Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.
Division of Clinical Neurology, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK.
Lancet Healthy Longev. 2022 Jun;3(6):e428-e436. doi: 10.1016/S2666-7568(22)00117-9.
Individual cardiometabolic disorders and genetic factors are associated with an increased dementia risk; however, the relationship between dementia and cardiometabolic multimorbidity is unclear. We investigated whether cardiometabolic multimorbidity increases the risk of dementia, regardless of genetic risk, and examined for associated brain structural changes.
We examined health and genetic data from 203 038 UK Biobank participants of European ancestry, aged 60 years or older without dementia at baseline assessment (2006-10) and followed up until March 31, 2021, in England and Scotland and Feb 28, 2018, in Wales, as well as brain structural data in a nested imaging subsample of 12 236 participants. A cardiometabolic multimorbidity index comprising stroke, diabetes, and myocardial infarction (one point for each), and a polygenic risk score for dementia (with low, intermediate, and high risk groups) were calculated for each participant. The main outcome measures were incident all-cause dementia and brain structural metrics.
The dementia risk associated with high cardiometabolic multimorbidity was three times greater than that associated with high genetic risk (hazard ratio [HR] 5·55, 95% CI 3·39-9·08, p<0·0001, and 1·68, 1·53-1·84, p<0·0001, respectively). Participants with both a high genetic risk and a cardiometabolic multimorbidity index of two or greater had an increased risk of developing dementia (HR 5·74, 95% CI 4·26-7·74, p<0·0001), compared with those with a low genetic risk and no cardiometabolic conditions. Crucially, we found no interaction between cardiometabolic multimorbidity and polygenic risk (p=0·18). Cardiometabolic multimorbidity was independently associated with more extensive, widespread brain structural changes including lower hippocampal volume (F = 10·70; p<0·0001) and total grey matter volume (F = 55·65; p<0·0001).
Cardiometabolic multimorbidity was independently associated with the risk of dementia and extensive brain imaging differences to a greater extent than was genetic risk. Targeting cardiometabolic multimorbidity might help to reduce the risk of dementia, regardless of genetic risk.
Wellcome Trust, Alzheimer's Research UK, Alan Turing Institute/Engineering and Physical Sciences Research Council, the National Institute for Health Research Applied Research Collaboration South West Peninsula, National Health and Medical Research Council, JP Moulton Foundation, and National Institute on Aging/National Institutes of Health.
个体的心脏代谢紊乱和遗传因素与痴呆风险增加有关；然而，痴呆与心脏代谢多病共存之间的关系尚不清楚。我们研究了无论遗传风险如何，心脏代谢多病共存是否会增加痴呆的风险，并检查了相关的大脑结构变化。
我们检查了来自 203038 名英国生物库参与者的健康和遗传数据，这些参与者为欧洲血统，在基线评估（2006-10 年）时年龄在 60 岁或以上且没有痴呆，随访至 2021 年 3 月 31 日，在英格兰和苏格兰，以及 2018 年 2 月 28 日在威尔士，以及 12236 名参与者的嵌套成像子样本中的大脑结构数据。为每位参与者计算了包括中风、糖尿病和心肌梗死在内的心脏代谢多病共存指数（各计 1 分）和痴呆的多基因风险评分（低、中、高风险组）。
高心脏代谢多病共存相关的痴呆风险是高遗传风险相关的痴呆风险的三倍（风险比[HR]5.55，95%CI3.39-9.08，p<0.0001，和 1.68，1.53-1.84，p<0.0001）。同时具有高遗传风险和两个或更多心脏代谢指标的参与者患痴呆的风险增加（HR5.74，95%CI4.26-7.74，p<0.0001），与遗传风险低且无心脏代谢疾病的参与者相比。至关重要的是，我们没有发现心脏代谢多病共存和多基因风险之间存在交互作用（p=0.18）。心脏代谢多病共存与更广泛的大脑结构变化独立相关，包括海马体体积较小（F=10.70；p<0.0001）和总灰质体积较小（F=55.65；p<0.0001）。
与遗传风险相比，心脏代谢多病共存更独立地与痴呆风险和广泛的大脑影像学差异相关。针对心脏代谢多病共存可能有助于降低痴呆风险，无论遗传风险如何。
惠康信托基金会、阿尔茨海默氏症研究英国、艾伦·图灵研究所/工程和物理科学研究委员会、国民保健制度应用研究合作南西南半岛、国家卫生和医疗研究委员会、JP 莫尔顿基金会、国家老龄化研究所/美国国立卫生研究院。
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