脑灌注与痴呆风险：一项基于人群的研究。

Cerebral Perfusion and the Risk of Dementia: A Population-Based Study.

机构信息

From Department of Epidemiology (F.J.W., H.I.Z., A.H., M.W.V., M.A.I.), Department of Neurology (F.J.W., P.J.K., M.A.I.), Department of Radiology and Nuclear Medicine (H.I.Z., A.v.d.L., M.W.V., M.A.I.), Erasmus Medical Center, Rotterdam, The Netherlands; and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (F.J.W., A.H.).

出版信息

Circulation. 2017 Aug 22;136(8):719-728. doi: 10.1161/CIRCULATIONAHA.117.027448. Epub 2017 Jun 6.

DOI:10.1161/CIRCULATIONAHA.117.027448

PMID:28588075

Abstract

BACKGROUND

Cerebral hypoperfusion has previously been associated with mild cognitive impairment and dementia in various cross-sectional studies, but whether hypoperfusion precedes neurodegeneration is unknown. We prospectively determined the association of cerebral perfusion with subsequent cognitive decline and development of dementia.

METHODS

Between 2005 and 2012, we measured cerebral blood flow by 2-dimensional phase-contrast magnetic resonance imaging in participants of the population-based Rotterdam Study without dementia. We determined the association of cerebral perfusion (mL/100mL/min) with risk of dementia (until 2015) using a Cox model, adjusting for age, sex, demographics, cardiovascular risk factors, and apolipoprotein E genotype. We repeated analyses for Alzheimer disease and accounting for stroke. We used linear regression to determine change in cognitive performance during 2 consecutive examination rounds in relation to perfusion. Finally, we investigated whether associations were modified by baseline severity of white matter hyperintensities.

RESULTS

Of 4759 participants (median age 61.3 years, 55.2% women) with a median follow-up of 6.9 years, 123 participants developed dementia (97 Alzheimer disease). Lower cerebral perfusion was associated with higher risk of dementia (adjusted hazard ratio, 1.31; 95% confidence interval per standard deviation decrease, 1.07-1.61), similar for Alzheimer disease only, and unaltered by accounting for stroke. Risk of dementia with hypoperfusion was higher with increasing severity of white matter hyperintensities (with severe white matter hyperintensities; hazard ratio, 1.54; 95% confidence interval, 1.11-2.14). At cognitive reexamination after on average 5.7 years, lower baseline perfusion was associated with accelerated decline in cognition (global cognition: β=-0.029, =0.003), which was similar after excluding those with incident dementia, and again most profound in individuals with higher volume of white matter hyperintensities ( value for interaction=0.019).

CONCLUSIONS

Cerebral hypoperfusion is associated with accelerated cognitive decline and an increased risk of dementia in the general population.

摘要

背景

在各种横断面研究中，脑灌注不足以前与轻度认知障碍和痴呆有关，但灌注不足是否先于神经退行性变尚不清楚。我们前瞻性地确定了脑灌注与随后认知下降和痴呆发展之间的关系。

方法

在 2005 年至 2012 年间，我们通过磁共振成像二维相位对比测量了没有痴呆的人群基础研究参与者的脑血流。我们使用 Cox 模型确定了脑灌注（mL/100mL/min）与痴呆风险（直至 2015 年）的关系，调整了年龄、性别、人口统计学、心血管危险因素和载脂蛋白 E 基因型。我们对阿尔茨海默病进行了重复分析，并考虑了中风。我们使用线性回归来确定与灌注相关的连续两次检查中认知表现的变化。最后，我们调查了这些关联是否受基线白质高信号严重程度的影响。

结果

在 4759 名参与者（中位年龄 61.3 岁，55.2%为女性）中，中位随访时间为 6.9 年，有 123 名参与者发展为痴呆（97 名阿尔茨海默病）。较低的脑灌注与痴呆风险增加相关（调整后的危险比，1.31；每标准偏差降低的 95%置信区间，1.07-1.61），对于阿尔茨海默病也是如此，并且在考虑中风后不会改变。灌注不足的痴呆风险随着白质高信号严重程度的增加而增加（严重白质高信号；危险比，1.54；95%置信区间，1.11-2.14）。在平均 5.7 年后的认知重新检查时，较低的基线灌注与认知能力加速下降相关（整体认知：β=-0.029，=0.003），在排除新发痴呆后类似，在白质高信号体积较高的个体中再次最为明显（交互值=0.019）。