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 - LipiDiDiet clinical study group
AU - Soininen, Hilkka
AU - Solomon, Alina
AU - Visser, Pieter Jelle
AU - Hendrix, Suzanne B.
AU - Blennow, Kaj
AU - Kivipelto, Miia
AU - Hartmann, Tobias
AU - Hallikainen, Ilona
AU - Hallikainen, Merja
AU - Helisalmi, Seppo
AU - Lappalainen, Tarja
AU - Liu, Yawu
AU - Paajanen, Teemu
AU - Wahlund, Lars Olof
AU - Freund-Levi, Yvonne
AU - Andreasen, Niels
AU - Hagman, Göran
AU - Lindblom, Stina
AU - Fassbender, Klaus
AU - Riemenschneider, Matthias
AU - Grimm, Marcus OW
AU - Klees-Rollmann, Aline
AU - Luley, Maxine
AU - Lyros, Epameinondas
AU - Schomburg, Robert
AU - Kennel, Jennifer
AU - Ramelli, Daniela
AU - Frölich, Lutz
AU - Hausner, Lucrezia
AU - Laske, Christoph
AU - Leyhe, Thomas
AU - Mychajliw, Christian
AU - Koehler, Niklas
AU - Schiekofer, Stephan
AU - Klünemann, Hans
AU - Schröder, Johannes
AU - Lütjohann, Dieter
AU - Scheltens, Philip
AU - van Rossum, Ineke
AU - Scheltens, Nienke
AU - Bertens, Daniela
AU - ten Kate, Mara
AU - Barkhof, Frederik
AU - Henselmans, Johanna ML
AU - Roks, Gerwin
AU - van Hees, Anneke MJ
AU - Ellison, Noel
PY - 2017/12/1
Y1 - 2017/12/1
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. Funding European Commission 7th Framework Programme.
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. Funding European Commission 7th Framework Programme.
UR - http://www.scopus.com/inward/record.url?scp=85033663926&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/S1474-4422(17)30332-0
DO - https://doi.org/10.1016/S1474-4422(17)30332-0
M3 - Article
SN - 1474-4422
VL - 16
SP - 965
EP - 975
JO - The Lancet Neurology
JF - The Lancet Neurology
IS - 12
ER -