Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET.
OBJECTIVE
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.
Bauer
Martin
M
Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
Karch
Rudolf
R
Neumann
Friederike
F
Abrahim
Aiman
A
Wagner
Claudia C
CC
Kletter
Kurt
K
Müller
Markus
M
Zeitlinger
Markus
M
Langer
Oliver
O
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D000679:Amygdala / Q000000981:diagnostic imaging / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002531:Cerebellum / Q000000981:diagnostic imaging / Q000378:metabolism; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D014665:Vasodilator Agents; D014700:Verapamil
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002250:Carbon Radioisotopes; D014665:Vasodilator Agents; D014700:Verapamil