TY - JOUR
T1 - 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet)
T2 - a randomised, double-blind, controlled trial
AU - Soininen, Hilkka
AU - Solomon, Alina
AU - Visser, Pieter Jelle
AU - Hendrix, Suzanne B.
AU - Blennow, Kaj
AU - Kivipelto, Miia
AU - Hartmann, Tobias
AU - LipiDiDiet Clinical Study Grp
PY - 2017/12
Y1 - 2017/12
N2 - Background Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial.Methods LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1: 1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705.Findings Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0.028 (SD 0.453) in the active group and -0.108 (0.528) in the control group; estimated mean treatment difference was 0.098 (95% CI -0.041 to 0.237; p=0.166). The decline in the control group was less than the prestudy estimate of -0.4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0.487), none of which were regarded as related to the study intervention.Interpretation The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
AB - Background Nutrition is an important modifiable risk factor in Alzheimer's disease. Previous trials of the multinutrient Fortasyn Connect showed benefits in mild Alzheimer's disease dementia. LipiDiDiet investigated the effects of Fortasyn Connect on cognition and related measures in prodromal Alzheimer's disease. Here, we report the 24-month results of the trial.Methods LipiDiDiet was a 24-month randomised, controlled, double-blind, parallel-group, multicentre trial (11 sites in Finland, Germany, the Netherlands, and Sweden), with optional 12-month double-blind extensions. The trial enrolled individuals with prodromal Alzheimer's disease, defined according to the International Working Group (IWG)-1 criteria. Participants were randomly assigned (1: 1) to active product (125 mL once-a-day drink containing Fortasyn Connect) or control product. Randomisation was computer-generated centrally in blocks of four, stratified by site. All study personnel and participants were masked to treatment assignment. The primary endpoint was change in a neuropsychological test battery (NTB) score. Analysis was by modified intention to treat. Safety analyses included all participants who consumed at least one study product dose. This trial is registered with the Dutch Trial Register, number NTR1705.Findings Between April 20, 2009, and July 3, 2013, 311 of 382 participants screened were randomly assigned to the active group (n=153) or control group (n=158). Mean change in NTB primary endpoint was -0.028 (SD 0.453) in the active group and -0.108 (0.528) in the control group; estimated mean treatment difference was 0.098 (95% CI -0.041 to 0.237; p=0.166). The decline in the control group was less than the prestudy estimate of -0.4 during 24 months. 66 (21%) participants dropped out of the study. Serious adverse events occurred in 34 (22%) participants in the active group and 30 (19%) in control group (p=0.487), none of which were regarded as related to the study intervention.Interpretation The intervention had no significant effect on the NTB primary endpoint over 2 years in prodromal Alzheimer's disease. However, cognitive decline in this population was much lower than expected, rendering the primary endpoint inadequately powered. Group differences on secondary endpoints of disease progression measuring cognition and function and hippocampal atrophy were observed. Further study of nutritional approaches with larger sample sizes, longer duration, or a primary endpoint more sensitive in this pre-dementia population, is needed. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
KW - MILD COGNITIVE IMPAIRMENT
KW - MEDICAL FOOD
KW - EFFICACY
KW - BRAIN
KW - RATS
KW - DIET
KW - SOUVENAID
KW - DIAGNOSIS
KW - CRITERIA
KW - MODEL
U2 - 10.1016/S1474-4422(17)30332-0
DO - 10.1016/S1474-4422(17)30332-0
M3 - Article
SN - 1474-4422
VL - 16
SP - 965
EP - 975
JO - Lancet Neurology
JF - Lancet Neurology
IS - 12
ER -