A 36-week, randomized, placebo-controlled trial of Citrus supplementation in subjective cognitive decline

Description

The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in 80 individuals with subjective cognitive decline (SCD). Participants were randomly assigned to active treatment (400 mg of Citrus peels extract containing 3.0 mf of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The mean age of participants was 68.5+4.2 years. They were in prevalence females (75%) and highly educated (13.7+3.4 years). The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and self-reported memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) over the 36-week trial period in a subsample of consecutive 60 participants. The RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time <.001, d=0.36, p time x treatment=.910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p <.001) and scales of subjective memory (p <.01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d=0.69 in short-term, and d=0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time=.010, d=0.21, p time x treatment=.772). The database contains cognitive and subjective memory variables at baseline, 18- and 36-weeks, and IL-8 at baseline and 36-weeks. Data dictionary is included.

Steps to reproduce

The primary analysis was performed by using a linear mixed-effects model for repeated measures with treatment group, time (weeks 0, 18 and 36), treatment group–by–time interaction as fixed effects, while subject ID was treated as random. Moreover, a robust standard error estimator was used. A generalized linear mixed model with the same fixed and random effect specifications was run with IL-8 as the dependent variable and batch as the covariate. Mixed-effects models with the same fixed and random effect specifications used for the primary endpoint were run with each composite score as the dependent variable.. Depending on the distribution of the outcome, linear mixed models or generalized linear mixed models were implemented. Since all outcome measures exhibited a nearly symmetrical, well-shaped distribution centered around a mean value, we applied the normal distribution with an identity link function and employed the maximum likelihood method for parameter estimation. To evaluate goodness-of-fit, we utilized a combination of the Akaike information criterion corrected in conjunction with the Bayesian information criterion. In the presence of outliers and/or imperfections in the shape of the distribution curve, we used a robust covariance matrix estimator.

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