Plasma phosphorylated-tau181 as a predictive biomarker for Alzheimer’s amyloid, tau and FDG PET status

AbstractPlasma phosphorylated-tau181 (p-tau181) showed the potential for Alzheimer’s diagnosis and prognosis, but its role in detecting cerebral pathologies is unclear. We aimed to evaluate whether it could serve as a marker for Alzheimer’s pathology in the brain. A total of 1189 participants with plasma p-tau181 and PET data of amyloid, tau or FDG PET were included from ADNI. Cross-sectional relationships of plasma p-tau181 with PET biomarkers were tested. Longitudinally, we further investigated whether different p-tau181 levels at baseline predicted different progression of Alzheimer’s pathological changes in the brain. We found plasma p-tau181 significantly correlated with brain amyloid (Spearman ρ = 0.45, P < 0.0001), tau (0.25, P = 0.0003), and FDG PET uptakes (−0.37, P < 0.0001), and increased along the Alzheimer’s continuum. Individually, plasma p-tau181 could detect abnormal amyloid, tau pathologies and hypometabolism in the brain, similar with or even better than clinical indicators. The diagnostic accuracy of plasma p-tau181 elevated significantly when combined with clinical information (AUC = 0.814 for amyloid PET, 0.773 for tau PET, and 0.708 for FDG PET). Relationships of plasma p-tau181 with brain pathologies were partly or entirely mediated by the corresponding CSF biomarkers. Besides, individuals with abnormal plasma p-tau181 level (>18.85 pg/ml) at baseline had a higher risk of pathological progression in brain amyloid (HR: 2.32, 95%CI 1.32–4.08) and FDG PET (3.21, 95%CI 2.06–5.01) status. Plasma p-tau181 may be a sensitive screening test for detecting brain pathologies, and serve as a predictive biomarker for Alzheimer’s pathophysiology.

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Biomarkers for Alzheimer’s Disease Early Diagnosis

Journal of Personalized Medicine ◽

10.3390/jpm10030114 ◽

2020 ◽

Vol 10 (3) ◽

pp. 114 ◽

Cited By ~ 2

Author(s):

Eva Ausó ◽

Violeta Gómez-Vicente ◽

Gema Esquiva

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Neuronal Loss ◽

Diagnostic Tools ◽

Csf Biomarkers ◽

Diagnosis And Prognosis ◽

Positron Emission ◽

The Central Nervous System ◽

Magnetic Resonance Imaging Mri ◽

The Brain

Alzheimer’s disease (AD) is the most common cause of dementia, affecting the central nervous system (CNS) through the accumulation of intraneuronal neurofibrillary tau tangles (NFTs) and β-amyloid plaques. By the time AD is clinically diagnosed, neuronal loss has already occurred in many brain and retinal regions. Therefore, the availability of early and reliable diagnosis markers of the disease would allow its detection and taking preventive measures to avoid neuronal loss. Current diagnostic tools in the brain, such as magnetic resonance imaging (MRI), positron emission tomography (PET) imaging, and cerebrospinal fluid (CSF) biomarkers (Aβ and tau) detection are invasive and expensive. Brain-secreted extracellular vesicles (BEVs) isolated from peripheral blood have emerged as novel strategies in the study of AD, with enormous potential as a diagnostic evaluation of therapeutics and treatment tools. In addition; similar mechanisms of neurodegeneration have been demonstrated in the brain and the eyes of AD patients. Since the eyes are more accessible than the brain, several eye tests that detect cellular and vascular changes in the retina have also been proposed as potential screening biomarkers. The aim of this study is to summarize and discuss several potential markers in the brain, eye, blood, and other accessible biofluids like saliva and urine, and correlate them with earlier diagnosis and prognosis to identify individuals with mild symptoms prior to dementia.

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Plasma Aβ42/40 ratio alone or combined with FDG-PET can accurately predict amyloid-PET positivity: a cross-sectional analysis from the AB255 Study

Alzheimer s Research & Therapy ◽

10.1186/s13195-019-0549-1 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 4

Author(s):

Virginia Pérez-Grijalba ◽

◽

Javier Arbizu ◽

Judith Romero ◽

Elena Prieto ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Predictive Value ◽

Fdg Pet ◽

Screening Tool ◽

Area Under The Curve ◽

Normal Subjects ◽

Amyloid Pet ◽

Cross Sectional ◽

Pet Scans

Abstract Background To facilitate population screening and clinical trials of disease-modifying therapies for Alzheimer’s disease, supportive biomarker information is necessary. This study was aimed to investigate the association of plasma amyloid-beta (Aβ) levels with the presence of pathological accumulation of Aβ in the brain measured by amyloid-PET. Both plasma Aβ42/40 ratio alone or combined with an FDG-PET-based biomarker of neurodegeneration were assessed as potential AD biomarkers. Methods We included 39 cognitively normal subjects and 20 patients with mild cognitive impairment from the AB255 Study who had undergone PiB-PET scans. Total Aβ40 and Aβ42 levels in plasma (TP42/40) were quantified using ABtest kits. Subjects were dichotomized as Aβ-PET positive or negative, and the ability of TP42/40 to detect Aβ-PET positivity was assessed by logistic regression and receiver operating characteristic analyses. Combination of plasma Aβ biomarkers and FDG-PET was further assessed as an improvement for brain amyloidosis detection and diagnosis classification. Results Eighteen (30.5%) subjects were Aβ-PET positive. TP42/40 ratio alone identified Aβ-PET status with an area under the curve (AUC) of 0.881 (95% confidence interval [CI] = 0.779–0.982). Discriminating performance of TP42/40 to detect Aβ-PET-positive subjects yielded sensitivity and specificity values at Youden’s cutoff of 77.8% and 87.5%, respectively, with a positive predictive value of 0.732 and negative predictive value of 0.900. All these parameters improved after adjusting the model for significant covariates. Applying TP42/40 as the first screening tool in a sequential diagnostic work-up would reduce the number of Aβ-PET scans by 64%. Combination of both FDG-PET scores and plasma Aβ biomarkers was found to be the most accurate Aβ-PET predictor, with an AUC of 0.965 (95% CI = 0.913–0.100). Conclusions Plasma TP42/40 ratio showed a relevant and significant potential as a screening tool to identify brain Aβ positivity in preclinical and prodromal stages of Alzheimer’s disease.

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The Regulation of MR Neuroimaging Research: Disentangling the Gordian Knot

American Journal of Law & Medicine ◽

10.1177/009885880703300207 ◽

2007 ◽

Vol 33 (2-3) ◽

pp. 295-317 ◽

Cited By ~ 6

Author(s):

Jennifer J. Kulynych

Keyword(s):

Brain Activity ◽

Clinical Information ◽

Test Results ◽

Cross Sectional ◽

Indirect Measurements ◽

Electromagnetic Pulses ◽

Serious Injury ◽

Magnetic Resonance Imaging Mri ◽

Mri Study ◽

The Brain

In a typical magnetic resonance imaging (“MRI”) study of the brain, subjects are screened for contraindications before being placed in the bore of a large machine, the MRI scanner, which contains a powerful magnet. The scanner produces cross-sectional images of brain tissue as the subjects undergo a series of brief electromagnetic pulses, perceptible only as noise and vibration. If the protocol involves functional MRI (“fMRI”), a popular research technique for obtaining indirect measurements of brain activity, equipment might be used to present stimuli (sounds or pictures) during the scan, but generally the study involves no invasive procedures, no physical discomfort, and no ionizing radiation. Upon completion of the scan, MRI data is transferred to an investigator's computer for further analysis, often in combination with behavioral test results and clinical information obtained from subjects or their medical records.This procedure sounds benign, and usually is. But an MRI scanner is a powerful medical device, capable of causing serious injury or death if operated carelessly.

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PLASMA A?42/40 RATIO DETECTS EARLY STAGES OF ALZHEIMER’S DISEASE AND CORRELATES WITH CSF AND NEUROIMAGING BIOMARKERS IN THE AB255 STUDY

Journal of Prevention of Alzheimer's Disease ◽

10.14283/jpad.2018.41 ◽

2018 ◽

pp. 1-8

Author(s):

V. Pérez-Grijalba ◽

J. Romero ◽

P. Pesini ◽

L. Sarasa ◽

I. Monleón ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Fdg Pet ◽

Large Population ◽

Csf Biomarkers ◽

Amyloid Pet ◽

Early Stages ◽

Normal Individuals ◽

Risk Of Progression ◽

Amyloid Aβ

Background: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer’s disease (AD) in large population screening strategies. Objectives: This study evaluated the potential of plasma β-amyloid (Aβ) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. Design: Total plasma Aβ42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. Results: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). Conclusions: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.

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An MRI measure of degenerative and cerebrovascular pathology in Alzheimer disease

Neurology ◽

10.1212/wnl.0000000000006310 ◽

2018 ◽

Vol 91 (15) ◽

pp. e1402-e1412 ◽

Cited By ~ 24

Author(s):

Adam M. Brickman ◽

Giuseppe Tosto ◽

Jose Gutierrez ◽

Howard Andrews ◽

Yian Gu ◽

...

Keyword(s):

Alzheimer Disease ◽

Neuronal Loss ◽

Quantitative Measure ◽

Quantitative Mri ◽

Csf Biomarkers ◽

Amyloid Pet ◽

Healthy Controls ◽

Cross Sectional ◽

Clinical Diagnoses ◽

Csf Levels

ObjectiveTo develop, replicate, and validate an MRI-based quantitative measure of both cerebrovascular and neurodegeneration in Alzheimer disease (AD) for clinical and potentially research purposes.MethodsWe used data from a cross-sectional and longitudinal community-based study of Medicare-eligible residents in northern Manhattan followed every 18–24 months (n = 1,175, mean age 78 years). White matter hyperintensities, infarcts, hippocampal volumes, and cortical thicknesses were quantified from MRI and combined to generate an MRI measure associated with episodic memory. The combined MRI measure was replicated and validated using autopsy data, clinical diagnoses, and CSF biomarkers and amyloid PET from the Alzheimer's Disease Neuroimaging Initiative.ResultsThe quantitative MRI measure was developed in a group of community participants (n = 690) and replicated in a similar second group (n = 485). Compared with healthy controls, the quantitative MRI measure was lower in patients with mild cognitive impairment and lower still in those with clinically diagnosed AD. The quantitative MRI measure correlated with neurofibrillary tangles, neuronal loss, atrophy, and infarcts at postmortem in an autopsy subset and was also associated with PET amyloid imaging and CSF levels of total tau, phosphorylated tau, and β-amyloid 42. The MRI measure predicted conversion to MCI and clinical AD among healthy controls.ConclusionWe developed, replicated, and validated an MRI measure of cerebrovascular and neurodegenerative pathologies that are associated with clinical and neuropathologic diagnosis of AD and related to established biomarkers.

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Bildgebende Verfahren in der Diagnostik von Demenzerkrankungen

Nervenheilkunde ◽

10.1055/s-0038-1628836 ◽

2010 ◽

Vol 29 (11) ◽

pp. 758-760

Author(s):

F Jessen

Keyword(s):

Fdg Pet ◽

Bildgebende Verfahren ◽

Amyloid Pet ◽

Neurodegenerative Erkrankungen ◽

Zerebrale Bildgebung ◽

Klinische Relevanz

ZusammenfassungDie zerebrale Bildgebung hat in der ätiologischen Diagnostik von Demenzerkrankungen die Funktion z. B. chirurgisch behandelbare Ursachen einer Demenz aufzudecken. Zusätzlich trägt sie zur Differenzialdiagnose von primären Demenzerkrankungen bei. Neurodegenerative Erkrankungen sind durch typische Atrophiemuster gekennzeichnet. Vaskuläre Läsionen können sensitiv mit der MRT erfasst werden. Zahlreiche neue MRT-Verfahren befinden sich in der klinischen Entwicklung. Als nuklearmedizinisches Verfahren ist insbesondere die 18F-Fluordesoxyglukose (FDG)-PET wertvoll. Die zukünftige klinische Relevanz von Amyloid-PET wird mit großer Wahrscheinlichkeit sehr hoch sein.

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Brain FDG PET for the Etiological Diagnosis of Clinically Uncertain Cognitive Impairment During Delirium in Remission

Journal of Alzheimer s Disease ◽

10.3233/jad-200530 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1609-1622

Author(s):

Franziska Mathies ◽

Catharina Lange ◽

Anja Mäurer ◽

Ivayla Apostolova ◽

Susanne Klutmann ◽

...

Keyword(s):

Cognitive Impairment ◽

Fdg Pet ◽

False Negative ◽

Ground Truth ◽

Etiological Diagnosis ◽

Geriatric Unit ◽

Positron Emission ◽

The Brain ◽

Hospitalized Geriatric Patients

Background: Positron emission tomography (PET) of the brain with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is widely used for the etiological diagnosis of clinically uncertain cognitive impairment (CUCI). Acute full-blown delirium can cause reversible alterations of FDG uptake that mimic neurodegenerative disease. Objective: This study tested whether delirium in remission affects the performance of FDG PET for differentiation between neurodegenerative and non-neurodegenerative etiology of CUCI. Methods: The study included 88 patients (82.0±5.7 y) with newly detected CUCI during hospitalization in a geriatric unit. Twenty-seven (31%) of the patients were diagnosed with delirium during their current hospital stay, which, however, at time of enrollment was in remission so that delirium was not considered the primary cause of the CUCI. Cases were categorized as neurodegenerative or non-neurodegenerative etiology based on visual inspection of FDG PET. The diagnosis at clinical follow-up after ≥12 months served as ground truth to evaluate the diagnostic performance of FDG PET. Results: FDG PET was categorized as neurodegenerative in 51 (58%) of the patients. Follow-up after 16±3 months was obtained in 68 (77%) of the patients. The clinical follow-up diagnosis confirmed the FDG PET-based categorization in 60 patients (88%, 4 false negative and 4 false positive cases with respect to detection of neurodegeneration). The fraction of correct PET-based categorization did not differ between patients with delirium in remission and patients without delirium (86% versus 89%, p = 0.666). Conclusion: Brain FDG PET is useful for the etiological diagnosis of CUCI in hospitalized geriatric patients, as well as in patients with delirium in remission.

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Status quo of Nursing Informatics Competencies for Nurses Under Standardized Training -A Cross-Sectional Study (Preprint)

10.2196/preprints.16244 ◽

2019 ◽

Author(s):

Kejimu Sunzi ◽

Cheng Lei ◽

Zhuoyuanyuan Chen ◽

Baolu Zhang

Keyword(s):

Influencing Factors ◽

Online Survey ◽

Rapid Development ◽

Professional Knowledge ◽

Clinical Information ◽

The Internet ◽

Nursing Informatics ◽

Self Assessment ◽

Cross Sectional ◽

Knowledge And Skills

BACKGROUND The rapid development of health information technology has an increasingly significant impact on nursing work. The development of informatization also puts forward higher requirements for nurses under standardized training (NUST). Informatics knowledge and skills are essential if clinicians are to master the large volume of information generated in healthcare today. Nurses with competent nursing informatics competencies (NIC) will be able to better adapt to the needs of work and the development of the times. OBJECTIVE This study aimed to explore, analyze, and discuss the current situation of NIC of NUST in China, and analyze the influencing factors, to provide references for improving the NIC of NUST. METHODS We conducted a cross-sectional survey of standard training nurses' NIC in a tertiary hospital in Sichuan Province, China, with convenience sampling. The study consists of two parts included socio-demographic characteristics and NIC, a self-designed general information questionnaire, and a Self-Assessment Nursing Informatics Competency Scale-SF28 were used as survey tools. An online survey collected the data, and the scores of nurses' NIC were analyzed, and the factors were determined by linear regression statistical analysis. RESULTS Overall 191 target population responded to the questionnaire, including 22 males (11.52%) and 169 females (88.48%), the age range was 21 to 28 years, the average age was 24.64 (SD 1.43). 53 persons without computer level certificate (27.75%), 138 persons with computer level certificate (72.25%), the total score of Self-Assessment Nursing Informatics Competency Scale was 68.65 (SD 10.47), the scores of each dimension were role of clinical information 10.12 (SD 2.17), basic computer knowledge and skills 26.64 (SD 4.96), application ability of computer skills 7.16 (SD 1.82), wireless equipment skills 8.02 (SD 2.04), nursing information attitude 16.73 (SD 3.25). In the analysis of influencing factors of NIC, “whether learned professional knowledge through the internet” is the influencing factor of NIC (P< .05). CONCLUSIONS The clinical nursing informatics (NC) of nurses was at a medium level, mainly influenced by “whether learned professional knowledge through the internet.” In the future regulation process, it is necessary to strengthen further the capacity training of information to improve their clinical information decision-making ability and better serve patients.

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POS1015 ANTI-TNF DRUGS AND CARDIOVASCULAR EVENTS IN PATIENTS WITH SPONDYLOARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.4133 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 775.2-776

Author(s):

C. W. S. Chan ◽

P. H. LI ◽

C. S. Lau ◽

H. Y. Chung

Keyword(s):

Risk Factors ◽

Psoriatic Arthritis ◽

Cardiovascular Events ◽

Clinical Information ◽

Incidence Rates ◽

Major Adverse Cardiovascular Events ◽

Cross Sectional ◽

Cerebrovascular Events ◽

Cardiovascular Morbidity And Mortality

Background:Cardiovascular (CVS) diseases are the leading cause of death worldwide and patients with rheumatic diseases have an increased CVS risk including stroke and myocardial infarction (MI) (1-3). CVS risk factors and CVS events are common in SpA (4). Delineating the CVS risk and the association with medications in patients with SpA would be useful.Objectives:The objective of this study was to delineate the CVS risk and the association with medications in patients with SpA.Methods:Patients with SpA and patients with non-specific back pain (NSBP) were identified in rheumatology and orthopedics clinics respectively. Clinical information and CVS events were retrieved. Incidence rates were calculated. Association analysis was performed to determine the CVS risk of SpA and other modifiable risk factors.Results:A total of 5046 patients (SpA 2616 and NSBP 2430) were included from eight centers. Over 56 484 person-years of follow-up, 160 strokes, 84 MI and 262 major adverse cardiovascular events (MACE) were identified. Hypercholesterolemia was more prevalent in SpA (SpA 34.2%, NSBP 28.7%, P<0.01). Crude incidence rates of stroke and MI were higher in SpA patients. SpA was associated with a higher risk of MACE (HR 1.66, 95%CI 1.22-2.27, P<0.01) and cerebrovascular events (HR 1.42, 95%CI 1.01-2.00, p=0.04). The use of anti-tumor necrosis factor (TNF) drugs was associated with a reduced risk of MACE (HR 0.37, 95%CI 0.17-0.80, P=0.01) and cerebrovascular events (HR 0.21, 95%CI 0.06-0.78, P=0.02).Conclusion:SpA is an independent CVS risk factor. Anti-TNF drugs were associated with a reduced CVS risk in these patients.References:[1]Crowson CS, Liao KP, Davis JM, 3rd, Solomon DH, Matteson EL, Knutson KL, et al. Rheumatoid arthritis and cardiovascular disease. Am Heart J. 2013;166(4):622-8 e1.[2]Verhoeven F, Prati C, Demougeot C, Wendling D. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine. 2020;87(5):413-8.[3]Liew JW, Ramiro S, Gensler LS. Cardiovascular morbidity and mortality in ankylosing spondylitis and psoriatic arthritis. Best Pract Res Clin Rheumatol. 2018;32(3):369-89.[4]Molto A, Etcheto A, van der Heijde D, Landewe R, van den Bosch F, Bautista Molano W, et al. Prevalence of comorbidities and evaluation of their screening in spondyloarthritis: results of the international cross-sectional ASAS-COMOSPA study. Ann Rheum Dis. 2016;75(6):1016-23.Disclosure of Interests:None declared.

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The trends of complementary alternative medicine use among cancer patients

BMC Complementary Medicine and Therapies ◽

10.1186/s12906-021-03338-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Abdul Rahman Jazieh ◽

Khadega A. Abuelgasim ◽

Husam I. Ardah ◽

Mohammad Alkaiyat ◽

Omar B. Da’ar

Keyword(s):

Alternative Medicine ◽

Cancer Patients ◽

Clinical Information ◽

Cross Sectional Study ◽

Complementary Alternative Medicine ◽

Cultural Changes ◽

Cross Sectional ◽

Patients With Cancer ◽

Cam Use ◽

The Individual

Abstract Background The use of complementary and alternative medicine (CAM) is common among cancer patients and it may reflect the individual and societal beliefs on cancer therapy. Our study aimed to evaluate the trends of CAM use among patients with cancer between 2006 and 2018. Methods We included 2 Cohorts of patients with cancer who were recruited for Cohort 1 between 2006 and 2008 and for Cohort 2 between 2016 and 2018. The study is a cross-sectional study obtaining demographic and clinical information and inquiring about the types of CAM used, the reasons to use them and the perceived benefits. We compared the changes in the patterns of CAM use and other variables between the two cohorts. Results A total of 1416 patients were included in the study, with 464 patients in Cohort 1 and 952 patients in Cohort 2. Patients in Cohort 2 used less CAM (78.9%) than Cohort 1 (96.8%). Cohort 1 was more likely to use CAM to treat cancer compared to Cohort 2 (84.4% vs. 73%, respectively, p < 0.0001,); while Cohort 2 used CAM for symptom management such as pain control and improving appetite among others. Disclosure of CAM use did not change significantly over time and remains low (31.6% in Cohort 1 and 35.7% for Cohort 2). However, physicians were more likely to express an opposing opinion against CAM use in Cohort 2 compared to Cohort 1 (48.7% vs. 19.1%, p < 0.001, respectively). Conclusion There is a significant change in CAM use among cancer patients over the decade, which reflects major societal and cultural changes in this population. Further studies and interventions are needed to improve the disclosure to physicians and to improve other aspects of care to these patients.

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