服用他汀类药物是否会影响尸检证实的阿尔茨海默病痴呆的病理负担？
Does taking statins affect the pathological burden in autopsy-confirmed Alzheimer's dementia?
机构信息
Arizona State University, Tempe, AZ, USA.
Department of Neurology, Barrow Neurological Institute, Phoenix, AZ, USA.
出版信息
Alzheimers Res Ther. 2018 Oct 2;10(1):104. doi: 10.1186/s13195-018-0430-7.
BACKGROUND
The efficacy of cholesterol lowering agents, specifically statins, in slowing the rate of decline of cognitive function in Alzheimer's disease (AD) patients is not yet fully understood. Our team's previously published paper showed that patients who used statins demonstrated no increase in cognitive decline in mild cognitive impairment when compared with nonusers. Further, AD patients on statins demonstrated a slight decreasing trend in cognitive decline. The purpose of this study is therefore to investigate the association between stain use in AD confirmed by clinical diagnosis and autopsy and the pathological burden (plaques, tangles, Braak stage). The hypothesis leading this investigation is that prolonged statin use associates with lower AD pathology at autopsy.
METHODS
We queried the National Alzheimer's Coordinating Center (NACC) database for autopsy-confirmed AD cases. Of the Uniform Data Set (UDS) participants who are deceased, 16,163 were diagnosed with dementia at their last UDS visit prior to death, and autopsy data are available for 3945 patients. These patients were then stratified into two groups based upon statin use. The two groups were then analyzed for their pathological AD burden, including total plaques, total tangles, age at death, age of onset, and Braak stage.
RESULTS
NACC data were available for 1816 subjects with clinically and pathologically confirmed AD; 1558 were not on statins and 258 were on statins. No significant differences in age at death, age at onset, Braak stages, mean total tau, and mean total amyloid were found between the two subject groups. When statin use was analyzed by apolipoprotein E (ApoE) genotype carrier statins, the presence of ApoE4 did not influence the effects (or lack thereof) of statin use.
CONCLUSIONS
Prolonged statin use in pathologically confirmed AD dementia does not appear to influence the amount of burden of plaques and tangles or Braak stage. These observations were not altered by the presence of absence of ApoE4.
背景
降脂药物，特别是他汀类药物，在减缓阿尔茨海默病（AD）患者认知功能下降速度方面的疗效尚不完全清楚。我们团队之前发表的论文表明，与未使用者相比，使用他汀类药物的患者在轻度认知障碍中认知能力下降没有增加。此外，AD 患者使用他汀类药物后认知能力下降呈略有下降趋势。因此，本研究的目的是调查通过临床诊断和尸检证实的 AD 患者使用他汀类药物与病理负担（斑块、缠结、Braak 分期）之间的关联。导致这项研究的假设是，长期使用他汀类药物与尸检时 AD 病理负担较低有关。
方法
我们查询了国家阿尔茨海默病协调中心（NACC）数据库中的尸检确诊 AD 病例。在 UDS 参与者中，有 16163 人在死亡前的最后一次 UDS 就诊时被诊断为痴呆，并且有 3945 名患者可获得尸检数据。然后，根据他汀类药物的使用情况，将这些患者分为两组。然后对两组患者的 AD 病理负担进行分析，包括总斑块、总缠结、死亡年龄、发病年龄和 Braak 分期。
结果
NACC 数据可用于 1816 名临床和病理确诊的 AD 患者；1558 名患者未服用他汀类药物，258 名患者服用他汀类药物。两组患者在死亡年龄、发病年龄、Braak 分期、平均总 tau 和平均总淀粉样蛋白方面无显著差异。当按载脂蛋白 E（ApoE）基因型携带者他汀类药物分析他汀类药物的使用时，ApoE4 的存在并不影响他汀类药物使用的效果（或缺乏效果）。
结论
在病理确诊的 AD 痴呆患者中，长期使用他汀类药物似乎不会影响斑块和缠结的负担量或 Braak 分期。这些观察结果不受 ApoE4 的存在或缺失的影响。
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