Automated Deep Learning Pipeline for Callosal Angle Quantification.

Background And Purpose: Normal pressure hydrocephalus (NPH) is a potentially treatable neurodegenerative disorder that remains underdiagnosed due to its clinical overlap with other conditions and the labor-intensive nature of manual imaging analyses. Imaging biomarkers, such as the callosal angle (CA), Evans Index (EI), and Disproportionately Enlarged Subarachnoid Space Hydrocephalus (DESH), play a crucial role in NPH diagnosis but are often limited by subjective interpretations. To address these challenges, we developed a fully automated and robust deep learning framework for measuring the CA directly from raw T1 MPRAGE and non-MPRAGE MRI scans.

The dependence of CO cerebrovascular reactivity (CVR) on caffeine.

Cerebrovascular reactivity (CVR) represents an important marker of brain vascular health, particularly in the context of small and large vessel diseases. However, an undesired feature of this measure is that there exist large variations in CVR values across individuals, which is mainly attributed to physiological factors. Here, we test the hypothesis that caffeine, a widely consumed neurostimulant, has a significant effect on CVR measured with MRI.

Neurofilament Light Chain Levels in a Large Idiopathic Peripheral Neuropathy Cohort.

Background: Neurofilament light chain (Nf-L) has been identified as a biomarker of neurodegeneration in many neuromuscular conditions, including several subtypes of polyneuropathies. The purpose of this research was to investigate whether Nf-L is also a promising biomarker for idiopathic peripheral neuropathy (IPN), the second most common subtype of axonal polyneuropathy.

Methods: Nf-L levels were quantified using an ultrasensitive digital immunoassay SiMoA in plasma samples from 294 subjects.

Change points for dynamic biomarkers in the Alzheimer's disease pathological cascade: A 30-year cohort study.

Introduction: This study aimed to delineate trajectories of biomarkers-amyloid beta (Aβ), phosphorylated tau, neurodegeneration, and inflammation-and to identify change points along these trajectories.

Methods: Longitudinal data were collected over 30 years from 349 cognitively unimpaired individuals enrolled in the Biomarkers for Older Controls at Risk for Dementia study. Piecewise regression models were used to identify change points in cerebrospinal fluid biomarkers, brain magnetic resonance imaging volumes, and a composite measure of global cognition.

Plasma GDF15 affects long-term dementia risk and alters neuro-immune signaling.

Growth/differentiation factor-15 (GDF15) is a secreted peptide hormone and cytokine that is strongly associated with dementia risk. However, the extent to which plasma GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15-to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular dementia compared to Alzheimer's disease (AD).

Rapid measurement of major cortical and subcortical venous oxygenation using EPI-based T-relaxation-under-phase-contrast.

Purpose: Cerebral venous oxygenation (Y) is an important physiological parameter indicating the brain's homeostasis of oxygen demand and supply. This study aims to develop a quantitative MRI technique to provide regional Y assessment in approximately 1 min.

Methods: The new pulse sequence is referred to as EPI-based T-relaxation-under-phase-contrast (EPI-TRUPC).

The Hydrocephalus Association Patient-Powered Interactive Engagement Registry (HAPPIER): Design and Initial Baseline Report.

Purpose: Hydrocephalus is a neurological condition characterized by an accumulation of cerebrospinal fluid (CSF) with no cure and limited treatments. There is a significant gap in hydrocephalus research where patients lack opportunities to voice their perspectives on their condition. The Hydrocephalus Association Patient-Powered Interactive Engagement Registry (HAPPIER) database captures the lived experiences of those affected by hydrocephalus and provides a platform for researchers to access these data or distribute their own surveys, ultimately aiming to improve patient-centered care and outcomes.

Proper Name Recall as an Early Indicator of Preclinical Alzheimer's Disease Pathology.

Background: Early detection of Alzheimer's disease (AD) is crucial; however, standard neuropsychological tests often lack sensitivity. Process scores, such as proper name (PN) recall from Logical Memory (LM), may improve the detection of AD-related biomarker positivity. We examined whether baseline PN recall predicted future cerebrospinal fluid (CSF) amyloid (Aβ42/Aβ40) and tau (pTau ) status, and whether biomarker status predicted PN recall trajectories.

Longitudinal progression of blood biomarkers reveals a key role of reactive astrocytosis in preclinical Alzheimer's disease.

Background: Defining the progression of blood biomarkers in Alzheimer's disease (AD) is essential for targeting treatments in patients most likely to benefit from early intervention. We delineated the temporal ordering of blood biomarkers a decade prior to the onset of AD, explored associations with AD brain pathology, and examined the relationship between reactive astrocytosis in the brain and plasma in a transgenic mouse model.

Methods: We analyzed plasma blood biomarkers using the Quanterix HD-X instrument in case-control and postmortem cohorts from the Baltimore Longitudinal Study on Aging (BLSA).

Clinical Features and Diagnosis of Normal Pressure Hydrocephalus.

Objective: This article serves as a practical guide for the assessment of patients with suspected idiopathic normal pressure hydrocephalus (NPH).

Latest Developments: Significant advancements in neuroimaging, biomarker identification, and neurosurgical techniques have considerably improved the diagnostic accuracy and outcomes of treatment for idiopathic NPH. The full triad of gait disturbance, cognitive impairment, and urinary incontinence is not present in all patients and is not a prerequisite to pursuing treatment.

Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration.

Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer's disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between viral antibody titers and neurocognitive outcomes may be attributed to altered expression in a subset of mechanistically relevant proteins in plasma.

NFκB1: a common biomarker linking Alzheimer's and Parkinson's disease pathology.

Introduction: Alzheimer's disease (AD) and Parkinson's disease (PD) are neurodegenerative disorders characterized by mitochondrial dysfunction and chronic inflammation. The transcription factor NF-κB1 is implicated in both neuroprotective and pro-inflammatory processes, with its activity varying between neurons and glial cells. While previous studies have explored the genetic and epigenetic contributions to these diseases, the infection hypothesis has re-emerged as a potential framework for identifying novel biomarkers and therapeutic targets.

Olfaction and Plasma Biomarkers of Alzheimer Disease and Neurodegeneration in the Atherosclerosis Risk in Communities Study.

Background And Objectives: Investigation of olfactory impairment, an early manifestation of Alzheimer disease (AD), in relation to plasma biomarkers of AD and neurodegeneration could provide insights into the disease's pathophysiology. Because few such studies based on large, diverse, community-based populations exist, we investigated associations of odor identification ability with plasma biomarkers of AD and other neurodegenerative pathologies in community-dwelling Black and White older adults.

Methods: This cross-sectional investigation included participants from the Atherosclerosis Risk in Communities study who attended visit 5 (2011-2013) and who completed olfactory testing and brain MRI examinations and had plasma biomarkers measured (namely, amyloid-beta [Aβ]/Aβ ratio, phosphorylated-tau at threonine-181 [p-tau], p-tau/Aβ ratio, glial fibrillary acidic protein [GFAP], and neurofilament light chain [NfL]).

Deformation Response of the Human Lamina Cribrosa to Intracranial Pressure Lowering.

The optic nerve head (ONH) is subjected to both intra-ocular pressure (IOP) and intracranial pressure (ICP). The translaminar pressure difference (TLPD) is defined as the difference between IOP and ICP. A change in TLPD, whether from changes in IOP or ICP, could subject the lamina cribrosa (LC) to altered deformation, potentially damaging the axons, activating the mechanosensitive glial cells, and promoting remodeling of the connective tissue structures in the ONH.

Alzheimer's disease cerebrospinal fluid biomarker levels and APOE genetic status are associated with hippocampal-cerebellar functional connectivity.

Recent research suggests that hippocampal-cerebellar (Hp-CB) functional connectivity may be altered early in the course of Alzheimer's disease (AD), given the early accumulation of AD pathology in the hippocampi and emerging evidence of cerebellar changes in early AD. This study analyzed the role of AD genetic risk (via APOE ε4 carrier status) and cerebrospinal fluid (CSF) biomarkers of AD pathology (ratio of phosphorylated tau (p-tau) to amyloid beta (Aβ/Aβ)) on the relationship between age and functional Hp-CB resting state fMRI connectivity in 161 cognitively unimpaired older adults (M age =67.3; SD =9.

Physical activity modifies associations between cerebrospinal fluid tau measures and executive function.

Background: Alzheimer's disease (AD) is characterized by the abnormal accumulation of amyloid-beta (Aβ) and tau that can be quantified in vivo through cerebrospinal fluid (CSF) sampling. Physical activity has emerged as a possible modifier of AD risk; however, its impact on CSF biomarkers and cognitive function is not yet fully understood. We examined whether higher levels of physical activity modifies associations between AD CSF biomarkers and cognitive function.

Transient vocal cord paralysis after transverse Sinus stenting.

We report the case of a young woman diagnosed with idiopathic intracranial hypertension, who did not tolerate long-term pharmacologic treatment and was deemed a candidate for transverse sinus stenting (TSS). Following the procedure, she developed transient palsies of the 10th and 11th cranial nerves. She underwent orotracheal examination and brain magnetic resonance imaging, which ruled out a local structural etiology or brainstem pathology.

Plasma biomarker trajectories: Impact of AD genetic risk and clinical progression.

Introduction: We examined long-term plasma biomarker trajectories among participants who were cognitively unimpaired and primarily middle aged at baseline and whether trajectories differed by Alzheimer's disease (AD) genetic risk and among those who developed cognitive impairment.

Methods: Plasma amyloid beta (Aβ)/Aβ, phosphorylated tau (p-tau), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), soluble triggering receptor expressed on myeloid cells, and chitinase 3-like protein 1 were measured longitudinally in 177 BIOCARD participants ( baseline age = 57.7 years; follow-up = 15.

Diagnostic and Prognostic Biomarkers of Idiopathic Normal Pressure Hydrocephalus in Cerebrospinal Fluid and Blood.

Idiopathic normal pressure hydrocephalus (iNPH) is a treatable condition marked by gait disturbances, cognitive decline, and urinary incontinence. Biomarkers play a crucial role in distinguishing iNPH from Alzheimer's disease (AD) and predicting shunt surgery outcomes. Aβ1-42, Aβ1-40, t-tau, and p-tau181 differentiate iNPH from AD, with iNPH showing a higher Aβ1-42/Aβ1-40 ratio and normal tau levels.

Longitudinal patterns of brain aging and neurodegeneration among older adults with dual decline in memory and gait.

Introduction: Dual cognitive and mobility decline is more strongly associated with dementia risk than cognitive decline only. It remains unknown whether this syndrome is associated with brain atrophy patterns, white matter (WM) damage, or pathology.

Methods: In the Baltimore Longitudinal Study of Aging participants with and without dual decline, we used linear mixed-effects models to compare up to 13-year longitudinal changes in MRI-derived atrophy patterns, WM hyperintensities (n = 339), microstructure (n = 307), plasma glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), amyloid beta 42/40 (Aβ) ratio (n = 349), and phosphorylated tau 181 (pTau181) (n = 258).

The Dementia SomaSignal Test (dSST): A plasma proteomic predictor of 20-year dementia risk.

Introduction: There is an unmet need for tools to quantify dementia risk during its multi-decade preclinical/prodromal phase, given that current biomarkers predict risk over shorter follow-up periods and are specific to Alzheimer's disease.

Methods: Using high-throughput proteomic assays and machine learning techniques in the Atherosclerosis Risk in Communities study (n = 11,277), we developed the Dementia SomaSignal Test (dSST).

Results: In addition to outperforming existing plasma biomarkers, the dSST predicted mid-life dementia risk over a 20-year follow-up across two independent cohorts with different ethnic backgrounds (areas under the curve [AUCs]: dSST 0.

Association of Plasma Biomarkers of Alzheimer Disease and Neurodegeneration With Longitudinal Intra-Network Functional Brain Connectivity.

Background And Objectives: Alzheimer disease (AD) is defined by cortical β-amyloid (Aβ), tau, and neurodegeneration, which contribute to cognitive decline, in part, by altering large-scale functional brain networks. While cortical Aβ and tau have been associated with changes in functional brain connectivity, it is unknown whether plasma biomarkers relate to such changes. In a healthy community sample of cognitively unimpaired adults free from major CNS disease from the Baltimore Longitudinal Study of Aging, we examined whether plasma biomarkers of AD pathology (Aβ, phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal changes in functional connectivity and whether changes in functional connectivity were related to longitudinal cognition.

Loneliness and Biomarkers of Alzheimer's Disease, Axonal Damage, and Astrogliosis: A Coordinated Analysis of Two Longitudinal Cohorts.

Objectives: Loneliness is associated with an elevated risk of dementia. There is mixed evidence from imaging studies on whether loneliness is associated with neuropathology in dementia-free adults. This study tests whether loneliness is associated with plasma neurobiomarkers of amyloid (Aβ42/Aβ40), phosphorylated tau 181 (pTau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and imaging measures of amyloid and tau.

Blood-Based Biomarkers and Risk of Onset of Mild Cognitive Impairment Over the Short and Long Term.

Background And Objectives: Blood-based biomarkers of amyloid and tau have been shown to predict Alzheimer disease (AD) dementia. Much less is known about their ability to predict risk of mild cognitive impairment (MCI), an earlier disease stage. This study examined whether levels of blood biomarkers of amyloid (Aβ/Aβ ratio), tau (p-tau), neurodegeneration (NfL), and glial activation and neuroinflammation (glial fibrillary acidic protein [GFAP], YKL40, soluble triggering receptor expressed on myeloid cells 2 [sTREM2]) collected when participants were cognitively normal are associated with the time to onset of MCI.

White matter free water mediates the associations between placental growth factor, white matter hyperintensities, and cognitive status.

Introduction: Placental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.

Methods: MarkVCID consortium participants ≥55 years old with plasma PlGF and brain MRI were included.