Pulse oximetry in the oesophagus

Pulse oximetry has been one of the most significant technological advances in clinical monitoring in the last two decades. Pulse oximetry is a non-invasive photometric technique that provides information about the arterial blood oxygen saturation (SpO(2)) and heart rate, and has widespread clinical applications. When peripheral perfusion is poor, as in states of hypovolaemia, hypothermia and vasoconstriction, oxygenation readings become unreliable or cease. The problem arises because conventional pulse oximetry sensors must be attached to the most peripheral parts of the body, such as finger, ear or toe, where pulsatile flow is most easily compromised. Since central blood flow may be preferentially preserved, this review explores a new alternative site, the oesophagus, for monitoring blood oxygen saturation by pulse oximetry. This review article presents the basic physics, technology and applications of pulse oximetry including photoplethysmography. The limitations of this technique are also discussed leading to the proposed development of the oesophageal pulse oximeter. In the majority, the report will be focused on the description of a new oesophageal photoplethysmographic/SpO(2) probe, which was developed to investigate the suitability of the oesophagus as an alternative monitoring site for the continuous measurement of SpO(2) in cases of poor peripheral circulation. The article concludes with a review of reported clinical investigations of the oesophageal pulse oximeter

The road ahead to cure Alzheimer’s disease: development of biological markers and neuroimaging methods for prevention trials across all stages and target populations

International audienceAlzheimer's disease (AD) is a slowly progressing non-linear dynamic brain disease in whichpathophysiological abnormalities, detectable in vivo by biological markers, precede overtclinical symptoms by many years to decades. Use of these biomarkers for the detection ofearly and preclinical AD has become of central importance following publication of twointernational expert working group's revised criteria for the diagnosis of AD dementia, mildcognitive impairment (MCI) due to AD, prodromal AD and preclinical AD. As a consequenceof matured research evidence six AD biomarkers are sufficiently validated and partlyqualified to be incorporated into operationalized clinical diagnostic criteria and use in primaryand secondary prevention trials. These biomarkers fall into two molecular categories:biomarkers of amyloid-beta (Aβ) deposition and plaque formation as well as of tau-proteinrelated hyperphosphorylation and neurodegeneration. Three of the six gold-standard ("corefeasible) biomarkers are neuroimaging measures and three are cerebrospinal fluid (CSF)analytes. CSF Aβ 1-42 (Aβ1-42), also expressed as Aβ1-42 : Aβ1-40 ratio, T-tau, and P-tau Thr181 &Thr231 proteins have proven diagnostic accuracy and risk enhancement in prodromal MCI andAD dementia. Conversely, having all three biomarkers in the normal range rules out AD.Intermediate conditions require further patient follow-up. Magnetic resonance imaging (MRI)at increasing field strength and resolution allows detecting the evolution of distinct types ofstructural and functional abnormality pattern throughout early to late AD stages. Anatomicalor volumetric MRI is the most widely used technique and provides local and global measuresof atrophy. The revised diagnostic criteria for “prodromal AD” and "mild cognitiveimpairment due to AD" include hippocampal atrophy (as the fourth validated biomarker),which is considered an indicator of regional neuronal injury. Advanced image analysistechniques generate automatic and reproducible measures both in regions of interest, such asthe hippocampus and in an exploratory fashion, observer and hypothesis-indedendent, throughout the entire brain. Evolving modalities such as diffusion-tensor imaging (DTI) andadvanced tractography as well as resting-state functional MRI provide useful additionallyuseful measures indicating the degree of fiber tract and neural network disintegration(structural, effective and functional connectivity) that may substantially contribute to earlydetection and the mapping of progression. These modalities require further standardizationand validation. The use of molecular in vivo amyloid imaging agents (the fifth validatedbiomarker), such as the Pittsburgh Compound-B and markers of neurodegeneration, such asfluoro-2-deoxy-D-glucose (FDG) (as the sixth validated biomarker) support the detection ofearly AD pathological processes and associated neurodegeneration. How to use, interpret, anddisclose biomarker results drives the need for optimized standardization. Multimodal ADbiomarkers do not evolve in an identical manner but rather in a sequential but temporallyoverlapping fashion. Models of the temporal evolution of AD biomarkers can take the form ofplots of biomarker severity (degree of abnormality) versus time. AD biomarkers can becombined to increase accuracy or risk. A list of genetic risk factors is increasingly included insecondary prevention trials to stratify and select individuals at genetic risk of AD. Althoughmost of these biomarker candidates are not yet qualified and approved by regulatoryauthorities for their intended use in drug trials, they are nonetheless applied in ongoingclinical studies for the following functions: (i) inclusion/exclusion criteria, (ii) patientstratification, (iii) evaluation of treatment effect, (iv) drug target engagement, and (v) safety.Moreover, novel promising hypothesis-driven, as well as exploratory biochemical, genetic,electrophysiological, and neuroimaging markers for use in clinical trials are being developed.The current state-of-the-art and future perspectives on both biological and neuroimagingderived biomarker discovery and development as well as the intended application inprevention trials is outlined in the present publication

Gray matter network disruptions and regional amyloid beta in cognitively normal adults

The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [18F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (ß = -0.12, p < 0.05), and small world values (ß = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria

During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations

Gray matter network disruptions and regional amyloid beta in cognitively normal adults

The accumulation of amyloid plaques is one of the earliest pathological changes in Alzheimer's disease (AD) and may occur 20 years before the onset of symptoms. Examining associations between amyloid pathology and other early brain changes is critical for understanding the pathophysiological underpinnings of AD. Alterations in gray matter networks might already start at early preclinical stages of AD. In this study, we examined the regional relationship between amyloid aggregation measured with positron emission tomography (PET) and gray matter network measures in elderly subjects with subjective memory complaints. Single-subject gray matter networks were extracted from T1-weigthed structural MRI in cognitively normal subjects (n = 318, mean age 76.1 ± 3.5, 64% female, 28% amyloid positive). Degree, clustering, path length and small world properties were computed. Global and regional amyloid load was determined using [18F]-Florbetapir PET. Associations between standardized uptake value ratio (SUVr) values and network measures were examined using linear regression models. We found that higher global SUVr was associated with lower clustering (Ã\u9f = -0.12, p < 0.05), and small world values (Ã\u9f = -0.16, p < 0.01). Associations were most prominent in orbito- and dorsolateral frontal and parieto-occipital regions. Local SUVr values showed less anatomical variability and did not convey additional information beyond global amyloid burden. In conclusion, we found that in cognitively normal elderly subjects, increased global amyloid pathology is associated with alterations in gray matter networks that are indicative of incipient network breakdown towards AD dementia

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations

Preclinical Alzheimer's disease: Definition, natural history, and diagnostic criteria.

During the past decade, a conceptual shift occurred in the field of Alzheimer's disease (AD) considering the disease as a continuum. Thanks to evolving biomarker research and substantial discoveries, it is now possible to identify the disease even at the preclinical stage before the occurrence of the first clinical symptoms. This preclinical stage of AD has become a major research focus as the field postulates that early intervention may offer the best chance of therapeutic success. To date, very little evidence is established on this "silent" stage of the disease. A clarification is needed about the definitions and lexicon, the limits, the natural history, the markers of progression, and the ethical consequence of detecting the disease at this asymptomatic stage. This article is aimed at addressing all the different issues by providing for each of them an updated review of the literature and evidence, with practical recommendations

Subjective cognitive decline and rates of incident Alzheimer's disease and non\u2013Alzheimer's disease dementia

Introduction: In this multicenter study on subjective cognitive decline (SCD) in community-based and memory clinic settings, we assessed the (1) incidence of Alzheimer's disease (AD) and non-AD dementia and (2) determinants of progression to dementia. Methods: Eleven cohorts provided 2978 participants with SCD and 1391 controls. We estimated dementia incidence and identified risk factors using Cox proportional hazards models. Results: In SCD, incidence of dementia was 17.7 (95% Poisson confidence interval 15.2-20.3)/1000 person-years (AD: 11.5 [9.6-13.7], non-AD: 6.1 [4.7-7.7]), compared with 14.2 (11.3-17.6) in controls (AD: 10.1 [7.7-13.0], non-AD: 4.1 [2.6-6.0]). The risk of dementia was strongly increased in SCD in a memory clinic setting but less so in a community-based setting. In addition, higher age (hazard ratio 1.1 [95% confidence interval 1.1-1.1]), lower Mini\u2013Mental State Examination (0.7 [0.66-0.8]), and apolipoprotein E \u3b54 (1.8 [1.3-2.5]) increased the risk of dementia. Discussion: SCD can precede both AD and non-AD dementia. Despite their younger age, individuals with SCD in a memory clinic setting have a higher risk of dementia than those in community-based cohorts

Differential default mode network trajectories in asymptomatic individuals at risk for Alzheimer's disease

International audienc