Novel mathematical modeling approach finds Fortasyn Connect affects memory through reducing hippocampal atrophy in the LipiDiDiet trial

Background LipiDiDiet is a 6-year, randomized, double-blind, placebo-controlled intervention in 311 individuals with prodromal Alzheimer’s disease (AD)/mild cognitive impairment receiving the specific multinutrient combination Fortasyn Connect (Souvenaid) or calorie-matched placebo control once daily.1 AD characterized by neurodegeneration including significant synapse loss, and hippocampal formation particularly vulnerable early stages of AD. Results over first 2 3 years showed that reduced atrophy slowed decline on clinical other measures related to cognition, function, progression.2,3 Here, possible mechanistic pathways through which may affect risk progression are being explored post-hoc. Method A new type multivariate joint model was applied 3-year trial data longitudinal outcomes MRI volume (HCV) neuropsychological test battery (NTB)-memory allowed be associated dropout, each directly. Specifically, for outcome linear mixed-effects used estimate its trajectory, where, second outcome, predictor included as time-varying covariate. compared both (HCV NTB-memory vice versa), results existing models have form so-called parallel mediator (i.e. merely correlated but not influence causally). Result Comparing models, we observed strong association between changes no direct treatment effect NTB-memory. Notably, there HCV changes, together progression. Moreover, indirect effects were mediated Conclusion This useful modeling pathways. Overall from application suggest partly reduction directly indirectly via NTB-memory, addition yet defined other/complementary 1 Funding includes EU-JPND. 2Lancet Neurol. 2017;16:965-975. 3Alz & Dementia. 2021;17:29-40.