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Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET


Bauer, M; Karch, R; Neumann, F; Abrahim, A; Wagner, C C; Kletter, K; Müller, M; Zeitlinger, M; Langer, O (2009). Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET. European Journal of Clinical Pharmacology, 65(9):941-946.

Abstract

PURPOSE: The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier. METHODS: Seven young (mean age: 27 +/- 4 years) and six elderly (mean age: 69 +/- 9 years) healthy volunteers underwent dynamic (R)-[(11)C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC). RESULTS: SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC. CONCLUSIONS: Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age.

PURPOSE: The aim of this study was to assess the influence of age on the functional activity of the multidrug efflux transporter P-glycoprotein (P-gp) at the human blood-brain barrier. METHODS: Seven young (mean age: 27 +/- 4 years) and six elderly (mean age: 69 +/- 9 years) healthy volunteers underwent dynamic (R)-[(11)C]verapamil (VPM) positron emission tomography (PET) scans and arterial blood sampling. Parametric distribution volume (DV) images were generated using Logan linearisation, and age groups were compared with statistical parametric mapping (SPM). Brain regions that SPM analysis had shown to be most affected by age were analysed by a region of interest (ROI)-based approach using a maximum probability brain atlas, before and after partial volume correction (PVC). RESULTS: SPM analysis revealed significant clusters of DV increases in cerebellum, temporal and frontal lobe of elderly compared to younger subjects. In the ROI-based analysis, elderly subjects showed significant DV increases in amygdala (+30%), insula (+26%) and cerebellum (+25%) before PVC, and in insula (+33%) after PVC. CONCLUSIONS: Increased VPM DV values in the brains of elderly subjects suggest a decrease in cerebral P-gp function with increasing age.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2009
Deposited On:15 Feb 2010 12:30
Last Modified:05 Apr 2016 13:54
Publisher:Springer
ISSN:0031-6970
Publisher DOI:https://doi.org/10.1007/s00228-009-0709-5
PubMed ID:19655132

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