Distinctive volumetric associations between plasma p-tau181 and hippocampal formation structures across the Alzheimer's disease continuum.

BackgroundPlasma p-tau181 is a promising diagnostic marker of Alzheimer's disease (AD) pathology, reflecting amyloid accumulation, tau deposition, and downstream neurodegeneration that leads to cognitive impairment. However, the specificity of plasma p-tau181 to AD-related tau pathology remains unclear.ObjectiveTo assess whether plasma p-tau181 is differentially associated with volumetric changes in distinct structures of the hippocampal formation and whether these structures mediate the relationship between plasma p-tau181 and cognition across the AD continuum.

Functional redundancy of the posterior hippocampi is selectively disrupted in non-demented older adults with -amyloid deposition.

Several neural mechanisms underlying resilience to Alzheimer's disease (AD) have been proposed, including redundant neural connections between the posterior hippocampi and all other brain regions, and global functional connectivity of the left frontal cortex (LFC). Here, we investigated if functional redundancy of the hippocampus (HC) and LFC underscores neural resilience in the presence of early AD pathologies. From the ADNI database, cognitively normal older adults (CN) (N = 220; 36 % A+) and patients with Mild Cognitive Impairment (MCI) (N = 143; 51 % A+) were utilized.

Radiomics of PET Using Neural Networks for Prediction of Alzheimer's Disease Diagnosis.

Positron emission tomography (PET) imaging technology is widely used for diagnosing Alzheimer's disease (AD) in people with dementia. Although various computational methods have been proposed for diagnosis of AD using PET images, prediction of disease diagnosis by leveraging longitudinal PET imaging data has not been widely studied. In this paper, we propose novel implementations of deep learning models graph neural network (GNN) and transformer encoder (TE), to leverage longitudinal sequences of PET images in addition to cognitive scores for prediction of AD diagnosis and prediction of conversion from cognitively unimpaired or mild cognitive impairment to AD using data collected in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study.

Distinctive associations between plasma p-tau181 levels and hippocampal subfield volume across the Alzheimer's disease continuum.

Background: Plasma p-tau181 is a promising diagnostic marker of Alzheimer's disease (AD) pathology, reflecting amyloid accumulation, tau deposition, and downstream neurodegeneration that leads to cognitive impairment. However, the specificity of plasma p-tau181 to AD-related tau pathology remains unclear.

Objective: To assess whether plasma p-tau181 is differentially associated with volumetric changes in distinct hippocampal subfields and whether they mediate the relationship between plasma p-tau181 and cognition across the AD continuum.

The POINTER Imaging baseline cohort: Associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition.

Introduction: The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

Introduction: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.

Methods: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments.

Optimizing quantification of MK6240 tau PET in unimpaired older adults.

Accurate measurement of Alzheimer's disease (AD) pathology in older adults without significant clinical impairment is critical to assessing intervention strategies aimed at slowing AD-related cognitive decline. The U.S.

Extraversion Is Associated With Lower Brain Beta-Amyloid Deposition in Cognitively Normal Older Adults.

Emerging evidence suggests that some personality traits may link to the vulnerability to or protection for Alzheimer's disease (AD). A causal mechanism underlying this relationship, however, remains largely unknown. Using F-Florbetaben positron emission tomography (PET) binding to beta-amyloid (Aβ) plaques, a pathological feature of AD, and functional magnetic resonance imaging (fMRI), we investigated pathological and functional correlates of extraversion and neuroticism in a group of healthy young and older subjects.

Safety and Tolerability of APOE Genotyping and Disclosure in Cognitively Normal Volunteers From the Butler Alzheimer's Prevention Registry.

Aims: Alzheimer's disease (AD) is a gradually progressive neurodegenerative disease that ultimately results in total loss of cognitive and functional independence in older adults. This study aimed to examine the safety and tolerability of disclosure in community-dwelling, cognitively normal (CN) older adults from the Butler Alzheimer's Prevention Registry (BAPR), and to determine whether disclosure impacted participant's decisions to participate in AD clinical research.

Methods: 186 (N = 106 ∊4 non-carriers, 80 ∊4 carriers) CN older adults aged 58-78 from the BAPR completed 2 visits: one for psychological readiness screening and genotyping and one for disclosure.

Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease.

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals.

Small vessel disease more than Alzheimer's disease determines diffusion MRI alterations in memory clinic patients.

Introduction: Microstructural alterations as assessed by diffusion tensor imaging (DTI) are key findings in both Alzheimer's disease (AD) and small vessel disease (SVD). We determined the contribution of each of these conditions to diffusion alterations.

Methods: We studied six samples (N = 365 participants) covering the spectrum of AD and SVD, including genetically defined samples.

Multiple pathways of reserve simultaneously present in cognitively normal older adults.

Objective: To examine neural correlates of intellectual activity underlying multiple pathways imparting reserve by testing that higher intellectual activity is associated with lower brain amyloid pathology, greater gray matter (GM) volume, and differential task-evoked brain activation levels as a function of amyloid positivity status among clinically intact older adults.

Methods: Eighty-two cognitively normal older adults and 46 healthy young participants underwent fMRI during task switching. All older participants completed F-florbetaben-PET and an individual's amyloid positivity status was determined.

Functional brain and age-related changes associated with congruency in task switching.

Alternating between completing two simple tasks, as opposed to completing only one task, has been shown to produce costs to performance and changes to neural patterns of activity, effects which are augmented in old age. Cognitive conflict may arise from factors other than switching tasks, however. Sensorimotor congruency (whether stimulus-response mappings are the same or different for the two tasks) has been shown to behaviorally moderate switch costs in older, but not younger adults.

Dynamic Patterns of Brain Structure-Behavior Correlation Across the Lifespan.

Although the brain/behavior correlation is one of the premises of cognitive neuroscience, there is still no consensus about the relationship between brain measures and cognitive function, and only little is known about the effect of age on this relationship. We investigated the age-associated variations on the spatial patterns of cortical thickness correlates of four cognitive domains. We showed that the spatial distribution of the cortical thickness correlates of each cognitive domain is distinctive and depicts varying age-association differences across the adult lifespan.

Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer's disease.

SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography.

β-Amyloid Deposition Is Associated with Decreased Right Prefrontal Activation during Task Switching among Cognitively Normal Elderly.

Unlabelled: The accumulation of β-amyloid (Aβ) peptides, a pathological hallmark of Alzheimer's disease (AD), has been associated with functional alterations, often in an episodic memory system with a particular emphasis on medial temporal lobe function. The topography of Aβ deposition, however, largely overlaps with frontoparietal control (FPC) regions implicated in cognitive control that has been shown to be impaired in early mild AD. To understand the neural mechanism underlying early changes in cognitive control with AD, we examined the impact of Aβ deposition on task-evoked FPC activation using functional magnetic resonance imaging (fMRI) in humans.

Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly.

The accumulation of amyloid-beta (Aβ) peptides, a pathologic hallmark of Alzheimer's disease, has been associated with functional alterations in cognitively normal elderly, most often in the context of episodic memory with a particular emphasis on the medial temporal lobes. The topography of Aβ deposition, however, highly overlaps with frontoparietal control (FPC) regions implicated in cognitive control/working memory. To examine Aβ-related functional alternations in the FPC regions during a working memory task, we imaged 42 young and 57 cognitively normal elderly using functional magnetic resonance imaging during a letter Sternberg task with varying load.

Neural compensation in older people with brain amyloid-β deposition.

Recruitment of extra neural resources may allow people to maintain normal cognition despite amyloid-β (Aβ) plaques. Previous fMRI studies have reported such hyperactivation, but it is unclear whether increases represent compensation or aberrant overexcitation. We found that older adults with Aβ deposition had reduced deactivations in task-negative regions, but increased activation in task-positive regions related to more detailed memory encoding.

Frontotemporal network connectivity during memory encoding is increased with aging and disrupted by beta-amyloid.

Approximately 30% of cognitively normal older adults harbor brain β-amyloid (Aβ), a prominent feature of Alzheimer's disease associated with neural alterations and episodic memory decline. We examined how aging and Aβ deposition affect neural function during memory encoding of visual scenes using functional magnetic resonance imaging (fMRI) in humans. Thirty-six cognitively normal older people underwent fMRI scanning, and positron emission tomography with [(11)C] Pittsburgh compound B to measure fibrillar brain Aβ; 15 young subjects were studied with fMRI.

Associations between Alzheimer disease biomarkers, neurodegeneration, and cognition in cognitively normal older people.

Importance: Criteria for preclinical Alzheimer disease (AD) propose β-amyloid (Aβ) plaques to initiate neurodegeneration within AD-affected regions. However, some cognitively normal older individuals harbor neural injury similar to patients with AD, without concurrent Aβ burden. Such findings challenge the proposed sequence and suggest that Aβ-independent precursors underlie AD-typical neurodegenerative patterns.

Meta-analysis of amyloid-cognition relations in cognitively normal older adults.

Objective: We conducted a meta-analysis of relationships between amyloid burden and cognition in cognitively normal, older adult humans.

Methods: Methods of assessing amyloid burden included were CSF or plasma assays, histopathology, and PET ligands. Cognitive domains examined were episodic memory, executive function, working memory, processing speed, visuospatial function, semantic memory, and global cognition.