scholarly journals Cerebrospinal Fluid Biomarkers for the Diagnosis of Prodromal Alzheimer’s Disease in Amnestic Mild Cognitive Impairment

2019 ◽  
Vol 9 (1) ◽  
pp. 100-113 ◽  
Author(s):  
Jung Eun Park ◽  
Kyu Yeong Choi ◽  
Byeong C. Kim ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Tau Protein ◽  
Amnestic Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Cutoff Values ◽  
Prodromal Ad ◽  
T Tau

Background/Aims: Disease-modifying therapy for Alzheimer’s disease (AD) has led to a need for biomarkers to identify prodromal AD and very early stage of AD dementia. We aimed to identify the cutoff values of cerebrospinal fluid (CSF) biomarkers for detecting prodromal AD. Methods: We assessed 56 patients with amnestic mild cognitive impairment (aMCI) who underwent lumbar puncture. Additionally, 87 healthy elderly individuals and 34 patients with AD dementia served as controls. Positron emission tomography was performed using florbetaben as a probe. We analyzed the concentration of Aβ1–42, total tau protein (t-Tau), and tau protein phosphorylated at threonine 181 (p-Tau181) in CSF with INNOTEST enzyme-linked immunosorbent assay. Results: For the detection of prodromal AD in patients with aMCI, the cutoff values of CSF Aβ1–42, t-Tau, and p-Tau181 were 749.5 pg/mL, 225.6 pg/mL, and 43.5 pg/mL, respectively. To discriminate prodromal AD in patients with aMCI, the t-Tau/Aβ1–42 and ­p-Tau181/Aβ1–42 ratios defined cutoff values at 0.298 and 0.059, respectively. Conclusions: CSF biomarkers are very useful tools for the differential diagnosis of prodromal AD in aMCI patients. The concentration of CSF biomarkers is well correlated with the stages of the AD spectrum.

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 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.

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.

Usefulness of CSF Biomarkers in Predicting the Progression of Amnesic and Nonamnesic Mild Cognitive Impairment to Alzheimer’s Disease

2019 ◽  
Vol 12 (1) ◽  
pp. 35-42
Author(s):  
Ricard L. Ortega ◽  
Farida Dakterzada ◽  
Alfonso Arias ◽  
Ester Blasco ◽  
Alba Naudí ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Prodromal Phase ◽  
Diagnosis And Prognosis ◽  
Amnestic Mci ◽  
Atypical Presentations ◽  
T Tau

Objective: The aim of this study was to investigate the usefulness of Alzheimer’s disease Cerebrospinal Fluid (CSF) biomarkers in predicting the progression to dementia in patients with Mild Cognitive Impairment (MCI). Methods: One hundred and thirteen patients were consecutively recruited from April 2012 to April 2014. Measurement of CSF biomarkers (amyloid-β42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau)) and a neuropsychological evaluation were performed for all patients. We categorized patients with MCI as A+A- and N+N- based on the presence/absence of amyloid pathology and neurodegeneration, respectively. Results: Of 72 patients with MCI, 26 (36%) progressed to dementia. These patients had lower CSF Aβ42 levels and higher p-tau and t-tau levels at baseline. The proportion that progressed to dementia was 14.3% (2/14), 36.8% (7/19), 66.7% (4/6) and 75% (12/16) in the A-N-, A+N-, A-N+ (SNAP), and A+N+ patients, respectively (p < 0.05). There were significant differences in the probability of progression from amnestic MCI (aMCI) to AD between the A+N+ and A-N- patients (OR = 8.1, 95% CI 1.5-42.3, p = 0.001) but not between SNAP (OR = 7.3, 95% CI 0.9-61, p = 0.02) or A+N- (OR = 2.1, 95% CI 0.4 to 10.4, p = 0.15) patients compared to the A-N- subgroup. None of the biomarker profiles of the subgroups predicted the time until the progression to AD. Conclusion: The use of CSF AD biomarkers in clinical practice improves the certainty of diagnosis and prognosis of patients, especially in patients in the prodromal phase or in patients with atypical presentations.

scholarly journals Clinical and biological predictors of Alzheimer's disease in patients with amnestic mild cognitive impairment

2010 ◽  
Vol 32 (3) ◽  
pp. 216-222 ◽  
Author(s):  
Orestes V. Forlenza ◽  
Breno S. Diniz ◽  
Leda L. Talib ◽  
Marcia Radanovic ◽  
Monica S. Yassuda ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Amnestic Mild Cognitive Impairment ◽  
Total Tau ◽  
Cerebrospinal Fluid Biomarkers ◽  
Antidementia Drugs ◽  
Beta Peptide

OBJECTIVE: To identify predictors of the progression from pre-dementia stages of cognitive impairment in Alzheimer's disease is relevant to clinical management and to substantiate the decision of prescribing antidementia drugs. METHOD: Longitudinal study of a cohort of elderly adults with amnestic mild cognitive impairment and healthy controls, carried out to estimate the risk and characterize predictors of the progression to Alzheimer's disease. RESULTS: Patients with amnestic mild cognitive impairment had a higher risk to develop Alzheimer's disease during follow-up (odds ratio = 4.5, CI95% [1.3-13.6], p = 0.010). At baseline, older age, lower scores on memory tests and presence of the APOE*4 allele predicted the progression from amnestic mild cognitive impairment to Alzheimer's disease. In a sub sample of amnestic mild cognitive impairment patients, those who progressed to Alzheimer's disease had lower cerebrospinal fluid concentrations of amyloid-beta peptide (Aβ42, p = 0.020) and higher concentrations of total TAU (p = 0.030) and phosphorylated TAU (p = 0.010), as compared to non-converters. DISCUSSION: This is the first Brazilian study to report cerebrospinal fluid biomarkers in the prediction of the conversion from MCI to Alzheimer's disease. Our data are in accordance with those reported in other settings. The measurement of cerebrospinal fluid total-TAU, phospho-TAU and Aβ42 may help identify patients with mild cognitive impairment at higher risk for developing Alzheimer's disease.

scholarly journals Cerebrospinal Fluid Biomarkers and Prediction of Conversion in Patients with Mild Cognitive Impairment: 4-Year Follow-Up in a Routine Clinical Setting

2009 ◽  
Vol 9 ◽  
pp. 961-966 ◽  
Author(s):  
Alessia Lanari ◽  
Lucilla Parnetti
Keyword(s):  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Setting ◽  
Cognitive Disorders ◽  
Correct Prediction ◽  
Csf Biomarkers ◽  
Routine Clinical Setting ◽  
T Tau

Mild cognitive impairment (MCI) is a very common syndrome in elderly people, with a high risk of conversion to dementia. Several investigations have shown the usefulness of cerebrospinal fluid (CSF) biomarkers (Aβ42, total tau [T-tau], and phosphorylated tau [P-tau]) in predicting the progression to Alzheimer's disease (AD). We report a 4-year follow-up of MCI patients who underwent CSF evaluation for biomarker assessment, in order to further evaluate the usefulness of CSF analysis in predicting the conversion to dementia in a routine clinical setting. We identified 55 patients with MCI among the consecutive patients, referred from 2001 to 2003 to our Memory Clinic for cognitive disorders, who underwent a complete diagnostic assessment, including lumbar puncture (n = 273). At the end of the follow-up, 31 MCI patients (56%) did not progress to dementia (stable MCI), while 24 (44%) developed a dementia condition. At baseline, the mean levels of CSF Aβ42, T-tau, and P-tau were significantly altered in MCI patients who were converting to dementia with respect to those with stable MCI. All MCI patients with the three altered CSF biomarkers developed dementia within 1 year. Among the stable MCI patients, none showed all three pathological values and only one subject had the pathological value of P-tau. Early diagnosis of dementia and, specifically, a correct prediction of MCI outcome represent a primary goal. To this respect, the role of CSF biomarkers seems to be crucial in a routine clinical setting.

scholarly journals Anxiety is related to Alzheimer cerebrospinal fluid markers in subjects with mild cognitive impairment

2012 ◽  
Vol 43 (5) ◽  
pp. 911-920 ◽  
Author(s):  
I. H. G. B. Ramakers ◽  
F. R. J. Verhey ◽  
P. Scheltens ◽  
H. Hampel ◽  
H. Soininen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Β ◽  
Screening Guidelines ◽  
Symptoms Of Depression ◽  
T Tau

BackgroundAnxiety, apathy and depression are common in subjects with mild cognitive impairment (MCI) and may herald Alzheimer's disease (AD). We investigated whether these symptoms correlated with cerebrospinal fluid (CSF) markers for AD in subjects with MCI.MethodSubjects with MCI (n=268) were selected from the ‘Development of screening guidelines and criteria for pre-dementia Alzheimer's disease’ (DESCRIPA) and Alzheimer's Disease Neuroimaging Initiative (ADNI) studies. We measured amyloid β(1-42)protein (Aβ42) and total tau (t-tau) in CSF. Neuropsychiatric symptoms were measured with the Neuropsychiatric Inventory.ResultsDepressive symptoms were reported by 55 subjects (21%), anxiety by 35 subjects (13%) and apathy by 49 subjects (18%). The presence of anxiety was associated with abnormal CSF Aβ42 [odds ratio (OR) 2.3, 95% confidence interval (CI) 1.6–3.3] and t-tau (OR 2.6, 95% CI 1.9–3.6) concentrations and with the combination of abnormal concentrations of both Aβ42 and t-tau (OR 3.1, 95% CI 2.0–4.7). The presence of agitation and irritability was associated with abnormal concentrations of Aβ42 (agitation: OR 1.6, 95% CI 1.1–2.3; irritability: OR 2.2, 95% CI 1.5–3.3). Symptoms of depression and apathy were not related to any of the CSF markers.ConclusionsIn subjects with MCI, symptoms of anxiety, agitation and irritability may reflect underlying AD pathology, whereas symptoms of depression and apathy do not.

Multiple category verbal fluency in mild cognitive impairment and correlation with CSF biomarkers for Alzheimer's disease

2017 ◽  
Vol 29 (6) ◽  
pp. 949-958 ◽  
Author(s):  
Roberta M. Mirandez ◽  
Ivan Aprahamian ◽  
Leda L. Talib ◽  
Orestes V. Forlenza ◽  
Marcia Radanovic
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Verbal Fluency ◽  
Csf Biomarkers ◽  
Healthy Elderly ◽  
Model Animal ◽  
Neuropsychological Evaluations ◽  
T Tau

ABSTRACTBackground:Verbal fluency (VF) tasks are widely used in neuropsychological evaluations, as a measure of executive/semantic dysfunction. The revised criteria for Alzheimer's disease (AD) diagnosis (National Institute on Aging and the Alzheimer Association, 2011) incorporating biomarkers has increased the interest in finding algorithms that combine neuropsychological and biomarkers features to better predict conversion from mild cognitive impairment (MCI) to AD. Our aim was to compare the most frequently used VF categories to determine which best discriminated cognitively healthy elderly from MCI patients, and whether cerebrospinal fluid (CSF) biomarkers levels (Aβ42, P-tau, T-tau, and Aβ42/P-tau) correlated with patient's performance in MCI.Methods:We studied 37 cognitively healthy elderly and 30 MCI patients in five VF tasks (animal, fruits, means of transportation, FAS-COWA, and verbs); 23 controls and 19 MCI patients had their CSF biomarkers for AD determined.Results:MCI group performed worse than controls in all VF tasks (p < 0.0001). The cut-off scores were: 14 (animals) (AUC = 0.794), 12 (fruits and means of transportation) (AUC = 0.740 and 0.719, respectively), 41 (FAS) (AUC = 0.744), and 11 (verbs) (AUC = 0.700). The model “animal plus FAS-COWA” was the best to discriminate both groups (AUC = 0.833) (all p < 0.05). MCI produced fewer words than controls in the second-half of the task for all categories (p < 0.001). T-tau levels were negatively correlated to animal fluency (r= −0.485, p = 0.035), and showed a trend for negative correlation with fruits fluency (r= −0.4429, p = 0.057).Conclusions:Animal fluency alone and combined to FAS-COWA was slightly superior in discriminating controls from MCI (p < 0.001), and correlated to T-tau levels.

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