近日，美国维克森林大学医学院Laura D. Baker团队研究了针对整体认知功能的有组织与自我引导式多领域生活方式干预对患者预后的影响。相关论文于2025年7月28日发表在《美国医学会杂志》上。

确定新的干预措施以减缓和预防与痴呆症相关的认知能力下降至关重要。针对可改变的危险因素的非药物干预是有前景的、相对低成本的、可获得的和安全的方法。

为了比较两种2年生活方式干预对有认知能力下降和痴呆风险的老年人认知轨迹的影响，2019年5月至2023年3月（最终随访时间为2025年5月14日），研究组在美国5个临床机构进行了一项单盲、多中心随机临床试验，纳入2111名参与者。参与者纳入标准增加了认知能力下降的风险，包括年龄60 - 79岁、久坐不动的生活方式和次优饮食，以及至少2个与记忆障碍家族史、心脏代谢风险、种族和民族、年龄和性别相关的额外标准。将参与者以相同的概率随机分配到结构化（n= 1056）或自我引导（n= 1055）干预中。两种干预措施都鼓励增加身体和认知活动、健康饮食、社会参与和心血管健康监测，但在结构、强度和责任方面有所不同。主要结局为比较干预组超过2年的时间内在全球认知功能年变化率上的差异，通过执行功能、情景记忆和处理速度的综合测量来评估。

在入组的2111例个体中，平均年龄68.2（SD， 5.2）岁，1455例为女性（68.9%），89%完成了第2年的评估。随着时间的推移，两组的平均整体认知综合z评分均较基线有所增加，结构化干预的平均年增长率为0.243 SD (95% CI, 0.227-0.258)，自我引导干预的平均年增长率为0.213 SD （95% CI, 0.198-0.229）。结构化组的平均年增长率比自我引导组高0.029 SD (95% CI, 0.008-0.050；P = .008)。根据预先设定的次要亚组比较，结构化干预的益处在APOE ε4携带者和非携带者中一致（交互作用P=0.95），但在基线认知水平较低的成年人中似乎比认知水平较高的成年人更大（交互作用P=0.02）。结构化干预组报告的不良事件（严重：151例；非严重：1091例）少于自我引导组（严重：190例；非严重：1225例），其中新冠病毒检测结果阳性是总体中最常见的不良事件，且在结构化干预组中更为常见。

研究结果表明，在有认知能力下降和痴呆风险的老年人中，与非结构化、自我引导的干预相比，结构化、高强度的干预在整体认知方面具有统计学上显著的更大益处。功能预后、生物标志物的进一步研究和持续的延长随访将有助于确定所观察到的认知益处的临床相关性和可持续性。

附：英文原文

Title: Structured vs Self-Guided Multidomain Lifestyle Interventions for Global Cognitive Function: The US POINTER Randomized Clinical Trial

Author: Laura D. Baker, Mark A. Espeland, Rachel A. Whitmer, Heather M. Snyder, Xiaoyan Leng, Laura Lovato, Kathryn V. Papp, Melissa Yu, Miia Kivipelto, Ashley S. Alexander, Susan Antkowiak, Maryjo Cleveland, Claire Day, Richard Elbein, Sarah Tomaszewski Farias, Deborah Felton, Katelyn R. Garcia, Darren R. Gitelman, Sarah Graef, Marjorie Howard, Jeffrey Katula, Katherine Lambert, Olivia Matongo, Anne Marie McDonald, Valory Pavlik, Rema Raman, Stephen Salloway, Christy Tangney, Jennifer Ventrelle, Sharon Wilmoth, Benjamin J. Willliams, Rena Wing, Nancy Woolard, Maria C. Carrillo

Issue&Volume: 2025-07-28

Abstract:

Importance  Identifying new interventions to slow and prevent cognitive decline associated with dementia is critical. Nonpharmacological interventions targeting modifiable risk factors are promising, relatively low-cost, accessible, and safe approaches.

Objective  To compare the effects of two 2-year lifestyle interventions on cognitive trajectory in older adults at risk of cognitive decline and dementia.

Design, Setting, and Participants  Single-blind, multicenter randomized clinical trial enrolling 2111 participants from May 2019 to March 2023 (final follow-up, May 14, 2025) at 5 clinical sites in the US. Participant inclusion criteria enriched risk of cognitive decline and included age 60 to 79 years, sedentary lifestyle, and suboptimal diet plus at least 2 additional criteria related to family history of memory impairment, cardiometabolic risk, race and ethnicity, older age, and sex.

Interventions  Participants were randomly assigned with equal probability to structured (n=1056) or self-guided (n=1055) interventions. Both interventions encouraged increased physical and cognitive activity, healthy diet, social engagement, and cardiovascular health monitoring, but differed in structure, intensity, and accountability.

Main Outcomes and Measures  The primary comparison was difference between intervention groups in annual rate of change in global cognitive function, assessed by a composite measure of executive function, episodic memory, and processing speed, over 2 years.

Results  Among the 2111 individuals enrolled (mean age, 68.2 [SD, 5.2] years; 1455 [68.9%] female), 89% completed the year 2 assessment. The mean global cognitive composite z score increased from baseline over time in both groups, with a mean rate of increase per year of 0.243 SD (95% CI, 0.227-0.258) for the structured intervention and 0.213 SD (95% CI, 0.198-0.229) for the self-guided intervention. The mean rate of increase per year was statistically significantly greater for the structured group than the self-guided group by 0.029 SD (95% CI, 0.008-0.050; P=.008). Based on prespecified secondary subgroup comparisons, the structured intervention benefit was consistent for APOE ε4 carriers and noncarriers (P=.95 for interaction) but appeared greater for adults with lower vs higher baseline cognition (P=.02 for interaction). Fewer ascertained adverse events were reported in the structured group (serious: 151; nonserious: 1091) vs the self-guided group (serious: 190; nonserious: 1225), with a positive COVID-19 test result being the most common adverse event overall and more frequent in the structured group.

Conclusions and Relevance  Among older adults at risk of cognitive decline and dementia, a structured, higher-intensity intervention had a statistically significant greater benefit on global cognition compared with an unstructured, self-guided intervention. Further investigation of functional outcomes, biomarkers, and ongoing extended follow-up will help address clinical relevance and sustainability of the observed cognitive benefits.

DOI: 10.1001/jama.2025.12923

Source: https://jamanetwork.com/journals/jama/fullarticle/2837046