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      Association between altered cognition and Loa loa microfilaremia: First evidence from a cross-sectional study in a rural area of the Republic of Congo

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          Abstract

          Background

          Individuals with high Loa loa microfilarial densities are at risk of developing severe encephalopathy after administration of antiparasitic drugs. Apart from this finding, loiasis is considered benign with no effect on brain function. However, recent epidemiological data suggest an increased mortality and morbidity in L. loa infected individuals, underscoring the importance of studies on the possible neurological morbidity associated with loiasis.

          Methodology

          Using MoCA tests and neurological ultrasounds, we conducted a cross-sectional study to assess cognitive alteration in a population living in a rural area endemic for loiasis in the Republic of Congo. Fifty individuals with high microfilarial densities (MFD) were matched on sex, age and residency with 50 individuals with low MFD and 50 amicrofilaremic subjects.

          Analyses focused on individuals with MoCA scores indicating an altered cognition (i.e. < 23/30) and on the total MoCA score according to Loa loa MFD, sociodemographic characteristics and neurological ultrasound results.

          Principal findings

          MoCA scores were very low in the studied population (mean of 15.6/30). Individuals with more than 15,000 microfilariae per milliliter of blood (mean predicted score:14.0/30) are more than twenty times more likely to have an altered cognition, compared to individuals with no microfilaremia (mean predicted score: 16.3/30). Years of schooling were strongly associated with better MoCA results. Extracranial and intracranial atheroma were not associated with L. loa MFD.

          Conclusion/significance

          Loaisis microfilaremia is probably involved in cognitive impairment, especially when the MFD are high. These results highlight the urgent need to better understand loaisis-induced morbidity. Further studies investigating neurological morbidity of loiasis are needed.

          Author summary

          Individuals with high Loa loa blood microfilarial densities are at risk of developing a serious encephalopathy after administration of antiparasitic drugs. Apart from this major inconvenience, L. loa filariasis (loiasis) is considered a benign disease, with no effect on brain function. However, recent epidemiological data suggest an increased mortality and morbidity in L. loa infected individuals, underscoring the importance of studies on the possible neurological morbidity associated with loiasis. This cross-sectional study assessed cognition using MoCA tests (Montreal Cognitive assessments, a tool for early detection of mild cognitive impairment) and neurological ultrasound among 143 matched individuals with either no microfilaremia, low microfilaremia or high microfilaremia. People with high microfilaremia were more than twenty times more likely to have an altered cognition, compared to individuals with no microfilaremia.

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          Most cited references41

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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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            The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

            The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. Copyright © 2011 The Alzheimer's Association. All rights reserved.
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              Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges.

              The term cerebral small vessel disease refers to a group of pathological processes with various aetiologies that affect the small arteries, arterioles, venules, and capillaries of the brain. Age-related and hypertension-related small vessel diseases and cerebral amyloid angiopathy are the most common forms. The consequences of small vessel disease on the brain parenchyma are mainly lesions located in the subcortical structures such as lacunar infarcts, white matter lesions, large haemorrhages, and microbleeds. Because lacunar infarcts and white matter lesions are easily detected by neuroimaging, whereas small vessels are not, the term small vessel disease is frequently used to describe the parenchyma lesions rather than the underlying small vessel alterations. This classification, however, restricts the definition of small vessel disease to ischaemic lesions and might be misleading. Small vessel disease has an important role in cerebrovascular disease and is a leading cause of cognitive decline and functional loss in the elderly. Small vessel disease should be a main target for preventive and treatment strategies, but all types of presentation and complications should be taken into account. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: InvestigationRole: SupervisionRole: Writing – review & editing
                Role: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                PLOS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                20 June 2023
                June 2023
                : 17
                : 6
                : e0011430
                Affiliations
                [1 ] AP-HP, Service des Urgences Cérébro-Vasculaires, Hôpital Pitié-Salpêtrière, Sorbonne Université, Paris, France
                [2 ] Programme National de Lutte contre l’Onchocercose, Direction de l’Épidémiologie et de la Lutte contre la Maladie, Ministère de la Santé et de la Population, Brazzaville, Republic of the Congo
                [3 ] UMI 233 TransVIHMI, Université Montpellier, Institut de Recherche pour le Développement (IRD), INSERM Unité, Montpellier, France
                University of Washington, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0002-4400-5204
                Article
                PNTD-D-23-00393
                10.1371/journal.pntd.0011430
                10313009
                37339123
                41fdce80-70ac-4155-9db7-00ba91b82e7c
                © 2023 Checkouri et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 29 March 2023
                : 3 June 2023
                Page count
                Figures: 1, Tables: 4, Pages: 15
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100019180, HORIZON EUROPE European Research Council;
                Award ID: 949963
                Award Recipient :
                This study was fully supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 949963, grant recipient: CBC). The funders had no role in the study design, data collection, data analysis, data interpretation, or writing of the report.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Invertebrates
                Nematoda
                Loa Loa
                Biology and Life Sciences
                Zoology
                Animals
                Invertebrates
                Nematoda
                Loa Loa
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Medical Conditions
                Tropical Diseases
                Neglected Tropical Diseases
                Loiasis
                Medicine and Health Sciences
                Medical Conditions
                Parasitic Diseases
                Nematode Infections
                Loiasis
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Dementia
                Medicine and Health Sciences
                Neurology
                Dementia
                Medicine and Health Sciences
                Vascular Medicine
                Atheromas
                Medicine and Health Sciences
                Health Care
                Health Statistics
                Morbidity
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Blood
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Blood
                Biology and Life Sciences
                Physiology
                Body Fluids
                Blood
                Custom metadata
                vor-update-to-uncorrected-proof
                2023-06-30
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting information file.

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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