Network-based amyloid-beta pathology predicts subsequent cognitive decline in cognitively normal older adults.

The deposition of amyloid-beta protein in the human brain is a hallmark of Alzheimer's disease and is related to cognitive decline. However, the relationship between early amyloid-beta deposition and future cognitive impairment remains poorly understood, particularly concerning its spatial distribution and network-level effects. Here, we employed a cross-validated machine learning approach and investigated whether integrating subject-specific brain connectome information with amyloid-beta burden measures improves predictive validity for subsequent cognitive decline.

Diagnostic accuracy of phosphorylated tau217 in detecting Alzheimer's disease pathology among cognitively impaired and unimpaired: A systematic review and meta-analysis.

Our review summarizes the diagnostic accuracy of plasma and cerebrospinal fluid (CSF) phosphorylated tau 217 (p-tau217) in detecting amyloid and tau pathology on positron emission tomography (PET). We systematically reviewed studies that reported the diagnostic accuracy of plasma and CSF p-tau217, searching MEDLINE/PubMed, Scopus, and Web of Science through August 2024. The accuracy of p-tau217 in predicting amyloid and tau pathology on PET was evaluated in 30 studies.

Negative BOLD Responses Surpass Positive Responses in Task Specificity, Reflecting Neural Reconfigurations Better Than Functional Connectivity.

Objective: To investigate whether the Negative BOLD Response (NBR) is more task-specific than the Positive BOLD Response (PBR) during cognitive tasks and to determine whether task-evoked activity reflects brain reconfigurations during different tasks better than functional connectivity.

Methods: Functional Magnetic Resonance Imaging (fMRI) data were collected from 214 participants under 50 years old (152 in Dataset 1 and 62 in Dataset 2) performing twelve cognitive tasks spanning vocabulary, speed of processing, fluid reasoning, and memory domains. Data analysis included subject-level and group-level analyses, focusing on comparing the spatial patterns and task specificity of NBR and PBR through similarity measures using Dice coefficients.

Relationship Between Alzheimer Disease Imaging Biomarkers and Performance on the NIH Toolbox Cognition Battery in Late-middle Age Hispanics.

Purpose: The National Institute of Health Toolbox Cognition Battery (NIHTB-CB) is increasingly used in Alzheimer disease (AD) research. We examined the relation of AD biomarkers with performance in the NIHTB-CB in late middle age.

Methods: This is a cross-sectional analysis of 334 Hispanic participants aged 64.

Increased between-network connectivity: A risk factor for tau elevation and disease progression.

One of the pathologic hallmarks of Alzheimer's disease (AD) is neurofibrillary tau tangles. Despite our knowledge that tau typically initiates in the medial temporal lobe (MTL), the mechanisms driving tau to spread beyond MTL remain unclear. Emerging evidence reveals distinct patterns of functional connectivity change during aging and preclinical AD: while connectivity within-network decreases, connectivity between-network increases.

Remote Associations Between Tau and Cortical Amyloid-β Are Stage-Dependent.

Background: Histopathologic studies of Alzheimer's disease (AD) suggest that extracellular amyloid-β (Aβ) plaques promote the spread of neurofibrillary tau tangles. However, these two proteinopathies initiate in spatially distinct brain regions, so how they interact during AD progression is unclear.

Objective: In this study, we utilized Aβ and tau positron emission tomography (PET) scans from 572 older subjects (476 healthy controls (HC), 14 with mild cognitive impairment (MCI), 82 with mild AD), at varying stages of the disease, to investigate to what degree tau is associated with cortical Aβ deposition.

Pulsatility analysis of the circle of Willis.

Purpose: To evaluate the phenomenological significance of cerebral blood pulsatility imaging in aging research.

Methods: N = 38 subjects from 20 to 72 years of age (24 females) were imaged with ultrafast MRI with a sampling rate of 100 ms and simultaneous acquisition of pulse oximetry data. Of these, 28 subjects had acceptable MRI and pulse data, with 16 subjects between 20 and 28 years of age, and 12 subjects between 61 and 72 years of age.

In vivo tau is associated with change in memory and processing speed, but not reasoning, in cognitively unimpaired older adults.

The relationship between tau deposition and cognitive decline in cognitively healthy older adults is still unclear. The tau PET tracer F-MK-6240 has shown favorable imaging characteristics to identify early tau deposition in aging. We evaluated the relationship between in vivo tau levels (F-MK-6240) and retrospective cognitive change over 5 years in episodic memory, processing speed, and reasoning.

Distinct and joint effects of low and high levels of Aβ and tau deposition on cortical thickness.

Alzheimer's disease (AD) is defined by the presence of Amyloid-β (Aβ),tau, and neurodegeneration (ATN framework) in the human cerebral cortex. Yet, prior studies have suggested that Aβ deposition can be associated with both cortical thinning and thickening. These contradictory results are attributed to small sample sizes, the presence versus absence of tau, and limited detectability in the earliest phase of protein deposition, which may begin in young adulthood and cannot be captured in studies enrolling only older subjects.

Disruption of early visual processing in amyloid-positive healthy individuals and mild cognitive impairment.

Background: Amyloid deposition is a primary predictor of Alzheimer's disease (AD) and related neurodegenerative disorders. Retinal changes involving the structure and function of the ganglion cell layer are increasingly documented in both established and prodromal AD. Visual event-related potentials (vERP) are sensitive to dysfunction in the magno- and parvocellular visual systems, which originate within the retinal ganglion cell layer.

Positron Emission Tomography reveals age-associated hypothalamic microglial activation in women.

In rodents, hypothalamic inflammation plays a critical role in aging and age-related diseases. Hypothalamic inflammation has not previously been assessed in vivo in humans. We used Positron Emission Tomography (PET) with a radiotracer sensitive to the translocator protein (TSPO) expressed by activated microglia, to assess correlations between age and regional brain TSPO in a group of healthy subjects (n = 43, 19 female, aged 23-78), focusing on hypothalamus.

Evidence suggesting common mechanisms underlie contralateral and ipsilateral negative BOLD responses in the human visual cortex.

The task-evoked positive BOLD response (PBR) to a unilateral visual hemi-field stimulation is often accompanied by robust and sustained contralateral as well as ipsilateral negative BOLD responses (NBRs) in the visual cortex. The signal characteristics and the neural and/or vascular mechanisms that underlie these two types of NBRs are not completely understood. In this paper, we investigated the properties of these two types of NBRs.

Plasma Amyloid and in vivo Brain Amyloid in Late Middle-Aged Hispanics.

Background: Determining amyloid positivity is possible with cerebrospinal fluid and brain imaging of amyloid, but these methods are invasive and expensive.

Objective: To relate plasma amyloid-β (Aβ), measured using Single-molecule array (Simoatrademark) assays, to in vivo brain Aβ, measured using positron emission tomography (PET), examine the accuracy of plasma Aβ to predict brain Aβ positivity, and the relation of APOE ɛ4 with plasma Aβ.

Methods: We performed a cross-sectional analysis in a cohort of 345 late middle-aged Hispanic men and women (age 64 years, 72% women).

Landmark-guided region-based spatial normalization for functional magnetic resonance imaging.

As the size of the neuroimaging cohorts being increased to address key questions in the field of cognitive neuroscience, cognitive aging, and neurodegenerative diseases, the accuracy of the spatial normalization as an essential preprocessing step becomes extremely important. Existing spatial normalization methods have poor accuracy particularly when dealing with the highly convoluted human cerebral cortex and when brain morphology is severely altered (e.g.

Tau PET following acute TBI: Off-target binding to blood products, tauopathy, or both?

Repeated mild Traumatic Brain Injury (TBI) is a risk factor for Chronic Traumatic Encephalopathy (CTE), characterized pathologically by neurofibrillary tau deposition in the depths of brain sulci and surrounding blood vessels. The mechanism by which TBI leads to CTE remains unknown but has been posited to relate to axonal shear injury leading to release and possibly deposition of tau at the time of injury. As part of an IRB-approved study designed to learn how processes occurring acutely after TBI may predict later proteinopathy and neurodegeneration, we performed tau PET using 18F-MK6240 and MRI within 14 days of complicated mild TBI in three subjects.

Topographical Overlapping of the Amyloid-β and Tau Pathologies in the Default Mode Network Predicts Alzheimer's Disease with Higher Specificity.

Background: While amyloid-β (Aβ) plaques and tau tangles are the well-recognized pathologies of Alzheimer's disease (AD), they are more often observed in healthy individuals than in AD patients. This discrepancy makes it extremely challenging to utilize these two proteinopathies as reliable biomarkers for the early detection as well as later diagnosis of AD.

Objective: We hypothesize and provide preliminary evidence that topographically overlapping Aβ and tau within the default mode network (DMN) play more critical roles in the underlying pathophysiology of AD than each of the tau and/or Aβ pathologies alone.

Patterns of tau pathology identified with F-MK-6240 PET imaging.

Introduction: Positron emission tomography (PET) imaging for neurofibrillary tau allows investigation of the in vivo spatiotemporal progression of Alzheimer's disease (AD) pathology. We evaluated the suitability of F-MK-6240 in a clinical sample and determined the relationships among F-MK-6240 binding, age, cognition, and cerebrospinal fluid (CSF)-based AD biomarkers.

Methods: Participants (n = 101, 72 ± 9 years, 52% women) underwent amyloid PET, tau PET, structural T1-weighted magnetic resonance imaging, and neuropsychological evaluation.

In Vivo Amyloid, Neurodegeneration, and Verbal Learning in Late Middle-Aged Hispanics.

Background: The National Institute on Aging (NIA)/Alzheimer's Association (AA) 2018 framework conceptualizes Alzheimer's disease (AD) biologically. Evidence of brain amyloid by biomarkers defines AD pathologic change and the Alzheimer's continuum. The presence of tau or neurodegeneration in the absence of amyloid defines non-AD pathologic change.

Sex differences in in vivo tau neuropathology in a multiethnic sample of late middle-aged adults.

It is unclear whether women have higher brain tau pathology. The objective of this study was to examine whether women have higher tau burden than men, and whether tau differences are independent of amyloid β (Aβ) burden. We conducted a cross-sectional analysis of a multiethnic sample of 252 nondemented late middle-aged (mean age: 64.

Predictive utility of task-related functional connectivity vs. voxel activation.

Functional connectivity, both in resting state and task performance, has steadily increased its share of neuroimaging research effort in the last 1.5 decades. In the current study, we investigated the predictive utility regarding behavioral performance and task information for 240 participants, aged 20-77, for both voxel activation and functional connectivity in 12 cognitive tasks, belonging to 4 cognitive reference domains (Episodic Memory, Fluid Reasoning, Perceptual Speed, and Vocabulary).

Attenuation of motion artifacts in fMRI using discrete reconstruction of irregular fMRI trajectories (DRIFT).

Purpose: Numerous studies report motion as the most detrimental source of noise and artifacts in fMRI. Current motion correction methods fail to completely address the motion problem. Retrospective techniques such as spatial realignment can correct for between-volume misalignment but fail to address within volume contamination and spin-history artifacts.

Metabolic syndrome and its components in relation to in vivo brain amyloid and neurodegeneration in late middle age.

Metabolic syndrome (MetS) is associated with dementia, but it is unclear whether MetS is related to Alzheimer's disease (AD). We investigated the association of MetS with brain amyloid, a key AD feature, and neurodegeneration. A community-based sample of 350 middle-aged Hispanics in New York City had cerebral amyloid β (Aβ) burden ascertained with F-Florbetaben positron emission tomography.

Brain Amyloid Burden and Resting-State Functional Connectivity in Late Middle-Aged Hispanics.

Non-linear relations of brain amyloid beta (Aβ) with task- based functional connectivity (tbFC) measured with functional magnetic resonance imaging (fMRI) have been reported in late middle age. Our objective was to examine the association between brain Aβ and resting-state functional connectivity (rsFC) in late middle-aged adults. Global brain Aβ burden was ascertained with F-Florbetaben Positron Emission Tomography (PET); rsFC was ascertained on 3T Magnetic Resonance Imaging (MRI) among 333 late middle-aged Hispanics adults without dementia in four major brain functional connectivity networks: default mode network (DMN), fronto-parietal control network (FPC), salience network (SAL) and dorsal attention network (DAN).