Differential regional decline in dopamine receptor availability across adulthood: Linear and nonlinear effects of age

• Published in: Human brain mapping 2019-07, Vol.40 (10), p.3125-3138
• Main Authors: Seaman, Kendra L., Smith, Christopher T., Juarez, Eric J., Dang, Linh C., Castrellon, Jaime J., Burgess, Leah L., San Juan, M. Danica, Kundzicz, Paul M., Cowan, Ronald L., Zald, David H., Samanez‐Larkin, Gregory R.
• Format: Article
• Language: English
• Subjects: Adult; Adults; Age; Age differences; Age factors; Aged; Aged, 80 and over; Aging; Aging - metabolism; Amygdala; Binding; Brain; Brain - metabolism; Cognitive ability; Cortex (frontal); Cortex (temporal); Cross-Sectional Studies; D2 receptors; Dopamine; Dopamine D2 receptors; Female; Humans; Magnetic Resonance Imaging; Male; Medical imaging; Middle Aged; Models, Statistical; Neostriatum; Neuroimaging; Neurology; Pallidum (ventral); Parahippocampal gyrus; Positron emission; Positron emission tomography; positron emission tomography imaging; Putamen; Radioactive tracers; Receptors, Dopamine D2 - metabolism; Receptors, Dopamine D3 - metabolism; Regional development; regional differences; Substantia alba; Substantia grisea; Thalamus; Tomography; Young Adult
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.24585

Theories of adult brain development, based on neuropsychological test results and structural neuroimaging, suggest differential rates of age‐related change in function across cortical and subcortical sub‐regions. However, it remains unclear if these trends also extend to the aging dopamine system. Here we examined cross‐sectional adult age differences in estimates of D2‐like receptor binding potential across several cortical and subcortical brain regions using PET imaging and the radiotracer [18F]Fallypride in two samples of healthy human adults (combined N = 132). After accounting for regional differences in overall radioligand binding, estimated percent difference in receptor binding potential by decade (linear effects) were highest in most temporal and frontal cortical regions (~6–16% per decade), moderate in parahippocampal gyrus, pregenual frontal cortex, fusiform gyrus, caudate, putamen, thalamus, and amygdala (~3–5%), and weakest in subcallosal frontal cortex, ventral striatum, pallidum, and hippocampus (~0–2%). Some regions showed linear effects of age while many showed curvilinear effects such that binding potential declined from young adulthood to middle age and then was relatively stable until old age. Overall, these data indicate that the rate and pattern of decline in D2 receptor availability is regionally heterogeneous. However, the differences across regions were challenging to organize within existing theories of brain development and did not show the same pattern of regional change that has been observed in gray matter volume, white matter integrity, or cognitive performance. This variation suggests that existing theories of adult brain development may need to be modified to better account for the spatial dynamics of dopaminergic system aging.