Publications by authors named "Tharick A. Pascoal"

Introduction: Late-life cognitive impairment and depression frequently co-occur and share many symptoms. However, the specific neural and clinical factors contributing to both their common and distinct profiles in older adults remain unclear.

Methods: We investigated resting-state correlates of cognitive and depressive symptoms in older adults (n = 248 and n = 95) using clinical, blood, and neuroimaging data.

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Background: Recent studies have focused on improving our understanding of gut microbiome dysbiosis and its impact on cognitive function. However, the relationship between gut microbiome composition, accelerated brain atrophy, and cognitive function has not yet been fully explored.

Methods: We recruited 292 participants from South Korean memory clinics to undergo brain magnetic resonance imaging, clinical assessments, and collected stool samples.

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Introduction: Epidemiological studies indicate a link between attention-deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear.

Methods: We computed weighted ADHD polygenic risk scores (ADHD-PRS) in 938 cognitively impaired participants (674 mild cognitive impairment [MCI] and 264 dementia; mean age 73.

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Patients with Alzheimer's disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking.

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Background: Latin American countries present major health-related inequities due to historical, cultural, and social aspects. Recent evidence highlights that factors related to social and health disparities outweigh classic demographic factors in determining healthy brain aging in these populations. However, these analyses have not been conducted with the Brazilian population, the largest and most ethnically diverse population in Latin America.

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Blood-based biomarkers have been revolutionizing the detection, diagnosis and screening of Alzheimer's disease. Specifically, phosphorylated-tau variants (p-tau, p-tau and p-tau) are promising biomarkers for identifying Alzheimer's disease pathology. Antibody-based assays such as single molecule arrays immunoassays are powerful tools to investigate pathological changes indicated by blood-based biomarkers and have been studied extensively in the Alzheimer's disease research field.

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The apolipoprotein E ( ) ε4 allele is the strongest genetic risk factor for Alzheimer's disease (AD). ApoE is glycosylated with an O-linked Core-1 sialylated glycan at several sites, yet the impact and function of this glycosylation on AD biomarkers remains unclear. We examined apoE glycosylation in a cohort of cerebrospinal fluid (CSF, n=181) and plasma (n= 178) samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) stratified into 4 groups: cognitively normal (CN), Mild Cognitive Impairment (MCI), progressors and non-progressors based on delayed word recall performance over 4 years.

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Article Synopsis
  • Recent advancements in Alzheimer's treatment now require verification of amyloid-β pathology using PET scans or cerebrospinal fluid, but blood tests could simplify this process.* -
  • A study involving nearly 7,000 individuals identified that the plasma biomarker p-tau217 can reliably indicate amyloid-β pathology, especially in patients with probable Alzheimer’s dementia.* -
  • The findings suggest that combining p-tau217 results with clinical assessments may allow for accurate diagnoses without the need for more invasive PET or CSF tests.*
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  • This study focuses on identifying individuals with advanced Alzheimer's disease (specifically Braak V or VI) using plasma biomarkers in those who are already confirmed to have amyloid-β (Aβ).
  • Researchers evaluated 595 participants from two studies, employing tests like amyloid-PET and tau-PET while measuring various plasma tau levels.
  • Findings suggest that elevated levels of plasma pTau-217 are strongly associated with Braak V positivity, indicating it could be a useful biomarker for patient stratification in treatment and clinical studies.
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  • The study aimed to compare the in vitro binding characteristics of three radiotracers ([F]flortaucipir, [F]MK6240, [F]PI2620) in postmortem brain samples from Alzheimer’s disease (AD) and control groups.
  • Significant differences in tracer binding were found in the whole-brain hemisphere, prefrontal cortex, and hippocampus between AD and control tissues, with [F]MK6240 and [F]PI2620 showing better performance in differentiating AD cases.
  • The results indicate that [F]MK6240 and [F]PI2620 have higher selectivity and binding to AD tissues compared to [F]flortaucipir,
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Background And Purpose: This study was undertaken to compare the performance of plasma p-tau181 with that of [F]fluorodeoxyglucose (FDG) positron emission tomography (PET) in the identification of early biological Alzheimer disease (AD).

Methods: We included 533 cognitively impaired participants from the Alzheimer's Disease Neuroimaging Initiative. Participants underwent PET scans, biofluid collection, and cognitive tests.

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Background: Blood-based biomarkers are gaining grounds for the detection of Alzheimer's disease (AD) and related disorders (ADRDs). However, two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction. A novel proteomic method for pre-selected analytes, based on proximity extension technology, was recently introduced.

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Biomarkers have been instrumental in population selection and disease monitoring in clinical trials of recently FDA-approved drugs targeting amyloid-β to slow the progression of Alzheimer's disease (AD). As new therapeutic strategies and biomarker techniques emerge, the importance of biomarkers in drug development is growing exponentially. In this emerging landscape, biomarkers are expected to serve a wide range of contexts of use in clinical trials focusing on AD and related dementias.

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In Alzheimer's disease (AD), neuropsychiatric symptoms (NPS) correlate with tau deposition in the brain. Here, we investigated the association of PET-based Braak stages with NPS and assessed whether they predict annual changes in NPS. We evaluated 231 individuals in the aging and AD continuum.

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Article Synopsis
  • The study examines how recent updates in Alzheimer's disease diagnostic guidelines from NIA-AA and IWG impact clinical diagnoses among cognitively unimpaired and impaired individuals.
  • It analyzed clinical and biomarker data from 1,195 participants, noting differences in diagnostic labels assigned under various guidelines and the frequency of discordant diagnoses among them.
  • The findings revealed significant variance in predictive value for cognitive impairment across different diagnostic frameworks, with older guidelines showing a clearer correlation than some of the more recent ones.
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Introduction: Brain glucose hypometabolism, indexed by the fluorodeoxyglucose positron emission tomography ([F]FDG-PET) imaging, is a metabolic signature of Alzheimer's disease (AD). However, the underlying biological pathways involved in these metabolic changes remain elusive.

Methods: Here, we integrated [F]FDG-PET images with blood and hippocampal transcriptomic data from cognitively unimpaired (CU, n = 445) and cognitively impaired (CI, n = 749) individuals using modular dimension reduction techniques and voxel-wise linear regression analysis.

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Background: Females represent approximately 70% of the Alzheimer's disease (AD) cases and the literature has proposed a connection between the decreased estrogen levels during menopause and an increased AD risk. Previous investigations have predominantly focused on assessing how hormone therapy (HT) affects the likelihood of AD development and cognitive deterioration. However, as the research framework has shifted toward a biomarker-defined AD and alterations in specific biomarkers could take place years before cognitive decline becomes discernible, it is crucial to examine how HT influences AD biomarkers.

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Background: Blood-based biomarkers are gaining grounds for Alzheimer's disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods for multi-analyte assessments and the need for markers of neuroinflammation, vascular, and synaptic dysfunction. Here, we evaluated a novel multi-analyte biomarker platform, NULISAseq CNS disease panel, a multiplex NUcleic acid-linked Immuno-Sandwich Assay (NULISA) targeting ~120 analytes, including classical AD biomarkers and key proteins defining various disease hallmarks.

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Alzheimer's disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of network connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that the distribution of tau and reactive microglia in humans follows spatial patterns of connectivity variation, the so-called gradients of brain organization.

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The reliability of plasma biomarkers of Alzheimer's disease (AD) can be compromised by protease-induced degradation. This can limit the feasibility of conducting plasma biomarker studies in environments that lack the capacity for immediate processing and appropriate storage of blood samples. We hypothesized that blood collection tube supplementation with protease inhibitors can improve the stability of plasma biomarkers at room temperatures (RT).

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Introduction: Plasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains.

Methods: In a prospective study with repeated assessments of a randomly selected population-based cohort (n = 787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aβ42/40) ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP).

Results: Cross-sectionally, memory showed the strongest associations with p-tau181, and attention, executive, and visuospatial functions with NfL.

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Alzheimer's disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This might be partly due to a lack of widely available and cost-effective modalities for diagnosis and prognosis. Recently, the blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity and precision of the assays and measurement platforms.

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Article Synopsis
  • - The study investigates the role of microglia in the brainstem related to Alzheimer's disease (AD) using TSPO PET imaging, focusing particularly on the inferior colliculi (IC) due to its potential link to auditory dysfunction.
  • - Results indicated that TSPO expression in the IC decreases with age and in AD patients, contrasting with increased TSPO expression in the cortex with aging and AD, suggesting different roles for microglia in these regions.
  • - The findings emphasize the need for further research on brainstem microglia, as their activation in the IC might serve a protective function, highlighting regional differences in the pathology of AD.
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Introduction: Alzheimer's disease (AD) is increasing in the Caribbean, especially for persons of African ancestry (PAA) and women. However, studies have mostly utilized surveys without AD biomarkers.

Methods: In the Tobago Health Study ( = 309; 109 women, mean age 70.

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