Vascular burden and Alzheimer disease pathologic progression

被引:133
|
作者
Lo, Raymond Y. [1 ,3 ,4 ]
Jagust, William J. [1 ,2 ,5 ]
机构
[1] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA
[3] Buddhist Tzu Chi Gen Hosp, Dept Neurol, Hualien, Taiwan
[4] Tzu Chi Univ, Coll Med, Hualien, Taiwan
[5] Univ Calif Berkeley, Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA 94720 USA
基金
加拿大健康研究院;
关键词
MATTER HYPERINTENSITY VOLUME; NEUROIMAGING INITIATIVE ADNI; NEUROVASCULAR MECHANISMS; COGNITIVE FUNCTION; RISK PROFILE; MRI; BIOMARKERS; DEMENTIA; DECLINE; GLUCOSE;
D O I
10.1212/WNL.0b013e31826c1b9d
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Objective: To investigate the vascular contribution to longitudinal changes in Alzheimer disease (AD) biomarkers. Methods: The Alzheimer's Disease Neuroimaging Initiative is a clinic based, longitudinal study with CSF, PET, and MRI biomarkers repeatedly measured in participants with normal cognition (NC), mild cognitive impairment (MCI), and mild AD. Participants with severe cerebrovascular risks were excluded. Cardiovascular risk scores and MRI white matter hyperintensities (WMHs) were treated as surrogate markers for vascular burden. Generalized estimating equations were applied, and both vascular burden and its interaction with time (vascular burden x time) or time-varying WMHs were entered into regression models to assess whether biomarker rates of change were modified by vascular burden. Results: Cardiovascular risk profiles were not predictive of progression in CSF beta(42)-amyloid, [F-18]fluorodeoxyglucose (FDG) PET uptake, and MRI hippocampal atrophy. Greater baseline cardiovascular risks or WMHs were generally associated with cognitive impairment, particularly poor executive function. WMHs increased over time with a faster rate in MCI and AD than in NC. Increased time-varying WMH was associated with faster decline in executive function and lower FDG uptake in NC. Otherwise, WMH was not associated with CSF and MRI biomarkers in the 3 groups. These findings remained unchanged after accounting for APOE4. Conclusion: Increased WMHs are associated with aging, decreased glucose metabolism, and decline in executive function but do not affect AD-specific pathologic progression, suggesting that the vascular contribution to dementia is probably additive although not necessarily independent of the amyloid pathway. Neurology (R) 2012;79:1349-1355
引用
收藏
页码:1349 / 1355
页数:7
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