Blood-brain barrier impairment in Alzheimer disease: Stability and functional significance

Gene Bowman, Jeffrey Kaye, M. Moore, D. Waichunas, N. E. Carlson, Joseph Quinn

Research output: Contribution to journalArticle

181 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1809-1814
Number of pages6
JournalNeurology
Volume68
Issue number21
DOIs
StatePublished - May 2007

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Blood-Brain Barrier
Albumins
Alzheimer Disease
Disease Progression
Immunoglobulin G
Neuroimaging
Dementia
Body Mass Index
Ischemia
Biomarkers
Blood Pressure

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Blood-brain barrier impairment in Alzheimer disease : Stability and functional significance. / Bowman, Gene; Kaye, Jeffrey; Moore, M.; Waichunas, D.; Carlson, N. E.; Quinn, Joseph.

In: Neurology, Vol. 68, No. 21, 05.2007, p. 1809-1814.

Research output: Contribution to journalArticle

Bowman, Gene ; Kaye, Jeffrey ; Moore, M. ; Waichunas, D. ; Carlson, N. E. ; Quinn, Joseph. / Blood-brain barrier impairment in Alzheimer disease : Stability and functional significance. In: Neurology. 2007 ; Vol. 68, No. 21. pp. 1809-1814.
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abstract = "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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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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