脑血管病和β淀粉样蛋白共病对阿尔茨海默病的影响。

Influence of Comorbidity of Cerebrovascular Disease and Amyloid-β on Alzheimer's Disease.

机构信息

Departments of Medicine and Neurology, Melbourne Brain Centre at The Royal Melbourne Hospital, University of Melbourne, Parkville, Australia.

Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

出版信息

J Alzheimers Dis. 2020;73(3):897-907. doi: 10.3233/JAD-191028.

DOI:10.3233/JAD-191028

PMID:31884485

Abstract

BACKGROUND

Quantifying the contribution of cerebrovascular disease to the clinical and pathological profile of Alzheimer's disease is challenging.

OBJECTIVE

We aimed to determine the influence of cerebrovascular disease, amyloid-β (Aβ), and their comorbidity on cognitive decline, hippocampal atrophy, and Aβ deposition, by evaluating data from the Australian Imaging, Biomarker and Lifestyle Study of Ageing.

METHODS

Two-hundred and eighteen participants underwent Aβ PET, MRI, and cognitive assessment at 18-month intervals for up to 90 months. Aβ status was determined on baseline PET. Participants were also classified as V+ on baseline MRI if they had≥1 large cortical infarcts, subcortical infarcts, or cortical cerebral microinfarcts; or white matter hyperintensity volume greater than the 90th percentile of healthy controls. Linear mixed models were conducted comparing slopes of change in cognition, hippocampal volume, and Aβ load between the four resultant groups.

RESULTS

Mean age at baseline was 74 years (range 59-96). One-hundred and fifteen participants were cognitively normal, 54 had mild cognitive impairment, and 49 had Alzheimer's disease. Compared to the Aβ-/V- group, the Aβ+/V- and Aβ+/V+ groups showed significantly faster cognitive decline and hippocampal atrophy over 90 months. V+ status was associated with greater cognitive decline (Cohen's d = 0.85, p < 0.001) and hippocampal atrophy (d = 2.05, p < 0.001) in the Aβ+ group but not in the Aβ- group. V+ status was not associated with Aβ accumulation in any group.

CONCLUSION

Comorbidity of cerebrovascular disease and Aβ was associated with cognitive decline and neurodegeneration. Cerebrovascular disease was not associated with the rate of Aβ accumulation.

摘要

背景

量化脑血管疾病对阿尔茨海默病临床和病理特征的贡献具有挑战性。

目的

通过评估澳大利亚成像、生物标志物和生活方式衰老研究的数据，我们旨在确定脑血管疾病、淀粉样蛋白-β（Aβ）及其共病对认知能力下降、海马体萎缩和 Aβ沉积的影响。

方法

218 名参与者在 18 个月的间隔内接受 Aβ PET、MRI 和认知评估，最长可达 90 个月。基线 PET 确定 Aβ 状态。如果基线 MRI 上有≥1 个大皮质梗死、皮质下梗死或皮质微梗死；或皮质脑微梗死；或白质高信号体积大于健康对照组的第 90 百分位数，则参与者也被分类为 V+。线性混合模型比较了四个结果组之间认知、海马体体积和 Aβ负荷变化的斜率。

结果

基线时的平均年龄为 74 岁（范围 59-96 岁）。115 名参与者认知正常，54 名患有轻度认知障碍，49 名患有阿尔茨海默病。与 Aβ-/V-组相比，Aβ+/V-和 Aβ+/V+组在 90 个月内表现出明显更快的认知能力下降和海马体萎缩。V+状态与 Aβ+组的认知能力下降（Cohen's d=0.85，p<0.001）和海马体萎缩（d=2.05，p<0.001）显著相关，但在 Aβ-组中则不相关。V+状态与任何组的 Aβ 积累均无关。