Biomarkers for better diagnosis: the case of Mild Cognitive Impairment
Posted on 21st October 2022 by Davide E. De Dominicis
Why use new biomarkers for a diagnostic process if lots of easy assessment methods are available?
According to the National Institute on Aging, about 10-20% of people aged 65 or over live with Mild Cognitive Impairment (MCI). The Alzheimer’s Association defines this clinical syndrome as a condition in which the patient presents a relevant decrease in cognitive functions, while the global functionalities remain fundamentally intact. Even if at first glance the patient’s relatives, and the patient themselves, may consider this syndrome as not particularly relevant as they can continue to be relatively autonomous in daily life activities, physicians have to consider the appearance of a set of symptoms consistent with an MCI diagnosis as a wake-up call for the future onset of Alzheimer’s disease (AD).
Today, neurologists can diagnose MCI exclusively on a neuropsychological tests assessment basis. Biomarkers could help them if used as confirmatory instruments in a more accurate diagnostic process. The systematic review summarized here aims to describe potential biomarkers in a recently discovered and complex world: microRNAs (miRNAs). Do you want to know more about what a systematic review is? Then have a look at this other S4BE blog: ‘The Systematic Review’.
Proposed biomarkers and the miRNAs dimension
Governments and health organizations recognize that fighting AD in its prodromic stages (when early signs or symptoms appear) is now an important public health issue. Scientific research has focused on preventing the disease’s onset by working therapeutically on MCI. Over the last 20 years, researchers have evaluated neuroimaging techniques and cerebrospinal fluid (CSF) analysis as biomarkers to help physicians in identifying MCI. Neuroimaging techniques, like the well-known magnetic resonance, allow the study of morphological and metabolic changes in the patient’s brain, especially in regions like the hippocampus or the temporal lobe. CSF analysis, instead, could be interesting to investigate modifications in some proteins’ concentration, in the case of amyloid beta and tau protein. High cost and difficulty in accessing the necessary instruments, especially in developing countries, are actively limiting the use of these procedures. For this reason, new biomarkers like miRNAs could present a valid and affordable solution.
The potentiality of MiRNAs as biomarkers
While most people know the general role of RNAs in protein synthesis well, miRNAs are not particularly well known. These 22 nucleotides long molecules are unique in terms of morphology and functionality. Their main roles seem to be RNA silencing and modulation of gene expression. Research from around the world discovered hundreds of organ-specific miRNAs in the last decades, as experimental evidence confirms.
The review summarized here shows that miRNAs could represent an important source of information about the patient’s personal risk assessment. These molecules could be crucial even in predicting the progression of MCI to AD. Because of the ease of obtaining miRNAs quickly from a blood sample, they are gaining great interest in the biomarkers’ world.
The authors recognized the mir-181 family and another 5 types of miRNAs as potential biomarkers. Their levels are often altered in patients affected by MCI and those concentrations could be monitored thanks to blood sample analysis.
What limits the use of miRNAs?
The authors highlight some limitations for miRNAs usage such as the concentration of these molecules in blood being very low. Analysts and researchers have to perform further procedures (like Quantitative Real Time-PCR) in order to obtain information from a sample. Moreover, about 70% of miRNAs that could be found in a blood sample can originate from sources like peripheral nerves, where these molecules play a key role in important metabolic processes. It’s important, for this reason, to set protocols for the validation of these biomarkers.
Additional research is therefore required to better verify miRNAs potentialities. Further efforts will probably eliminate the existing limits summarized above. In the future, however, clinical assessment of conditions such as MCI will surely be driven by the analysis of biomarkers. Thanks to them we will be capable of obtaining more accurate diagnosis and more effective therapeutic strategies.
The review: Ogonowski, N., Salcidua, S., Leon, T., Chamorro-Veloso, N., Valls, C., Avalos, C., Bisquertt, A., Rentería, M. E., Orellana, P., & Duran-Aniotz, C. (2022). Systematic Review: microRNAs as Potential Biomarkers in Mild Cognitive Impairment Diagnosis. Frontiers in aging neuroscience, 13, 807764. https://doi.org/10.3389/fnagi.2021.807764.
Other references: National Institute on Aging. n.d. “What is Mild Cognitive Impairment?” Available at: https://www.alzheimers.gov/alzheimers-dementias/mild-cognitive-impairment (Accessed 21 October 2022)
You may also be interested in this video from Cochrane: “What is a diagnostic test accuracy review?”