Clinical value of plasma ALZpath pTau217 immunoassay for assessing mild cognitive impairment.

BACKGROUND: Among plasma biomarkers for Alzheimer's disease (AD), pTau181 and pTau217 are the most promising. However, transition from research to routine clinical use will require confirmation of clinical performance in prospective cohorts and evaluation of cofounding factors. METHOD: pTau181 and pTau217 were quantified using, Quanterix and ALZpath, SIMOA assays in the well-characterised prospective multicentre BALTAZAR (Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk) cohort of participants with mild cognitive impairment (MCI). RESULTS: Among participants with MCI, 55% were Aß+ and 29% developed dementia due to AD. pTau181 and pTau217 were higher in the Aß+ population with fold change of 1.5 and 2.7, respectively. MCI that converted to AD also had higher levels than non-converters, with HRs of 1.38 (1.26 to 1.51) for pTau181 compared with 8.22 (5.45 to 12.39) for pTau217. The area under the curve for predicting Aß+ was 0.783 (95% CI 0.721 to 0.836; cut-point 2.75 pg/mL) for pTau181 and 0.914 (95% CI 0.868 to 0.948; cut-point 0.44 pg/mL) for pTau217. The high predictive power of pTau217 was not improved by adding age, sex and apolipoprotein E ε4 (APOEε4) status, in a logistic model. Age, APOEε4 and renal dysfunction were associated with pTau levels, but the clinical performance of pTau217 was only marginally altered by these factors. Using a two cut-point approach, a 95% positive predictive value for Aß+ corresponded to pTau217 >0.8 pg/mL and a 95% negative predictive value at <0.23 pg/mL. At these two cut-points, the percentages of MCI conversion were 56.8% and 9.7%, respectively, while the annual rates of decline in Mini-Mental State Examination were -2.32 versus -0.65. CONCLUSIONS: Plasma pTau217 and pTau181 both correlate with AD, but the fold change in pTau217 makes it better to diagnose cerebral amyloidosis, and predict cognitive decline and conversion to AD dementia.

The role of nutrition in the prevention of cognitive decline.

PURPOSE OF REVIEW: Dementia is a growing concern and underscores the urgent need for effective preventive measures targeting modifiable risk factors. Nutrition is a key player in the onset and progression of inflammation and cognitive decline. This review provides a comprehensive overview of the effects of different dietary patterns, vitamins and nutrients for preventing cognitive decline, mainly among healthy individuals and those with mild cognitive impairment. RECENT FINDINGS: The Mediterranean diet, omega-3 long-chain polyunsaturated fatty acids and B vitamins are the most investigated, with evidence supporting protection against cognitive decline among older adults varying across studies. More recent interventions examined in this review, such as MIND Diet, are promising with positive results, but further research is needed to conclusively establish their efficacy. It is also crucial to consider complete lifestyle as physical activity for preventing cognitive decline. SUMMARY: Definitive conclusions are difficult to draw. Future studies should adopt a comprehensive approach and focus on multinutrient strategies and whole diets.

Association of caffeine consumption with cerebrospinal fluid biomarkers in mild cognitive impairment and Alzheimer's disease: A BALTAZAR cohort study.

INTRODUCTION: We investigated the link between habitual caffeine intake with memory impairments and cerebrospinal fluid (CSF) biomarkers in mild cognitive impairment (MCI) and Alzheimer's disease (AD) patients. METHODS: MCI (N = 147) and AD (N = 116) patients of the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) cohort reported their caffeine intake at inclusion using a dedicated survey. Associations of caffeine consumption with memory impairments and CSF biomarkers (tau, p-tau181, amyloid beta 1-42 [Aß1-42], Aß1-40) were analyzed using logistic and analysis of covariance models. RESULTS: Adjusted on Apolipoprotein E (APOE ε4), age, sex, education level, and tobacco, lower caffeine consumption was associated with higher risk to be amnestic (OR: 2.49 [95% CI: 1.13 to 5.46]; p = 0.023) and lower CSF Aß1-42 (p = 0.047), Aß1-42/Aß1-40 (p = 0.040), and Aß1-42/p-tau181 (p = 0.020) in the whole cohort. DISCUSSION: Data support the beneficial effect of caffeine consumption to memory impairments and CSF amyloid markers in MCI and AD patients. HIGHLIGHTS: We studied the impact of caffeine consumption in the BALTAZAR cohort. Low caffeine intake is associated with higher risk of being amnestic in MCI/AD patients. Caffeine intake is associated with CSF biomarkers in AD patients.

Blood Neurofilament Levels Predict Cognitive Decline across the Alzheimer's Disease Continuum.

Neurofilament light chain (NfL) is a potential diagnostic and prognostic plasma biomarker for numerous neurological diseases including Alzheimer's disease (AD). In this study, we investigated the relationship between baseline plasma concentration of Nfl and Mild Cognitive Impairment in participants who did and did not have a clinically determined diagnosis of dementia by the end of the three-year study. Additionally, we explored the connection between baseline plasma concentration of NfL and AD dementia patients, considering their demographics, clinical features, and cognitive profiles. A total of 350 participants from the Biomarker of AmyLoid pepTide and AlZheimer's diseAse Risk (BALTAZAR) multicenter prospective study were investigated: 161 AD dementia participants and 189 MCI participants (of which 141 had amnestic MCI and 48 non-amnestic MCI). Plasma biomarkers were measured at baseline and the progression of clinical and cognitive profiles was followed over the three years of follow-up. Baseline plasma NfL concentration increased across the Alzheimer's disease continuum with a mean NfL value of 17.1 ng/mL [SD = 6.1] in non-amnestic MCI, 20.7 ng/mL [SD = 12.0] in amnestic MCI, and 23.1 ng/mL [SD = 22.7] in AD dementia patients. Plasma NfL concentration correlated with age, body mass index (BMI), and global cognitive performance and decline, as measured by the Mini-Mental State Examination (MMSE). MMSE scores decreased in parallel with increasing plasma NfL concentration, independently of age and BMI. However, NfL concentration did not predict MCI participants' conversion to dementia within three years. Discussion: Baseline plasma NfL concentration is associated with cognitive status along the AD continuum, suggesting its usefulness as a potential informative biomarker for cognitive decline follow-up in patients.

[Natriuretic peptides in the diagnosis and monitoring of heart failure]. / Peptides natriurétiques dans le diagnostic et le suivi de l'insuffisance cardiaque.

NATRIURETIC PEPTIDES IN THE DIAGNOSIS AND MONITORING OF CARDIAC FAILURE. Heart failure (HF) is a serious and common disease requiring a prompt diagnosis for appropriate management. Natriuretic peptides, such as BNP and NT-proBNP, play a crucial role in diagnosing HF due to their s pecificity and reproducibility. It is important to measuring natriuretic peptides, especially in cases of acute dyspnea, to differentiate cardiac causes from others. Specific thresholds are recommended, with high values strongly suggest HF, while normal levels rule out the diagnosis. Clinical characteristics, such as age, renal function, atrial fibrillation, obesity, and gender, influence natriuretic peptides levels and should be considered in interpretation. For diabetic, hypertensive, and obese patients, early screening for HF through natriuretic peptides measurement is crucial. Furthermore, these natriuretic peptides are useful for monitoring chronic heart failure patients. They assist in confirming decompensation, titrating treatment, evaluating treatment response, and establishing prognosis. However, it's essential to choose a single biomarker (BNP or NT-proBNP) to avoid confusion.

DANS LE DIAGNOSTIC ET LE SUIVI DE L'INSUFFISANCE CARDIAQUE. L'insuffisance cardiaque (IC) est une maladie grave et fréquente nécessitant un diagnostic rapide pour une prise en charge adéquate. Les peptides natriurétiques, tels que le BNP et le NT-proBNP, jouent un rôle essentiel dans le diagnostic de l'IC en raison de leur spécificité et de leur reproductibilité. Il est important de doser les peptides natriurétiques, en particulier lors d'une dyspnée aiguë, pour différencier les causes cardiaques des autres. Des seuils spécifiques sont recommandés, et des valeurs élevées évoquent fortement une IC, tandis que des taux normaux écartent le diagnostic. Les caractéristiques cliniques ­ telles que l'âge, la fonction rénale, la fibrillation atriale, l'obésité et le sexe ­ modifient les taux de peptides natriurétiques et doivent être prises en compte dans l'interprétation. Chez les patients diabétiques, hypertendus et obèses, le dépistage précoce de l'IC par le dosage des peptides natriurétiques est crucial. De plus, ces peptides natriurétiques sont utiles pour le suivi des patients insuffisants cardiaques chroniques. Ils aident à confirmer une décompensation, à titrer le traitement, à en évaluer la réponse et à établir un pronostic. Cependant, il est essentiel de choisir un seul biomarqueur (BNP ou NT-proBNP) pour éviter toute confusion.

Correction: Medico-economic comparison of two anticoagulant treatment strategies: Vitamin K antagonists vs. direct oral anticoagulants in older adults in nursing homes in France. The "MIKADO" study.

[This corrects the article DOI: 10.1371/journal.pone.0283604.].

Optimización de los tratamientos de la insuficiencia cardiaca con fracción de eyección reducida en la práctica diaria: propuesta de un grupo de expertos / Optimisation of treatments for heart failure with reduced ejection fraction in routine practice: a position statement from a panel of experts

El tratamiento de los pacientes con insuficiencia cardiaca con fracción de eyección reducida (IC-FEr) con una combinación de 4 clases de fármacos se recomienda en las principales guías de práctica clínica internacionales. Sin embargo, no especifican cómo deben introducirse y ajustarse estos tratamientos. En consecuencia, muchos pacientes con IC-FEr no pasan a un régimen de tratamiento optimizado. El objetivo de esta revisión es proponer un algoritmo pragmático para optimizar el tratamiento, diseñado para que sea lo más fácil posible de aplicar en la práctica diaria. El primer objetivo es garantizar que las 4 clases de medicación recomendadas se inicien cuanto antes para establecer una terapia eficaz, incluso a dosis bajas. Esto se considera preferible a iniciar menos medicamentos a una dosis máxima. El segundo objetivo es garantizar que los intervalos entre la introducción de los medicamentos y entre los distintos pasos de titulación sean lo más breves posible, por la seguridad del paciente. Se hacen propuestas específicas para los pacientes de edad avanzada (> 75 años) frágiles, y para aquellos con trastornos del ritmo cardiaco. La aplicación de este algoritmo debería permitir alcanzar un protocolo de tratamiento óptimo en un plazo de 2 meses para la mayoría de los pacientes. Este debe ser nuestro objetivo en el tratamiento de la IC-FEr. (AU)

Major international practice guidelines recommend the use of a combination of 4 medication classes in the treatment of patients with heart failure with reduced ejection fraction (HFrEF) but do not specify how these treatments should be introduced and up-titrated. Consequently, many patients with HFrEF do not receive an optimized treatment regimen. This review proposes a pragmatic algorithm for treatment optimization designed to be easily applied in routine practice. The first goal is to ensure that all 4 recommended medication classes are initiated as early as possible to establish effective therapy, even at a low dose. This is considered preferable to starting fewer medications at a maximum dose. The second goal is to ensure that the intervals between the introduction of different medications and between different titration steps are as short as possible to ensure patient safety. Specific proposals are made for older patients (> 75 years) who are frail, and for those with cardiac rhythm disorders. Application of this algorithm should allow an optimal treatment protocol to be achieved within 2-months in most patients, which should the treatment goal in HFrEF. (AU)