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 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 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 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.

scholarly journals Statistically Derived Subtypes and Associations with Cerebrospinal Fluid and Genetic Biomarkers in Mild Cognitive Impairment: A Latent Profile Analysis

2017 ◽  
Vol 23 (7) ◽  
pp. 564-576 ◽  
Author(s):  
Joel S. Eppig ◽  
Emily C. Edmonds ◽  
Laura Campbell ◽  
Mark Sanderson-Cimino ◽  
Lisa Delano-Wood ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Latent Profile Analysis ◽  
Profile Analysis ◽  
Diagnostic Methods ◽  
Csf Biomarkers ◽  
Latent Profile

AbstractObjectives: Research demonstrates heterogeneous neuropsychological profiles among individuals with mild cognitive impairment (MCI). However, few studies have included visuoconstructional ability or used latent mixture modeling to statistically identify MCI subtypes. Therefore, we examined whether unique neuropsychological MCI profiles could be ascertained using latent profile analysis (LPA), and subsequently investigated cerebrospinal fluid (CSF) biomarkers, genotype, and longitudinal clinical outcomes between the empirically derived classes. Methods: A total of 806 participants diagnosed by means of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) MCI criteria received a comprehensive neuropsychological battery assessing visuoconstructional ability, language, attention/executive function, and episodic memory. Test scores were adjusted for demographic characteristics using standardized regression coefficients based on “robust” normal control performance (n=260). Calculated Z-scores were subsequently used in the LPA, and CSF-derived biomarkers, genotype, and longitudinal clinical outcome were evaluated between the LPA-derived MCI classes. Results: Statistical fit indices suggested a 3-class model was the optimal LPA solution. The three-class LPA consisted of a mixed impairment MCI class (n=106), an amnestic MCI class (n=455), and an LPA-derived normal class (n=245). Additionally, the amnestic and mixed classes were more likely to be apolipoprotein e4+ and have worse Alzheimer’s disease CSF biomarkers than LPA-derived normal subjects. Conclusions: Our study supports significant heterogeneity in MCI neuropsychological profiles using LPA and extends prior work (Edmonds et al., 2015) by demonstrating a lower rate of progression in the approximately one-third of ADNI MCI individuals who may represent “false-positive” diagnoses. Our results underscore the importance of using sensitive, actuarial methods for diagnosing MCI, as current diagnostic methods may be over-inclusive. (JINS, 2017, 23, 564–576)

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 Obstructive sleep apnea and Alzheimer’s disease-related cerebrospinal fluid biomarkers in mild cognitive impairment

SLEEP ◽  
2020 ◽  
Author(s):  
Mónica Díaz-Román ◽  
Matias M Pulopulos ◽  
Miguel Baquero ◽  
Alicia Salvador ◽  
Ana Cuevas ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Obstructive Sleep Apnea ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Sleep Apnea ◽  
Apnea Hypopnea Index ◽  
Obstructive Sleep ◽  
T Tau

Abstract Previous studies have demonstrated that sleep-breathing disorders, and especially obstructive sleep apnea (OSA), can be observed in patients with a higher risk of progression to Alzheimer’s disease (AD). Recent evidence indicates that cerebrospinal fluid (CSF) AD-biomarkers are associated with OSA. In this study, we investigated these associations in a sample of patients with mild cognitive impairment (MCI), a condition that is considered the first clinical phase of AD, when patients showed biomarkers consistent with AD pathology. A total of 57 patients (mean age = 66.19; SD = 7.13) with MCI were included in the study. An overnight polysomnography recording was used to assess objective sleep parameters (i.e. apnea/hypopnea index [AHI], total sleep time, sleep efficiency, sleep latency, arousal index, awakening, stage 1, 2, and slow-wave sleep and rapid eye movement sleep, periodic limb movement index, O2 saturation during sleep, and percentage of time O2 saturation &lt;90%). Phosphorylated-tau (P-tau), total-tau (T-tau), and amyloid-beta 42 (Aβ42) were measured in CSF. Unadjusted correlation analyses showed that a higher AHI (reflecting higher OSA severity) was related to higher P-tau and T-tau (both results remained significant after Bonferroni correction, p = 0.001). Importantly, these associations were observed even after adjusting for potential confounders (i.e. age, sex, body mass index, sleep medication, smoking, hypertension, and heart disease). Although more research is needed to establish a causal link, our findings provide evidence that OSA could be related to the pathophysiological mechanisms involved in neurodegeneration in MCI patients.

scholarly journals Unique Sleep and Circadian Rhythm Dysfunction Neuroinflammatory and Immune Profiles in Alzheimer’s Disease with Mild Cognitive Impairment

2021 ◽  
pp. 1-6
Author(s):  
Jagan A. Pillai ◽  
James Bena ◽  
Lynn M. Bekris ◽  
Nancy Foldvary-Schaefer ◽  
Catherine Heinzinger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Circadian Rhythm ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cerebrospinal Fluid Biomarkers ◽  
Circulating Markers

Sleep dysfunction has been identified in the pathophysiology of Alzheimer’s disease (AD); however, the role and mechanism of circadian rhythm dysfunction is less well understood. In a well-characterized cohort of patients with AD at the mild cognitive impairment stage (MCI-AD), we identify that circadian rhythm irregularities were accompanied by altered humoral immune responses detected in both the cerebrospinal fluid and plasma as well as alterations of cerebrospinal fluid biomarkers of neurodegeneration. On the other hand, sleep disruption was more so associated with abnormalities in circulating markers of immunity and inflammation and decrements in cognition.

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