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.

scholarly journals What is the clinical impact of cerebrospinal fluid biomarkers on final diagnosis and management in patients with mild cognitive impairment in clinical practice? Results from a nation-wide prospective survey in France

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e026380 ◽  
Author(s):  
Emmanuel Cognat ◽  
François Mouton Liger ◽  
Anne-Cécile Troussière ◽  
David Wallon ◽  
Julien Dumurgier ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Clinical Practice ◽  
Mild Cognitive Impairment ◽  
Final Diagnosis ◽  
National Database ◽  
Csf Biomarkers ◽  
Prospective Survey ◽  
Memory Clinics ◽  
The Impact

ObjectivesNew diagnostic criteria for Alzheimer’s disease (AD) include cerebrospinal fluid (CSF) biomarkers that allow diagnosis at the stage of mild cognitive impairment (MCI). However, the impact of CSF biomarkers in MCI populations in clinical practice has been poorly evaluated. The objective of this study is to assess the use and impact in clinical practice of AD CSF biomarkers in French memory clinics.DesignWe performed a nation-wide, prospective survey between March 2012 and September 2014. Data over the same period was extracted from the French National Database (Banque Nationale Alzheimer, BNA) and compared with the results of the survey.Setting29 secondary and tertiary memory clinics in France.ParticipantsClinicians prescribing lumbar puncture (LP) in order to measure AD CSF biomarkers. Clinicians completed a two-part questionnaire for each of their patients undergoing LP.Primary and secondary outcome measuresAssessment of diagnosis, level of confidence before and after CSF biomarkers and impact on management in patients who underwent LP for CSF AD biomarkers in clinical routine.Results977 questionnaires were completed, of which 61 were excluded because of unknown initial/final diagnosis or non-contributory CSF results. Of 916 patients reported, 153 (16.7%) had MCI as the initial diagnosis, of which 51 (33.3%) displayed an AD profile. CSF biomarkers resulted in a change in diagnosis in 44 patients (28.8%). Confidence level significantly increased after LP (8.3±1.4vs 6.73±1.18, p<0.0001), and CSF results modified management in 71/156 patients (46.4%), including 36 (23.5%) enrolled in clinical trials. Comparison of change in diagnosis with the BNA population revealed no difference (32.24%, p=0.4).ConclusionThis nation-wide survey, reflecting clinical practice in French memory clinics, describes the impact of CSF AD biomarkers in patients with MCI in clinical practice.

CFD Modeling for Patient-Specific Analysis of Cerebrospinal Fluid Flow

2007 ◽  
Author(s):  
Alejandro Roldán ◽  
Andrew Wentland ◽  
Oliver Wieben ◽  
Victor Haughton ◽  
Tim Osswald ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Spinal Canal ◽  
Chiari Malformation ◽  
Cfd Modeling ◽  
Patient Specific ◽  
Variable Response ◽  
Cervical Spinal Canal ◽  
Upper Cervical ◽  
The Impact ◽  
Cerebellar Tonsils

Chiari malformations are characterized by the cerebellar tonsils extending into the upper cervical spinal canal. Many patients with Chiari malformation experience headaches or develop a cyst in the spinal cord inferior to the cerebellar tonsils. Some symptomatic patients benefit from a surgical procedure to enlarge the foramen magnum and others do not. The causes of symptoms and variable response to surgery remain unknown. Imaging studies have shown that patients with a Chiari malformation exhibit increased cerebrospinal fluid (CSF) velocities compared to subjects without the malformation. Improved methods of analyzing the CSF fluid dynamics are needed to evaluate the impact of increased fluid velocities on pressure differentials in the upper cervical spinal canal and the potential impact of surgery on flow dynamics in patient specific geometries.

scholarly journals 0057 Actigraphy-Based Circadian Measures and Cerebrospinal Fluid Biomarkers of Neurodegeneration in Alzheimer’s Disease with Mild Cognitive Impairment

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A23-A23
Author(s):  
R Mehra ◽  
R Bhambra ◽  
J Bena ◽  
L Bekris ◽  
J Leverenz ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Significance Level ◽  
Unit Increase ◽  
T Tau ◽  
Age And Sex

Abstract Introduction Although recent data implicates sleep and circadian disruption to neurodegeneration in Alzheimer’s Disease (AD), the association of objective circadian biomarkers and neurodegeneration remains understudied. We hypothesize that actigraphy-based circadian measures are associated with cerebrospinal fluid (CSF) biomarkers of neurodegeneration in those mild cognitive impairment due to AD (MCI-AD). Methods Eighteen patients with CSF biomarker-confirmed MCI-AD underwent actigraphy monitoring generating the following circadian measures: amplitude, F-ratio and mesor and morning collection of CSF biomarkers of neurodegeneration (Aβ42,t-tau,p-tau). Linear models were used to evaluate the association of circadian and CSF measures; logarithmic transformations were performed on neurodegenerative markers for greater normality. Analysis was performed using SAS software. A significance level of 0.05 was assumed for all tests. Results Eighteen MCI-AD patients who were 68± 6.2 years, 44% female, with median AHI=12 and underwent actigraphy monitoring for 8.2+/-3.2 days were included. There was no significant association of circadian measures and Aβ42 nor with mesor and neurodegeneration biomarkers. Amplitude was associated with both p-tau and t-tau, such that each 10 unit increase in amplitude resulted in a predicted increase in p-tau of 8% (95% CI:1%-15%, p=0.018) and an increase of 13% (3%-23%; p=0.01) in t-tau. F-ratio was positively associated with p-tau and t-tau; each 1000 unit increase in F-ratio resulted in a predicted 12% (4%-22%; p=0.007) increase in P-tau and 20%(6%-35%; p=0.005) increase in t-tau. Associations of these circadian measures and CSF levels of p-tau and t-tau remained statistically significant after adjustment for age and sex. Conclusion Among patients with symptomatic MCI stages of AD, objective measures of circadian rhythm disruption are associated with CSF-based biomarkers of neurodegeneration even after consideration of age and sex. Future investigation should clarify directionality of this association and potential utility of circadian-based interventions in the mitigation of AD progression. Support N/A

scholarly journals Association of amyloid-β CSF/PET discordance and tau load 5 years later

Neurology ◽  
2020 ◽  
Vol 95 (19) ◽  
pp. e2648-e2657 ◽  
Author(s):  
Juhan Reimand ◽  
Lyduine Collij ◽  
Philip Scheltens ◽  
Femke Bouwman ◽  
Rik Ossenkoppele ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amyloid Β ◽  
Csf Biomarkers ◽  
Tau Pathology ◽  
Cognitively Normal ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Tau Pet

ObjectiveTo investigate the association between discordant β-amyloid (Aβ) PET and CSF biomarkers at baseline and the emergence of tau pathology 5 years later.MethodsWe included 730 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants without dementia (282 cognitively normal, 448 mild cognitive impairment) with baseline [18F]florbetapir PET and CSF Aβ42 available. Aβ CSF/PET status was determined at baseline using established cutoffs. Longitudinal data were available for [18F]florbetapir (Aβ) PET (baseline to 4.3 ± 1.9 years), CSF (p)tau (baseline to 2.0 ± 0.1 years), cognition (baseline to 4.3 ± 2.0 years), and [18F]flortaucipir (tau) PET (measured 5.2 ± 1.2 years after baseline to 1.6 ± 0.7 years later). We used linear mixed modeling to study the association between Aβ CSF/PET status and tau pathology measured in CSF or using PET. We calculated the proportion of CSF+/PET− participants who during follow-up (1) progressed to Aβ CSF+/PET+ or (2) became tau-positive based on [18F]flortaucipir PET.ResultsAβ CSF+/PET+ (n = 318) participants had elevated CSF (p)tau levels and worse cognitive performance at baseline, while CSF+/PET− (n = 80) participants were overall similar to the CSF−/PET− (N = 306) group. Five years after baseline, [18F]flortaucipir PET uptake in the CSF+/PET− group (1.20 ± 0.13) did not differ from CSF−/PET− (1.18 ± 0.08, p = 0.69), but was substantially lower than CSF+/PET+ (1.48 ± 0.44, p < 0.001). Of the CSF+/PET− participants, 21/64 (33%) progressed to Aβ CSF+/PET+, whereas only one (3%, difference p < 0.05) became tau-positive based on [18F]flortaucipir PET.ConclusionsAβ load detectable by both CSF and PET seems to precede substantial tau deposition. Compared to participants with abnormal Aβ levels on both PET and CSF, the CSF+/PET− group has a distinctly better prognosis.

scholarly journals Cerebrospinal fluid profiles with increasing number of cerebral microbleeds in a continuum of cognitive impairment

2015 ◽  
Vol 36 (3) ◽  
pp. 621-628 ◽  
Author(s):  
Sara Shams ◽  
Tobias Granberg ◽  
Juha Martola ◽  
Xiaozhen Li ◽  
Mana Shams ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Serum Albumin ◽  
Amyloid Β ◽  
Cerebral Microbleeds ◽  
Csf Biomarkers ◽  
Barrier Dysfunction ◽  
T Tau

Cerebral microbleeds (CMBs) are hypothesised to have an important yet unknown role in the dementia disease pathology. In this study we analysed increasing number of CMBs and their independent associations with routine cerebrospinal fluid (CSF) biomarkers in a continuum of cognitive impairment. A total of 1039 patients undergoing dementia investigation were analysed and underwent lumbar puncture, and an MRI scan. CSF samples were analysed for amyloid β (Aβ) 42, total tau (T-tau), tau phosphorylated at threonine 18 (P-tau) and CSF/serum albumin ratios. Increasing number of CMBs were independently associated with low Aβ42 levels, in the whole cohort, Alzheimer’s disease and mild cognitive impairment ( p < 0.05). CSF/serum albumin ratios were high with multiple CMBs ( p < 0.001), reflecting accompanying blood–brain barrier dysfunction. T-tau and P-tau levels were lower in Alzheimer’s patients with multiple CMBs when compared to zero CMBs, but did not change in the rest of the cohort. White matter hyperintensities were associated with low Aβ42 in the whole cohort and Alzheimer’s disease ( p < 0.05). Aβ42 is the routine CSF-biomarker mainly associated with CMBs in cognitive impairment, and there is an accumulative effect with increasing number of CMBs.

scholarly journals Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease in the Era of Disease-Modifying Treatments

2021 ◽  
Vol 11 (10) ◽  
pp. 1258
Author(s):  
George P. Paraskevas ◽  
Elisabeth Kapaki
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Small Vessel Disease ◽  
Lewy Bodies ◽  
Plaque Burden ◽  
Csf Biomarkers ◽  
Β Amyloid ◽  
Disease Modifying

Correct in vivo diagnosis of Alzheimer’s disease (AD) helps to avoid administration of disease-modifying treatments in non-AD patients, and allows the possible use of such treatments in clinically atypical AD patients. Cerebrospinal fluid (CSF) biomarkers offer a tool for AD diagnosis. A reduction in CSF β-amyloid (marker of amyloid plaque burden), although compatible with Alzheimer’s pathological change, may also be observed in other dementing disorders, including vascular cognitive disorders due to subcortical small-vessel disease, dementia with Lewy bodies and normal-pressure hydrocephalus. Thus, for the diagnosis of AD, an abnormal result of CSF β-amyloid may not be sufficient, and an increase in phospho-tau (marker of tangle pathology) is also required in order to confirm AD diagnosis in patients with a typical amnestic presentation and reveal underlying AD in patients with atypical or mixed and diagnostically confusing clinical presentations.

Neuroimaging and fluid biomarkers of Alzheimer’s disease

2020 ◽  
pp. 9-20
Author(s):  
Vijay R Varma ◽  
Yi-Fang Chuang ◽  
Madhav Thambisetty
Keyword(s):  
Public Health ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Evidence Base ◽  
Clinical Settings ◽  
Global Public Health ◽  
Public Health Challenges

Neuroimaging and fluid biomarkers have revolutionized the way we define Alzheimer’s disease (AD), identify at-risk individuals, diagnose those with symptoms, and may eventually enable us to treat patients in the earliest stages of the disease. We review advances in imaging the principal pathological hallmarks and functional perturbations in the AD brain and map progress in identifying cerebrospinal fluid and blood biomarkers of AD. Together, these modalities have provided invaluable insights into the evolution of AD decades before the onset of cognitive impairment. While they have been rapidly adopted into clinical settings, the evidence base for this remains contested. However, the clear value of neuroimaging and fluid biomarkers is in their relevance to clinical trials and the recruitment of individuals who perceive themselves to be at sufficiently high risk to warrant joining research studies testing experimental AD treatments. This marks a paradigm shift in our efforts to overcome one of the global public health challenges of our time.

scholarly journals Influence of APOE Genotype on Alzheimer’s Disease CSF Biomarkers in a Spanish Population

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
J. A. Monge-Argilés ◽  
R. Gasparini-Berenguer ◽  
M. Gutierrez-Agulló ◽  
C. Muñoz-Ruiz ◽  
J. Sánchez-Payá ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Apoe Genotype ◽  
Amnestic Mild Cognitive Impairment ◽  
Spanish Population ◽  
Csf Biomarkers ◽  
Csf Levels

Objectives. To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer’s disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population.Material and Methods. The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aβratios were obtained. ANOVA and adjusted odds ratios were calculated.Results. We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status.Conclusions. APOE status influences CSF AD variables. However, the presence of APOEε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

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