血浆瘦素水平与阿尔茨海默病发病及脑老化 MRI 测量指标的相关性。
Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging.
机构信息
Framingham Heart Study, Framingham, Massachusetts, USA.
出版信息
JAMA. 2009 Dec 16;302(23):2565-72. doi: 10.1001/jama.2009.1836.
CONTEXT
The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes beta-amyloid clearance, and improves memory function in animal models of aging and Alzheimer disease (AD).
OBJECTIVE
To relate baseline circulating leptin concentrations in a community-based sample of individuals without dementia to incident dementia and AD during follow-up and magnetic resonance imaging (MRI) measures of brain aging in survivors.
DESIGN, SETTING, AND PARTICIPANTS: Prospective study of plasma leptin concentrations measured in 785 persons without dementia (mean [SD] age, 79 [5] years; 62% female), who were in the Framingham original cohort at the 22nd examination cycle (1990-1994). A subsample of 198 dementia-free survivors underwent volumetric brain MRI between 1999 and 2005, approximately 7.7 years after leptin was assayed. Two measures of brain aging, total cerebral brain volume and temporal horn volume (which is inversely related to hippocampal volume) were assessed.
MAIN OUTCOME MEASURE
Incidence of dementia and AD during follow-up until December 31, 2007.
RESULTS
During a median follow-up of 8.3 years (range, 0-15.5 years), 111 participants developed incident dementia; 89 had AD. Higher leptin levels were associated with a lower risk of incident dementia and AD in multivariable models (hazard ratio per 1-SD increment in log leptin was 0.68 [95% confidence interval, 0.54-0.87] for all-cause dementia and 0.60 [95% confidence interval, 0.46-0.79] for AD). This corresponds to an absolute AD risk over a 12-year follow-up of 25% for persons in the lowest quartile (first quartile) vs 6% for persons in the fourth quartile of sex-specific leptin levels. In addition, a 1-SD elevation in plasma leptin level was associated with higher total cerebral brain volume and lower temporal horn volume, although the association of leptin level with temporal horn volume did not reach statistical significance.
CONCLUSION
Circulating leptin was associated with a reduced incidence of dementia and AD and with cerebral brain volume in asymptomatic older adults.
背景
脂肪细胞因子瘦素促进海马体的长期增强和突触可塑性，促进β-淀粉样蛋白清除，并改善衰老和阿尔茨海默病（AD）动物模型的记忆功能。
目的
将社区样本中无痴呆个体的基础循环瘦素浓度与随访期间的痴呆和 AD 发生率以及幸存者的磁共振成像（MRI）脑老化测量相关联。
设计、地点和参与者：前瞻性研究了 785 名无痴呆个体（平均[标准差]年龄为 79[5]岁，62%为女性）的血浆瘦素浓度，这些个体在第 22 个检查周期（1990-1994 年）时处于弗雷明汉原队列中。亚组 198 名无痴呆幸存者在 1999 年至 2005 年之间进行了容积脑 MRI 检查，大约在测定瘦素后 7.7 年。评估了两种脑老化测量值，总脑容量和颞角体积（与海马体体积呈反比）。
主要观察指标
随访期间至 2007 年 12 月 31 日的痴呆和 AD 发生率。
结果
在中位随访 8.3 年（范围，0-15.5 年）期间，111 名参与者发生了痴呆事件；89 名患有 AD。多变量模型中，较高的瘦素水平与痴呆和 AD 事件的风险降低相关（每 1-SD 对数瘦素递增的风险比为 0.68[95%置信区间，0.54-0.87]，所有原因痴呆和 0.60[95%置信区间，0.46-0.79]AD）。这相当于在 12 年的随访中，最低四分位数（第一四分位数）人群的 AD 绝对风险为 25%，而第四四分位数人群的 AD 绝对风险为 6%。此外，血浆瘦素水平升高 1-SD 与总脑容量增加和颞角体积减少相关，尽管瘦素水平与颞角体积的关联未达到统计学意义。
结论
在无症状的老年人群中，循环瘦素与痴呆和 AD 发生率降低以及大脑脑容量增加相关。
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