Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
Nina Karalija, Jarkko Johansson, Goran Papenberg, Anders Wåhlin, Alireza Salami, Ylva Köhncke, Andreas M. Brandmaier, Micael Andersson, Jan Axelsson, Katrine Riklund, Martin Lövdén, Ulman Lindenberger, Lars Bäckman, Lars Nyberg
Abstract
Background and Objectives Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates. Methods We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity. Results Longitudinal analyses of the sample (baseline: n = 181, ages: 64–68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion. Discussion These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline. ACC= : anterior cingulate cortex; ANOVA= : analysis of variance; BMI= : body mass index; BPND= : DRD2 binding potential; COBRA= : Cognition, Brain, and Aging; DA= : dopamine; DRD2= : DA D2-like receptor; GM= : gray matter; MMSE= : Mini-Mental State Examination; MRTM= : multilinear reference tissue model; OFC= : orbitofrontal cortex; PCA= : principal component analysis; pcASL= : pseudocontinuous arterial spin labeling; PVE= : partial volume effect; ROI= : region of interest; WM= : white matter