Circulating MicroRNAs as Diagnostic Biomarkers of Clinical Cognitive Impairment: A Meta-Analysis

Abstract

Background: Minimally invasive diagnostic biomarkers of neurodegenerative diseases such as Alzheimer’s disease (AD) facilitate patient selection and cognitive progressive decline monitoring. However, the diagnostic value of circulating microRNAs (miRNAs) for early cognitive impairment and progression to dementia is currently under debate. Thus, this study aimed to assess the diagnostic performance of circulating, cerebrospinal fluid (CSF) and exosomal miRNAs in the detection of clinical cognitive impairment in mild cognitive impairment (MCI), AD, and MCI-AD. Methods: We searched PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), VIP Chinese Science and Technology Journals Database (CQVIP), and Chinese Medicine Premier (Wanfang) to identify potentially eligible studies related to noncoding RNAs and cognitive dysfunction biomarkers published before November 2018. The quality assessment of the studies was performed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) checklist. Meta-analysis of the literature data was performed using Stata/MP 14.0 software. The corresponding effects models were selected to calculate the summary sensitivity, specificity, positive and negative likelihood ratios (PLR and NLR), and diagnostic odds ratio (DOR) and to plot the summary receiver operating characteristic curves (SROCs) and calculate the areas under the curves (AUCs). Results: A total of 18 studies involving 729 patients with AD, 283 patients with MCI, and 15 patients with MCI-AD were pooled. The results revealed that the sensitivity and specificity of miRNAs in the diagnosis of AD were 0.78 and 0.79, respectively, and the area under the summary receiver operating characteristic curve (AUSROC) was 0.90. The sensitivity and specificity of miRNAs in the diagnosis of MCI were 0.89 and 0.85, respectively, and the AUSROC was 0.94. The sensitivity and specificity of microRNAs in the diagnosis of MCI-AD were 0.87 and 0.84, respectively, and the AUSROC was 0.92. Conclusion: Our study found that miRNAs have certain diagnostic value for cognitive impairment, with high sensitivity and specificity, especially in diagnostics with multiple miRNAs and serum-based miRNA assays.

A Comprehensive Review on the Role of Non-Coding RNAs in the Pathophysiology of Bipolar Disorder

“…Moreover, miRNAs have been shown to serve as diagnostic markers for cognitive impairment. Certain panels of miRNAs have high sensitivity and specificity values in this regard [ 62 ].…”

Fission Impossible: Stabilized miRNA-Based Analogs in Neurodegenerative Disease

“…The essential neuro-pathological features of AD have been known for almost ~120 years, and currently the presence and abundance of pathological lipoprotein-rich aggregates including amyloid-beta (Aβ) peptide-enriched “senile plaques” (SP) and the accumulation of abnormally hyper-phosphorylated tau (pTau) proteins into twisted neurofilament bundles known as neurofibrillary tangles (NFT) in the AD affected neocortex and hippocampus are still required for an accurate pathological diagnosis of AD at post-mortem examination of the brain (Alzheimer et al, 1995 ; DeTure and Dickson, 2019 ). Recent developments and advancements in RNA sequencing technologies and molecular imaging involving specialized positron emission tomography (PET)-based technologies and the use of multiple biofluid biomarkers have become increasingly useful for assisting in the early diagnosis, prognosis, prediction of time-to-symptom onset and drug treatment-monitoring of complex lipoproteinopathies including AD (Swarbrick et al, 2019 ; Shi et al, 2020 ; Wei et al, 2020 ; Zhao et al, 2020 ; Beach and Malek-Ahmadi, 2021 ; Ni and Nitsch, 2022 ; Ogonowski et al, 2022 ).…”

Nucleic acid liquid biopsies in Alzheimer's disease: current state, challenges, and opportunities

“…Provided that findings describing the potential of miRNAs to detect neurodegenerative diseases, specifically AD (recently reviewed in [ 98 , 99 , 100 , 101 ]), are validated further experimentally and computationally, miRNAs have the potential to drive forward the development of early-detection diagnostic tools for AD. Recent efforts from meta-analyses that aim to identify circulating miRNAs for AD detection have and will further increase our understanding of miRNAs as liquid biopsy markers in AD [ 102 , 103 , 104 ]. Therefore, the aforementioned meta-analyses and the propositions of biofluid panels for the detection of AD may allow liquid biopsy establishment in AD diagnosis.…”