TY - JOUR
T1 - Blood-brain barrier impairment in Alzheimer disease
T2 - Stability and functional significance
AU - Bowman, G. L.
AU - Kaye, J. A.
AU - Moore, M.
AU - Waichunas, D.
AU - Carlson, N. E.
AU - Quinn, J. F.
PY - 2007/5
Y1 - 2007/5
N2 - OBJECTIVE: To determine the stability and functional significance of blood-brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD). METHODS: Thirty-six patients (mean age 71 ± 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 ± 5) participated in a biomarker study involving clinical assessments, brain imaging, and CSF and plasma collection over 1 year. BBB integrity was assessed with the CSF-albumin index (CSF-AI). RESULTS: BBB disruption was present in an important subgroup of patients (n = 8/36, 22%) at all time points measured. CSF-AI was highly reproducible over 1 year with an intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived white matter hyperintensity, body mass index) were not strongly associated with CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a manner indicating that peripheral IgG has greater access to the CNS in patients with an impaired BBB. Further evidence for the physiologic significance of the CSF-AI was noted in the form of correlations with rates of disease progression, including annual change on MMSE (r = 0.11, p = 0.023), annual Clinical Dementia Rating sum-of-boxes change (r = 0.29, p = 0.001), and annual ventricular volume change (r = 0.17, p = 0.007). CONCLUSIONS: Blood-brain barrier (BBB) impairment is a stable characteristic over 1 year and present in an important subgroup of patients with Alzheimer disease. Age, gender, APOE status, vascular risk factors, and baseline Mini-Mental State Examination score did not explain the variability in BBB integrity. A role for BBB impairment as a modifier of disease progression is suggested by correlations between CSF-albumin index and measures of disease progression over 1 year.
AB - OBJECTIVE: To determine the stability and functional significance of blood-brain barrier (BBB) integrity in patients with mild to moderate Alzheimer disease (AD). METHODS: Thirty-six patients (mean age 71 ± 7 years) with mild to moderate AD (Mini-Mental State Examination [MMSE] 19 ± 5) participated in a biomarker study involving clinical assessments, brain imaging, and CSF and plasma collection over 1 year. BBB integrity was assessed with the CSF-albumin index (CSF-AI). RESULTS: BBB disruption was present in an important subgroup of patients (n = 8/36, 22%) at all time points measured. CSF-AI was highly reproducible over 1 year with an intraclass correlation of 0.96. Age, sex, and APOE status did not correlate with CSF-AI. Vascular factors (blood pressure, Hachinski ischemia score, MR-derived white matter hyperintensity, body mass index) were not strongly associated with CSF-AI levels (p = 0.066). CSF/plasma IgG ratio correlated with CSF-AI in a manner indicating that peripheral IgG has greater access to the CNS in patients with an impaired BBB. Further evidence for the physiologic significance of the CSF-AI was noted in the form of correlations with rates of disease progression, including annual change on MMSE (r = 0.11, p = 0.023), annual Clinical Dementia Rating sum-of-boxes change (r = 0.29, p = 0.001), and annual ventricular volume change (r = 0.17, p = 0.007). CONCLUSIONS: Blood-brain barrier (BBB) impairment is a stable characteristic over 1 year and present in an important subgroup of patients with Alzheimer disease. Age, gender, APOE status, vascular risk factors, and baseline Mini-Mental State Examination score did not explain the variability in BBB integrity. A role for BBB impairment as a modifier of disease progression is suggested by correlations between CSF-albumin index and measures of disease progression over 1 year.
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U2 - 10.1212/01.wnl.0000262031.18018.1a
DO - 10.1212/01.wnl.0000262031.18018.1a
M3 - Article
C2 - 17515542
AN - SCOPUS:34249040510
SN - 0028-3878
VL - 68
SP - 1809
EP - 1814
JO - Neurology
JF - Neurology
IS - 21
ER -