Enhancement of visuospatial working memory by the differential outcomes procedure in Mild Cognitive Impairment and Alzheimer’s Disease

In the present study we investigated the efficacy of the differential outcome procedure (DOP) to improve visuospatial working memory in patients with Alzheimer’s disease and Mild Cognitive Impairment (MCI). The DOP associates correct responses to the to-be-remember stimulus with unique outcomes. Eleven patients diagnosed with Alzheimer’s disease, 11 participants with MCI, and 17 healthy matched controls performed a spatial delayed memory task under the DOP and a control condition (non-differential outcomes –NOP-). We found that performance (terminal accuracy) was significantly better in the DOP condition relative to the NOP condition in all three groups of participants. AD patients performed worse, and took longer to benefit from the DOP. In line with previous animal and human research, we propose that the DOP activates brain structures and cognitive mechanisms that are less affected by healthy and pathological aging, optimizing in this way the function of the cognitive system

Detecting neurophysiological alterations during Mild Cognitive Impairment and Dementia using wavelet-based energy computation and a Mahalanobis Distance classifier

Recently, a transitional stage, called Mild Cognitive Impairment (MCI) has been identified. Early MCI detection is of crucial importance for preventing dementia onset. The aim of this study is to provide a classification framework able to discriminate subtle alterations due to neurodegenerative processes. Primary attention was given at the MCI stage. Therefore two MCI groups were formed according the patient's performance in the Montreal Cognitive Assessment (MoCA) test; a group of 39 patient with a low cognitive decline (MCI-1; MoCA ≥ 25), and a group of 31 patients with moderate cognitive decline group (MCI-2; MoCA < 25). In addition, we tested 17 healthy control participants, and 14 mild demented patients. Participants underwent a full neuropsychologic examination. Application of the Independent Component Analysis (ICA) and visual inspection of EEG data during resting state condition with eyes closed was initially adopted for noise rejection. Then, the energy for each frequency band was computed through discrete wavelet transform (DWT). These spectral components for 57 electrodes served as an input to a classification system employing Mahalanobis Distance. Classification results (84.16% overall accuracy) demonstrated the system's robustness and reliability. Discrimination reached 82.35% for healthy controls, 92.31% for MCI-1, 74.19% for MCI-2 and 85.71% for mild demented patients. The classification system is proposed in order to supplement the neuropsychologic examination and to correlate subtle cognitive deficits revealed by MoCA with modified neurophysiological patterns, providing thus a better understanding to the progression of neurodegenerative mechanisms

Efficacy and safety of nintedanib in a greek multicentre idiopathic pulmonary fibrosis registry: A retrospective, observational, cohort study

Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis (IPF). In a retrospective, real-world study across seven Greek hospitals, we evaluated the effectiveness and safety of nintedanib in routine clinical practice. Patients diagnosed with IPF, as per guideline criteria or multidisciplinary diagnosis, received nintedanib between January 2013 and January 2018. We evaluated 244 patients: mean±SD age 71.8±7.5 years, 79.1% male, 45.1% current smokers and 33.1% ex-smokers at treatment initiation. At baseline, predicted forced vital capacity (FVC) was 73.3±20.7% and predicted diffusing capacity of the lungs for carbon monoxide (DLCO) was 42.6±16.7%. On average, patients spent 23.6±15.0 months on nintedanib. At 3 years, 78 patients had died, equating to a 3-year survival rate of 59.4% (unaffected by treatment discontinuation or dose reduction). FVC% pred and DLCO% pred were largely stable at 3 years, with no significant difference from baseline (FVC 73.3±20.7% pred versus 78±20.1% pred, p=0.074; DLCO 42.6±16.7% pred versus 40.4±18.1% pred, p=0.334). Of the 244 patients, 55.7% reported an adverse event. Gastrointestinal events were the most common (173 (77.2%) out of 224 total events) and 45.0% of patients experienced diarrhoea. Only 32 (13.1%) patients had to permanently discontinue nintedanib due to an adverse event. This real-world study shows a 3-year survival rate of 59.4% and a low discontinuation rate due to adverse events. Our experience is consistent with previous findings in clinical trials of nintedanib in IPF. © ERS 2020

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis

Background: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count < 0.60 K/μL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2–79.2) vs. 78.3, (95% CI 76.0–81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW < 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5–41.1) vs. 45.5, (95% CI 41.9–49.4), (P < 0.001)] and RDW [37.9, (95% CI 33.4–40.7) vs. 44.4, (95% CI 41.5–48.9), (P < 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (< 0.60 K/μL) [HR 2.05, (95% CI 1.19–3.53), (P = 0.01)]. Conclusions: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF. © 2021, The Author(s)

Increased monocyte count and red cell distribution width as prognostic biomarkers in patients with Idiopathic Pulmonary Fibrosis

Background: Idiopathic Pulmonary Fibrosis (IPF) represents a chronic lung disease with unpredictable course. Methods: We aimed to investigate prognostic performance of complete blood count parameters in IPF. Treatment-naïve patients with IPF were retrospectively enrolled from two independent cohorts (derivation and validation) and split into subgroups (high and low) based on median baseline monocyte count and red cell distribution width (RDW). Results: Overall, 489 patients (derivation cohort: 300, validation cohort: 189) were analyzed. In the derivation cohort, patients with monocyte count ≥ 0.60 K/μL had significantly lower median FVC%pred [75.0, (95% CI 71.3–76.7) vs. 80.9, (95% CI 77.5–83.1), (P = 0.01)] and DLCO%pred [47.5, (95% CI 44.3–52.3) vs. 53.0, (95% CI 48.0–56.7), (P = 0.02)] than patients with monocyte count &lt; 0.60 K/μL. Patients with RDW ≥ 14.1% had significantly lower median FVC%pred [75.5, (95% CI 71.2–79.2) vs. 78.3, (95% CI 76.0–81.0), (P = 0.04)] and DLCO%pred [45.4, (95% CI 43.3–50.5) vs. 53.0, (95% CI 50.8–56.8), (P = 0.008)] than patients with RDW &lt; 14.1%. Cut-off thresholds from the derivation cohort were applied to the validation cohort with similar discriminatory value, as indicated by significant differences in median DLCO%pred between patients with high vs. low monocyte count [37.8, (95% CI 35.5–41.1) vs. 45.5, (95% CI 41.9–49.4), (P &lt; 0.001)] and RDW [37.9, (95% CI 33.4–40.7) vs. 44.4, (95% CI 41.5–48.9), (P &lt; 0.001)]. Patients with high monocyte count and RDW of the validation cohort exhibited a trend towards lower median FVC%pred (P = 0.09) and significantly lower median FVC%pred (P = 0.001), respectively. Kaplan–Meier analysis in the derivation cohort demonstrated higher all-cause mortality in patients with high (≥ 0.60 K/μL) vs. low monocyte count (&lt; 0.60 K/μL) [HR 2.05, (95% CI 1.19–3.53), (P = 0.01)]. Conclusions: Increased monocyte count and RDW may represent negative prognostic biomarkers in patients with IPF. © 2021, The Author(s)