Factors affecting nursing staff use of a communication tool to reduce potentially preventable acute care transfers in long-term care.

Although specialized communication tools can effectively reduce acute care transfers, few studies have assessed the factors that may influence the use of such tools by nursing staff at the individual level. We evaluated the associations between years of experience, tool-related training, nursing attitudes, and intensity of use of a communication tool developed to reduce transfers in a long-term care facility. We employed a mixed methods design using data from medical charts, electronic records, and semi-structured interviews. Experienced nurses used the tool significantly less than inexperienced nurses, and training had a significant positive impact on tool use. Nurses found the purpose of the tool to be confusing. No significant differences in attitude were observed based on years of experience or intensity of use. Project findings indicate that focused efforts to enrich training may increase intervention adherence. Experienced nurses in particular should be made aware of the benefits of utilizing communication tools.

Assessment of algorithms for identifying patients with triple-class refractory multiple myeloma using real-world data.

Objective: Patients with triple-class refractory (TCR) multiple myeloma (MM) have limited treatment options and poor prognoses. This high unmet need has prompted the development of new therapies allowing for improved outcomes for these patients. Recently, new targeted therapies for the treatment of patients with relapsed or refractory MM have been approved based on single-arm clinical trial results. Real-world (RW) data enable a better understanding of the effectiveness of new therapies in clinical practice and provide external controls for single-arm studies. However, using RW data to identify patients with TCR MM is challenging and subject to limitations. Methods: In this retrospective cohort study of an analysis of the COTA electronic health record (EHR) database, we used four algorithms to define refractory status and created four groups of patients with TCR MM initiating post-TCR therapy. Each algorithm relied on slightly different criteria to identify TCR patients, but all were based on the International Myeloma Working Group (IMWG)-derived and/or healthcare provider (HCP)-reported progressions within the database. Results: A total of 3815 patients with newly diagnosed MM met the eligibility criteria for this study. The choice of the algorithm did not impact the characteristics of identified patients with TCR MM (Algorithm 1 [n = 404], Algorithm 2 [n = 123], Algorithm 3 [n = 404], and Algorithm 4 [n = 375]), including their demographic and disease characteristics, MM treatment history, or treatment patterns received after becoming TCR. However, identifying TCR MM using a combination of IMWG-derived and HCP-reported progressions allowed up to a 70% increase in the size of the identified group of patients compared with using only IMWG-derived progressions. Conclusion: In RW settings, progressions from both IMWG-derived data and physician reports may be used to identify patients with TCR MM.

Memantine versus donepezil in mild to moderate Alzheimer's disease: a randomized trial with magnetic resonance spectroscopy.

BACKGROUND AND PURPOSE: To compare memantine with the most prescribed cholinesterase inhibitor (donepezil) from a clinical viewpoint when administered in early phases of Alzheimer disease (AD), and to find out whether memantine may produce changes in brain metabolite concentrations in comparison with donepezil. METHODS: In this comparative rater-blinded parallel group randomized trial we recruited a consecutive sample of patients with probable mild to moderate AD. At baseline we carried out neuropsychological assessment with mini-mental, Clinical Dementia Rating Scale (CDR), Blessed Dementia Rating Scale, Alzheimer's Disease Assessment Scale, cognitive part (ADAS-cog), neuropsychiatric inventory (NPI), and disability assessment for dementia (DAD), as well as (1)H magnetic resonance spectroscopy (MRS) in several areas of the brain. Patients were randomized to receive either donepezil or memantine for 6 months. After this elapse of time we repeated the same procedures and observed the changes in clinical scales (ADAS-cog, NPI, DAD), as well as the changes in metabolite levels in every area of exploration (temporal, pre-frontal, posterior cingulated (PCG), and occipital), especially those of N-acetyl-aspartate (NAA) which is regarded as a surrogate marker of neuronal density. RESULTS: A total of sixty-three patients completed the trial. We did not see significant differences in clinical scales and metabolite levels between those on donepezil (n = 32) and those on memantine (n = 31). In general, more patients worsened than improved on either of the drugs. The changes in the NAA/creatine ratio in the PCG correlated significantly with the changes in the ADAS-cog (P = 0.004). CONCLUSIONS: Donepezil and memantine have similar modest clinical and spectroscopic effect on mild to moderate AD. MRS could be useful to monitor progression of the disease.

[Measuring linezolid in biological fluids using high-efficiency liquid chromatography]. / Determinación de linezolid en fluidos biológicos mediante cromatografía líquida de alta eficacia.

OBJECTIVE: Evaluation of an analytic method for determining linezolid concentrations in biological fluids including plasma, vitreous humour and cerebrospinal fluid using high-efficiency liquid chromatography and subsequent ultraviolet detection. METHOD: The method was validated by studying the following parameters: accuracy, precision, sensitivity, linearity and recovery. The drug was extracted from the biological matrix by means of a protein precipitation with perchloric acid. Chromatographic separation was performed by eluting linezolid with a mobile phase consisting of 80% K2HPO4 buffer solution (15 mM; pH=5) and 20% acetonitrile, and a stationary phase, NOVAPAK C18 150x3.9 mm with precolumn. The wavelength reading was 254 nm and the working flow rate was 1 ml/min. RESULTS: We obtained values with accuracies between 94.4 and 106.1%, and precisions between 0.88-6% and 3.7-5.6% for intra-and inter-day variability, respectively. Recovery obtained after analysing the plasma samples was at 93%. The method showed itself to be linear for the concentration levels under study. DISCUSSION: The method's behaviour can be described as linear, precise and accurate. Furthermore, the method is fast, sensitive, and inexpensive. It is useful for determining linezolid concentrations in multiple biological matrices. It can also be used as a basis for further clinical pharmacokinetic studies.

[Direct embolization of stomal varices in portal hypertension after the treatment of liver metastases]. / Embolización directa de varices estomales en la hipertensión portal tras el tratamiento de metástasis hepáticas.

We present the case of a man with a history of colorectal carcinoma and metastatic liver involvement who developed portal hypertension and recurrent bleeding from stomal varices after treatment with intra-arterial oxaliplatin and radioembolization with yttrium-90 microspheres. The definitive treatment for the bleeding episodes was embolization of the varices with coils using a direct percutaneous approach.

Addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in treatment of experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

This study evaluated the activity of daptomycin combined with either gentamicin or rifampin against three methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates in vitro and one isolate in vivo against a representative strain (MRSA-572). Time-kill experiments showed that daptomycin was bactericidal against these strains at concentrations over the MIC. Daptomycin at sub-MIC concentrations plus gentamicin at 1x and 2x the MIC yielded synergy, while the addition of rifampin at 2 to 4 microg/ml resulted in indifference (two strains) or antagonism (one strain). The in vivo activity of daptomycin (6 mg/kg of body weight once a day) was evaluated +/- gentamicin (1 mg/kg intravenously [i.v.] every 8 h [q8h]) or rifampin (300 mg i.v. q8h) in a rabbit model of infective endocarditis by simulating human pharmacokinetics. Daptomycin plus gentamicin (median, 0 [interquartile range, 0 to 2] log10 CFU/g vegetation) was as effective as daptomycin alone (0 [0 to 2] log10 CFU/g vegetation) in reducing the density of bacteria in valve vegetations (P = 0.83), and both were more effective than daptomycin plus rifampin (3 [2 to 3.5] log10 CFU/g vegetation; P < 0.05) for the strain studied. In addition, daptomycin sterilized a ratio of vegetations that was similar to that of daptomycin plus gentamicin (10/15 [67%] versus 9/15 [60%]; P = 0.7), and both regimens did so more than daptomycin plus rifampin (3/15 [20%]; P = 0.01 and P = 0.02, respectively). No statistical difference was noted between daptomycin plus gentamicin and daptomycin alone for MRSA treatment. In the combination arm, all isolates from vegetations remained susceptible to daptomycin, gentamicin, and rifampin. Sixty-one percent of the isolates (8/13) acquired resistance to rifampin during monotherapy. In the daptomycin arm, resistance was detected in only one case, in which the daptomycin MIC rose to 2 microg/ml among the recovered bacteria. In conclusion, the addition of gentamicin or rifampin does not enhance the effectiveness of daptomycin in the treatment of experimental endocarditis due to MRSA.

[Exploring the experience of living with a heart transplant: a systematic review of the literature]. / Explorando la experiencia de vivir con un trasplante cardíaco: una revisión sistemática de la literatura.

The focus of healthcare professionals is shifting from illness to health and the individual experience of each person. However, current health care continues to focus on the prevention and treatment of medical complications, leaving aside other important aspects of the experience of cardiac transplant patients. The aim of this systematic review of the literature was to explore how living with a transplanted heart affects their lives. We searched the databases Pubmed, Cinahl, Scielo, Scopus, Dialnet, Cuiden and PsyINFO, and specialized journals. Twenty-five articles were included for study. The analysis and interpretation of the results was based on the methodology by Dixon-Woods et al and by Evans. The results were grouped into seven categories: spiritual repercussions, psychological repercussions, social repercussions, relationship with the donor and the organ, repercussions in the physical environment and quality of life, coping strategies, and feelings towards the healthcare professionals. The results confirm the need for a change in the care given to cardiac transplant patients given that, although transplantation has been shown to improve the quality and quantity of life, it has multiple psychosocial implications that affect the well-being and day-to-day life of these patients.

Guidelines for seizure management in palliative care: Proposal for an updated clinical practice model based on a systematic literature review. / Guía para el manejo de las crisis epilépticas en cuidados paliativos: propuesta de un modelo actualizado de práctica clínica basado en una revisión sistemática de la literatura.

INTRODUCTION: Very little has been written on seizure management in palliative care (PC). Given this situation, and considering the forthcoming setting up of the Palliative Care Unit at our neurorehabilitation centre, the Clínica San Vicente, we decided to establish a series of guidelines on the use of antiepileptic drugs (AEDs) for handling seizures in PC. METHODS: We conducted a literature search in PubMed to identify articles, recent manuals, and clinical practice guidelines on seizure management in PC published by the most relevant scientific societies. RESULTS: Clinical practice guidelines are essential to identify patients eligible for PC, manage seizures adequately, and avoid unnecessary distress to these patients and their families. Given the profile of these patients, we recommend choosing AEDs with a low interaction potential and which can be administered by the parenteral route, preferably intravenously. Diazepam and midazolam appear to be the most suitable AEDs during the acute phase whereas levetiracetam, valproic acid, and lacosamide are recommended for refractory cases and long-term treatment. CONCLUSIONS: These guidelines provide general recommendations that must be adapted to each particular clinical case. Nevertheless, we will require further well-designed randomised controlled clinical trials including large samples of patients eligible for PC to draft a consensus document recommending adequate, rational, and effective use of AEDs, based on a high level of evidence, in this highly complex area of medical care.

Plasma Aß42/40 Ratio Detects Early Stages of Alzheimer's Disease and Correlates with CSF and Neuroimaging Biomarkers in the AB255 Study.

BACKGROUND: Easily accessible biomarkers are needed for the early identification of individuals at risk of developing Alzheimer's disease (AD) in large population screening strategies. OBJECTIVES: This study evaluated the potential of plasma ß-amyloid (Aß) biomarkers in identifying early stages of AD and predicting cognitive decline over the following two years. DESIGN: Total plasma Aß42/40 ratio (TP42/40) was determined in 83 cognitively normal individuals (CN) and 145 subjects with amnestic mild cognitive impairment (a-MCI) stratified by an FDG-PET AD-risk pattern. RESULTS: Significant lower TP42/40 ratio was found in a-MCI patients compared to CN. Moreover, a-MCIs with a high-risk FDG-PET pattern for AD showed even lower plasma ratio levels. Low TP42/40 at baseline increased the risk of progression to dementia by 70%. Furthermore, TP42/40 was inversely associated with neocortical amyloid deposition (measured with PiB-PET) and was concordant with the AD biomarker profile in cerebrospinal fluid (CSF). CONCLUSIONS: TP42/40 demonstrated value in the identification of individuals suffering a-MCI, in the prediction of progression to dementia, and in the detection of underlying AD pathology revealed by FDG-PET, Amyloid-PET and CSF biomarkers, being, thus, consistently associated with all the well-established indicators of AD.

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. / Evidencias actuales sobre la estimulación magnética transcraneal y su utilidad potencial en la neurorrehabilitación postictus: Ampliando horizontes en el tratamiento de la enfermedad cerebrovascular.

INTRODUCTION: Repetitive transcranial magnetic stimulation (rTMS) is a therapeutic reality in post-stroke rehabilitation. It has a neuroprotective effect on the modulation of neuroplasticity, improving the brain's capacity to retrain neural circuits and promoting restoration and acquisition of new compensatory skills. DEVELOPMENT: We conducted a literature search on PubMed and also gathered the latest books, clinical practice guidelines, and recommendations published by the most prominent scientific societies concerning the therapeutic use of rTMS in the rehabilitation of stroke patients. The criteria of the International Federation of Clinical Neurophysiology (2014) were followed regarding the inclusion of all evidence and recommendations. CONCLUSIONS: Identifying stroke patients who are eligible for rTMS is essential to accelerate their recovery. rTMS has proven to be safe and effective for treating stroke complications. Functional brain activity can be optimised by applying excitatory or inhibitory electromagnetic pulses to the hemisphere ipsilateral or contralateral to the lesion, respectively, as well as at the level of the transcallosal pathway to regulate interhemispheric communication. Different studies of rTMS in these patients have resulted in improvements in motor disorders, aphasia, dysarthria, oropharyngeal dysphagia, depression, and perceptual-cognitive deficits. However, further well-designed randomized controlled clinical trials with larger sample size are needed to recommend with a higher level of evidence, proper implementation of rTMS use in stroke subjects on a widespread basis.

Correlations between plasma and PET beta-amyloid levels in individuals with subjective cognitive decline: the Fundació ACE Healthy Brain Initiative (FACEHBI).

BACKGROUND: Peripheral biomarkers that identify individuals at risk of developing Alzheimer's disease (AD) or predicting high amyloid beta (Aß) brain burden would be highly valuable. To facilitate clinical trials of disease-modifying therapies, plasma concentrations of Aß species are good candidates for peripheral AD biomarkers, but studies to date have generated conflicting results. METHODS: The Fundació ACE Healthy Brain Initiative (FACEHBI) study uses a convenience sample of 200 individuals diagnosed with subjective cognitive decline (SCD) at the Fundació ACE (Barcelona, Spain) who underwent amyloid florbetaben(18F) (FBB) positron emission tomography (PET) brain imaging. Baseline plasma samples from FACEHBI subjects (aged 65.9 ± 7.2 years) were analyzed using the ABtest (Araclon Biotech). This test directly determines the free plasma (FP) and total plasma (TP) levels of Aß40 and Aß42 peptides. The association between Aß40 and Aß42 plasma levels and FBB-PET global standardized uptake value ratio (SUVR) was determined using correlations and linear regression-based methods. The effect of the APOE genotype on plasma Aß levels and FBB-PET was also assessed. Finally, various models including different combinations of demographics, genetics, and Aß plasma levels were constructed using logistic regression and area under the receiver operating characteristic curve (AUROC) analyses to evaluate their ability for discriminating which subjects presented brain amyloidosis. RESULTS: FBB-PET global SUVR correlated weakly but significantly with Aß42/40 plasma ratios. For TP42/40, this observation persisted after controlling for age and APOE ε4 allele carrier status (R2 = 0.193, p = 1.01E-09). The ROC curve demonstrated that plasma Aß measurements are not superior to APOE and age in combination in predicting brain amyloidosis. It is noteworthy that using a simple preselection tool (the TP42/40 ratio with an empirical cut-off value of 0.08) optimizes the sensitivity and reduces the number of individuals subjected to Aß FBB-PET scanners to 52.8%. No significant dependency was observed between APOE genotype and plasma Aß measurements (p value for interaction = 0.105). CONCLUSION: Brain and plasma Aß levels are partially correlated in individuals diagnosed with SCD. Aß plasma measurements, particularly the TP42/40 ratio, could generate a new recruitment strategy independent of the APOE genotype that would improve identification of SCD subjects with brain amyloidosis and reduce the rate of screening failures in preclinical AD studies. Independent replication of these findings is warranted.

FACEHBI: A Prospective Study of Risk Factors, Biomarkers and Cognition in a Cohort of Individuals with Subjective Cognitive Decline. Study Rationale and Research Protocols.

BACKGROUND: Long-term longitudinal studies with multimodal biomarkers are needed to delve into the knowledge of preclinical AD. Subjective cognitive decline has been proposed as a risk factor for the development of cognitive impairment. Thus, including individuals with SCD in observational studies may be a cost-effective strategy to increase the prevalence of preclinical AD in the sample. OBJECTIVES: To describe the rationale, research protocols and baseline characteristics of participants in the Fundació ACE Healthy Brain Initiative (FACEHBI). DESIGN: FACEHBI is a clinical trial (EudraCT: 2014-000798-38) embedded within a long-term observational study of individuals with SCD. SETTING: Participants have been recruited at the memory clinic of Fundació ACE (Barcelona) from two different sources: patients referred by a general practitioner and individuals from an Open House Initiative. PARTICIPANTS: 200 individuals diagnosed with SCD with a strictly normal performance in a comprehensive neuropsychological battery. MEASUREMENTS: Individuals will undergo an extensive neuropsychological protocol, risk factor assessment and a set of multimodal biomarkers including florbetaben PET, structural and functional MRI, diffusion tensor imaging, determination of amyloid species in plasma and neurophthalmologic assessment with optical coherence tomography. RESULTS: Two hundred individuals have been recruited in 15 months. Mean age was 65.9 years; mean MMSE was 29.2 with a mean of 14.8 years of education. CONCLUSIONS: FACEHBI is a long-term study of cognition, biomarkers and lifestyle that has been designed upon an innovative symptom-based approach using SCD as target population. It will shed light on the pathophysiology of preclinical AD and the role of SCD as a risk marker for the development of cognitive impairment.

[Experimental models for Alzheimer's disease research]. / Modelos experimentales de la enfermedad de Alzheimer.

INTRODUCTION AND DEVELOPMENT: Current animal models for Alzheimer's research include transgenic mice that express a mutant form of human beta-amyloid precursor protein (APP). However, the mutant mice with the human APP transgene also have their own endogenous APP gene, which may interfere with APP processing to generate beta-amyloid peptide. CONCLUSION: By genetic and immunochemical analyses, our laboratory has discovered that there are animals in the nature, the chick embryo and the dog in particular, which may be better experimental models than the transgenic mice, because they contain the same machinery as humans to process APP and they are easier to access, manipulate or explore their neurology. These species may be natural experimental models to study the cell biology of Alzheimer's APP and potential assay systems for drugs used to regulate beta-amyloid production as well as for the assay of new therapeutic strategies against so devasting disease.

[Revision of obstructive sleep apnea syndrome in the child]. / Revision del síndrome de apnea obstructiva del sueño en el niño.

The obstructive sleep apnea syndrome (OSAS) is frequent in infancy and childhood. It is caused by a prolonged upper respiratory airway obstructioon during sleep, and adenotonsillar hypertrophy is the most important cause. OSAS may have an impact on physical and cognitive development, but syntoms in children are subtle and may pass unrecognised. Polysomnography is the gold standard technique for OSAS diagnosis and surgical approach with adenotonsillectomy is the most frequently treatment indicated. Early diagnosis and treatment and adequate follow up are important to prevent physical disturbances secondary to chronic hypoxemia and to avoid cognitive deficits associated with disrupted sleep architecture.

Mortality risk of sotalol and amiodarone for post-CABG atrial fibrillation.

BACKGROUND: Sotalol and amiodarone are commonly prescribed antiarrhythmics for the treatment of post-operative atrial fibrillation (POAF). Though they are effective in maintaining sinus rhythm in this population, little is known about their association with mortality. OBJECTIVES: To examine the association between sotalol and amiodarone exposure and total mortality in individuals with new-onset POAF following CABG. METHODS: The computerised health databases of Quebec, Canada were used to identify all patients over 65 who had undergone CABG and were newly diagnosed with POAF (January 1993 to June 2003). A time-matched nested-case-control approach was used to compare current users of sotalol and amiodarone with those not exposed to either medication during the same period. Rate ratios of mortality were estimated using conditional logistic regression. RESULTS: 4770 eligible patients were identified (930 cases, 4648 matched controls). Sotalol users had fewer comorbidities and used fewer concomitant medications than amiodarone users at baseline. Current users of sotalol were at decreased risk of mortality compared to individuals not exposed to either study drug during the same period (RRadj. 0.56 (0.39, 0.80)) while current users of amiodarone were at increased risk of mortality (RRadj. 1.50 (1.15, 1.94)). However this association was not consistently observed across all sensitivity and subgroup analyses. CONCLUSIONS: Current use of sotalol was associated with a decreased risk of mortality. Current use of amiodarone was associated with an increased risk of mortality but not for all subgroups. Additional research is required to better understand the safety of sotalol and amiodarone in individuals with POAF.

The chick embryo appears as a natural model for research in beta-amyloid precursor protein processing.

This study reveals that the chick embryo has active the machinery for the production and degradation of the amyloid beta peptide characteristic of Alzheimer's disease. We cloned the principal beta-amyloid precursor protein isoforms in the chick embryo and observed that they are highly homologous to the human sequences and identical at the C-terminal sequence, including the amyloid beta domain. Mammals such as rat or mouse, more commonly used as animal models of human diseases, have a distinct amyloid beta sequence. The distribution of beta-amyloid precursor protein isoforms in the chick embryo revealed that, as in humans, their expression is ubiquitous and the prototype beta-amyloid precursor protein-695 predominated in the nervous system. We also found that the chick embryo expresses the genes for the main proteolytic proteases implicated in the production of amyloid beta, including BACE-1, BACE-2, presenilin-1, presenilin-2 and nicastrin, as well as the amyloid beta-degrading enzyme neprilysin, or ADAM-17, a protease implicated in the non-amyloidogenic processing of beta-amyloid precursor protein. We have also found that between amyloid beta40 and amyloid beta42, this latter seems to be the major amyloid beta peptide produced during chick embryogenesis. The chick embryo appears as a suitable natural model to study cell biology and developmental function of beta-amyloid precursor protein and a potential assay system for drugs that regulate beta-amyloid precursor protein processing.

Alzheimer beta-amyloid precursor proteins display specific patterns of expression during embryogenesis.

The beta-amyloid precursor proteins (betaAPPs) are a family of glycosylated transmembrane proteins that include in their sequences the beta-amyloid peptide, a major component of the characteristic amyloid deposits or senile plaques found in the brains of Alzheimer's disease patients and aged Down's syndrome subjects. Various betaAPP isoforms, mainly betaAPP-695, betaAPP-714, betaAPP-751 and betaAPP-770, the number corresponding to the number of amino acids they encode, resulting from the alternative splicing of a single primary transcript have been described. Using oligonucleotides recognizing each of the four major Alzheimer's betaAPP mRNAs, we have found that each betaAPP mRNA displays a specific temporal and spatial pattern of expression. The prototype isoform betaAPP-695 occurs early in cells actively implicated in morphogenetic events, as those mesodermal cells invaginating at the level of the primitive streak, and it is later restricted to the neurectodermal (neural tube, neural crest and neurogenic placode) derivatives. By contrast, the longest isoform betaAPP-770 appears later and restricted to mesodermal and endodermal derivatives. The isoforms betaAPP-714 and betaAPP-751 are still expressed later than the other two isoforms and distributed ubiquitously, though betaAPP-714 transcripts predominate typically within the neural tube.

The two mature transcripts of the chick calcitonin gene are expressed within the central nervous system during embryogenesis.

Calcitonin mRNA and calcitonin gene-related peptide (CGRP) mRNA both are generated from the calcitonin gene because of tissue-specific alternative splicing of the primary transcript. It is currently established that, of the two mature transcripts, calcitonin mRNA is far the predominant transcript produced in thyroid C-cells whereas only CGRP mRNA is produced in the nervous system. However, here we provide evidence that the two splicing forms of the chick calcitonin primary transcript are found within the developing central nervous system, although displaying specific patterns of expression. While CGRP mRNA is first expressed in motor neurons at rather advanced stages of embryogenesis, calcitonin mRNA is expressed in the floor plate and dorsal rhombencephalon from earliest stages.

Beyond the Controversy on Aß Blood-Based Biomarkers.

Central biomarkers of Alzheimer's disease (AD) have been proven to have diagnostic and prognostic capacity. However, both amyloid positron emission tomography and cerebrospinal fluid collection studies present problems that limit their widespread acceptability in global clinical trials. Thus, development of other measures as potential surrogates of amyloid positivity should be pursued. Results from numerous experimental studies strongly suggest that the association between Aß plasma levels, particularly the Aß42/Aß40 ratio, and AD diagnosis goes beyond what could be attributable to pure chance, although this association is still controversial. The aim of this review is to consider selected works that may help to improve the design of blood based biomarkers studies by controlling a number of confounding sources related to the clinical gold standard, the time-course of central and peripheral biomarkers, and the metabolism of Aß in blood that may be blurring the presumptive association between Aß blood levels and AD. Based on these data and to get pass the controversy, we tentatively postulate that at early stages of preclinical AD, blood Aß levels and central Aß biomarkers would follow parallel but temporally displaced trajectories. This association would become eventually lost as the disease progresses and the clearance mechanisms in the blood brain barrier are increasingly impaired.