Alzheimer's Disease Composite Score: A Post-Hoc Analysis Using Data from the LipiDiDiet Trial in Prodromal Alzheimer's Disease.

As research evolves in prodromal AD, the need to validate sufficiently sensitive outcome measures, e.g. the Alzheimer's Disease Composite Score (ADCOMS) is clear. In the LipiDiDiet randomized trial in prodromal AD, cognitive decline in the study population was much less than expected in the timeframe studied. While the primary composite endpoint was insufficiently sensitive to detect a difference in the modified intention to treat population, the per-protocol population showed less decline in the active than the control group, indicating better treatment effects with regular product intake. These results were further strengthened by significant benefits on secondary endpoints of cognition and function, and brain atrophy. The present post-hoc analysis investigated whether ADCOMS could detect a difference between groups in the LipiDiDiet population (138 active, 140 control). The estimated mean change in ADCOMS from baseline (standard error) was 0.085 (0.018) in the active and 0.133 (0.018) in the control group; estimated mean treatment difference -0.048 (95% confidence intervals -0.090, -0.007; p=0.023), or 36% less decline in the active group. This suggests ADCOMS identified the cognitive and functional benefits observed previously, confirming the sensitivity of this composite measure.
Competing Interests: SBH and NNE report financial compensation for statistical analysis from Danone Nutricia Research. HS reports personal fees from ACImmune and MERCK, outside the submitted work. AMJH and AA are employees of Danone Nutricia Research. PJV reports grants from Inn ovative Medicine Initiative and ZonMw, during the conduct of the study, and non-financial support from GE Healthcare and grants from Biogen, outside the submitted work. AS reports grants from Academy of Finland, during the conduct of the study, and grants from Alzheimerfonden Sweden and Stockholm County Council (ALF), outside the submitted work. MK reports grants from EU Joint Program - Neurodegenerative Disease Research (MIND-AD), during the conduct of the study, and grants from Alzheimerfonden Sweden, Stockholm County Council (ALF), Academy of Finland, Swedish Research Council, Knut and Alice Wallenberg Foundation, Center for Innovative Medicine at Karolinska Institutet, Sweden, and Stiftelsen Stockholms Sjukhem, Sweden, outside the submitted work. TH reports grants from EU FP7 (LipiDiDiet), EU Joint Program - Neurodegenerative Disease Research (MIND-AD), and Danone Nutricia Research (LipiDiDiet Extension), during the conduct of the study. KB has nothing to disclose.