Dementia incidence trend over 1992-2014 in the Netherlands: analysis of primary care data

$\textbf{Background:}$ Recent reports have suggested declining age-specific incidence rates of dementia in high-income countries over time. Improved education and cardiovascular health in early age have been suggested to bring about this effect. The aim of this study was to estimate the age- specific dementia-incidence trend in primary care records from a large population in the Netherlands. $\textbf{Methods and findings:}$ A dynamic cohort representative of the Dutch population was composed using primary care records from general practice registration networks (GPRN) across the country. Data regarding dementia incidence were obtained using general practitioner-recorded diagnosis of dementia within the electronic health records. Age-specific dementia incidence rates were calculated for all persons aged 60 years and over; negative binomial regression analysis was used to estimate the time trend. Nine out of eleven GPRNs provided data on more than 800,000 older people between 1992 and 2014, corresponding to over 4 million person- years and 23,186 incident dementia cases. The annual growth in dementia incidence rate was estimated to be 2.1% (95%CI 0.5 to 3.8%), and incidence rates were 1.08 (95%CI 1.04 to 1.13) times higher for women compared to men. There was no significant overall change since the start of a national dementia program in 2003. Despite their relatively low numbers of person years, the highest age groups contributed most to the increasing trend. Increased awareness of dementia by patients and doctors in more recent years may have influenced dementia diagnosis in GPs’ electronic health records, and needs to be taken into account when interpreting the data. $\textbf{Conclusions:}$ Within the clinical records of a large, representative sample of the Dutch population, we found no evidence for a declining incidence trend of dementia in the Netherlands. This could indicate true stability in incidence rates, or a balance between increased detection and a true reduction. Irrespective of the exact rates and mechanisms underlying these findings, they illustrate that the burden of work for physicians and nurses in general practice associated with newly diagnosed dementia has not been subject to substantial change in the past two decades. Hence, with the ageing of Western societies, we still need to anticipate on a dramatic absolute increase of dementia occurrence over the years to come

Pharmacokinetic and pharmacodynamic effects of high-dose monoclonal antibody therapy in a rat model of immune thrombocytopenia

Intravenous administration of pooled, polyvalent human immunoglobulin (IVIG) has been used for over 20 years as a therapy for immune thrombocytopenia (ITP). IVIG is available in limited quantities, and clinical preparations have been associated with the transfer of human pathogens. We have proposed that high-dose monoclonal antibody may be used in lieu of IVIG to achieve beneficial effects in the treatment of ITP. The current study investigates the effects of high-dose monoclonal antibody therapy in a rat model of ITP. Hybridoma cells secreting a murine monoclonal antiplatelet antibody (7E3) and murine monoclonal anti-methotrexate IgG (AMI) were grown in serum-free media. Next, 7E3, 8 mg kg−1, was administered intravenously to rats following pretreatment with saline or AMI (1 g kg−1 IV). AMI and 7E3 plasma concentrations were determined via enzyme-linked immunosorbent assay, and platelet count was determined with a Cell-Dyne hematology analyzer. Severe, transient thrombocytopenia was induced by 7E3. Platelet counts dropped to ≈8% of initial values within 1 hour after 7E3 administration. AMI pretreatment dramatically affected 7E3-induced thrombocytopenia, significantly altering the time course of throm-bocytopenia (P<.05) and significantly decreasing the severity of 7E3-induced thrombocytopenia (ie, following AMI pretreatment, nadir platelet count was greater than 8-fold that of the control group,P<.05). In addition, AMI pretreatment induced a 57% increase in 7E3 clearance (1.13±0.13 mL h−1 kg−1 vs 0.72±0.08 mL h−1 kg−1,P<.05). Consequently, high-dose monoclonal antibody therapy attenuated thrombocytopenia and produced a moderate increase in the clearance of antiplatelet antibodies in a rat model of ITP

Reconstruction of Functional Connectivity from Multielectrode Recordings and Calcium Imaging

In the last two decades, increasing research efforts in neuroscience have been focused on determining both structural and functional connectivity of brain circuits, with the main goal of relating the wiring diagram of neuronal systems to their emerging properties, from the microscale to the macroscale. While combining multisite parallel recordings with structural circuits' reconstruction in vivo is still very challenging, the reductionist in vitro approach based on neuronal cultures offers lower technical difficulties and is much more stable under control conditions. In this chapter, we present different approaches to infer the connectivity of cultured neuronal networks using multielectrode array or calcium imaging recordings. We first formally introduce the used methods, and then we will describe into details how those methods were applied in case studies. Since multielectrode array and calcium imaging recordings provide distinct and complementary spatiotemporal features of neuronal activity, in this chapter we present the strategies implemented with the two different methodologies in distinct sections.In the last two decades, increasing research efforts in neuroscience have been focused on determining both structural and functional connectivity of brain circuits, with the main goal of relating the wiring diagram of neuronal systems to their emerging properties, from the microscale to the macroscale. While combining multisite parallel recordings with structural circuits\u2019 reconstruction in vivo is still very challenging, the reductionist in vitro approach based on neuronal cultures offers lower technical difficulties and is much more stable under control conditions. In this chapter, we present different approaches to infer the connectivity of cultured neuronal networks using multielectrode array or calcium imaging recordings. We first formally introduce the used methods, and then we will describe into details how those methods were applied in case studies. Since multielectrode array and calcium imaging recordings provide distinct and complementary spatiotemporal features of neuronal activity, in this chapter we present the strategies implemented with the two different methodologies in distinct sections