scholarly journals Currently Available Biomarkers and Strategies for the Validation of Novel Candidates for Neurochemical Dementia Diagnostics in Alzheimer’s Disease and Mild Cognitive Impairment

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Piotr Lewczuk
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Symptoms ◽  
Tau Proteins ◽  
Csf Biomarkers ◽  
General Acceptance ◽  
Diagnostic Role ◽  
Dementia Diagnostics

The number of people afflicted with Alzheimer’s disease (AD) and other types of dementing conditions has grown exponentially in the last decades. This review focuses on the diagnostic role of the classic cerebrospinal fluid (CSF) biomarkers of neurochemical dementia diagnostics (NDD) and critically discusses potential strategies for the development and validation of novel potential candidates. In some countries, NDD is already established as a routine diagnostic tool, used for the evaluation of patients with cognitive impairments. On the other hand, preanalytical and technical issues, partly discussed in this paper, prevent NDD from the general acceptance worldwide. Currently, two groups of biomarkers in the CSF are considered in NDD: amyloid β (Aβ) peptides and Tau proteins, including the hyperphosphorylated forms of the latter (pTau). The analyses of these two groups of biomarkers can reveal pathologic alterations as early as twenty years before the onset of clinical symptoms. In mild cognitive impairment (MCI), NDD can reliably predict which individuals are at risk of converting to AD. The roles of biomarkers of amyloid β deposition in the brain tissue (including the CSF concentration of Aβ42) and biomarkers of neurodegeneration (including the CSF concentrations of Tau/pTau proteins) are reflected in the currently proposed diagnostic criteria for AD and MCI.

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 Independent morphological variables correlate with Aging, Mild Cognitive Impairment, and Alzheimer's Disease

2022 ◽  
Author(s):  
Fernanda Hansen Pacheco de Moraes ◽  
Felipe Sudo ◽  
Marina Monteiro Carneiro ◽  
Bruno R. P. de Melo ◽  
Paulo Mattos ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cortical Thickness ◽  
Healthy Aging ◽  
Brain Morphology ◽  
Elderly Subjects ◽  
Csf Biomarkers ◽  
Morphological Criteria

This manuscript presents a study with recruited volunteers that comprehends three sorts of events present in Alzheimer's Disease (AD) evolution (structural, biochemical, and cognitive) to propose an update in neurodegeneration biomarkers for AD. The novel variables, K, I, and S, suggested based on physics properties and empirical evidence, are defined by power-law relations between cortical thickness, exposed and total area, and natural descriptors of brain morphology. Our central hypothesis is that variable K, almost constant in healthy human subjects, is a better discriminator of a diseased brain than the current morphological biomarker, Cortical Thickness, due to its aggregated information. We extracted morphological features from 3T MRI T1w images of 123 elderly subjects: 77 Healthy Cognitive Unimpaired Controls (CTL), 33 Mild Cognitive Impairment (MCI) patients, and 13 Alzheimer's Disease (AD) patients. Moreover, Cerebrospinal Fluid (CSF) biomarkers and clinical data scores were correlated with K, intending to characterize health and disease in the cortex with morphological criteria and cognitive-behavioral profiles. K distinguishes Alzheimer's Disease, Mild Cognitive Impairment, and Healthy Cognitive Unimpaired Controls globally and locally with reasonable accuracy (CTL-AD, 0.82; CTL-MCI, 0.58). Correlations were found between global and local K associated with clinical behavioral data (executive function and memory assessments) and CSF biomarkers (t-Tau, Aβ-40, and Aβ-42). The results suggest that the cortical folding component, K, is a premature discriminator of healthy aging, Mild Cognitive Impairment, and Alzheimer's Disease, with significant differences within diagnostics. Despite the non-concomitant events, we found correlations between brain structural degeneration (K), cognitive tasks, and biochemical markers.

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 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 Specific EEG Changes Associated with Atrophy of Hippocampus in Subjects with Mild Cognitive Impairment and Alzheimer's Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
D. V. Moretti ◽  
A. Prestia ◽  
C. Fracassi ◽  
G. Binetti ◽  
O. Zanetti ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Hippocampal Atrophy ◽  
Power Ratio ◽  
Relative Power ◽  
Diagnostic Role ◽  
Eeg Changes

We evaluated the association between hippocampal atrophy and increase of the EEG markers alpha3/alpha2 relative power ratio in mild cognitive impairment (MCI) and Alzheimer's disease patients. Seventy-nine subjects with MCI and 11 patients with AD underwent EEG recording and MRI scan. The MCI group was subdivided in three subgroups according to growing hippocampal atrophy. The groups were characterized by alpha3/alpha2 relative power ratio. In AD patients group mapped hippocampal regions were computed and related with alpha3/alpha2 power ratio. Results show that the increase of alpha3/alpha2 power ratio is correlated with atrophy of hippocampus both in MCI and in Alzheimer's disease patients. This finding confirms the possible diagnostic role of EEG markers as diagnostic and prognostic factors in patient with prodromal and declared Alzheimer's disease.

scholarly journals CSF Biomarkers in Prediction of Cerebral and Clinical Change in Mild Cognitive Impairment and Alzheimer's Disease

2010 ◽  
Vol 30 (6) ◽  
pp. 2088-2101 ◽  
Author(s):  
A. M. Fjell ◽  
K. B. Walhovd ◽  
C. Fennema-Notestine ◽  
L. K. McEvoy ◽  
D. J. Hagler ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Csf Biomarkers ◽  
Clinical Change

scholarly journals Early MCI-to-AD Conversion Prediction Using Future Value Forecasting of Multimodal Features

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Sidra Minhas ◽  
Aasia Khanum ◽  
Atif Alvi ◽  
Farhan Riaz ◽  
Shoab A. Khan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Clinical Symptoms ◽  
Piecewise Linear ◽  
Support Vector ◽  
Standard Support Vector Machine ◽  
Multimodal Features ◽  
The Future

In Alzheimer’s disease (AD) progression, it is imperative to identify the subjects with mild cognitive impairment before clinical symptoms of AD appear. This work proposes a technique for decision support in identifying subjects who will show transition from mild cognitive impairment (MCI) to Alzheimer’s disease (AD) in the future. We used robust predictors from multivariate MRI-derived biomarkers and neuropsychological measures and tracked their longitudinal trajectories to predict signs of AD in the MCI population. Assuming piecewise linear progression of the disease, we designed a novel weighted gradient offset-based technique to forecast the future marker value using readings from at least two previous follow-up visits. Later, the complete predictor trajectories are used as features for a standard support vector machine classifier to identify MCI-to-AD progressors amongst the MCI patients enrolled in the Alzheimer’s disease neuroimaging initiative (ADNI) cohort. We explored the performance of both unimodal and multimodal models in a 5-fold cross-validation setup. The proposed technique resulted in a high classification AUC of 91.2% and 95.7% for 6-month- and 1-year-ahead AD prediction, respectively, using multimodal markers. In the end, we discuss the efficacy of MRI markers as compared to NM for MCI-to-AD conversion prediction.

Sign in / Sign up

Export Citation Format

Share Document