI and autopsy.

Neck disability in patients with cervical spondylosis is associated with altered brain functional connectivity.

Cervical degenerative disease is a major cause of neck disability, but it has been understudied in patients with cervical spondylotic (CS), largely due to the fact that the neurological impairment associated with this condition tends to be the primary treatment focus. This observational study examined the cerebral functional alterations occurring in advanced cervical spondylosis and myelopathy using resting state functional MRI. Associations between functional connectivity (FC) and neck disability using the Neck Disability Index (NDI) were assessed.

White Matter Hyperintensities and Hippocampal Atrophy in Relation to Cognition: The 90+ Study.

Objectives: To study the interactive effect of white matter hyperintensities (WMH) and hippocampal atrophy on cognition in the oldest old.

Design: Ongoing longitudinal study.

Setting: In Southern California, brain magnetic resonance imaging (MRI) scans were conducted between May 2014 and December 2017.

Spinal Cord Perfusion MR Imaging Implicates Both Ischemia and Hypoxia in the Pathogenesis of Cervical Spondylosis.

Objectives: Although a number of studies have implicated ischemia and hypoxia in the pathogenesis of cervical spondylosis, quantification remains difficult and the role of ischemia and hypoxia on disease progression and disease severity in human cervical spondylosis remains largely unknown. Therefore, the objective of this study was to assess spinal cord perfusion and oxygenation in human cervical spondylosis and examine the relationship between perfusion, degree of spinal cord compression, and neurological status.

Methods: Twenty-two patients with cervical spondylosis with or without myelopathy received a dynamic susceptibility contrast perfusion MRI exam consisting of a novel spin-and-gradient echo echoplanar acquisition before, during, and following gadolinium-based contrast injection.

Changes in brain white matter structure are associated with urine proteins in urologic chronic pelvic pain syndrome (UCPPS): A MAPP Network study.

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network has yielded neuroimaging and urinary biomarker findings that highlight unique alterations in brain structure and in urinary proteins related to tissue remodeling and vascular structure in patients with Urological Chronic Pelvic Pain Syndrome (UCPPS). We hypothesized that localized changes in diffusion tensor imaging (DTI) measurements might be associated with corresponding changes in urinary protein levels in UCPPS. To test this hypothesis, we created statistical parameter maps depicting the linear correlation between DTI measurements (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) and urinary protein quantification (MMP2, MMP9, NGAL, MMP9/NGAL complex, and VEGF) in 30 UCPPS patients from the MAPP Research Network, after accounting for clinical covariates.

Resting-State Functional Magnetic Resonance Imaging Connectivity of the Brain Is Associated with Altered Sensorimotor Function in Patients with Cervical Spondylosis.

Objective: To determine the relationship between functional connectivity (FC) using resting-state functional magnetic resonance imaging (MRI) and neurological impairment in patients with cervical spondylosis and healthy controls.

Methods: A total of 24 patients with cervical spondylosis with or without myelopathy and 17 neurologically intact, healthy volunteer subjects were prospectively enrolled in a cross-sectional study involving observational MRI and evaluation of neurological function using the modified Japanese Orthopedic Association (mJOA) score. Seed-to-seed connectivity and seed-to-voxel connectivity on functional MRI data were performed using a general linear model of connectivity with respect to age and mJOA score.

Mono-exponential, diffusion kurtosis and stretched exponential diffusion MR imaging response to chemoradiation in newly diagnosed glioblastoma.

Purpose: To quantify changes and prognostic value of diffusion MRI measurements obtained using mono-exponential, diffusion kurtosis imaging (DKI) and stretched exponential (SE) models prior and after chemoradiation in newly diagnosed glioblastoma (GBM).

Methods: Diffusion-weighted images (DWIs) were acquired in twenty-three patients following surgery, prior chemoradiation and within 7 days following completion of treatment, using b-values ranging from 0 to 5000s/mm. Mono-exponential diffusion (apparent diffusion coefficient: ADC), isotropic (non-directional) DKI model with apparent diffusivity (Dapp) and kurtosis (Kapp) estimates as well as SE model with distributed-diffusion coefficient (DDC) and mean intra-voxel heterogeneity (α) were computed for all patients prior and after chemoradiation.

Volumetric response quantified using T1 subtraction predicts long-term survival benefit from cabozantinib monotherapy in recurrent glioblastoma.

Background: To overcome challenges with traditional response assessment in anti-angiogenic agents, the current study uses T1 subtraction maps to quantify volumetric radiographic response in monotherapy with cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2), hepatocyte growth factor receptor (MET), and AXL, in an open-label, phase II trial in patients with recurrent glioblastoma (GBM) (NCT00704288).

Methods: A total of 108 patients with adequate imaging data and confirmed recurrent GBM were included in this retrospective study from a phase II multicenter trial of cabozantinib monotherapy (XL184-201) at either 100 mg (N = 87) or 140 mg (N = 21) per day. Contrast enhanced T1-weighted digital subtraction maps were used to define volume of contrast-enhancing tumor at baseline and subsequent follow-up time points.

Alterations in Cortical Thickness and Subcortical Volume are Associated With Neurological Symptoms and Neck Pain in Patients With Cervical Spondylosis.

Background: Advanced cervical spondylosis (CS) can cause structural damage to the spinal cord resulting in long-term neurological impairment including neck pain and motor weakness. We hypothesized long-term structural reorganization within the brain in patients with CS.

Objective: To explore the associations between cortical thickness, subcortical volumes, neurological symptoms, and pain severity in CS patients with or without myelopathy and healthy controls (HCs).

Reproducibility, temporal stability, and functional correlation of diffusion MR measurements within the spinal cord in patients with asymptomatic cervical stenosis or cervical myelopathy.

OBJECTIVE The purpose of this study was to quantify the reproducibility, temporal stability, and functional correlation of diffusion MR characteristics in the spinal cord in patients with cervical stenosis with or without myelopathy. The association between longitudinal diffusion tensor imaging (DTI) measurements and serial neurological function assessment was explored at both the group and individual level. METHODS Sixty-six nonoperatively treated patients with cervical stenosis were prospectively followed (3 months to > 5 years) using synchronous serial MRI and functional outcome assessment.

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

Unlabelled: Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]).

Diffusion MRI Phenotypes Predict Overall Survival Benefit from Anti-VEGF Monotherapy in Recurrent Glioblastoma: Converging Evidence from Phase II Trials.

Anti-VEGF therapies remain controversial in the treatment of recurrent glioblastoma (GBM). In the current study, we demonstrate that recurrent GBM patients with a specific diffusion MR imaging signature have an overall survival (OS) advantage when treated with cediranib, bevacizumab, cabozantinib, or aflibercept monotherapy at first or second recurrence. These findings were validated using a separate trial comparing bevacizumab with lomustine.

Baseline pretreatment contrast enhancing tumor volume including central necrosis is a prognostic factor in recurrent glioblastoma: evidence from single and multicenter trials.

Background: The prognostic significance of baseline contrast enhancing tumor prior to second- or third-line therapy in recurrent glioblastoma (GBM) for overall survival (OS) remains controversial, particularly in the context of repeated surgical resection and/or use of anti-angiogenic therapy. In the current study, we examined recurrent GBM patients from both single and multicenter clinical trials to test whether baseline enhancing tumor volume, including central necrosis, is a significant prognostic factor for OS in recurrent GBM.

Methods: Included were 497 patients with recurrent GBM from 4 data sources: 2 single-center sites (University of Toronto, University of California Los Angeles) and 2 phase II multicenter trials (AVF3708G, Bevacizumab ± Irinotecan, NCT00345163; XL184-201, Cabozantinib, NCT00704288).

Multisite, multimodal neuroimaging of chronic urological pelvic pain: Methodology of the MAPP Research Network.

The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network is an ongoing multi-center collaborative research group established to conduct integrated studies in participants with urologic chronic pelvic pain syndrome (UCPPS). The goal of these investigations is to provide new insights into the etiology, natural history, clinical, demographic and behavioral characteristics, search for new and evaluate candidate biomarkers, systematically test for contributions of infectious agents to symptoms, and conduct animal studies to understand underlying mechanisms for UCPPS. Study participants were enrolled in a one-year observational study and evaluated through a multisite, collaborative neuroimaging study to evaluate the association between UCPPS and brain structure and function.