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. 2024;11(4):992-997.
doi: 10.14283/jpad.2024.55.

Evaluation of Clinical Meaningfulness of Fortasyn Connect in Terms of "Time Saved"

S P Dickson  1 , A Solomon, M Kivipelto, T Hartmann, A M J van Hees, A Brownlee, B Haaland, C H Mallinckrodt, S B Hendrix
Affiliations

Evaluation of Clinical Meaningfulness of Fortasyn Connect in Terms of "Time Saved"

S P Dickson et al. J Prev Alzheimers Dis. 2024.

Abstract

Assessment of meaningfulness in randomized clinical trials (RCTs) in Alzheimer's disease (AD) is challenging, particularly in early disease. Converting clinical outcomes to disease progression time allows assessment of treatment effects using a metric that is understandable and meaningful: time. We demonstrate time savings assessments using meta time component tests (TCTs) in the LipiDiDiet multinutrient RCT. Dietary patterns are important for dementia prevention, likely due to individual cumulative nutrient effects. LipiDiDiet used a multinutrient (Fortasyn Connect) formulation in patients with prodromal AD, benefitting cognition (5-item composite NTB, effect 0.089), cognition and function (CDR-SB, -0.605), and slowing hippocampal atrophy (0.122 cm3). Meaningfulness of point differences is unclear. However, a combination TCT showed 9-month disease time savings at 24 months (38% slowing of disease time): 9.0, 10.5, and 7.2 months for NTB, CDR-SB, and hippocampal volume, underscoring the value of TCTs in AD RCTs and the need for continued validation of this approach.

Keywords: Alzheimer’s disease and mild cognitive impairment; Fortasyn Connect; Souvenaid; Time saved; clinical relevance and meaningfulness; nutritional supplements.

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Conflict of interest statement

S. Dickson, A. Brownlee, B. Haaland, C. Mallinckrodt, and S. Hendrix are employees of Pentara Corporation, a company which consults for Danone Nutricia Research. A.M.J. van Hees is an employee of Danone Nutricia Research. Funding was partly provided by Danone Nutricia Research. T. Hartmann is the LipiDiDiet Coordinator.

Figures

Figure 1
Figure 1
An illustration of a disease-modifying effect, whereby treatment delays disease progression Footnote: At time point Y, the change on the clinical outcome over time is less with active treatment than placebo (or natural disease progression). At this time point, the decline on the clinical outcome with active treatment (A) was reached at time point X with placebo. The difference between X and Y is the time gained with active treatment. As an example, a 25% reduction in the progression on an outcome measure with a DMT is equivalent to delaying disease progress by 3 months over 12 months of treatment. Adapted from Dickson, et al. 2023, Journal of Prevention of Alzheimer's Disease – https://creativecommons.org/licenses/by/4.0/.
Figure 2
Figure 2
Mixed model results, time component tests, and time savings with intervention in the LipiDiDiet 2-year dataset Footnote: Panel A: Least square means (+/− SE) over time for the NTB 5-item, CDR-SB, and MRI hippocampal volume based on the pre-specified sensitivity MMRM analysis in the LipiDiDiet 2-year dataset. Panel B: Months (mean + /− SE) of disease progression relative to the control group disease progression over time. Panel C: Months (mean and 95% confidence interval) saved by intervention compared to the control group over time based on the TCT analyses in Panel B. Abbreviations: SE: standard error; NTB: neuropsychological test battery; CDR-SB: clinical dementia rating – sum of boxes; MRI: magnetic resonance imaging; MMRM: mixed model for repeated measures.
Figure 3
Figure 3
Combined evidence from gTCT in addition to summary findings from meta time component tests (TCTs) applied to the NTB 5-item, CDR-SB, and hippocampal volume; data from the LipiDiDiet 2-year dataset Based on 24-month datapoint in the LipiDiDiet 2-year dataset. Abbreviations: SE: standard error; NTB: neuropsychological test battery; CDR-SB: clinical dementia rating – sum of boxes; MRI: magnetic resonance imaging; MMRM: mixed model for repeated measures.
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