Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK.
J Gerontol A Biol Sci Med Sci. 2021 Feb 25;76(3):491-498. doi: 10.1093/gerona/glaa279.
Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60-77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).
This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was -0.016 (0.19) in the intervention group and -0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI -0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: -0.005 (95% CI -0.010 to -0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI -0.011 to 0.264).
This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.
NCT01041989.
端粒长度较短与衰老和痴呆有关。生活方式改变对端粒长度的影响，以及与认知和痴呆遗传易感性的关系，尚未在随机对照试验 (RCT) 中进行研究。
芬兰老年干预研究预防认知障碍和残疾是一项为期 2 年的 RCT，纳入了来自普通人群的 1260 名有痴呆风险的参与者，年龄在 60-77 岁之间，随机分配（1:1）接受多领域生活方式干预或对照组。主要结局是认知变化（神经心理学测试电池 z 评分）。相对端粒长度使用实时定量聚合酶链反应进行测量（试验注册：NCT01041989）。
这项探索性端粒长度子研究包括 756 名参与者（377 名干预组，379 名对照组），具有基线和 24 个月的端粒长度测量值。干预组的平均年端粒长度变化（SD）为-0.016（0.19），对照组为-0.023（0.17）。组间差异无统计学意义（未标准化β系数 0.007，95%CI-0.015 至 0.030）。交互分析表明，载脂蛋白 E（APOE）-ε4 携带者的端粒长度维持情况优于非携带者：0.054（95%CI0.007 至 0.102）；年龄较小的参与者优于年龄较大的参与者：-0.005（95%CI-0.010 至 -0.001）；健康生活方式改变较多的参与者优于改变较少的参与者：0.047（95%CI0.005 至 0.089）。在执行功能（0.227，95%CI0.057 至 0.396）和长期记忆（0.257，95%CI0.024 至 0.489）方面，端粒长度维持较好的参与者认知干预获益更为明显，神经心理测试电池总分也呈现出类似的趋势（0.127，95%CI-0.011 至 0.264）。
这是第一项大型 RCT 研究表明，多领域生活方式干预有助于痴呆高危老年人亚组的端粒长度维持，包括 APOE-ε4 携带者。端粒长度维持与认知干预益处更为显著相关。
NCT01041989。
