将多模式生活方式干预与前驱期阿尔茨海默病的医学食品相结合：MIND-AD 随机对照试验。
Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-AD randomized controlled trial.
机构信息
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research QA32, Karolinska Institute, Karolinska Vägen 37 A, Solna, 171 64, Sweden.
Theme Inflammation and Aging, Karolinska University Hospital, Karolinska Vägen 37 A, Solna, Stockholm, 171 64, Sweden.
出版信息
Alzheimers Res Ther. 2024 May 30;16(1):118. doi: 10.1186/s13195-024-01468-x.
BACKGROUND
The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear.
METHODS
MIND-AD was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale.
RESULTS
During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (β = 1.11, P = 0.038; β = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions.
CONCLUSIONS
The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03249688.
背景
芬兰认知干预研究预防认知障碍和残疾（FINGER）表明，在有患病风险的老年人中，进行多领域生活方式干预可以带来认知益处。LipiDiDiet 试验强调了在前驱期阿尔茨海默病（AD）中使用医疗食品的益处。然而，在前驱期 AD 中结合生活方式和医疗食品的多模式干预的可行性和影响尚不清楚。
方法
MIND-AD 是一项为期 6 个月的多国家（瑞典、芬兰、德国、法国）概念验证随机对照试验（RCT）。参与者年龄在 60-85 岁之间，患有前驱期 AD（国际工作组-1 标准）和血管/生活方式风险因素。该平行组 RCT 有三个组：多模式生活方式干预（营养指导、运动、认知训练、血管/代谢风险管理和社会刺激）；多模式生活方式干预+医疗食品（Fortasyn Connect）；以及常规健康咨询/护理（对照组）。参与者按 1:1:1（在每个站点使用计算机生成的分配）随机分组。结果评估者对随机分组情况不知情。主要结局是多模式干预的可行性，通过 6 个月的招募阶段的招募率、每个干预组的总体依从性和 6 个月的保留率来评估。成功的依从性被预先指定为参加≥40%的课程/领域（≥2/4 个领域的生活方式干预），并消费≥60%的医疗食品（生活方式干预+医疗食品）。次要结局包括每个干预成分的依从性/参与度和健康生活方式改变的总体依从性，使用健康生活方式的综合评分进行衡量。认知评估作为探索性结局包括在内，例如临床痴呆评定量表。
结果
在 2017 年 9 月至 2019 年 5 月期间，共有 93 人被随机分组（生活方式干预组 32 人，生活方式+医疗食品组 31 人，对照组 30 人）。总体招募率为 76.2%（前 6 个月为 64.8%）。总体 6 个月保留率为 91.4%（生活方式干预组 87.5%；生活方式+医疗食品组 90.3%；对照组 96.7%）。生活方式干预组中认知训练的依从率为 71.9%，运动为 78.1%，营养指导为 68.8%，血管风险管理为 81.3%；生活方式+医疗食品组中认知训练的依从率为 90.3%，运动为 87.1%，营养指导为 80.7%，血管风险管理为 87.1%，医疗食品为 87.1%。与对照组相比，两个干预组均显示出健康饮食的改善（β=1.11，P=0.038；β=1.43，P=0.007）；生活方式+医疗食品组还显示出血管风险降低（P=0.043）和认知功能下降减少（P<0.05，探索性分析）。有 5 例严重不良事件（对照组 1 例；生活方式干预组 3 例；生活方式+医疗食品组 1 例）与干预无关。
结论
在前驱期 AD 中，单独或联合使用医疗食品的多领域生活方式干预具有良好的可行性和依从性。在更大规模的试验中应进一步研究其长期认知和其他健康益处。
试验注册
ClinicalTrials.gov NCT03249688。
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