Impaired Vagal Activity in Long-COVID-19 Patients.

Long-COVID-19 refers to the signs and symptoms that continue or develop after the "acute COVID-19" phase. These patients have an increased risk of multiorgan dysfunction, readmission, and mortality. In Long-COVID-19 patients, it is possible to detect a persistent increase in D-Dimer, NT-ProBNP, and autonomic nervous system dysfunction. To verify the dysautonomia hypothesis in Long-COVID-19 patients, we studied heart rate variability using 12-lead 24-h ECG monitoring in 30 Long-COVID-19 patients and 20 No-COVID patients. Power spectral analysis of heart rate variability was lower in Long-COVID-19 patients both for total power (7.46 ± 0.5 vs. 8.08 ± 0.6; p < 0.0001; Cohens-d = 1.12) and for the VLF (6.84 ± 0.8 vs. 7.66 ± 0.6; p < 0.0001; Cohens-d = 1.16) and HF (4.65 ± 0.9 vs. 5.33 ± 0.9; p = 0.015; Cohens-d = 0.76) components. The LF/HF ratio was significantly higher in Long-COVID-19 patients (1.46 ± 0.27 vs. 1.23 ± 0.13; p = 0.001; Cohens-d = 1.09). On multivariable analysis, Long-COVID-19 is significantly correlated with D-dimer (standardized ß-coefficient = 0.259), NT-ProBNP (standardized ß-coefficient = 0.281), HF component of spectral analysis (standardized ß-coefficient = 0.696), and LF/HF ratio (standardized ß-coefficient = 0.820). Dysautonomia may explain the persistent symptoms in Long COVID-19 patients. The persistence of a procoagulative state and an elevated myocardial strain could explain vagal impairment in these patients. In Long-COVID-19 patients, impaired vagal activity, persistent increases of NT-ProBNP, and a prothrombotic state require careful monitoring and appropriate intervention.

The Cross-Talk between Thrombosis and Inflammatory Storm in Acute and Long-COVID-19: Therapeutic Targets and Clinical Cases.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) commonly complicates with coagulopathy. A syndrome called Long-COVID-19 is emerging recently in COVID-19 survivors, characterized, in addition to the persistence of symptoms typical of the acute phase, by alterations in inflammatory and coagulation parameters due to endothelial damage. The related disseminated intravascular coagulation (DIC) can be associated with high death rates in COVID-19 patients. It is possible to find a prothrombotic state also in Long-COVID-19. Early administration of anticoagulants in COVID-19 was suggested in order to improve patient outcomes, although exact criteria for their application were not well-established. Low-molecular-weight heparin (LMWH) was commonly adopted for counteracting DIC and venous thromboembolism (VTE), due to its pharmacodynamics and anti-inflammatory properties. However, the efficacy of anticoagulant therapy for COVID-19-associated DIC is still a matter of debate. Thrombin and Factor Xa (FXa) are well-known components of the coagulation cascade. The FXa is known to strongly promote inflammation as the consequence of increased cytokine expression. Endothelial cells and mononuclear leucocytes release cytokines, growth factors, and adhesion molecules due to thrombin activation. On the other hand, cytokines can activate coagulation. The cross-talk between coagulation and inflammation is mediated via protease-activated receptors (PARs). These receptors might become potential targets to be considered for counteracting the clinical expressions of COVID-19. SARS-CoV-2 is effectively able to activate local and circulating coagulation factors, thus inducing the generation of disseminated coagula. LMWH may be considered as the new frontier in the treatment of COVID-19 and Long-COVID-19. Indeed, direct oral anticoagulants (DOACs) may be an alternative option for both early and later treatment of COVID-19 patients due to their ability to inhibit PARs. The aim of this report was to evaluate the role of anticoagulants-and DOACs in particular in COVID-19 and Long-COVID-19 patients. We report the case of a COVID-19 patient who, after administration of enoxaparin developed DIC secondary to virosis and positivity for platelet factor 4 (PF4) and a case of Long-COVID with high residual cardiovascular risk and persistence of blood chemistry of inflammation and procoagulative state.

A Systematic Review of the Efficacy and Safety of Direct Oral Anticoagulants in Atrial Fibrillation Patients with Diabetes Using a Risk Index.

Diabetes mellitus (DM) represents an independent risk factor for chronic AF and is associated with unfavorable outcomes. We aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AF), with and without diabetes mellitus (DM), using a new risk index (RI) defined as: RI =Rate of EventsRate of Patients at Risk. In particular, an RI lower than 1 suggests a favorable treatment effect. We searched MEDLINE, MEDLINE In-Process, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. The risk index (RI) was calculated in terms of efficacy (rate of stroke/systemic embolism (stroke SEE)/rate of patients with and without DM; rate of cardiovascular death/rate of patients with and without DM) and safety (rate of major bleeding/rate of patients with and without DM) outcomes. AF patients with DM (n = 22,057) and 49,596 without DM were considered from pivotal trials. DM doubles the risk index for stroke/SEE, major bleeding (MB), and cardiovascular (CV) death. The RI for stroke/SEE, MB, and CV death was comparable in patients treated with warfarin or DOACs. The lowest RI was in DM patients treated with Rivaroxaban (stroke/SEE, RI = 0.08; CV death, RI = 0.13). The RIs for bleeding were higher in DM patients treated with Dabigatran (RI110 = 0.32; RI150 = 0.40). Our study is the first to use RI to homogenize the efficacy and safety data reported in the DOACs pivotal studies against warfarin in patients with and without DM. Anticoagulation therapy is effective and safe in DM patients. DOACs appear to have a better efficacy and safety profile than warfarin. The use of DOACs is a reasonable alternative to vitamin-K antagonists in AF patients with DM. The RI can be a reasonable tool to help clinicians choose between DOACs or warfarin in the peculiar set of AF patients with DM.

DIC-Like Syndrome Following Administration of ChAdOx1 nCov-19 Vaccination.

In recent weeks, adverse reactions have been reported after administration of Oxford-AstraZeneca chimpanzee adenovirus vectored vaccine ChAdOx1 nCoV-19 (AZD1222), in particular thrombus formation, which has led several European Countries to discontinue administration of this vaccine. On March 8, 2021, the European Medicines Agency Safety Committee did not confirm this probable association. We report the case of a patient who developed disseminated intravascular coagulation after the first dose of Oxford-Astra Zeneca vaccine, which resolved in a few days with the administration of dexamethasone and enoxaparin. This work demonstrates the safety of the Oxford-Astra Zeneca vaccine and that any development of side effects can be easily managed with a prompt diagnosis and in a short time with a few commonly used drugs.

The Cross-Talk between Age, Hypertension and Inflammation in COVID-19 Patients: Therapeutic Targets.

This paper presents a brief overview of the complex interaction between age, hypertension, the renin-angiotensin-aldosterone system (RAAS), inflammation, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. Coronavirus disease 2019 (COVID-19) is more frequent and more severe in comorbid elderly patients, especially those with hypertension, diabetes, obesity, or cardiovascular diseases. There are concerns regarding the use of RAAS inhibitors in patients with COVID-19. Some physicians have considered the need for interrupting RAAS inhibition in order to reduce the possibility of SARS-CoV2 entering lung cells after binding to angiotensin-converting enzyme 2 (ACE2) receptors. We offer a different point of view in relation to the need for continuing to use RAAS inhibitors in patients with COVID-19. We focused our article on elderly patients because of the distinctive imbalance between the immune response, which is depressed, and the exacerbated inflammatory response, 'inflammaging', which makes the geriatric patient an appropriate candidate for therapeutic strategies aimed at modulating the inflammatory response. Indeed, COVID-19 is an inflammatory storm that starts and worsens during the course of the disease. During the COVID-19 pandemic, various therapeutic approaches have been tested, including antiviral drugs, interferon, anti-interleukins, hydroxychloroquine, anti-inflammatories, immunoglobulins from recovered patients, and heparins. Some of these therapeutic approaches did not prove to be beneficial, or even induced serious complications. Based on current evidence, in the early stages of the disease modulation of the inflammatory response through the inhibition of neprilysin and modulation of the RAAS could affect the course and outcome of COVID-19.

Biomechanical and neuroautonomic adaptation to acute blood volume displacement in ischemic dilated cardiomyopathy: the predictive value of the CD25 test.

We aimed to examine biomechanical and neuroautonomic adaptation to blood volume displacement induced by tilt test in patients with previous inferoapical/inferolateral (IA-IL) or basal/apical septal (BS-AS) myocardial infarction (MI). Twenty-four patients with heart failure (HF) and previous IA-IL MI and 30 patients with HF and previous BS-AS MI were enrolled. All patients underwent head-up tilt test, radionuclide ventricular function monitoring (VEST), sympathovagal balance evaluation, and chronotropic 25-dose isoproterenol infusion test (CD25). Physiopathological reactions to stress-tests were assessed in both groups. Follow-up lasted 36 mo. IA-IL patients showed lower stroke volume (SV), cardiac output (CO), and left ventricle ejection fraction (LVEF) compared with BS-AS. End-diastolic volume decreased in IA-IL group (F = 3.1, P = 0.043) more than in BS-AS group during tilt test. The time trend of end-systolic volume, SV, CO, LVEF, and peak filling rate were similar in the two groups. Norepinephrine (IA-IL supine→tilting 499.5 (SD:28.8)→719.3 (SD:41.5) pg/mL vs. BS-AS supine→tilting 533.9 (SD:33.3)→768.8 (SD:47.9) pg/mL; P < 0.001) and epinephrine plasma concentrations (IA-IL supine→ tilting 125.7 (SD:9.8)→193.7 (SD:9.6) pg/mL vs. BS-AS supine→ tilting 118.8 (SD:8.9)→191.7 (SD:10.2) pg/mL; P < 0.001) increased in both groups. Low-to-high frequencies ratio significantly increased in IA-IL and decreased in BS-AS patients. CD25 was similar in IA-IL and BS-AS patients (IA-IL = 4.6 (SD:0.94), BS-AS = 5.0 (SD:1.06) µg; P = 0.79). CD25 predicted all-cause mortality (hazard ratio 1.48, 95% confidence interval 1.32-1.67; P < 0.0001) after adjusting for age/heart rate. In conclusion, patients with ischemic HF show abnormal biomechanical adaptation to volume displacement and compensatory sympathetic overdrive. The association of reduced ß-adrenergic sensitivity and sympathetic denervation in such patients warrants for careful therapeutic choices.NEW & NOTEWORTHY The adaptation to volume displacement induced by tilt test was assessed in patients with heart failure and previous inferoapical/inferolateral or basal/apical septal myocardial infarction. The responsiveness of cardiac muscle to sympathetic nervous system stimulation predicts the mortality in patients with ischemic heart failure and may represent a useful tool for clinicians in the general assessment of this kind of patients.

Early Initiation of Sacubitril/Valsartan in Patients with Chronic Heart Failure After Acute Decompensation: A Case Series Analysis.

BACKGROUND AND OBJECTIVE: Sacubitril/valsartan improved the prognosis of patients with heart failure with reduced ejection fraction in the PARADIGM-HF study. Recently, the TRANSITION and PIONEER-HF studies demonstrated the safety and efficacy of sacubitril/valsartan in patients hospitalized for acute decompensated heart failure, with treatment initiated after hemodynamic and clinical stabilization. In this case series study, we assessed the short-term effects of sacubitril/valsartan on exercise capacity, inflammation, and biomarkers in patients with acute decompensated heart failure. METHODS: Patients admitted for acute decompensated heart failure to the Department of Internal Medicine of Telese Terme Hospital and Cardiovascular Department, University of Bari, from 9 March, 2017 to 9 June, 2018 were enrolled. Following hemodynamic stabilization, patients initiated sacubitril/valsartan 24/26 mg twice a day for 4 weeks, with up-titration to 49/51 mg twice a day based on tolerability after 1 week. Efficacy outcomes included the 6-min walking test, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and lymphocyte count. Safety outcomes included renal function, hyperkalemia, and symptomatic hypotension. RESULTS: In total, 40 patients completed the study and 27 (67.5%) patients were up-titrated. Compared with baseline, exercise capacity and relative lymphocyte count increased significantly after 4 weeks of treatment, while N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein decreased significantly. N-terminal pro-B-type natriuretic peptide and relative lymphocyte count independently predicted the 6-min walking test distance (p = 0.021). No patients experienced any relevant side effects. CONCLUSIONS: Early initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction after acute decompensated heart failure may be safe and effective in terms of functional capacity and biomarkers.

Efficacy and Safety of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and High Thromboembolic Risk. A Systematic Review.

Background: The aim of the study was to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in a subgroup of patients with atrial fibrillation (AF), CHADS2 score ≥3, advanced age, and heart failure (HF) coming from the main DOACs randomized clinical trials. Methods: We searched MEDLINE, MEDLINE In-Process, and Other Non-Indexed Citations, EMBASE, PubMed, and the Cochrane Central Register of Controlled Trials. English-language articles published from 2002 to March 2019 dealing with DOACs for preventing thrombotic events in AF were considered. We did not conduct any statistical analyses, as indirect comparison between DOACs represents hypothesis generators. Results: This systematic review was restricted to the subgroup of patients with CHADS2 score ≥3 (n = 31,203), elderly (n = 24,788), and with HF (n = 29,297) derived from the pivotal trials. Risk index (RI) was calculated. The RI for stroke/systemic embolism was similar in all of the patients treated with DOACs or warfarin. The lowest RI was in rivaroxaban patients (CHADS2 score ≥3: RI = 0.04; elderly: RI = 0.09; HF: RI = 0.05). The RIs for bleeding were higher in patients treated with dabigatran (CHADS2 score ≥3: RI110 = 0.23; elderly: RI110 = 0.22; HF: RI110 = 0.16; CHADS2score ≥3: RI150 = 0.30; elderly: RI150 = 0.24; HF: RI150 = 0.16). The bleeding RIs were higher with apixaban (CHADS2 score ≥3: RI = 0.23; elderly: RI = 0.25; HF: RI = 0.14) and dabigatran (CHADS2 score ≥3: RI = 0.28; elderly: RI = 0.21; HF: RI = 0.19). Conclusions: The use of DOACs is a reasonable alternative to vitamin K antagonists in AF patients with CHADS2 score ≥3, advanced age, and HF. The RI constitutes a useful, additional tool to facilitate clinicians in choosing DOACs or warfarin in particular category of AF patients.

Relative lymphocyte count as an indicator of 3-year mortality in elderly people with severe COPD.

BACKGROUND: Prognostic stratification of elderly patients with chronic obstructive pulmonary disease (COPD) is difficult due to the wide inter-individual variability in the course of the disease. No marker can exactly stratify the evolution and natural history of COPD patients. Studies have shown that leukocyte count is associated with increased risk of mortality in COPD patients. The aim of this study was to evaluate the possible role of relative lymphocyte count as a risk marker for mortality in elderly patients with COPD. METHODS AND RESULTS: This is a3-year prospective study. A total of 218patients, mean age 75.2±7 years, with moderate to severe COPD and free from conditions affecting lymphocyte count were enrolled. The population was divided into two groups according to the relative lymphocyte count, with a cut-off of 20%. Eighty-five patients (39%) had a relative lymphocyte count ≤20%. Three-year mortality rates from any cause in patients with relative lymphocyte count ≤ or > 20% were 68 and 51%, respectively (p = 0.0012). Survival curve analysis showed higher mortality in patients with relative lymphocyte count ≤20% (p = 0.0005). After adjustment for age and sex, the hazard ratio for mortality risk according to lymphocyte count was 1.79 (95% confidence interval [CI]: 1.26-2.57, p = 0.0013), even in the analysis limited to the 171 patients without congestive heart failure (1.63; 95% CI: 1.03-2.58, p = 0.038). CONCLUSIONS: Low relative lymphocyte count was associated with higher mortality in elderly patients with severe COPD.

Exercise training effects on elderly and middle-age patients with chronic heart failure after acute decompensation: A randomized, controlled trial.

BACKGROUND: The aim of this study was to evaluate the effect of exercise training on cardiac function in heart failure (HF) patients recently suffering from acute decompensation. Radionuclide ambulatory ventricular function monitoring (VEST) was used to detect variations in cardiac hemodynamics during training period. METHODS: This was a monocentric, randomized, controlled trial. We enrolled 72 HF patients [left ventricle ejection fraction (LVEF) <40%] within two weeks after acute cardiogenic pulmonary edema: 40 in the elderly group, 32 in the middle-aged group. Trained patients underwent a specific four-weeks exercise program (closed-chain resistive activities and abdominal exercises) which was supervised by a therapist in agreement with patients' characteristics. Catecholamines at rest, echocardiography, right-heart catheterization, and bicycle ergometer were performed. VEST was performed at the end of the 4weeks-training in all patients in order to assess patients' cardiac hemodynamics [LVEF, cardiac output (CO), stroke volume]. RESULTS: Exercise training significantly improved exercise duration, peak oxygen consumption, and ventilatory threshold both in elderly and middle-aged patients (p<0.0001) after the 4-week controlled training. Despite age (F=35.086, p<0.0001; F=16.967, p<0.0001; F=42.574, p=0.03, respectively), training reliably influence previous cardiopulmonary parameters (F=29.402, F=16.421, F=26.80, p<0.0001, respectively). Norepinephrine and epinephrine were significantly reduced in both trained groups. Peak LVEF (37.3±4.7% vs 34±6.2%, p=0.002), peak stroke volume (43.3±3.9% vs 37.5±4.3%, p=0.001), and peak CO (63.4±6.1% vs 48.2±4.7%, p<0.0001) increased in middle-aged patients after 4-week training. CONCLUSIONS: Exercise training improves cardiac performance indexes and pulmonary function in both middle-aged and elderly HF patients early after an acute episode of cardiac decompensation.

Safety and Feasibility of Treatment with Rivaroxaban for Non-Canonical Indications: A Case Series Analysis.

BACKGROUND AND OBJECTIVES: The new oral anticoagulants (NOACs) are used for the prevention of thromboembolic complications in patients with non-valvular atrial fibrillation (AF) and those at risk of deep venous thrombosis. Their rapid onset of action and predictable pharmacokinetic and pharmacodynamic profiles make them the optimal alternative to warfarin in the treatment of these two categories of patients. Unfortunately, however, NOACs cannot be used in patients with valvular AF or valvular cardiac prostheses. Although mechanical valves are effectively a contraindication to NOAC use due to several pathophysiological mechanisms that promote the use of warfarin rather than NOACs, few data exist regarding the use of such new pharmacological compounds on patients with cardiac biological valves or those who have undergone mitral repair or tubular aortic graft implantation. METHODS: Our case series involved 27 patients [mean age 70 ± 10 years; mean CHA2DS2-VASc (Congestive heart failure, Hypertension, Age ≥75 years (doubled), Diabetes mellitus, Stroke/transient ischemic attack (doubled), Vascular disease, Age 65-74 years, Sex category): 6 ± 1.4; and mean HAS-BLED (Hypertension, Abnormal renal and liver function, Stroke, Bleeding, Labile international normalized ratios, Elderly, Drugs or alcohol): 4 ± 1] with AF and biological prostheses, repaired mitral valves, or tubular aortic graft who were treated with the factor Xa inhibitor rivaroxaban due to inefficacy or adverse effects of warfarin. RESULTS: The mean left ventricular ejection fraction was 48 ± 9 %, the left atrial diameter was 46.5 ± 7 mm, and the estimated glomerular filtration rate was 45 ± 21 mL/min/1.73 m(2). The mean duration of treatment was 15 ± 2 months. No relevant complications or recurrent thromboembolic events occurred. Three patients had recurrent nose bleeding and two had hematuria that led to reduction of the rivaroxaban dose by the treating physician to 15 mg once a day after 4 months of therapy. No further bleeding episode was recorded after escalating the dose. CONCLUSIONS: Rivaroxaban is a valuable treatment option for patients with biological prostheses, repaired mitral valves, or a tubular aortic graft in order to prevent thromboembolic complications.

Heart rate variability and drawing impairment in hypoxemic COPD.

We studied 54 patients with hypoxemic chronic obstructive pulmonary disease (COPD). The Mini Mental State Examination and the Mental Deterioration Battery were used for neuropsychological assessment. Heart rate variability (HRV) was assessed based on 24-h Holter ECG recording. Mann-Whitney test was used to compare HRV parameters of patients performing normally or abnormally on individual neuropsychological tasks. Spearman's rho was used to investigate the correlations between HRV parameters and neuropsychological scores, indexes of health status or COPD severity. Patients with defective performance at copying drawings with landmarks (CDL) test (N = 23) had lower very low frequency (VLF) power with respect to patients with normal performance (N = 31) (24 h: median 213; interquartile range 120-282 vs. 309; 188-431 ms2, p = 0.043; daytime: 202; 111-292 vs. 342; 194-397 ms2, p = 0.039). The CDL score correlated with the VLF power (24 h: rho = 0.27, p = 0.049; daytime: rho = 0.30, p = 0.028), and the normalized low frequency/high frequency (LF/HF) ratio (24 h: rho = 0.27, p = 0.05; daytime: rho = 0.33, p = 0.015). Sympathetic modulation decreased for increasing severity of COPD. In conclusion, drawing impairment correlates with depressed sympathetic modulation in patients with COPD, and both might be indexes of COPD severity.

Correlation between cognitive impairment and dependence in hypoxemic COPD.

We studied 149 patients with stable chronic obstructive pulmonary disease (COPD). Three clusters were generated (high, mid, and low level of cognitive function) based on 11 neuropsychologic scores; personal independence in basic/instrumental activities of daily living (BADL/IADL) of clusters was compared by discriminant analysis. Pattern of BADL/IADL was cluster-specific in 79.2% of high and 54.9% of low clusters, but only 20.8% of mid cluster. Self-administering drugs, continence, managing money, and dressing items had the greatest discriminatory capacity. Clusters had comparable respiratory function. In older COPD patients, dependence parallels cognitive impairment only to some extent. Indices of COPD severity are poor correlates of dependence.

Hypermagnesemia predicts mortality in elderly with congestive heart disease: relationship with laxative and antacid use.

The aim of this study was to evaluate the role of magnesium levels on 3-year survival in the elderly with congestive heart failure (CHF) admitted to the Rehabilitative Cardiology Unit of S. Maugeri Foundation Scientific Institute of Telese/Campoli. All elderly patients > or = 65 years old with a diagnosis of CHF underwent clinical and instrumental examination, and their demographics, co-morbidity, and in-hospital and 3-year mortality rates were recorded. Hypomagnesemia was found in 4.8%, normomagnesemia in 67.5%, and hypermagnesemia in 27.8% of subjects. The hypomagnesemic group was excluded for numerical exiguity; the analysis was performed on a total of 199 elderly patients. Hypermagnesemia was found in 29.1% and normomagnesemia in 70.9%. At the univariate analysis no differences were found in hypermagnesemia in respect to normomagnesemia group, except for slightly higher levels of creatininemia (1.35 +/- 0.61 vs. 1.13 +/- 0.55 mg/dL, respectively; p < 0.02), greater disability (lost ADL, 2.69 +/- 1.57 vs. 2.15 +/- 1.56, respectively; p < 0.05), more mortality for CHF (32.6 vs. 48.3%; p < 0.05), and higher antacid and laxative use (82.7 vs. 24.8%, respectively; p < 0.0001). Patients with higher magnesium showed less probability to survive at a 3-year follow-up than did patients with lower levels (17.32 +/- 15.93 vs. 22.46 +/- 16.16 months; p < 0.05), and this finding remained significant in the multivariate analysis after adjusting for some confounders. Finally hypermagnesemia should also be considered in the absence of pre-existing renal failure clinical evidence because of its negative prognostic value, especially in elderly patients with CHF. The shown relationship between hypermagnesemia and laxative/antacid use should induce physicians to pay more attention to abuse of these drugs.

Cognitive training is ineffective in hypoxemic COPD: a six-month randomized controlled trial.

Cognitive impairment is highly prevalent in chronic obstructive pulmonary disease (COPD) complicated by chronic hypoxemia, but the effect of cognitive training in patients with COPD has not been studied. The aim of the present study was to verify whether cognitive training can preserve cognitive abilities of patients with hypoxemic COPD. Our series consisted of 105 COPD patients with at rest (n = 36) or effort (n = 69) hypoxemia and free from concurrent dementing diseases. Neuropsychologic assessment included a screening test, the Mini Mental State Examination (MMSE), and a standardized confirmatory battery of neuropsychological tests, the Mental Deterioration Battery (MDB). After baseline assessment, patients were randomized to receive standardized multidimensional care (standardization of pharmacological therapy, health education, selection of inhalers according to patient's ability, respiratory rehabilitation, nutritional counseling, oxygen therapy, and control visits) with (n = 53) or without (n = 52) cognitive training aimed at stimulating attention, learning, and logical-deductive thinking. Cognitive performance was reassessed after 1.5, 4, and 6 months. The analysis of variance for repeated measures (ANOVA) having the group membership (study vs. control) as grouping factor was used to assess changes in cognitive performance. Both intervention and control groups showed no significant changes in cognitive performance except for a trend toward improvement in verbal fluency and verbal memory, but cognitive intervention had no significant effect. In conclusion, cognitive training seems ineffective in COPD. However, a multidimensional standardized therapeutic approach, as it was indistinctly provided to all patients, could help to slow or prevent cognitive decline.

Screening of cognitive impairment in chronic obstructive pulmonary disease.

Cognitive dysfunction is common and clinically important in severe chronic obstructive pulmonary disease (COPD). We investigated the diagnostic accuracy of the Mini Mental State Examination (MMSE) and Instrumental Activities of Daily Living (IADL) scale in screening severe cognitive dysfunction in 149 patients with COPD, mean age 69.3+/-8.5 years, forced expiratory volume in 1 s=36.6+/-17.8% of the predicted. Patients underwent the MMSE and an in-depth neuropsychological assessment based upon the Mental Deterioration Battery (MDB). The 5-item IADL scale was assessed. The sample was randomly divided into a training (n=73) and a testing (n=76) population. The diagnostic accuracy of MMSE, IADL scale or both versus cognitive dysfunction corresponding to abnormal performance in 3 or more MDB tests was assessed in the training population and the model obtained was tested in the testing population. The combination of MMSE<24 and dependence in at least 1 IADL had better diagnostic accuracy than either MMSE or IADL, with sensitivity=52.4, specificity=82.7, positive predictive value=55.0% and negative predictive value=81.1% in the testing population. MMSE and the 5-item IADL scale can be used to exclude, but not to detect cognitive dysfunction in COPD patients. A confirmatory cognitive test should be administered to patients with an MMSE score of <24 and who are dependent in at least 1 IADL.