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Introduction Sleep is increasingly recognized as a major risk factor for neurodegenerative disorders such as Alzheimer's disease (AD). Methods Using an magnetic resonance imaging (MRI)–based AD score based on clinical data from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) case‐control cohort, we investigated the associations between polysomnography‐based sleep macro‐architecture and AD‐related brain atrophy patterns in 712 pre‐symptomatic, healthy subjects from the population‐based Study of Health in Pomerania. Results We identified a robust inverse association between slow‐wave sleep and the AD marker (estimate: −0.019; 95% confidence interval: −0.03 to −0.0076; false discovery rate [FDR] = 0.0041), as well as with gray matter (GM) thicknesses in typical individual cortical AD‐signature regions. No effects were identified regarding rapid eye movement or non–rapid eye movement (NREM) stage 2 sleep, and NREM stage 1 was positively associated with GM thickness, mainly in the prefrontal cortical regions. Discussion There is a cross‐sectional relationship between AD‐related neurodegenerative patterns and the proportion of sleep spent in slow‐wave sleep.

Introduction Abnormal cerebrospinal fluid amyloid beta (Aβ)42 and tau levels have been revealed decades before symptoms onset in Alzheimer's disease (AD); however, the examination is usually invasive and inaccessible to most people. We thus aimed to develop a non‐invasive behavioral test that targets early potential cognitive changes to gauge cognitive decline. Specifically, we hypothesized that older cognitive healthy participants would exhibit comparable performance when the task was explicit and relied on conscious cognition. However, when the task was implicit, the performance of participants at high and low risks for AD would bifurcate. That is, early changes in unconscious cognition could be linked to cognitive health. Methods We measured implicit interference elicited by an imperceptible distractor in cognitively healthy elderly participants with normal (low risk) and pathological (high risk) Aβ42/total tau ratio. Participants were required to perform a Stroop task (word‐naming or color‐naming on an ink‐semantics inconsistent word) with a visually masked distractor presented prior to the target task. Results We found that, under a high‐effort task (i.e., color‐naming in the Stroop task), high‐risk participants suffered interference when the imperceptible distractor and the subsequent target were incongruent in the responses they triggered. Their reaction times were slowed down by approximately 4%. This implicit interference was not found in the low‐risk participants. Discussion These findings indicate that weakened inhibition of distracting implicit information can be a potential behavioral biomarker of early identification of AD pathology. Our study thus offers a new experimental paradigm to reveal early pathological aging by assessing how individuals respond to subperceptual threshold visual stimuli.

Background Screening is an important part of preventive medicine. Ideally, screening tools identify patients early enough to provide treatment and avoid or reduce symptoms and other consequences, improving health outcomes of the population at a reasonable cost. Cost-effectiveness analyses combine the expected benefits and costs of interventions and can be used to assess the value of screening tools. Objective This review seeks to evaluate the latest cost-effectiveness analyses on screening tools to identify the current challenges encountered and potential methods to overcome them. Methods A systematic literature search of EMBASE and MEDLINE identified cost-effectiveness analyses of screening tools published in 2017. Data extracted included the population, disease, screening tools, comparators, perspective, time horizon, discounting, and outcomes. Challenges and methodological suggestions were narratively synthesized. Results Four key categories were identified: screening pathways, pre-symptomatic disease, treatment outcomes, and non-health benefits. Not all studies included treatment outcomes; 15 studies (22%) did not include treatment following diagnosis. Quality-adjusted life years were used by 35 (51.4%) as the main outcome. Studies that undertook a societal perspective did not report non-health benefits and costs consistently. Two important challenges identified were (i) estimating the sojourn time, i.e., the time between when a patient can be identified by screening tests and when they would have been identified due to symptoms, and (ii) estimating the treatment effect and progression rates of patients identified early. Conclusions To capture all important costs and outcomes of a screening tool, screening pathways should be modeled including patient treatment. Also, false positive and false negative patients are likely to have important costs and consequences and should be included in the analysis. As these patients are difficult to identify in regular data sources, common treatment patterns should be used to determine how these patients are likely to be treated. It is important that assumptions are clearly indicated and that the consequences of these assumptions are tested in sensitivity analyses, particularly the assumptions of independence of consecutive tests and the level of patient and provider compliance to guidelines and sojourn times. As data is rarely available regarding the progression of undiagnosed patients, extrapolation from diagnosed patients may be necessary.

Mibyou, or pre-symptomatic diseases, refers to state of health in which a disease is slowly developing within the body yet the symptoms are not apparent. Common examples of mibyou in modern medicine include inflammatory diseases that are caused by chronic inflammation. It is known that chronic inflammation is triggered by the uncontrolled release of proinflammatory cytokines by neutrophils and macrophages in the innate immune system. In a recent study, it was shown that molecular hydrogen (H2) has the ability to treat chronic inflammation by eliminating hydroxyl radicals (·OH), a mitochondrial reactive oxygen species (ROS). In doing so, H2 suppresses oxidative stress, which is implicated in several mechanisms at the root of chronic inflammation, including the activation of NLRP3 inflammasomes. This review explains these mechanisms by which H2 can suppress chronic inflammation and studies its applications as a protective agent against different inflammatory diseases in their pre-symptomatic state. While mibyou cannot be detected nor treated by modern medicine, H2 is able to suppress the pathogenesis of pre-symptomatic diseases, and thus exhibits prospects as a novel protective agent.

Resting state functional connectivity (rs-fMRI) is impaired early in persons who subsequently develop Alzheimer’s disease (AD) dementia. This impairment may be leveraged to aid investigation of the pre-clinical phase of AD. We developed a model that predicts brain age from resting state (rs)-fMRI data, and assessed whether genetic determinants of AD, as well as beta-amyloid (Aβ) pathology, can accelerate brain aging. Using data from 1340 cognitively unimpaired participants between 18–94 years of age from multiple sites, we showed that topological properties of graphs constructed from rs-fMRI can predict chronological age across the lifespan. Application of our predictive model to the context of pre-clinical AD revealed that the pre-symptomatic phase of autosomal dominant AD includes acceleration of functional brain aging. This association was stronger in individuals having significant Aβ pathology. Alzheimer’s disease has been associated with increased structural brain aging. Here the authors describe a model that predicts brain aging from resting state functional connectivity data, and demonstrate this is accelerated in individuals with pre-clinical familial Alzheimer’s disease.

Xylella fastidiosa, a gram-negative bacterium vectored to plants via feeding of infected insects, causes a number of notorious plant diseases throughout the world, such as Pierce’s disease (grapes), olive quick decline syndrome, and coffee leaf scorch. Detection of Xf in infected plants can be challenging because the early foliar disease symptoms are subtle and may be attributed to multiple minor physiological stresses and/or borderline nutrient deficiencies. Furthermore, Xf may reside within an infected plant for one or more growing seasons before traditional visible diagnostic disease symptoms emerge. Any method that can identify infection during the latent period or pre-diagnostic disease progress state could substantially improve the outcome of disease control interventions. Because Xf locally and gradually impairs water movement through infected plant stems and leaves over time, infected plants may not be able to effectively dissipate heat through transpiration-assisted cooling, and this heat signature may be an important pre-diagnostic disease trait. Here, we report on the association between thermal imaging, the early stages of Xf infection, and disease development in blueberry plants, and discuss the benefits and limitations of using thermal imaging to detect bacterial leaf scorch of blueberries.

Adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, encoding for the adrenoleukodystrophy protein (ALDP), leading to defective peroxisomal β-oxidation of very long-chain and branched-chain fatty acids (VLCFA). ALD manifests in both sexes with a spectrum of phenotypes, but approximately 35% of affected males develop childhood cerebral adrenoleukodystrophy (CCALD), which is lethal without hematopoietic stem cell transplant performed before symptoms start. Hence, ALD was added to the Recommended Uniform Screening Panel after the successful implementation in New York State (2013–2016). To date, thirty-five states have implemented newborn screening (NBS) for ALD, and a few programs have reported on the successes and challenges experienced. However, the overall impact of NBS on early detection of ALD has yet to be fully determined. Here, we conducted a retrospective analysis of VLCFA testing performed by our reference laboratory (ARUP Laboratories, Salt Lake City, UT, USA) over 10 years. Rate of detection, age at diagnosis, and male-to-female ratio were evaluated in patients with abnormal results before and after NBS implementation. After NBS inclusion, a significant increase in abnormal results was observed (471/6930, 6.8% vs. 384/11,670, 3.3%; p < 0.0001). Patients with ALDP deficiency identified via NBS were significantly younger (median age: 30 days vs. 21 years; p < 0.0001), and males and females were equally represented. ALD inclusion in NBS programs has increased pre-symptomatic detection of this disease, which is critical in preventing adrenal crisis as well as the severe cerebral form.

Background Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is an emerging viral pandemic disease. In the last 6 months, SARS-CoV-2 has caused millions of reported cases and hundreds of thousands of deaths. As other world regions, South America has not contained the pandemic’s advance since it lacks the hospital and economic capacities. Public health implications of transmission, while the asymptomatic/presymptomatic infection is a critical concern at the current pandemic. Objective Describe the socio-demographic, clinical, and viral features of a cohort of SARS-CoV-2 infected individuals from the Colombian Caribbean. Methods Six hundred eighty-six clinical samples of suspected SARS-CoV-2 infection cases and contacts individuals from several hospital centers in the department of Córdoba, Colombia, were received at our laboratory between April 9th and May 16th, 2020. RNA was extracted using lysis buffers and spin columns. The samples were tested for SARS-CoV-2 by reverse transcription real-time polymerase chain reaction (RT-qPCR) using commercially available multiplex real-time PCR assay for simultaneous detection of 3 target genes of SARS-CoV-2 (Allplex™, 2019-nCoV assay, Korea). Viral copies quantification was done using a standard curve constructed from seriated dilutions of a SARS-CoV-2 positive control. Statics descriptive methods were used. Results Thirty-five nasopharyngeal samples were positive for SARS-CoV-2 infection; the average age was 43 (range, 1–95 years). Seventeen of 35 (49%) of the patients showed symptoms. Most of them had a cough, fever, and odynophagia; three of the patients reported having arthralgia. Only two patients required hospitalization. None of the patients had known co-morbidities. RT-qPCR results show that two of the symptomatic patients had significantly higher RNA copies than the rest. Eighteen of 35 (51%) individuals were asymptomatic, and the average age was 30 (range, 6–61 years). Four asymptomatic individuals showed a higher copy than some symptomatic patients; nonetheless, the average of RNA copies 8.26 × 10 10 was lower than the symptomatic. Conclusions This study shows that asymptomatic patients may develop infections with a high number of RNA copies. Since a considerable percentage of infections may be asymptomatic/presymptomatic, enhanced testing approaches may be needed to detect these persons. Due the occurrence of a large proportion of infections being a result from transmission originated in asymptomatic/presymptomatic individuals, public health interventions in Colombia should be based on two steps: a massive molecular screening, and viral load quantification. Finally, a remarkable issue in our study is the average age of symptomatic and asymptomatic groups (43 and 30 respectively) which may be important because of the economic impact that has been caused by the coronavirus pandemic and may be probably the cause of the reduced lethality observed in the country and the department at the time of this study.

Background/Objectives: Huntington’s disease (HD) is a fully penetrant neurodegenerative disease with a profound effect on quality of life. In recent years, there has been rapid growth in the description of its pathogenesis and diagnosis. Magnetic resonance spectroscopy (MRS) measurements can aid in the discrimination between premanifest Huntington’s disease (Pre-HD) and healthy control (HC) subjects to establish early supportive and symptomatic management. Our objective was to evaluate metabolic changes using MRS to shed light on its potential as a biomarker through a systematic review. Methods: We followed the PRISMA guidelines, extracting articles from PubMed, Scopus, and the Virtual Health Library. We included patients with pre-HD, HD, and HC subjected to MRS, reporting the concentration of metabolites in at least one brain region. Results: In the putamen, N-acetyl Aspartate (NAA) was significantly decreased in 77.9% and total NAA (tNAA) was decreased in 72.4% of cases; no significant difference was found in 27.5% (n = 19) of cases. Furthermore, when looking into HD vs. pre-HD in the putamen, tNAA and NAA were decreased in 100% of participants. In the caudate nucleus, NAA and creatine were significantly decreased in 100% of HD in comparison to pre-HD participants, whereas tNAA showed a significant decrease in only 50%. Conclusions: MRS can be a relevant tool for the early diagnosis of HD; potential objective biomarkers related to its onset and pathogenesis exist and show differences between controls, pre-HD and HD patients. However, an effort should be made to standardize MRS methodology and reporting in subsequent studies.

Early screening to determine patient risk of developing Alzheimer’s will allow better interventions and planning but necessitates accessible methods such as behavioral biomarkers. Previously, we showed that cognitively healthy older individuals whose cerebrospinal fluid amyloid/tau ratio indicates high risk of cognitive decline experienced implicit interference during a high-effort task, signaling early changes in attention. To further investigate attention’s effect on implicit interference, we analyzed two experiments completed sequentially by the same high- and low-risk individuals. We hypothesized that if attention modulates interference, practice would affect the influence of implicit distractors. Indeed, while both groups experienced a strong practice effect, the association between practice and interference effects diverged between groups: stronger practice effects correlated with more implicit interference in high-risk participants, but less interference in low-risk individuals. Furthermore, low-risk individuals showed a positive correlation between implicit interference and EEG low-range alpha event-related desynchronization when switching from high- to low-load tasks. This suggests that lower attention on the task was correlated with stronger interference, a typical phenomenon in the younger population. These results demonstrate how attention impacts implicit interference and highlight early differences in perception between high- and low-risk individuals.