Time-of-day effects in brain volume (brain volumes are larger in the morning) (!)

There was a statistically significant effect of time-of-day on the BPF change in MS clinical trial datasets (− 0.180 per day, that is, 0.180% of intracranial volume, p = 0.019) as well as the ADNI dataset (− 0.438 per day, that is, 0.438% of intracranial volume, p < 0.0001), showing that the brain volume is greater in the morning. Linearly correcting the BPF values with the time-of-day reduced the required sample size to detect a 25% treatment effect (80% power and 0.05 significance level) on change in brain volume from 2 time-points over a period of 1 year by 2.6%.