Neuroimaging Methods for MRI Analysis in CSF Biomarkers Studies

2018 ◽  
pp. 165-184
Author(s):  
Carles Falcon ◽  
Grégory Operto ◽  
José Luis Molinuevo ◽  
Juan Domingo Gispert
Keyword(s):  
Csf Biomarkers

scholarly journals Progression to dementia in memory clinic patients with mild cognitive impairment and normal β-amyloid

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna Rosenberg ◽  
Alina Solomon ◽  
Vesna Jelic ◽  
Göran Hagman ◽  
Nenad Bogdanovic ◽  
...  
Keyword(s):  
Medial Temporal Lobe ◽  
Predictive Performance ◽  
Csf Biomarkers ◽  
Memory Clinic ◽  
Alzheimer Type ◽  
Normal Range ◽  
Medial Temporal Lobe Atrophy ◽  
Dementia Risk ◽  
Β Amyloid ◽  
Lobe Atrophy

Abstract Background Determination of β-amyloid (Aβ) positivity and likelihood of underlying Alzheimer’s disease (AD) relies on dichotomous biomarker cut-off values. Individuals with mild cognitive impairment (MCI) and Aβ within the normal range may still have a substantial risk of developing dementia, primarily of Alzheimer type. Their prognosis, as well as predictors of clinical progression, are not fully understood. The aim of this study was to explore the associations of cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau, phosphorylated tau) and other characteristics, including modifiable vascular factors, with the risk of progression to dementia among patients with MCI and normal CSF Aβ42. Methods Three hundred eighteen memory clinic patients with CSF and clinical data, and at least 1-year follow-up, were included. Patients had normal CSF Aβ42 levels based on clinical cut-offs. Cox proportional hazard models with age as time scale and adjusted for sex, education, and cognition (Mini-Mental State Examination) were used to investigate predictors of progression to dementia and Alzheimer-type dementia. Potential predictors included CSF biomarkers, cognitive performance (verbal learning and memory), apolipoprotein E (APOE) ε4 genotype, medial temporal lobe atrophy, family history of dementia, depressive symptoms, and vascular factors, including the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) risk score. Predictive performance of patient characteristics was further explored with Harrell C statistic. Results Lower normal Aβ42 and higher total tau and phosphorylated tau were associated with higher dementia risk, and the association was not driven by Aβ42 values close to cut-off. Additional predictors included poorer cognition, APOE ε4 genotype, higher systolic blood pressure, and lower body mass index, but not the CAIDE dementia risk score. Aβ42 individually and in combination with other CSF biomarkers improved the risk prediction compared to age and cognition alone. Medial temporal lobe atrophy or vascular factors did not increase the predictive performance. Conclusions Possibility of underlying AD pathology and increased dementia risk should not be ruled out among MCI patients with CSF Aβ42 within the normal range. While cut-offs may be useful in clinical practice to identify high-risk individuals, personalized risk prediction tools incorporating continuous biomarkers may be preferable among individuals with intermediate risk. The role of modifiable vascular factors could be explored in this context.

scholarly journals The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1287
Author(s):  
T. Walter ◽  
Jennifer Iudicello ◽  
Debra Cookson ◽  
Donald Franklin ◽  
Bin Tang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Immune System ◽  
Public Health Problem ◽  
Control Group ◽  
Csf Biomarkers ◽  
Immune System Dysfunction ◽  
Immune Biomarkers ◽  
Plasma Factor ◽  
History Of ◽  
Hiv 1

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = −0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.

scholarly journals Lipid Peroxidation Assessment in Preclinical Alzheimer Disease Diagnosis

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1043
Author(s):  
Carmen Peña-Bautista ◽  
Lourdes Álvarez-Sánchez ◽  
Inés Ferrer ◽  
Marina López-Nogueroles ◽  
Antonio José Cañada-Martínez ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Area Under Curve ◽  
Disease Diagnosis ◽  
Csf Biomarkers ◽  
Preclinical Ad ◽  
Aging Populations ◽  
Advanced Stages ◽  
Preclinical Diagnosis ◽  
T Tau ◽  
And Oxidative Stress

Background: Alzheimer disease (AD) is an increasingly common neurodegenerative disease, especially in countries with aging populations. Its diagnosis is complex and is usually carried out in advanced stages of the disease. In addition, lipids and oxidative stress have been related to AD since the earliest stages. A diagnosis in the initial or preclinical stages of the disease could help in a more effective action of the treatments. Methods: Isoprostanoid biomarkers were determined in plasma samples from preclinical AD participants (n = 12) and healthy controls (n = 31) by chromatography and mass spectrometry (UPLC-MS/MS). Participants were accurately classified according to cerebrospinal fluid (CSF) biomarkers and neuropsychological examination. Results: Isoprostanoid levels did not show differences between groups. However, some of them correlated with CSF biomarkers (t-tau, p-tau) and with cognitive decline. In addition, a panel including 10 biomarkers showed an area under curve (AUC) of 0.96 (0.903–1) and a validation AUC of 0.90 in preclinical AD prediction. Conclusions: Plasma isoprostanoids could be useful biomarkers in preclinical diagnosis for AD. However, these results would require a further validation with an external cohort.

scholarly journals Peripheral Markers of Vascular Endothelial Dysfunction Show Independent but Additive Relationships with Brain-Based Biomarkers in Association with Functional Impairment in Alzheimer’s Disease

2021 ◽  
pp. 1-13
Author(s):  
Jonathan D. Drake ◽  
Alison B. Chambers ◽  
Brian R. Ott ◽  
Lori A. Daiello ◽  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Functional Impairment ◽  
Amyloid Β ◽  
Intercellular Adhesion Molecule ◽  
Csf Biomarkers ◽  
Linear Regression Models ◽  
Cognitively Normal

Background: Cerebrovascular dysfunction confers risk for functional decline in Alzheimer’s disease (AD), yet the clinical interplay of these two pathogenic processes is not well understood. Objective: We utilized Alzheimer’s Disease Neuroimaging Initiative (ADNI) data to examine associations between peripherally derived soluble cell adhesion molecules (CAMs) and clinical diagnostic indicators of AD. Methods: Using generalized linear regression models, we examined cross-sectional relationships of soluble plasma vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-Selectin to baseline diagnosis and functional impairment (clinical dementia rating sum-of-boxes, CDR-SB) in the ADNI cohort (n = 112 AD, n = 396 mild cognitive impairment (MCI), n = 58 cognitively normal). We further analyzed associations of these biomarkers with brain-based AD biomarkers in a subset with available cerebrospinal fluid (CSF) data (n = 351). p-values derived from main effects and interaction terms from the linear regressions were used to assess the relationship between independent and dependent variables for significance (significance level was set at 0.05 a priori for all analysis). Results: Higher mean VCAM-1 (p = 0.0026) and ICAM-1 (p = 0.0189) levels were found in AD versus MCI groups; however, not in MCI versus cognitively normal groups. Only VCAM-1 was linked with CDR-SB scores (p = 0.0157), and APOE ɛ4 genotype modified this effect. We observed independent, additive associations when VCAM-1 and CSF amyloid-β (Aβ 42), total tau, phosphorylated tau (P-tau), or P-tau/Aβ 42 (all <  p = 0.01) were combined in a CDR-SB model; ICAM-1 showed a similar pattern, but to a lesser extent. Conclusion: Our findings indicate independent associations of plasma-based vascular biomarkers and CSF biomarkers with AD-related clinical impairment.

scholarly journals Sex differences in CSF biomarkers for neurodegeneration and blood‐brain barrier integrity

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Tobias Skillbäck ◽  
Kaj Blennow ◽  
Henrik Zetterberg ◽  
Sara Shams ◽  
Alejandra Machado ◽  
...  
Keyword(s):  
Sex Differences ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Csf Biomarkers ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Blood Brain Barrier Integrity

scholarly journals Effect of Patient-Specific Preanalytic Variables on CSF Aβ1–42 Concentrations Measured on an Automated Chemiluminescent Platform

2020 ◽  
Author(s):  
Jacqueline A Darrow ◽  
Amanda Calabro ◽  
Sara Gannon ◽  
Amanze Orusakwe ◽  
Rianne Esquivel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Patient Specific ◽  
Csf Biomarkers ◽  
Clinical Settings ◽  
Blood Contamination ◽  
Gradient Effect ◽  
Β Amyloid ◽  
The Impact ◽  
Gradient Effects

Abstract Background Cerebrospinal fluid (CSF) biomarkers are increasingly used to confirm the accuracy of a clinical diagnosis of mild cognitive impairment or dementia due to Alzheimer disease (AD). Recent evidence suggests that fully automated assays reduce the impact of some preanalytical factors on the variability of these measures. This study evaluated the effect of several preanalytical variables common in clinical settings on the variability of CSF β-amyloid 1–42 (Aβ1–42) concentrations. Methods Aβ1–42 concentrations were measured using the LUMIPULSE G1200 from both freshly collected and frozen CSF samples. Preanalytic variables examined were: (1) patient fasting prior to CSF collection, (2) blood contamination of specimens, and (3) aliquoting specimens sequentially over the course of collection (i.e., CSF gradients). Results Patient fasting did not significantly affect CSF Aβ1–42 levels. While assessing gradient effects, Aβ1–42 concentrations remained stable within the first 5 1-mL aliquots. However, there is evidence of a gradient effect toward higher concentrations over successive aliquots. Aβ1–42 levels were stable when fresh CSF samples were spiked with up to 2.5% of blood. However, in frozen CSF samples, even 0.25% blood contamination significantly decreased Aβ1–42 concentrations. Conclusions The preanalytical variables examined here do not have significant effects on Aβ1–42 concentrations if fresh samples are processed within 2 h. However, a gradient effect can be observed on Aβ1–42 concentrations after the first 5 mL of collection and blood contamination has a significant impact on Aβ1–42 concentrations once specimens have been frozen.

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