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Coronavirus 2 (SARS-CoV2) (COVID-19) causes severe acute respiratory syndrome. Severe illness of COVID-19 largely occurs in older people and recent evidence indicates that demented patients have higher risk for COVID-19. Additionally, COVID-19 further enhances the vulnerability of older adults with cognitive damage. A balance between the immune and inflammatory response is necessary to control the infection. Thus, antimicrobial and anti-inflammatory drugs are hopeful therapeutic agents for the treatment of COVID-19. Accumulating evidence suggests that lactoferrin (Lf) is active against SARS-CoV-2, likely due to its potent antiviral and anti-inflammatory actions that ultimately improves immune system responses. Remarkably, salivary Lf levels are significantly reduced in different Alzheimer’s disease (AD) stages, which may reflect AD-related immunological disturbances, leading to reduced defense mechanisms against viral pathogens and an increase of the COVID-19 susceptibility. Overall, there is an urgent necessity to protect AD patients against COVID-19, decreasing the risk of viral infections. In this context, we propose bovine Lf (bLf) as a promising preventive therapeutic tool to minimize COVID-19 risk in patients with dementia or AD.

BackgroundCognitive impairment and dementia have a high prevalence among the elderly and cause significant socio-economic impact. Any progress in their prevention can benefit millions of people. Current data indicate that cardiovascular risk (CVR) factors increase the risk of developing cognitive impairment and dementia. Using models to calculate CVR specific for the Spanish population can be useful for estimating the risk of cognitive deterioration since research on this topic is limited and predicting this risk is mainly based on outcomes in the Anglo-Saxon population. The aim of this study is to assess the relationship between CVR in the Spanish population, as calculated using the FRESCO (Función de Riesgo Española de acontecimientos Coronarios y Otros) and REGICOR (Registre Gironí del Cor) CVR tables, and the change in cognitive performance at a 5-year follow-up.MethodsDesign: Observational, analytic, prospective cohort study, with a 5-year follow-up. Ambit: Population. Population: Subjects 55 to 74 years of age, included in the NEDICES2 (2014-2017) cohort, who did not present dementia and had undergone the neuropsychological evaluation (N = 962). Variables: Exposure factors (CVR factors and estimated risk according to the CVR predictors by REGICOR and FRESCO), dependent variables (change in the score of the brief neuropsychological test in the study NEDICES2 five years after the first evaluation), and clinical and socio-demographic variables. Statistical analysis: Analysis of data quality. Descriptive analysis: socio-demographic and clinical variables of subjects. Bivariate analysis: relationship between basal CVR and change in neuropsychological tests. Multivariate analysis: relationship between basal CVR and change in neuropsychological tests adjusted by co-variables. Analysis and comparison of the reliable change in independent samples.DiscussionThe Spanish population can benefit from determining if individuals with high CVR, which is commonly detected in usual clinical practice, will present decreased cognitive performance compared to subjects with lower CVR. This study can affect how to address CVR factors and the design of effective prevention strategies for cognitive deterioration.Trial registrationClinicaltrials.gov, NCT03925844.

Background Cognitive impairment and dementia have a high prevalence among the elderly and cause significant socio-economic impact. Any progress in their prevention can benefit millions of people. Current data indicate that cardiovascular risk (CVR) factors increase the risk of developing cognitive impairment and dementia. Using models to calculate CVR specific for the Spanish population can be useful for estimating the risk of cognitive deterioration since research on this topic is limited and predicting this risk is mainly based on outcomes in the Anglo-Saxon population. The aim of this study is to assess the relationship between CVR in the Spanish population, as calculated using the FRESCO (Función de Riesgo Española de acontecimientos Coronarios y Otros) and REGICOR (Registre Gironí del Cor) CVR tables, and the change in cognitive performance at a 5-year follow-up. Methods Design: Observational, analytic, prospective cohort study, with a 5-year follow-up. Ambit: Population. Population: Subjects 55 to 74 years of age, included in the NEDICES2 (2014–2017) cohort, who did not present dementia and had undergone the neuropsychological evaluation (N = 962). Variables: Exposure factors (CVR factors and estimated risk according to the CVR predictors by REGICOR and FRESCO), dependent variables (change in the score of the brief neuropsychological test in the study NEDICES2 five years after the first evaluation), and clinical and socio-demographic variables. Statistical analysis: Analysis of data quality. Descriptive analysis: socio-demographic and clinical variables of subjects. Bivariate analysis: relationship between basal CVR and change in neuropsychological tests. Multivariate analysis: relationship between basal CVR and change in neuropsychological tests adjusted by co-variables. Analysis and comparison of the reliable change in independent samples. Discussion The Spanish population can benefit from determining if individuals with high CVR, which is commonly detected in usual clinical practice, will present decreased cognitive performance compared to subjects with lower CVR. This study can affect how to address CVR factors and the design of effective prevention strategies for cognitive deterioration. Trial registration Clinicaltrials.gov, NCT03925844.

The purpose of this study is to determine the possible alterations that may occur in the thickness of the retinal nerve fibre layer (RNFL), ganglion cell layer (GCL), and macular thickness in patients with chronic migraines compared with healthy controls. Hence, we examined some of the possibilities that are offered by optical coherence tomography (OCT) in order to study different neurological diseases and to study its application, in this case, how it may be applied to patients with chronic migraines. This was an observational cross-sectional study in adults aged 18–65 years. The study group consisted of 90 patients (90 eyes) with chronic migraines who met the inclusion criteria, and 90 healthy controls (90 eyes) matched for age and sex. Retinal thickness was measured by spectral domain OCT (SD-OCT). The thickness of the superior quadrant of the peripapillary RNFL, as well as the mean thickness in the macula, RNFL macular, and GCL was significantly thinner in chronic migraine patients than in healthy controls (p ≤ 0.05). Chronic migraines are associated with a decrease in retinal thickness which is detectable by an OCT diagnostic technique. The quantification of the axonal damage could be used as a biomarker to help in the diagnosis and monitoring of this pathology. Further studies will be needed to confirm these findings.

Impaired brain clearance mechanisms may result in the accumulation of aberrant proteins that define Alzheimer’s disease (AD). The water channel protein astrocytic aquaporin 4 (AQP4) is essential for brain amyloid-β clearance, but it is known to be abnormally expressed in AD brains. The expression of AQPs is differentially regulated during diverse brain injuries, but, whereas AQP4 expression and function have been studied in AD, less is known about AQP5. AQP5 functions include not only water transport but also cell migration mediated by cytoskeleton regulation. Moreover, AQP5 has been reported to be expressed in astrocytes, which are regulated after ischemic and traumatic injury. Additionally, AQP5 is particularly abundant in the salivary glands suggesting that it may be a crucial factor in gland dysfunction associated with AD. Herein, we aim to determine whether AQP5 expression in submandibular glands and the brain was altered in AD. First, we demonstrated impaired AQP5 expression in submandibular glands in APP/PS1 mice and AD patients. Subsequently, we observed that AQP5 expression was upregulated in APP/PS1 cerebral cortex and confirmed its expression both in astrocytes and neurons. Our findings propose AQP5 as a significant role player in AD pathology, in addition to AQP4, representing a potential target for the treatment of AD.

Background: Ischemic stroke is the most common and severe arterial thrombotic event in Antiphospholipid syndrome (APS). APS is an autoimmune disease characterized by the presence of thrombosis and antiphospholipid antibodies (aPL), which provide a pro-coagulant state. The aPL included in the classification criteria are lupus anticoagulant, anti-cardiolipin (aCL) and anti-β2-glycoprotein-I antibodies (aB2GPI) of IgG and IgM isotypes. Extra-criteria aPL, especially IgA aB2GPI and IgG/IgM anti-phosphatidylserine/prothrombin antibodies (aPS/PT), have been strongly associated with thrombosis. However, their role in the general population suffering from stroke is unknown. We aim (1) to evaluate the aPL prevalence in ischemic stroke patients, (2) to determine the role of aPL as a risk factor for stroke, and (3) to create an easy-to-use tool to stratify the risk of ischemic stroke occurrence considering the presence of aPL and other risk factors.Materials and Methods: A cohort of 245 consecutive ischemic stroke patients was evaluated in the first 24 h after the acute event for the presence of classic aPL, extra-criteria aPL (IgA aB2GPI, IgG, and IgM aPS/PT) and conventional cardiovascular risk factors. These patients were followed-up for 2-years. A group of 121 healthy volunteers of the same age range and representative of the general population was used as reference population. The study was approved by the Ethics Committee for Clinical Research (Reference numbers CEIC-14/354 and CEIC-18/182).Results: The overall aPL prevalence in stroke patients was 28% and IgA aB2GPI were the most prevalent (20%). In the multivariant analysis, the presence of IgA aB2GPI (OR 2.40, 95% CI: 1.03–5.53), dyslipidemia (OR 1.70, 95% CI: 1.01–2.84), arterial hypertension (OR 1.82, 95% CI: 1.03–3.22), atrial fibrillation (OR 4.31, 95% CI: 1.90–9.78), and active smoking (OR 3.47, 95% CI: 1.72–6.99) were identified as independent risk factors for ischemic stroke. A risk stratification tool for stroke was created based on these factors (AUC: 0.75).Conclusions: IgA aB2GPI are an important independent risk factor for ischemic stroke. Evaluation of aPL (including extra-criteria) in cardiovascular risk factor assessment for stroke can potentially increase the identification of patients at risk of thrombotic event, facilitating a decision on preventive treatments.

To analyze whether Physical activity (PA) reduces mortality risk at thirteen years' follow-up in a population-based cohort of Spanish older adults. The NEDICES (Neurological Disorders in Central Spain) is a prospective population-based survey of older adults (age ≥ 65 years) that comprised 5278 participants at baseline. A modified version of the Rosow-Breslau questionnaire was applied to categorize the PA (sedentary, light, moderate and high) and dates of death were collected from the Official Spanish Death Registry. Cox regression models adjusted for different covariates (age, sex, marital status, smoking, previous stroke, Parkinson disease, incident dementia, body mass index, comorbidity indexes and functional assessment) were used to evaluate the hazard of death at thirteen years' interval according to different levels of PA. 1710 deaths (52.9% men vs. 47.1% women) were identified among 3633 individuals at thirteen years' follow-up. Hazard ratios (HRs) of the light, moderate, and high PA groups (vs. sedentary group) were 0.64 (95% confidence interval (CI) [0.56, 0.72], p

Background: Our aim was to assess the diagnostic agreement among the neurologists in the Neurological Disorders in Central Spain 2 (NEDICES‐2) study; these neurologists were assigning diagnoses of essential tremor (ET) vs. no ET.Methods: Clinical histories and standardized video‐taped neurological examinations of 26 individuals (11 ET, seven Parkinson’s disease, three diagnostically unclear, four normal, one with a tremor disorder other than ET) were provided to seven consultant neurologists, six neurology residents, and five neurology research fellows (18 neurologists total). For each of the 26 individuals, neurologists were asked to assign a diagnosis of “ET” or “no ET” using diagnostic criteria proposed by the Movement Disorders Society (MDS). Inter‐rater agreement was assessed both with percent concordance and non‐weighted Κ statistics. Results: Overall Κ was 0.61 (substantial agreement), with no differences between consultant neurologists (Κ = 0.60), neurology residents (Κ = 0.61), and neurology research fellows (Κ = 0.66) in subgroup analyses. Subanalyses of agreement only among those 15 subjects with a previous diagnosis of ET (11 patients) and those with a previous diagnosis of being normal (four individuals) showed an overall Κ of 0.51 (moderate agreement). Discussion In a population‐based epidemiological study, substantial agreement was demonstrated for the diagnosis of ET among neurologists of different levels of expertise. However, agreement was lower than that previously reported using the Washington Heights–Inwood Genetic Study of Essential Tremor criteria, and a head‐to‐head comparison is needed to assess which is the tool of choice in epidemiological research in ET.

Objective: Describe the characteristics and prevalence of headache in patients with mitochondrial diseases (MDs), as well as sleep quality, trying to observe possible associations. To assess whether these patients are more likely to suffer headaches in relation to poorer quality of sleep. Background: Sleep disorders and headache are considered to be common in MDs. We present the largest sample analyzed to date. Methods: Observational, descriptive, cross-sectional study that analyzed a database of 232 patients with MDs, including age, sex, genotype, phenotype, presence and characteristics of headache. All patients fulfilled the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and, in migraine, the Migraine Disability Assessment questionnaire (MIDAS). Headache was divided into two groups: migraine headache, according to criteria of the International Classification of Headache Disorders (ICHD-III beta), and non-migraine headache. Results: A total of 203 cases were analyzed, 124 women (61%) and 79 men (39%). Average age was 46 years. Most frequent DNA mutation was m.3243 A > G in MITL1 gene (33%). Most frequent phenotype was MELAS syndrome: 28 patients (13.8%). Ninety-two patients (45.3%), reported headache, 44 fulfilling migraine criteria (21.7%). Headache was more frequent in MELAS syndrome ( p < 0.01). Statistically significant differences were found in the number of disabling episodes per month in patients with migraine ( p < 0.001). Patients with headache scored higher in Epworth ( p = 0.01) and Pittsburgh scales ( p < 0.001). Conclusions: A higher prevalence of migraine is observed in patients with mitochondrial diseases, independent of genotype and phenotype. MD-associated migraine tends to be chronic and more disabling. A higher frequency of headache, not specifically migraine, has also been observed in patients with MELAS syndrome. Mitochondrial dysfunction could be one of the pathophysiological mechanisms of migraine and a factor of chronification and severity. Poor sleep quality could also be associated with headache in patients with MDs. Assessment of headache and sleep disturbances should be part of the routine workup of patients with mitochondrial disease. Trial registration: N/A.