title: Blood-Brain Barrier Leakage in Patients with Early Alzheimer Disease.
abstract: Purpose To investigate whether the blood-brain barrier (BBB) leaks blood-circulating substances in patients with early forms of Alzheimer disease (AD), and if so, to examine the extent and pattern of leakage. Materials and Methods This study was approved by the local medical ethical committees of the Maastricht University Medical Center and Leiden University Medical Center, and written informed consent was obtained from all subjects. For this pilot study, 16 patients with early AD and 17 healthy age-matched control subjects underwent dynamic contrast material-enhanced magnetic resonance (MR) imaging sequence with dual time resolution for 25 minutes. The Patlak graphical approach was used to quantify the BBB leakage rate and local blood plasma volume. Subsequent histogram analysis was used to determine the volume fraction of the leaking brain tissue. Differences were assessed with linear regression analysis, adjusted for confounding variables. Results The BBB leakage rate was significantly higher in patients compared with that in control subjects in the total gray matter (P < .05) and cortex (P = .03). Patients had a significantly higher volume fraction of the leaking brain tissue in the gray matter (P = .004), normal-appearing white matter (P < .04), deep gray matter (P = .01), and cortex (P = .004). When all subjects were considered, scores on the Mini-Mental State Examination decreased significantly with increasing leakage in the deep gray matter (P = .007) and cortex (P < .05). Conclusion The results of this study showed global BBB leakage in patients with early AD that is associated with cognitive decline. A compromised BBB may be part of a cascade of pathologic events that eventually lead to cognitive decline and dementia.©RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Harm J
authors.initials: HJ
authors.lastname: van de Haar
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Saartje
authors.initials: S
authors.lastname: Burgmans
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Jacobus F A
authors.initials: JF
authors.lastname: Jansen
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Matthias J P
authors.initials: MJ
authors.lastname: van Osch
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Mark A
authors.initials: MA
authors.lastname: van Buchem
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Majon
authors.initials: M
authors.lastname: Muller
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Hofman
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Frans R J
authors.initials: FR
authors.lastname: Verhey
authors.affiliation: From the Departments of Radiology and Nuclear Medicine (H.J.v.d.H., J.F.A.J., P.A.M.H., W.H.B.) and Department of Neuropsychology and Psychiatry/Alzheimer Center Limburg (H.J.v.d.H., S.B., F.R.J.V.), Maastricht University Medical Center, PO Box 5800, 6202 AZ, Maastricht, the Netherlands; School for Mental Health and Neuroscience, Maastricht University, Maastricht, the Netherlands (H.J.v.d.H., S.B., J.F.A.J., P.A.M.H., F.R.J.V., W.H.B.); and Departments of Radiology (M.J.P.v.O., M.A.v.B.) and Gerontology and Geriatrics (M.M.), Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Backes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000473:pathology*; D001810:Blood Volume; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging* / Q000473:pathology*; D016022:Case-Control Studies; D003287:Contrast Media; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects
chemical_list: D003287:Contrast Media