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(Stroke. 2009;40:3455.)
© 2009 American Heart Association, Inc.

Original Contributions

Patients With Alzheimer Disease With Multiple Microbleeds

Relation With Cerebrospinal Fluid Biomarkers and Cognition

Jeroen D.C. Goos, MD; M.I. Kester, MD; Frederik Barkhof, MD, PhD; Martin Klein, PhD; Marinus A. Blankenstein, PhD; Philip Scheltens, MD, PhD Wiesje M. van der Flier, PhD

From the Departments of Neurology (J.D.C.G., M.I.K., P.S., W.M.v.d.F.), Radiology (F.B.), Medical Psychology (M.K.), Clinical Chemistry (M.A.B.), and Epidemiology and Biostatistics (W.M.v.d.F.), VU University Medical Center, Amsterdam, The Netherlands.

Correspondence to Jeroen D.C. Goos, MD, Department of Neurology and Alzheimer Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail j.goos{at}vumc.nl

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 β 1-42, total and 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 β 1-42 levels (307±61) than patients without MBs (505±201, P<0.05). Adjusted for the same covariates, total , and 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.

Key Words: CSF biomarkers • dementia • magnetic resonance imaging • microbleeds