Introduction
It has been hypothesised that the blood brain barrier (BBB) integrity might decrease during ageing. In addition, it has been postulated that loss of P-glycoprotein (P-gp) function with age may be one factor in the development and progression of neurodegenerative diseases. Verapamil is a substrate for P-gp, located in the BBB. The volume of distribution of [11C](R)-verapamil in the brain (inversely) reflects P-gp function in the BBB 1 . This tracer can, therefore, be used to assess P-gp function in neurodegenerative diseases. For correct interpretation of results obtained in those studies, however, the effects of normal ageing on P-gp function need to be known.
Aim
The aim of the present pilot study was to assess the role of ageing on P-gp function in the BBB using [11C](R)-verapamil and PET.
Methods
Five young (age 21–27 years) and 5 elderly (age 59–68 years) healthy volunteers were included in this study. A dynamic 3D emission scan with a total scan duration of 60 minutes was acquired following intravenous injection of ∼370 MBq [11C](R)-verapamil. During the scan arterial blood was monitored continuously and, at set times, additional samples were taken for metabolite analysis in order to generate a metabolite corrected input function. Volume of distribution (Vd) images were generated using Logan analysis. These images were segmented based on co-registered MRI data, resulting in whole brain grey matter Vd values.
Results
Whole brain grey matter verapamil Vd as function of age is shown in figure 1. Average (±SD) Vd for young and elderly volunteers was 0.61 (±0.06) and 0.75 (±0.07), respectively. This difference was significant (p<0.01).
Grey matter [11C](R)-verapamil Vd as function of age
Conclusion
This prospective study showed significantly decreased P-gp activity, i. e. reduced integrity of the BBB transport function, during ageing.