Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging.
Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging.
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DOI：
10.1001/jama.2009.1836
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发表时间：
2009-12-16
影响因子：
120.7
通讯作者：
Seshadri, Sudha
中科院分区：
文献类型：
--
作者：
Lieb, Wolfgang;Beiser, Alexa S.;Vasan, Ramachandran S.;Tan, Zaldy S.;Au, Rhoda;Harris, Tamara B.;Roubenoff, Ronenn;Auerbach, Sanford;DeCarli, Charles;Wolf, Philip A.;Seshadri, Sudha
脂肪因子瘦素促进海马体的长时程增强和突触可塑性，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。将无痴呆社区样本中的基线循环瘦素浓度前瞻性地与1）随访期间的痴呆和AD事件和2）幸存者脑老化的MRI（磁共振成像）测量相关联。在第22个检查周期（1990-1994年），对来自Fragrance Original队列的785名无痴呆患者（平均年龄79岁[SD，5岁]，62%为女性）的血浆瘦素浓度进行了测量。在1999年至2005年期间，对198名无痴呆症的幸存者进行了体积脑MRI检查，大约在瘦素检测后7.7年。评估了脑老化的两种测量方法，总脑容量（TCBV）和颞角体积（THV;与海马体积呈负相关）。随访至2007年12月31日期间痴呆和AD的发病率。在中位随访8.3年（范围0至15.5年）期间，111名参与者发生了痴呆症，89名患有AD。在多变量模型中，较高的瘦素水平与较低的痴呆和AD发病风险相关（全因痴呆和AD的风险比[HR]分别为0.68 [0.54-0.87]和0.60 [0.46-0.79]）。这对应于在12年的随访中，最低四分位数（Q1）的人的绝对AD风险为25%，而性别特异性瘦素水平的Q4的人的绝对AD风险为6%。此外，虽然瘦素与THV的相关性没有达到统计学显著性，但血浆瘦素水平升高一个SD与TCBV升高和THV降低相关。循环中的瘦素与无症状成年人的大脑健康指数直接相关，与痴呆和AD的发病风险呈负相关。我们的发现需要在独立样本中进行确认。
The adipokine leptin facilitates long-term potentiation and synaptic plasticity in the hippocampus, promotes β-amyloid clearance and improves memory function in animal models of aging and Alzheimer’s disease (AD). To relate baseline circulating leptin concentrations in a dementia-free community-based sample prospectively to 1) incident dementia and AD during follow-up and 2) to MRI (magnetic resonance imaging) measures of brain aging in survivors. Plasma leptin concentrations were measured in 785 dementia-free persons (mean age 79 [SD, 5 yrs], 62% women) from the Framingham Original cohort at the 22nd examination cycle (1990–1994). A sub-sample 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, the total cerebral brain volume (TCBV) and temporal horn volume (THV; inversely related to hippocampal volume) were assessed. Incidence of dementia and AD during follow-up till December 31st, 2007. During a median follow-up of 8.3 (range 0 to 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 ratios [HR] per one-SD increment in log-leptin were 0.68 [0.54–0.87] for all-cause dementia and 0.60 [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 (Q1) versus 6% for persons in Q4 of sex-specific leptin levels. In addition, a one SD elevation in plasma leptin was associated with higher TCBV and lower THV, although the association of leptin with THV did not reach statistical significance. Circulating leptin is directly related to indices of brain health in asymptomatic adults and inversely related to risk of incident dementia and AD. Our findings require confirmation in independent samples.
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