Soininen Hilkka, Solomon Alina, Visser Pieter Jelle, Hendrix Suzanne B, Blennow Kaj, Kivipelto Miia, Hartmann Tobias
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Neurocenter, Department of Neurology, Kuopio University Hospital, Kuopio, Finland.
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Huddinge, Sweden; Clinical Trials Unit, Department of Geriatric Medicine, Karolinska University Hospital, Huddinge, Sweden.
Lancet Neurol. 2017 Dec;16(12):965-975. doi: 10.1016/S1474-4422(17)30332-0. Epub 2017 Oct 30.
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.
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.
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.
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.
European Commission 7th Framework Programme.
营养是阿尔茨海默病中一个重要的可改变风险因素。先前对多种营养素组合的“福达适联合营养剂”（Fortasyn Connect）进行的试验显示，其对轻度阿尔茨海默病性痴呆有益。“脂质饮食”（LipiDiDiet）研究了福达适联合营养剂对前驱期阿尔茨海默病认知及相关指标的影响。在此，我们报告该试验的24个月结果。
“脂质饮食”是一项为期24个月的随机、对照、双盲、平行组、多中心试验（在芬兰、德国、荷兰和瑞典的11个地点开展），有可选的12个月双盲延长期。该试验纳入了根据国际工作组（IWG）-1标准定义的前驱期阿尔茨海默病患者。参与者被随机分配（1:1）至活性产品组（每日一次饮用125 mL含福达适联合营养剂的饮品）或对照产品组。随机分组由计算机在中心以每组4个的区组进行，按地点分层。所有研究人员和参与者均对治疗分配情况不知情。主要终点是神经心理测试组合（NTB）评分的变化。分析采用改良意向性分析。安全性分析包括所有服用过至少一剂研究产品的参与者。该试验已在荷兰试验注册库注册，注册号为NTR1705。
在2009年4月20日至2013年7月3日期间，382名筛查参与者中的311名被随机分配至活性组（n = 153）或对照组（n = 158）。活性组NTB主要终点的平均变化为-0.028（标准差0.453），对照组为-0.108（0.528）；估计平均治疗差异为0.098（95%置信区间-0.041至0.237；p = 0.166）。对照组在24个月期间的下降幅度小于研究前估计的-0.4。66名（21%）参与者退出了研究。活性组34名（22%）参与者和对照组30名（19%）参与者发生了严重不良事件（p = 0.487），其中无一被认为与研究干预相关。
该干预措施在2年时间里对前驱期阿尔茨海默病的NTB主要终点没有显著影响。然而，该人群的认知衰退远低于预期，导致主要终点的检验效能不足。在测量认知、功能和海马萎缩的疾病进展次要终点上观察到了组间差异。需要对营养方法进行进一步研究，样本量更大、持续时间更长或采用对该痴呆前期人群更敏感的主要终点。
欧盟委员会第七框架计划。
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