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      Aftereffects in Epigenetic Age Related to Cognitive Decline and Inflammatory Markers in Healthcare Personnel with Post-COVID-19: A Cross-Sectional Study

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          Abstract

          Purpose

          Epigenetic age and inflammatory markers have been proposed as indicators of severity and mortality in patients with COVID-19. Furthermore, they have been associated with the occurrence of neurological symptoms, psychiatric manifestations, and cognitive impairment. Therefore, we aimed to explore the possible associations between epigenetic age, neuropsychiatric manifestations and inflammatory markers (neutrophil-lymphocyte ratio [NLR], platelet-lymphocyte ratio [PLR], monocyte-lymphocyte ratio [MLR], and systemic immune-inflammation index [SII]) in healthcare personnel with post-COVID condition.

          Patients and Methods

          We applied the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) tests to 51 Mexican healthcare workers with post-COVID-19 condition; we also estimated their epigenetic age using the PhenoAge calculator.

          Results

          The participants had a post-COVID condition that lasted a median of 14 months (range: 1–20). High NLR (>1.73) had association with mild cognitive impairment by MMSE (p=0.013). Likewise, high MLR (>0.24) were associated with language domain in MOCA (p=0.046). Low PLR (<103.9) was also related to delayed recall in MOCA (p=0.040). Regarding comorbidities, hypertension was associated with SII (p=0.007), overweight with PLR (p=0.047) and alcoholism was associated with MLR (p=0.043). Interestingly, we observed associations of low PLR (<103.9) and low SII (<1.35) levels with increased duration of post-COVID condition (p=0.027, p=0.031). Likewise, increases in PhenoAge were associated with high levels of SII (OR=1.11, p=0.049), PLR (OR=1.12, p=0.035) and MLR (OR=1.12, p=0.030).

          Conclusion

          We observed neurocognitive changes related to inflammatory markers and increases in epigenetic age in healthcare personnel with post-COVID-19 condition. Future research is required to assess mental and physical health in individuals with post-COVID-19 symptoms.

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          Most cited references64

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            An epigenetic biomarker of aging for lifespan and healthspan

            Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge, that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.
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              DNA methylation-based biomarkers and the epigenetic clock theory of ageing

              Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: why do we age?
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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                ijgm
                International Journal of General Medicine
                Dove
                1178-7074
                31 October 2023
                2023
                : 16
                : 4953-4964
                Affiliations
                [1 ]División Académica de Ciencias de la Salud, Universidad Juarez Autónoma de Tabasco , Villahermosa, Tabasco, México
                [2 ]Hospital Regional de Alta Especialidad de Salud Mental , Villahermosa, Tabasco, México
                [3 ]Department of Psychiatry, Yale University School of Medicine , New Haven, CT, USA
                [4 ]Hospital Psiquiátrico Infantil “Dr. Juan N. Navarro” , Ciudad de México, México
                [5 ]División Académica Multidisciplinaria de Jalpa de Méndez, Universidad Juarez Autónoma de Tabasco , Jalpa de Méndez, Tabasco, México
                [6 ]División Académica Multidisciplinaria de Comalcalco, Universidad Juarez Autónoma de Tabasco , Comalcalco, Tabasco, México
                [7 ]Departamento de Genética Psiquiátrica, Instituto Nacional de Medicina Genómica (INMEGEN) , Ciudad de México, México
                Author notes
                Correspondence: Isela Esther Juárez-Rojop, División Académica de Ciencias de la Salud, Universidad Juarez Autónoma de Tabasco , Av. Gregorio Méndez 2838-A, Col. Tamulté, Villahermosa, 86100, México, Email iselajuarezrojop@hotmail.com
                Humberto Nicolini, Instituto Nacional de Medicina Genómica (INMEGEN) , Ciudad de México, 86100, México, Email hnicolini@inmegen.gob.mx
                [*]

                These authors contributed equally to this work

                Author information
                http://orcid.org/0000-0001-5536-3173
                http://orcid.org/0000-0001-8046-6908
                http://orcid.org/0000-0001-8170-8171
                http://orcid.org/0000-0002-8228-1314
                http://orcid.org/0000-0003-2494-0067
                http://orcid.org/0000-0003-3760-7394
                Article
                426249
                10.2147/IJGM.S426249
                10625328
                77f5bd3e-5b4d-4b30-b04f-4e9f03e8f837
                © 2023 Nolasco-Rosales et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 01 July 2023
                : 16 October 2023
                Page count
                Figures: 2, Tables: 2, References: 64, Pages: 12
                Categories
                Original Research

                Medicine
                post-covid-19,cognitive manifestation,inflammatory markers,epigenetic age
                Medicine
                post-covid-19, cognitive manifestation, inflammatory markers, epigenetic age

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