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肾素-血管紧张素系统阻滞剂可影响阿尔茨海默病患者认知能力下降和血清脂肪细胞因子水平。

Renin-angiotensin system blockers affect cognitive decline and serum adipocytokines in Alzheimer's disease.

机构信息

Department of Neurology, Nara Medical University, Nara, Japan.

出版信息

Alzheimers Dement. 2013 Sep;9(5):512-8. doi: 10.1016/j.jalz.2012.06.007. Epub 2012 Nov 8.

Abstract

BACKGROUND

Accumulating evidence indicates an association of Alzheimer's disease (AD) with the metabolic syndrome (MetS), characterized by visceral fat accumulation with insulin resistance and altered secretion of adipocytokines such as adiponectin and leptin. The renin-angiotensin system (RAS) regulates blood pressure and insulin resistance. Recent studies suggest that the RAS plays crucial roles in cognitive functions and that adipocytokines exert neuroprotective activity in the brain. We investigated whether RAS blockers (RASB) affect adipocytokines and cognitive function in patients with AD.

METHODS

We studied 78 patients with a diagnosis of probable AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition and 106 nondemented control subjects who visited our clinic with a main complaint of headache or dizziness. We examined retrospectively the effects of RASB on adipocytokines and cognitive decline in patients with AD who were divided into three groups: hypertension treated with RASB (HT-RASB; n = 17), hypertension treated with other antihypertensive drugs (HT-other; n = 34), and no hypertension (non-HT; n = 27).

RESULTS

The HT-RASB group had a significantly higher serum leptin level and a relatively larger visceral fat area than the other groups, because of the bias toward patients with MetS in this group. The HT-RASB group also had a significantly lower immunoreactive insulin level, a relatively low homeostasis model assessment as an index of insulin resistance, and a relatively high serum adiponectin level among the three groups. Cognitive decline, estimated on the basis of the mean annual decline using the Hasegawa Dementia Scale score was significantly low in the HT-RASB group.

CONCLUSION

Treatment with RASB might modulate serum adipocytokines and glucose homeostasis, potentially slowing cognitive decline in patients with AD.

摘要

背景

越来越多的证据表明阿尔茨海默病(AD)与代谢综合征(MetS)有关,其特征是内脏脂肪堆积伴胰岛素抵抗以及脂联素和瘦素等脂肪细胞因子的分泌改变。肾素-血管紧张素系统(RAS)调节血压和胰岛素抵抗。最近的研究表明,RAS 在认知功能中发挥着关键作用,而脂肪细胞因子在大脑中具有神经保护作用。我们研究了 RAS 阻滞剂(RASB)是否会影响 AD 患者的脂肪细胞因子和认知功能。

方法

我们研究了 78 名根据《精神障碍诊断与统计手册》第 4 版诊断为可能 AD 的患者和 106 名因头痛或头晕为主诉就诊于我们诊所的非痴呆对照受试者。我们回顾性地检查了 RASB 对 AD 患者脂肪细胞因子和认知下降的影响,AD 患者分为三组:用 RASB 治疗的高血压(HT-RASB;n = 17)、用其他降压药治疗的高血压(HT-other;n = 34)和无高血压(non-HT;n = 27)。

结果

HT-RASB 组的血清瘦素水平显著较高,内脏脂肪面积相对较大,这是因为该组中存在 MetS 患者的偏倚。HT-RASB 组的免疫反应性胰岛素水平也显著较低,作为胰岛素抵抗指标的稳态模型评估相对较低,而血清脂联素水平相对较高。基于 Hasegawa 痴呆量表评分的平均年度下降,HT-RASB 组的认知下降显著较低。

结论

用 RASB 治疗可能会调节血清脂肪细胞因子和葡萄糖稳态,从而可能减缓 AD 患者的认知下降。

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