Patients With Alzheimer Disease With Multiple Microbleeds Relation With Cerebrospinal Fluid Biomarkers and Cognition

被引:179
作者
Goos, Jeroen D. C. [1 ]
Kester, M. I. [1 ]
Barkhof, Frederik [2 ]
Klein, Martin [3 ]
Blankenstein, Marinus A. [4 ]
Scheltens, Philip [1 ]
van der Flier, Wiesje M. [1 ,5 ]
机构
[1] Vrije Univ Amsterdam, Med Ctr, Dept Neurol, NL-1007 MB Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Dept Radiol, NL-1007 MB Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Med Ctr, Dept Med Psychol, NL-1007 MB Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, NL-1007 MB Amsterdam, Netherlands
[5] Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands
关键词
CSF biomarkers; dementia; magnetic resonance imaging; microbleeds; CEREBRAL AMYLOID ANGIOPATHY; WHITE-MATTER LESIONS; RISK-FACTORS; INTRACEREBRAL HEMORRHAGE; BRAIN MICROBLEEDS; PREVALENCE; ASSOCIATION; ATROPHY; MRI;
D O I
10.1161/STROKEAHA.109.558197
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose-Microbleeds (MBs) are commonly observed in Alzheimer disease. A minority of patients has multiple MBs. We aimed to investigate associations of multiple MBs in Alzheimer disease with clinical and MRI characteristics and cerebrospinal fluid biomarkers. Methods-Patients with Alzheimer disease with multiple (>= 8) MBs on T2*-weighted MRI were matched for age, sex, and field strength with patients with Alzheimer disease without MBs on a 1:2 basis. We included 21 patients with multiple MBs (73 +/- 7 years, 33% female) and 42 patients without MBs (72 +/- 7 years, 38% female). Mini-Mental State Examination was used to assess dementia severity. Cognitive functions were assessed using neuropsychological tests. Medial temporal lobe atrophy (0 to 4), global cortical atrophy (0 to 3), and white matter hyperintensities (0 to 30) were assessed using visual rating scales. In a subset, apolipoprotein E genotype and cerebrospinal fluid amyloid beta 1-42, total tau and tau phosphorylated at threonine 181 were determined. Results-Patients with multiple MBs performed worse on Mini-Mental State Examination (multiple MB: 17 +/- 7; no MB: 22 +/- 4, P<0.05) despite similar disease duration. Atrophy was not related to presence of MBs, but patients with multiple MBs had more white matter hyperintensities (multiple MB: 8.8 +/- 4.8; no MB: 3.2 +/- 3.6, P<0.05). Adjusted for age, sex, white matter hyperintensities, and medial temporal lobe atrophy, the multiple MB group additionally performed worse on Visual Association Test object naming and animal fluency. Patients with multiple MBs had lower cerebrospinal fluid amyloid beta 1-42 levels (307 +/- 61) than patients without MBs (505 +/- 201, P<0.05). Adjusted for the same covariates, total tau, and tau phosphorylated at threonine 181 were higher in the multiple MB group. Conclusion-Microbleeds are associated with the clinical manifestation and biochemical hallmarks of Alzheimer disease, suggesting possible involvement of MBs in the pathogenesis of Alzheimer disease. (Stroke. 2009; 40: 3455-3460.)
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收藏
页码:3455 / 3460
页数:6
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