%0 Journal Article
%T Cardiac 11C
%A Aage K.O. Alstrup
%A Allan K. Hansen
%A Jacob Horsager
%A Karoline Knudsen
%A Klaus Krogh
%A Lars Gormsen
%A Mette W. Klinge
%A Nathalie V.D. Berge
%A Per Borghammer
%A Tatyana D. Fedorova
%J Journal of Cardiovascular Pharmacology and Therapeutics
%@ 1940-4034
%D 2019
%R 10.1177/1074248419838509
%X Donepezil may have cardioprotective properties, but the mechanism is unclear. Using positron-emission tomography (PET), we explored 11C-donepezil uptake in the heart of humans in relation to age. The results are discussed in the context of the cardioprotective property of donepezil. We included data from 57 patients with cardiac 11C-donepezil PET scans. Linear regression analyses were performed to explore the correlation between cardiac 11C-donepezil standardized uptake value (SUV) and age. Subgroup analyses were performed for healthy controls, patients with prodromal or diagnosed Parkinson disease (PD), males, and females. In the total group of 57 patients, linear regression analysis revealed a significant positive correlation between cardiac 11C-donepezil uptake and age (r2 = .63, P < .0001). The average increase was ¡Ö1.25 SUV per decade and a 2-fold increase in SUV from age 30 to 65 years. Subgroup analyses also showed significant correlations: healthy control patients alone (n = 28, r2 = .73, P < .0001), prodromal or diagnosed PD (n = 29, r2 = .28, P = .03), male patients (n = 34, r2 = .49, P < .0001), and female patients (n = 23, r2 = .82, P < .0001). No other organs showed increased 11C-donepezil binding with age. 11C-donepezil SUV increases robustly with age in the normal human heart. We speculate that the increased donepezil binding is caused primarily by sigma-1 receptor upregulation. If our interpretation is correct, it shows that sigma-1 receptors are dynamically regulated and may represent an overlooked target for pharmacological intervention studies
%K 11C-donepezil PET
%K donepezil
%K heart
%K ageing
%K cardiac protection
%U https://journals.sagepub.com/doi/full/10.1177/1074248419838509