scholarly journals Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease

2021 ◽  
Author(s):  
Zhenxu Xiao ◽  
Xue Wu ◽  
Wanqing Wu ◽  
Jingwei Yi ◽  
Xiaoniu Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Single Molecule ◽  
Disease Diagnosis ◽  
Clinical Dementia Rating ◽  
Neurofilament Protein ◽  
Cognitive Domains ◽  
Global Cognition ◽  
T Tau

AbstractBackgroundPlasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the association with cognitive domains along the spectrum of cognitive performance deterioration have seldom been reported.MethodsWe recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis of AD, amnestic mild cognitive impairment, and normal cognition (NC). Each participant was administered the neuropsychological tests assessing the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the Single molecule array platform.ResultsAlong with plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, and NfL, p-tau181 significantly increased across the groups with the incremental CDR scores from NC (CDR = 0) to severe AD (CDR = 3). Compared with other biomarkers, p-tau181 had a stronger correlation with Global cognition (r = −0.494, P < 0.001), Memory (r = −0.417, P < 0.001), Attention (r = −0.388, P < 0.001), Visuospatial function (r = −0.328, P < 0.001), and Language (r = −0.123, P = 0.014). Among AD participants with CDR ≥ 1, higher p-tau181 was correlated with worse Global cognition (r = −0.295, P < 0.001), Memory (r = −0.172, P = 0.045), and Attention (r = −0.184, P = 0.031).ConclusionsPlasma p-tau181 had a stronger correlation with cognitive domains than other biomarkers, especially in late-stage AD. It could reflect the AD pathology in vivo and may be a promising blood-based biomarker in clinical settings.

scholarly journals Plasma biomarker profiles and the correlation with cognitive function across the clinical spectrum of Alzheimer’s disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Zhenxu Xiao ◽  
Xue Wu ◽  
Wanqing Wu ◽  
Jingwei Yi ◽  
Xiaoniu Liang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Single Molecule ◽  
Disease Diagnosis ◽  
Clinical Dementia Rating ◽  
Neurofilament Protein ◽  
Cognitive Domains ◽  
Global Cognition ◽  
T Tau

Abstract Background Plasma biomarkers showed a promising value in the disease diagnosis and management of Alzheimer’s disease (AD). However, profiles of the biomarkers and the associations with cognition across a spectrum of cognitive stages have seldom been reported. Methods We recruited 320 individuals with cognitive impairment and 131 cognitively normal participants from a memory clinic and a community cohort. Participants were classified into 6 groups based on their Clinical Dementia Rating (CDR) scores and clinical diagnosis, including AD, amnestic mild cognitive impairment (aMCI), and normal cognition (NC). A battery of neuropsychological tests was used to assess the global and domain-specific cognition. Plasma Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, total tau (t-tau), neurofilament protein light chain (NfL), and phosphorylated tau at threonine 181 (p-tau181) were quantified using the single-molecule array (Simoa) platform. Results All the plasma markers (Aβ1-40, Aβ1-42, Aβ1-42/Aβ1-40, t-tau, NfL, p-tau181) showed certain discrepancies among NC, aMCI, and AD groups. The p-tau181 level showed a continuous escalating trend as the CDR scores increased from 0 (NC group) to 3 (severe AD). Compared with other biomarkers, p-tau181 had correlations with broader cognitive domains, covering global cognition (r = −0.536, P < 0.0001), memory (r = −0.481, P < 0.0001), attention (r = −0.437, P < 0.0001), visuospatial function (r = −0.385, P < 0.0001), and language (r = −0.177, P = 0.0003). Among participants with CDR ≥ 1, higher p-tau181 was correlated with worse global cognition (r = −0.301, P < 0.001). Conclusions Plasma p-tau181 had correlations with broader cognitive domains, suggesting its potential as a promising clinical-relevant blood-based biomarker.

Different cognitive profiles between mild cognitive impairment due to cerebral small vessel disease and mild cognitive impairment of Alzheimer’s disease origin

2009 ◽  
Vol 15 (6) ◽  
pp. 898-905 ◽  
Author(s):  
AIHONG ZHOU ◽  
JIANPING JIA
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Processing Speed ◽  
Small Vessel Disease ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Cognitive Domains ◽  
Vessel Disease

AbstractControversy surrounds the differences of the cognitive profile between mild cognitive impairment resulting from cerebral small vessel disease (MCI-SVD) and mild cognitive impairment associated with prodromal Alzheimer’s disease (MCI-AD). The aim of this study was to explore and compare the cognitive features of MCI-SVD and MCI-AD. MCI-SVD patients (n = 56), MCI-AD patients (n = 30), and normal control subjects (n = 80) were comprehensively evaluated with neuropsychological tests covering five cognitive domains. The performance was compared between groups. Tests that discriminated between MCI-SVD and MCI-AD were identified. Multiple cognitive domains were impaired in MCI-SVD group, while memory and executive function were mainly impaired in MCI-AD group. Compared with MCI-SVD, MCI-AD patients performed relatively worse on memory tasks, but better on processing speed measures. The AVLT Long Delay Free Recall, Digit Symbol Test, and Stroop Test Part A (performance time) in combination categorized 91.1% of MCI-SVD patients and 86.7% of MCI-AD patients correctly. Current study suggested a nonspecific neuropsychological profile for MCI-SVD and a more specific cognitive pattern in MCI-AD. MCI-AD patients demonstrated greater memory impairment with relatively preserved mental processing speed compared with MCI-SVD patients. Tests tapping these two domains might be potentially useful for differentiating MCI-SVD and MCI-AD patients. (JINS, 2009, 15, 898–905.)

scholarly journals The utility of questionnaires in cognitive and functional assessment in Alzheimer's disease

2010 ◽  
Vol 23 (2) ◽  
pp. 333-334
Author(s):  
V M Aziz ◽  
J. Yagoub ◽  
K. Saba ◽  
M. Asaad
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Functional Assessment ◽  
Clinical Picture ◽  
Behavioral Changes ◽  
Cognitive Domains ◽  
Amnesic Syndrome ◽  
Insidious Onset ◽  
Progressive Cognitive Impairment

Alzheimer's disease (AD) manifests clinically with an insidious onset and slow but progressive cognitive impairment. The clinical picture of AD can be classified into cognitive and behavioral changes. The initial deficit usually manifests as an amnesic syndrome which may progress very gradually for several years before impairment in other cognitive domains, such as language, semantic memory and visuospatial function, becomes apparent (Hodges and Patterson, 1995).

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

Performance of Validated MicroRNA Biomarkers for Alzheimer’s Disease in Mild Cognitive Impairment

2020 ◽  
Vol 78 (1) ◽  
pp. 245-263
Author(s):  
Ursula S. Sandau ◽  
Jack T. Wiedrick ◽  
Sierra J. Smith ◽  
Trevor J. McFarland ◽  
Theresa A. Lusardi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Early Stage ◽  
Linear Trend ◽  
Area Under The Curve ◽  
Classification Performance ◽  
T Tau ◽  
Median Expression

Background: Cerebrospinal fluid (CSF) microRNA (miRNA) biomarkers of Alzheimer’s disease (AD) have been identified, but have not been evaluated in prodromal AD, including mild cognitive impairment (MCI). Objective: To assess whether a set of validated AD miRNA biomarkers in CSF are also sensitive to early-stage pathology as exemplified by MCI diagnosis. Methods: We measured the expression of 17 miRNA biomarkers for AD in CSF samples from AD, MCI, and cognitively normal controls (NC). We then examined classification performance of the miRNAs individually and in combination. For each miRNA, we assessed median expression in each diagnostic group and classified markers as trending linearly, nonlinearly, or lacking any trend across the three groups. For trending miRNAs, we assessed multimarker classification performance alone and in combination with apolipoprotein E ɛ4 allele (APOE ɛ4) genotype and amyloid-β42 to total tau ratio (Aβ42:T-Tau). We identified predicted targets of trending miRNAs using pathway analysis. Results: Five miRNAs showed a linear trend of decreasing median expression across the ordered diagnoses (control to MCI to AD). The trending miRNAs jointly predicted AD with area under the curve (AUC) of 0.770, and MCI with AUC of 0.705. Aβ42:T-Tau alone predicted MCI with AUC of 0.758 and the AUC improved to 0.813 (p = 0.051) after adding the trending miRNAs. Multivariate correlation of the five trending miRNAs with Aβ42:T-Tau was weak. Conclusion: Selected miRNAs combined with Aβ42:T-Tau improved classification performance (relative to protein biomarkers alone) for MCI, despite a weak correlation with Aβ42:T-Tau. Together these data suggest that that these miRNAs carry novel information relevant to AD, even at the MCI stage. Preliminary target prediction analysis suggests novel roles for these biomarkers.

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 Novelty detection-based approach for Alzheimer’s disease and mild cognitive impairment diagnosis from EEG

2021 ◽  
Author(s):  
Matous Cejnek ◽  
Oldrich Vysata ◽  
Martin Valis ◽  
Ivo Bukovsky
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Novelty Detection ◽  
Disease Diagnosis ◽  
Eeg Signal ◽  
New Approach ◽  
Activity Assessment ◽  
Adaptive Filtration

AbstractAlzheimer’s disease is diagnosed via means of daily activity assessment. The EEG recording evaluation is a supporting tool that can assist the practitioner to recognize the illness, especially in the early stages. This paper presents a new approach for detecting Alzheimer’s disease and potentially mild cognitive impairment according to the measured EEG records. The proposed method evaluates the amount of novelty in the EEG signal as a feature for EEG record classification. The novelty is measured from the parameters of EEG signal adaptive filtration. A linear neuron with gradient descent adaptation was used as the filter in predictive settings. The extracted feature (novelty measure) is later classified to obtain Alzheimer’s disease diagnosis. The proposed approach was cross-validated on a dataset containing EEG records of 59 patients suffering from Alzheimer’s disease; seven patients with mild cognitive impairment (MCI) and 102 controls. The results of cross-validation yield 90.73% specificity and 89.51% sensitivity. The proposed method of feature extraction from EEG is completely new and can be used with any classifier for the diagnosis of Alzheimer’s disease from EEG records.

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