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胆固醇水平的波动与老年痴呆症风险增加60%有关 精选
2025-1-31 09:03
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胆固醇水平的波动与老年痴呆症风险增加60%有关

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Damaged-Brain-Dementia-777x777.webp.jpg 

A large study found that cholesterol changes over time — not just high cholesterol itself — may predict dementia risk in older adults. Those with the most extreme fluctuations had a 60% higher chance of developing dementia than those with stable levels.Credit: SciTechDaily.com  

WHO2021年《公共卫生领域应对痴呆症全球现状报告》报道,2019年,全球估计有5520万人患有痴呆症。世卫组织西太平洋区域的痴呆症患者人数最多(2010万),其次是 欧洲区域(1410万)、美洲区域(1030万)、东南亚区域(650 万)、东地中海区域(230万)和非洲区域(190万)。

假设年龄别流行率在今后几十年里不会发生变化,按照联合国人口预测,估计全球在2030年约有7800万痴呆症患者,在2050年约有1.39亿人。不过,在大多数地区,痴呆症风险和保护因素的流行率一直在变化,并且会继续变化。这可能会极大地影响对痴呆流行率和发病率估计数字的预测。

无论是在高收入国家,还是在低收入国家,痴呆症都是老年依赖照护和残疾的主要原因之一。在60岁及以上人群中,痴呆症是因残疾而丧失的健康生命年的十大原因之一。考虑到所有年龄,痴呆症是导致全球残疾调整生命年的第25个原因,并且呈现令人担忧的增长趋势。在过去20年里,因痴呆症而导致的残疾调整生命年增长了一倍多,是残疾调整生命年30种主要原因中增长速度最快的。同样令人担忧的是,全球女性残疾调整生命年比男性约高60%。人口增长和寿命延长,加上某些痴呆症风险因素增加,导致过去20年里因痴呆症而死亡的人数急剧增加。2019年,全球有160万人死于痴呆症,使其成为第七大死亡原因。采取必要的预防和干预措施,是一个全球面临的难题。

据美国神经病学学会(American Academy of Neurology)2025年1月29日提供的消息,胆固醇水平的波动与老年痴呆症风险增加60%有关(Fluctuating Cholesterol Levels Linked to 60% Higher Dementia Risk)。

胆固醇的变化可能是痴呆的警告信号吗?(Could changes in cholesterol be a warning sign of dementia?

来自澳大利亚、美国、芬兰、德国以及中国的研究人员合作的一项新研究表明,胆固醇随时间大幅波动的老年人比胆固醇水平稳定的老年人更容易患痴呆症。

波动胆固醇与痴呆风险Fluctuating Cholesterol and Dementia Risk

与胆固醇水平稳定的老年人相比,胆固醇水平随时间波动的老年人患痴呆症的风险可能更高,无论他们的实际胆固醇水平如何。这一发现来自2025129日发表在美国神经病学学会American Academy of Neurology)的医学杂志《神经病学》(Neurology)上的一项研究。原文详见:Zhen Zhou, Chris Moran, Anne M. Murray, Sophia Zoungas, Costan Magnussen, Trevor T.-J. Chong, Raj C. Shah, Kerry M. Sheets, Mark Nelson, Chao Zhu, Andrew M. Tonkin, Stella Talic, Michael E. Ernst, Suzanne G. Orchard, John J. McNeil, Rory Wolfe, Robyn L. Woods, Johannes T. Neumann, Peng Qiu, Joanne Ryan. Association of Year-to-Year Lipid Variability With Risk of Cognitive Decline and Dementia in Community-Dwelling Older Adults. Neurology, February 25, 2025 issue, 104(4): e210247. DOI: 10.1212/WNL.0000000000210247. E-Published 29 January 2025. https://doi.org/10.1212/WNL.0000000000210247

参与此项研究的有来自澳大利亚莫纳什大学School of Public Health and Preventive Medicine, Monash University, Melbourne, AustraliaTurner Institute for Brain & Mental Health, Monash University, Notting Hill, AustraliaSchool of Translational Medicine, Monash University, Melbourne, Australia)、美国明尼阿波利斯市的亨尼平医疗保健公司(Berman Center for Outcomes and Clinical Research, Hennepin Healthcare Research Institute, Division of Geriatrics, Department of Medicine Hennepin HealthCare, Minneapolis, MN, USA;Division of Geriatric Medicine, Department of Medicine, Hennepin Healthcare, Minneapolis, MN, USA)、澳大利亚墨尔本的贝克心脏和糖尿病研究所(Baker Heart and Diabetes Institute, Melbourne, Australia)、芬兰图尔库大学(Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Finland)、芬兰图尔库大学和图尔库大学附属医院人口健康研究中心(Centre for Population Health Research, University of Turku and Turku University Hospital, Finland)、美国芝加哥的拉什大学医学中心(Department of Family and Preventive Medicine and Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA)、澳大利亚.塔斯马尼亚大学(Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia)、美国爱荷华大学(Department of Pharmacy Practice and Science, College of Pharmacy, The University of Iowa, Iowa City, USA;Department of Family Medicine, Carver College of Medicine, The University of Iowa, Iowa City, USA)、德国汉堡-埃彭多夫大学医学中心(Department of Cardiology, University Heart & Vascular Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany)、德国心血管研究中心{German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany}、中国上海交通大学医学院上海第九人民医院(Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China)的研究人员。

需要注意的是,这项研究并没有证明胆固醇的变化会导致痴呆,只是证明两者之间存在联系。

研究报告的第一作者、澳大利亚墨尔本莫纳什大学的周震博士(Zhen Zhou, PhD音译)说这些结果表明,每年测量的波动胆固醇水平可能是识别痴呆症风险人群的一种新的生物标志物,它提供的信息比在单个时间点测量的实际胆固醇水平更多。

随时间追踪胆固醇Tracking Cholesterol Over Time

这项研究追踪了9846名平均年龄为74岁的参与者,他们在开始时都没有痴呆症或其他记忆问题。研究人员在研究开始时和三年的年度随访中测量了胆固醇水平。在最后一次胆固醇检查后,研究人员对参与者进行了平均5.5年的监测,并每年进行记忆测试以评估认知功能。

服用他汀类降胆固醇药物的参与者被允许参加研究,除非他们在胆固醇测量期间停止或开始服用药物。

根据第一次和第四次胆固醇测量值之间的变化量,参与者被分为四组。在总胆固醇变化最大的一组中,连续一年测量的差异平均为91毫克/分升91 mg/dL,而在变化最小的一组中,差异平均为22毫克/分升22 mg/dL)。

波动越大,患痴呆症的风险就越大Higher Fluctuations, Higher Dementia Risk

在研究期间,509人患上了痴呆症。总胆固醇变化最大的那组2408人中,有147人患上了痴呆症,每1000-中有11.3人罹患痴呆症。在总胆固醇变化最小的一组中,2437人中有98人患上了痴呆症,每1000-中有7.1人患痴呆症。人-Person-years)代表参与研究的人数和每个人在此项研究中花费的时间。

在调整了其他可能影响痴呆症风险的因素,如年龄、吸烟状况和高血压后,研究人员发现,高变化组的人患痴呆症的可能性比低变化组的人高60%。该研究还发现,胆固醇水平的变化与不符合痴呆症标准的认知障碍或记忆问题之间存在联系。

LDLHDL的作用The Role of LDL vs. HDL

通过观察不同类型的胆固醇,研究人员发现,低密度脂蛋白胆固醇(LDL cholesterol)也就是通常所说的胆固醇的波动与痴呆和认知障碍的风险之间存在联系。他们没有发现这与高密度脂蛋白(high density lipoprotein简称HDL)、也就是通常所说的“好”胆固醇或甘油三酯(triglycerides)有关。

周震说老年人的胆固醇应该随着时间的推移进行监测,以帮助识别可能有认知障碍或痴呆症风险的人,并从干预措施中受益,包括改变生活方式,或确保他们开始或持续服用他汀类药物,以防止胆固醇波动,并潜在地降低患痴呆症的风险。

研究的局限性和考虑事项(Study Limitations and Considerations

这项研究的一个局限性是,虽然开始或停止服用降胆固醇药物的人没有被纳入研究,以消除药物引起的胆固醇波动,但研究人员没有关于剂量变化或未按规定服药的人的任何信息,这可能会影响胆固醇的变化。

这项研究是由澳大利亚国家心脏基金会National Heart Foundation of Australia支持的。

上述介绍仅供参考,欲了解更多信息敬请注意浏览原文相关报道

根据上述介绍,各地社区卫生保健服务中心,根据多年来实施的65岁以上老年人的体检结果,对于那些胆固醇水平波动大的人群,重点关注,提醒或者指导提早预防和干预是必要的。

Abstract

Background and Objectives

Lipid metabolism in older adults is affected by various factors including biological aging, functional decline, reduced physiologic reserve, and nutrient intake. The dysregulation of lipid metabolism could adversely affect brain health. This study investigated the association between year-to-year intraindividual lipid variability and subsequent risk of cognitive decline and dementia in community-dwelling older adults.

Methods

ASPirin in Reducing Events in the Elderly (ASPREE) was a randomized trial of aspirin, involving 19,114 participants aged 65 years and older from Australia and the United States who were free of dementia and major cognitive impairment. ASPREE-eXTension is the post-trial observational follow-up of participants, currently to a maximum of 11 years. This post hoc analysis included participants who had lipid levels measured at baseline and in years 1, 2, and 3. Year-to-year variability in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triglycerides over the first 3 years was quantified using variability independent of the mean. Individuals who initiated or discontinued lipid-lowering therapy during this period were excluded. Multivariable Cox proportional hazards regression was used to analyze associations with incident dementia, adjudicated by expert panels, and cognitive impairment with no dementia (CIND) confirmed by a battery of cognitive tests, occurring after year 3. A linear mixed model was used for assessing the association with changes in 4 cognitive function domains, including global, memory, processing speed, verbal fluency, and a composite score from baseline to the end of follow-up.

Results

The analysis included 9,846 individuals (median [interquartile range] age: 73.9 [71.7–77.3] years, 54.9% female). 509 incident dementia and 1,760 CIND events were recorded over a median follow-up of 5.8 and 5.4 years after variability assessment. The hazard ratios (95% CI) comparing the highest and lowest quartiles of TC and LDL-c variability were 1.60 (1.23–2.08) and 1.48 (1.15–1.91) for dementia and 1.23 (1.08–1.41) and 1.27 (1.11–1.46) for CIND. Higher TC and LDL-c variability was also associated with a faster decline in global cognition, episodic memory, psychomotor speed, and the composite score (all p < 0.001). No strong evidence was found for an association of HDL-c and triglyceride variability with dementia and cognitive change.

Discussion

Tracking variability of TC and LDL-c may serve as a novel biomarker of incident dementia and cognitive decline in older adults.

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