A combination of levobupivacaine and lidocaine for paravertebral block in breast cancer patients undergoing quadrantectomy causes greater hemodynamic oscillations than levobupivacaine alone

Aim To test for differences in hemodynamic and analgesic properties in patients with breast cancer undergoing quadrantectomy with paravertebral block (PVB) induced with a solution of either one or two local anesthetics. Method A prospective, single-center, randomized, double- blinded, controlled trial was conducted from June 2014 until September 2015. A total of 85 women with breast cancer were assigned to receive PVB with either 0.5% levobupivacaine (n = 42) or 0.5% levobupivacaine with 2% lidocaine (n = 43). Hemodynamic variables of interest included intraoperative stroke volume variation (SVV), mean arterial pressure, heart rate, cardiac output, episodes of hypotension, use of crystalloids, and use of inotropes. Analgesic variables of interest were time to block onset, duration of analgesia, and postoperative serial pain assessment using a visual analogue scale. Results Although the use of 0.5% levobupivacaine with 2% lidocaine solution for PVB decreased the mean timeto- block onset (14 minutes; P < 0.001), it also caused significantly higher SVV values over the 60 minutes of monitoring (mean difference: 4.33; P < 0.001). Furthermore, the patients who received 0.5% levobupivacaine with 2% lidocaine experienced shorter mean duration of analgesia (105 minutes; P = 0.006) and more episodes of hypotension (17.5%; P = 0.048) and received more intraoperative crystalloids (mean volume: 550 mL; P < 0.001). Conclusion The use of 0.5% levobupivacaine in comparison with 0.5% levobupivacaine with 2% lidocaine solution for PVB had a longer time-to-block onset, but it also reduced hemodynamic disturbances and prolonged the analgesic effect

METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration: an initiative of the Joint Programme for Neurodegenerative Disease Research

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long-term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow-up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular-related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention

Effect of clonidine on the cutaneous silent period during spinal anesthesia

Aim: To investigate the effect of clonidine on the cutaneous silent period (CSP) during spinal anesthesia. ----- Methods: A total of 67 adult patients were included in this randomized, prospective, single-center, double-blind trial. They did not have neurological disorders and were scheduled for inguinal hernia repair surgery. This trial was registered on ClinicalTrials.gov (NTC03121261). The patients were randomized into two groups with regards to the intrathecally administered solution: (1) 15 mg of 0.5% levobupivacaine with 50 µg of 0.015% clonidine, or (2) 15 mg of 0.5% levobupivacaine alone. There were 34 patients in the levobupivacaine-clonidine (LC) group and 33 patients in the levobupivacaine (L) group. CSP and its latency were measured four times: prior to the subarachnoid block (SAB), after motor block regression to the 0 level of the Bromage scale, with ongoing sensory blockade, and both 6 and 24 h after SAB. ----- Results: Only data from 30 patients in each group were analyzed. There were no significant differences between the groups investigated preoperatively and after 24 h. The CSP of the L group at the time point when the Bromage scale was 0 was 44.8 ± 8.1 ms, while in the LC group it measured 40.2 ± 3.8 ms (P = 0.007). The latency in the L group at the time point when the Bromage scale was 0 was 130.3 ± 10.2 ms, and in the LC group it was 144.7 ± 8.3 ms (P < 0.001). The CSP of the L group after 6 h was 59.6 ± 9.8 ms, while in the LC group it was 44.5 ± 5.0 ms (P < 0.001). The latency in the L group after 6 h was 110.4 ± 10.6 ms, while in LC group it was 132.3 ± 9.7 ms (P < 0.001). ----- Conclusion: Intrathecal addition of clonidine to levobupivacaine for SAB in comparison with levobupivacaine alone results in a diminished inhibitory tonus and shortened CSP

Self-reported sleep relates to microstructural hippocampal decline in beta-amyloid positive Adults beyond genetic risk

Study Objectives: A critical role linking sleep with memory decay and beta-amyloid (A beta) accumulation, two markers of Alzheimer's disease (AD) pathology, may be played by hippocampal integrity. We tested the hypotheses that worse self-reported sleep relates to decline in memory and intra-hippocampal microstructure, including in the presence of A beta. Methods: Two-hundred and forty-three cognitively healthy participants, aged 19-81 years, completed the Pittsburgh Sleep Quality Index once, and two diffusion tensor imaging sessions, on average 3 years apart, allowing measures of decline in intra-hippocampal microstructure as indexed by increased mean diffusivity. We measured memory decay at each imaging session using verbal delayed recall. One session of positron emission tomography, in 108 participants above 44 years of age, yielded 23 A beta positive. Genotyping enabled control for APOE epsilon 4 status, and polygenic scores for sleep and AD, respectively. Results: Worse global sleep quality and sleep efficiency related to more rapid reduction of hippocampal microstructure over time. Focusing on efficiency (the percentage of time in bed at night spent asleep), the relation was stronger in presence of A beta accumulation, and hippocampal integrity decline mediated the relation with memory decay. The results were not explained by genetic risk for sleep efficiency or AD. Conclusions: Worse sleep efficiency related to decline in hippocampal microstructure, especially in the presence of A beta accumulation, and A beta might link poor sleep and memory decay. As genetic risk did not account for the associations, poor sleep efficiency might constitute a risk marker for AD, although the driving causal mechanisms remain unknown

Reproducibility and variability of quantitative MRI markers in cerebral small vessel disease

International audienceBrain imaging is essential for the diagnosis and characterization of cerebral small vessel disease. Several magnetic resonance imaging markers have therefore emerged, providing new information on the diagnosis, progression, and mechanisms of small vessel disease. Yet, the reproducibility of these small vessel disease markers has received little attention despite being widely used in cross-sectional and longitudinal studies. This review focuses on the main small vessel disease-related markers on magnetic resonance imaging including: white matter hyperintensities, lacunes, dilated perivascular spaces, microbleeds, and brain volume. The aim is to summarize, for each marker, what is currently known about: (1) its reproducibility in studies with a scan-rescan procedure either in single or multicenter settings; (2) the acquisition-related sources of variability; and, (3) the techniques used to minimize this variability. Based on the results, we discuss technical and other challenges that need to be overcome in order for these markers to be reliably used as outcome measures in future clinical trials. We also highlight the key points that need to be considered when designing multicenter magnetic resonance imaging studies of small vessel disease

Food for thought: association between dietary tyrosine and cognitive performance in younger and older adults

The fact that tyrosine increases dopamine availability that, in turn, may enhance cognitive performance has led to numerous studies on healthy young participants taking tyrosine as a food supplement. As a result of this dietary intervention, participants show performance increases in working memory and executive functions. However, the potential association between habitual dietary tyrosine intake and cognitive performance has not been investigated to date. The present study aims at clarifying the association of episodic memory (EM), working memory (WM) and fluid intelligence (Gf), and tyrosine intake in younger and older adults. To this end, we acquired habitual tyrosine intake (food frequency questionnaire) from 1724 participants of the Berlin Aging Study II (1383 older adults, 341 younger adults) and modelled its relations to cognitive performance assessed in a broad battery of cognitive tasks using structural equation modeling. We observed a significant association between tyrosine intake and the latent factor capturing WM, Gf, and EM in the younger and the older sample. Due to partial strong factorial invariance between age groups for a confirmatory factor analysis on cognitive performance, we were able to compare the relationship between tyrosine and cognition between age groups and found no difference. Above and beyond previous studies on tyrosine food supplementation the present result extend this to a cross-sectional association between habitual tyrosine intake levels in daily nutrition and cognitive performance (WM, Gf, and EM). This corroborates nutritional recommendations that are thus far derived from single-dose administration studies.Action Contro

Soluble TAM receptors sAXL and sTyro3 predict structural and functional protection in Alzheimer's disease

There is an urgent need to improve the understanding of neuroinflammation in Alzheimer's disease (AD). We analyzed cerebrospinal fluid inflammatory biomarker correlations to brain structural volume and longitudinal cognitive outcomes in the DELCODE study and in a validation cohort of the F.ACE Alzheimer Center Barcelona. We investigated whether respective biomarker changes are evident before onset of cognitive impairment. YKL-40; sTREM2; sAXL; sTyro3; MIF; complement factors C1q, C4, and H; ferritin; and ApoE protein were elevated in pre-dementia subjects with pathological levels of tau or other neurodegeneration markers, demonstrating tight interactions between inflammation and accumulating neurodegeneration even before onset of symptoms. Intriguingly, higher levels of ApoE and soluble TAM receptors sAXL and sTyro3 were related to larger brain structure and stable cognitive outcome at follow-up. Our findings indicate a protective mechanism relevant for intervention strategies aiming to regulate neuroinflammation in subjects with no or subjective symptoms but underlying AD pathology profile