27-羟胆固醇、认知功能与大脑影像学标志物在 FINGER 随机对照试验中的表现
27-Hydroxycholesterol, cognition, and brain imaging markers in the FINGER randomized controlled trial.
机构信息
Division of Neurogeriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden.
出版信息
Alzheimers Res Ther. 2021 Mar 6;13(1):56. doi: 10.1186/s13195-021-00790-y.
BACKGROUND
27-Hydroxycholesterol (27-OH), the main circulating oxysterol in humans and the potential missing link between peripheral hypercholesterolemia and Alzheimer's disease (AD), has not been investigated previously in relation to cognition and neuroimaging markers in the context of preventive interventions.
METHODS
The 2-year Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) included older individuals (60-77 years) at increased risk for dementia but without dementia or substantial cognitive impairment from the general population. Participants were randomized to a multidomain intervention (diet, exercise, cognitive training, and vascular risk management) or control group (general health advice) in a 1:1 ratio. Outcome assessors were masked to group allocation. This FINGER exploratory sub-study included 47 participants with measures of 27-OH, cognition, brain MRI, brain FDG-PET, and PiB-PET. Linear regression models were used to assess the cross-sectional and longitudinal associations between 27-OH, cognition, and neuroimaging markers, considering several potential confounders/intervention effect modifiers.
RESULTS
27-OH reduction during the intervention was associated with improvement in cognition (especially memory). This was not observed in the control group. The intervention reduced 27-OH particularly in individuals with the highest 27-OH levels and younger age. No associations were found between changes in 27-OH levels and neuroimaging markers. However, at baseline, a higher 27-OH was associated with lower total gray matter and hippocampal volume, and lower cognitive scores. These associations were unaffected by total cholesterol levels. While sex seemed to influence associations at baseline, it did not affect longitudinal associations.
CONCLUSION
27-OH appears to be a marker not only for dementia/AD risk, but also for monitoring the effects of preventive interventions on cholesterol metabolism.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT01041989 . Registered on 4 January 2010.
背景
27-羟胆固醇（27-OH）是人类循环中主要的氧化固醇，也是外周高胆固醇血症与阿尔茨海默病（AD）之间潜在的缺失环节，但在预防干预的背景下，其与认知和神经影像学标志物的关系尚未得到研究。
方法
为期 2 年的芬兰老年干预研究预防认知障碍和残疾（FINGER）纳入了来自普通人群中处于痴呆高风险但没有痴呆或明显认知障碍的老年人（60-77 岁）。参与者按 1:1 的比例随机分为多领域干预（饮食、运动、认知训练和血管风险管理）组或对照组（一般健康建议）。结果评估者对分组情况不知情。这项 FINGER 探索性子研究纳入了 47 名参与者，对他们进行了 27-OH、认知、脑 MRI、脑 FDG-PET 和 PiB-PET 测量。考虑到几种潜在的混杂因素/干预效果修饰剂，使用线性回归模型评估了 27-OH 与认知和神经影像学标志物之间的横断面和纵向关联。
结果
干预过程中 27-OH 的降低与认知（尤其是记忆力）的改善有关。这在对照组中没有观察到。该干预措施特别降低了 27-OH 水平较高且年龄较小的个体的 27-OH 水平。27-OH 水平的变化与神经影像学标志物之间没有关联。然而，在基线时，较高的 27-OH 与总灰质和海马体积较低以及认知评分较低相关。这些关联不受总胆固醇水平的影响。尽管性别似乎会影响基线时的关联，但它不会影响纵向关联。
结论
27-OH 似乎不仅是痴呆/AD 风险的标志物，也是监测预防干预对胆固醇代谢影响的标志物。
试验注册
ClinicalTrials.gov ，NCT01041989 。于 2010 年 1 月 4 日注册。
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