Lipid level and risk of Alzheimer′s disease: a systematic review and meta-analysis
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摘要:
目的 系统评价多种血脂水平在预测阿尔茨海默病(AD)发病风险过程中的作用。 方法 检索中国知网数据库、万方数据知识服务平台、维普数据库、Pubmed、Web of Science、Springer、Cocharne Library,并辅以手工检索和文献追溯法收集建库至2021年6月国内外公开发表的关于血脂水平与AD发病风险的相关文献;按照纽卡斯尔-渥太华质量量表评价纳入研究的质量;用RevMan5.3软件对纳入的文献进行meta分析。 结果 按照纳入和排除标准共筛选出15篇符合要求的研究文献,收集1435名健康老年人以及2162例患有AD老年人的多种血脂水平。经过meta分析结果显示,AD组老年人的总胆固醇、甘油三酯水平与健康对照组老年人差异无统计学意义;低密度脂蛋白胆固醇(LDL-C)水平显著高于对照组(MD = 3.59,95 % CI = 0.98~6.21);高密度脂蛋白胆固醇(HDL-C)水平显著低于对照组(MD = – 3.47,95 % CI = – 5.94~– 0.99)。 结论 老年人LDL-C水平偏高以及HDL-C水平偏低预示可能将有更高的AD患病风险。 Abstract:Objective To systematically evaluate the role of blood lipid level in predicting the risk of Alzheimer′s disease (AD). Methods We searched Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), Pubmed, Web of Science, Springer, and Cocharne Library for literatures on the correlation between AD incidence and blood lipid level published in Chinese or English till June 2021 and supplementary manual tracing for some of the references was also conducted. Newcastle-Ottawa-Scale literature quality evaluation scale was adopted to evaluate the quality of the included studies. Statistical analyses were performed with RevMan5.3 software. Results A total of 15 eligible studies were selected according to the inclusion and exclusion criteria, and the data on blood lipid level were collected from 1 435 healthy elderly people and 2 162 elderly people with AD. Meta-analysis showed that there was no significant difference in total cholesterol (TC) and triglyceride (TG) level between the AD sufferers and the healthy controls; low-density lipoprotein cholesterol (LDL-C) was significantly higher in the AD sufferers than that in the healthy controls (mean difference [MD] = 3.59, 95% confidence interval [95% CI]: 0.98 – 6.21); while, high-density lipoprotein cholesterol (HDL-C) was significantly lower in the AD sufferers than that in the healthy controls (MD = – 3.47, 95% CI: – 5.94 – – 0.99). Conclusion Higher LDL-C level but lower HDL-C level may indicate a higher risk of AD in older adults. -
Key words:
- Alzheimer’s disease /
- blood lipid level /
- incidence risk /
- meta-analysis
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表 1 纳入的15篇文献的基本信息
纳入研究及年份 国家 研究对象 样本量 年龄
(岁,$\bar x \pm s$)HDL-C
(mg/dL,$\bar x \pm s$)LDL-C
(mg/dL,$\bar x \pm s$)TC
(mg/dL,$\bar x \pm s$)TG
(mg/dL,$\bar x \pm s$)2017[8] 中国 AD组 118 71.81 ± 9.66 48.43 ± 13.9 — — 106.29 ± 50.5 对照组 120 70.45 ± 9.52 52.52 ± 13.1 105.40 ± 38.1 2012[9] 中国 AD组 104 77.8 ± 6.74 51.43 ± 12 95.13 ± 25.5 173.24 ± 34.4 120.46 ± 54.9 对照组 104 76.5 ± 6.14 55.68 ± 12 92.81 ± 31.7 158.55 ± 40.2 116.92 ± 62.9 2014[10] 中国 AD组 44 80.00 ± 8.92 — — 171.31 ± 40.2 118.69 ± 68.2 对照组 62 79.63 ± 7.85 164.35 ± 48.0 124.89 ± 85.9 2014[11] 中国 AD组 48 69.32 ± 5.53 45.9 ± 10.3 138.2 ± 34.7 — — 对照组 37 71.06 ± 5.87 57.8 ± 14.6 136.8 ± 16.4 2015[12] 中国 AD组 201 76.79 ± 5.65 51.04 ± 13.9 100.54 ± 24.2 197.99 ± 37.9 163.86 ± 99.2 对照组 257 75.88 ± 6.50 51.43 ± 29.8 95.13 ± 43.7 188.32 ± 26.7 175.38 ± 124.0 2016[13] 中国 AD组 207 80.67 ± 8.188 50.27 ± 13.1 107.5 ± 34.4 184.07 ± 41.4 — 对照组 256 81.66 ± 6.382 53.36 ± 15.9 104.41 ± 38.7 176.72 ± 48 2005[14] 中国 AD组 35 69.1 ± 8.2 56.84 ± 11.6 158.55 ± 34.42 246.71 ± 41.8 — 对照组 16 69.6 ± 6.9 55.3 ± 10.1 141.53 ± 24.0 222.35 ± 34.4 2000[15] 日本 AD组 36 77.3 ± 4.9 69 ± 21 110 ± 26 194 ± 33 103 ± 52 对照组 15 71.8 ± 6.1 64 ± 19 114 ± 36 207 ± 40 142 ± 96 2017[16] 日本 AD组 42 80.5 ± 5.7 — 118.8 ± 39.4 199.3 ± 45.1 119.1 ± 68.4 对照组 18 75.6 ± 5.5 119.2 ± 35.7 211.1 ± 39.9 140.7 ± 66.3 2009[17] 日本 AD组 197 80 ± 14 58 ± 14 123 ± 28 82 ± 42.0 对照组 47 75 ± 6.86 56 ± 20.6 121 ± 27.4 — 86 ± 27.4 2005[18] 日本 AD组 106 79 ± 7 — 106 ± 34 181 ± 37 92 ± 50.0 对照组 227 76 ± 10 100 ± 37 184 ± 41 104 ± 42.0 2005[19] 土耳其 AD组 120 74.0 ± 7.6 — 129.1 ± 44.2 213.9 ± 44.6 147.1 ± 86.5 对照组 803 71.4 ± 5.9 130.3 ± 60.9 212.0 ± 46.5 144.7 ± 76.0 2017[20] 塞尔维亚 AD组 62 73.1 ± 5.8 50.27 ± 11.6 — — 132.86 ± 62.0 对照组 40 68.4 ± 5.5 61.48 ± 11.6 141.72 ± 97.4 2018[21] 巴西 AD组 40 78 ± 8.4 — 95.16 ± 25.01 157.01 ± 24.91 — 对照组 40 76.5 ± 7.6 88.57 ± 28.15 165.32 ± 34.03 2014[22] 印度 AD组 75 — 40.5 ± 9.5 104.4 ± 28.8 170.7 ± 31.7 129.0 ± 43.7 对照组 120 42.4 ± 8.3 100.6 ± 21.8 167.6 ± 22.8 122.6 ± 31.3 -
[1] Masters CL, Bateman R, Blennow K, et al. Alzheimer’s disease[J]. Nature Reviews Disease Primers, 2015, 1: 15056. doi: 10.1038/nrdp.2015.56 [2] 王志会, 齐士格, 张晗, 等. 老年期重点疾病预防和干预项目设计与实施[J]. 中国公共卫生, 2021, 37(11): 1585 – 1589. doi: 10.11847/zgggws1133281 [3] Ferri CP, Prince M, Brayne C, et al. Global prevalence of dementia: a Delphi consensus study[J]. The Lancet, 2005, 366(9503): 2112 – 2117. doi: 10.1016/S0140-6736(05)67889-0 [4] Anstey KJ, Ashby-Mitchell K, Peters R. Updating the evidence on the association between serum cholesterol and risk of late-life dementia: review and meta-analysis[J]. Journal of Alzheimer′s Disease, 2017, 56(1): 215 – 228. doi: 10.3233/JAD-160826 [5] Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[J]. European Journal of Epidemiology, 2010, 25(9): 603 – 605. doi: 10.1007/s10654-010-9491-z [6] 张兴会, 陈明珠, 宗晓郁, 等. 药物流行病学研究中亚组分析和效应修饰的探讨[J]. 药物流行病学杂志, 2021, 30(9): 575 – 578, 595. [7] 王树月, 陈明珠, 张兴会, 等. 药物流行病学研究混杂因素的控制[J]. 药物流行病学杂志, 2021, 30(8): 503 – 507. [8] Li H, Zhou JX, Yue ZW, et al. A complex association between ABCA7genotypes and blood lipid levels in Southern Chinese Han patients of sporadic Alzheimer′s disease[J]. Journal of the Neurological Sciences, 2017, 382: 13 – 17. doi: 10.1016/j.jns.2017.09.016 [9] Xiao ZJ, Wang J, Chen WR, et al. Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease[J]. Lipids in Health and Disease, 2012, 11: 163. doi: 10.1186/1476-511X-11-163 [10] Chang L, Wang YL, Ji HH, et al. Elevation of peripheral BDNF promoter methylation links to the risk of Alzheimer′s disease[J]. PLoS One, 2014, 9(11): e110773. doi: 10.1371/journal.pone.0110773 [11] Zhao Z, Zhou H, Peng Y, et al. Expression and significance of plasma 3-NT and ox-LDL in patients with Alzheimer′s disease[J]. Genetics and Molecular Research, 2014, 13(4): 8428 – 8435. doi: 10.4238/2014.October.20.19 [12] Yu ZL, Li W, Hou DR, et al. Relationship between adiponectin gene polymorphisms and late-onset Alzheimer’s disease[J]. PLoS One, 2015, 10(4): e0125186. doi: 10.1371/journal.pone.0125186 [13] Zheng JQ, Yan HC, Shi L, et al. The CYP19A1 rs3751592 variant confers susceptibility to Alzheimer disease in the Chinese Han population[J]. Medicine, 2016, 95(35): e4742. doi: 10.1097/MD.0000000000004742 [14] 王春玉, 方莹莹, 褚文政, 等. 阿尔茨海默病及血管性痴呆患者血清胆固醇、Vit B12和叶酸变化的临床研究[J]. 中国神经精神疾病杂志, 2005, 31(3): 188 – 191. doi: 10.3969/j.issn.1002-0152.2005.03.008 [15] Wada H. Analyses of serum concentrations of apolipoproteins in the demented elderly[J]. Internal Medicine, 2000, 39(3): 220 – 222. doi: 10.2169/internalmedicine.39.220 [16] Kouzuki M, Nagano M, Suzuki T, et al. Cerebrospinal fluid biomarkers of Alzheimer′s disease are associated with carotid plaque score and hemodynamics in intra- and extra-cranial arteries on ultrasonography[J]. Journal of Clinical Neuroscience, 2018, 49: 32 – 36. doi: 10.1016/j.jocn.2017.12.006 [17] Ban Y, Watanabe T, Suguro T, et al. Increased plasma urotensin-II and carotid atherosclerosis are associated with vascular dementia[J]. Journal of Atherosclerosis and Thrombosis, 2009, 16(3): 179 – 187. doi: 10.5551/jat.E608 [18] Watanabe T, Miyazaki A, Katagiri T, et al. Relationship between serum insulin-like growth factor-1 levels and Alzheimer′s disease and vascular dementia[J]. Journal of the American Geriatrics Society, 2005, 53(10): 1748 – 1753. doi: 10.1111/j.1532-5415.2005.53524.x [19] Cankurtaran M, Yavuz BB, Halil M, et al. Are serum lipid and lipoprotein levels related to dementia?[J]. Archives of Gerontology and Geriatrics, 2005, 41(1): 31 – 39. doi: 10.1016/j.archger.2004.10.008 [20] Macesic M, Lalic NM, Kostic VS, et al. Impaired insulin sensitivity and secretion in patients with Alzheimer’s disease: the relationship with other atherosclerosis risk factors[J]. Current Vascular Pharmacology, 2017, 15(2): 158 – 166. doi: 10.2174/1570161114666160905170644 [21] Grossi MF, Carvalho MDG, Silveira JN, et al. OxLDL plasma levels in patients with Alzheimer′s disease[J]. Arquivos de Neuro-Psiquiatria, 2018, 76(4): 241 – 246. doi: 10.1590/0004-282x20180012 [22] Alam R, Tripathi M, Mansoori N, et al. Synergistic epistasis of paraoxonase 1 (rs662 and rs85460) and apolipoprotein E4 genes in pathogenesis of Alzheimer′s disease and vascular dementia[J]. American Journal of Alzheimer’s Disease and Other Dementias, 2014, 29(8): 769 – 776. doi: 10.1177/1533317514539541 [23] Li J, Wang YJ, Zhang M, et al. Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease[J]. Neurology, 2011, 76(17): 1485 – 1491. doi: 10.1212/WNL.0b013e318217e7a4 [24] 宫建, 张灵健, 王树月, 等. 新公卫背景下循证药学教学模式探讨[J]. 中国公共卫生, 2021, 37(9): 1447 – 1448. doi: 10.11847/zgggws1136797 -