scholarly journals Plasma Biomarkers Ascertained With Immunomagnetic Reduction Diagnosing Early-Stage Alzheimer's Disease: A Systematic Review

2020 ◽  
Author(s):  
Pui-Un Tang ◽  
I-Hsieh Wu ◽  
Ian-Hou Lao ◽  
Wai Leong ◽  
Chaur-Jong Hu
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Final Analysis ◽  
Public Health Issue ◽  
Healthy Population ◽  
Control Groups ◽  
Ageing Society ◽  
T Tau

ABSTRACT Introduction Alzheimer's disease (AD) will become a prominent public health issue in the future given its cognitively debilitating nature. As the advent of global ageing society is expected, AD may bring tremendous socioeconomical costs if current diagnosis methods stay put. In this article, we performed a systematic review of a recent (less than 10 years) ultrasensitive technology, the immunomagnetic reduction (IMR), which shows promising potential of early diagnosis of AD. Methods We searched the Pubmed and Embase databases for studies that included keywords “early-stage Alzheimer's disease” and “immunomagnetic signal reduction.” Results After full-text review, a total of 7 studies were included for final analysis. Most included studies have reported on Aβ40, Aβ42, t-tau, and levels of these biomarkers in the plasma of early AD patients comparing those in the healthy population. The ranges of the mean Aβ40 levels are as follows: 59.2 to 60.9 for control groups and 36.9 to 39.5 pg/mL for AD. Aβ42 and t-tau concentrations are both markedly lower than Aβ40, Aβ42 at 15.5 to 16.1 for control groups and 17.9 to 19 pg/mL for AD; t-tau levels were 13.5 to 14.3 for control groups and 39.4 to 46.7 pg/mL for AD. There is a significant increasing level of plasma Aβ42 by IMR assays in early AD patients across nearly all the included studies. There is a possible relationship between plasma levels of IMR AD biomarkers and (1) degree of hippocampal atrophy using magnetic resonance imaging, and (2) amount of brain amyloid accumulation using positron emission tomography. Conclusion IMR assay is an ultrasensitivity technique that is useful for detection of early AD, which can provide benefits on understanding the disease progression of AD and encourage early medical invention for AD patients.

scholarly journals Association between methylation of BIN1 promoter in peripheral blood and preclinical Alzheimer’s disease

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hao Hu ◽  
Lan Tan ◽  
Yan-Lin Bi ◽  
Wei Xu ◽  
Lin Tan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Peripheral Blood ◽  
Late Onset ◽  
Early Stage ◽  
Susceptibility Gene ◽  
Subjective Cognitive Decline ◽  
Preclinical Ad ◽  
T Tau ◽  
New Evidence

AbstractThe bridging integrator 1 (BIN1) gene is the second most important susceptibility gene for late-onset Alzheimer’s disease (LOAD) after apolipoprotein E (APOE) gene. To explore whether the BIN1 methylation in peripheral blood changed in the early stage of LOAD, we included 814 participants (484 cognitively normal participants [CN] and 330 participants with subjective cognitive decline [SCD]) from the Chinese Alzheimer’s Biomarker and LifestylE (CABLE) database. Then we tested associations of methylation of BIN1 promoter in peripheral blood with the susceptibility for preclinical AD or early changes of cerebrospinal fluid (CSF) AD-related biomarkers. Results showed that SCD participants with significant AD biological characteristics had lower methylation levels of BIN1 promoter, even after correcting for covariates. Hypomethylation of BIN1 promoter were associated with decreased CSF Aβ42 (p = 0.0008), as well as increased p-tau/Aβ42 (p = 0.0001) and t-tau/Aβ42 (p < 0.0001) in total participants. Subgroup analysis showed that the above associations only remained in the SCD subgroup. In addition, hypomethylation of BIN1 promoter was also accompanied by increased CSF p-tau (p = 0.0028) and t-tau (p = 0.0130) in the SCD subgroup, which was independent of CSF Aβ42. Finally, above associations were still significant after correcting single nucleotide polymorphic sites (SNPs) and interaction of APOE ɛ4 status. Our study is the first to find a robust association between hypomethylation of BIN1 promoter in peripheral blood and preclinical AD. This provides new evidence for the involvement of BIN1 in AD, and may contribute to the discovery of new therapeutic targets for AD.

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 Diagnostic Biomarkers for Alzheimer’s Disease Using Non-Invasive Specimens

2020 ◽  
Vol 9 (6) ◽  
pp. 1673 ◽  
Author(s):  
Maria Paraskevaidi ◽  
David Allsop ◽  
Salman Karim ◽  
Francis L. Martin ◽  
StJohn Crean
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Clinical Samples ◽  
Great Promise ◽  
Non Invasive ◽  
To Come ◽  
Sampling Procedures ◽  
T Tau ◽  
Analytical Approaches

Studies in the field of Alzheimer’s disease (AD) have shown the emergence of biomarkers in biologic fluids that hold great promise for the diagnosis of the disease. A diagnosis of AD at a presymptomatic or early stage may be the key for a successful treatment, with clinical trials currently investigating this. It is anticipated that preventative and therapeutic strategies may be stage-dependent, which means that they have a better chance of success at a very early stage—before critical neurons are lost. Several studies have been investigating the use of cerebrospinal fluid (CSF) and blood as clinical samples for the detection of AD with a number of established core markers, such as amyloid beta (Aβ), total tau (T-tau) and phosphorylated tau (P-tau), being at the center of clinical research interest. The use of oral samples—including saliva and buccal mucosal cells—falls under one of the least-investigated areas in AD diagnosis. Such samples have great potential to provide a completely non-invasive alternative to current CSF and blood sampling procedures. The present work is a thorough review of the results and analytical approaches, including proteomics, metabolomics, spectroscopy and microbiome analyses that have been used for the study and detection of AD using salivary samples and buccal cells. With a few exceptions, most of the studies utilizing oral samples were performed in small cohorts, which in combination with the existence of contradictory results render it difficult to come to a definitive conclusion on the value of oral markers. Proteins such as Aβ, T-tau and P-tau, as well as small metabolites, were detected in saliva and have shown some potential as future AD diagnostics. Future large-cohort studies and standardization of sample preparation and (pre-)analytical factors are necessary to determine the use of these non-invasive samples as a diagnostic tool for AD.

scholarly journals Impact of physical exercise on quality of life of older adults with depression or Alzheimer's disease: a systematic review

2014 ◽  
Vol 36 (3) ◽  
pp. 134-139 ◽  
Author(s):  
Bianca Boscarino Tavares ◽  
Helena Moraes ◽  
Andrea Camaz Deslandes ◽  
Jerson Laks
Keyword(s):  
Quality Of Life ◽  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Physical Exercise ◽  
The Elderly ◽  
Pharmacological Intervention ◽  
Older Individuals ◽  
Control Groups

INTRODUCTION: Physical exercise has been associated with improvement of quality of live (QoL), but its effect among the elderly with depression and Alzheimer's disease (AD) is still unclear. This systematic review evaluated randomized and controlled studies about the effect of physical exercise on QoL of older individuals with a clinical diagnosis of depression and AD.METHODS:We searched PubMed, ISI, SciELO and Scopus from December 2011 to June 2013 using the following keywords: physical exercise, quality of life, elderly, depression, Alzheimer's disease. Only six studies met inclusion criteria: two examined patients with AD and four, patients with depression.RESULTS: The studies used different methods to prescribe exercise and evaluate QoL, but all had high quality methods. Findings of most studies with individuals with depression suggested that exercise training improved QoL, but studies with patients with AD had divergent results.CONCLUSIONS: Although different methods were used, results suggested that physical exercise is an effective non-pharmacological intervention to improve the QoL of elderly individuals with depression and AD. Future studies should investigate the effect of other factors, such as the use of specific scales for the elderly, controlled exercise prescriptions and type of control groups.

scholarly journals Speech- and Language-Based Classification of Alzheimer’s Disease: A Systematic Review

2022 ◽  
Vol 9 (1) ◽  
pp. 27
Author(s):  
Inês Vigo ◽  
Luis Coelho ◽  
Sara Reis
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Best Practices ◽  
Early Stage ◽  
Low Cost ◽  
Clinical Stage ◽  
Invasive Procedure ◽  
The Impact

Background: Alzheimer’s disease (AD) has paramount importance due to its rising prevalence, the impact on the patient and society, and the related healthcare costs. However, current diagnostic techniques are not designed for frequent mass screening, delaying therapeutic intervention and worsening prognoses. To be able to detect AD at an early stage, ideally at a pre-clinical stage, speech analysis emerges as a simple low-cost non-invasive procedure. Objectives: In this work it is our objective to do a systematic review about speech-based detection and classification of Alzheimer’s Disease with the purpose of identifying the most effective algorithms and best practices. Methods: A systematic literature search was performed from Jan 2015 up to May 2020 using ScienceDirect, PubMed and DBLP. Articles were screened by title, abstract and full text as needed. A manual complementary search among the references of the included papers was also performed. Inclusion criteria and search strategies were defined a priori. Results: We were able: to identify the main resources that can support the development of decision support systems for AD, to list speech features that are correlated with the linguistic and acoustic footprint of the disease, to recognize the data models that can provide robust results and to observe the performance indicators that were reported. Discussion: A computational system with the adequate elements combination, based on the identified best-practices, can point to a whole new diagnostic approach, leading to better insights about AD symptoms and its disease patterns, creating conditions to promote a longer life span as well as an improvement in patient quality of life. The clinically relevant results that were identified can be used to establish a reference system and help to define research guidelines for future developments.

scholarly journals The Association Between Impaired Awareness and Depression, Anxiety, and Apathy in Mild to Moderate Alzheimer's Disease: A Systematic Review

2021 ◽  
Vol 12 ◽  
Author(s):  
Ignacia Azocar ◽  
Gill Livingston ◽  
Jonathan Huntley
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Depressive Symptoms ◽  
Protective Factor ◽  
Early Stage ◽  
Anxiety Symptoms ◽  
Future Research ◽  
High Quality ◽  
Impaired Awareness

Objectives: Impaired awareness of cognitive and functional deficits is a common feature of Alzheimer's disease (AD). Although a lack of awareness has been suggested to be a protective factor against experiencing affective symptoms, such as depression, anxiety, and apathy which are common in AD, there is conflicting evidence about the links between them. This systematic review examines the evidence for an association between impaired awareness and depressive, anxiety, and apathy symptoms in mild to moderate AD.Method: We searched four databases (OvidMedline, Embase, PsycInfo, and PsycArticles) using terms encompassing awareness, apathy, depression, anxiety, and mild-moderate AD. We included studies that assessed the relationship between awareness and depressive symptoms, anxiety symptoms, or apathy. We assessed included papers for quality and report results using a narrative approach, prioritizing high quality studies.Results: We identified 1,544 articles, and twenty-seven studies fulfilled inclusion criteria (high-quality = 15; moderate-quality = 12). Most high-quality studies reported that impaired awareness in early-stage AD is cross-sectionally linked with fewer depressive symptoms and anxiety symptoms (correlation ranged from −0.3 to −0.7), but with more apathy.Conclusions: High-quality studies suggested that in people with early AD, impaired awareness is related to fewer depressive and anxiety symptoms and to more apathy. Future research should focus on elucidating causality among impaired awareness and these symptoms in AD.

scholarly journals Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

2021 ◽  
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Early Stage ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Preclinical Ad ◽  
T Tau

Abstract Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β 1-42 (Aβ 1-42 ), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential. Methods: We measured NFL and Aβ 1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum. Results: With disease progression, concentrations of NFL increased, and those of Aβ 1-42 were decreases. The plasma and CSF values of NFL/Aβ 1-42 were strongly correlated ( r = 0.558). In addition, the plasma value of NFL/Aβ 1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ 1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ 1-42 changed more rapidly than did either the t-Tau or the p-Tau 181 values measured in the CSF. Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ 1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

scholarly journals Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

2021 ◽  
Author(s):  
Jung Eun Park ◽  
Tamil Iniyan Gunasekaran ◽  
Yeong Hee Cho ◽  
Seong-Min Choi ◽  
Min-Kyung Song ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Disease Progression ◽  
Early Stage ◽  
Amyloid Β ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Preclinical Ad ◽  
T Tau

Abstract Background: Potential biomarkers for Alzheimer’s disease (AD) include amyloid β1-42 (Aβ1-42), t-Tau, p-Tau 181 , neurofilament light chain (NFL), and neuroimaging, but the feasibility of using these for the diagnosis and monitoring of AD has not been reported. Therefore, further development of these biomarkers is essential.Methods: We measured NFL and Aβ1-42 concentrations in CSF and plasma samples from 136 participants and performed correlation analysis to evaluate the utility of these biomarkers for early diagnosis and monitoring of disease progression in AD spectrum.Results: With disease progression, concentrations of NFL increased, and those of Aβ1-42 were decreases. The plasma and CSF values of NFL/Aβ1-42 were strongly correlated (r = 0.558). In addition, the plasma value of NFL/Aβ1-42 was strong correlated with hippocampal volume/ICV ( r = 0.409). In the early stage of AD, the plasma_NFL/Aβ1-42 was associated with higher diagnostic accuracy than were the individual biomarkers. Moreover, in preclinical AD, plasma_NFL/Aβ1-42 changed more rapidly than did either the t-Tau or the p-Tau181 values measured in the CSF.Conclusions: Taken together, our findings highlight the utility of plasma_NFL/Aβ1-42 as a biomarker for early diagnosis and monitoring of disease progression in AD spectrum.

Economic Evaluations of Treatment Options in Patients with Alzheimer's Disease – A Systematic Review

2011 ◽  
Vol 73 (08/09) ◽  
Author(s):  
L Pouryamout ◽  
A Neumann ◽  
J Dams ◽  
J Wasem ◽  
R Dodel
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Treatment Options ◽  
Economic Evaluations
Sign in / Sign up

Export Citation Format

Share Document