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Purpose: To compare the incremental diagnostic value of amyloid-PET and CSF (Aβ42, tau, and phospho-tau) in AD diagnosis in patients with mild cognitive impairment (MCI) or mild dementia, in order to improve the definition of diagnostic algorithm. Methods: Two independent dementia experts provided etiological diagnosis and relative diagnostic confidence in 71 patients on 3 rounds, based on (1) clinical, neuropsychological, and structural MRI information alone; (2) adding one biomarker (CSF amyloid and tau levels or amyloid-PET with a balanced randomized design); and (3) adding the other biomarker. Results: Among patients with a pre-biomarker diagnosis of AD, negative PET induced significantly more diagnostic changes than amyloid-negative CSF at both rounds 2 (CSF 67%, PET 100%, P = 0.028) and 3 (CSF 0%; PET 78%, P < 0.001); PET induced a diagnostic confidence increase significantly higher than CSF on both rounds 2 and 3. Conclusions: Amyloid-PET should be prioritized over CSF biomarkers in the diagnostic workup of patients investigated for suspected AD, as it provides greater changes in diagnosis and diagnostic confidence. Trial registration: EudraCT no.: 2014-005389-31 [ABSTRACT FROM AUTHOR]

In the past, little or no attention was paid to cognitive disorders associated with depression (a condition sometimes termed pseudodementia). However, recent years have seen a growing interest in these changes, not only because of their high frequency in acute-stage depression, but also because they have been found to persist, as residual symptoms (in addition to affective and psychomotor ones), in many patients who respond well to antidepressant treatment. These cognitive symptoms seem to impact significantly not only on patients' functioning and quality of life, but also on the risk of recurrence of depression. Therefore, over the past decade, pharmacological research in this field has focused on the development of new agents able to counteract not only depressive symptoms, but also cognitive and functional ones. In this context, novel antidepressants with multimodal activity have emerged. This review considers the different issues, in terms of disease evolution, raised by the presence of cognitive disorders associated with depression and considers, particularly from the neurologist's perspective, the ways in which the clinical approach to cognitive symptoms, and their interpretation to diagnostic and therapeutic ends, have changed in recent years. Finally, after outlining the pharmacodynamics and pharmacokinetics of the first multimodal antidepressant, vortioxetine, it reports the main results obtained with the drug in depressed patients, also in consideration of the ever-increasing evidence on its different mechanisms of action in animal models. [ABSTRACT FROM AUTHOR]

Purpose: The present study was carried out in order to assess the effects of chronic administration of flunitrazepam (as an oral hypnotic) on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults.Materials and methods: Following a 2-week placebo run-in period, 28 healthy volunteers (13 males and 15 females) between 21 and 30 years were randomized to receive either flunitrazepam 1 mg or placebo (both administered once a day in the evening) for 4 weeks in two cross-over periods; each separated by a 2-week placebo period. At the end of each study period, non-invasive 24-h BP and HR ambulatory monitoring was performed.Results: Flunitrazepam produced a significant decrease in nighttime systolic blood pressure (SBP) (− 6.4 mmHg) and diastolic blood pressure (DBP) (− 4.1 mmHg) (both P < 0.05 vs placebo) without affecting nocturnal HR. During the morning hours, significantly higher values of SBP (+ 7.4 mmHg, P < 0.01), DBP (+ 3.4 mmHg, P < 0.05) and HR (+ 3.9 beats/min, P < 0.05) were observed in the flunitrazepam group compared to the placebo-treated group. No significant differences were noted between the two groups during afternoon and evening hours.Conclusions: These results suggest that chronic oral administration of 1 mg flunitrazepam as a hypnotic agent causes a significant nocturnal fall in BP and a transient rebound increase of both BP and HR at awakening in the morning. Mechanisms underlying these cardiovascular effects remain unclear, although the direct vasodilatory effect, which is typical of flunitrazepam (with consequent reflex counter-regulatory responses), and the attenuation of baroreflex sensitivity are likely to play a major role. [ABSTRACT FROM AUTHOR]

Aim: To assess the effects of evening chronic administration of diazepam on 24-h blood pressure (BP) and heart rate (HR) in healthy young adults. Methods: This randomized double blind, cross-over study evaluated the effects of diazepam 5 mg or placebo, both ingested in the evening, on 24-h ambulatory BP and HR in healthy subjects aged 21-30. Results: A total of 30 subjects were included in the analysis. At the end of 4-week diazepam intake, an increase in 24-h HR mean values was found (+5.2 beats/min, p < 0.05). Analysis of subperiods showed that diazepam produced a 10.1% increase in night-time HR (+6.1 beats/min, p < 0.01) without affecting BP. A significant HR rise (+4.9 beats/min, p < 0.05) and SBP reduction (-3.8 mm Hg, p < 0.05) were observed in the morning hours. The HR increase persisted in day-time hours (+4.6 beats/min, p < 0.05), while BP values resulted unaffected. Conclusions: In healthy subjects, diazepam taken as a hypnotic agent induces a significant HR increase, possibly mediated mediated by a decrease in vagal tone. This effect might be of clinical relevance due to the role that HR plays as an independent cardiovascular risk factor. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the effect of ramipril/canrenone versus ramipril/hydrochlorothiazide (HCTZ) combination on atrial fibrillation (AF) recurrence in type 2 diabetic hypertensives with and without cardiac autonomic neuropathy (CAN). Material and methods: A total of 289 hypertensive type 2 diabetic patients, 95 with CAN, in sinus rhythm but with at least two episodes of AF in the previous 6 months were randomized to ramipril 5 mg plus canrenone 50 mg (titrated to 10/100 mg) or to ramipril 5 mg plus HCTZ 12.5 mg (titrated to 10/25 mg) or to amlodipine 5 mg (titrated to 10 mg) for 1 year. Clinic blood pressure (BP) and a 24-h ECG were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. Serum procollagen type I carboxy-terminal peptide (PIP) and carboxy-terminal telopeptide of collagen type I (CITP) were evaluated before and after each treatment period. Results: Blood pressure was similarly and significantly reduced by all treatments. A total of 51% of patients with amlodipine had a recurrence of AF, as did 31% of patients with ramipril/HCTZ (p < 0.05 vs. amlodipine) and 13% of patients with ramipril/canrenone (p < 0.01 vs. amlodipine and p < 0.05 vs. ramipril/HCTZ). A similar trend was found in diabetic patients with CAN. Both combinations reduced PIP and increased CITP, but the effects of ramipril/canrenone were significantly more marked. Conclusions: These findings suggest that in type 2 diabetic hypertensives, ramipril/canrenone treatment was more effective than ramipril/HCTZ in reducing AF recurrence. This could be related to the greater improvement in cardiac fibrosis. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to compare the effect of ramipril/canrenone versus ramipril/hydrochlorothiazide (HCTZ) combination on atrial fibrillation (AF) recurrence in type 2 diabetic hypertensives with and without cardiac autonomic neuropathy (CAN).Material and Methods: A total of 289 hypertensive type 2 diabetic patients, 95 with CAN, in sinus rhythm but with at least two episodes of AF in the previous 6 months were randomized to ramipril 5 mg plus canrenone 50 mg (titrated to 10/100 mg) or to ramipril 5 mg plus HCTZ 12.5 mg (titrated to 10/25 mg) or to amlodipine 5 mg (titrated to 10 mg) for 1 year. Clinic blood pressure (BP) and a 24-h ECG were evaluated monthly. Patients were asked to report any episode of symptomatic AF and to perform an ECG as early as possible. Serum procollagen type I carboxy-terminal peptide (PIP) and carboxy-terminal telopeptide of collagen type I (CITP) were evaluated before and after each treatment period.Results: Blood pressure was similarly and significantly reduced by all treatments. A total of 51% of patients with amlodipine had a recurrence of AF, as did 31% of patients with ramipril/HCTZ (p < 0.05 vs. amlodipine) and 13% of patients with ramipril/canrenone (p < 0.01 vs. amlodipine and p < 0.05 vs. ramipril/HCTZ). A similar trend was found in diabetic patients with CAN. Both combinations reduced PIP and increased CITP, but the effects of ramipril/canrenone were significantly more marked.Conclusions: These findings suggest that in type 2 diabetic hypertensives, ramipril/canrenone treatment was more effective than ramipril/HCTZ in reducing AF recurrence. This could be related to the greater improvement in cardiac fibrosis. [ABSTRACT FROM AUTHOR]