In this inaugural post we will get straight to the point. More information on the Journal of Robustness Reports is available on this site and on BayesianSpectacles. The article that I wish to highlight as a candidate for a set of Robustness Reports is the following:
Aron, L., Ngian, Z.K., Qiu, C. et al. Lithium deficiency and the onset of Alzheimer’s disease. Nature 645, 712–721 (2025). https://doi.org/10.1038/s41586-025-09335-x.
The main reason for selecting this article is, frankly, because it may hold the key to cure one of the most debilitating diseases that humanity has to face. The abstract:
“The earliest molecular changes in Alzheimer’s disease (AD) are poorly understood1,2,3,4,5. Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in the brain by depleting it from the diet of wild-type and AD mouse models. Reducing endogenous cortical Li by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons and myelin, and accelerated cognitive decline. These effects were mediated, at least in part, through activation of the kinase GSK3β. Single-nucleus RNA-seq showed that Li deficiency gives rise to transcriptome changes in multiple brain cell types that overlap with transcriptome changes in AD. Replacement therapy with lithium orotate, which is a Li salt with reduced amyloid binding, prevents pathological changes and memory loss in AD mouse models and ageing wild-type mice. These findings reveal physiological effects of endogenous Li in the brain and indicate that disruption of Li homeostasis may be an early event in the pathogenesis of AD. Li replacement with amyloid-evading salts is a potential approach to the prevention and treatment of AD.”
It is clear that such a high-impact article would benefit from a robustness analysis. The overall results look compelling [but would be much more compelling had the experiments been preregistered, ideally as a Registered Report (Chambers, 2013, 2015), so we can be certain that the presented results are not cherry-picked!] but I did notice some comparisons in which the variances were clearly unequal. What conclusions would have followed from a Bayesian model-averaged t-test (Maier et al., 2025)?
Author
References
Aron, L., Ngian, Z.K., Qiu, C. et al. Lithium deficiency and the onset of Alzheimer’s disease. Nature 645, 712–721 (2025). https://doi.org/10.1038/s41586-025-09335-x.
Chambers, C. D. (2013). Registered Reports: A new publishing initiative at Cortex. Cortex, 49, 609-610.
Chambers, C. D. (2015). Ten reasons why journals must review manuscripts before results are known. Addiction, 110, 10-11.
Maier, M., Bartoš, F., Quintana, D., Dablander, F., van den Bergh, D., Marsman, M., Ly, A., & Wagenmakers, E.-J. (2025). Model-averaged Bayesian t-tests. Psychonomic Bulletin & Review, 32, 1007-1031.