38 research outputs found
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Actigraphy-based sleep estimation in adolescents and adults: a comparison with polysomnography using two scoring algorithms
Objectives: Actigraphy is widely used to estimate sleep–wake time, despite limited information regarding the comparability of different devices and algorithms. We compared estimates of sleep–wake times determined by two wrist actigraphs (GT3X+ versus Actiwatch Spectrum [AWS]) to in-home polysomnography (PSG), using two algorithms (Sadeh and Cole–Kripke) for the GT3X+ recordings. Subjects and methods Participants included a sample of 35 healthy volunteers (13 school children and 22 adults, 46% male) from Boston, MA, USA. Twenty-two adults wore the GT3X+ and AWS simultaneously for at least five consecutive days and nights. In addition, actigraphy and PSG were concurrently measured in 12 of these adults and another 13 children over a single night. We used intraclass correlation coefficients (ICCs), epoch-by-epoch comparisons, paired t-tests, and Bland–Altman plots to determine the level of agreement between actigraphy and PSG, and differences between devices and algorithms. Results: Each actigraph showed comparable accuracy (0.81–0.86) for sleep–wake estimation compared to PSG. When analyzing data from the GT3X+, the Cole–Kripke algorithm was more sensitive (0.88–0.96) to detect sleep, but less specific (0.35–0.64) to detect wake than the Sadeh algorithm (sensitivity: 0.82–0.91, specificity: 0.47–0.68). Total sleep time measured using the GT3X+ with both algorithms was similar to that obtained by PSG (ICC=0.64–0.88). In contrast, agreement between the GT3X+ and PSG wake after sleep onset was poor (ICC=0.00–0.10). In adults, the GT3X+ using the Cole–Kripke algorithm provided data comparable to the AWS (mean bias=3.7±19.7 minutes for total sleep time and 8.0±14.2 minutes for wake after sleep onset). Conclusion: The two actigraphs provided comparable and accurate data compared to PSG, although both poorly identified wake episodes (i.e., had low specificity). Use of actigraphy scoring algorithm influenced the mean bias and level of agreement in sleep–wake times estimates. The GT3X+, when analyzed by the Cole–Kripke, but not the Sadeh algorithm, provided comparable data to the AWS
A systematic review of progranulin concentrations in biofluids in over 7,000 people—assessing the pathogenicity of GRN mutations and other influencing factors
Background: Pathogenic heterozygous mutations in the progranulin gene (GRN) are a key cause of frontotemporal dementia (FTD), leading to significantly reduced biofluid concentrations of the progranulin protein (PGRN). This has led to a number of ongoing therapeutic trials aiming to treat this form of FTD by increasing PGRN levels in mutation carriers. However, we currently lack a complete understanding of factors that affect PGRN levels and potential variation in measurement methods. Here, we aimed to address this gap in knowledge by systematically reviewing published literature on biofluid PGRN concentrations. Methods: Published data including biofluid PGRN concentration, age, sex, diagnosis and GRN mutation were collected for 7071 individuals from 75 publications. The majority of analyses (72%) had focused on plasma PGRN concentrations, with many of these (56%) measured with a single assay type (Adipogen) and so the influence of mutation type, age at onset, sex, and diagnosis were investigated in this subset of the data. Results: We established a plasma PGRN concentration cut-off between pathogenic mutation carriers and non-carriers of 74.8 ng/mL using the Adipogen assay based on 3301 individuals, with a CSF concentration cut-off of 3.43 ng/mL. Plasma PGRN concentration varied by GRN mutation type as well as by clinical diagnosis in those without a GRN mutation. Plasma PGRN concentration was significantly higher in women than men in GRN mutation carriers (p = 0.007) with a trend in non-carriers (p = 0.062), and there was a significant but weak positive correlation with age in both GRN mutation carriers and non-carriers. No significant association was seen with weight or with TMEM106B rs1990622 genotype. However, higher plasma PGRN levels were seen in those with the GRN rs5848 CC genotype in both GRN mutation carriers and non-carriers. Conclusions: These results further support the usefulness of PGRN concentration for the identification of the large majority of pathogenic mutations in the GRN gene. Furthermore, these results highlight the importance of considering additional factors, such as mutation type, sex and age when interpreting PGRN concentrations. This will be particularly important as we enter the era of trials for progranulin-associated FTD.</p