IntroductionUnderstanding the biological mechanism of subjective cognitive decline (SCD) in preclinical Alzheimer’s disease (AD) and identifying those who will soon convert to mild cognitive impairment (MCI) are critical for developing appropriate strategies for early diagnosis and intervention of AD. We present the study protocol of the Sino Longitudinal Study on Cognitive Decline (SILCODE), a longitudinal observational study focusing on SCD in the context of AD.Methods and analysisWithin SILCODE, approximately 800 subjects with SCD who are between 50 and 79 years old will be recruited through standardised public advertisements or memory clinics. They will undergo extensive assessment, including clinical and neuropsychological assessments, blood sample collection for plasma beta-amyloid and ApoE genotype, urine samples collection for AD7c-NTP, and multimodal MRI scans (structural MRI, diffusion tensor imaging, resting-state functional MRI and optional task-based functional MRI) as well as optional glucose metabolism and amyloid positron emission tomography. Subjects will be contacted by telephone every 3 months and interviewed, on average, every 15 months for 5 years. The study endpoint is the development of mild cognitive impairment or dementia. Jak & Bondi’s actuarial neuropsychological method will be used for diagnosis of MCI. The least absolute shrinkage and selection operator logistic regression model followed by the sub-distribution hazard function model with death as a competing risk will be constructed to establish risk prediction models.Ethics and disseminationThe ethics committee of the Xuanwu Hospital of Capital Medical University has approved this study protocol (ID: [2017]046). The results will be published in peer-reviewed journals and presented at national and international scientific conferences.Trial registration numberNCT03370744; Pre-results.
Core-shell hybrid nanoparticles (NPs) for drug delivery have attracted numerous attentions due to their enhanced therapeutic efficacy and good biocompatibility. In this work, we fabricate a two-stage microfluidic chip to implement a high-throughput, one-step, and size-tunable synthesis of mono-disperse lipid-poly (lactic-co-glycolic acid) NPs. The size of hybrid NPs is tunable by varying the flow rates inside the two-stage microfluidic chip. To elucidate the mechanism of size-controllable generation of hybrid NPs, we observe the flow field in the microchannel with confocal microscope and perform the simulation by a numerical model. Both the experimental and numerical results indicate an enhanced mixing effect at high flow rate, thus resulting in the assembly of small and mono-disperse hybrid NPs. In vitro experiments show that the large hybrid NPs are more likely to be aggregated in serum and exhibit a lower cellular uptake efficacy than the small ones. This microfluidic chip shows great promise as a robust platform for optimization of nano drug delivery system.
Subjective cognitive decline (SCD) may be an at-risk stage of Alzheimer's disease (AD) occurring prior to amnestic mild cognitive impairment (aMCI). To examine white matter (WM) defects in SCD, diffusion images from 27 SCD (age=65.3±8.0), 35 aMCI (age=69.2±8.6) and 25 AD patients (age=68.3±9.4) and 37 normal controls (NC) (age=65.1±6.8) were compared using Tract-Based Spatial Statistics (TBSS). WM impairments common to the three patient groups were extracted, and fractional anisotropy (FA) values were averaged in each group. As compared to NC subjects, SCD patients displayed widespread WM alterations represented by decreased FA (p<0.05), increased mean diffusivity (MD; p<0.05), and increased radial diffusivity (RD; p<0.05). In addition, localized WM alterations showed increased axial diffusivity (AxD; p<0.05) similar to what was observed in aMCI and AD patients (p<0.05). In the shared WM impairment tracts, SCD patients had FA values between the NC group and the other two patient groups. In the NC and SCD groups, the AVLT-delayed recall score correlated with higher AxD (r=−0.333, p=0.045), MD (r=−0.351, p=0.03) and RD (r=−0.353, p=0.025). In both the aMCI and AD groups the diffusion parameters were highly correlated with cognitive scores. Our study suggests that SCD patients present with widespread WM changes, which may contribute to the early memory decline they experience.
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